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  • Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalities, and this correlated with restoration of Gja5 (connexin 40) expression in the heart. This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3'UTR has demonstrated benefit on the key DM1 phenotypes of myotonia and cardiac conduction defects. Our data also shows for the first time, that ASOs may be a viable option for treating cardiac pathology in DM1. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, differentially by clinical characteristics or by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases and models provided evidence for superspreading. This is the first study to assess support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving superspreading. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020.BACKGROUND This study examined whether biological mechanisms linking dementia caregiving with an increased risk of coronary heart disease can be modified by psychosocial interventions and which caregivers might benefit the most from an intervention. METHODS Spousal dementia caregivers were randomized to 12-week treatment with either a behavioral activation intervention (i.e., Pleasant Events Program PEP; n=60), or an active control Information and Support (IS; n=63) condition. Indicators of caregiving stress were assessed pre-treatment and circulating cardiovascular biomarkers were measured pre- and post-treatment. RESULTS There were no significant changes in biomarker levels from pre- to post-treatment both by treatment condition and across all caregivers. Regardless of the treatment condition, exploratory regression analysis revealed that caregivers were more likely to show significant decreases in C-reactive protein (CRP) and D-dimer when their spouse had severe functional impairment; in interleukin (IL)-6 and CRP when they had greater distress due to care recipient's problem behaviors; in tumor necrosis factor (TNF)-α when they had higher levels of negative affect; and in IL-6, CRP, TNF-α and D-dimer when they had higher personal mastery. Within the PEP group, caregivers with higher negative affect and those with higher positive affect were more likely to show a reduction in von Willebrand factor and D-dimer, respectively. Within the IS group, caregivers whose spouse had severe functional impairment were more likely to show a decrease in IL-6. CONCLUSIONS Unlike the average caregiver, caregivers high in burden/distress and resources might benefit from psychosocial interventions to improve cardiovascular risk, although these observations need confirmation. ClinicalTrials.gov #NCT02317523. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Mutations in the RYR1 gene are the most common cause of human congenital myopathies and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in extraocular muscles from compound heterozygous RyR1p.Q1970fsX16 + p.A4329D mutant **** was significantly reduced compared to that observed in wild type, single heterozygous mutant carriers or homozygous RyR1p.A4329D ****. The decrease in muscle force was also accompanied by approximately a 40% reduction in RyR1 protein content, a decrease in electrically evoked calcium transients, disorganization of the muscle ultrastructure and a decrease in the number of calcium release units. Unexpectedly, the superfast and ocular-muscle specific myosin heavy chain-EO isoform was almost undetectable in RyR1p.Q1970fsX16 + p.A4329D mutant ****. The results of this study show for the first time that the extraocular muscle phenotype caused by the RyR1p.Q1970fsX16 + p.A4329D compound heterozygous Ryr1 mutations is complex and due to a combination of modifications including a direct effect on the macromolecular complex involved in calcium release and indirect effects on the expression of myosin heavy chain isoforms. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.OBJECTIVES To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. DESIGN Cross-sectional study. SETTING Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS Older adult men (average age, 85y) from the MrOS study. https://www.selleckchem.com/products/bt-11.html MEASUREMENTS Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity.
    Of note, we demonstrate that the ASO treatment reversed the cardiac conduction abnormalities, and this correlated with restoration of Gja5 (connexin 40) expression in the heart. This is the first time that an ASO targeting a non-CUG sequence within the DMPK 3'UTR has demonstrated benefit on the key DM1 phenotypes of myotonia and cardiac conduction defects. Our data also shows for the first time, that ASOs may be a viable option for treating cardiac pathology in DM1. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, differentially by clinical characteristics or by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases and models provided evidence for superspreading. This is the first study to assess support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving superspreading. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020.BACKGROUND This study examined whether biological mechanisms linking dementia caregiving with an increased risk of coronary heart disease can be modified by psychosocial interventions and which caregivers might benefit the most from an intervention. METHODS Spousal dementia caregivers were randomized to 12-week treatment with either a behavioral activation intervention (i.e., Pleasant Events Program PEP; n=60), or an active control Information and Support (IS; n=63) condition. Indicators of caregiving stress were assessed pre-treatment and circulating cardiovascular biomarkers were measured pre- and post-treatment. RESULTS There were no significant changes in biomarker levels from pre- to post-treatment both by treatment condition and across all caregivers. Regardless of the treatment condition, exploratory regression analysis revealed that caregivers were more likely to show significant decreases in C-reactive protein (CRP) and D-dimer when their spouse had severe functional impairment; in interleukin (IL)-6 and CRP when they had greater distress due to care recipient's problem behaviors; in tumor necrosis factor (TNF)-α when they had higher levels of negative affect; and in IL-6, CRP, TNF-α and D-dimer when they had higher personal mastery. Within the PEP group, caregivers with higher negative affect and those with higher positive affect were more likely to show a reduction in von Willebrand factor and D-dimer, respectively. Within the IS group, caregivers whose spouse had severe functional impairment were more likely to show a decrease in IL-6. CONCLUSIONS Unlike the average caregiver, caregivers high in burden/distress and resources might benefit from psychosocial interventions to improve cardiovascular risk, although these observations need confirmation. ClinicalTrials.gov #NCT02317523. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Mutations in the RYR1 gene are the most common cause of human congenital myopathies and patients with recessive mutations are severely affected and often display ptosis and/or ophthalmoplegia. In order to gain insight into the mechanism leading to extraocular muscle involvement, we investigated the biochemical, structural and physiological properties of eye muscles from mouse models we created knocked-in for Ryr1 mutations. Ex vivo force production in extraocular muscles from compound heterozygous RyR1p.Q1970fsX16 + p.A4329D mutant mice was significantly reduced compared to that observed in wild type, single heterozygous mutant carriers or homozygous RyR1p.A4329D mice. The decrease in muscle force was also accompanied by approximately a 40% reduction in RyR1 protein content, a decrease in electrically evoked calcium transients, disorganization of the muscle ultrastructure and a decrease in the number of calcium release units. Unexpectedly, the superfast and ocular-muscle specific myosin heavy chain-EO isoform was almost undetectable in RyR1p.Q1970fsX16 + p.A4329D mutant mice. The results of this study show for the first time that the extraocular muscle phenotype caused by the RyR1p.Q1970fsX16 + p.A4329D compound heterozygous Ryr1 mutations is complex and due to a combination of modifications including a direct effect on the macromolecular complex involved in calcium release and indirect effects on the expression of myosin heavy chain isoforms. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.OBJECTIVES To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men. DESIGN Cross-sectional study. SETTING Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16). PARTICIPANTS Older adult men (average age, 85y) from the MrOS study. https://www.selleckchem.com/products/bt-11.html MEASUREMENTS Men who were in the highest tertiles for dietary fiber density and the percentage of whole body lean mass were defined as T3T3 (n=42), whereas men who were in the lowest and intermediate tertiles for these variables were defined as T1T1 (n=32), T1T3 (n=24), and T3T1 (n=13), respectively. Additionally, measures of physical function, including the short physical performance battery (SPPB) score and grip strength were higher in T3T3 when compared with T1T1. Gut bacterial abundance was quantified with use of 16S v4 rRNA sequencing, and the bacterial functional potential was derived from the 16S data with PICRUSt. Chao1, ACE, Shannon, Simpson, and Fisher indices were used as measures of α-diversity.
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  • This review focuses on the emerging roles of these molecules in the outcome of HTLV-1-associated diseases. Copyright © 2020 Zargari, Mahdifar, Mohammadi, Vahidi, Hassanshahi and Rafatpanah.Erysipelas, caused by the bacterium Erysipelothrix rhusiopathiae, is re-emerging in ***** and poultry production systems worldwide. While the global genomic diversity of this species has been characterized, how **** of this genomic and functional diversity is maintained at smaller scales is unclear. Specifically, while several key immunogenic surface proteins have been identified for E. rhusiopathiae, little is known about their presence among field strains and their divergence from vaccines, which could result in vaccine failure. Here, a comparative genomics approach was taken to determine the diversity of E. rhusiopathiae strains in pigs in Great Britain over nearly three decades, as well as to assess the field strains' divergence from the vaccine strain most commonly used in British pigs. In addition, the presence/absence and variability of 13 previously described immunogenic surface proteins was determined, including SpaA which is considered a key immunogen. We found a high diversity of E. rhusiopathiae suence variants in these proteins could be responsible for differences in the efficacy of the immune response. https://www.selleckchem.com/products/pmx-53.html Our results provide the necessary basis for testing this hypothesis through in vitro and in vivo studies. Copyright © 2020 Forde, Kollanandi Ratheesh, Harvey, Thomson, Williamson, Biek and Opriessnig.Pseudorabies virus (PRV) infection brings about great economic losses to the ***** industry worldwide, as there are currently no effective therapeutic agents or vaccines against this disease, and mutations in endemic wild virulent PRV strains result in immune failure of traditional vaccines. Heme oxygenase-1 (HO-1) catalyzes the conversion of heme into biliverdin (BV), iron and carbon monoxide (CO), all of which have been demonstrated to protect cells from various stressors. However, the role of HO-1 in PRV replication remains unknown. Thus, the present study aimed to investigate the effect of HO-1 on PRV replication and determine its underlying molecular mechanisms. The results demonstrated that induction of