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  • 7,8-DHF treatment significantly reduced HFD and EtOH-induced oxidative stress as evidenced by the reduction of lipid peroxidation and augmentation of reduced glutathione level. Moreover, IL-1β level was found significantly reduced in 7,8-DHF treated EtOH, HFD and EtOH+HFD groups. The semi-quantitative RT-PCR results indicated down-regulation of Nrf-2 and HO-1 and up-regulation of NF-KB and iNOS mRNA expression level in the liver of HFD and EtOH-fed rats, which was ameliorated by 7,8-DHF treatment. CONCLUSION The present study suggested that 7,8-DHF could be an effective pharmacological intervention in combating HFD and EtOH-induced hepatotoxicity.BACKGROUND Coumarin and 3,4-dihydroquinolinone nuclei are two heterocyclic rings that are important and widely exploited for the development of bioactive molecules. Here, we designed and synthesized a series of 3,4-dihydroquinolinone and coumarin derivatives (Compounds 8,9,11,14,15,18-20, 23, 24 and 28 are new compounds) and studied their antidepressant activities. https://www.selleckchem.com/products/pp1.html METHODS Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The most active compound was used to evaluate the exploratory activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate if the compound has an effect on the mouse brain, by using ELISA. A 5-HT1A binding assay was also performed. The biological activities of the compounds were verified by molecular docking studies. The physicochemical and pharmacokinetic properties of the target compounds were predicted by Discovery Studio and ChemBioDraw Ultra. RESULTS Of all the compounds tested, compound 7 showed the best antidepressant activity, which decreased the immobility time by 65.52 s in FST. However, in the open-field test, compound 7 did not affect spontaneous activity. The results of 5-HT concentration estimation in vivo showed that compound 7 may have an effect on the mouse brain. Molecular docking results indicated that compound 7 showed significant interactions with residues at the 5-HT1A receptor using homology modeling. The results show that compound 7 exhibits good affinity for the 5-HT1A receptor. CONCLUSION Coumarin and 3,4-dihydroquinolinone derivatives synthesized in this study have a significant antidepressant activity. These findings can be useful in the design and synthesis of novel antidepressants.BACKGROUND The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of chohnesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. METHOD We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schrodinger, LLC, New York, NY, 2019). RESULTS The title compounds showed moderate inhibition at 100 μg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. CONCLUSION This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.BACKGROUND Anxiety is a disorder of multi-factorial pathogenesis involving interrelated pathways of neurotransmitters, oxidative stress and metamorphosed calcium-signaling that negatively affects brain functions. Modulation of Ca2+-channels outlines a promising strategy to curb the progression of anxietylike disorders through attenuation of redox-imbalance. The current research scheme was designed to explore the anxiolytic effects of lacidipine (I-type Ca2+-channel blocker; LCD) pretreatment in caffeine-induced anxiety-like symptom model in ****. METHODS Forty-two Swiss albino **** (25-30g) were distributed to 7 groups (n = 6) Vehicle control, caffeine, alprazolam + caffeine, lacidipine(0.3,1 and 3 mg/kg, ip)+caffeine and Bay-K8644+LCD (3)+caffeine. Caffeine (25 mg/kg, ip) was administered from day 8 to 14 to induce anxiety-like symptoms in ****. Lacidipine (0.3,1 and 3 mg/kg, ip) and alprazolam (0.25 mg/kg, ip) were administered from day 1 to 14 in separate groups. Bay-K8644 (Ca2+-channel agonist) was injected on day 14 to delineate the role of Ca2+ in anti-anxiety effect of LCD in caffeine-treated ****. Elevated zero maze and mirror chamber test were employed to assess anxiety-like behavior. Afterwards, the **** were sacrificed and whole brains were harvested for estimation of biomarkers of oxido-nitrosative stress, such as TBARS, GSH, ***, catalase and total nitrite content. RESULTS An increase in brain oxido-nitrosative stress and anxiety-like behavior was observed in caffeine treated ****. LCD pretreatment attenuated the brain oxido-nitrosative stress and anxiety-like behavior in **** in caffeine treated ****. Anxiolytic effect of LCD was attenuated by Bay-K8644 (0.5 mg/kg) in caffeine treated ****. CONCLUSION LCD (I-type Ca2+-channel antagonist) pretreatment attenuated caffeine-induced oxido-nitrosative stress and anxiety-like behavior.
    7,8-DHF treatment significantly reduced HFD and EtOH-induced oxidative stress as evidenced by the reduction of lipid peroxidation and augmentation of reduced glutathione level. Moreover, IL-1β level was found significantly reduced in 7,8-DHF treated EtOH, HFD and EtOH+HFD groups. The semi-quantitative RT-PCR results indicated down-regulation of Nrf-2 and HO-1 and up-regulation of NF-KB and iNOS mRNA expression level in the liver of HFD and EtOH-fed rats, which was ameliorated by 7,8-DHF treatment. CONCLUSION The present study suggested that 7,8-DHF could be an effective pharmacological intervention in combating HFD and EtOH-induced hepatotoxicity.BACKGROUND Coumarin and 3,4-dihydroquinolinone nuclei are two heterocyclic rings that are important and widely exploited for the development of bioactive molecules. Here, we designed and synthesized a series of 3,4-dihydroquinolinone and coumarin derivatives (Compounds 8,9,11,14,15,18-20, 23, 24 and 28 are new compounds) and studied their antidepressant activities. https://www.selleckchem.com/products/pp1.html METHODS Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The most active compound was used to evaluate the exploratory activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate if the compound has an effect on the mouse brain, by using ELISA. A 5-HT1A binding assay was also performed. The biological activities of the compounds were verified by molecular docking studies. The physicochemical and pharmacokinetic properties of the target compounds were predicted by Discovery Studio and ChemBioDraw Ultra. RESULTS Of all the compounds tested, compound 7 showed the best antidepressant activity, which decreased the immobility time by 65.52 s in FST. However, in the open-field test, compound 7 did not affect spontaneous activity. The results of 5-HT concentration estimation in vivo showed that compound 7 may have an effect on the mouse brain. Molecular docking results indicated that compound 7 showed significant interactions with residues at the 5-HT1A receptor using homology modeling. The results show that compound 7 exhibits good affinity for the 5-HT1A receptor. CONCLUSION Coumarin and 3,4-dihydroquinolinone derivatives synthesized in this study have a significant antidepressant activity. These findings can be useful in the design and synthesis of novel antidepressants.BACKGROUND The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of chohnesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. METHOD We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schrodinger, LLC, New York, NY, 2019). RESULTS The title compounds showed moderate inhibition at 100 μg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. CONCLUSION This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.BACKGROUND Anxiety is a disorder of multi-factorial pathogenesis involving interrelated pathways of neurotransmitters, oxidative stress and metamorphosed calcium-signaling that negatively affects brain functions. Modulation of Ca2+-channels outlines a promising strategy to curb the progression of anxietylike disorders through attenuation of redox-imbalance. The current research scheme was designed to explore the anxiolytic effects of lacidipine (I-type Ca2+-channel blocker; LCD) pretreatment in caffeine-induced anxiety-like symptom model in mice. METHODS Forty-two Swiss albino mice (25-30g) were distributed to 7 groups (n = 6) Vehicle control, caffeine, alprazolam + caffeine, lacidipine(0.3,1 and 3 mg/kg, ip)+caffeine and Bay-K8644+LCD (3)+caffeine. Caffeine (25 mg/kg, ip) was administered from day 8 to 14 to induce anxiety-like symptoms in mice. Lacidipine (0.3,1 and 3 mg/kg, ip) and alprazolam (0.25 mg/kg, ip) were administered from day 1 to 14 in separate groups. Bay-K8644 (Ca2+-channel agonist) was injected on day 14 to delineate the role of Ca2+ in anti-anxiety effect of LCD in caffeine-treated mice. Elevated zero maze and mirror chamber test were employed to assess anxiety-like behavior. Afterwards, the mice were sacrificed and whole brains were harvested for estimation of biomarkers of oxido-nitrosative stress, such as TBARS, GSH, SOD, catalase and total nitrite content. RESULTS An increase in brain oxido-nitrosative stress and anxiety-like behavior was observed in caffeine treated mice. LCD pretreatment attenuated the brain oxido-nitrosative stress and anxiety-like behavior in mice in caffeine treated mice. Anxiolytic effect of LCD was attenuated by Bay-K8644 (0.5 mg/kg) in caffeine treated mice. CONCLUSION LCD (I-type Ca2+-channel antagonist) pretreatment attenuated caffeine-induced oxido-nitrosative stress and anxiety-like behavior.
