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961.
Michael Olamoyegun Waheed Ibraheem Sandra Iwuala Morenike Audu Babatope Kolawole 《African health sciences》2015,15(4):1136-1141
Introduction
Diabetes mellitus (DM) afflicts at least 5 million people in Nigeria, with more than 80% having type 2 diabetes mellitus (T2DM). Microvascular complications increase both morbidity and mortality inpatients with T2DM. The aims of this study were to report the burden of various microvascular complications in T2DM and to identify various factors associated with these complications in patients with T2DM attending the diabetes outpatients'' clinic.Methods
Ninety (90) patients with T2DM who have attended diabetes clinic for at least 3 months were recruited for this study. Detailed history, physical examination and biochemical analysis was done in each of the patients. All patients underwent a detailed standard evaluation to detect diabetic retinopathy (fundoscopy), neuropathy (10g monofilament and/or diabetes neuropathy scores), and nephropathy (microalbuminuria, macroalbuminuria, serum creatinine and estimated glomerular filtration rate).Results
There was high prevalence of microvascular complications among patients with T2DM. Almost half of patients with T2DM had some form of microvascular complications; diabetic neuropathy being the commonest (69.6%),followed by nephropathy (54.5%) and retinopathy (48.9%). The factors associated with developing these complications were increasing age, duration of diabetes, hypertension and dyslipidaemia for nephropathy and neuropathy.Conclusion
There is a high burden of microvascular complications in patients with type 2 diabetes. Age, male gender, hypertension, glycaemic control, BMI and duration of diabetes, and glycaemic control were factors associated with microvasular complications. 相似文献962.
Amanda L. Hernandez Alexandra Kitz Chuan Wu Daniel E. Lowther Donald M. Rodriguez Nalini Vudattu Songyan Deng Kevan C. Herold Vijay K. Kuchroo Markus Kleinewietfeld David A. Hafler 《The Journal of clinical investigation》2015,125(11):4212-4222
FOXP3+ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ — either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown — restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways. 相似文献
963.
Simone Susser Mathieu Flinders Henk W. Reesink Stefan Zeuzem Glenn Lawyer Anne Ghys Veerle Van Eygen James Witek Sandra De Meyer Christoph Sarrazin 《Antimicrobial agents and chemotherapy》2015,59(5):2746-2755
In treating hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, the rapid reselection of resistance-associated variants (RAVs) is well known in patients with repeated exposure to the same class of antiviral agents. For chronic hepatitis C patients who have experienced virologic failure with direct-acting antiviral drugs, the potential for the reselection of persistent RAVs is unknown. Nine patients who received 14 days of telaprevir monotherapy were retreated with telaprevir-based triple therapy 4.3 to 5.7 years later. In four patients with virologic failure with both telaprevir-containing regimens, population-based and deep sequencing (454 GS-FLX) of the NS3 protease gene were performed before and at treatment failure (median coverage, 4,651 reads). Using deep sequencing, with a threshold of 1.0% for variant calling, no isolates were found harboring RAVs at the baseline time points. While population-based sequencing uncovered similar resistance patterns (V36M plus R155K for subtype 1a and V36A for subtype 1b) in all four patients after the first and second telaprevir treatments, deep sequencing analysis revealed a median of 7 (range, 4 to 23) nucleotide substitutions on the NS3 backbone of the resistant strains, together with large phylogenetic differences between viral quasispecies, making the survival of resistant isolates highly unlikely. In contrast, in a comparison of the two baseline time points, the median number of nucleotide exchanges in the wild-type isolates was only 3 (range, 2 to 8), reflecting the natural evolution of the NS3 gene. In patients with repeated direct antiviral treatment, a continuous evolution of HCV quasispecies was observed, with no clear evidence of persistence and reselection but strong signs of independent de novo generation of resistance. Antiviral therapy for chronic viral infections, like HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV), faces several challenges. These viruses have evolved survival strategies and proliferate by escaping the host''s immune system. The development of direct-acting antiviral agents is an important achievement in fighting these infections. Viral variants conferring resistance to direct antiviral drugs lead to treatment failure. For HIV/HBV, it is well known that viral variants associated with treatment failure will be archived and reselected rapidly during retreatment with the same drug/class of drugs. We explored the mechanisms and rules of how resistant variants are selected and potentially reselected during repeated direct antiviral therapies in chronically HCV-infected patients. Interestingly, in contrast to HIV and HBV, we could not prove long-term persistence and reselection of resistant variants in HCV patients who failed protease inhibitor-based therapy. This may have important implications for the potential to reuse direct-acting antivirals in patients who failed the initial direct antiviral treatment. (The phase IIIb study described in this paper is registered at ClinicalTrials.gov under registration number .) NCT01054573相似文献
964.
Christian S. Lentz Julia M. Sattler Martina Fendler Simon Gottwalt Victoria S. Halls Silke Strassel Sandra Arriens Jeffrey S. Hannam Sabine Specht Michael Famulok Ann-Kristin Mueller Achim Hoerauf Kenneth M. Pfarr 《Antimicrobial agents and chemotherapy》2015,59(1):654-658
wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum
in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates. 相似文献
965.
966.
967.
Andrew M. Zeiger Meghan E. McGarry Angel C. Y. Mak Vivian Medina Sandra Salazar Celeste Eng Amy K. Liu Sam S. Oh Thomas J. Nuckton Deepti Jain Thomas W. Blackwell Hyun Min Kang Goncalo Abecasis Leandra Cordero Oate Max A. Seibold Esteban G. Burchard Jose Rodriguez‐Santana 《Pediatric pulmonology》2020,55(2):533-540
968.
969.
Kelly K. O’Brien Aileen M. Davis Sandra Gardner Ahmed M. Bayoumi Sergio Rueda Trevor A. Hart Curtis Cooper Patricia Solomon Sean B. Rourke Steven Hanna 《AIDS and behavior》2014,18(2):357-367
As individuals age with HIV it is increasingly important to consider the health-related consequences of HIV and multiple morbidities, known as disability. We assessed relationships between four dimensions of disability among adults living with HIV. We conducted a structural equation modeling analysis using data from 913 participants in the Ontario HIV Treatment Network Cohort Study to determine relationships between four latent variables of disability in the Episodic Disability Framework: physical symptoms and impairments, mental health symptoms and impairments, difficulties with day-to-day activities, and challenges to social inclusion. Results indicated that physical symptoms and impairments, mental health symptoms and impairments and difficulties with day-to-day activities directly or indirectly predicted challenges to social inclusion for adults living with HIV. Challenges to social inclusion were directly predicted by mental health symptoms and indirectly by physical health symptoms via (mediated by) having difficulties carrying out day-to-day activities and mental health symptoms and impairments. These findings provide a basis for conceptualizing disability experienced by people living with HIV. 相似文献
970.