Iveyastrup8820
Understanding how mutations render a drug ineffective is a problem of immense relevance. Often the mechanism through which mutations cause drug resistance can be explained purely through thermodynamics. However, the more perplexing situation is when two proteins have the same drug binding affinities but different residence times. In this work, we demonstrate how all-atom molecular dynamics simulations using recent developments grounded in statistical mechanics can provide a detailed mechanistic rationale for such variances. We discover dissociation mechanisms for the anti-cancer drug Imatinib (Gleevec) against wild-type and the N368S mutant of Abl kinase. We show how this point mutation triggers far-reaching changes in the protein's flexibility and leads to a different, much faster, drug dissociation pathway. We believe that this work marks an efficient and scalable approach to obtain mechanistic insight into resistance mutations in biomolecular receptors that are hard to explain using a structural perspective.Despite improvements in patient and renal death rates following the introduction of potent immunosuppressive drugs in earlier decades, a sizeable fraction of patients with lupus nephritis is burdened with suboptimal or delayed responses, relapses, chronic use of glucocorticoids and accrual of renal (chronic renal insufficiency) and extra-renal organ damage. The recently approved combinatory treatments comprising belimumab or voclosporin added to conventional agents, especially mycophenolate, hold promise for further improving disease outcomes and enabling a faster steroid tapering, thus being relevant to the treat-to-target context. However, it remains uncertain whether these dual regimens should become the first-line choice for all patients or instead be prioritized to certain subgroups. In the present article, we summarize the existing lupus nephritis management recommendations, followed by a critical appraisal of the randomized trials of belimumab and voclosporin, as well as the available data on obinutuzumab and other novel compounds under development. We conclude that pending the identification of accurate clinical, histological, or translational predictors for guiding personalized decisions, it is of utmost importance that lupus nephritis patients are monitored closely with appropriate treatment adjustments aiming at a prompt, deep response to ensure long-term preservation of kidney function.A linear accelerator has three independent axes that are nominally intersecting at the isocenter. Modern treatment techniques require the coincidence of these axes to lie within a 1-mm diameter sphere. A solution to verify this requirement is to wrap a film on a cylindrical surface, align the cylinder to the linac's isocenter and gantry axis, and take multiple exposures of slits, rotating either the gantry, collimator, or couch between exposures. The resulting exposure pattern is the 3D equivalent of the 2D star shot and encodes sufficient information to determine each axis' position in 3D. Moreover, this method uses a single sheet 8"x10" film, a standard film scanner, and a phantom that can be readily built in-house, making a practical solution to this 3D-measurement problem.
Empathy and quality of educational environment appear to be inversely correlated with burnout but the relationship between the two is largely unknown. Our primary objective was to examine the relationship between postgraduate educational environment and empathy. Secondary objectives included impact of gender, residency year and on- versus off-service context on levels of empathy and educational environment.
A modified Dillman approach was used to conduct an email survey of Canadian Royal College Emergency Medicine residents in June 2020. The survey instrument included demographic data, Toronto Empathy Questionnaire (TEQ) and Scan of Postgraduate Educational Environment Domains (SPEED). Logistic and linear regressions evaluated the association between TEQ and SPEED, and mean SPEED scores and covariates, respectively.
Response rate was 38% (138/363) with representation from all programs. Respondents were mean 30years of age, 59% men and 25%, 20%, 18%, 24%, and 13% in postgraduate year (PGY) 1-5, respectively. There was no statistically significant association between high/low TEQ scores and mean SPEED score (p = 0.97). There were no statistically significant associations between any of the covariates and high/low TEQ scores (gender, p = 0.21; PGY, p = 0.58; on-versus off-service, p = 0.46) or mean SPEED score (gender, p = 0.95; PGY, p = 0.48; on- versus off-service, p = 0.07). Emergency medicine residents rated their educational environment on average 3.44 (+/- 0.43) out of four. 39 of 134 residents were found to have low empathy.
There was no association between empathy and educational environment. Further research is needed to elucidate modifiable factors contributing to the development of low empathy in emergency medicine residents.
There was no association between empathy and educational environment. Further research is needed to elucidate modifiable factors contributing to the development of low empathy in emergency medicine residents.