HO-1 via cobalt-protoporphyrin (CoPP) markedly suppressed PRV replication, while HO-1 specific small interfering RNA or inhibitor zinc-protoporphyrin partially reversed the inhibitory effect of CoPP on PRV replication. Furthermore, overexpression of HO-1 notably inhibited PRV replication, while knockdown of endogenous HO-1 expression promoted PRV replication. Mechanism analyses indicated that the HO-1 downstream metabolites, CO and BV/BR partially mediated the virus suppressive effect of HO-1. Taken together, the results of the present study suggest that HO-1 may be developed as a novel endogenous antiviral factor against PRV, and the HO-1/BV/CO system may constitute a unique antiviral protection network during PRV infection and interaction with host cells. Copyright © 2020 Zhang, Wan, Jiang, Wu, Ji, Du and Zhang.Here, we experimentally expand understanding of the reactions and enzymes involved in Acidithiobacillus thiooxidans ATCC 19377 S0 and S 2 ⁢ O 3 2 - metabolism by developing models that integrate gene expression analyzed by RNA-Seq, solution sulfur speciation, electron microscopy and spectroscopy. The A. thiooxidans S 2 ⁢ O 3 2 - metabolism model involves the conversion of S 2 ⁢ O 3 2 - to SO 4 2 - , S0 and S 4 ⁢ O 6 2 - , mediated by the sulfur oxidase complex (Sox), tetrathionate hydrolase (TetH), sulfide quinone reductase (Sqr), and heterodisulfate reductase (Hdr) proteins. These same proteins, with the addition of rhodanese (Rhd), were identified to convert S0 to SO 3 2 - , S 2 ⁢ O 3 2 - and polythionates in the A. thiooxidans S0 metabolism model. Our combined results shed light onto the important role specifically of TetH in S 2 ⁢ O 3 2 - metabolism. Also, we show that activity of Hdr proteins rather than Sdo are likely associated with S0 oxidation. Finally, our data suggest that formation of intracellular S 2 ⁢ O 3 2 - is a critical step in S0 metabolism, and that recycling of internally generated SO 3 2 - occurs, through comproportionating reactions that result in S 2 ⁢ O 3 2 - . Electron microscopy and spectroscopy confirmed intracellular production and storage of S0 during growth on both S0 and S 2 ⁢ O 3 2 - substrates. Copyright © 2020 Camacho, Frazao, Fouillen, Nanci, Lang, Apte, Baron and Warren.Bacterial glycoproteins have been investigated as vaccine candidates as well as diagnostic biomarkers. However, they are poorly understood in Mycobacterium bovis strain bacille Calmette-**érin (BCG), a non-pathogenic model of Mycobacterium tuberculosis. To understand the roles of secreted O-mannosylated glycoproteins in BCG, we conducted a ConA lectin-affinity chromatography and mass spectra analysis to identify O-mannosylated proteins in BCG culture filtrate. Subsequent screening of antigens was performed using polyclonal antibodies obtained from a BCG-immunized mouse, with 15 endogenous O-mannosylated proteins eventually identified. Of these, BCG_0470 and BCG_0980 (PstS3) were revealed as the immunodominant antigens. To examine the protective effects of the antigens, recombinant antigens proteins were first expressed in Mycobacterium smegmatis and Escherichia coli, with the purified proteins then used to boost BCG primed-****. Overall, the treated **** showed a greater delayed-type hypersensitivity response in vivo, as well as stronger Th1 responses, including higher level of IFN-γ, TNF-α, and specific-IgG. Therefore, mannosylated proteins BCG_0470 and BCG_0980 effectively amplified the immune responses induced by BCG in ****. Together, our results suggest that the oligosaccharide chains containing mannose are the antigenic determinants of glycoproteins, providing key insight for future vaccine optimization and design. Copyright © 2020 Deng, Zhang, Ji, Zhai, Shi, Liu and Yang.Fluctuating environments force bacteria to constantly adapt and optimize the uptake of substrates to maintain cellular and nutritional homeostasis. Our recent findings revealed that LrgAB functions as a pyruvate uptake system in Streptococcus mutans, and its activity is modulated in response to glucose and oxygen levels. Here, we show that the composition of the growth medium dramatically influences the magnitude and pattern of lrgAB activation. Specifically, tryptone (T) medium does not provide a preferred environment for stationary phase lrgAB activation, which is independent of external pyruvate concentration. The addition of pyruvate to T medium can elicit PlrgA activation during exponential growth, enabling the cell to utilize external pyruvate for improvement of cell growth. Through comparison of the medium composition and a series of GFP quantification assays for measurement of PlrgA activation, we found that acetate and potassium (K+) play important roles in eliciting PlrgA activation at stationary phase.
    This review focuses on the emerging roles of these molecules in the outcome of HTLV-1-associated diseases. Copyright © 2020 Zargari, Mahdifar, Mohammadi, Vahidi, Hassanshahi and Rafatpanah.Erysipelas, caused by the bacterium Erysipelothrix rhusiopathiae, is re-emerging in swine and poultry production systems worldwide. While the global genomic diversity of this species has been characterized, how much of this genomic and functional diversity is maintained at smaller scales is unclear. Specifically, while several key immunogenic surface proteins have been identified for E. rhusiopathiae, little is known about their presence among field strains and their divergence from vaccines, which could result in vaccine failure. Here, a comparative genomics approach was taken to determine the diversity of E. rhusiopathiae strains in pigs in Great Britain over nearly three decades, as well as to assess the field strains' divergence from the vaccine strain most commonly used in British pigs. In addition, the presence/absence and variability of 13 previously described immunogenic surface proteins was determined, including SpaA which is considered a key immunogen. We found a high diversity of E. rhusiopathiae suence variants in these proteins could be responsible for differences in the efficacy of the immune response. https://www.selleckchem.com/products/pmx-53.html Our results provide the necessary basis for testing this hypothesis through in vitro and in vivo studies. Copyright © 2020 Forde, Kollanandi Ratheesh, Harvey, Thomson, Williamson, Biek and Opriessnig.Pseudorabies virus (PRV) infection brings about great economic losses to the swine industry worldwide, as there are currently no effective therapeutic agents or vaccines against this disease, and mutations in endemic wild virulent PRV strains result in immune failure of traditional vaccines. Heme oxygenase-1 (HO-1) catalyzes the conversion of heme into biliverdin (BV), iron and carbon monoxide (CO), all of which have been demonstrated to protect cells from various stressors. However, the role of HO-1 in PRV replication remains unknown. Thus, the present study aimed to investigate the effect of HO-1 on PRV replication and determine its underlying molecular mechanisms. The results demonstrated that induction of HO-1 via cobalt-protoporphyrin (CoPP) markedly suppressed PRV replication, while HO-1 specific small interfering RNA or inhibitor zinc-protoporphyrin partially reversed the inhibitory effect of CoPP on PRV replication. Furthermore, overexpression of HO-1 notably inhibited PRV replication, while knockdown of endogenous HO-1 expression promoted PRV replication. Mechanism analyses indicated that the HO-1 downstream metabolites, CO and BV/BR partially mediated the virus suppressive effect of HO-1. Taken together, the results of the present study suggest that HO-1 may be developed as a novel endogenous antiviral factor against PRV, and the HO-1/BV/CO system may constitute a unique antiviral protection network during PRV infection and interaction with host cells. Copyright © 2020 Zhang, Wan, Jiang, Wu, Ji, Du and Zhang.Here, we experimentally expand understanding of the reactions and enzymes involved in Acidithiobacillus thiooxidans ATCC 19377 S0 and S 2 ⁢ O 3 2 - metabolism by developing models that integrate gene expression analyzed by RNA-Seq, solution sulfur speciation, electron microscopy and spectroscopy. The A. thiooxidans S 2 ⁢ O 3 2 - metabolism model involves the conversion of S 2 ⁢ O 3 2 - to SO 4 2 - , S0 and S 4 ⁢ O 6 2 - , mediated by the sulfur oxidase complex (Sox), tetrathionate hydrolase (TetH), sulfide quinone reductase (Sqr), and heterodisulfate reductase (Hdr) proteins. These same proteins, with the addition of rhodanese (Rhd), were identified to convert S0 to SO 3 2 - , S 2 ⁢ O 3 2 - and polythionates in the A. thiooxidans S0 metabolism model. Our combined results shed light onto the important role specifically of TetH in S 2 ⁢ O 3 2 - metabolism. Also, we show that activity of Hdr proteins rather than Sdo are likely associated with S0 oxidation. Finally, our data suggest that formation of intracellular S 2 ⁢ O 3 2 - is a critical step in S0 metabolism, and that recycling of internally generated SO 3 2 - occurs, through comproportionating reactions that result in S 2 ⁢ O 3 2 - . Electron microscopy and spectroscopy confirmed intracellular production and storage of S0 during growth on both S0 and S 2 ⁢ O 3 2 - substrates. Copyright © 2020 Camacho, Frazao, Fouillen, Nanci, Lang, Apte, Baron and Warren.Bacterial glycoproteins have been investigated as vaccine candidates as well as diagnostic biomarkers. However, they are poorly understood in Mycobacterium bovis strain bacille Calmette-Guérin (BCG), a non-pathogenic model of Mycobacterium tuberculosis. To understand the roles of secreted O-mannosylated glycoproteins in BCG, we conducted a ConA lectin-affinity chromatography and mass spectra analysis to identify O-mannosylated proteins in BCG culture filtrate. Subsequent screening of antigens was performed using polyclonal antibodies obtained from a BCG-immunized mouse, with 15 endogenous O-mannosylated proteins eventually identified. Of these, BCG_0470 and BCG_0980 (PstS3) were revealed as the immunodominant antigens. To examine the protective effects of the antigens, recombinant antigens proteins were first expressed in Mycobacterium smegmatis and Escherichia coli, with the purified proteins then used to boost BCG primed-mice. Overall, the treated mice showed a greater delayed-type hypersensitivity response in vivo, as well as stronger Th1 responses, including higher level of IFN-γ, TNF-α, and specific-IgG. Therefore, mannosylated proteins BCG_0470 and BCG_0980 effectively amplified the immune responses induced by BCG in mice. Together, our results suggest that the oligosaccharide chains containing mannose are the antigenic determinants of glycoproteins, providing key insight for future vaccine optimization and design. Copyright © 2020 Deng, Zhang, Ji, Zhai, Shi, Liu and Yang.Fluctuating environments force bacteria to constantly adapt and optimize the uptake of substrates to maintain cellular and nutritional homeostasis. Our recent findings revealed that LrgAB functions as a pyruvate uptake system in Streptococcus mutans, and its activity is modulated in response to glucose and oxygen levels. Here, we show that the composition of the growth medium dramatically influences the magnitude and pattern of lrgAB activation. Specifically, tryptone (T) medium does not provide a preferred environment for stationary phase lrgAB activation, which is independent of external pyruvate concentration. The addition of pyruvate to T medium can elicit PlrgA activation during exponential growth, enabling the cell to utilize external pyruvate for improvement of cell growth. Through comparison of the medium composition and a series of GFP quantification assays for measurement of PlrgA activation, we found that acetate and potassium (K+) play important roles in eliciting PlrgA activation at stationary phase.
