Knightmorton6847
Cells have a rich inner structure that is commonly explored by microscopy. Classical biochemical methods that break apart the cells and fractionate them along a gradient have now gotten a new lease on life through modern methods of mass spectrometry-based proteomics. Their common principle is to comprehensively measure all the proteins in each of the fractions. The resulting quantitative profile then associates thousands of proteins to their cellular homes. Here, the author recounts how protein correlation profiling, the first such technique, was conceived and how it was applied to answer intricate cell biological questions.Dyskeratosis Congenita (DKC) is a systemic disorder caused by mutations resulting in impaired telomere maintenance. Clinical features include bone marrow failure and an increased risk of developing hematological malignancies. There are conflicting data whether androgen derivatives (AD) can elongate telomeres in vivo and whether AD treatment enhances the risk of gaining myelodysplastic syndrome-related mutations. Seven TERC or TERT-mutated DKC patients underwent AD treatment. All patients revealed hematological response. Telomere length of lymphocytes and granulocytes increased significantly and no MDS-related mutations were detected. Pending longer follow-up, treatment with AD seems to represent an efficient and safe therapy for DKC patients.Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P 30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Pifithrin-μ Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.Health professionals managing patients with COVID-19 disease are at high risk of contagion. All medical personnel involved in caring for patients need coordination, knowledge and trust. Empirical work on human resources has tended to focus on the effects of human resource practices on performance, whereas leadership and social interactions have been overlooked. Based upon interviews with medical staff working in specialised medical units, this study uses the social capital theory to examine relationships among shared leadership, social capital, and contagion rates. First, shared leadership was found to positively affect COVID-19 contagion among health professionals. Second, by sharing information and a common language, and showing high levels of trust, namely social capital, medical units seem to reduce contagion rates of COVID-19. In other words, shared leadership plays a fundamental role in improving performance in healthcare by means of social capital.The purpose of this article is to identify the effects of dark tetrad personality traits (such as narcissism, psychopathy, Machiavellianism and sadism) on counterproductive work behavior with the mediating role of psychological contract breach and the moderating effect of political skills. Previous researches have focused on the direct effect of the dark triad to measure the counterproductive work behavior of individuals. Recently, everyday sadism has been added to the dark triad and become dark tetrad personality traits. Therefore, this study examines the dark tetrad personality traits to study counterproductive work behavior. This study applied structural equation modeling using partial least square to test the hypotheses on a sample of 400 doctors from the health sector of Pakistan. The results of this study reveal that dark tetrad has a positive and significant effect on counterproductive work behavior, and psychological contract breach significantly partially mediates in the relationship between dark tetrad and counterproductive work behavior. Furthermore, findings show that the moderating effect of political skills also positively and significantly strengthening the link between dark tetrad and the psychological contract breach. The conclusion of this study is made an innovative contribution to the Pakistan health sector, researchers and policy makers to designing the relevant practical implications.
The risk of neurodegenerative disorders in idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with residual injurious symptoms (RIS) after symptomatic treatment with clonazepam and/or melatonin is unclear.
The objective of this study was to determine the rate and correlates of RIS and its association with the risk of neurodegenerative diseases in patients with iRBD.
This was a retrospective cohort study. RIS was defined by the RBD Questionnaire-Hong Kong (RBDQ-HK) as the presence of residual sleep-related injuries or potential injurious behaviors for at least once a month after at least 1 year of treatment.
A total of 15 out of 133 (11.3%) patients with iRBD (age at diagnosis = 66.5 ± 7.3 years, 77.4% male) had RIS after 2.7 years of treatment. Patients with RIS were younger at both onset and polysomnography-confirmed diagnosis of iRBD (years, mean ± standard deviation, 56.3 ± 6.9 vs. 61.8 ± 7.6, P = 0.01; 61.2 ± 4.2 vs. 67.2 ± 7.4, P < 0.001, respectively), had more severe behavdementia with Lewy bodies but not PD suggests that RIS may probably help to identify the specific risk of different subtypes of α-synucleinopathy. © 2020 International Parkinson and Movement Disorder Society.
