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A new coronavirus disease, SARS-CoV-2, has spread into a global pandemic in December 2019. Since no specific therapeutic drugs for treating COVID-19 have been approved by FDA, recent studies suggest that the known antimalarial quinine and its derivatives (chloroquine and hydroxychloroquine) inhibit receptor binding of the viral particles and inhibits the strong "cytokine storm", which is the main cause of death among infected patients. In particular, the natural alkaloid quinine has shown to possess a better safety profile and greater tolerability compared to its derivatives. Dosage optimization of quinine is still necessary as the currently available dosage forms have controversial pharmacokinetics and safety profiles. Therefore, repurposing quinine dosage forms to improve its pharmacokinetics and safety profile may be necessary to support its use against SARS-CoV-2. In this context, biodegradable/biocompatible polymeric nanoparticles may provide a safe site-specific and controlled quinine delivery, reducing the frequency of drug administration and the dose. In this study, a full atomistic molecular dynamics simulation approach has been used to investigate the use of poly-(glycolic acid) and poly-(lactic acid) and their copolymer poly-(lactic-co-glycolic acid) as potential delivery systems for lipophilic quinine to get insights into the mechanism of quinine encapsulation and release at the atomic/molecular level.We propose a new methodological framework for studying status exchange in marriage. As shown in recent debates on status-race or status-beauty exchange, the conventional loglinear modeling approach is prone to controversial specifications and alternative interpretations. In this study, we develop a simple method - the Exchange Index - with cohort-and-gender-specific relative status measures, statistical distribution balancing, and nonparametric matching. While allowing for multiple covariate controls, our Exchange Index measures the average difference in spouse's status between intermarriages and matched ingroup marriages. read more To demonstrate the new framework, we use two analytical examples of status-race and status-age exchange, based on the IPUMS 2000 US Census 5% microdata sample. To verify our new method, we also conduct replication and simulation studies. Our approach reduces model dependency, improves flexibility to account for confounders, allows for examination of heterogeneous patterns, speaks to fundamental concepts in status exchange theory, and takes advantage of increasingly available large-scale microdata.We follow Medicare cohorts to estimate Hurricane Katrina's long-run mortality effects on victims initially living in New Orleans. Including the initial shock, the hurricane improved eight-year survival by 2.07 percentage points. Migration to lower-mortality regions explains most of this survival increase. Those migrating to low-versus high-mortality regions look similar at baseline, but their subsequent mortality is 0.83-1.01 percentage points lower per percentage point reduction in local mortality, quantifying causal effects of place on mortality among this population. Migrants' mortality is also lower in destinations with healthier behaviors and higher incomes but is unrelated to local medical spending and quality.Hydroxychloroquine is an antimalarial drug with immunomodulatory, anti-inflammatory, antibacterial, and antiviral properties. It has a good safety profile, can be used in children and in pregnant and breastfeeding women, and does not suppress the immune system. Regular screening for retinopathy, one of the drug's most feared adverse effects, is necessary. Hydroxychloroquine is a widely used, essential drug in dermatology. Clinical response rates are good in lupus erythematous, where it is a first-line therapy, as well in numerous autoimmune/inflammatory diseases, including lichen planus, polymorphic light eruption, porphyria cutanea tarda, granuloma annulare, and sarcoidosis. In 2020, it was widely prescribed both to prevent and to treat COVID-19 caused by SARS-CoV-2. Its increased use led to serious supply shortages and in some cases stocks were entirely depleted. Recent meta-analyses have concluded that hydroxychloroquine is ineffective against COVID-19 and have advised against its use.
Test web-based implementation for the science of enhancing resilience (WISER) intervention efficacy in reducing healthcare worker (HCW) burnout.
RCT using two cohorts of HCWs of four NICUs each, to improve HCW well-being (primary outcome burnout). Cohort 1 received WISER while Cohort 2 acted as a waitlist control.
Cohorts were similar, mostly female (83%) and nurses (62%). In Cohorts 1 and 2 respectively, 182 and 299 initiated WISER, 100 and 176 completed 1-month follow-up, and 78 and 146 completed 6-month follow-up. Relative to control, WISER decreased burnout (-5.27 (95% CI -10.44, -0.10), p = 0.046). Combined adjusted cohort results at 1-month showed that the percentage of HCWs reporting concerning outcomes was significantly decreased for burnout (-6.3% (95%CI -11.6%, -1.0%); p = 0.008), and secondary outcomes depression (-5.2% (95%CI -10.8, -0.4); p = 0.022) and work-life integration (-11.8% (95%CI -17.9, -6.1); p < 0.001). Improvements endured at 6 months.
WISER appears to durably improve HCW well-being.
NCT02603133; https//clinicaltrials.gov/ct2/show/NCT02603133.