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  • In the most recent Brazilian yellow fever (YF) outbreak, a group of clinicians and researchers initiated in mid-January 2018 a considerable effort to develop a multicenter randomized controlled clinical trial to evaluate the effect of sofosbuvir on YF viremia and clinical outcomes (Brazilian Clinical Trials Registry RBR-93dp9n). The approval of this protocol had urgency given the seasonal/short-lived pattern of YF transmission, large number of human cases, and epidemic transmission at the outskirts of a large urban center. However, many intricacies in the research regulatory and ethical submission systems in Brazil were indomitable even under such pressing conditions. By April 2018, we had enrolled 29 patients for a target sample size of 90 participants. Had enrollment been initiated 3 weeks earlier, an additional 31 patients could have been enrolled, reaching the prespecified sample size for the interim analysis. This recent experience highlights the urgent need to improve local preparedness for research in the setting of explosive outbreaks, as has been seen in the last few years in different countries.A novel bacterium, designated strain PS13T, was isolated from marine sediment collected from the coast of Jeju Island. Strain PS13T was a Gram stain-negative, catalase- and oxidase-positive, aerobic, yellow-pigmented, motile by gliding, and rod-shaped bacterium. Strain PS13T grew optimally at 25 °C and pH 8.0 and in the presence of 3 % (w/v) NaCl. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain PS13T belonged to the genus Formosa and was closely related to Formosa algae KMM3553T (98.3 % sequence similarity). The DNA-DNA relatedness (17.3-21.8 %) and average nucleotide identity (83.6-84.6 %) values clearly indicated that strain PS13T represents a distinct species of the genus Formosa. The major fatty acids were C15  0 iso, C16  1 ω6c/C16  1 ω7c and C15  1 iso G. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html The genomic DNA G+C content of the strain PS13T was 32.2 mol%. On the basis of polyphasic characteristics, it is suggested that strain PS13T be assigned to the genus Formosa as the type strain of a novel species, for which the name Formosa sediminum PS13T (=KCCM 43301T=CECT 9918T) sp. nov. is proposed.The reclassification of Leptotrichia goodfellowii as Pseudoleptotrichia goodfellowii gen. nov., comb. nov. is proposed because of the separate phylogenetic position on the basis of the results of 16S rRNA gene sequence analysis, the genomic differences from all other Leptotrichia species and phenotypic differences from Leptotrichia species. The species Pseudoleptotrichia goodfellowii is the type species of the genus. The type strain is LB 57T, CCUG 32286 T, DSM 19756T.Three isolates, 5K138T, 8K307T and KC603T, with typical morphological characteristics of members of the genus Jiangella were obtained during a study searching for novel actinobacteria with biosynthetic potential from the Karakum Desert. A polyphasic approach was adopted to determine taxonomic affiliations of the strains. The strains showed chemotaxonomic properties consistent with their classification as representing members of the genus Jiangella such as ll-diaminopimelic acid in the cell wall peptidoglycan, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as major polar lipids as well as MK-9(H4) as a major menaquinone. Pairwise sequence comparisons of the 16S rRNA genes showed that the strains were closely related to Jiangella alba DSM 45237T, Jiangella rhizosphaerae NEAU-YY265T and Jiangella mangrovi 3SM4-07T with higher than 99 % sequence identities. However, a combination of phenotypic and phylogenetic approaches as well as genome-based comparative analyses confirmed the taxonomic positions of these strains as representing distinct species within the genus Jiangella. Therefore, strains 5K138T, 8K307T and KC603T should each be classified as representing a novel species within the genus Jiangella, for which the names Jiangella asiatica sp. nov., Jiangella aurantiaca sp. nov. and Jiangella ureilytica sp. nov. are proposed, respectively. The type strains of the proposed novel species are as follows Jiangella asiatica 5K138T (=JCM 33518T=CGMCC 4.7672T), Jiangella aurantiaca 8K307T (=JCM 33519T=CGMCC 4.7621T) and Jiangella ureilytica KC603T (=JCM 33520T=CGMCC 4.7618T).A novel lactic acid bacterium, strain MB7T, was isolated from lychee in Taiwan. MB7T is Gram-staining-positive, catalase-negative, non-motile, non-haemolytic, facultatively anaerobic, coccoid-shaped, heterofermentative and mainly produces d-lactic acid from glucose. Comparative analysis of 16S rRNA, pheS and rpoA gene sequences has demonstrated that the novel strain represented a member of the genus Leuconostoc. 16S rRNA gene sequencing results indicated that MB7T had the same sequence similarity of 99.25 % to four type strains of members of the genus Leuconostoc Leuconostoc mesenteroides subsp. dextranicum DSM 20484T, Leuconostoc mesenteroides subsp. jonggajibkimchii DRC 1506T, Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T and Leuconostoc suionicum DSM 20241T. Additionally, high 16S rRNA sequence similarities were also observed with Leuconostoc mesenteroides subsp. cremoris ATCC 19254T (99.12 %) and Leuconostoc pseudomesenteroides NRIC 1777T (98.69 %). When comparing the genomes of these type strains, the average nucleotide identity values and digital DNA-DNA hybridization values of MB7T with these type strains were 76.57-80.53 and 22.0-22.6 %, respectively. MB7T also showed different phenotypic characteristics to other most closely related species of the genus Leuconostoc, such as carbohydrate metabolizing ability, halotolerance and growth at various pHs. On the basis of phenotypic and genotypic properties, strain MB7T represents a novel species belonging to the genus Leuconostoc, for which the name Leuconostoc litchii sp. nov. is proposed. The type strain is MB7T (=BCRC 81077T=NBRC 113542T).We describe a new multidrug resistant Chitinophaga species that was isolated from patients with type 2 diabetes in Vietnam. Strain BD 01T was cultivated in 2017 from a blood sample of a patient suffering from bacteremia. Strain VP 7442 was isolated in 2018 from a pleural fluid sample of a patient who had presented with lung abscess and pleural effusion. Both strains are aerobic, Gram-negative, non-motile and non-spore-forming. The 16S rRNA gene sequences of both strains are 100 % similar and share a highest 16S sequence identity with Chitinophaga polysaccharea MRP-15T of 97.42 %. Their predominant fatty acid is iso-C15  0 (73.8 % for strain BD 01T and 79.8 % for strain VP 7442). The draft genome sizes of strains BD 01T and VP 7442 are 6 308 408 and 6 308 579 bp, respectively. They are resistant to beta-lactams, aminoglycosides, fluoroquinolones, metronidazole, fosfomycin, vancomycin and macrolides, and exhibit 20 and 18 antimicrobial resistance-related genes, respectively. Using the multiphasic taxonogenomic approach, we propose that strains BD 01T (=CSUR P9622=VTCC 70981) and VP 7442 (=CSUR P9623=VTCC 70982) represent a new species, for which we propose the name Chitinophaga vietnamensis sp.
    In the most recent Brazilian yellow fever (YF) outbreak, a group of clinicians and researchers initiated in mid-January 2018 a considerable effort to develop a multicenter randomized controlled clinical trial to evaluate the effect of sofosbuvir on YF viremia and clinical outcomes (Brazilian Clinical Trials Registry RBR-93dp9n). The approval of this protocol had urgency given the seasonal/short-lived pattern of YF transmission, large number of human cases, and epidemic transmission at the outskirts of a large urban center. However, many intricacies in the research regulatory and ethical submission systems in Brazil were indomitable even under such pressing conditions. By April 2018, we had enrolled 29 patients for a target sample size of 90 participants. Had enrollment been initiated 3 weeks earlier, an additional 31 patients could have been enrolled, reaching the prespecified sample size for the interim analysis. This recent experience highlights the urgent need to improve local preparedness for research in the setting of explosive outbreaks, as has been seen in the last few years in different countries.A novel bacterium, designated strain PS13T, was isolated from marine sediment collected from the coast of Jeju Island. Strain PS13T was a Gram stain-negative, catalase- and oxidase-positive, aerobic, yellow-pigmented, motile by gliding, and rod-shaped bacterium. Strain PS13T grew optimally at 25 °C and pH 8.0 and in the presence of 3 % (w/v) NaCl. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain PS13T belonged to the genus Formosa and was closely related to Formosa algae KMM3553T (98.3 % sequence similarity). The DNA-DNA relatedness (17.3-21.8 %) and average nucleotide identity (83.6-84.6 %) values clearly indicated that strain PS13T represents a distinct species of the genus Formosa. The major fatty acids were C15  0 iso, C16  1 ω6c/C16  1 ω7c and C15  1 iso G. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html The genomic DNA G+C content of the strain PS13T was 32.2 mol%. On the basis of polyphasic characteristics, it is suggested that strain PS13T be assigned to the genus Formosa as the type strain of a novel species, for which the name Formosa sediminum PS13T (=KCCM 43301T=CECT 9918T) sp. nov. is proposed.The reclassification of Leptotrichia goodfellowii as Pseudoleptotrichia goodfellowii gen. nov., comb. nov. is proposed because of the separate phylogenetic position on the basis of the results of 16S rRNA gene sequence analysis, the genomic differences from all other Leptotrichia species and phenotypic differences from Leptotrichia species. The species Pseudoleptotrichia goodfellowii is the type species of the genus. The type strain is LB 57T, CCUG 32286 T, DSM 19756T.Three isolates, 5K138T, 8K307T and KC603T, with typical morphological characteristics of members of the genus Jiangella were obtained during a study searching for novel actinobacteria with biosynthetic potential from the Karakum Desert. A polyphasic approach was adopted to determine taxonomic affiliations of the strains. The strains showed chemotaxonomic properties consistent with their classification as representing members of the genus Jiangella such as ll-diaminopimelic acid in the cell wall peptidoglycan, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as major polar lipids as well as MK-9(H4) as a major menaquinone. Pairwise sequence comparisons of the 16S rRNA genes showed that the strains were closely related to Jiangella alba DSM 45237T, Jiangella rhizosphaerae NEAU-YY265T and Jiangella mangrovi 3SM4-07T with higher than 99 % sequence identities. However, a combination of phenotypic and phylogenetic approaches as well as genome-based comparative analyses confirmed the taxonomic positions of these strains as representing distinct species within the genus Jiangella. Therefore, strains 5K138T, 8K307T and KC603T should each be classified as representing a novel species within the genus Jiangella, for which the names Jiangella asiatica sp. nov., Jiangella aurantiaca sp. nov. and Jiangella ureilytica sp. nov. are proposed, respectively. The type strains of the proposed novel species are as follows Jiangella asiatica 5K138T (=JCM 33518T=CGMCC 4.7672T), Jiangella aurantiaca 8K307T (=JCM 33519T=CGMCC 4.7621T) and Jiangella ureilytica KC603T (=JCM 33520T=CGMCC 4.7618T).A novel lactic acid bacterium, strain MB7T, was isolated from lychee in Taiwan. MB7T is Gram-staining-positive, catalase-negative, non-motile, non-haemolytic, facultatively anaerobic, coccoid-shaped, heterofermentative and mainly produces d-lactic acid from glucose. Comparative analysis of 16S rRNA, pheS and rpoA gene sequences has demonstrated that the novel strain represented a member of the genus Leuconostoc. 16S rRNA gene sequencing results indicated that MB7T had the same sequence similarity of 99.25 % to four type strains of members of the genus Leuconostoc Leuconostoc mesenteroides subsp. dextranicum DSM 20484T, Leuconostoc mesenteroides subsp. jonggajibkimchii DRC 1506T, Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T and Leuconostoc suionicum DSM 20241T. Additionally, high 16S rRNA sequence similarities were also observed with Leuconostoc mesenteroides subsp. cremoris ATCC 19254T (99.12 %) and Leuconostoc pseudomesenteroides NRIC 1777T (98.69 %). When comparing the genomes of these type strains, the average nucleotide identity values and digital DNA-DNA hybridization values of MB7T with these type strains were 76.57-80.53 and 22.0-22.6 %, respectively. MB7T also showed different phenotypic characteristics to other most closely related species of the genus Leuconostoc, such as carbohydrate metabolizing ability, halotolerance and growth at various pHs. On the basis of phenotypic and genotypic properties, strain MB7T represents a novel species belonging to the genus Leuconostoc, for which the name Leuconostoc litchii sp. nov. is proposed. The type strain is MB7T (=BCRC 81077T=NBRC 113542T).We describe a new multidrug resistant Chitinophaga species that was isolated from patients with type 2 diabetes in Vietnam. Strain BD 01T was cultivated in 2017 from a blood sample of a patient suffering from bacteremia. Strain VP 7442 was isolated in 2018 from a pleural fluid sample of a patient who had presented with lung abscess and pleural effusion. Both strains are aerobic, Gram-negative, non-motile and non-spore-forming. The 16S rRNA gene sequences of both strains are 100 % similar and share a highest 16S sequence identity with Chitinophaga polysaccharea MRP-15T of 97.42 %. Their predominant fatty acid is iso-C15  0 (73.8 % for strain BD 01T and 79.8 % for strain VP 7442). The draft genome sizes of strains BD 01T and VP 7442 are 6 308 408 and 6 308 579 bp, respectively. They are resistant to beta-lactams, aminoglycosides, fluoroquinolones, metronidazole, fosfomycin, vancomycin and macrolides, and exhibit 20 and 18 antimicrobial resistance-related genes, respectively. Using the multiphasic taxonogenomic approach, we propose that strains BD 01T (=CSUR P9622=VTCC 70981) and VP 7442 (=CSUR P9623=VTCC 70982) represent a new species, for which we propose the name Chitinophaga vietnamensis sp.
