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In the current study, we examined the durability of intervention gains over a 6- and 12-month follow-up period after the implementation of a CBT-based group intervention "Adolescent Coping with Depression Course" (ACDC) for adolescents with subclinical or mild-to-moderate depression. Data were collected from 228 youth, 133 of whom were allocated to the 14-week ACDC intervention and 95 to the usual care (UC) control condition. Analyses for the main outcome variable of depressive symptoms were performed using a random effects repeated measures piecewise growth model to estimate trajectory shape over time on an intention-to-treat basis. Results revealed that the reduction in depressive symptoms achieved during the intervention phase continued across the follow-up period for both ACDC and UC (i.e., depressive symptoms showed a significantly decreasing trend in both groups in intervention and follow-up phases); however, no differential effects between conditions were found during the follow-up phase. The direct and indirect effects of the intervention on the other outcome variables' follow-up results were also presented. ISRCTN registry ISRCTN19700389. Registered 6 October 2015. https//doi.org/10.1186/ISRCTN19700389 . Full Protocol https//doi.org/10.1186/s12888-016-0954-y.We present a case of a young adult male who was treated successfully for renal AA-amyloidosis secondary to human immunodeficiency virus (HIV) infection using highly active anti-retroviral therapy (HAART). He presented with lobar pneumonia, acute kidney injury, nephrotic syndrome and newly diagnosed HIV infection and was initiated on HARRT and haemodialysis. Kidney biopsy was consistent with amyloid deposition of the AA-type. His clinical condition improved gradually and after 10 months of therapy, he regained sufficient excretory function to become dialysis independent. Two years later, he remained well, with a recovered CD4 count and a glomerular filtration rate of 63 mL/min/1.73 m2. Patients with renal AA-amyloidosis typically present with slowly progressive chronic kidney disease, often leading to end-stage kidney disease within months. To our knowledge, this is the first reported case of biopsy proven renal AA-amyloidosis in a newly diagnosed HIV positive patient to present with acute kidney injury leading to dialysis dependence over a period of 2 weeks, which was successfully treated using HAART.Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant articles with experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected for the review. Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. https://www.selleckchem.com/EGFR(HER).html Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. Although the risk of dementia among patients with type 2 diabetes mellitus (T2DM) is double that of those without T2DM, the mechanism remains to be elucidated and the glycemic goal to prevent progression of cognitive impairment is unclear. Results from cross-sectional studies suggest that glucose fluctuations are associated with impairment of cognitive function among T2DM patients. Therefore, the aim of the longitudinal study described here is to evaluate the relationships between glucose fluctuation indexes assessed by continuous glucose monitoring (CGM) and cognitive function among elderly patients with T2DM. This will be a prospective, single-center, 2-year longitudinal study in which a total of 100 elderly patients with T2DM showing mild cognitive impairment (MCI) will be enrolled. Glucose fluctuations, assessed using the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories), and results of cognitive tests, namely the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale (ADAS), will be evaluated at baseline, 1-year visit and 2-year visit.
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In the current study, we examined the durability of intervention gains over a 6- and 12-month follow-up period after the implementation of a CBT-based group intervention "Adolescent Coping with Depression Course" (ACDC) for adolescents with subclinical or mild-to-moderate depression. Data were collected from 228 youth, 133 of whom were allocated to the 14-week ACDC intervention and 95 to the usual care (UC) control condition. Analyses for the main outcome variable of depressive symptoms were performed using a random effects repeated measures piecewise growth model to estimate trajectory shape over time on an intention-to-treat basis. Results revealed that the reduction in depressive symptoms achieved during the intervention phase continued across the follow-up period for both ACDC and UC (i.e., depressive symptoms showed a significantly decreasing trend in both groups in intervention and follow-up phases); however, no differential effects between conditions were found during the follow-up phase. The direct and indirect effects of the intervention on the other outcome variables' follow-up results were also presented. ISRCTN registry ISRCTN19700389. Registered 6 October 2015. https//doi.org/10.1186/ISRCTN19700389 . Full Protocol https//doi.org/10.1186/s12888-016-0954-y.We present a case of a young adult male who was treated successfully for renal AA-amyloidosis secondary to human immunodeficiency virus (HIV) infection using highly active anti-retroviral therapy (HAART). He presented with lobar pneumonia, acute kidney injury, nephrotic syndrome and newly diagnosed HIV infection and was initiated on HARRT and haemodialysis. Kidney biopsy was consistent with amyloid deposition of the AA-type. His clinical condition improved gradually and after 10 months of therapy, he regained sufficient excretory function to become dialysis independent. Two years later, he remained well, with a recovered CD4 count and a glomerular filtration rate of 63 mL/min/1.73 m2. Patients with renal AA-amyloidosis typically present with slowly progressive chronic kidney disease, often leading to end-stage kidney disease within months. To our knowledge, this is the first reported case of biopsy proven renal AA-amyloidosis in a newly diagnosed HIV positive patient to present with acute kidney injury leading to dialysis dependence over a period of 2 weeks, which was successfully treated using HAART.Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. Relevant articles with experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected for the review. Number of drugs such as remdesivir, favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, tocilizumab and interferons have shown inhibitory effects against the SARS-CoV2 in-vitro as well as in clinical conditions. These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. https://www.selleckchem.com/EGFR(HER).html Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. Although the risk of dementia among patients with type 2 diabetes mellitus (T2DM) is double that of those without T2DM, the mechanism remains to be elucidated and the glycemic goal to prevent progression of cognitive impairment is unclear. Results from cross-sectional studies suggest that glucose fluctuations are associated with impairment of cognitive function among T2DM patients. Therefore, the aim of the longitudinal study described here is to evaluate the relationships between glucose fluctuation indexes assessed by continuous glucose monitoring (CGM) and cognitive function among elderly patients with T2DM. This will be a prospective, single-center, 2-year longitudinal study in which a total of 100 elderly patients with T2DM showing mild cognitive impairment (MCI) will be enrolled. Glucose fluctuations, assessed using the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories), and results of cognitive tests, namely the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale (ADAS), will be evaluated at baseline, 1-year visit and 2-year visit.
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