Medicare has become an increasingly complex program to navigate with numerous choices available to beneficiaries with important implications for their financial exposure and access to care. Although research has identified poor health literacy as a barrier to understanding Medicare, little information is available on the experience of individuals with hearing loss. This study examined how hearing loss impacts Medicare beneficiaries in understanding the program, their ability to compare and review plan options, and their satisfaction with available information.
Cross-sectional analysis using multivariate ordinal logistic regression.
Nationally representative survey of Medicare beneficiaries in the United States (Medicare Current Beneficiary Survey [MCBS]) 2017.
A total of 10,510 Medicare beneficiaries were analyzed, representing 50,084,169 beneficiaries with survey weights applied.
The primary outcome was difficulty understanding Medicare, determined by this MCBS question "Overall, how easy or difficof those with hearing loss, a highly prevalent condition among Medicare beneficiaries. J Am Geriatr Soc 682336-2342, 2020.
The existing tools to support Medicare beneficiaries' understanding and navigation of the program must evolve to meet the needs of those with hearing loss, a highly prevalent condition among Medicare beneficiaries. J Am Geriatr Soc 682336-2342, 2020.
Marijuana is the most-used illicit substance during pregnancy in the USA, but only two cohort studies, begun over 30years ago, were specifically established to assess the association of pregnancy use with childhood outcomes. They found use to be associated with specific deficits in executive function at 8+years, but did not focus on these outcomes earlier in life when intervention may be more successful. Two general purpose cohorts found increased aggression in exposed female toddlers and increased behavioural problems and tic disorders in exposed school-age children.
The Lifestyle and Early Achievement in Families (LEAF) study assesses the association of in utero marijuana exposure, documented prospectively by biomarker, self-report, and medical records, with executive function and aggression at age 3½-7years.
This ambidirectional cohort (historical cohort with continued follow-up) includes women enrolled in the Perinatal Research Repository during prenatal care at Ohio State University Wexner Medical se effects among children.
The LEAF Study will document the association of prenatal marijuana exposure with development and behaviour in the current era when marijuana is more potent than when previous cohorts were studied. The results may inform policy and interventions to counsel reproductive-aged women about the risks of use during pregnancy and guide prevention and treatment of adverse effects among children.Unlike microglia and NG2 glia, astrocytes are incapable of migrating to sites of injury in the posttraumatic cerebral cortex, instead relying on proliferation to replenish their numbers and distribution in the affected region. However, neither the spectrum of their proliferative repertoire nor their postinjury distribution has been examined in vivo. Using a combination of different thymidine analogs and clonal analysis in a model of repetitive traumatic brain injury, we show for the first time that astrocytes that are quiescent following an initial injury can be coerced to proliferate after a repeated insult in the cerebral cortex grey matter. Interestingly, this process is promoted by invasion of monocytes to the injury site, as their genetic ablation (using CCR2-/- mice) increased the number of repetitively dividing astrocytes at the expense of newly proliferating astrocytes in repeatedly injured parenchyma. These differences profoundly affected both the distribution of astrocytes and recovery period for posttraumatic behavior deficits suggesting key roles of astrocyte self-renewal in brain repair after injury.An accurate and sensitive ultrasound-dispersive liquid-liquid microextraction technique followed by high-performance liquid chromatography separation coupled with electrospray ionization tandem mass spectrometry detection method to determine the presence of tetrabromobisphenol A (TBBPA) in complex environmental matrices is proposed. The miniaturized procedure was used to extract and quantify the analyte in domestic sewage, anaerobic sludge, and the aquatic test organism species Daphnia magna and Chironomus sancticaroli, which are standardized organisms for ecotoxicity bioassays. Limits of detection of 2 ng L-1 (domestic sewage), 2 ng g-1 (anaerobic sludge), 0.25 ng g-1 (D. magna), and 5 ng g-1 (C. tentans) were obtained. The presence of TBBPA was determined in domestic sewage and anaerobic sludge from an anaerobic batch bioreactor at a concentration of 0.2 ± 0.03 μg L-1 and 507 ± 79 ng g-1 , respectively. In D. magna and C. sancticaroli exposed to TBBPA in an acute toxicity bioassay, the micropollutant accumulated at 3.