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  • The ACR recognizes that radiology practices are grappling with when and how to safely resume routine radiology care during the coronavirus disease 2019 (COVID-19) pandemic. Although it is unclear how long the pandemic will last, it may persist for many months. Throughout this time, it will be important to perform safe, comprehensive, and effective care for patients with and patients without COVID-19, recognizing that asymptomatic transmission is common with this disease. Local idiosyncrasies prevent a single prescriptive strategy. However, general considerations can be applied to most practice environments. A comprehensive strategy will include consideration of local COVID-19 statistics; availability of personal protective equipment (PPE); local, state, and federal government mandates; institutional regulatory guidance; local safety measures; health care worker availability; patient and health care worker risk factors; factors specific to the indication(s) for radiology care; and examination or procedure acuity. An accurate risk-benefit analysis of postponing versus performing a given routine radiology examination or procedure often is not possible due to many unknown and complex factors. However, this is the overriding principle If the risk of illness or death to a health care worker or patient from health care-acquired COVID-19 is greater than the risk of illness or death from delaying radiology care, the care should be delayed; however, if the opposite is true, the radiology care should proceed in a timely fashion.The purpose of this study was to estimate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in western French Guiana and to analyze associated factors with both infections. A retrospective study was conducted in a sexually transmitted infections clinic in 2017. Women (n=338) were tested by real-time polymerase chain reaction for vaginal, anal and throat CT and NG infections. Men (n=192) were evaluated using urine specimens. Socio-demographic and sexual behaviour data were collected by nurses with a structured questionnaire. The prevalence of CT and NG infections among women were 24.3% and 13.3%, respectively, and 12.0% and 7.3% among men. Women aged under 25 years had a higher risk of CT and NG infections than women aged 35 years or more. Another risk factor for CT infection was low educational level, and occasional unprotected sex for NG infection. CT and NG infections were associated with reporting symptoms among men. Very high prevalences of CT and NG infections among women and men were found, which suggest that a large-scale screening strategy should be implemented in French Guiana.Purpose Localized amyloidosis of the tongue is a benign condition in which surgical management may be considered. The aim of the study was to review the current literature and report a case. Materials and methods We searched the PubMed database for all relevant articles reporting cases of localized tongue amyloidosis published between 1980 and February 2020. In addition, we updated 1 case diagnosed and treated in our department. Results A 49-year-old male patient presented with an asymptomatic tongue nodule of the dorsum mimicking median rhomboid glossitis. The results of an incisional biopsy showed an amyloid on Congo red staining and positive findings for the κ light chain by immunohistochemical analysis. The findings of the systemic workup were negative. Therefore, a diagnosis of localized κ light-chain amyloidosis was made. The patient underwent a resection of the lesion, and no recurrence or progression was observed during a period of 18 months. The literature review showed 12 reports describing 21 patients (11 men, 52.3%) with localized tongue amyloidosis. The most common clinical presentation was nodular with a single lesion of the tongue dorsum (15 patients, 71.4%). All cases showed positive findings on Congo red staining. Immunohistochemical analysis findings were available for only 9 patients (42.8%) and showed light-chain amyloidosis. No case showed any systemic involvement or the development of systemic disease. Surgical excision was performed in 9 cases, with recurrence at the site of operation in 2 cases. Conclusions Localized amyloidosis of the tongue is a rare disease in which surgical excision may be therapeutic when a multidisciplinary evaluation does not show any systemic disease. We recommend an excision when the lesion is persistent or shows an enlargement or when discomfort is reported. In the case of any further local recurrence, resection may be repeated.Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors.Aberrant chromosome numbers in cancer cells may impose distinct constraints on the emergence of drug resistance-a major factor limiting the long-term efficacy of molecularly targeted therapeutics. However, for most anticancer drugs we lack analyses of drug-resistance mechanisms in cells with different karyotypes. Here, we focus on GSK923295, a mitotic kinesin CENP-E inhibitor that was evaluated in clinical trials as a cancer therapeutic. We performed unbiased selections to isolate inhibitor-resistant clones in diploid and near-haploid cancer cell lines. In diploid cells we identified single-point mutations that can suppress inhibitor binding. https://www.selleckchem.com/products/cct128930.html In contrast,transcriptome analyses revealed that the C-terminus of CENP-E was disrupted in GSK923295-resistant near-haploid cells. While chemical inhibition of CENP-E is toxic to near-haploid cells, knockout of the CENPE gene does not suppress haploid cell proliferation, suggesting that deletion of the CENP-E C-terminus can confer resistance to GSK923295. Together, these findings indicate that different chromosome copy numbers in cells can alter epistatic dependencies and lead to distinct modes of chemotype-specific resistance.
    The ACR recognizes that radiology practices are grappling with when and how to safely resume routine radiology care during the coronavirus disease 2019 (COVID-19) pandemic. Although it is unclear how long the pandemic will last, it may persist for many months. Throughout this time, it will be important to perform safe, comprehensive, and effective care for patients with and patients without COVID-19, recognizing that asymptomatic transmission is common with this disease. Local idiosyncrasies prevent a single prescriptive strategy. However, general considerations can be applied to most practice environments. A comprehensive strategy will include consideration of local COVID-19 statistics; availability of personal protective equipment (PPE); local, state, and federal government mandates; institutional regulatory guidance; local safety measures; health care worker availability; patient and health care worker risk factors; factors specific to the indication(s) for radiology care; and examination or procedure acuity. An accurate risk-benefit analysis of postponing versus performing a given routine radiology examination or procedure often is not possible due to many unknown and complex factors. However, this is the overriding principle If the risk of illness or death to a health care worker or patient from health care-acquired COVID-19 is greater than the risk of illness or death from delaying radiology care, the care should be delayed; however, if the opposite is true, the radiology care should proceed in a timely fashion.The purpose of this study was to estimate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in western French Guiana and to analyze associated factors with both infections. A retrospective study was conducted in a sexually transmitted infections clinic in 2017. Women (n=338) were tested by real-time polymerase chain reaction for vaginal, anal and throat CT and NG infections. Men (n=192) were evaluated using urine specimens. Socio-demographic and sexual behaviour data were collected by nurses with a structured questionnaire. The prevalence of CT and NG infections among women were 24.3% and 13.3%, respectively, and 12.0% and 7.3% among men. Women aged under 25 years had a higher risk of CT and NG infections than women aged 35 years or more. Another risk factor for CT infection was low educational level, and occasional unprotected sex for NG infection. CT and NG infections were associated with reporting symptoms among men. Very high prevalences of CT and NG infections among women and men were found, which suggest that a large-scale screening strategy should be implemented in French Guiana.Purpose Localized amyloidosis of the tongue is a benign condition in which surgical management may be considered. The aim of the study was to review the current literature and report a case. Materials and methods We searched the PubMed database for all relevant articles reporting cases of localized tongue amyloidosis published between 1980 and February 2020. In addition, we updated 1 case diagnosed and treated in our department. Results A 49-year-old male patient presented with an asymptomatic tongue nodule of the dorsum mimicking median rhomboid glossitis. The results of an incisional biopsy showed an amyloid on Congo red staining and positive findings for the κ light chain by immunohistochemical analysis. The findings of the systemic workup were negative. Therefore, a diagnosis of localized κ light-chain amyloidosis was made. The patient underwent a resection of the lesion, and no recurrence or progression was observed during a period of 18 months. The literature review showed 12 reports describing 21 patients (11 men, 52.3%) with localized tongue amyloidosis. The most common clinical presentation was nodular with a single lesion of the tongue dorsum (15 patients, 71.4%). All cases showed positive findings on Congo red staining. Immunohistochemical analysis findings were available for only 9 patients (42.8%) and showed light-chain amyloidosis. No case showed any systemic involvement or the development of systemic disease. Surgical excision was performed in 9 cases, with recurrence at the site of operation in 2 cases. Conclusions Localized amyloidosis of the tongue is a rare disease in which surgical excision may be therapeutic when a multidisciplinary evaluation does not show any systemic disease. We recommend an excision when the lesion is persistent or shows an enlargement or when discomfort is reported. In the case of any further local recurrence, resection may be repeated.Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors.Aberrant chromosome numbers in cancer cells may impose distinct constraints on the emergence of drug resistance-a major factor limiting the long-term efficacy of molecularly targeted therapeutics. However, for most anticancer drugs we lack analyses of drug-resistance mechanisms in cells with different karyotypes. Here, we focus on GSK923295, a mitotic kinesin CENP-E inhibitor that was evaluated in clinical trials as a cancer therapeutic. We performed unbiased selections to isolate inhibitor-resistant clones in diploid and near-haploid cancer cell lines. In diploid cells we identified single-point mutations that can suppress inhibitor binding. https://www.selleckchem.com/products/cct128930.html In contrast,transcriptome analyses revealed that the C-terminus of CENP-E was disrupted in GSK923295-resistant near-haploid cells. While chemical inhibition of CENP-E is toxic to near-haploid cells, knockout of the CENPE gene does not suppress haploid cell proliferation, suggesting that deletion of the CENP-E C-terminus can confer resistance to GSK923295. Together, these findings indicate that different chromosome copy numbers in cells can alter epistatic dependencies and lead to distinct modes of chemotype-specific resistance.