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  • optimal clinical management strategies. https://www.selleckchem.com/products/ory-1001-rg-6016.html © AlphaMed Press 2020.in English, Spanish OBJETIVO La Anorexia Nerviosa (AN) está asociada con características neuropsicológicas como alteraciones en la coherencia central, flexibilidad cognitiva, y reconocimiento de emociones. Las mismas características también se manifiestan en los trastornos del espectro autista (TEA), y se ha sugerido que se asocian con una prolongación de la enfermedad de la AN. El propósito de este meta-análisis fue examinar si las características neuropsicológicas pronunciadas relacionadas al TEA están asociadas con la duración de la enfermedad en la AN. MÉTODOS Se investigó en cuatro bases de datos (Medline, PsycINFO, Scopus, PubMed) para encontrar estudios elegibles. Los términos de búsqueda fueron 1) “anorexia nerviosa”, y 2) “flexibilidad cognitiva” o “cambio de un tipo de información a otro (set shifting)” o “coherencia central” o “reconocimiento de emociones” o “teoría de la mente”. La muestra final consistió en 53 estudios. La duración de la AN fue dividida en tres categorías para poder investigar las diferencias entre los grupos con una duración variable de la enfermedad. El meta-análisis fue realizado con Review Manager utilizando un modelo de efecto aleatorio. RESULTADOS Los déficits en la coherencia central, flexibilidad cognitiva, y el reconocimiento de emociones fueron más pronunciados en los individuos con AN prolongada en comparación con aquellos con una menor duración de la enfermedad. DISCUSIÓN Un curso prolongado de AN parece estar asociado con características neuropsicológicas subyacentes que también son distintivas de los TEA. Las alteraciones neuropsicológicas pueden llevar a una AN prolongada y la enfermedad prolongada puede contribuir al posterior “efecto de cicatriz neurológica”, reforzando aún más estas alteraciones.Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis (CT) serovars L1-L3 1 . In Europe, it is endemic among men who have sex with men (MSM) causing proctitis, mainly co-infected with HIV, since 2003 2 . Its presentation as a genital lesion has been rarely described and accounts for around 5% of cases in the United Kingdom and France 3,4 . Increasing STIs rates in MSM have been reported during the last decade in several Western countries 5 , and it is plausible that HIV pre-exposure prophylaxis (PrEP) might contribute to maintaining this trend 6 . We report 2 cases with genital primary LGV mimicking primary syphilis seen at in our clinic in Barcelona. This article is protected by copyright. All rights reserved.BACKGROUND Alpha1-antitrypsin deficiency (AATD) is an under-diagnosed hereditary disorder characterized by reduced serum levels of alpha1-antitrypsin (AAT) and increased risk to develop lung and liver diseases at an early age. AAT is encoded by the highly polymorphic SERPINA1 gene. The most common deficiency alleles are S and Z, but more than 150 rare variants lead to low levels of the protein. To identify these pathological allelic variants, sequencing is required. Since traditional sequencing is expensive and time-consuming, we evaluated the accuracy of A1AT Genotyping Test, a new diagnostic genotyping kit which allows to simultaneously identify and genotype 14 deficiency variants of the SERPINA1 gene based on Luminex technology. METHODS A total of 418 consecutive samples with AATD suspicion and submitted to the Italian Reference laboratory between January and April 2016 were analyzed both by applying the diagnostic algorithm currently in use, and by applying A1AT Genotyping Test. RESULTS The assay gave the following results 101 samples (24.2%) were positive for at least one of the 14 deficiency variants, 316 (75.6%) were negative for all the variants analyzed. The identified mutations showed a 100% correlation with the results obtained with our diagnostic algorithm. Seventeen samples (4%) resulted negative for the assay but sequencing identified other rare pathological variants in SERPINA1 gene. CONCLUSION The A1AT Genotyping Test assay was highly reliable and robust and allowed shorter diagnostic times. In few cases, it has been necessary to sequence the SERPINA1 gene to identify other rare mutations not included in the kit. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.Facile synthesis of various benzonaphthofurans was achieved by intramolecular hydroarylation of 1,4-disilyl-2-aryloxy-1,3-enynes followed by cycloaddition with arynes or alkenes and finally desilylaromatization. The three-step transformation can be operated sequentially in one-pot, providing with a range of furanoacenes easily and highly effectively. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy. © 2020 Wiley Periodicals, Inc.
    optimal clinical management strategies. https://www.selleckchem.com/products/ory-1001-rg-6016.html © AlphaMed Press 2020.in English, Spanish OBJETIVO La Anorexia Nerviosa (AN) está asociada con características neuropsicológicas como alteraciones en la coherencia central, flexibilidad cognitiva, y reconocimiento de emociones. Las mismas características también se manifiestan en los trastornos del espectro autista (TEA), y se ha sugerido que se asocian con una prolongación de la enfermedad de la AN. El propósito de este meta-análisis fue examinar si las características neuropsicológicas pronunciadas relacionadas al TEA están asociadas con la duración de la enfermedad en la AN. MÉTODOS Se investigó en cuatro bases de datos (Medline, PsycINFO, Scopus, PubMed) para encontrar estudios elegibles. Los términos de búsqueda fueron 1) “anorexia nerviosa”, y 2) “flexibilidad cognitiva” o “cambio de un tipo de información a otro (set shifting)” o “coherencia central” o “reconocimiento de emociones” o “teoría de la mente”. La muestra final consistió en 53 estudios. La duración de la AN fue dividida en tres categorías para poder investigar las diferencias entre los grupos con una duración variable de la enfermedad. El meta-análisis fue realizado con Review Manager utilizando un modelo de efecto aleatorio. RESULTADOS Los déficits en la coherencia central, flexibilidad cognitiva, y el reconocimiento de emociones fueron más pronunciados en los individuos con AN prolongada en comparación con aquellos con una menor duración de la enfermedad. DISCUSIÓN Un curso prolongado de AN parece estar asociado con características neuropsicológicas subyacentes que también son distintivas de los TEA. Las alteraciones neuropsicológicas pueden llevar a una AN prolongada y la enfermedad prolongada puede contribuir al posterior “efecto de cicatriz neurológica”, reforzando aún más estas alteraciones.Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis (CT) serovars L1-L3 1 . In Europe, it is endemic among men who have sex with men (MSM) causing proctitis, mainly co-infected with HIV, since 2003 2 . Its presentation as a genital lesion has been rarely described and accounts for around 5% of cases in the United Kingdom and France 3,4 . Increasing STIs rates in MSM have been reported during the last decade in several Western countries 5 , and it is plausible that HIV pre-exposure prophylaxis (PrEP) might contribute to maintaining this trend 6 . We report 2 cases with genital primary LGV mimicking primary syphilis seen at in our clinic in Barcelona. This article is protected by copyright. All rights reserved.BACKGROUND Alpha1-antitrypsin deficiency (AATD) is an under-diagnosed hereditary disorder characterized by reduced serum levels of alpha1-antitrypsin (AAT) and increased risk to develop lung and liver diseases at an early age. AAT is encoded by the highly polymorphic SERPINA1 gene. The most common deficiency alleles are S and Z, but more than 150 rare variants lead to low levels of the protein. To identify these pathological allelic variants, sequencing is required. Since traditional sequencing is expensive and time-consuming, we evaluated the accuracy of A1AT Genotyping Test, a new diagnostic genotyping kit which allows to simultaneously identify and genotype 14 deficiency variants of the SERPINA1 gene based on Luminex technology. METHODS A total of 418 consecutive samples with AATD suspicion and submitted to the Italian Reference laboratory between January and April 2016 were analyzed both by applying the diagnostic algorithm currently in use, and by applying A1AT Genotyping Test. RESULTS The assay gave the following results 101 samples (24.2%) were positive for at least one of the 14 deficiency variants, 316 (75.6%) were negative for all the variants analyzed. The identified mutations showed a 100% correlation with the results obtained with our diagnostic algorithm. Seventeen samples (4%) resulted negative for the assay but sequencing identified other rare pathological variants in SERPINA1 gene. CONCLUSION The A1AT Genotyping Test assay was highly reliable and robust and allowed shorter diagnostic times. In few cases, it has been necessary to sequence the SERPINA1 gene to identify other rare mutations not included in the kit. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.Facile synthesis of various benzonaphthofurans was achieved by intramolecular hydroarylation of 1,4-disilyl-2-aryloxy-1,3-enynes followed by cycloaddition with arynes or alkenes and finally desilylaromatization. The three-step transformation can be operated sequentially in one-pot, providing with a range of furanoacenes easily and highly effectively. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy. © 2020 Wiley Periodicals, Inc.
