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71.
72.
Elliasu Y. Salifu Clement Agoni Fisayo A. Olotu Yussif M. Dokurugu Mahmoud E. S. Soliman 《Chemical biology & drug design》2019,94(5):1905-1918
The experimental inhibitory potency of benzamidine (BEN) paved way for further design and development of inhibitors that target β‐FXIIa. Structural dynamics of the loops and catalytic residues that encompass the binding pocket of β‐FXIIa and all serine proteases are crucial to their overall activity. Employing molecular dynamics and post‐MD analysis, this study sorts to unravel the structural and molecular events that accompany the inhibitory activity of BEN on human β‐FXIIa upon selective non‐covalent binding. Analysis of conformational dynamics of crucial loops revealed prominent alterations of the original conformational posture of FXIIa, evidenced by increased flexibility, decreased compactness, and an increased exposure to solvent upon binding of BEN, which could have in turn interfered with the essential roles of these loops in enhancing their procoagulation interactions with biological substrates and cofactors, altogether resulting in the consequential inactivation of FXIIa. A sustained interaction of the catalytic triad residues and key residues of the autolysis loop impeded their roles in catalysis which equally enhanced the inhibitory potency of BEN toward β‐FXIIa evidenced by a favorable binding. Findings provide essential structural and molecular insights that could facilitate the structure‐based design of novel antithrombotic compounds with enhanced inhibitory activities and low therapeutic risk. 相似文献
73.
Emukah E Gutman J Eguagie J Miri ES Yinkore P Okocha N Jibunor V Nebe O Nwoye AI Richards FO 《Acta tropica》2012,122(1):126-131
Nigeria is highly endemic for infection with Schistosoma haematobium, which most commonly manifests itself with blood in urine. To monitor the impact of annual mass drug administration (MDA) with Praziquantel for S. haematobium in Delta State, Nigeria, cross-sectional hematuria surveys of school children were conducted in 8 sentinel villages (SVs) at baseline (n=240) and after two annual doses (n=402). We assessed the comparability of three assessments of hematuria (child's reported history, nurse visual diagnosis (NVD) and dipstick) to determine the need for mass treatment. Dipstick was considered to be the gold standard. Prior to treatment, history and NVD each identified only the 3 most highly prevalent SVs, and overall this represented just 37.5% of the 8 SVs in need of treatment. Following treatment, after dipstick prevalence decreased by 88.5% (p<0.001), and history and NVD identified only one of two villages still needing treatment. The study suggests that dipsticks should be the recommended method for launching and monitoring mass treatment for S. haematobium. 相似文献
74.
75.
Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis. 相似文献
76.
Type 1 diabetes mellitus--characterized by the permanent destruction of insulin-secreting β-cells--is responsive to cell-based treatments that replace lost β-cell populations. The current gold standard of pancreas transplantation provides only temporary independence from exogenous insulin and is fraught with complications, including increased mortality. Stem cells offer a number of theoretical advantages over current therapies. Our review will focus on the development of treatments involving tissue stem cells from bone marrow, liver and pancreatic cells, as well as the potential use of embryonic and induced pluripotent stem cells for Type 1 diabetes therapy. While the body of research involving stem cells is at once promising and inconsistent, bone marrow-derived mesenchymal stem cell transplantation seems to offer the most compelling evidence of efficacy. These cells have been demonstrated to increase endogenous insulin production, while partially mitigating the autoimmune destruction of newly formed β-cells. However, recently successful experiments involving induced pluripotent stem cells could quickly move them into the foreground of therapeutic research. We address the limitations encountered by present research and look toward the future of stem cell treatments for Type 1 diabetes. 相似文献
77.
BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) has been routinely used for the treatment of some movement disorders. However, DBS may be associated with adverse psychiatric effects, such as depression, anxiety and impulsivity.ObjectiveTo compare DBS applied to the entopeduncular nucleus (EPN; the rodent homolog of the GPi) and STN in terms of their effects on depressive- and anxiety-like behavior in rats.MethodsDBS was applied for 21 days (4 h a day) to either the STN or EPN. Rats then underwent behavioral testing on learned helplessness and elevated plus maze tasks before being sacrificed for brain analyses of zif268, BDNF and trkB mRNA as well as BDNF protein levels.ResultsRepeated DBS of the STN, but not of the EPN, led to impaired performance in the learned helplessness task, suggesting that STN-DBS induces or potentiates depressive-like behavior. There was no effect of DBS on elevated plus maze or on open field behavior. Repeated STN-DBS, but not EPN-DBS, led to decreased levels of BDNF and trkB mRNA in hippocampus. Acute stimulation of the STN or EPN resulted in similar changes in zif268 levels in several brain areas, except for the raphe where decreases were seen only after STB-DBS.ConclusionsTogether these results indicate that the effects of STN- and EPN-DBS differ in behavioral and neurochemical respects. Results further suggest that the EPN may be a preferable target for clinical DBS when psychiatric side effects are considered insofar as it may be associated with a lower incidence of depressive-like behavior than the STN. 相似文献
78.