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  • Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their "view" of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.The importance of reported neurological manifestations of coronavirus disease 2019 (COVID-19) is still unclear. Nevertheless, an immediate and ongoing neurological challenge posed by the COVID-19 pandemic is the management of patients who are undergoing immunotherapy for existing neuroimmunological disease.We considered the magnetized micro polar fluid with hybrid nanomaterial flow over a curved stretching surface. We discussed the effects of single wall carbon nanotube and multiwall carbon nanotube with base fluids (water and propylene glycol). Under the flow assumptions, we developed the mathematical model and applied the boundary layer approximations to reduce the system of partial differential equations. Further, the suitable similarity transformations are applied on the partial differential equations to make dimensionless system. The dimensionless system solved by means of numerical scheme via bvp4c shooting methods. https://www.selleckchem.com/products/cct251545.html Involving the dimensionless physical parameters effects are highlighted in the form of graphs and tables. Additionally, significant physical quantities i.e. Nusselt number, Couple stress coefficient and Skin friction coefficient are also presented and evaluated numerically. These results are more important which may use in the field of engineering and industrial.Inhalation of asbestos fibres can cause lung and pleural diseases in humans and constitutes a severe public health threat worldwide. The aim of the present study was to assess the biological effects induced in both pulmonary cells (A549) and monocyte/macrophage (RAW 264.7) cell lines by combustion slags obtained from asbestos through a self-sustained high-temperature synthesis (SHS) reaction. The SHS reaction involves rapid thermal treatment and displays great ability to neutralise asbestos. Cytotoxicity, redox status imbalance, lipid peroxide production, DNA strand breaks (comet assay) and chromosomal aberrations (cytokinesis block micronucleus test) were evaluated in cells exposed either to untreated asbestos fibres or to grinded SHS-generated slags of different granulometry, tested in cultured cells at varying doses and for varying exposure times. Our results show that asbestos fibres cause redox status imbalance, especially in monocyte/macrophage cell lines. Moreover, they promote lipid peroxidation and trigger genomic alterations. When the cells were exposed to **** powders, which are the products of SHS asbestos treatment, generation of lipid peroxides and induction of DNA strand breaks still persisted, due to the high content in iron and other metals detected in these samples. However, there was an attenuation of redox status imbalance and an absence of chromosomal aberrations, which probably reflects the loss of the asbestos fibrous structure following SHS reaction, as demonstrated by electron microscopy analyses. In conclusions, SHS-treated asbestos wastes can potentially have deleterious health effects due to the oxidative stress induced by inhaled powders but they loose the asbestos ability to induce chromosomal alterations.Molybdenum modified LiNi0.84Co0.11Mn0.05O2 cathode with different doping concentrations (0-5 wt.%) is successfully prepared and its electrochemical performances are investigated. It is demonstrated that molybdenum in LiNi0.84Co0.11Mn0.05O2 has a positive effect on structural stability and extraordinary electrochemical performances, including improved long-term cycling and high-rate capability. Among all samples, the 1 wt. % molybdenum LiNi0.84Co0.11Mn0.05O2 delivers superior initial discharge capacity of 205 mAh g-1 (0.1 C), cycling stability of 89.5% (0.5 C) and rate capability of 165 mAh g-1 (2 C) compared to those of others. Therefore, we can conclude that the 1 wt. % molybdenum is an effective strategy for Ni-rich LiNi0.84Co0.11Mn0.05O2 cathode used in lithium ion batteries.Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient's overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns.
    Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their "view" of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.The importance of reported neurological manifestations of coronavirus disease 2019 (COVID-19) is still unclear. Nevertheless, an immediate and ongoing neurological challenge posed by the COVID-19 pandemic is the management of patients who are undergoing immunotherapy for existing neuroimmunological disease.We considered the magnetized micro polar fluid with hybrid nanomaterial flow over a curved stretching surface. We discussed the effects of single wall carbon nanotube and multiwall carbon nanotube with base fluids (water and propylene glycol). Under the flow assumptions, we developed the mathematical model and applied the boundary layer approximations to reduce the system of partial differential equations. Further, the suitable similarity transformations are applied on the partial differential equations to make dimensionless system. The dimensionless system solved by means of numerical scheme via bvp4c shooting methods. https://www.selleckchem.com/products/cct251545.html Involving the dimensionless physical parameters effects are highlighted in the form of graphs and tables. Additionally, significant physical quantities i.e. Nusselt number, Couple stress coefficient and Skin friction coefficient are also presented and evaluated numerically. These results are more important which may use in the field of engineering and industrial.Inhalation of asbestos fibres can cause lung and pleural diseases in humans and constitutes a severe public health threat worldwide. The aim of the present study was to assess the biological effects induced in both pulmonary cells (A549) and monocyte/macrophage (RAW 264.7) cell lines by combustion slags obtained from asbestos through a self-sustained high-temperature synthesis (SHS) reaction. The SHS reaction involves rapid thermal treatment and displays great ability to neutralise asbestos. Cytotoxicity, redox status imbalance, lipid peroxide production, DNA strand breaks (comet assay) and chromosomal aberrations (cytokinesis block micronucleus test) were evaluated in cells exposed either to untreated asbestos fibres or to grinded SHS-generated slags of different granulometry, tested in cultured cells at varying doses and for varying exposure times. Our results show that asbestos fibres cause redox status imbalance, especially in monocyte/macrophage cell lines. Moreover, they promote lipid peroxidation and trigger genomic alterations. When the cells were exposed to slag powders, which are the products of SHS asbestos treatment, generation of lipid peroxides and induction of DNA strand breaks still persisted, due to the high content in iron and other metals detected in these samples. However, there was an attenuation of redox status imbalance and an absence of chromosomal aberrations, which probably reflects the loss of the asbestos fibrous structure following SHS reaction, as demonstrated by electron microscopy analyses. In conclusions, SHS-treated asbestos wastes can potentially have deleterious health effects due to the oxidative stress induced by inhaled powders but they loose the asbestos ability to induce chromosomal alterations.Molybdenum modified LiNi0.84Co0.11Mn0.05O2 cathode with different doping concentrations (0-5 wt.%) is successfully prepared and its electrochemical performances are investigated. It is demonstrated that molybdenum in LiNi0.84Co0.11Mn0.05O2 has a positive effect on structural stability and extraordinary electrochemical performances, including improved long-term cycling and high-rate capability. Among all samples, the 1 wt. % molybdenum LiNi0.84Co0.11Mn0.05O2 delivers superior initial discharge capacity of 205 mAh g-1 (0.1 C), cycling stability of 89.5% (0.5 C) and rate capability of 165 mAh g-1 (2 C) compared to those of others. Therefore, we can conclude that the 1 wt. % molybdenum is an effective strategy for Ni-rich LiNi0.84Co0.11Mn0.05O2 cathode used in lithium ion batteries.Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient's overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns.
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  • Given a set of species whose evolution is represented by a species tree, a gene family is a group of genes having evolved from a single ancestral gene. A gene family evolves along the branches of a species tree through various mechanisms, including-but not limited to-speciation ([Formula see text]), gene duplication ([Formula see text]), gene loss ([Formula see text]), and horizontal gene transfer ([Formula see text]). The reconstruction of a gene tree representing the evolution of a gene family constrained by a species tree is an important problem in phylogenomics. However, unlike in the multispecies coalescent evolutionary model that considers only speciation and incomplete lineage sorting events, very little is known about the search space for gene family histories accounting for gene duplication, gene loss and horizontal gene transfer (the [Formula see text]-model). In this work, we introduce the notion of evolutionary histories defined as a binary ordered rooted tree describing the evolution of a gene faof the species tree topology. These results establish firm foundations for the development of ensemble methods for the prediction of reconciliations.Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL.Few studies exist that compare local flap repair designs either mathematically or clinically. Previous mathematical studies use a two-dimensional modeling approach, which is not suited to complex structures like the nose. To quantitatively analyze and compare flap designs for nasal repair using three-dimensional, photographic models. via a three-dimensional imaging system (Vectra M3, Canfield Scientific, Parsippany, NJ, USA), images were captured of actual post-Mohs nasal defects on 12 consecutive patients. Transposition, rotation, and advancement flap designs were designed and assessed based on tissue efficiency (Et = SAwound/(SAwound + SAtrimmed) × 100), suture efficiency (Es = SAwound/Lengthsutured × 100), total area undermined, combined 1° and 2° flap motion efficiency (Efm = SAwound/(SAundermined - (SAwound + SAtrimmed)) × 100), incision efficiency (Ei = SAwound/lengthincision × 100), and undermining efficiency (Eu = SAwound/SAundermined × 100). Rotation flap designs are the most tissue efficient (p  less then  0.001). Transposition designs are the least suture efficient (p = 0.012) and require less undermining than the corresponding rotation ***** (although not statistically significant). Advancement ***** have the highest flap motion efficiency (p = 0.027). Incision and undermining efficiency is equivalent between all three designs (p = 0.308 and p = 0.158, respectively). While statistically significant differences exist between the ***** studied, the clinical significance is unknown. Consequently, the choice in repair design should be made based on its ability to attain a functionally and aesthetically successful reconstruction.PURPOSE Lapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine. METHODS We used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib. RESULTS Rats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide. CONCLUSIONS Elsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea.PURPOSE One of the oldest procedures performed by man is trepanning of the bone and yet it was only in the last 40 years that bone marrow aspiration has been used to treat nonunion disorders. MATERIAL AND METHODS These advances were possible due to improvements in instruments and in techniques to make holes in the bone, an history that began with skull trephinations around 8000-10,000 years ago, and continued with sternum bone marrow injection for trauma resuscitation in the beginning of the twentieth century; this procedure had improved at the beginning of the twenty-first century to allow pelvis bone marrow aspiration for the treatment of nonunion. RESULTS Trephined skulls from antiquity have been found in many parts of world, showing that trephining was ancient and widespread. Beginning with Neolithic period and the pre-Columbian Andean civilizations, the authors have traced the development of this surgical skill by describing the various surgical tools used to perform holes in the skull. These tools (trephines or trepan) were proposed at the end of the nineteenth century to study the bone marrow.