    0 Commentarios 0 Acciones 8 Views 0 Vista previa

  • eir implant choice to a nonreactive metal component, and 22.85% would choose not to perform TMJR. CONCLUSIONS The results from the present study have demonstrated that respondent TMJ surgeons agree that metal hypersensitivity occurs with TMJR. However, their approaches to screening and managing metal hypersensitivity vary. Further research of this topic is required to eventually develop specific management pre- and postoperative guidelines for the treatment of patients with metal sensitivities. PURPOSE In reconstructive microsurgery, severe arteriosclerosis is a known predictor for free flap failure because of problems with the vascular anastomosis. We investigated whether the ankle brachial index (ABI) could be a suitable preoperative measurement for the prediction of compromise regarding vascular anastomosis in patients undergoing microsurgical reconstruction. https://www.selleckchem.com/products/odm-201.html MATERIAL AND METHODS We conducted a prospective cohort study of patients who had undergone reconstructive microvascular surgery in a tertiary care center from 2015 to 2017. The ABI was preoperatively assessed by dividing the systolic blood pressure measured at the ankle by the brachial systolic blood pressure. Results from 0.9 to 1.3 are within the physiologic range. Values less than 0.9 indicate moderate to severe arteriosclerosis, and those greater than 1.3 indicate the major form of arteriosclerosis with complete calcification of the tunica media. The ABI value correlated with the ease of the anastomosis (rated from 1 [very straightforwarSIONS A pathologic ABI was associated with increased difficulty with the microvascular anastomosis. BACKGROUND The effectiveness of contact isolation for decreasing the spread of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) has been questioned. The aim of this study was to establish the benefits of contact isolation over standard precautions for reducing the incidence density of ESBL-E colonisation and infection in adult medical and surgical wards with an active surveillance culture programme. METHODS We did a cluster-randomised crossover trial in adult wards in four European university hospitals. Medical, surgical, or combined medical-surgical wards without critical care were randomised to continue standard precautions alone or implement contact isolation alongside standard precautions for 12 months, followed by a 1 month washout period and 12 months of the alternate strategy. Randomisation was done via a computer-generated sequence, with a block size of two consecutive wards. Only laboratory technicians and data analysts were masked to allocation. Patients were screened for ESBL-E car7) during periods of standard precautions (p=0·9710). Multivariable analysis adjusted for length of stay, percentage of patients screened, and prevalence in first screening cultures yielded an incidence rate ratio of 0·99 (95% CI 0·80-1·22; p=0·9177) for care under contact isolation compared with standard precautions. INTERPRETATION Contact isolation showed no benefit when added to standard precautions for controlling the spread of ESBL-E on non-critical care wards with extensive surveillance screening. FUNDING European Commission. Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the patterns of usage and neuropsychobiological effects of both mephedrone and MDMA. Both drugs share common psychoactive effects, the duration of which is significantly shorter with mephedrone use, attributing towards a pattern of binge use among users. Both drugs have also been associated with adverse health, psychiatric, and neurocognitive problems. Whilst there is extensive research into the psychobiological problems induced by MDMA, the evidence for mephedrone is comparatively limited. The adverse effect profile of mephedrone appears to be less severe than that of MDMA. Users often believe it to be safer, although both drugs have been associated with overdoses. The neurotoxic potential of mephedrone appears to be low, whereas MDMA can cause long-term damage to the serotonergic system, although this needs further investigation. The abuse liability of mephedrone is significantly greater than that of MDMA, raising concerns regarding the impact of lifetime usage on users. Given that mephedrone is relatively new, the effects of long-term exposure are yet to be documented. Future research focused on lifetime users may highlight more severe neuropsychobiological effects from the drug. V.Sleep is involved in metabolic system, mental health and cognitive functions. Evidence shows that sleep deprivation (SD) negatively affects mental health and impairs cognitive functions, including learning and memory. Furthermore, the metabotropic glutamate receptor subtype 5 (mGluR5) is a metabolic biomarker, which is affected by various conditions, including stress, sleep deprivation, and cognitive and psychiatric disorders. In this research, we investigated the effect of SD and reverse circadian (RC), and two models of napping (continuous and non-continuous) combined with SD or RC on fear-conditioning memory, anxiety-like behavior and mGluR5 fluctuations in the amygdala. 64 male Wistar rats were used in this study. The water box apparatus was used to induce SD/RC for 48 h, and fear-conditioning memory apparatus was used to assess fear memory. The results showed, fear-conditioning memory was impaired following SD and RC, especially in contextual stage. However, anxiety-like behavior was increased. Furthermore, mGluR5 was increased in the left amygdala more than the right amygdala. Additionally, continuous napping significantly improved fear-conditioning memory, especially freezing behavior. In conclusion, following SD and RC, fear-conditioning memory in contextual stage is more vulnerable than in auditory stage. Furthermore, increase in anxiety-like behavior is related to increase in the activity of left amygdala and mGluR5 receptors. Acetylcholinesterase (AChE) terminates cholinergic neurotransmission by hydrolyzing acetylcholine. The collagen-tailed AChE tetramer is a product of 2 genes, ACHE and ColQ. The AChE tetramer consists of 4 identical AChE subunits and one polyproline-rich peptide, whose function is to hold the 4 AChE subunits together. Our goal was to determine the amino acid sequence of the polyproline-rich peptide(s) in Torpedo californica AChE (TcAChE) tetramers to aid in the analysis of images that will be acquired by cryo-EM. Collagen-tailed AChE was solubilized from Torpedo californica electric organ, converted to 300 kDa tetramers by digestion with trypsin, and purified by affinity chromatography. Polyproline-rich peptides were released by denaturing the TcAChE tetramers in a boiling water bath, and reducing disulfide bonds with dithiothreitol. Carbamidomethylated peptides were separated from TcAChE protein on a spin filter before they were analyzed by liquid chromatography tandem mass spectrometry on a high resolution Orbitrap Fusion Lumos mass spectrometer.
    eir implant choice to a nonreactive metal component, and 22.85% would choose not to perform TMJR. CONCLUSIONS The results from the present study have demonstrated that respondent TMJ surgeons agree that metal hypersensitivity occurs with TMJR. However, their approaches to screening and managing metal hypersensitivity vary. Further research of this topic is required to eventually develop specific management pre- and postoperative guidelines for the treatment of patients with metal sensitivities. PURPOSE In reconstructive microsurgery, severe arteriosclerosis is a known predictor for free flap failure because of problems with the vascular anastomosis. We investigated whether the ankle brachial index (ABI) could be a suitable preoperative measurement for the prediction of compromise regarding vascular anastomosis in patients undergoing microsurgical reconstruction. https://www.selleckchem.com/products/odm-201.html MATERIAL AND METHODS We conducted a prospective cohort study of patients who had undergone reconstructive microvascular surgery in a tertiary care center from 2015 to 2017. The ABI was preoperatively assessed by dividing the systolic blood pressure measured at the ankle by the brachial systolic blood pressure. Results from 0.9 to 1.3 are within the physiologic range. Values less than 0.9 indicate moderate to severe arteriosclerosis, and those greater than 1.3 indicate the major form of arteriosclerosis with complete calcification of the tunica media. The ABI value correlated with the ease of the anastomosis (rated from 1 [very straightforwarSIONS A pathologic ABI was associated with increased difficulty with the microvascular anastomosis. BACKGROUND The effectiveness of contact isolation for decreasing the spread of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) has been questioned. The aim of this study was to establish the benefits of contact isolation over standard precautions for reducing the incidence density of ESBL-E colonisation and infection in adult medical and surgical wards with an active surveillance culture programme. METHODS We did a cluster-randomised crossover trial in adult wards in four European university hospitals. Medical, surgical, or combined medical-surgical wards without critical care were randomised to continue standard precautions alone or implement contact isolation alongside standard precautions for 12 months, followed by a 1 month washout period and 12 months of the alternate strategy. Randomisation was done via a computer-generated sequence, with a block size of two consecutive wards. Only laboratory technicians and data analysts were masked to allocation. Patients were screened for ESBL-E car7) during periods of standard precautions (p=0·9710). Multivariable analysis adjusted for length of stay, percentage of patients screened, and prevalence in first screening cultures yielded an incidence rate ratio of 0·99 (95% CI 0·80-1·22; p=0·9177) for care under contact isolation compared with standard precautions. INTERPRETATION Contact isolation showed no benefit when added to standard precautions for controlling the spread of ESBL-E on non-critical care wards with extensive surveillance screening. FUNDING European Commission. Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the patterns of usage and neuropsychobiological effects of both mephedrone and MDMA. Both drugs share common psychoactive effects, the duration of which is significantly shorter with mephedrone use, attributing towards a pattern of binge use among users. Both drugs have also been associated with adverse health, psychiatric, and neurocognitive problems. Whilst there is extensive research into the psychobiological problems induced by MDMA, the evidence for mephedrone is comparatively limited. The adverse effect profile of mephedrone appears to be less severe than that of MDMA. Users often believe it to be safer, although both drugs have been associated with overdoses. The neurotoxic potential of mephedrone appears to be low, whereas MDMA can cause long-term damage to the serotonergic system, although this needs further investigation. The abuse liability of mephedrone is significantly greater than that of MDMA, raising concerns regarding the impact of lifetime usage on users. Given that mephedrone is relatively new, the effects of long-term exposure are yet to be documented. Future research focused on lifetime users may highlight more severe neuropsychobiological effects from the drug. V.Sleep is involved in metabolic system, mental health and cognitive functions. Evidence shows that sleep deprivation (SD) negatively affects mental health and impairs cognitive functions, including learning and memory. Furthermore, the metabotropic glutamate receptor subtype 5 (mGluR5) is a metabolic biomarker, which is affected by various conditions, including stress, sleep deprivation, and cognitive and psychiatric disorders. In this research, we investigated the effect of SD and reverse circadian (RC), and two models of napping (continuous and non-continuous) combined with SD or RC on fear-conditioning memory, anxiety-like behavior and mGluR5 fluctuations in the amygdala. 64 male Wistar rats were used in this study. The water box apparatus was used to induce SD/RC for 48 h, and fear-conditioning memory apparatus was used to assess fear memory. The results showed, fear-conditioning memory was impaired following SD and RC, especially in contextual stage. However, anxiety-like behavior was increased. Furthermore, mGluR5 was increased in the left amygdala more than the right amygdala. Additionally, continuous napping significantly improved fear-conditioning memory, especially freezing behavior. In conclusion, following SD and RC, fear-conditioning memory in contextual stage is more vulnerable than in auditory stage. Furthermore, increase in anxiety-like behavior is related to increase in the activity of left amygdala and mGluR5 receptors. Acetylcholinesterase (AChE) terminates cholinergic neurotransmission by hydrolyzing acetylcholine. The collagen-tailed AChE tetramer is a product of 2 genes, ACHE and ColQ. The AChE tetramer consists of 4 identical AChE subunits and one polyproline-rich peptide, whose function is to hold the 4 AChE subunits together. Our goal was to determine the amino acid sequence of the polyproline-rich peptide(s) in Torpedo californica AChE (TcAChE) tetramers to aid in the analysis of images that will be acquired by cryo-EM. Collagen-tailed AChE was solubilized from Torpedo californica electric organ, converted to 300 kDa tetramers by digestion with trypsin, and purified by affinity chromatography. Polyproline-rich peptides were released by denaturing the TcAChE tetramers in a boiling water bath, and reducing disulfide bonds with dithiothreitol. Carbamidomethylated peptides were separated from TcAChE protein on a spin filter before they were analyzed by liquid chromatography tandem mass spectrometry on a high resolution Orbitrap Fusion Lumos mass spectrometer.
