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  • The same species also stood out in terms of relative abundance, Penilia avirostris (87%) and Pseudevadne tergestina (11%). The absence of Cladocera in the innermost parts of the lagoon suggests that their entrance to these locations is possibly inhibited by the salinity and temperature gradient of the lagoon, being the main factors influencing the dynamics of the Cladocera assemblages.A first checklist of Rotifera species in freshwater environments in Bahia State, in northeastern Brazil, is provided. The list includes sampling data from 26 aquatic environments (lotic and lentic) undertaken from 2010 to 2016. One hundred and fifty-five species were recorded, with 68 new records for the state. The family Brachionidae and Lecanidae were the most representative (54.8%). The greatest richness was recorded in the Colônia River (57 species). Those results reflect the low numbers of studies previously undertaken in the region, indicating more research needs to be focused on Rotifera biodiversity in Bahia, the fifth largest state in Brazil (567,295 km2) with large numbers of freshwater bodies.Water stress is one of the major factor restricting the growth and development of chickpea plants by inducing various morphological and physiological changes. Therefore, the present research activity was designed to improve the chickpea productivity under water stress conditions by modulating antioxidant enzyme system. Experimental treatments comprised of two chickpea genotypes i.e. Bhakhar 2011 (drought tolerant) and DUSHT (drought sensitive), two water stress levels i.e. water stress at flowering stage and water stress at flowering + pod formation + grain filling stage including well watered (control) and three exogenous application of nutrients i.e. KCl 200 ppm, MgCl2, 50 ppm and CaCl2, 10 mM including distilled water (control). Results indicated that water stress at various growth stages adversely affects the growth, yield and quality attributes of both chickpea cultivars. https://www.selleckchem.com/products/zebularine.html Exogenous application of nutrients improved the growth, yield and antioxidant enzyme activities of both chickpea genotypes even under water stress conditions. However, superior results were obtained with foliar spray of potassium chloride on Bhakhar 2011 under well-watered conditions. Similarly, foliar spray of potassium chloride on chickpea cultivar Bhakhar 2011 cultivated under stress at flowering + pod formation + grain filling stage produced significantly higher contents of superoxide dismutase, peroxidase and catalase. These results suggests that the application of potassium chloride mitigates the adverse effects of water stress and enhanced tolerance in chickpea mainly due to higher antioxidant enzymes activity, demonstrating the protective measures of plant cells in stress conditions.Galls, neo-formed plant structures that can occur in different organs, are generated by species-specific interaction with an inducing organism. Inducers manipulate the metabolism of its host. Microgramma vacciniifolia (Langsd. & Fisch.) Copel. is a Neotropical epiphytic fern that hosted two stem galls, one induced by a midge species (Diptera) and other by a micromoth species (Lepidoptera). The aim of this study was to evaluate the impact of these two gall-inducing insects on the biochemistry of phenolic acids and the cyanogenesis in galls, stems and leaves of M. vacciniifolia. High performance liquid chromatography (HPLC) indicated a total of 14 phenol derivatives, including caffeic and coumaric acid. Principal Coordinates Analysis (PCoA) of the phenolic substances indicated three groups consisting (1) non-galled stems and micromoth-induced galls; (2) midge-induced galls; (3) midge-induced galls with parasitoids. Regarding the frequency of cyanogenesis assessed by the picrate paper test, the chi-squared test showed significant difference between fertile leaves (8.3%), sterile leaves (27.7%), non-galled stems (0%) and galls. Among galls, only the midge-induced galls analyzed were cyanogenic (15%). Our results indicated that the different gall-inducers (midge and micromoth) promote species-specific alterations to the phenolic substance composition of the host fern.In the tropical region, savannas and seasonal forests, both highly diverse biomes, occur side by side, under the same climate. If so, that mosaic cannot be explained solely by climatic variables, but also by fire, water availability and soil status. Nutrient availability in the soil, especially nitrogen and phosphorus, has been postulated to explain the abrupt transitions between savannas and seasonal forests in tropical regions. Plants from these two biomes may present different nutritional strategies to cope with nitrogen and phosphorus limitation. We used two congeneric pairs of trees - each pair with a species from the savanna and another from the neighboring seasonal forest - to test whether savanna and forest species presented different nutritional strategies during their early development. We cultivated 56 individuals from each of these species in a hydroponics system with four treatments (1) complete Hoagland solution, (2) Hoagland solution without nitrogen, (3) Hoagland solution without phosphorus, and (4) Hoagland solution without nitrogen and phosphorus. After 45 days, we harvested the plants and measured total biomass, root to shoot ratio, height, leaf area, and specific leaf area. Overall, savanna species were lighter, shorter, with smaller leaves, higher specific leaf areas, and higher root to shoot ratios when compared to the forest species. Nitrogen increased the performance of species from both biomes. Phosphorus improved the performance of the forest species and caused toxicity symptoms in the savanna species. Hence, savanna and forest species presented different demands and were partially distinct already as seedlings concerning their nutritional strategies.Plants that produce secondary metabolites with allelopathic activity or phytotoxicity can be biotechnologically important, serving as sources of allelochemicals, and thus contributing to the agroindustrial sector. Vismia japurensis (Hypericaceae) is an Amazonian species that grows in clumps called vismiais, from which most other plants are absent. Accordingly, the objective of this study was to identify possible phytotoxicity effects of hexane and methanol extracts of Vismia japurensis leaves and branches in vivo and from seedlings grown in vitro on Lactuca sativa. In addition, fresh and dry leaves were assayed by the sandwich method in order to determine their ability to release allelochemicals. The hexanic extract from in vitro seedlings reduced germination by 10%, while the methanol extract produced a 16% reduction in germination speed. Root growth of Lactuca sativa was inhibited by 64.7% when subjected to hexane leaf extract, by 39.3% under the influence of hexane branch extract, and by 96.09% for in vitro seedling hexanic extract.
    The same species also stood out in terms of relative abundance, Penilia avirostris (87%) and Pseudevadne tergestina (11%). The absence of Cladocera in the innermost parts of the lagoon suggests that their entrance to these locations is possibly inhibited by the salinity and temperature gradient of the lagoon, being the main factors influencing the dynamics of the Cladocera assemblages.A first checklist of Rotifera species in freshwater environments in Bahia State, in northeastern Brazil, is provided. The list includes sampling data from 26 aquatic environments (lotic and lentic) undertaken from 2010 to 2016. One hundred and fifty-five species were recorded, with 68 new records for the state. The family Brachionidae and Lecanidae were the most representative (54.8%). The greatest richness was recorded in the Colônia River (57 species). Those results reflect the low numbers of studies previously undertaken in the region, indicating more research needs to be focused on Rotifera biodiversity in Bahia, the fifth largest state in Brazil (567,295 km2) with large numbers of freshwater bodies.Water stress is one of the major factor restricting the growth and development of chickpea plants by inducing various morphological and physiological changes. Therefore, the present research activity was designed to improve the chickpea productivity under water stress conditions by modulating antioxidant enzyme system. Experimental treatments comprised of two chickpea genotypes i.e. Bhakhar 2011 (drought tolerant) and DUSHT (drought sensitive), two water stress levels i.e. water stress at flowering stage and water stress at flowering + pod formation + grain filling stage including well watered (control) and three exogenous application of nutrients i.e. KCl 200 ppm, MgCl2, 50 ppm and CaCl2, 10 mM including distilled water (control). Results indicated that water stress at various growth stages adversely affects the growth, yield and quality attributes of both chickpea cultivars. https://www.selleckchem.com/products/zebularine.html Exogenous application of nutrients improved the growth, yield and antioxidant enzyme activities of both chickpea genotypes even under water stress conditions. However, superior results were obtained with foliar spray of potassium chloride on Bhakhar 2011 under well-watered conditions. Similarly, foliar spray of potassium chloride on chickpea cultivar Bhakhar 2011 cultivated under stress at flowering + pod formation + grain filling stage produced significantly higher contents of superoxide dismutase, peroxidase and catalase. These results suggests that the application of potassium chloride mitigates the adverse effects of water stress and enhanced tolerance in chickpea mainly due to higher antioxidant enzymes activity, demonstrating the protective measures of plant cells in stress conditions.Galls, neo-formed plant structures that can occur in different organs, are generated by species-specific interaction with an inducing organism. Inducers manipulate the metabolism of its host. Microgramma vacciniifolia (Langsd. & Fisch.) Copel. is a Neotropical epiphytic fern that hosted two stem galls, one induced by a midge species (Diptera) and other by a micromoth species (Lepidoptera). The aim of this study was to evaluate the impact of these two gall-inducing insects on the biochemistry of phenolic acids and the cyanogenesis in galls, stems and leaves of M. vacciniifolia. High performance liquid chromatography (HPLC) indicated a total of 14 phenol derivatives, including caffeic and coumaric acid. Principal Coordinates Analysis (PCoA) of the phenolic substances indicated three groups consisting (1) non-galled stems and micromoth-induced galls; (2) midge-induced galls; (3) midge-induced galls with parasitoids. Regarding the frequency of cyanogenesis assessed by the picrate paper test, the chi-squared test showed significant difference between fertile leaves (8.3%), sterile leaves (27.7%), non-galled stems (0%) and galls. Among galls, only the midge-induced galls analyzed were cyanogenic (15%). Our results indicated that the different gall-inducers (midge and micromoth) promote species-specific alterations to the phenolic substance composition of the host fern.In the tropical region, savannas and seasonal forests, both highly diverse biomes, occur side by side, under the same climate. If so, that mosaic cannot be explained solely by climatic variables, but also by fire, water availability and soil status. Nutrient availability in the soil, especially nitrogen and phosphorus, has been postulated to explain the abrupt transitions between savannas and seasonal forests in tropical regions. Plants from these two biomes may present different nutritional strategies to cope with nitrogen and phosphorus limitation. We used two congeneric pairs of trees - each pair with a species from the savanna and another from the neighboring seasonal forest - to test whether savanna and forest species presented different nutritional strategies during their early development. We cultivated 56 individuals from each of these species in a hydroponics system with four treatments (1) complete Hoagland solution, (2) Hoagland solution without nitrogen, (3) Hoagland solution without phosphorus, and (4) Hoagland solution without nitrogen and phosphorus. After 45 days, we harvested the plants and measured total biomass, root to shoot ratio, height, leaf area, and specific leaf area. Overall, savanna species were lighter, shorter, with smaller leaves, higher specific leaf areas, and higher root to shoot ratios when compared to the forest species. Nitrogen increased the performance of species from both biomes. Phosphorus improved the performance of the forest species and caused toxicity symptoms in the savanna species. Hence, savanna and forest species presented different demands and were partially distinct already as seedlings concerning their nutritional strategies.Plants that produce secondary metabolites with allelopathic activity or phytotoxicity can be biotechnologically important, serving as sources of allelochemicals, and thus contributing to the agroindustrial sector. Vismia japurensis (Hypericaceae) is an Amazonian species that grows in clumps called vismiais, from which most other plants are absent. Accordingly, the objective of this study was to identify possible phytotoxicity effects of hexane and methanol extracts of Vismia japurensis leaves and branches in vivo and from seedlings grown in vitro on Lactuca sativa. In addition, fresh and dry leaves were assayed by the sandwich method in order to determine their ability to release allelochemicals. The hexanic extract from in vitro seedlings reduced germination by 10%, while the methanol extract produced a 16% reduction in germination speed. Root growth of Lactuca sativa was inhibited by 64.7% when subjected to hexane leaf extract, by 39.3% under the influence of hexane branch extract, and by 96.09% for in vitro seedling hexanic extract.
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  • Objective Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms.Method Anesthetized rats were placed in a heating chamber (42 °C) to elevate the core body temperature attaining to 42.9 °C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure.Results Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-α, IL-6, IL-1β, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62.Conclusion In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy.
    Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects.