    Given a set of species whose evolution is represented by a species tree, a gene family is a group of genes having evolved from a single ancestral gene. A gene family evolves along the branches of a species tree through various mechanisms, including-but not limited to-speciation ([Formula see text]), gene duplication ([Formula see text]), gene loss ([Formula see text]), and horizontal gene transfer ([Formula see text]). The reconstruction of a gene tree representing the evolution of a gene family constrained by a species tree is an important problem in phylogenomics. However, unlike in the multispecies coalescent evolutionary model that considers only speciation and incomplete lineage sorting events, very little is known about the search space for gene family histories accounting for gene duplication, gene loss and horizontal gene transfer (the [Formula see text]-model). In this work, we introduce the notion of evolutionary histories defined as a binary ordered rooted tree describing the evolution of a gene faof the species tree topology. These results establish firm foundations for the development of ensemble methods for the prediction of reconciliations.Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL.Few studies exist that compare local flap repair designs either mathematically or clinically. Previous mathematical studies use a two-dimensional modeling approach, which is not suited to complex structures like the nose. To quantitatively analyze and compare flap designs for nasal repair using three-dimensional, photographic models. via a three-dimensional imaging system (Vectra M3, Canfield Scientific, Parsippany, NJ, USA), images were captured of actual post-Mohs nasal defects on 12 consecutive patients. Transposition, rotation, and advancement flap designs were designed and assessed based on tissue efficiency (Et = SAwound/(SAwound + SAtrimmed) × 100), suture efficiency (Es = SAwound/Lengthsutured × 100), total area undermined, combined 1° and 2° flap motion efficiency (Efm = SAwound/(SAundermined - (SAwound + SAtrimmed)) × 100), incision efficiency (Ei = SAwound/lengthincision × 100), and undermining efficiency (Eu = SAwound/SAundermined × 100). Rotation flap designs are the most tissue efficient (p  less then  0.001). Transposition designs are the least suture efficient (p = 0.012) and require less undermining than the corresponding rotation flaps (although not statistically significant). Advancement flaps have the highest flap motion efficiency (p = 0.027). Incision and undermining efficiency is equivalent between all three designs (p = 0.308 and p = 0.158, respectively). While statistically significant differences exist between the flaps studied, the clinical significance is unknown. Consequently, the choice in repair design should be made based on its ability to attain a functionally and aesthetically successful reconstruction.PURPOSE Lapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine. METHODS We used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib. RESULTS Rats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide. CONCLUSIONS Elsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea.PURPOSE One of the oldest procedures performed by man is trepanning of the bone and yet it was only in the last 40 years that bone marrow aspiration has been used to treat nonunion disorders. MATERIAL AND METHODS These advances were possible due to improvements in instruments and in techniques to make holes in the bone, an history that began with skull trephinations around 8000-10,000 years ago, and continued with sternum bone marrow injection for trauma resuscitation in the beginning of the twentieth century; this procedure had improved at the beginning of the twenty-first century to allow pelvis bone marrow aspiration for the treatment of nonunion. RESULTS Trephined skulls from antiquity have been found in many parts of world, showing that trephining was ancient and widespread. Beginning with Neolithic period and the pre-Columbian Andean civilizations, the authors have traced the development of this surgical skill by describing the various surgical tools used to perform holes in the skull. These tools (trephines or trepan) were proposed at the end of the nineteenth century to study the bone marrow.
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  • ndation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation. Obesity is a chronic condition that requires long-term management and is associated with unprecedented stigma in different settings, including during interactions with the health-care system. This stigma has a negative effect on the mental and physical health of people with obesity and can lead to avoidance of health care and disruption of the doctor-patient relationship. Considerable evidence exists to suggest that simply having a conversation about obesity can lead to weight loss, which translates into health benefits. However, both health-care practitioners and people living with obesity report apprehension in initiating this conversation. We have collaborated with stakeholders from Obesity UK, physicians, dieticians, clinical psychologists, obesity researchers, conversation analysts, nurses, and representatives from National Health Service England Diabetes and Obesity. This group has contributed to the production of this consensus statement, which addresses how people living with obesity wish to have their condition referred to and provides practical guidance for health-care professionals to facilitate collaborative and supportive discussions about obesity. Expert stakeholders consider that changes to language used at the point of care can alleviate the stigma of obesity within the health-care system and support improved outcomes for both people living with obesity and for the health-care system. Diabetic ketoacidosis (DKA) is a serious acute complication of type 1 diabetes, which is receiving more attention given the increased DKA risk associated with SGLT inhibitors. Sociodemographic and modifiable risk factors were identified with strong evidence for an increased risk of DKA, including socioeconomic disadvantage, adolescent age (13-25 years), female sex, high HbA1c, previous DKA, and psychiatric comorbidities (eg, eating disorders and depression). Possible prevention strategies, which include the identification of people at risk based on non-modifiable sociodemographic risk factors, are proposed. As a second risk mitigation strategy, structured diabetes self-management education that addresses modifiable risk factors can be used. Evidence has found that structured education leads to reduced DKA rates. Knowledge of these risk factors and potent risk mitigation strategies are important to identify subgroups of people with an elevated DKA risk. This knowledge should also be used when adjunct therapy options with an increased DKA risk are considered. Prevention of DKA in people with type 1 diabetes is an important clinical task, which should also be addressed when SGLT inhibitors are part of therapy. BACKGROUND In our 2015 systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes, we reported a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure, but with heterogeneous effects by drug or intervention type. In view of the completion of many large cardiovascular outcome trials since our previous analysis, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes, we aimed to update our analysis to incorporate these findings. METHODS We did an updated systematic review and meta-analysis of large cardiovascular outcome trials of glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes. We searched Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013 to Nov 20, 2019. We included randomised controlled trials with a minimum of 100RPRETATION Glucose-lowering drugs or strategies overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall but varied substantially by intervention type, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of interventions associated with weight loss might extend to patients without established cardiovascular disease. FUNDING None. BACKGROUND Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (111) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distficant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. https://www.selleckchem.com/products/hth-01-015.html FUNDING Aalborg University Hospital and Aalborg University, Denmark. BACKGROUND New glucose-lowering medications need to be investigated in east Asian populations, as the clinical characteristics of type 2 diabetes differ between western and east Asian patients. The PIONEER 10 study aimed to evaluate the safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes. METHODS PIONEER 10 was an open-label, randomised, active-controlled, phase 3a trial done at 36 sites (clinics and university hospitals) in Japan. Patients aged 20 years and older with uncontrolled type 2 diabetes were randomly assigned (2221) to receive once-daily oral semaglutide 3 mg, 7 mg, or 14 mg, or once-weekly subcutaneous dulaglutide 0·75 mg for 52 weeks, as an add-on to their background medication. The primary endpoint was the number of treatment-emergent adverse events over 57 weeks. Supportive secondary endpoints (not controlled for multiplicity) included mean change from baseline in HbA1c and bodyweight at 52 weeks. This trial is registered with ClinicalTrials.gov, NCT03015220.
    ndation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation. Obesity is a chronic condition that requires long-term management and is associated with unprecedented stigma in different settings, including during interactions with the health-care system. This stigma has a negative effect on the mental and physical health of people with obesity and can lead to avoidance of health care and disruption of the doctor-patient relationship. Considerable evidence exists to suggest that simply having a conversation about obesity can lead to weight loss, which translates into health benefits. However, both health-care practitioners and people living with obesity report apprehension in initiating this conversation. We have collaborated with stakeholders from Obesity UK, physicians, dieticians, clinical psychologists, obesity researchers, conversation analysts, nurses, and representatives from National Health Service England Diabetes and Obesity. This group has contributed to the production of this consensus statement, which addresses how people living with obesity wish to have their condition referred to and provides practical guidance for health-care professionals to facilitate collaborative and supportive discussions about obesity. Expert stakeholders consider that changes to language used at the point of care can alleviate the stigma of obesity within the health-care system and support improved outcomes for both people living with obesity and for the health-care system. Diabetic ketoacidosis (DKA) is a serious acute complication of type 1 diabetes, which is receiving more attention given the increased DKA risk associated with SGLT inhibitors. Sociodemographic and modifiable risk factors were identified with strong evidence for an increased risk of DKA, including socioeconomic disadvantage, adolescent age (13-25 years), female sex, high HbA1c, previous DKA, and psychiatric comorbidities (eg, eating disorders and depression). Possible prevention strategies, which include the identification of people at risk based on non-modifiable sociodemographic risk factors, are proposed. As a second risk mitigation strategy, structured diabetes self-management education that addresses modifiable risk factors can be used. Evidence has found that structured education leads to reduced DKA rates. Knowledge of these risk factors and potent risk mitigation strategies are important to identify subgroups of people with an elevated DKA risk. This knowledge should also be used when adjunct therapy options with an increased DKA risk are considered. Prevention of DKA in people with type 1 diabetes is an important clinical task, which should also be addressed when SGLT inhibitors are part of therapy. BACKGROUND In our 2015 systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes, we reported a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure, but with heterogeneous effects by drug or intervention type. In view of the completion of many large cardiovascular outcome trials since our previous analysis, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes, we aimed to update our analysis to incorporate these findings. METHODS We did an updated systematic review and meta-analysis of large cardiovascular outcome trials of glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes. We searched Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013 to Nov 20, 2019. We included randomised controlled trials with a minimum of 100RPRETATION Glucose-lowering drugs or strategies overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall but varied substantially by intervention type, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of interventions associated with weight loss might extend to patients without established cardiovascular disease. FUNDING None. BACKGROUND Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (111) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distficant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. https://www.selleckchem.com/products/hth-01-015.html FUNDING Aalborg University Hospital and Aalborg University, Denmark. BACKGROUND New glucose-lowering medications need to be investigated in east Asian populations, as the clinical characteristics of type 2 diabetes differ between western and east Asian patients. The PIONEER 10 study aimed to evaluate the safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes. METHODS PIONEER 10 was an open-label, randomised, active-controlled, phase 3a trial done at 36 sites (clinics and university hospitals) in Japan. Patients aged 20 years and older with uncontrolled type 2 diabetes were randomly assigned (2221) to receive once-daily oral semaglutide 3 mg, 7 mg, or 14 mg, or once-weekly subcutaneous dulaglutide 0·75 mg for 52 weeks, as an add-on to their background medication. The primary endpoint was the number of treatment-emergent adverse events over 57 weeks. Supportive secondary endpoints (not controlled for multiplicity) included mean change from baseline in HbA1c and bodyweight at 52 weeks. This trial is registered with ClinicalTrials.gov, NCT03015220.