This study describes the supply, distribution, and characteristics of international medical graduate (IMG) psychiatrists who provide services in the USA.
Cross-sectional study design, using descriptive statistics based on combined data from the American Medical Association (2020 Physician Masterfile) and the Educational Commission for Foreign Medical Graduates.
International medical graduates continue to make significant contributions to the US physician workforce. As a group, they represent 29% of active psychiatrists in the USA, compared to 23% in all other medical specialties. Many IMG psychiatrists were US citizens who obtained their medical degrees outside the USA or Canada, often in the Caribbean. In some states (i.e., Florida, New Jersey), over 40% of active psychiatrists are IMGs. Over 30% of IMG psychiatrists graduated from medical schools in India and Pakistan.
This study provides an overview of the psychiatric workforce in the USA, quantifying the specific contribution of IMGs. Several factors, including immigration policies, continued expansion of US medical schools, and the number of available residency positions, could impact the flow of IMGs to the US. Longitudinal studies are needed to better understand the implications for workforce composition and distribution, and their potential impact on the care of psychiatric patients.
This study provides an overview of the psychiatric workforce in the USA, quantifying the specific contribution of IMGs. Several factors, including immigration policies, continued expansion of US medical schools, and the number of available residency positions, could impact the flow of IMGs to the US. Longitudinal studies are needed to better understand the implications for workforce composition and distribution, and their potential impact on the care of psychiatric patients.This study aimed to examine the effect of an educational brochure about testicular cancer and its early diagnosis on the health beliefs and self-examination of participants. The pretests/posttests were conducted in a quasi-experimental design with non-randomized groups and a control group of university students. The study recruited students enrolled in the psychological counseling and guidance department of a Turkish public university. The research sample comprised 92 students, 48 in the experimental and 44 in the control group. An educational brochure about testicular cancer and self-examination was provided to the experimental group. The data includes a personal information form, testicular cancer and health beliefs scale about testicular self-examination, and the form for self-examination. Mann Whitney U, Wilcoxon, and chi-square analyses were performed for data analysis. Bulevirtide A significant difference was found between the scores of the experimental and control groups regarding seriousness/caring, benefit and health motivation, obstacles, and self-efficacy (p less then 0.05). Moreover, the testicular self-examination ratio was determined as 83.3% in the experimental group and 4.5% in the control group. It can be asserted that the training brochure is effective in promoting the self-examination of testicles. It may be recommended to conduct experimental studies with larger study groups to increase testicular self-examination.
Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods.
Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed.
Mean age was 80years (± 11.1) and 10% of the deceased were younger than 65years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate.
This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.
This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.
The success of intravitreal treatment for neovascular age-related macular degeneration (nAMD) depends on maximal adherence to treatment, which in turn requires patient satisfaction.
The aim of this study was to assess the factors associated with nAMD patient satisfaction to implement actions to improve treatment experiences and increase adherence.
This was a prospective, observational, analytical, cross-sectional study.
Our study included 100 consecutive nAMD patients under intravitreal treatment for at least 1year.
Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) and the EuroQol Visual Analog Scale (EQ VAS). A logistic regression was estimated to model the low values of the satisfaction score (MacTSQ <50).
The mean age of patients was 82.1±7.8 years and 62% were female. Males (p=0.002) and patients who improved their visual acuity (p=0.004) were more satisfied, while patients who received a higher number of injections (p=0.036) and treatment in both eyes (p=0.001) were less satisfied. Higher health-related quality of life was related to higher satisfaction. The sensitivity and specificity of the predictive model were 75.8% and 76.1%, respectively. Factors independently associated with low satisfaction were female sex (odds ratio [OR] 6.84), going to the clinic alone (OR 8.51), longer duration of treatment (OR 0.62), receiving treatment in both eyes (OR 3.54), and suffering a decline in visual acuity (OR 3.30). The questionnaire revealed patients' needs for more information and injection points closer to their homes.
Well-defined areas for improvement were identified, i.e. to improve the information offered to each patient, to incorporate new long-acting drugs, and to establish locations for injection services in peripheral areas.
Well-defined areas for improvement were identified, i.e. to improve the information offered to each patient, to incorporate new long-acting drugs, and to establish locations for injection services in peripheral areas.