    The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL.

    IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL)
    . The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca
    was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c **** (5 ****/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days.

    HXZQ-OL not only inhibited degranulation of mast cells (IC
    , 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC
    , 171.4 μg/mL), TNF-α (IC
    , 88.4 μg/mL), LTC4 (IC
    , 52.9 μg/mL) and PGD2 (IC
    , 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in ****.

    HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.
    HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.Introduction In the context of limited research assessing outcomes following mild traumatic brain injury (mTBI) in older adults, this study evaluated cognitive outcomes through prospective memory, and expected that performance of an older mTBI group (≥65 years) would be lower compared to orthopedic and community controls. The study also explored whether cognitive resources (retrospective memory, executive function) moderated any association between presenting Glasgow Coma Scale (GCS) and prospective memory.Method At three-months post-injury, a mTBI group (n = 39), an orthopedic control group (n = 63), and a community control group (n = 46) completed a neuropsychological assessment, including (i) prospective memory, using a standardized paper-and-pencil task (Cambridge Prospective Memory Test), an augmented reality task and a naturalistic task, and (ii) standardized measures of retrospective memory (Hopkins Verbal Learning Test) and executive function (Trail Making Test). Group performances were compared, and esolve or persist over time.Background The monoamine neurotransmitter disorders are neurometabolic syndromes caused by disturbances in the synthesis, transport and metabolism of the biogenic amines (the catecholamines dopamine, norepinephrine and epinephrine; serotonin), which are increasingly recognized as an expanding group of inherited neurometabolic syndromes.Case Description A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene SLC18A2, which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in SLC18A2 has been identified in three families in different countries. The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved.Conclusion This case confirmed the causal mutation of SLC18A2 gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals.
    Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC.

    We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay.

    Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68-0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76-1.07). https://www.selleckchem.com/products/iu1.html However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA.
    Objective Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms.Method Anesthetized rats were placed in a heating chamber (42 °C) to elevate the core body temperature attaining to 42.9 °C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure.Results Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-α, IL-6, IL-1β, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62.Conclusion In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy. Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects. The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL. IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL) . The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c mice (5 mice/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days. HXZQ-OL not only inhibited degranulation of mast cells (IC , 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC , 171.4 μg/mL), TNF-α (IC , 88.4 μg/mL), LTC4 (IC , 52.9 μg/mL) and PGD2 (IC , 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in mice. HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases. HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.Introduction In the context of limited research assessing outcomes following mild traumatic brain injury (mTBI) in older adults, this study evaluated cognitive outcomes through prospective memory, and expected that performance of an older mTBI group (≥65 years) would be lower compared to orthopedic and community controls. The study also explored whether cognitive resources (retrospective memory, executive function) moderated any association between presenting Glasgow Coma Scale (GCS) and prospective memory.Method At three-months post-injury, a mTBI group (n = 39), an orthopedic control group (n = 63), and a community control group (n = 46) completed a neuropsychological assessment, including (i) prospective memory, using a standardized paper-and-pencil task (Cambridge Prospective Memory Test), an augmented reality task and a naturalistic task, and (ii) standardized measures of retrospective memory (Hopkins Verbal Learning Test) and executive function (Trail Making Test). Group performances were compared, and esolve or persist over time.Background The monoamine neurotransmitter disorders are neurometabolic syndromes caused by disturbances in the synthesis, transport and metabolism of the biogenic amines (the catecholamines dopamine, norepinephrine and epinephrine; serotonin), which are increasingly recognized as an expanding group of inherited neurometabolic syndromes.Case Description A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene SLC18A2, which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in SLC18A2 has been identified in three families in different countries. The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved.Conclusion This case confirmed the causal mutation of SLC18A2 gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals. Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC. We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay. Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68-0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76-1.07). https://www.selleckchem.com/products/iu1.html However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA.
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  • SHORT syndrome is a rare autosomal dominant disorder characterized by multiple congenital defects and is historically defined by its acronym short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay. Herein, we report a male infant with SHORT syndrome who presented with transient neonatal diabetes mellitus (TNDM) with insulin resistance. The proband was born at 38 weeks of gestation but displayed facial dysmorphic features. Intrauterine growth restriction (IUGR) was detected on a prenatal ultrasonography test. His birth weight was 1.8 kg (T (p.Arg649Trp) in exon 15 of the phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) known as the causative gene for SHORT syndrome. Examination of the patient at 10 months of age revealed no hyperglycemic episode and glycated hemoglobin level was 5.2%. To the best of our knowledge, this is the first case of TNDM in SHORT syndrome due to a pathogenic variant of PIK3R1. We believe that our case can aid in expanding the phenotypes of SHORT syndrome.The COVID-19 pandemic has highlighted the necessity for scientists from diverse disciplines to collaboratively mitigate the singular calamity facing humanity this century. The ability of researchers to combine exponential advances in technology and scientific acumen has resulted in landmark discoveries in pediatric research and is surmounting the COVID-19 challenge. Several of these discoveries exist in a realm of research that is not classically "basic" or "clinical." Translational research characterizes this domain partially, but does not fully capture the integrated research approaches that have spurred these discoveries. Herein, we share our perspective on the common themes underpinning the basic and clinical research. We also highlight major differences in the scope, emphasis, approach, and limitations of basic and clinical research that impede multi-disciplinary approaches that facilitate truly transformative research. These differences in research thinking and methodology are ingrained during training wherein the limitations of the chosen discipline, and strengths of alternate disciplines are not adequately explored. Insular approaches are particularly limited in impacting complex diseases pathophysiology in the era of precision medicine. We propose that integration of -omics technologies, systems biology, adaptive clinical trial designs, humanized animal models, and precision pre-clinical model systems must be incorporated into research training of future scientists. Several initiatives from the NIH and other institutions are facilitating such broad-based "research without frontiers" training that paves the way for seamless, multi-disciplinary, research. Such efforts become "transformative" when scientific challenges are tackled in partnership with a willingness to share ideas, tackle challenges, and develop tools/models from the very beginning.Objective Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. https://www.selleckchem.com/products/caspofungin-acetate.html This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT).
    The rising prevalence of diabetes shows high health and socio-economic burdens. Therefore, the development and evaluation of new diagnostic methods may improve the detection of disease and its complications in the early stages. This study aimed to analyze the scope of the studies related to diabetes diagnosis.

    Publications from January 2015 until December 2019 (5 years) were searched with keywords of (diabetes OR diabetic) AND (Iran) in Scopus and PubMed databases. All data were reviewed by two reviewers and the included publications were categorized based on the subjects, study design, and publication year.