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  • f 136 [27.9%] vs 66 of 411 [16.1%]; adjusted odds ratio, 2.37; 95% CI, 1.06-5.29), alcohol use (25 of 136 [18.4%] vs 30 of 411 [7.3%]; adjusted odds ratio, 2.98; 95% CI, 1.26-7.04), and clinical externalizing behaviors (31 of 136 [22.8%] vs 47 of 411 [11.4%]; adjusted odds ratio, 2.76; 95% CI, 1.11-6.84) at follow-up, controlling for baseline variables. Conclusion and Relevance This study suggests that recent immigration policy changes may be associated with critical outcomes jeopardizing the health of Latino or Latina adolescents. Since 95% of US Latino or Latina adolescents are citizens, compromised mental health and risk behavior tied to family member detention or deportation raises concerns regarding the association of current immigration policies with the mental health of Latino and Latina adolescents in the United States.MOTIVATION Low-dimensional representations of high-dimensional data are routinely employed in biomedical research to visualize, interpret and communicate results from different pipelines. In this article, we propose a novel procedure to directly estimate t-SNE embeddings that are not driven by batch effects. Without correction, interesting structure in the data can be obscured by batch effects. The proposed algorithm can therefore significantly aid visualization of high-dimensional data. RESULTS The proposed methods are based on linear algebra and constrained optimization, leading to efficient algorithms and fast computation in many high-dimensional settings. Results on artificial single-cell transcription profiling data show that the proposed procedure successfully removes multiple batch effects from t-SNE embeddings, while retaining fundamental information on cell types. When applied to single-cell gene expression data to investigate mouse medulloblastoma, the proposed method successfully removes batches related with **** identifiers and the date of the experiment, while preserving clusters of oligodendrocytes, astrocytes, and endothelial cells and microglia, which are expected to lie in the stroma within or adjacent to the tumors. AVAILABILITY Source code implementing the proposed approach is available as an R package at https//github.com/emanuelealiverti/BC_tSNE, including a tutorial to reproduce the simulation studies. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.in English, Portuguese Esse estudo objetivou avaliar a perda dentária severa e seus fatores associadas em idosos. Um estudo transversal, de base populacional, usando uma amostra probabilística, foi condu zido com os idosos de Cruz Alta, Rio Grande do Sul, Brasil. Exames de saúde bucal e um questionário estruturado foram realizados. Associações entre perda dentária severa e as variáveis independentes foram feitas, utilizando regressão de Poisson com variância robusta. O nível de significância adotado foi de 5%. No total, 287 idosos foram incluídos. Entre os idosos, 86 (29,9%) eram edêntulos, e 282 (98,3%) apresen tavam pelo menos uma perda dentária. Nessa amostra, a mediana de perda dentária foi 21 (média ± desvio padrão 19,69±8,21). A amostra foi dividida em dois grupos de acordo com a definição de perda dentária severa menos de nove dentes remanescentes ou ≥9 dentes presentes. A prevalência de perda dentária severa foi de 60,3% (n=173). As mulheres estiveram associadas com maior razão de prevalência (RP) de terem perda dentária severa (RP; IC95% 1,77; 1,39 – 2,24). Alto nível educacional esteve associados com menor RP de ter perda dentária severa (RP; IC95% 0,48; 0,30 – 0,77). A falta de acesso ao dentista esteve associada com maiores taxas de perda de dentária severa (RP; IC95% 1,38; 1,13 – 1,67). Por outro lado, frequência de escovação não esteve significati vamente associada perda dentária severa (RP; IC95% 0,88; 0,73 – 1,06). Alta prevalência de perda dentária severa foi detectada entre os idosos e ela foi associada com sexo, nível educacional, e acesso ao dentista.in English, Portuguese A halitose é altamente prevalente na periodontite e é atribuída principalmente à presença de compostos sulforosos voláteis (CSV), sendo o sulfeto de hidrogênio (H2S) o principal gás relacionado ao mau odor e que pode estar envolvido na patogênese da doença periodontal. O objetivo deste estudo foi avaliar o efeito agudo, intermediário e crônico do H2S na resposta imunoinflamatória e na perda óssea alveolar em ratos, com e sem doença periodontal induzida. Trinta e seis ratos foram divididos em 2 grupos teste (n = 18), ratos expostos ao H2S (NaHS molécula doadora de H2S) e grupo controle (n = 18), ratos tratados apenas com solução salina (Ctrl). Todos os animais tiveram um dos seus segundos molares inferiores submetidos à colocação de uma ligadura para o desenvolvimento da doença periodontal (DP), em comparação com o dente contralateral saudável (H). https://www.selleckchem.com/products/pp1.html Cada grupo foi subdividido em 3 (n = 6), de acordo com o tempo de eutanásia (3h, 5 dias e 14 dias). Os tecidos gengivais foram utilizados para a análise da expressão gênica (IL1, IL6, RANKL, OPG e SOFAT) por PCR em tempo real e as mandíbulas foram analisadas morfometricamente. Análise dos dados demonstrou que a ligadura promoveu perda óssea alveolar, observada principalmente aos 14 dias, tanto no grupo exposto ao H2S quanto no grupo Ctrl. A administração de H2S não resultou em perda óssea adicional. A expressão gênica demonstrou aumento significativo de IL1, IL6, RANKL e SOFAT apenas no grupo CtrlPD (p less then 0,05). Uma significativa regulação negativa na expressão de OPG foi observada ao longo do tempo no grupo CtrlPD (p less then 0,05). Podese concluir que o H2S não teve efeito adicional na perda óssea alveolar, na ausência de ligadura. Entretanto, na presença de ligadura, a exposição ao H2S teve um efeito imunorregulatório na expressão de citocinas próinflamatórias e próreabsortivas.in English, Portuguese O objetivo deste estudo foi determinar a ocorrência de hipersensibilidade dentinária (HD) autorreportada e seus indicadores de risco de uma cidade do sul do Brasil. 736 estudantes (1519 anos) foram selecionados aleatoriamente em 20 escolas públicas e privadas da cidade de Passo Fundo, Brasil. HD foi aferida pela resposta em escala Likert à pergunta “Você tem sensibilidade nos dentes?”. O exame clínico incluía a contagem de dentes presentes e um questionário estruturado foi aplicado incluindo dados sociodemográficos, história de clareamento dental, tratamento ortodôntico e hábitos de saúde bucal.A variável de pendentes (HD) foi dicotomizada no ponto que a hipersensibilidade ocorria repetidamente ou sempre. Os dados foram analisados por meio de regressão logística multivariada, incluindo variáveis demográficas, histórico de saúde, dados socioeconômicos e comportamentais. Nos resultados 556 (75.5%) indivíduos reportaram experiência de sensibilidade dentinária, nunca raramente ou às vezes, enquanto 180 (24.