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  • Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT.

    A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT).

    After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vinistration of IV heparin (OR 2.077), platelet count < 100,000/mm
    (OR 4.798), bacterial endocarditis (OR 15.069), neoplasm with increased hemorrhagic risk (OR 6.046), and severe liver disease (OR 6.124).

    Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.
    Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.α-L-Arabinofuranosidase (PsGH43_12) of family 43 glycoside hydrolase and subfamily 12 from Pseudopedobacter saltans was cloned, over-expressed and biochemically characterized. PsGH43_12 displayed molecular mass, ~ 65 kDa. It exhibited activity in pH (5-9) and temperature range (35-55 °C) with maxima at pH 6.5 and 50 °C. PsGH43_12 gave 88.7 U/mg specific activity against rye arabinoxylan and 78.9 U/mg against wheat arabinoxylan. PsGH43_12 displayed Km and Vmax, 3.02 mg/ml and 103 µmole/min/mg, respectively, against rye arabinoxylan and 2.17 mM and 100.7 µmole/min/mg, respectively, against pNP-α-L-arabinofuranoside. 10 mM Mg2+ or Ca2+ ions enhanced PsGH43_12 activity by 54% or 33%, respectively. PsGH43_12 hydrolyzed rye arabinoxylan and released only L-arabinosyl moiety as main product, confirming its specificity towards α-L-arabinofuranoside. The regioselective analysis by NMR showed that PsGH43_12 belongs to type III α-L-arabinofuranoside. The synergistic behavior of PsGH43_12 in saccharification of mild alkali pretreated finger miller stalk (FMS) along with xylanase (CtXyn11A) from Clostridium thermocellum and xylosidase (BoGH43) from Bacteroides ovatus gave twofold higher total reducing sugar (TRS) yield. TLC analysis of pretreated FMS hydrolysed by CtXyn11A and BoGH43 showed xylooligosaccharides and xylose. Addition of PsGH43_12 to above combination gave mostly xylose and arabinose confirming their synergistic behavior and displaying their applicability in hydrolysis of hemicellulosic biomass.A 66-year-old woman had experienced abnormal bleeding since the age of 7. Thrombocytopenia was not detected until she was 48, and immune thrombocytopenia was diagnosed at age 66. She also reported experiencing hearing disturbance since the age of 30 and acute renal failure since the age of 61 but reported no visual disturbance. Her younger son, who was 40 years old, also experienced abnormal bleeding since the age of 6, but immune thrombocytopenia was diagnosed as late as age 35. He had no other associated disorders. Laboratory examinations of both mother and son revealed a low platelet count (8000 and 29,000 µL, respectively), giant platelets and Döhle body-like granulocyte inclusion bodies. The mother had a high creatinine level (15.4 mg/dL) and normal liver enzyme levels. MYH9 genetic analysis identified a heterozygous mutation, c.101T>A, p.Val34Glu at exon 2 in both patients. These clinical and laboratory findings were consistent with a diagnosis of an MYH9-related disorder with different phenotypes observed in the same family. MYH9-related disorders were recognised in 2003, but were often misdiagnosed as immune thrombocytopenia, and hence, they have rarely been reported in Taiwan.
    To report our experience and management strategies during 10years for 137 childhood craniopharyngiomas treated at a single institution.

    Medical records of children with craniopharyngioma treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 to December 2017 were retrospectively reviewed. Beta-catenin as an immunohistochemical marker was assessed also in available specimens.

    Our registry included 137 patients. Headache (n = 122), visual failure (n = 118), and hypothyroidism(n = 78) were the most common findings on presentation. Three management protocols were identified; 65 patients were primarily followed up after surgery, 71 patients had radiotherapy after surgery, and one patient underwent surgery for Ommaya insertion with intracystic interferon injection. Overall, gross total resection/near total resection was achieved in 48 cases (35.04%), subtotal resection was achieved in 58 patients (42.33%), 29 (21.16%) had biopsy and Ommaya reservoir, and two patients with calcified lesions hay of life and the best tumor control rates. Beta-catenin mutations more than 5% are associated with statistically trending aggressive clinical behavior. The CCHE-57357 algorithm of individualized management protocol was presented.
    To describe a case series of children with thalamic tumors treated at our institution in a 5-year period.

    A retrospective and observational study was performed. The records of 15 patients between 2013 and 2018 were analyzed.

    From 2013 to 2018, 15 patients were treated at our institution. The male to female index was 1.5, and the median age was 8.9 (IQR 4.75-13). Seven (46%) tumors were left-sided, seven (46%) were right-sided, and one (6%) was bilateral. All patients were symptomatic at the time of treatment. Motor deficit was the most common form of presentation (73%). Gross-total resection was performed in two (13.3%) patients, subtotal resection was performed in two other patients (13.3%), and for the rest of the patients (73.3%), the chosen surgical approach was a stereotactic-guided biopsy. https://www.selleckchem.com/products/hth-01-015.html The average of procedures was 3.4, mostly related to the treatment for hydrocephalus. Twelve patients (80%) received treatment for hydrocephalus. Nine patients (75%) were treated with ventriculoperitoneal shunts, and four patients (33%) underwent endoscopic third ventriculostomy.
    Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT. A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT). After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vinistration of IV heparin (OR 2.077), platelet count < 100,000/mm (OR 4.798), bacterial endocarditis (OR 15.069), neoplasm with increased hemorrhagic risk (OR 6.046), and severe liver disease (OR 6.124). Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT. Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.α-L-Arabinofuranosidase (PsGH43_12) of family 43 glycoside hydrolase and subfamily 12 from Pseudopedobacter saltans was cloned, over-expressed and biochemically characterized. PsGH43_12 displayed molecular mass, ~ 65 kDa. It exhibited activity in pH (5-9) and temperature range (35-55 °C) with maxima at pH 6.5 and 50 °C. PsGH43_12 gave 88.7 U/mg specific activity against rye arabinoxylan and 78.9 U/mg against wheat arabinoxylan. PsGH43_12 displayed Km and Vmax, 3.02 mg/ml and 103 µmole/min/mg, respectively, against rye arabinoxylan and 2.17 mM and 100.7 µmole/min/mg, respectively, against pNP-α-L-arabinofuranoside. 10 mM Mg2+ or Ca2+ ions enhanced PsGH43_12 activity by 54% or 33%, respectively. PsGH43_12 hydrolyzed rye arabinoxylan and released only L-arabinosyl moiety as main product, confirming its specificity towards α-L-arabinofuranoside. The regioselective analysis by NMR showed that PsGH43_12 belongs to type III α-L-arabinofuranoside. The synergistic behavior of PsGH43_12 in saccharification of mild alkali pretreated finger miller stalk (FMS) along with xylanase (CtXyn11A) from Clostridium thermocellum and xylosidase (BoGH43) from Bacteroides ovatus gave twofold higher total reducing sugar (TRS) yield. TLC analysis of pretreated FMS hydrolysed by CtXyn11A and BoGH43 showed xylooligosaccharides and xylose. Addition of PsGH43_12 to above combination gave mostly xylose and arabinose confirming their synergistic behavior and displaying their applicability in hydrolysis of hemicellulosic biomass.A 66-year-old woman had experienced abnormal bleeding since the age of 7. Thrombocytopenia was not detected until she was 48, and immune thrombocytopenia was diagnosed at age 66. She also reported experiencing hearing disturbance since the age of 30 and acute renal failure since the age of 61 but reported no visual disturbance. Her younger son, who was 40 years old, also experienced abnormal bleeding since the age of 6, but immune thrombocytopenia was diagnosed as late as age 35. He had no other associated disorders. Laboratory examinations of both mother and son revealed a low platelet count (8000 and 29,000 µL, respectively), giant platelets and Döhle body-like granulocyte inclusion bodies. The mother had a high creatinine level (15.4 mg/dL) and normal liver enzyme levels. MYH9 genetic analysis identified a heterozygous mutation, c.101T>A, p.Val34Glu at exon 2 in both patients. These clinical and laboratory findings were consistent with a diagnosis of an MYH9-related disorder with different phenotypes observed in the same family. MYH9-related disorders were recognised in 2003, but were often misdiagnosed as immune thrombocytopenia, and hence, they have rarely been reported in Taiwan. To report our experience and management strategies during 10years for 137 childhood craniopharyngiomas treated at a single institution. Medical records of children with craniopharyngioma treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 to December 2017 were retrospectively reviewed. Beta-catenin as an immunohistochemical marker was assessed also in available specimens. Our registry included 137 patients. Headache (n = 122), visual failure (n = 118), and hypothyroidism(n = 78) were the most common findings on presentation. Three management protocols were identified; 65 patients were primarily followed up after surgery, 71 patients had radiotherapy after surgery, and one patient underwent surgery for Ommaya insertion with intracystic interferon injection. Overall, gross total resection/near total resection was achieved in 48 cases (35.04%), subtotal resection was achieved in 58 patients (42.33%), 29 (21.16%) had biopsy and Ommaya reservoir, and two patients with calcified lesions hay of life and the best tumor control rates. Beta-catenin mutations more than 5% are associated with statistically trending aggressive clinical behavior. The CCHE-57357 algorithm of individualized management protocol was presented. To describe a case series of children with thalamic tumors treated at our institution in a 5-year period. A retrospective and observational study was performed. The records of 15 patients between 2013 and 2018 were analyzed. From 2013 to 2018, 15 patients were treated at our institution. The male to female index was 1.5, and the median age was 8.9 (IQR 4.75-13). Seven (46%) tumors were left-sided, seven (46%) were right-sided, and one (6%) was bilateral. All patients were symptomatic at the time of treatment. Motor deficit was the most common form of presentation (73%). Gross-total resection was performed in two (13.3%) patients, subtotal resection was performed in two other patients (13.3%), and for the rest of the patients (73.3%), the chosen surgical approach was a stereotactic-guided biopsy. https://www.selleckchem.com/products/hth-01-015.html The average of procedures was 3.4, mostly related to the treatment for hydrocephalus. Twelve patients (80%) received treatment for hydrocephalus. Nine patients (75%) were treated with ventriculoperitoneal shunts, and four patients (33%) underwent endoscopic third ventriculostomy.