    Based on the selected criteria, 103 articles were included. The highest number of publications was observed in 2019. The trend of publication was slightly increased during the study period (2015-2019). Case-control and cross-sectional studies were the most common type of study design used in the included documents. Publications in the field of diagnostic models, biomarkers, and biosensors from 2015 to 2019 showed an increasing trend compared to others subjects.
    SHORT syndrome is a rare autosomal dominant disorder characterized by multiple congenital defects and is historically defined by its acronym short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay. Herein, we report a male infant with SHORT syndrome who presented with transient neonatal diabetes mellitus (TNDM) with insulin resistance. The proband was born at 38 weeks of gestation but displayed facial dysmorphic features. Intrauterine growth restriction (IUGR) was detected on a prenatal ultrasonography test. His birth weight was 1.8 kg (T (p.Arg649Trp) in exon 15 of the phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) known as the causative gene for SHORT syndrome. Examination of the patient at 10 months of age revealed no hyperglycemic episode and glycated hemoglobin level was 5.2%. To the best of our knowledge, this is the first case of TNDM in SHORT syndrome due to a pathogenic variant of PIK3R1. We believe that our case can aid in expanding the phenotypes of SHORT syndrome.The COVID-19 pandemic has highlighted the necessity for scientists from diverse disciplines to collaboratively mitigate the singular calamity facing humanity this century. The ability of researchers to combine exponential advances in technology and scientific acumen has resulted in landmark discoveries in pediatric research and is surmounting the COVID-19 challenge. Several of these discoveries exist in a realm of research that is not classically "basic" or "clinical." Translational research characterizes this domain partially, but does not fully capture the integrated research approaches that have spurred these discoveries. Herein, we share our perspective on the common themes underpinning the basic and clinical research. We also highlight major differences in the scope, emphasis, approach, and limitations of basic and clinical research that impede multi-disciplinary approaches that facilitate truly transformative research. These differences in research thinking and methodology are ingrained during training wherein the limitations of the chosen discipline, and strengths of alternate disciplines are not adequately explored. Insular approaches are particularly limited in impacting complex diseases pathophysiology in the era of precision medicine. We propose that integration of -omics technologies, systems biology, adaptive clinical trial designs, humanized animal models, and precision pre-clinical model systems must be incorporated into research training of future scientists. Several initiatives from the NIH and other institutions are facilitating such broad-based "research without frontiers" training that paves the way for seamless, multi-disciplinary, research. Such efforts become "transformative" when scientific challenges are tackled in partnership with a willingness to share ideas, tackle challenges, and develop tools/models from the very beginning.Objective Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. https://www.selleckchem.com/products/caspofungin-acetate.html This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT). The rising prevalence of diabetes shows high health and socio-economic burdens. Therefore, the development and evaluation of new diagnostic methods may improve the detection of disease and its complications in the early stages. This study aimed to analyze the scope of the studies related to diabetes diagnosis. Publications from January 2015 until December 2019 (5 years) were searched with keywords of (diabetes OR diabetic) AND (Iran) in Scopus and PubMed databases. All data were reviewed by two reviewers and the included publications were categorized based on the subjects, study design, and publication year. Based on the selected criteria, 103 articles were included. The highest number of publications was observed in 2019. The trend of publication was slightly increased during the study period (2015-2019). Case-control and cross-sectional studies were the most common type of study design used in the included documents. Publications in the field of diagnostic models, biomarkers, and biosensors from 2015 to 2019 showed an increasing trend compared to others subjects.
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  • A phase dynamic model of the tongue tip was simulated for structural optimization. With the model-based feedback controller, the bionic soft tongue could achieve a fast step response and precise position control. Experimental results showed that the bionic soft tongue could grasp different kinds of objects, including of water, rice, and gel *****. This work is expected to expand the application scope of soft grippers.Cancer is a set of genetic diseases that are driven by mutations. It was recently discovered that the temporal order of genetic mutations affects the cancer evolution and even the nature of the decease itself. The mechanistic origin of these observations, however, remain not well understood. Here we present a theoretical model for cancer initiation dynamics that allows us to quantify the impact of the temporal order of mutations. In our approach, the cancer initiation process is viewed as a set of stochastic transitions between discrete states defined by the different numbers of mutated cells. Using a first-passage analysis, probabilities and times before the cancer initiation are explicitly evaluated for two alternative sequences of two mutations. It is found that the probability of cancer initiation is determined only by the first mutation, while the dynamics depends on both mutations. In addition, it is shown that the acquisition of a mutation with higher fitness before mutation with lower fitness increases the probability of the tumor formation but delays the cancer initiation. Theoretical results are explained using effective free-energy landscapes.The Inter-Agency Committee on Radiation Safety (IACRS) was constituted in 1990, as a forum for collaboration and coordination between international bodies with regards to radiation safety. It consists today of representatives of eight intergovernmental member organizations (EC, FAO, IAEA, ILO, OECD/NEA, PAHO, UNSCEAR and WHO) and five observer non-governmental organizations (ICRP, ICRU, IEC, IRPA and ISO). The IACRS provides a platform for interaction between these relevant international bodies to contribute to a common understanding of the scientific basis and legal framework for the application of the system of radiation protection, towards global harmonization of radiation safety standards. The IACRS played a key role in the development of the International Basic Safety Standards (BSS) in 1996 and in its revision in 2014. Further, an IACRS specific Task Group-chaired by the IAEA-fosters the implementation of the BSS in a consistent and coherent manner in all Member States of the United Nations. The IACRS operates via a standing secretariat jointly provided by the IAEA and OECD/NEA and is chaired by one of its member organizations on a rotating basis for periods of about 18 months. This approach has proved to be effective and was the foundation for ensuring continuity of the work of the committee and at the same time allowing a rotating leadership for all member organizations. Currently, the IACRS is chaired by WHO.Objective. Electrical brain stimulation has been used to ameliorate symptoms associated with neurologic and psychiatric disorders. The astrocytic activation and its interaction with neurons may contribute to the therapeutic effects of electrical stimulation. However, how the astrocytic activity is affected by electrical stimulation and its calcium signaling mechanisms remain largely unknown. This study is to explore the influence of electrical stimulus parameters on cellular calcium responses and corresponding calcium signaling mechanisms, with a focus on the heretofore largely overlooked astrocytes.Approach. Usingin vivotwo-photon microscopy in mouse somatosensory cortex, the calcium activity in neurons and astrocytes were recorded.Main results. The cathodal stimulation evoked larger responses in both neurons and astrocytes than anodal stimulation. Both neuronal and astrocytic response profiles exhibited the unimodal frequency dependency, the astrocytes prefer higher frequency stimulation than neurons. Astrocytes need longer pulse width and higher current intensity than neurons to activate. Compared to neurons, the astrocytes were not capable of keeping sustained calcium elevation during prolonged electrical stimulation. The neuronal Ca2+influx involves postsynaptic effects and direct depolarization. The Ca2+surge of astrocytes has a neuronal origin, the noradrenergic and glutamatergic signaling act synergistically to induce astrocytic activity.Significance. The astrocytic activity can be regulated by manipulating stimulus parameters and its calcium activation should be fully considered when interpreting the mechanisms of action of electrical neuromodulation. This study brings considerable benefits in the application of electrical stimulation and provides useful insights into cortical signal transduction, which contributes to the understanding of mechanisms underlying the therapeutic efficacy of electrical stimulation for neurorehabilitation applications.The surface modification of nano particles is very important in nanotechnology. Grafting from (GF) and grafting to (GT) are two main methods to prepare surface modified nanoparticles like nanocellulose crystalline (NCC) grafted with polylactic acid (PLA) chains. In the GF method, the NCC can get high grafting degree but short side chains to improve its compatibility with the polymer matrix. The GT method can help obtain long side chains to increase the chain entanglements but owns low grafting density. To take the advantage of both methods, a mixed modification method combining GT and GF methods was put forward to synthesize comb-like NCC-g-PLA (NP) as a macromolecular modifying agent of PLA. Firstly, GT Method was used to obtain long side-chain NP to improve chain entanglement. Secondly, the GF method was applied to obtain NP-g-PLA (NPL) and NP-g-PDLA (NPD) with additional short side chains to improve its dispersion and compatibility in the PLA matrix. https://www.selleckchem.com/peptide/bulevirtide-myrcludex-b.html The products showed an enhanced nucleation effect, the degree of crystallinity (Xc) of PLA composites increased almost four times with only 1 wt% NPD or NPL. What's more, the storage modulus and loss modulus of the composite melts also increased with 1 wt% NPL or NPD. The NPD/PLA shows a higher effect than NPL/PLA owning to stronger interaction originated from the stereocomplex (SC) network of PLA matrix with PDLA short chains in NPD.
    A phase dynamic model of the tongue tip was simulated for structural optimization. With the model-based feedback controller, the bionic soft tongue could achieve a fast step response and precise position control. Experimental results showed that the bionic soft tongue could grasp different kinds of objects, including of water, rice, and gel balls. This work is expected to expand the application scope of soft grippers.Cancer is a set of genetic diseases that are driven by mutations. It was recently discovered that the temporal order of genetic mutations affects the cancer evolution and even the nature of the decease itself. The mechanistic origin of these observations, however, remain not well understood. Here we present a theoretical model for cancer initiation dynamics that allows us to quantify the impact of the temporal order of mutations. In our approach, the cancer initiation process is viewed as a set of stochastic transitions between discrete states defined by the different numbers of mutated cells. Using a first-passage analysis, probabilities and times before the cancer initiation are explicitly evaluated for two alternative sequences of two mutations. It is found that the probability of cancer initiation is determined only by the first mutation, while the dynamics depends on both mutations. In addition, it is shown that the acquisition of a mutation with higher fitness before mutation with lower fitness increases the probability of the tumor formation but delays the cancer initiation. Theoretical results are explained using effective free-energy landscapes.The Inter-Agency Committee on Radiation Safety (IACRS) was constituted in 1990, as a forum for collaboration and coordination between international bodies with regards to radiation safety. It consists today of representatives of eight intergovernmental member organizations (EC, FAO, IAEA, ILO, OECD/NEA, PAHO, UNSCEAR and WHO) and five observer non-governmental organizations (ICRP, ICRU, IEC, IRPA and ISO). The IACRS provides a platform for interaction between these relevant international bodies to contribute to a common understanding of the scientific basis and legal framework for the application of the system of radiation protection, towards global harmonization of radiation safety standards. The IACRS played a key role in the development of the International Basic Safety Standards (BSS) in 1996 and in its revision in 2014. Further, an IACRS specific Task Group-chaired by the IAEA-fosters the implementation of the BSS in a consistent and coherent manner in all Member States of the United Nations. The IACRS operates via a standing secretariat jointly provided by the IAEA and OECD/NEA and is chaired by one of its member organizations on a rotating basis for periods of about 18 months. This approach has proved to be effective and was the foundation for ensuring continuity of the work of the committee and at the same time allowing a rotating leadership for all member organizations. Currently, the IACRS is chaired by WHO.Objective. Electrical brain stimulation has been used to ameliorate symptoms associated with neurologic and psychiatric disorders. The astrocytic activation and its interaction with neurons may contribute to the therapeutic effects of electrical stimulation. However, how the astrocytic activity is affected by electrical stimulation and its calcium signaling mechanisms remain largely unknown. This study is to explore the influence of electrical stimulus parameters on cellular calcium responses and corresponding calcium signaling mechanisms, with a focus on the heretofore largely overlooked astrocytes.Approach. Usingin vivotwo-photon microscopy in mouse somatosensory cortex, the calcium activity in neurons and astrocytes were recorded.Main results. The cathodal stimulation evoked larger responses in both neurons and astrocytes than anodal stimulation. Both neuronal and astrocytic response profiles exhibited the unimodal frequency dependency, the astrocytes prefer higher frequency stimulation than neurons. Astrocytes need longer pulse width and higher current intensity than neurons to activate. Compared to neurons, the astrocytes were not capable of keeping sustained calcium elevation during prolonged electrical stimulation. The neuronal Ca2+influx involves postsynaptic effects and direct depolarization. The Ca2+surge of astrocytes has a neuronal origin, the noradrenergic and glutamatergic signaling act synergistically to induce astrocytic activity.Significance. The astrocytic activity can be regulated by manipulating stimulus parameters and its calcium activation should be fully considered when interpreting the mechanisms of action of electrical neuromodulation. This study brings considerable benefits in the application of electrical stimulation and provides useful insights into cortical signal transduction, which contributes to the understanding of mechanisms underlying the therapeutic efficacy of electrical stimulation for neurorehabilitation applications.The surface modification of nano particles is very important in nanotechnology. Grafting from (GF) and grafting to (GT) are two main methods to prepare surface modified nanoparticles like nanocellulose crystalline (NCC) grafted with polylactic acid (PLA) chains. In the GF method, the NCC can get high grafting degree but short side chains to improve its compatibility with the polymer matrix. The GT method can help obtain long side chains to increase the chain entanglements but owns low grafting density. To take the advantage of both methods, a mixed modification method combining GT and GF methods was put forward to synthesize comb-like NCC-g-PLA (NP) as a macromolecular modifying agent of PLA. Firstly, GT Method was used to obtain long side-chain NP to improve chain entanglement. Secondly, the GF method was applied to obtain NP-g-PLA (NPL) and NP-g-PDLA (NPD) with additional short side chains to improve its dispersion and compatibility in the PLA matrix. https://www.selleckchem.com/peptide/bulevirtide-myrcludex-b.html The products showed an enhanced nucleation effect, the degree of crystallinity (Xc) of PLA composites increased almost four times with only 1 wt% NPD or NPL. What's more, the storage modulus and loss modulus of the composite melts also increased with 1 wt% NPL or NPD. The NPD/PLA shows a higher effect than NPL/PLA owning to stronger interaction originated from the stereocomplex (SC) network of PLA matrix with PDLA short chains in NPD.