    f 136 [27.9%] vs 66 of 411 [16.1%]; adjusted odds ratio, 2.37; 95% CI, 1.06-5.29), alcohol use (25 of 136 [18.4%] vs 30 of 411 [7.3%]; adjusted odds ratio, 2.98; 95% CI, 1.26-7.04), and clinical externalizing behaviors (31 of 136 [22.8%] vs 47 of 411 [11.4%]; adjusted odds ratio, 2.76; 95% CI, 1.11-6.84) at follow-up, controlling for baseline variables. Conclusion and Relevance This study suggests that recent immigration policy changes may be associated with critical outcomes jeopardizing the health of Latino or Latina adolescents. Since 95% of US Latino or Latina adolescents are citizens, compromised mental health and risk behavior tied to family member detention or deportation raises concerns regarding the association of current immigration policies with the mental health of Latino and Latina adolescents in the United States.MOTIVATION Low-dimensional representations of high-dimensional data are routinely employed in biomedical research to visualize, interpret and communicate results from different pipelines. In this article, we propose a novel procedure to directly estimate t-SNE embeddings that are not driven by batch effects. Without correction, interesting structure in the data can be obscured by batch effects. The proposed algorithm can therefore significantly aid visualization of high-dimensional data. RESULTS The proposed methods are based on linear algebra and constrained optimization, leading to efficient algorithms and fast computation in many high-dimensional settings. Results on artificial single-cell transcription profiling data show that the proposed procedure successfully removes multiple batch effects from t-SNE embeddings, while retaining fundamental information on cell types. When applied to single-cell gene expression data to investigate mouse medulloblastoma, the proposed method successfully removes batches related with mice identifiers and the date of the experiment, while preserving clusters of oligodendrocytes, astrocytes, and endothelial cells and microglia, which are expected to lie in the stroma within or adjacent to the tumors. AVAILABILITY Source code implementing the proposed approach is available as an R package at https//github.com/emanuelealiverti/BC_tSNE, including a tutorial to reproduce the simulation studies. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.in English, Portuguese Esse estudo objetivou avaliar a perda dentária severa e seus fatores associadas em idosos. Um estudo transversal, de base populacional, usando uma amostra probabilística, foi condu zido com os idosos de Cruz Alta, Rio Grande do Sul, Brasil. Exames de saúde bucal e um questionário estruturado foram realizados. Associações entre perda dentária severa e as variáveis independentes foram feitas, utilizando regressão de Poisson com variância robusta. O nível de significância adotado foi de 5%. No total, 287 idosos foram incluídos. Entre os idosos, 86 (29,9%) eram edêntulos, e 282 (98,3%) apresen tavam pelo menos uma perda dentária. Nessa amostra, a mediana de perda dentária foi 21 (média ± desvio padrão 19,69±8,21). A amostra foi dividida em dois grupos de acordo com a definição de perda dentária severa menos de nove dentes remanescentes ou ≥9 dentes presentes. A prevalência de perda dentária severa foi de 60,3% (n=173). As mulheres estiveram associadas com maior razão de prevalência (RP) de terem perda dentária severa (RP; IC95% 1,77; 1,39 – 2,24). Alto nível educacional esteve associados com menor RP de ter perda dentária severa (RP; IC95% 0,48; 0,30 – 0,77). A falta de acesso ao dentista esteve associada com maiores taxas de perda de dentária severa (RP; IC95% 1,38; 1,13 – 1,67). Por outro lado, frequência de escovação não esteve significati vamente associada perda dentária severa (RP; IC95% 0,88; 0,73 – 1,06). Alta prevalência de perda dentária severa foi detectada entre os idosos e ela foi associada com sexo, nível educacional, e acesso ao dentista.in English, Portuguese A halitose é altamente prevalente na periodontite e é atribuída principalmente à presença de compostos sulforosos voláteis (CSV), sendo o sulfeto de hidrogênio (H2S) o principal gás relacionado ao mau odor e que pode estar envolvido na patogênese da doença periodontal. O objetivo deste estudo foi avaliar o efeito agudo, intermediário e crônico do H2S na resposta imunoinflamatória e na perda óssea alveolar em ratos, com e sem doença periodontal induzida. Trinta e seis ratos foram divididos em 2 grupos teste (n = 18), ratos expostos ao H2S (NaHS molécula doadora de H2S) e grupo controle (n = 18), ratos tratados apenas com solução salina (Ctrl). Todos os animais tiveram um dos seus segundos molares inferiores submetidos à colocação de uma ligadura para o desenvolvimento da doença periodontal (DP), em comparação com o dente contralateral saudável (H). https://www.selleckchem.com/products/pp1.html Cada grupo foi subdividido em 3 (n = 6), de acordo com o tempo de eutanásia (3h, 5 dias e 14 dias). Os tecidos gengivais foram utilizados para a análise da expressão gênica (IL1, IL6, RANKL, OPG e SOFAT) por PCR em tempo real e as mandíbulas foram analisadas morfometricamente. Análise dos dados demonstrou que a ligadura promoveu perda óssea alveolar, observada principalmente aos 14 dias, tanto no grupo exposto ao H2S quanto no grupo Ctrl. A administração de H2S não resultou em perda óssea adicional. A expressão gênica demonstrou aumento significativo de IL1, IL6, RANKL e SOFAT apenas no grupo CtrlPD (p less then 0,05). Uma significativa regulação negativa na expressão de OPG foi observada ao longo do tempo no grupo CtrlPD (p less then 0,05). Podese concluir que o H2S não teve efeito adicional na perda óssea alveolar, na ausência de ligadura. Entretanto, na presença de ligadura, a exposição ao H2S teve um efeito imunorregulatório na expressão de citocinas próinflamatórias e próreabsortivas.in English, Portuguese O objetivo deste estudo foi determinar a ocorrência de hipersensibilidade dentinária (HD) autorreportada e seus indicadores de risco de uma cidade do sul do Brasil. 736 estudantes (1519 anos) foram selecionados aleatoriamente em 20 escolas públicas e privadas da cidade de Passo Fundo, Brasil. HD foi aferida pela resposta em escala Likert à pergunta “Você tem sensibilidade nos dentes?”. O exame clínico incluía a contagem de dentes presentes e um questionário estruturado foi aplicado incluindo dados sociodemográficos, história de clareamento dental, tratamento ortodôntico e hábitos de saúde bucal.A variável de pendentes (HD) foi dicotomizada no ponto que a hipersensibilidade ocorria repetidamente ou sempre. Os dados foram analisados por meio de regressão logística multivariada, incluindo variáveis demográficas, histórico de saúde, dados socioeconômicos e comportamentais. Nos resultados 556 (75.5%) indivíduos reportaram experiência de sensibilidade dentinária, nunca raramente ou às vezes, enquanto 180 (24.
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  • BACKGROUND AND OBJECTIVE Deployment of Body Area Networks (BAN) in hospitals can enable real time data collection and analysis for patient health. Such networks have a two-tier structure the primary layer consists of nodes that are installed on hospital facilities, while the second tier contains sensors on patient body. The unique two-tier network structure poses challenges to secure and continuous information transmission between sensors and data servers, especially when patients are moving. We plan to design a suite of mechanisms to support power efficient and secure data collection and smooth hand-over of sensors when patients move freely in a hospital. METHODS We assume that both group and individual secrets can be provided to BAN sensors when a patient checks in to the hospital. We first design mechanisms that use hash chains and double exclusive-or operations to protect data confidentiality and authenticity from BAN sensors. When a patient moves, the top tier nodes installed on the hospital facilities can provide smooth hand-over of the BAN sensors through secret updates. Our mechanisms can support network dynamics and changes of sensors in BAN networks. RESULTS We present the proposed mechanisms in details. We analyze the power efficiency of the approaches. We compare the power consumption of the proposed approach to those of the three security levels of IEEE 802.15.6 standard. Using formal methods, we prove the safety of the mechanisms. We also study the robustness of the approaches against various attacks. CONCLUSIONS In summary, we design a suite of mechanisms to support secure and continuous data collection from body sensors on patients in hospitals. The approaches are secure and efficient, which satisfy the requirements of future smart health applications. In this article, a content-aware specular reflection suppression scheme was developed based on adaptive image inpainting and neural network for endoscopic images. To decrease the impact of specular reflection on visual quality, the proposed scheme consists of three parts reflection detection, reflection region classification, and reflection concealment. To automatically locate specular reflection regions, a thresholding algorithm with a morphological dilation operation is employed. To reduce the effect of specular reflection, an adaptive image inpainting algorithm is devised to deal with different reflection regions. To achieve content-aware image inpainting, a reflection region classification algorithm is designed by analyzing the local image content to adjust the parameters in the proposed image inpainting algorithm. The experimental results demonstrate that the proposed scheme can automatically and correctly not only locate but also conceal specular reflection regions in endoscopic images. Furthermore, since the average SSIM (structural similarity index) value of the proposed scheme is higher than those of the existing methods, our specular reflection suppression scheme is superior to the existing methods. V.BACKGROUND AND OBJECTIVE Non-fusion dynamic stabilization surgery is increasingly popular for treating degenerative lumbar disc disease. However, changes in spine biomechanics after application of posterior dynamic fixation devices during whole-body vibration (WBV) remain unclear. The study aimed to examine the effects of non-fusion dynamic stabilization on biomechanical responses of the implanted lumbar spine to vertical WBV. METHODS By modifying L4-L5 segment of the healthy human L1-sacrum finite element model, single-level disc degeneration, dynamic fixation using the BioFlex system and anterior lumbar interbody fusion (ALIF) with rigid fixation were simulated, respectively. Dynamic responses of stress and strain in the spinal levels for the healthy, degenerated, BioFlex and ALIF models under an axial cyclic loading were investigated and compared. RESULTS The results showed that endplate stress at implant level was lower in the BioFlex model than in the degenerated and ALIF models, but stress of the connecting rod in the BioFlex system was greater than that in the rigid fixation system used in the ALIF. Compared with the healthy model, stress and strain responses in terms of disc bulge, annulus stress and nucleus pressure at adjacent levels were decreased in the degenerated, BioFlex and ALIF models, but no obvious difference was observed in these responses among the three models. CONCLUSIONS This study may be helpful to understand variations in vibration characteristics of the lumbar spine after application of non-fusion dynamic stabilization system. BACKGROUND - Far too many newborns die or face serious morbidity in Zambia, as in many other sub-Saharan African countries. https://www.selleckchem.com/products/uc2288.html New knowledge is needed to enhance our understanding of newborn care and the cultural factors influencing the ways mothers seek newborn care. This study adds to the literature about rural Zambians' cultural beliefs and practices related to newborn care and health-seeking practices that influence maternal-newborn health. OBJECTIVE - The goal of this study was to describe the factors associated with newborn care in rural Zambia. DESIGN - Sixty focus groups were conducted. Each group contained a minimum of 8 and maximum of 12 participants. Recruitment was conducted orally by word of mouth through the nurse in charge at the health facilities and village chiefs. SETTING - Data were collected between June and August 2016 in 20 communities located in Zambia's rural Lundazi (Eastern province), Mansa, and Chembe (Luapula province) Districts. PARTICIPANTS - The study included community members (n s aimed at improving maternal-child health outcomes. IMPLICATIONS FOR PRACTICE - There were findings about the culture-specific prevention of cough, care of the umbilical cord, and early introduction of traditional porridge that carry implications for nursing practice. There is an obvious need to reinforce the importance of partner testing for STIs during routine ANC even though there is a desire to preserve dignity. Mercury (Hg) is recognized as a global pollutant, which can be transported to the sea by suspended particulate matter (SPM) via rivers constituting the main source of mercury in the southern Baltic sea. The aim of the present study was to characterize the mercury fractions in suspended particulate matter, as well as the transformations of Hg during its riverine transportation into the sea. The thermo-desorption method was used to determine the labile and stable mercury fractions in SPM of rivers (Reda, Zagórska Struga, Gizdepka, Płutnica) within the Baltic Sea basin. In this paper six "periods" were designated (heating, non-heating, drought, rains, downpour/flood and thaws), during which the river suspended particulate matter was enriched with various fractions of mercury. Meteorological and hydrological phenomena such as downpours and thaws intensified surface runoff, causing an increase in the share of Hgabs and Hgads1 mercury fractions in suspended particulate matter. Whereas, droughts contributed to the formation of HgS in a large river and to an inflow of adsorbed Hg in smaller rivers decrease of air temperature leads to increase of fossil fuel combustion and then increases the share of adsorbed Hg (mainly bound with halides) in riverine particulate matter.