NCT02603133; https//clinicaltrials.gov/ct2/show/NCT02603133.Radiometric calibration (RC) is an essential solution to guarantee measurements from infrared photonic sensors with certain accuracy, the main task of which is to determine the radiometric responsivity of sensor and usually be solved by comparing with some radiation source (i.e., blackbody), called source-based RC (SBRC). In addition to the complexity in manufacture, the nonideal characteristics of an available source will inevitably introduce unexpected uncertainties to reduce the final calibration accuracy by around 0.2-0.5 K in SBRC. Therefore, we propose an original source-independent RC (SIRC) principle based on modeling instead of comparing for SBRC, where the incident background radiation to detector, as a dominated factor influencing the responsivity characteristics of a photonic sensor, is modeled to implement RC for both two fundamental types (photoconductive and photovoltaic) of HgCdTe photonic detectors. The SIRC merely requires the temperature information of main components of a sensor other than some complex source and its assembly, and provides a traceable way at lower uncertainty costs relative to the traditional SBRC. The SIRC is being implemented in Fengyun-2 satellites since 2019, which ensures a long-term stable service of Chinese geostationary meteorological satellites for the global observation system under the framework of World Meteorological Organization. Moreover, a 20-year-period traceable Fengyun-2 dataset to be recalibrated with SIRC will benefit the further climate applications.The World Health Organization (WHO) estimated that in 2019, 10.0 million people worldwide developed tuberculosis (TB), with 1.4 million deaths from TB in that year. Infection with Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampin and an additional chemotherapeutic agent is known as multidrug-resistant TB (MDR TB). Until recently, the prevalence of drug resistance in patients with TB has been poorly understood due to a lack of infection surveillance and molecular testing. Countries with the highest prevalence of TB, including MDR TB, are also those most affected by the COVID-19 pandemic. The identification of MDR TB requires careful monitoring and resources for molecular testing. Previous treatment regimens have required intravenous treatments of long duration and high cost. The 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB have included oral treatment regimens and reduced treatment duration. This Editorial aims to present the rationale for the 2020 and 2021 recommendations from the WHO for the management of drug-susceptible TB and MDR TB.BACKGROUND Pfeiffer syndrome (PS) is a fibroblast growth factor receptor (FGFR)-associated craniosynostosis syndrome, characterized by abnormally broad and medially deviated thumbs and great toes. Tracheal cartilage sleeve (TCS) is associated with several FGFR-associated craniosynostosis syndromes, including PS. TCS is an airway malformation in which the tracheal cartilage rings fuse with each other to form a sleeve of cartilage. CASE REPORT The patient was a 4-year-old girl with PS, TCS, and abnormal hyperplasia of non-fused intrapulmonary cartilages. The patient showed cranial dysplasia on prenatal ultrasonography. At birth, a cloverleaf skull in association with hydrocephalus and digital malformations was apparent. These findings were consistent with PS type 2. The diagnosis of PS type 2 was confirmed from a genetic test detecting a FGFR2 mutation (Y340C). During the clinical course, she underwent several surgeries, including ventriculoperitoneal shunts, sequential cranioplasty surgeries, and tracheotomy due to upper airway abnormalities. link2 At 4 years old, she died of multiple organ failure following aspiration pneumonia. The autopsy revealed that the tracheal cartilages had fused with each other, resulting in a condition called TCS, in which the cartilage rings and tracheal ligaments were absent. The lungs were poorly aerated, and the dilated bronchi had thickened walls surrounded by many cartilage fragments, mainly at the hilum. These cartilages tended to overlap at both ends, did not fuse, and were greatly altered in size and shape. link3 CONCLUSIONS We report the results of autopsy for PS with the first histopathological findings for the lungs and other visceral organs.This manuscript has been retracted at the author's request due to possible conflict of interest.ReferenceDinah V. Parums. Editorial mRNA Vaccines and Immunotherapy in Oncology A New Era for Personalized Medicine. Med Sci Monit 2021;27e933088. DOI 10.12659/MSM.933088.BACKGROUND Acute chemical liver injury needs to be further explored. The present study aimed to compare the effects of intraperitoneal injection with carbon tetrachloride on acute liver toxicity after 24 h in male and female Kunming mice. MATERIAL AND METHODS In this study, female and male mice were simultaneously divided into 3 different groups. Each group was treated differently, and after 24 h, blood samples were collected to check for changes in the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were used to assess liver toxicity. Liver samples were used for hematoxylin-eosin staining, and periodic acid Schiff reagent staining was performed to detect the pathological changes of each group. The expression level of biomarker molecules in liver cells was also systematically analyzed. RESULTS Our results showed that, compared with male mice, female mice showed more serious damage reduced glycogen and higher degree of necrosis, and the levels of heatshock protein 27 (HSP27), heat-shock protein 70 (HSP70), proliferating cell nuclear antigen (PCNA) and B cell lymphoma/lewkmia-2 (Bcl-2) were significantly lower than in the male group (P less then 0.05 or P less then 0.01), while the results of Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase 3 (Caspase3), and cytochrome P450 2E1 (CYP2E1) were the opposite (P less then 0.05 or P less then 0.01). CONCLUSIONS The findings from this study showed that, compared with male mice, at 24 h after CCl₄ toxicity, female mice showed more severe changes of hepatocyte necrosis and PAS-positivity, with significantly reduced expression of HSP27, HSP70, PCNA, and Bcl-2, and significantly increased expression of Bax, caspase-3, and CYP2E1.