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  • When tumor cells are killed by targeted therapy, radiotherapy, or chemotherapy, they trigger their primary tumor by releasing pro-inflammatory cytokines. Microenvironmental interactions can also promote tumor heterogeneity and development. In this line, several immune cells within the tumor microenvironment, including macrophages, dendritic cells, regulatory T-cells, and CD8+ and CD4+ T cells, are involved in the clearance of apoptotic tumor cells through a process called efferocytosis. Although the efficiency of apoptotic tumor cell efferocytosis is positive under physiological conditions, there are controversies regarding its usefulness in treatment-induced apoptotic tumor cells (ATCs). Efferocytosis can show the limitation of cytotoxic treatments, such as chemotherapy and radiotherapy. Since cytotoxic treatments lead to extensive cell mortality, efferocytosis, and macrophage polarization toward an M2 phenotype, the immune response may get involved in tumor recurrence and metastasis. Tumor cells can use the anti-inflammatory effect of apoptotic tumor cell efferocytosis to induce an immunosuppressive condition that is tumor-tolerant. Since M2 polarization and efferocytosis are tumor-promoting processes, the receptors on macrophages act as potential targets for cancer therapy. Moreover, researchers have shown that efferocytosis-related molecules/pathways are potential targets for cancer therapy. These include phosphatidylserine and calreticulin, Tyro3, Axl, and Mer tyrosine kinase (MerTK), receptors of tyrosine kinase, indoleamine-2,3-dioxygenase 1, annexin V, CD47, TGF-β, IL-10, and macrophage phenotype switch are combined with conventional therapy, which can be more effective in cancer treatment. Thus, we set out to investigate the advantages and disadvantages of efferocytosis in treatment-induced apoptotic tumor cells.Several terpenoids were isolated from Ganoderma colossum with potential chemotherapeutic properties against different solid tumor cells. Herein, we further assessed the potential chemomodulatory effects of colossolactone-G to gemcitabine (GCB) and 5-fluorouracil (5-FU) against colorectal cancer cells. Colossolactone-G induced moderate cell killing effects against both HT-29 and HCT-116 cells, with IC50's of 90.5 ± 1.7 µM and 22.3 ± 3.9 µM, respectively. Equitoxic combination demonstrated a synergistic effect between colossolactone-G and GCB, or 5-FU with combination indices ranging from 0.22 to 0.67. https://www.selleckchem.com/products/od36.html Both GCB and 5-FU induced moderate cell cycle arrest at G0/G1-phase and S-phase. Despite colossolactone-G's lack of influence on cell cycle distribution, it significantly potentiated GCB- and 5-FU-induced cell cycle arrest. Similarly, colossolactone-G treatment alone did not induce pronounced apoptosis in both cell lines. However, 5-FU and GCB induced significant apoptosis which was further potentiated via combination with colossolactone-G. Furthermore, colossolactone-G significantly increased autophagic cell death response in both HCT-116 and HT-29 cells and potentiated 5-FU- and GCB-induced autophagic cell death. The influence of colossolactone-G alone or in combination with GCB or 5-FU on the apoptosis and autophagy were confirmed by qPCR analysis for the expression of several key apoptosis and autophagy genes such as, TRAIL, TP53INP1, BNIP3, hp62, ATG5, ATG7, Lamp2A and the golden standard for autophagy (LC3-II). In conclusion, a synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, where it influenced both apoptosis and autophagic cell death mechanisms.The present article reviews and compares the immunomodulatory activities of Crocus sativus (C. sativus) and Nigella sativa (N. sativa) and their main bioactive compounds. Immunomodulatory effects of these plants, especially with respect to Th1 and Th2 cytokines, are discussed based on relevant articles, books, and conference papers published in English until the end of April 2020, that were retrieved from Web of Science, PubMed, Scopus and Google Scholar databases. C. sativus and its constituents increase immunoglobulin (Ig-)G, interleukin 2 (IL)-2, interferon gamma (IFN-γ), and IFN-γ/IL-4 ratio, but decreased IgM, IL-10 and IL-4 secretion. N. sativa extract and thymoquinone reduce the levels of IL-2, -4, -10, and -12, while enhance IFN-γ and serum IgG1 and 2a. The reviewed articles indicate that C. sativus and N. sativa and their constituents could be potentially considered promising treatments for disorders associated with immune-dysregulation such as asthma and cancer.The cytoskeleton is a supramolecular structure consisting of interacting protein networks that support cell dynamics in essential processes such as migration and division, as well as in responses to stress. Fast cytoskeletal remodeling is achieved with the participation of regulatory proteins and posttranslational modifications (PTMs). Redox-related PTMs are emerging as critical players in cytoskeletal regulation. Here we used a cellular model of mild nitroxidative stress in which a peroxynitrite donor induced transient changes in the organization of three key cytoskeletal proteins, i.e., vimentin, actin and tubulin. Nitroxidative stress-induced reconfiguration of intermediate filaments, microtubules and actin structures were further correlated with their PTM profiles and dynamics of the PTM landscape. Using high-resolution mass spectrometry, 62 different PTMs were identified and relatively quantified in vimentin, actin and tubulin, including 12 enzymatic, 13 oxidative and 2 nitric oxide-derived modifications as well as 35 modifications by carbonylated lipid peroxidation products, thus evidencing the occurrence of a chain reaction with formation of numerous reactive species and activation of multiple signaling pathways. Our results unveil the presence of certain modifications under basal conditions and their modulation in response to stress in a target-, residue- and reactive species-dependent manner. Thus, some modifications accumulated during the experiment whereas others varied transiently. Moreover, we identified protein PTM "hot spots", such as the single cysteine residue of vimentin, which was detected in seven modified forms, thus, supporting its role in PTM crosstalk and redox sensing. Finally, identification of novel PTMs in these proteins paves the way for unveiling new cytoskeleton regulatory mechanisms.
    When tumor cells are killed by targeted therapy, radiotherapy, or chemotherapy, they trigger their primary tumor by releasing pro-inflammatory cytokines. Microenvironmental interactions can also promote tumor heterogeneity and development. In this line, several immune cells within the tumor microenvironment, including macrophages, dendritic cells, regulatory T-cells, and CD8+ and CD4+ T cells, are involved in the clearance of apoptotic tumor cells through a process called efferocytosis. Although the efficiency of apoptotic tumor cell efferocytosis is positive under physiological conditions, there are controversies regarding its usefulness in treatment-induced apoptotic tumor cells (ATCs). Efferocytosis can show the limitation of cytotoxic treatments, such as chemotherapy and radiotherapy. Since cytotoxic treatments lead to extensive cell mortality, efferocytosis, and macrophage polarization toward an M2 phenotype, the immune response may get involved in tumor recurrence and metastasis. Tumor cells can use the anti-inflammatory effect of apoptotic tumor cell efferocytosis to induce an immunosuppressive condition that is tumor-tolerant. Since M2 polarization and efferocytosis are tumor-promoting processes, the receptors on macrophages act as potential targets for cancer therapy. Moreover, researchers have shown that efferocytosis-related molecules/pathways are potential targets for cancer therapy. These include phosphatidylserine and calreticulin, Tyro3, Axl, and Mer tyrosine kinase (MerTK), receptors of tyrosine kinase, indoleamine-2,3-dioxygenase 1, annexin V, CD47, TGF-β, IL-10, and macrophage phenotype switch are combined with conventional therapy, which can be more effective in cancer treatment. Thus, we set out to investigate the advantages and disadvantages of efferocytosis in treatment-induced apoptotic tumor cells.Several terpenoids were isolated from Ganoderma colossum with potential chemotherapeutic properties against different solid tumor cells. Herein, we further assessed the potential chemomodulatory effects of colossolactone-G to gemcitabine (GCB) and 5-fluorouracil (5-FU) against colorectal cancer cells. Colossolactone-G induced moderate cell killing effects against both HT-29 and HCT-116 cells, with IC50's of 90.5 ± 1.7 µM and 22.3 ± 3.9 µM, respectively. Equitoxic combination demonstrated a synergistic effect between colossolactone-G and GCB, or 5-FU with combination indices ranging from 0.22 to 0.67. https://www.selleckchem.com/products/od36.html Both GCB and 5-FU induced moderate cell cycle arrest at G0/G1-phase and S-phase. Despite colossolactone-G's lack of influence on cell cycle distribution, it significantly potentiated GCB- and 5-FU-induced cell cycle arrest. Similarly, colossolactone-G treatment alone did not induce pronounced apoptosis in both cell lines. However, 5-FU and GCB induced significant apoptosis which was further potentiated via combination with colossolactone-G. Furthermore, colossolactone-G significantly increased autophagic cell death response in both HCT-116 and HT-29 cells and potentiated 5-FU- and GCB-induced autophagic cell death. The influence of colossolactone-G alone or in combination with GCB or 5-FU on the apoptosis and autophagy were confirmed by qPCR analysis for the expression of several key apoptosis and autophagy genes such as, TRAIL, TP53INP1, BNIP3, hp62, ATG5, ATG7, Lamp2A and the golden standard for autophagy (LC3-II). In conclusion, a synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, where it influenced both apoptosis and autophagic cell death mechanisms.The present article reviews and compares the immunomodulatory activities of Crocus sativus (C. sativus) and Nigella sativa (N. sativa) and their main bioactive compounds. Immunomodulatory effects of these plants, especially with respect to Th1 and Th2 cytokines, are discussed based on relevant articles, books, and conference papers published in English until the end of April 2020, that were retrieved from Web of Science, PubMed, Scopus and Google Scholar databases. C. sativus and its constituents increase immunoglobulin (Ig-)G, interleukin 2 (IL)-2, interferon gamma (IFN-γ), and IFN-γ/IL-4 ratio, but decreased IgM, IL-10 and IL-4 secretion. N. sativa extract and thymoquinone reduce the levels of IL-2, -4, -10, and -12, while enhance IFN-γ and serum IgG1 and 2a. The reviewed articles indicate that C. sativus and N. sativa and their constituents could be potentially considered promising treatments for disorders associated with immune-dysregulation such as asthma and cancer.The cytoskeleton is a supramolecular structure consisting of interacting protein networks that support cell dynamics in essential processes such as migration and division, as well as in responses to stress. Fast cytoskeletal remodeling is achieved with the participation of regulatory proteins and posttranslational modifications (PTMs). Redox-related PTMs are emerging as critical players in cytoskeletal regulation. Here we used a cellular model of mild nitroxidative stress in which a peroxynitrite donor induced transient changes in the organization of three key cytoskeletal proteins, i.e., vimentin, actin and tubulin. Nitroxidative stress-induced reconfiguration of intermediate filaments, microtubules and actin structures were further correlated with their PTM profiles and dynamics of the PTM landscape. Using high-resolution mass spectrometry, 62 different PTMs were identified and relatively quantified in vimentin, actin and tubulin, including 12 enzymatic, 13 oxidative and 2 nitric oxide-derived modifications as well as 35 modifications by carbonylated lipid peroxidation products, thus evidencing the occurrence of a chain reaction with formation of numerous reactive species and activation of multiple signaling pathways. Our results unveil the presence of certain modifications under basal conditions and their modulation in response to stress in a target-, residue- and reactive species-dependent manner. Thus, some modifications accumulated during the experiment whereas others varied transiently. Moreover, we identified protein PTM "hot spots", such as the single cysteine residue of vimentin, which was detected in seven modified forms, thus, supporting its role in PTM crosstalk and redox sensing. Finally, identification of novel PTMs in these proteins paves the way for unveiling new cytoskeleton regulatory mechanisms.
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  • compared with other Caucasian populations. The incidence of glaucoma in those with PEX was higher compared with the incidence of glaucoma in those without PEX.
    To present the case of a family with a novel PRPH2/RDS mutation.