    BACKGROUND AND OBJECTIVE Deployment of Body Area Networks (BAN) in hospitals can enable real time data collection and analysis for patient health. Such networks have a two-tier structure the primary layer consists of nodes that are installed on hospital facilities, while the second tier contains sensors on patient body. The unique two-tier network structure poses challenges to secure and continuous information transmission between sensors and data servers, especially when patients are moving. We plan to design a suite of mechanisms to support power efficient and secure data collection and smooth hand-over of sensors when patients move freely in a hospital. METHODS We assume that both group and individual secrets can be provided to BAN sensors when a patient checks in to the hospital. We first design mechanisms that use hash chains and double exclusive-or operations to protect data confidentiality and authenticity from BAN sensors. When a patient moves, the top tier nodes installed on the hospital facilities can provide smooth hand-over of the BAN sensors through secret updates. Our mechanisms can support network dynamics and changes of sensors in BAN networks. RESULTS We present the proposed mechanisms in details. We analyze the power efficiency of the approaches. We compare the power consumption of the proposed approach to those of the three security levels of IEEE 802.15.6 standard. Using formal methods, we prove the safety of the mechanisms. We also study the robustness of the approaches against various attacks. CONCLUSIONS In summary, we design a suite of mechanisms to support secure and continuous data collection from body sensors on patients in hospitals. The approaches are secure and efficient, which satisfy the requirements of future smart health applications. In this article, a content-aware specular reflection suppression scheme was developed based on adaptive image inpainting and neural network for endoscopic images. To decrease the impact of specular reflection on visual quality, the proposed scheme consists of three parts reflection detection, reflection region classification, and reflection concealment. To automatically locate specular reflection regions, a thresholding algorithm with a morphological dilation operation is employed. To reduce the effect of specular reflection, an adaptive image inpainting algorithm is devised to deal with different reflection regions. To achieve content-aware image inpainting, a reflection region classification algorithm is designed by analyzing the local image content to adjust the parameters in the proposed image inpainting algorithm. The experimental results demonstrate that the proposed scheme can automatically and correctly not only locate but also conceal specular reflection regions in endoscopic images. Furthermore, since the average SSIM (structural similarity index) value of the proposed scheme is higher than those of the existing methods, our specular reflection suppression scheme is superior to the existing methods. V.BACKGROUND AND OBJECTIVE Non-fusion dynamic stabilization surgery is increasingly popular for treating degenerative lumbar disc disease. However, changes in spine biomechanics after application of posterior dynamic fixation devices during whole-body vibration (WBV) remain unclear. The study aimed to examine the effects of non-fusion dynamic stabilization on biomechanical responses of the implanted lumbar spine to vertical WBV. METHODS By modifying L4-L5 segment of the healthy human L1-sacrum finite element model, single-level disc degeneration, dynamic fixation using the BioFlex system and anterior lumbar interbody fusion (ALIF) with rigid fixation were simulated, respectively. Dynamic responses of stress and strain in the spinal levels for the healthy, degenerated, BioFlex and ALIF models under an axial cyclic loading were investigated and compared. RESULTS The results showed that endplate stress at implant level was lower in the BioFlex model than in the degenerated and ALIF models, but stress of the connecting rod in the BioFlex system was greater than that in the rigid fixation system used in the ALIF. Compared with the healthy model, stress and strain responses in terms of disc bulge, annulus stress and nucleus pressure at adjacent levels were decreased in the degenerated, BioFlex and ALIF models, but no obvious difference was observed in these responses among the three models. CONCLUSIONS This study may be helpful to understand variations in vibration characteristics of the lumbar spine after application of non-fusion dynamic stabilization system. BACKGROUND - Far too many newborns die or face serious morbidity in Zambia, as in many other sub-Saharan African countries. https://www.selleckchem.com/products/uc2288.html New knowledge is needed to enhance our understanding of newborn care and the cultural factors influencing the ways mothers seek newborn care. This study adds to the literature about rural Zambians' cultural beliefs and practices related to newborn care and health-seeking practices that influence maternal-newborn health. OBJECTIVE - The goal of this study was to describe the factors associated with newborn care in rural Zambia. DESIGN - Sixty focus groups were conducted. Each group contained a minimum of 8 and maximum of 12 participants. Recruitment was conducted orally by word of mouth through the nurse in charge at the health facilities and village chiefs. SETTING - Data were collected between June and August 2016 in 20 communities located in Zambia's rural Lundazi (Eastern province), Mansa, and Chembe (Luapula province) Districts. PARTICIPANTS - The study included community members (n s aimed at improving maternal-child health outcomes. IMPLICATIONS FOR PRACTICE - There were findings about the culture-specific prevention of cough, care of the umbilical cord, and early introduction of traditional porridge that carry implications for nursing practice. There is an obvious need to reinforce the importance of partner testing for STIs during routine ANC even though there is a desire to preserve dignity. Mercury (Hg) is recognized as a global pollutant, which can be transported to the sea by suspended particulate matter (SPM) via rivers constituting the main source of mercury in the southern Baltic sea. The aim of the present study was to characterize the mercury fractions in suspended particulate matter, as well as the transformations of Hg during its riverine transportation into the sea. The thermo-desorption method was used to determine the labile and stable mercury fractions in SPM of rivers (Reda, Zagórska Struga, Gizdepka, Płutnica) within the Baltic Sea basin. In this paper six "periods" were designated (heating, non-heating, drought, rains, downpour/flood and thaws), during which the river suspended particulate matter was enriched with various fractions of mercury. Meteorological and hydrological phenomena such as downpours and thaws intensified surface runoff, causing an increase in the share of Hgabs and Hgads1 mercury fractions in suspended particulate matter. Whereas, droughts contributed to the formation of HgS in a large river and to an inflow of adsorbed Hg in smaller rivers decrease of air temperature leads to increase of fossil fuel combustion and then increases the share of adsorbed Hg (mainly bound with halides) in riverine particulate matter.