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  • BACKGROUND Some studies have reported that the electromagnetic navigation (EN) technique is better than the free-hand (FH) method. Nevertheless, there are few clinical trials. In recent years, several clinical trials have been conducted, providing sufficient information to compare the two methods. METHODS We compared the FH and EN techniques (SURESHOT, Smith and Nephew, Inc., Memphis, TN) in terms of the distal locking time, exposure time, first success rate, healing time and operative time. We comprehensively searched the Medline, Embase, and Cochrane library databases according to predetermined inclusion and exclusion criteria, and then we extracted data for specific variables from these reports. The risk of bias was assessed. https://www.selleckchem.com/products/pilaralisib-xl147.html Stata 13.0 was used for analysis. RESULTS Nine studies involving 579 patients were pooled in this study. The meta-analysis showed that EN was associated with a shorter distal locking time (P = 0.001) and exposure time (P = 0.001) than FH performed by surgeons who are not proficient in using the FH technique. No significant differences were found in the first success rate (P = 0.231), healing time (P = 0.09) or operative time (P = 0.510). CONCLUSION The EN technique has the advantages of a shorter distal locking time and smaller amount of ionizing radiation exposure compared with the FH technique.PURPOSE To assess macular capillary perfusion in patients with inactive Vogt-Koyanagi-Harada (VKH) disease by using optical coherence tomography angiography (OCTA). METHODS A total of 51 eyes of 51 patients with inactive VKH (group 1, n = 23) and healthy volunteers (group 2, n = 28) underwent detailed eye examination including OCTA (RTVue-XR Avanti) scanning. OCTA images (6 × 6 mm) were assessed for central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), vessel densities (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris (CC) flow area and vessel flow density (VFD), foveal avascular zone (FAZ) area and acircularity index (AI). RESULTS The mean ages of group 1 (13 female, 10 male) and group 2 (15 female, 13 male) were 39.9 ± 11.8 (range, 24-58) and 38.9 ± 8.5 (range, 29-51) years, respectively (p = 0.773). CRT and SFCT were 218.2 ± 39.4 μm and 195.6 ± 28.6 μm in group 1, while 243.5 ± 9.7 μm and 316.7 ± 20.1 μm in group 2, respectively (p  0.05). There was weak negative correlation between BCVA (logMAR) and parafoveal and perifoveal VD in SCP and DCP of group 1 (p  less then  0.05). CONCLUSION Macular capillary perfusion was significantly reduced both in SCP and DCP in patients with inactive VKH disease.PURPOSE To evaluate the correlations between anatomical and functional changes in idiopathic macular hole (IMH) surgery in long-term follow-up. METHODS This is a prospective, interventional single centre case series. The final sample is formed by 14 eyes of 14 patients who had undergone IMH surgery in our institution between 2005 and 2009 and were still followed up in 2019. Reported data were pre- and post-operative best-corrected visual acuity (BCVA), retinal sensitivity and fixation stability values on MP-1 and structural macular features on spectral domain optical coherence tomography. Optical coherence tomography angiography (OCTA) was utilized to assess microvascular characteristics at the final visit. Only patients with a successful MH closure were enrolled, excluding eyes affected by other relevant pathologies. RESULTS Mean BCVA improvement was significant after surgery (t test, p value less then  0.001) and presented a slight, not statistically significant raise, between the post-operative and long-term follow-up. Differently, mean retinal sensibility (dB) showed a highly statistically significant difference between pre-operative and post-operative (t test, p value = .002) and post-operative and last follow-up (p value less then  0.001). In the long-term follow-up, subjects having integrity of the inner segment/outer segment (IS/OS) layer showed no statistically significant difference in BCVA compared with subjects with IS/OS discontinuity (t test, p value = 0.72). OCTA parameters of the operated eye showed no statistical significance compared with the fellow eye. CONCLUSIONS In successfully closed MHs, retinal sensibility measured by microperimetry significatively increases after a long follow-up period even when BCVA remains stable or raises slightly. Vessel density organization tends to be quantitatively similar to fellow eye several years after surgery.There is increasing interest in the use of polyether ether ketone (PEEK) for orthopedic and dental implant applications due to its elastic modulus (close to that of bone), biocompatibility and radiolucent properties. However, PEEK is still categorized as bioinert owing to its low integration with surrounding tissues. Methods such as depositing hydroxyapatite (HA) onto the PEEK surface could increase its bioactivity. However, depositing HA without damaging the PEEK substrate is still required further investigation. Friction stir processing is a solid-state processing method that is widely used for composite substrate fabrication. In this study, a pinless tool was used to fabricate a HA/PEEK surface nanocomposite for orthopedic and dental applications. Microscopical images of the modified substrate confirmed homogenous distribution of the HA on the surface of the PEEK. The resultant HA/PEEK surface nanocomposites demonstrated improved surface hydrophilicity coupled with better apatite formation capacity (as shown in the simulated body fluid) in comparison to the pristine PEEK, making the newly developed material more suitable for biomedical application. This surface deposition method that is carried out at low temperature would not damage the PEEK substrate and thus could be a good alternative for existing commercial methods for PEEK surface modification.Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen.
    BACKGROUND Some studies have reported that the electromagnetic navigation (EN) technique is better than the free-hand (FH) method. Nevertheless, there are few clinical trials. In recent years, several clinical trials have been conducted, providing sufficient information to compare the two methods. METHODS We compared the FH and EN techniques (SURESHOT, Smith and Nephew, Inc., Memphis, TN) in terms of the distal locking time, exposure time, first success rate, healing time and operative time. We comprehensively searched the Medline, Embase, and Cochrane library databases according to predetermined inclusion and exclusion criteria, and then we extracted data for specific variables from these reports. The risk of bias was assessed. https://www.selleckchem.com/products/pilaralisib-xl147.html Stata 13.0 was used for analysis. RESULTS Nine studies involving 579 patients were pooled in this study. The meta-analysis showed that EN was associated with a shorter distal locking time (P = 0.001) and exposure time (P = 0.001) than FH performed by surgeons who are not proficient in using the FH technique. No significant differences were found in the first success rate (P = 0.231), healing time (P = 0.09) or operative time (P = 0.510). CONCLUSION The EN technique has the advantages of a shorter distal locking time and smaller amount of ionizing radiation exposure compared with the FH technique.PURPOSE To assess macular capillary perfusion in patients with inactive Vogt-Koyanagi-Harada (VKH) disease by using optical coherence tomography angiography (OCTA). METHODS A total of 51 eyes of 51 patients with inactive VKH (group 1, n = 23) and healthy volunteers (group 2, n = 28) underwent detailed eye examination including OCTA (RTVue-XR Avanti) scanning. OCTA images (6 × 6 mm) were assessed for central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), vessel densities (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris (CC) flow area and vessel flow density (VFD), foveal avascular zone (FAZ) area and acircularity index (AI). RESULTS The mean ages of group 1 (13 female, 10 male) and group 2 (15 female, 13 male) were 39.9 ± 11.8 (range, 24-58) and 38.9 ± 8.5 (range, 29-51) years, respectively (p = 0.773). CRT and SFCT were 218.2 ± 39.4 μm and 195.6 ± 28.6 μm in group 1, while 243.5 ± 9.7 μm and 316.7 ± 20.1 μm in group 2, respectively (p  0.05). There was weak negative correlation between BCVA (logMAR) and parafoveal and perifoveal VD in SCP and DCP of group 1 (p  less then  0.05). CONCLUSION Macular capillary perfusion was significantly reduced both in SCP and DCP in patients with inactive VKH disease.PURPOSE To evaluate the correlations between anatomical and functional changes in idiopathic macular hole (IMH) surgery in long-term follow-up. METHODS This is a prospective, interventional single centre case series. The final sample is formed by 14 eyes of 14 patients who had undergone IMH surgery in our institution between 2005 and 2009 and were still followed up in 2019. Reported data were pre- and post-operative best-corrected visual acuity (BCVA), retinal sensitivity and fixation stability values on MP-1 and structural macular features on spectral domain optical coherence tomography. Optical coherence tomography angiography (OCTA) was utilized to assess microvascular characteristics at the final visit. Only patients with a successful MH closure were enrolled, excluding eyes affected by other relevant pathologies. RESULTS Mean BCVA improvement was significant after surgery (t test, p value less then  0.001) and presented a slight, not statistically significant raise, between the post-operative and long-term follow-up. Differently, mean retinal sensibility (dB) showed a highly statistically significant difference between pre-operative and post-operative (t test, p value = .002) and post-operative and last follow-up (p value less then  0.001). In the long-term follow-up, subjects having integrity of the inner segment/outer segment (IS/OS) layer showed no statistically significant difference in BCVA compared with subjects with IS/OS discontinuity (t test, p value = 0.72). OCTA parameters of the operated eye showed no statistical significance compared with the fellow eye. CONCLUSIONS In successfully closed MHs, retinal sensibility measured by microperimetry significatively increases after a long follow-up period even when BCVA remains stable or raises slightly. Vessel density organization tends to be quantitatively similar to fellow eye several years after surgery.There is increasing interest in the use of polyether ether ketone (PEEK) for orthopedic and dental implant applications due to its elastic modulus (close to that of bone), biocompatibility and radiolucent properties. However, PEEK is still categorized as bioinert owing to its low integration with surrounding tissues. Methods such as depositing hydroxyapatite (HA) onto the PEEK surface could increase its bioactivity. However, depositing HA without damaging the PEEK substrate is still required further investigation. Friction stir processing is a solid-state processing method that is widely used for composite substrate fabrication. In this study, a pinless tool was used to fabricate a HA/PEEK surface nanocomposite for orthopedic and dental applications. Microscopical images of the modified substrate confirmed homogenous distribution of the HA on the surface of the PEEK. The resultant HA/PEEK surface nanocomposites demonstrated improved surface hydrophilicity coupled with better apatite formation capacity (as shown in the simulated body fluid) in comparison to the pristine PEEK, making the newly developed material more suitable for biomedical application. This surface deposition method that is carried out at low temperature would not damage the PEEK substrate and thus could be a good alternative for existing commercial methods for PEEK surface modification.Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen.
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