    A case report.

    A 44 year old female and her immediate family, including a father and sister who shared her PRPH2/RDS mutation.

    A 44 year old female presented with exam findings consistent with a butterfly-type pattern dystrophy. A sister had a similar butterfly-type dystrophy, while their father had a severe cone-rod dystrophy. Genetic testing revealed the same novel PRPH2/RDS mutation in all three affected individuals, suggesting that this single mutation can produce at least two disparate retinal disease phenotypes.

    This case describes a novel p.Y225X nonsense mutation in the PRPH2/RDS gene and demonstrates that it is both pathologic and capable of significant phenotypic variability.
    This case describes a novel p.Y225X nonsense mutation in the PRPH2/RDS gene and demonstrates that it is both pathologic and capable of significant phenotypic variability.
    To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy.

    Retrospective chart review of one patient.

    A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 x 3.3 x 1.9 mm. On optical coherence tomography, the egg-like structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through 8 months follow-up. The other metastatic lesions responded well to therapy.

    We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.
    We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.
    The prevalent method for investigating the effect of therapeutic interventions on walking in the individuals with chronic low **** pain (CLBP) is component-level approach in which all measurements focus on the spine component alone. However, this approach cannot disclose information about the overall function of the movement system such as complex walking patterns, which, in turn, reveal the underlying movement control.

    To compare the effect of 3-week wearing of lumbosacral orthosis (LSO) along with routine physical therapy with routine physical therapy alone on walking complexity in the individuals with nonspecific CLBP on the basis of the systems approach.

    Preliminary randomized clinical trial.

    Twenty-four subjects were randomly allocated to two groups. The control group received the routine physical therapy for 3 weeks. The intervention group received the same program plus an LSO. Nonlinear analysis was used to quantify walking complexity, as behavior of the entire movement system, before and afterocuses on the whole context that fosters LBP symptoms.
    Sarcoidosis associated pulmonary hypertension (SAPH) is a well-recognised complication, associated with a seven-fold increase in mortality. This comprehensive review will summarise these recent developments and proposes the use of a phenotype-based management approach in SAPH.

    Recent registry-based studies have highlighted the adverse outcomes associated with SAPH and shown that reduced 6-min walk distance and diffusion capacity for carbon monoxide are predictive of poor prognosis. There is increasing interest in methods for early detection of SAPH, although whether early diagnosis impacts on survival remains uncertain. The pathophysiology underpinning SAPH is complex and often incorporates multiple mechanisms. Once the diagnosis is confirmed, understanding the underlying phenotypes of SAPH is key to providing the most effective management plan. https://www.selleckchem.com/products/Atazanavir.html There is some evidence that treating patients with precapillary PH with pulmonary vasodilators may improve some haemodynamic and quality life measures. However, m The role of immunosuppressive agents for improving pulmonary pressures is unclear. Urgent controlled trials are needed.
    The coronavirus disease 2019 (COVID-19) pandemic has led to almost 3,000,000 deaths across 139 million people infected worldwide. Involvement of the pulmonary vasculature is considered a major driving force for morbidity and mortality. We set out to summarize current knowledge on the acute manifestations of pulmonary vascular disease (PVD) resulting from COVID-19 and prioritize long-term complications that may result in pulmonary hypertension (PH).

    Acute COVID-19 infection can result in widespread involvement of the pulmonary vasculature, myocardial injury, evidence of persistent lung disease, and venous thromboembolism. Post COVID-19 survivors frequently report ongoing symptoms and may be at risk for the spectrum of PH, including group 1 pulmonary arterial hypertension, group 2 PH due to left heart disease, group 3 PH due to lung disease and/or hypoxia, and group 4 chronic thromboembolic PH.

    The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.
    The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.
    compared with other Caucasian populations. The incidence of glaucoma in those with PEX was higher compared with the incidence of glaucoma in those without PEX. To present the case of a family with a novel PRPH2/RDS mutation. A case report. A 44 year old female and her immediate family, including a father and sister who shared her PRPH2/RDS mutation. A 44 year old female presented with exam findings consistent with a butterfly-type pattern dystrophy. A sister had a similar butterfly-type dystrophy, while their father had a severe cone-rod dystrophy. Genetic testing revealed the same novel PRPH2/RDS mutation in all three affected individuals, suggesting that this single mutation can produce at least two disparate retinal disease phenotypes. This case describes a novel p.Y225X nonsense mutation in the PRPH2/RDS gene and demonstrates that it is both pathologic and capable of significant phenotypic variability. This case describes a novel p.Y225X nonsense mutation in the PRPH2/RDS gene and demonstrates that it is both pathologic and capable of significant phenotypic variability. To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy. Retrospective chart review of one patient. A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 x 3.3 x 1.9 mm. On optical coherence tomography, the egg-like structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through 8 months follow-up. The other metastatic lesions responded well to therapy. We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy. We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy. The prevalent method for investigating the effect of therapeutic interventions on walking in the individuals with chronic low back pain (CLBP) is component-level approach in which all measurements focus on the spine component alone. However, this approach cannot disclose information about the overall function of the movement system such as complex walking patterns, which, in turn, reveal the underlying movement control. To compare the effect of 3-week wearing of lumbosacral orthosis (LSO) along with routine physical therapy with routine physical therapy alone on walking complexity in the individuals with nonspecific CLBP on the basis of the systems approach. Preliminary randomized clinical trial. Twenty-four subjects were randomly allocated to two groups. The control group received the routine physical therapy for 3 weeks. The intervention group received the same program plus an LSO. Nonlinear analysis was used to quantify walking complexity, as behavior of the entire movement system, before and afterocuses on the whole context that fosters LBP symptoms. Sarcoidosis associated pulmonary hypertension (SAPH) is a well-recognised complication, associated with a seven-fold increase in mortality. This comprehensive review will summarise these recent developments and proposes the use of a phenotype-based management approach in SAPH. Recent registry-based studies have highlighted the adverse outcomes associated with SAPH and shown that reduced 6-min walk distance and diffusion capacity for carbon monoxide are predictive of poor prognosis. There is increasing interest in methods for early detection of SAPH, although whether early diagnosis impacts on survival remains uncertain. The pathophysiology underpinning SAPH is complex and often incorporates multiple mechanisms. Once the diagnosis is confirmed, understanding the underlying phenotypes of SAPH is key to providing the most effective management plan. https://www.selleckchem.com/products/Atazanavir.html There is some evidence that treating patients with precapillary PH with pulmonary vasodilators may improve some haemodynamic and quality life measures. However, m The role of immunosuppressive agents for improving pulmonary pressures is unclear. Urgent controlled trials are needed. The coronavirus disease 2019 (COVID-19) pandemic has led to almost 3,000,000 deaths across 139 million people infected worldwide. Involvement of the pulmonary vasculature is considered a major driving force for morbidity and mortality. We set out to summarize current knowledge on the acute manifestations of pulmonary vascular disease (PVD) resulting from COVID-19 and prioritize long-term complications that may result in pulmonary hypertension (PH). Acute COVID-19 infection can result in widespread involvement of the pulmonary vasculature, myocardial injury, evidence of persistent lung disease, and venous thromboembolism. Post COVID-19 survivors frequently report ongoing symptoms and may be at risk for the spectrum of PH, including group 1 pulmonary arterial hypertension, group 2 PH due to left heart disease, group 3 PH due to lung disease and/or hypoxia, and group 4 chronic thromboembolic PH. The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors. The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.
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  • The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection.

    This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function.

    There was no significant correlation between the ACR values and the resected weights [correlation coefficient mammography- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x
    ), in which any resected weight can be used for the variable x to calculate the implant volume.