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  • 92% skulls). Exclusively unilateral observations included bifurcation of foramen (16.22% skulls), foramen situated deep inside skull groove (5.41% skulls) and foramen interrupted by bony spur (2.7% skulls). No significant differences were observed between the mean diameters (antero-posterior and transverse) of the stylomastoid foramen. CONCLUSIONS The unilateral variations along with rare variations in terms of shape such as serrated, bean and irregular foramen (which were also unilateral findings) could be potential risk factors towards injury of facial nerve at the point of exit from skull base leading to ****'s palsy.The main source of energy for brain and other organs is glucose. To obtain an energy for all tissue glucose has to come through glycolysis then as pyruvate is converting to acetyl-CoA due to pyruvate dehydrogenase complex (PDC) and finally join to citric acid cycle. What happens when one of these stages become disturb? Mutation in genes encoding subunits of PDC leads to pyruvate dehydrogenase deficiency. Abnormalities in PDC activity result in severe metabolic and broad brain malformations. For better understanding the development and mechanism of pyruvate dehydrogenase deficiency the murine model of this disease has been created. Studies on a murine model showed similar malformation in brain structures as in the patients suffered from pyruvate dehydrogenase deficiency such as reduced neuronal density, heterotopias of grey matter, reduced size of corpus callosum and pyramids. There is still no effective cure for PDC-deficiency. Promising therapy seemed to be ketogenic diet, which substitutes glucose to ketone bodies as a source of energy. Studies have shown that ketogenic diet decrease lactic acidosis and inhibit brain malformations, but not the mortality in early childhood. The newest reports say that phenylbutyrate increases level of PDC in brain, because reduced level of inactive form of PDH. Experiments on human fibroblast and zebra fish PDC-deficiency model showed that phenylbutyrate is promising cure to PDC-deficiency. This review summarizes the most important findings on the metabolic and morphological effects of PDC-deficiency and research for treatment therapy.Colon cancer is considered to be the third most common cancer worldwide. At diagnosis of colon cancer, 3.7-11% developed bone metastasis. Diet based strategies are important for prevention and treatment of colon cancer. This study investigated the effect of vitamin B17 on a DMH induced rat model of colon cancer. Eighty young adult male albino rats were divided into five groups. Group I (control group), Group II (vitamin B17), Group III (CC), Group IV (protected) and Group V (treated). https://www.selleckchem.com/products/muvalaplin.html Distal colon sections were prepared for light & scanning electron microscopic examination. Lumbar vertebrae specimens were prepared for light microscopic study. Morphometric and statistical analysis were done. In comparison with the control, both CC & treated groups showed invasion of the colonic tissue by pleomorphic branching colonic glands of variable shapes and sizes lined with dysplastic elongated hyperchromatic nuclei with frequent mitotic figures or stratified multilayered crowded nuclei with an extremely significant (p˂0.0001) reduction of goblet cell number when compared to the control together with major pathological bone changes were observed in cc and the treated groups. While the protected group showed impressive improvement of all previously mentioned diameters.BACKGROUND The vertebral artery originates from the subclavian artery and is divided into four segments. The aim of this study is to investigate the anatomical variations in the course and branches of the vertebral artery. M ATERIALS AND METHODS A research was performed via Pubmed database, using the terms; "variations of vertebral artery AND cadaveric study", "variations of vertebral artery AND cadavers" and "anomalies of vertebral artery AND cadavers". RESULTS A total of 24 articles met the inclusion criteria, 13 of them referring to variations of the origin of the vertebral artery, 9 to variations of the course and 3 to variations of its branches. On a total sample of 1192 cadavers of different population, origin of the left vertebral artery directly from the aortic arch was observed at 6.7%. In addition, among 311 cadavers, 17.4% were found with partially or fully ossified foramen of the atlas for the passage of the vertebral artery, while the bibliographic review also showed variants at the exit site of the artery from the transverse foramen of the axis. CONCLUSIONS Despite the fact that variations of both the course and the branches of vertebral artery are in most cases asymptomatic, good knowledge of anatomy and its variants is of particular importance for the prevention of vascular complications during surgical and radiological procedures in the cervix area.CD63, a member of the tetraspanin family, is expressed in endosomes and enriched in exosomes. Tetraspanins participate in a variety of physiological processes, including cellular differentiation, cell-cell fusion, and cell migration. CD63 reportedly carries both protumorigenic and tumor suppressor properties, and appears to be upregulated in breast cancer, astrocytoma, and melanoma. Yet, the effect of CD63 on cancer prognosis remains unclear, and no previous reports examined it in colorectal cancer (CRC). Identifying novel biomarkers will allow us to better differentiate patients with an increased risk of recurrence and who might benefit from adjuvant therapy. We applied immunohistochemistry with antibodies to human CD63 on 620 consecutive CRC patients treated at the Helsinki University Hospital. We evaluated the associations between CD63 expression and clinicopathological parameters and patient prognosis. We found that CD63 expression associated with an advanced stage, poor differentiation, and mucinous histology. We found no association between CD63 expression and age, sex or tumor location. CD63 expression predicted an unfavorable prognosis in CRC (p=0.00001, log-rank test) and in a subgroup of patients with metastasized CRC (p=0.011). Cox's multivariate analysis identified CD63 as an independent factor predicting an unfavorable prognosis in CRC and in the subgroup with metastasized disease. We show for the first time that CD63 immunohistochemistry expression represents an independent marker of an unfavorable prognosis in CRC and associates with unfavorable clinicopathological parameters. Our results support the hypothesis that a higher tissue expression of CD63 in CRC, indicating an epithelial-to-mesenchymal transition (EMT)-associated secretory phenotype, associated with an adverse outcome.
    92% skulls). Exclusively unilateral observations included bifurcation of foramen (16.22% skulls), foramen situated deep inside skull groove (5.41% skulls) and foramen interrupted by bony spur (2.7% skulls). No significant differences were observed between the mean diameters (antero-posterior and transverse) of the stylomastoid foramen. CONCLUSIONS The unilateral variations along with rare variations in terms of shape such as serrated, bean and irregular foramen (which were also unilateral findings) could be potential risk factors towards injury of facial nerve at the point of exit from skull base leading to Bell's palsy.The main source of energy for brain and other organs is glucose. To obtain an energy for all tissue glucose has to come through glycolysis then as pyruvate is converting to acetyl-CoA due to pyruvate dehydrogenase complex (PDC) and finally join to citric acid cycle. What happens when one of these stages become disturb? Mutation in genes encoding subunits of PDC leads to pyruvate dehydrogenase deficiency. Abnormalities in PDC activity result in severe metabolic and broad brain malformations. For better understanding the development and mechanism of pyruvate dehydrogenase deficiency the murine model of this disease has been created. Studies on a murine model showed similar malformation in brain structures as in the patients suffered from pyruvate dehydrogenase deficiency such as reduced neuronal density, heterotopias of grey matter, reduced size of corpus callosum and pyramids. There is still no effective cure for PDC-deficiency. Promising therapy seemed to be ketogenic diet, which substitutes glucose to ketone bodies as a source of energy. Studies have shown that ketogenic diet decrease lactic acidosis and inhibit brain malformations, but not the mortality in early childhood. The newest reports say that phenylbutyrate increases level of PDC in brain, because reduced level of inactive form of PDH. Experiments on human fibroblast and zebra fish PDC-deficiency model showed that phenylbutyrate is promising cure to PDC-deficiency. This review summarizes the most important findings on the metabolic and morphological effects of PDC-deficiency and research for treatment therapy.Colon cancer is considered to be the third most common cancer worldwide. At diagnosis of colon cancer, 3.7-11% developed bone metastasis. Diet based strategies are important for prevention and treatment of colon cancer. This study investigated the effect of vitamin B17 on a DMH induced rat model of colon cancer. Eighty young adult male albino rats were divided into five groups. Group I (control group), Group II (vitamin B17), Group III (CC), Group IV (protected) and Group V (treated). https://www.selleckchem.com/products/muvalaplin.html Distal colon sections were prepared for light & scanning electron microscopic examination. Lumbar vertebrae specimens were prepared for light microscopic study. Morphometric and statistical analysis were done. In comparison with the control, both CC & treated groups showed invasion of the colonic tissue by pleomorphic branching colonic glands of variable shapes and sizes lined with dysplastic elongated hyperchromatic nuclei with frequent mitotic figures or stratified multilayered crowded nuclei with an extremely significant (p˂0.0001) reduction of goblet cell number when compared to the control together with major pathological bone changes were observed in cc and the treated groups. While the protected group showed impressive improvement of all previously mentioned diameters.BACKGROUND The vertebral artery originates from the subclavian artery and is divided into four segments. The aim of this study is to investigate the anatomical variations in the course and branches of the vertebral artery. M ATERIALS AND METHODS A research was performed via Pubmed database, using the terms; "variations of vertebral artery AND cadaveric study", "variations of vertebral artery AND cadavers" and "anomalies of vertebral artery AND cadavers". RESULTS A total of 24 articles met the inclusion criteria, 13 of them referring to variations of the origin of the vertebral artery, 9 to variations of the course and 3 to variations of its branches. On a total sample of 1192 cadavers of different population, origin of the left vertebral artery directly from the aortic arch was observed at 6.7%. In addition, among 311 cadavers, 17.4% were found with partially or fully ossified foramen of the atlas for the passage of the vertebral artery, while the bibliographic review also showed variants at the exit site of the artery from the transverse foramen of the axis. CONCLUSIONS Despite the fact that variations of both the course and the branches of vertebral artery are in most cases asymptomatic, good knowledge of anatomy and its variants is of particular importance for the prevention of vascular complications during surgical and radiological procedures in the cervix area.CD63, a member of the tetraspanin family, is expressed in endosomes and enriched in exosomes. Tetraspanins participate in a variety of physiological processes, including cellular differentiation, cell-cell fusion, and cell migration. CD63 reportedly carries both protumorigenic and tumor suppressor properties, and appears to be upregulated in breast cancer, astrocytoma, and melanoma. Yet, the effect of CD63 on cancer prognosis remains unclear, and no previous reports examined it in colorectal cancer (CRC). Identifying novel biomarkers will allow us to better differentiate patients with an increased risk of recurrence and who might benefit from adjuvant therapy. We applied immunohistochemistry with antibodies to human CD63 on 620 consecutive CRC patients treated at the Helsinki University Hospital. We evaluated the associations between CD63 expression and clinicopathological parameters and patient prognosis. We found that CD63 expression associated with an advanced stage, poor differentiation, and mucinous histology. We found no association between CD63 expression and age, sex or tumor location. CD63 expression predicted an unfavorable prognosis in CRC (p=0.00001, log-rank test) and in a subgroup of patients with metastasized CRC (p=0.011). Cox's multivariate analysis identified CD63 as an independent factor predicting an unfavorable prognosis in CRC and in the subgroup with metastasized disease. We show for the first time that CD63 immunohistochemistry expression represents an independent marker of an unfavorable prognosis in CRC and associates with unfavorable clinicopathological parameters. Our results support the hypothesis that a higher tissue expression of CD63 in CRC, indicating an epithelial-to-mesenchymal transition (EMT)-associated secretory phenotype, associated with an adverse outcome.