Boris Ionin Robert J. Hopkins Brett Pleune Gloria S. Sivko Frances M. Reid Kristin H. Clement Thomas L. Rudge Jr. Gregory V. Stark Alison Innes Suha Sari Tina Guina Cris Howard Jeffrey Smith M. Lisa Swoboda Ekaterina Vert-Wong Virginia Johnson Gary S. Nabors Mario H. Skiadopoulos 《Clinical and Vaccine Immunology : CVI》2013,20(7):1016-1026
Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone. 相似文献
79.
R. Carter Clement MD MBA Yoonhee P. Ha MSc Bartholt Clagett BA Ginger E. Holt MD John P. Dormans MD 《Clinical orthopaedics and related research》2013,471(11):3689-3698
Background
Interest in developing national health care has been increasing in many fields of medicine, including orthopaedics. One manifestation of this interest has been the development of global health opportunities during residency training.Questions/purposes
We assessed global health activities and opportunities in orthopaedic residency in terms of resident involvement, program characteristics, sources of funding and support, partner site relationships and geography, and program director opinions on global health participation and the associated barriers.Methods
An anonymous 24-question survey was circulated to all US orthopaedic surgery residency program directors (n = 153) by email. Five reminder emails were distributed over the next 7 weeks. A total of 59% (n = 90) program directors responded.Results
Sixty-one percent of responding orthopaedic residencies facilitated clinical experiences in developing countries. Program characteristics varied, but most used clinical rotation or elective time for travel (76%), which most frequently occurred during Postgraduate Year 4 (57%) and was used to provide pediatric (66%) or trauma (60%) care. The majority of programs (59%) provided at least some funding to traveling residents and sent accompanying attendings on all ventures (56%). Travel was most commonly within North America (85%), and 51% of participating programs have established international partner sites although only 11% have hosted surgeons from those partnerships. Sixty-nine percent of residency directors believed global health experiences during residency shape future volunteer efforts, 39% believed such opportunities help attract residents to a training program, and the major perceived challenges were funding (73%), faculty time (53%), and logistical planning (43%).Conclusions
Global health interest and activity are common among orthopaedic residency programs. There is diversity in the characteristics and geographical locations of such activity, although some consensus does exist among program directors around funding and faculty time as the largest challenges. 相似文献80.
Chandramouli Kulshreshtha Arul Clement Torbjrn Pascher Villy Sundstrm Piotr Matyba 《RSC advances》2020,10(11):6618
Here, we show a new diketopyrrole based polymeric hole-transport material (PBDTP-DTDPP, (poly[[2,5-bis(2-hexyldecyl)-2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]pyrrole-1,4-diyl]-alt-[[2,2′-(4,8-bis(4-ethylhexyl-1-phenyl)-benzo[1,2-b:4,5-b′]dithiophene)bis-thieno[3,2-b]thiophen]-5,5′-diyl]])) for application in perovskite solar cells. The material performance was tested in a solar cell with an optimized configuration, FTO/SnO2/perovskite/PBDTP-DTDPP/Au, and the device showed a power conversion efficiency of 14.78%. The device charge carrier dynamics were investigated using transient absorption spectroscopy. The charge separation and recombination kinetics were determined in a device with PBDTP-DTDPP and the obtained results were compared to a reference device. We find that PBDTP-DTDPP enables similar charge separation time (<∼4.8 ps) to the spiro-OMeTAD but the amount of nongeminate recombination is different. Specifically, we find that the polymeric PBDTP-DTDPP hole-transport layer (HTL) slows-down the second-order recombination much less than spiro-OMeTAD. This effect is of particular importance in studying the charge transportation in optimized solar cell devices with diketopyrrole based HTL materials.Diketopyrrole based hole-transport organic semiconductor was employed in perovskite solar cells and charge carrier dynamics was explained. 相似文献