    We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.
    We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.Escherichia coli strains are generally sensitive to hydrophobic organic solvents such as n-hexane and cyclohexane. Oxidative stress in E. coli by exposure to these hydrophobic organic solvents has been poorly understood. In the present study, we examined organic solvent tolerance and oxygen radical generation in E. coli mutants deficient in reactive oxygen species (ROS)-scavenging enzymes. https://www.selleckchem.com/products/azd7545.html The organic solvent tolerances in single gene mutants lacking genes encoding superoxide dismutase (sodA, sodB, and sodC), catalase (katE and katG), and alkyl hydroperoxide reductase (ahpCF) were similar to that of parent strain BW25113. We constructed a BW25113-based katE katG double mutant (BW25113∆katE∆katG) and sodA sodB double mutant (BW25113sodA∆sodB). These double-gene mutants were more sensitive to hydrophobic organic solvents than BW25113. In addition, the intracellular ROS levels in E. coli strains increased by the addition of n-hexane or cyclohexane. The ROS levels in BW25113∆katE∆katG and BW25113∆sodA∆sodB induced by exposure to the solvents were higher than that in BW25113. These results suggested that ROS-scavenging enzymes contribute to the maintenance of organic solvent tolerance in E. coli. In addition, the promoter activities of sodA and sodB were significantly increased by exposure to n-hexane.Emotion dysregulation and intimacy problems are theoretically underpinned correlates of hypersexuality (i.e., uncontrollable sexual urges, fantasies, and behaviors resulting in distress and impairment in different areas of functioning), but the directionality of these associations has not been established, as work in this area has relied on cross-sectional designs. Moreover, although hypersexuality may have significant adverse effects on romantic relationships and approximately half of treatment-seeking individuals are in a relationship, prior studies almost exclusively involved samples of men, regardless of their relationship status. The aim of the present study was to examine the directionality of associations between both partners' emotion dysregulation, physical (i.e., partnered sexual frequency) and relationship intimacy, and hypersexuality using a longitudinal, dyadic framework. Self-reported data of 267 mixed-sex couples (Mage_men = 29.9 years, SD = 8.2; Mage_women = 27.7 years, SD = 6.7) at baseline (T1) and six-month follow-up (T2) were analyzed using a crossed-lagged model within an actor-partner interdependence framework. Prior greater emotion dysregulation (T1) in both men and women was associated with their own later greater hypersexuality (T2). Women's prior greater hypersexuality (T1) was associated with their later lower relationship intimacy (T2). Lower levels of intimacy were not significantly associated with later hypersexuality. No partner effects were found in relation to hypersexuality. Findings suggest that men and women may use sexual behaviors to cope with negative emotions, which could, in turn, lead to hypersexuality. Intimacy problems did not precede hypersexuality, although women's hypersexuality may reduce their own relationship intimacy over time.Many genetic disorders associated with intellectual disability are characterized by unique behavioral phenotypes which may have serious psychological consequences such as increasing the risk for sexual abuse (SA). Prader-Willi Syndrome (PWS), a severe neurogenetic syndrome with uncontrollable hyperphagia and high threshold for pain, is an excellent example of this issue. The absence of reports on SA in PWS highlights the lack of awareness to the topic. Our aim was to report on SA in individuals with PWS, describe its unique characteristics, and offer recommendations for its prevention. Caregivers of all individuals with genetically confirmed PWS living in the only two residential facilities designated for PWS in Israel were interviewed for a history of sexual behavior and abuse, and medical data were collected from their files. SA was reported in a quarter of the sample. In most of the cases (78%), food reward was used by the perpetrators to attract their victims. Age at SA ranged from 11 to 29 years. Most of the individuals did not disclose the event and some continued to initiate inappropriate sexual activity to obtain food.
    The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. There was no significant correlation between the ACR values and the resected weights [correlation coefficient mammography- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x ), in which any resected weight can be used for the variable x to calculate the implant volume. We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner. We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.Escherichia coli strains are generally sensitive to hydrophobic organic solvents such as n-hexane and cyclohexane. Oxidative stress in E. coli by exposure to these hydrophobic organic solvents has been poorly understood. In the present study, we examined organic solvent tolerance and oxygen radical generation in E. coli mutants deficient in reactive oxygen species (ROS)-scavenging enzymes. https://www.selleckchem.com/products/azd7545.html The organic solvent tolerances in single gene mutants lacking genes encoding superoxide dismutase (sodA, sodB, and sodC), catalase (katE and katG), and alkyl hydroperoxide reductase (ahpCF) were similar to that of parent strain BW25113. We constructed a BW25113-based katE katG double mutant (BW25113∆katE∆katG) and sodA sodB double mutant (BW25113sodA∆sodB). These double-gene mutants were more sensitive to hydrophobic organic solvents than BW25113. In addition, the intracellular ROS levels in E. coli strains increased by the addition of n-hexane or cyclohexane. The ROS levels in BW25113∆katE∆katG and BW25113∆sodA∆sodB induced by exposure to the solvents were higher than that in BW25113. These results suggested that ROS-scavenging enzymes contribute to the maintenance of organic solvent tolerance in E. coli. In addition, the promoter activities of sodA and sodB were significantly increased by exposure to n-hexane.Emotion dysregulation and intimacy problems are theoretically underpinned correlates of hypersexuality (i.e., uncontrollable sexual urges, fantasies, and behaviors resulting in distress and impairment in different areas of functioning), but the directionality of these associations has not been established, as work in this area has relied on cross-sectional designs. Moreover, although hypersexuality may have significant adverse effects on romantic relationships and approximately half of treatment-seeking individuals are in a relationship, prior studies almost exclusively involved samples of men, regardless of their relationship status. The aim of the present study was to examine the directionality of associations between both partners' emotion dysregulation, physical (i.e., partnered sexual frequency) and relationship intimacy, and hypersexuality using a longitudinal, dyadic framework. Self-reported data of 267 mixed-sex couples (Mage_men = 29.9 years, SD = 8.2; Mage_women = 27.7 years, SD = 6.7) at baseline (T1) and six-month follow-up (T2) were analyzed using a crossed-lagged model within an actor-partner interdependence framework. Prior greater emotion dysregulation (T1) in both men and women was associated with their own later greater hypersexuality (T2). Women's prior greater hypersexuality (T1) was associated with their later lower relationship intimacy (T2). Lower levels of intimacy were not significantly associated with later hypersexuality. No partner effects were found in relation to hypersexuality. Findings suggest that men and women may use sexual behaviors to cope with negative emotions, which could, in turn, lead to hypersexuality. Intimacy problems did not precede hypersexuality, although women's hypersexuality may reduce their own relationship intimacy over time.Many genetic disorders associated with intellectual disability are characterized by unique behavioral phenotypes which may have serious psychological consequences such as increasing the risk for sexual abuse (SA). Prader-Willi Syndrome (PWS), a severe neurogenetic syndrome with uncontrollable hyperphagia and high threshold for pain, is an excellent example of this issue. The absence of reports on SA in PWS highlights the lack of awareness to the topic. Our aim was to report on SA in individuals with PWS, describe its unique characteristics, and offer recommendations for its prevention. Caregivers of all individuals with genetically confirmed PWS living in the only two residential facilities designated for PWS in Israel were interviewed for a history of sexual behavior and abuse, and medical data were collected from their files. SA was reported in a quarter of the sample. In most of the cases (78%), food reward was used by the perpetrators to attract their victims. Age at SA ranged from 11 to 29 years. Most of the individuals did not disclose the event and some continued to initiate inappropriate sexual activity to obtain food.
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  • Background Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and survival in adults but has not been studied in pediatric cardiac arrest. We characterized AMSA during pediatric cardiac arrest from a Pediatric Resuscitation Quality Collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods and Results Children aged 20 minutes without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category were performed. Primary end points were TOF and ROSC. Secondary end points were 24-hour survival and survival to discharge. Between 2015 and 2019, 50 children from 14 hospitals with 111 shocks were identified. In univariate analyses AMSA was not associated with TOF and AMS-Aavg was not associated with ROSC. Multivariable logistic regression showed no association between AMSA and TOF but controlling for defibrillation average current and illness category, there was a trend to significant association between AMSA-avg and ROSC (odds ratio, 1.10 [1.00‒1.22] P=0.058). There was no significant association between AMSA-avg and 24-hour survival or survival to hospital discharge. Conclusions In pediatric patients, AMSA was not associated with TOF, whereas AMSA-avg had a trend to significance for association in ROSC, but not 24-hour survival or survival to hospital discharge. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT02708134.
    Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products.

    PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)).

    Narrative review of studies assessing lead content in mineral or MVM products.

    Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts.

    It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration's Interim Reference Level.

    The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.
    The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.
    The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA.

    This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo).

    Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). https://www.selleckchem.com/products/Atazanavir.html We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. SS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article Bone Joint Res 2021;10(6)354-362.Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta Stroke Program Early CT Score, onset to groin puncture time, occlusion site, and final recanalization. Out of 3025 patients with MT, 182 (6%) patients required RT because of underlying ICAS. Balloon angioplasty was performed on 122 patients, and 117 patients had intracranial stenting. In the matched analysis, 141 patients who received RT matched to a similar number of controls. The number of thrombectomy passes was higher (3 versus 1, P less then 0.001), and procedural time was longer in the RT group (52 minutes versus 36 minutes, P=0.004). There was a higher rate of symptomatic hemorrhagic transformation in the RT group (7.8% versus 4.3%, P=0.211), however, the difference was not significant. There was no difference in 90-day modified Rankin scale of 0 to 2 (44% versus 47.5%, P=0.543) between patients in the RT and control groups. Conclusions In patients with ELVO with underlying ICAS requiring RT, despite longer procedure time and a more thrombectomy passes, the 90 days favorable outcomes were comparable with patients with embolic ELVO.
    Background Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and survival in adults but has not been studied in pediatric cardiac arrest. We characterized AMSA during pediatric cardiac arrest from a Pediatric Resuscitation Quality Collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods and Results Children aged 20 minutes without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category were performed. Primary end points were TOF and ROSC. Secondary end points were 24-hour survival and survival to discharge. Between 2015 and 2019, 50 children from 14 hospitals with 111 shocks were identified. In univariate analyses AMSA was not associated with TOF and AMS-Aavg was not associated with ROSC. Multivariable logistic regression showed no association between AMSA and TOF but controlling for defibrillation average current and illness category, there was a trend to significant association between AMSA-avg and ROSC (odds ratio, 1.10 [1.00‒1.22] P=0.058). There was no significant association between AMSA-avg and 24-hour survival or survival to hospital discharge. Conclusions In pediatric patients, AMSA was not associated with TOF, whereas AMSA-avg had a trend to significance for association in ROSC, but not 24-hour survival or survival to hospital discharge. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT02708134. Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products. PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)). Narrative review of studies assessing lead content in mineral or MVM products. Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts. It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration's Interim Reference Level. The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid. The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid. The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo). Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). https://www.selleckchem.com/products/Atazanavir.html We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. SS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article Bone Joint Res 2021;10(6)354-362.Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta Stroke Program Early CT Score, onset to groin puncture time, occlusion site, and final recanalization. Out of 3025 patients with MT, 182 (6%) patients required RT because of underlying ICAS. Balloon angioplasty was performed on 122 patients, and 117 patients had intracranial stenting. In the matched analysis, 141 patients who received RT matched to a similar number of controls. The number of thrombectomy passes was higher (3 versus 1, P less then 0.001), and procedural time was longer in the RT group (52 minutes versus 36 minutes, P=0.004). There was a higher rate of symptomatic hemorrhagic transformation in the RT group (7.8% versus 4.3%, P=0.211), however, the difference was not significant. There was no difference in 90-day modified Rankin scale of 0 to 2 (44% versus 47.5%, P=0.543) between patients in the RT and control groups. Conclusions In patients with ELVO with underlying ICAS requiring RT, despite longer procedure time and a more thrombectomy passes, the 90 days favorable outcomes were comparable with patients with embolic ELVO.
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  • The performance was compared according to the number of layers and the size of the metal sheet. The results are expected to contribute to sensor-based DLB detection technology.Background To compare the skeletal, dental, and esthetic changes produced by three functional devices, Fränkel-2 appliance (FR-2), Twin Block (TB), and Occlus-o-Guide® (O-o-G®), for the treatment of Class II malocclusion. Methods Sixty-five patients with Class II Division 1 malocclusion were divided into three groups and were analyzed through cephalometric analysis of skeletal, dental, and esthetic variables before and after treatment. The first group of 23 patients (F 9; M 14; mean age 10.3 ± 1.08 years) was treated with FR-2, the second group of 18 patients (F 8; M 10; mean age 10.7 ± 1.05 years) was treated with TB, the third group (F 11; M 13; mean age 9.05 ± 0.39 years) of 24 patients was treated with O-o-G®. The structural effects of the three devices were compared with a control group generated by the growth variations reported in the cephalometric atlas of Bhatia and Leighton. Esthetic analysis was performed comparing the results of the patients treated with a control group of 20 subjects with mandibular retrognathia and Class II Division 1 malocclusion, not subjected to therapy. Results The three devices resulted in a significant increase in mandibular length, with higher results obtained for FR-2 and TB. A statistically significant increase in the IMPA angle was found for the O-o-G® group, and a notable reduction of both overjet and overbite was detected in all three groups of treated patients. The esthetic evaluation showed overall more significant results in the TB group, especially with regard to the reduction of facial convexity. The retrusion of the upper lip was on average more significant in the O-o-G® group, followed by that in the TB. Conclusions All three devices have proven to be effective overall in resolving skeletal changes and improving facial esthetics.Severe or major burns induce a pathophysiological, immune, and inflammatory response that can persist for a long time and affect morbidity and mortality. Severe burns are followed by a "hypermetabolic response", an inflammatory process that can be extensive and become uncontrolled, leading to a generalized catabolic state and delayed healing. Catabolism causes the upregulation of inflammatory cells and innate immune markers in various organs, which may lead to multiorgan failure and death. Burns activate immune cells and cytokine production regulated by damage-associated molecular patterns (DAMPs). Trauma has similar injury-related immune responses, whereby DAMPs are massively released in musculoskeletal injuries and elicit widespread systemic inflammation. Hemorrhagic shock is the main cause of death in trauma. It is hypovolemic, and the consequence of volume loss and the speed of blood loss manifest immediately after injury. In burns, the shock becomes evident within the first 24 h and is hypovolemic-distributive due to the severely compromised regulation of tissue perfusion and oxygen delivery caused by capillary leakage, whereby fluids shift from the intravascular to the interstitial space. https://www.selleckchem.com/products/td139.html In this review, we compare the pathophysiological responses to burns and trauma including their associated clinical patterns.Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.Understanding the degradation mechanisms of aliphatic polymers by thermal oxidation and radio-oxidation is very important in order to assess their lifetime in a variety of industrial applications. We focus here on polyethylene as a prototypical aliphatic polymer. Kinetic models describing the time evolution of the concentration of chain defects and radicals species in the material identify a relevant step in the formation and subsequent decomposition of transient hydroperoxides species, finally leading to carbonyl defects, in particular ketones. In this paper, we first summarize the most relevant mechanistic paths proposed in the literature for hydroperoxide formation and decomposition and, second, revisit them using first principles calculations based on Density Functional Theory (DFT). Our results partially confirm commonly accepted reaction energies, but also propose alternative, more favourable, reaction paths. We highlight the influence of the environment-crystalline or not-on the outcome of some of the studied chemical reactions.
    The performance was compared according to the number of layers and the size of the metal sheet. The results are expected to contribute to sensor-based DLB detection technology.Background To compare the skeletal, dental, and esthetic changes produced by three functional devices, Fränkel-2 appliance (FR-2), Twin Block (TB), and Occlus-o-Guide® (O-o-G®), for the treatment of Class II malocclusion. Methods Sixty-five patients with Class II Division 1 malocclusion were divided into three groups and were analyzed through cephalometric analysis of skeletal, dental, and esthetic variables before and after treatment. The first group of 23 patients (F 9; M 14; mean age 10.3 ± 1.08 years) was treated with FR-2, the second group of 18 patients (F 8; M 10; mean age 10.7 ± 1.05 years) was treated with TB, the third group (F 11; M 13; mean age 9.05 ± 0.39 years) of 24 patients was treated with O-o-G®. The structural effects of the three devices were compared with a control group generated by the growth variations reported in the cephalometric atlas of Bhatia and Leighton. Esthetic analysis was performed comparing the results of the patients treated with a control group of 20 subjects with mandibular retrognathia and Class II Division 1 malocclusion, not subjected to therapy. Results The three devices resulted in a significant increase in mandibular length, with higher results obtained for FR-2 and TB. A statistically significant increase in the IMPA angle was found for the O-o-G® group, and a notable reduction of both overjet and overbite was detected in all three groups of treated patients. The esthetic evaluation showed overall more significant results in the TB group, especially with regard to the reduction of facial convexity. The retrusion of the upper lip was on average more significant in the O-o-G® group, followed by that in the TB. Conclusions All three devices have proven to be effective overall in resolving skeletal changes and improving facial esthetics.Severe or major burns induce a pathophysiological, immune, and inflammatory response that can persist for a long time and affect morbidity and mortality. Severe burns are followed by a "hypermetabolic response", an inflammatory process that can be extensive and become uncontrolled, leading to a generalized catabolic state and delayed healing. Catabolism causes the upregulation of inflammatory cells and innate immune markers in various organs, which may lead to multiorgan failure and death. Burns activate immune cells and cytokine production regulated by damage-associated molecular patterns (DAMPs). Trauma has similar injury-related immune responses, whereby DAMPs are massively released in musculoskeletal injuries and elicit widespread systemic inflammation. Hemorrhagic shock is the main cause of death in trauma. It is hypovolemic, and the consequence of volume loss and the speed of blood loss manifest immediately after injury. In burns, the shock becomes evident within the first 24 h and is hypovolemic-distributive due to the severely compromised regulation of tissue perfusion and oxygen delivery caused by capillary leakage, whereby fluids shift from the intravascular to the interstitial space. https://www.selleckchem.com/products/td139.html In this review, we compare the pathophysiological responses to burns and trauma including their associated clinical patterns.Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.Understanding the degradation mechanisms of aliphatic polymers by thermal oxidation and radio-oxidation is very important in order to assess their lifetime in a variety of industrial applications. We focus here on polyethylene as a prototypical aliphatic polymer. Kinetic models describing the time evolution of the concentration of chain defects and radicals species in the material identify a relevant step in the formation and subsequent decomposition of transient hydroperoxides species, finally leading to carbonyl defects, in particular ketones. In this paper, we first summarize the most relevant mechanistic paths proposed in the literature for hydroperoxide formation and decomposition and, second, revisit them using first principles calculations based on Density Functional Theory (DFT). Our results partially confirm commonly accepted reaction energies, but also propose alternative, more favourable, reaction paths. We highlight the influence of the environment-crystalline or not-on the outcome of some of the studied chemical reactions.
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  • Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (**) is the leading cause of cancer death and ovarian cancer has a high mortality rate.

    Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost
    /
    (
    ) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews.

    Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased an innovative multicomponent implementation intervention, combining low-cost **** testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.
    Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort.

    To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care.

    Randomized, controlled, parallel-group trial. (ClinicalTrials.gov NCT03210987).

    3 Swiss teaching hospitals.

    Adult medical patients who were hospitalized.

    Patients were randomly assigned to bedside or outside the room case presentation.

    The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100) understanding their disease, the therapeutic approach being used, and further plans for care.

    Compared with patients in the outside the room group (
    = 443), those in the bedside presentation group (
    = 476) reported similar knowledge about their m).
    Swiss National Foundation (10531C_ 182422).
    Use of robot-assisted surgery has increased dramatically since its advent in the 1980s, and nearly all surgical subspecialties have adopted it. However, whether it has advantages compared with laparoscopy or open surgery is unknown.

    To assess the quality of evidence and outcomes of robot-assisted surgery compared with laparoscopy and open surgery in adults.

    PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception to April 2021.

    Randomized controlled trials that compared robot-assisted abdominopelvic surgery with laparoscopy, open surgery, or both.

    Two reviewers independently extracted study data and risk of bias.

    A total of 50 studies with 4898 patients were included. Of the 39 studies that reported incidence of Clavien-Dindo complications, 4 (10%) showed fewer complications with robot-assisted surgery. The majority of studies showed no difference in intraoperative complications, conversion rates, and long-term outcomes. Overall, robot-assisted surgery had longer operative duration than laparoscopy, but no obvious difference was seen versus open surgery.

    Heterogeneity was present among and within the included surgical subspecialties, which precluded meta-analysis. Several trials may not have been powered to assess relevant differences in outcomes.

    There is currently no clear advantage with existing robotic platforms, which are costly and increase operative duration. With refinement, competition, and cost reduction, future versions have the potential to improve clinical outcomes without the existing disadvantages.