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  • Therefore, the developed system should be helpful for evaluating the potential of compounds to cause DILI under conditions where inducers of CYP1A2 are present. Effect of long-term treatment with cigarette smoke extract (CSE) on the function and expression of P-glycoprotein (P-gp) in lung alveolar epithelial cells was examined using A549/P-gp cell line expressing P-gp. CSE treatment suppressed P-gp activity in a concentration- and treatment time-dependent manner. The suppression of P-gp activity by CSE was irreversible for at least 96 h after removal of CSE. In addition, CSE treatment suppressed the expression of P-gp mRNA and protein. In order to understand the mechanisms underlying P-gp suppression by CSE, the role of reactive oxygen species (ROS) was examined. CSE treatment increased intracellular ROS level, and suppressed catalase activity. α-Tocopherol suppressed ROS production by CSE, and ameliorated the suppression of P-gp activity by CSE, suggesting that ROS is involved in CSE-induced suppression of P-gp. The role of intracellular signaling pathways such as the nuclear factor κB and mitogen-activated protein kinase pathways was also examined. Among these pathways, the involvement of extracellular signal-regulated kinase (ERK) pathway was suggested. Taken together, long-term CSE treatment may suppress P-gp via modulation of ROS level and ERK pathway in alveolar epithelial cells. OBJECTIVE To examine the association between polymorphisms of the ciliary neurotrophic factor gene (CNTF) and total and central adiposity markers in adolescents. STUDY DESIGN This cross-sectional study involved 1057 European adolescents aged 12-18 years enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Five polymorphisms of CNTF were genotyped, and the weight, height, waist and hip circumference, and triceps and subscapular skinfold thickness of the subjects were measured and recorded. RESULTS The T allele of rs2509914, the C allele of rs2515363, and the G allele of rs2515362 were significantly associated (after Bonferroni correction) with higher values for several adiposity markers under different inheritance models. The CNTF CCGGA haplotype (rs2509914, rs17489568, rs2515363 rs1800169, and rs2515362) was also significantly associated with lower body mass index, waist circumference, waist/height ratio, and waist/hip ratio values compared with the TCCGG haplotype under several inheritance models. CONCLUSIONS Three polymorphisms-rs2509914, rs2515363, and rs2515362-and the CCGGA haplotype of CNTF were significantly associated with adiposity in European adolescents. These results suggest the potential role of CTNF in the development of obesity-related phenotypes. Nationally representative data of 140 000 children in 2-parent households showed that fathers were more likely than mothers to report that a child was in good health and less likely to report the presence of a specific health condition, special health care needs, or unmet health service needs. OBJECTIVE To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. STUDY DESIGN We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age less then 60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. RESULTS We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment. CONCLUSIONS Among our cohort of infants exposed to acyclovir, the rate of AKI was low. https://www.selleckchem.com/products/tpca-1.html Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring. OBJECTIVES To evaluate accuracy of systemic inflammatory response syndrome (SIRS) criteria in identifying culture-proven late-onset neonatal sepsis and to assess prevalence of organ dysfunction and its relationship with SIRS criteria. STUDY DESIGN This was a retrospective case-control study of patients in the Children's Hospital of Philadelphia level IV neonatal intensive care unit undergoing sepsis evaluations (concurrent blood culture and antibiotics). During calendar years 2016-2017, 77 case and 77 control sepsis evaluations were identified. Cases included infants who had sepsis evaluations with positive blood cultures and antibiotic duration ≥7 days. Controls were matched by gestational and postmenstrual age, and had sepsis evaluations with negative blood cultures and antibiotic duration ≤48 hours. SIRS criteria were determined at time of sepsis evaluation, and organ dysfunction evaluated in the 72 hours following sepsis evaluation. Statistical analysis included descriptive statistics, Mann-Whitney tests, and χ2 (Fisher exact) tests. RESULTS At time of sepsis evaluation, 42% of cases and 26% of controls met SIRS criteria. Among infants of ≤37 weeks postmenstrual age, SIRS criteria were met in only 17% of sepsis evaluations (4 of 23 in both cases and controls). Test characteristics for SIRS at diagnosis of culture-proven sepsis included sensitivity 42% and specificity 74%. Cases had higher rates of new organ dysfunction within 72 hours (40% vs 21%); however, 58% of cases developing organ dysfunction did not meet SIRS criteria at time of sepsis evaluation. Of 6 deaths (all cases with organ dysfunction), 2 did not meet SIRS criteria at sepsis evaluation. CONCLUSIONS SIRS criteria did not accurately identify culture-proven late-onset sepsis, with poorest accuracy in preterm infants. SIRS criteria did not predict later organ dysfunction or mortality.
    Therefore, the developed system should be helpful for evaluating the potential of compounds to cause DILI under conditions where inducers of CYP1A2 are present. Effect of long-term treatment with cigarette smoke extract (CSE) on the function and expression of P-glycoprotein (P-gp) in lung alveolar epithelial cells was examined using A549/P-gp cell line expressing P-gp. CSE treatment suppressed P-gp activity in a concentration- and treatment time-dependent manner. The suppression of P-gp activity by CSE was irreversible for at least 96 h after removal of CSE. In addition, CSE treatment suppressed the expression of P-gp mRNA and protein. In order to understand the mechanisms underlying P-gp suppression by CSE, the role of reactive oxygen species (ROS) was examined. CSE treatment increased intracellular ROS level, and suppressed catalase activity. α-Tocopherol suppressed ROS production by CSE, and ameliorated the suppression of P-gp activity by CSE, suggesting that ROS is involved in CSE-induced suppression of P-gp. The role of intracellular signaling pathways such as the nuclear factor κB and mitogen-activated protein kinase pathways was also examined. Among these pathways, the involvement of extracellular signal-regulated kinase (ERK) pathway was suggested. Taken together, long-term CSE treatment may suppress P-gp via modulation of ROS level and ERK pathway in alveolar epithelial cells. OBJECTIVE To examine the association between polymorphisms of the ciliary neurotrophic factor gene (CNTF) and total and central adiposity markers in adolescents. STUDY DESIGN This cross-sectional study involved 1057 European adolescents aged 12-18 years enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Five polymorphisms of CNTF were genotyped, and the weight, height, waist and hip circumference, and triceps and subscapular skinfold thickness of the subjects were measured and recorded. RESULTS The T allele of rs2509914, the C allele of rs2515363, and the G allele of rs2515362 were significantly associated (after Bonferroni correction) with higher values for several adiposity markers under different inheritance models. The CNTF CCGGA haplotype (rs2509914, rs17489568, rs2515363 rs1800169, and rs2515362) was also significantly associated with lower body mass index, waist circumference, waist/height ratio, and waist/hip ratio values compared with the TCCGG haplotype under several inheritance models. CONCLUSIONS Three polymorphisms-rs2509914, rs2515363, and rs2515362-and the CCGGA haplotype of CNTF were significantly associated with adiposity in European adolescents. These results suggest the potential role of CTNF in the development of obesity-related phenotypes. Nationally representative data of 140 000 children in 2-parent households showed that fathers were more likely than mothers to report that a child was in good health and less likely to report the presence of a specific health condition, special health care needs, or unmet health service needs. OBJECTIVE To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants. STUDY DESIGN We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age less then 60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment. RESULTS We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment. CONCLUSIONS Among our cohort of infants exposed to acyclovir, the rate of AKI was low. https://www.selleckchem.com/products/tpca-1.html Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring. OBJECTIVES To evaluate accuracy of systemic inflammatory response syndrome (SIRS) criteria in identifying culture-proven late-onset neonatal sepsis and to assess prevalence of organ dysfunction and its relationship with SIRS criteria. STUDY DESIGN This was a retrospective case-control study of patients in the Children's Hospital of Philadelphia level IV neonatal intensive care unit undergoing sepsis evaluations (concurrent blood culture and antibiotics). During calendar years 2016-2017, 77 case and 77 control sepsis evaluations were identified. Cases included infants who had sepsis evaluations with positive blood cultures and antibiotic duration ≥7 days. Controls were matched by gestational and postmenstrual age, and had sepsis evaluations with negative blood cultures and antibiotic duration ≤48 hours. SIRS criteria were determined at time of sepsis evaluation, and organ dysfunction evaluated in the 72 hours following sepsis evaluation. Statistical analysis included descriptive statistics, Mann-Whitney tests, and χ2 (Fisher exact) tests. RESULTS At time of sepsis evaluation, 42% of cases and 26% of controls met SIRS criteria. Among infants of ≤37 weeks postmenstrual age, SIRS criteria were met in only 17% of sepsis evaluations (4 of 23 in both cases and controls). Test characteristics for SIRS at diagnosis of culture-proven sepsis included sensitivity 42% and specificity 74%. Cases had higher rates of new organ dysfunction within 72 hours (40% vs 21%); however, 58% of cases developing organ dysfunction did not meet SIRS criteria at time of sepsis evaluation. Of 6 deaths (all cases with organ dysfunction), 2 did not meet SIRS criteria at sepsis evaluation. CONCLUSIONS SIRS criteria did not accurately identify culture-proven late-onset sepsis, with poorest accuracy in preterm infants. SIRS criteria did not predict later organ dysfunction or mortality.
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