    None. (PROSPERO CRD42020182027).
    None. (PROSPERO CRD42020182027).Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19 mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols. The master protocols were also designed to test several agent classes prioritized by ACTIV that covered the spectrum of the disease pathophysiology. Each protocol, either adaptive or pragmatic, was designed to efficiently select those treatments that provide benefit to patients while rapidly eliminating those that were either ineffective or unsafe. The ACTIV Therapeutics-Clinical Working Group members describe the process by which these master protocols were designed, developed, and launched. Lessons learned that may be useful in meeting the challenges of a future pandemic are also described.Grey mould caused by Botrytis cinerea is a common post-harvest disease in strawberries, reducing shelf life considerably. We investigated the potential of the yeast-like biocontrol fungus Aureobasidium pullulans (AP-SLU6) vectored by bumblebees (Bombus terrestris) in the Flying Doctors® system to inhibit the pathogen and increase the shelf life of harvested strawberries (cv. Sonata). Using bumblebees as vectors of various biocontrol agents is becoming increasingly popular, but any potentially negative effects on bee performance have been under-studied. https://www.selleckchem.com/JNK.html Our results show that over the 4-week period of the trial the performance and activity of the bees were not negatively affected by A. pullulans. The bees successfully picked up the powder formulation, carried and deposited it on the flowers. The vectoring of the biocontrol agent significantly reduced grey mould development on the harvested fruits by 45 % and increased shelf life by 100 % in comparison to control treatments. This suggests that the biocontrol fungus applied during flowering successfully reduced Botrytis infection and thus effectively protected the fruits from grey mould.
    Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost / ( ) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality. Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. Randomized, controlled, parallel-group trial. (ClinicalTrials.gov NCT03210987). 3 Swiss teaching hospitals. Adult medical patients who were hospitalized. Patients were randomly assigned to bedside or outside the room case presentation. The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100) understanding their disease, the therapeutic approach being used, and further plans for care. Compared with patients in the outside the room group ( = 443), those in the bedside presentation group ( = 476) reported similar knowledge about their m). Swiss National Foundation (10531C_ 182422). Use of robot-assisted surgery has increased dramatically since its advent in the 1980s, and nearly all surgical subspecialties have adopted it. However, whether it has advantages compared with laparoscopy or open surgery is unknown. To assess the quality of evidence and outcomes of robot-assisted surgery compared with laparoscopy and open surgery in adults. PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception to April 2021. Randomized controlled trials that compared robot-assisted abdominopelvic surgery with laparoscopy, open surgery, or both. Two reviewers independently extracted study data and risk of bias. A total of 50 studies with 4898 patients were included. Of the 39 studies that reported incidence of Clavien-Dindo complications, 4 (10%) showed fewer complications with robot-assisted surgery. The majority of studies showed no difference in intraoperative complications, conversion rates, and long-term outcomes. Overall, robot-assisted surgery had longer operative duration than laparoscopy, but no obvious difference was seen versus open surgery. Heterogeneity was present among and within the included surgical subspecialties, which precluded meta-analysis. Several trials may not have been powered to assess relevant differences in outcomes. There is currently no clear advantage with existing robotic platforms, which are costly and increase operative duration. With refinement, competition, and cost reduction, future versions have the potential to improve clinical outcomes without the existing disadvantages. None. (PROSPERO CRD42020182027). None. (PROSPERO CRD42020182027).Working in an unprecedented time frame, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership developed and launched 9 master protocols between 14 April 2020 and 31 May 2021 to allow for the coordinated and efficient evaluation of multiple investigational therapeutic agents for COVID-19. The ACTIV master protocols were designed with a portfolio approach to serve the following patient populations with COVID-19 mild to moderately ill outpatients, moderately ill inpatients, and critically ill inpatients. To facilitate the execution of these studies and minimize start-up time, ACTIV selected several existing networks to launch the master protocols. The master protocols were also designed to test several agent classes prioritized by ACTIV that covered the spectrum of the disease pathophysiology. Each protocol, either adaptive or pragmatic, was designed to efficiently select those treatments that provide benefit to patients while rapidly eliminating those that were either ineffective or unsafe. The ACTIV Therapeutics-Clinical Working Group members describe the process by which these master protocols were designed, developed, and launched. Lessons learned that may be useful in meeting the challenges of a future pandemic are also described.Grey mould caused by Botrytis cinerea is a common post-harvest disease in strawberries, reducing shelf life considerably. We investigated the potential of the yeast-like biocontrol fungus Aureobasidium pullulans (AP-SLU6) vectored by bumblebees (Bombus terrestris) in the Flying Doctors® system to inhibit the pathogen and increase the shelf life of harvested strawberries (cv. Sonata). Using bumblebees as vectors of various biocontrol agents is becoming increasingly popular, but any potentially negative effects on bee performance have been under-studied. https://www.selleckchem.com/JNK.html Our results show that over the 4-week period of the trial the performance and activity of the bees were not negatively affected by A. pullulans. The bees successfully picked up the powder formulation, carried and deposited it on the flowers. The vectoring of the biocontrol agent significantly reduced grey mould development on the harvested fruits by 45 % and increased shelf life by 100 % in comparison to control treatments. This suggests that the biocontrol fungus applied during flowering successfully reduced Botrytis infection and thus effectively protected the fruits from grey mould.
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  • Generally, in Nigeria dumpsites are open and elevate the pollution by increasing the total environment contamination level. This affects not only the site of dumpsites but also the surrounding buildings and area. In the present work, indoor radon activity concentration is tested inside some buildings in the vicinity of dumpsites in Lagos, Nigeria. A passive technique with CR-39 detectors is used. Different buildings around different eight dumpsites were chosen. Radon concentration had ranged from 16.00 ± 3 to 931.00 ± 186 Bqm-3 in the dumpsites. With Mean concentrations range from 120 ± 24 at OKE-ODO to 334 ± 67, at Solus-4 respectively. The present results explain that 63% of the radon activity concentration in indoor air around the selected dumpsites at Lagos city in Nigeria is below the allowed limit from ICRP 200 Bq m-3 while 37% is more than this limit. Based on the measured radon concentration, the annual effective dose and cancer risk are evaluated. The range of ELC is from 242 to 14086 with mean value 3114 ± 1111.The advances of laser-driven electron acceleration offer the promise of great reductions in the size of high-energy electron accelerator facilities. Accordingly, it is desirable to design compact radiation shielding for such facilities. A key component of radiation shielding is the high-energy electron beam dump. In an effort to optimize the electron beam dump design, different material combinations have been simulated with the FLUKA Monte Carlo code in the range of 1-40 GeV. The studied beam dump configurations consist of alternating layers of high-Z material (lead or iron) and low-Z material (high-density concrete or borated polyethylene) in either three-layer or five-layer structures. The designs of various beam dump configuration have been compared and it has been found that the iron and concrete stacking in a three-layer structure with a thick iron layer results in the lowest dose at 1, 10, and 40 GeV. The performance of the beam dump exhibits a strong dependence on the selected materials, the stacking method, the beam dump thickness, as well as the electron energy. This parametric study provides general insights that can be used for compact shielding design of future electron accelerator facilities.This paper analyses the relationship between health and socioeconomic disadvantage by adopting a dynamic approach accounting for spatial and temporal changes across ten domains including social isolation, environment, financial hardship and security. As a first step we develop a measure of overall multidimensional deprivation and undertake a decomposition analysis to explore the role of breadth and duration of deprivation on shaping the deprivation gradient in health. Subsequently, we employ unconditional quantile regression to conduct a distributional analysis of the gradient to understand how the gradient evolves for people with vulnerability in health. https://www.selleckchem.com/products/piperlongumine.html In contrast to the majority of existing studies, we capture health status using a range of nurse measured biomarkers, rather than self reported health measures, taken from the UKHLS and BHPS databases. The first main finding is that the socioeconomic gradient in most of our health measures is not solely attributed to income as it accounts for only 3.8% of total deprivation and thus it is important to account for other domains through a multidimensional deprivation measure in health gradient analysis. Our second finding is the existence of a systematic deprivation gradient for BMI, waist circumference, heart rate, C-reactive protein and HbA1c where evolution over time is an important factor particularly for individuals with greater burden of illness lying at the right tail of the biomarker distribution. Thus cost effective health policy would need to adopt targeted interventions prioritising people experiencing persistent deprivation in dimensions such as housing conditions and social isolation.We compare COVID-19 case loads and mortality across counties that hosted more versus fewer NHL hockey games, NBA basketball games, and NCAA basketball games during the early months of 2020, before any large outbreaks were identified. We find that hosting one additional NHL/NBA game in March 2020 leads to an additional 7520 cases and 658 deaths. Similarly, we find that hosting an additional NCAA Division 1 men's basketball game in March 2020 results in an additional 34 deaths. ****-of-the-envelope calculations suggest that the per-game fatality costs were 200-300 times greater than per-game spending.
    Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures.

    We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 21 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model.

    Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001).

    In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
    In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
    Generally, in Nigeria dumpsites are open and elevate the pollution by increasing the total environment contamination level. This affects not only the site of dumpsites but also the surrounding buildings and area. In the present work, indoor radon activity concentration is tested inside some buildings in the vicinity of dumpsites in Lagos, Nigeria. A passive technique with CR-39 detectors is used. Different buildings around different eight dumpsites were chosen. Radon concentration had ranged from 16.00 ± 3 to 931.00 ± 186 Bqm-3 in the dumpsites. With Mean concentrations range from 120 ± 24 at OKE-ODO to 334 ± 67, at Solus-4 respectively. The present results explain that 63% of the radon activity concentration in indoor air around the selected dumpsites at Lagos city in Nigeria is below the allowed limit from ICRP 200 Bq m-3 while 37% is more than this limit. Based on the measured radon concentration, the annual effective dose and cancer risk are evaluated. The range of ELC is from 242 to 14086 with mean value 3114 ± 1111.The advances of laser-driven electron acceleration offer the promise of great reductions in the size of high-energy electron accelerator facilities. Accordingly, it is desirable to design compact radiation shielding for such facilities. A key component of radiation shielding is the high-energy electron beam dump. In an effort to optimize the electron beam dump design, different material combinations have been simulated with the FLUKA Monte Carlo code in the range of 1-40 GeV. The studied beam dump configurations consist of alternating layers of high-Z material (lead or iron) and low-Z material (high-density concrete or borated polyethylene) in either three-layer or five-layer structures. The designs of various beam dump configuration have been compared and it has been found that the iron and concrete stacking in a three-layer structure with a thick iron layer results in the lowest dose at 1, 10, and 40 GeV. The performance of the beam dump exhibits a strong dependence on the selected materials, the stacking method, the beam dump thickness, as well as the electron energy. This parametric study provides general insights that can be used for compact shielding design of future electron accelerator facilities.This paper analyses the relationship between health and socioeconomic disadvantage by adopting a dynamic approach accounting for spatial and temporal changes across ten domains including social isolation, environment, financial hardship and security. As a first step we develop a measure of overall multidimensional deprivation and undertake a decomposition analysis to explore the role of breadth and duration of deprivation on shaping the deprivation gradient in health. Subsequently, we employ unconditional quantile regression to conduct a distributional analysis of the gradient to understand how the gradient evolves for people with vulnerability in health. https://www.selleckchem.com/products/piperlongumine.html In contrast to the majority of existing studies, we capture health status using a range of nurse measured biomarkers, rather than self reported health measures, taken from the UKHLS and BHPS databases. The first main finding is that the socioeconomic gradient in most of our health measures is not solely attributed to income as it accounts for only 3.8% of total deprivation and thus it is important to account for other domains through a multidimensional deprivation measure in health gradient analysis. Our second finding is the existence of a systematic deprivation gradient for BMI, waist circumference, heart rate, C-reactive protein and HbA1c where evolution over time is an important factor particularly for individuals with greater burden of illness lying at the right tail of the biomarker distribution. Thus cost effective health policy would need to adopt targeted interventions prioritising people experiencing persistent deprivation in dimensions such as housing conditions and social isolation.We compare COVID-19 case loads and mortality across counties that hosted more versus fewer NHL hockey games, NBA basketball games, and NCAA basketball games during the early months of 2020, before any large outbreaks were identified. We find that hosting one additional NHL/NBA game in March 2020 leads to an additional 7520 cases and 658 deaths. Similarly, we find that hosting an additional NCAA Division 1 men's basketball game in March 2020 results in an additional 34 deaths. Back-of-the-envelope calculations suggest that the per-game fatality costs were 200-300 times greater than per-game spending. Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures. We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 21 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model. Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001). In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events. In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.
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