Castanedadrachmann7145
Endosomal transport and positioning cooperate in the establishment of neuronal compartment architecture, dynamics, and function, contributing to neuronal intracellular logistics. Furthermore, dysfunction of endo-lysosomal has been identified as a common mechanism in neurodegenerative diseases. Here, we analyzed endo-lysosomal transport when α-synuclein (α-syn) fibrillar polymorphs, β-amyloid (Aβ) fibrils, and oligomers were externally applied on primary cultures of mouse cortical neurons. To measure this transport, we used a simple readout based on the spontaneous endocytosis in cultured neurons of fluorescent nanodiamonds (FNDs), a perfectly stable nano-emitter, and the subsequent automatic extraction and quantification of their directed motions at high-throughput. α-Syn fibrillar polymorphs, Aβ fibrils, and oligomers induce a 2-fold decrease of the fraction of nanodiamonds transported along microtubules, while only slightly reducing their interaction with cortical neurons. This important decrease in moving endosomes is expected to have a huge impact on neuronal homeostasis. We next assessed lysosomes dynamics, using LysoTracker. Neurons exposure to Aβ oligomers led to an increase in the number of lysosomes, a decrease in the fraction of moving lysosome and an increase in their size, reminiscent of that found in APP transgenic model of Alzheimer's disease. We then analyzed the effect of α-syn fibrillar polymorphs, Aβ fibrils, and oligomers on endosomal and lysosomal transport and quantified directed transport of those assemblies within cortical neurons. We report different impacts on endosomal and lysosomal transport parameters and differences in the trajectory lengths of cargoes loaded with pathogenic protein assemblies. Our results suggest that intraneuronal pathogenic protein aggregates internalization and transport may represent a target for novel neuroprotective therapeutic strategies.
There remains considerable global unmet contraceptive need, with almost 200 million women reporting desire to limit or space childbearing without contraceptive use. Researchers have documented worldwide interest in an oral, on-demand contraceptive option were it available. Candidates for use include ulipristal acetate (UA), levonorgestrel and cyclo-oxygenase-2 (COX-2) inhibitors alone or in combination.
We performed an exploratory, prospective study of matched menstrual cycles one baseline cycle and one treatment cycle of UA 30 mg plus meloxicam 30 mg just prior to ovulation. The primary outcome was ovulation disruption, defined as unruptured dominant follicle for 5 days. Secondary outcomes included comparing cycle length, endometrial stripe thickness, and side effects.
Nine participants completed all study procedures in both cycles. Ovulatory disruption occurred in 66.7% (n=6) of treatment cycles and all but one demonstrated features of ovulatory dysfunction. Cycle length (mean±SD) was longer in the treatment cycle (31.9
4.0 vs 28.6
3.5 days, p<0.01). Secondary outcomes did not differ between the two cycles.
UA plus the COX-2 inhibitor meloxicam disrupts ovulation at peak luteal surge and is a promising candidate for evaluation as a pericoital oral contraceptive.
NCT03354117.
NCT03354117.
This study aimed to determine the COVID-19 risk perceptions, vaccination intentions and predictive factors of family physicians and family healthcare staff working in primary care in Üsküdar.
A cross-sectional study was performed using an online questionnaire to determine the demographic and general characteristics of the participants and their willingness to be vaccinated.
An online questionnaire was applied to family physicians and family health workers working in primary care family health centres in Üsküdar between 25 and 29 December 2020. Multivariate analysis was performed to identify independent predictors of the willingness of individuals to be vaccinated.
Out of 323 health workers working in 44 family health centres in the district, a total of 276 health workers were reached, including 126 physicians (n=158, 79.7%) and 150 midwives/nurses (n=165, 90.9%) (response rate 85.4%).
50.4% (n=139) of the healthcare workers were willing to have the COVID-19 vaccine, 29% (n=80) were undecided and 20.on rates. For evidence-based planning in vaccination studies, there is a need to investigate the reasons for COVID-19 vaccine acceptance by healthcare workers at all levels.
To examine the association between gestational age at birth and risk of clinically diagnosed intellectual disability (ID) week by week to provide a detailed description of ID risk across the entire range of gestational ages and by severity of ID.
All individuals born alive in Sweden 1974-2017 were prospectively followed up from birth until 2017 using national registers. The HRs for ID according to weekly gestational age and gestational age categories were determined using Cox models. Sibling analyses were conducted to adjust for familial confounding.
The study included 3 572 845 live births. During the follow-up, 26 596 ID cases were registered. The adjusted weekly estimates showed a gradual increase in risk of ID from week 40 to week 24 (adjusted HR
=1.80 (1.74 to 1.87), aHR
=3.93 (3.73 to 4.13), aHR
=7.53 (6.95 to 8.16), aHR
=21.58 (18.62 to 25.00)) and from week 41 onwards (aHR
=1.26 (1.19 to 1.32)), with statistically significantly higher risks across the range of gestational age compared with infants born at week 40. The associations were consistent in mild, moderate and severe/profound ID but most prominent for severe/profound ID.
The risk of ID increased weekly as the date of delivery moved away from 40 weeks, both preterm and post-term. The results remained robust after detailed adjustment for confounding, including familial confounding.
The risk of ID increased weekly as the date of delivery moved away from 40 weeks, both preterm and post-term. The results remained robust after detailed adjustment for confounding, including familial confounding.
Shorter courses of intravenous antibiotics for young infants with urinary tract infection (UTI) have myriad advantages. As practice shifts toward shorter intravenous treatment courses, this study aimed to determine the safety of early intravenous-to-oral antibiotic switch and identify risk factors for bacteraemia with UTI.
Retrospective audit of infants aged ≤90 days with a positive urine culture at a quaternary paediatric hospital over 4 years (2016-2020). Data were collected from the hospital electronic medical record and laboratory information system. Short-course intravenous antibiotic duration was defined as <48 hours for non-bacteraemic UTI and <7 days for bacteraemic UTI. Multivariate analysis was used to determine patient factors predicting bacteraemia.
Among 427 infants with non-bacteraemic UTI, 257 (60.2%) were treated for <48 hours. Clinicians prescribed shorter intravenous courses to infants who were female, aged >30 days, afebrile and those without bacteraemia or cerebrospinal fe rare in young infants with UTI.
The association of apixaban compared with warfarin for the treatment of venous thromboembolism in patients receiving maintenance dialysis is not well studied.
We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries receiving dialysis using United States Renal Data System data from 2013 to 2018. The study included patients who received a new prescription for apixaban or warfarin following a venous thromboembolism diagnosis. The outcomes were recurrent venous thromboembolism, major bleeding, and death. Outcomes were analyzed using Cox proportional hazards regression for intention-to-treat and censored-at-drug-switch-or-discontinuation analyses. Models incorporated inverse probability of treatment and censoring weights to minimize confounding and informative censoring.
In 12,206 individuals, apixaban, compared with warfarin, was associated with lower risks of both recurrent venous thromboembolism (hazard ratio [HR], 0.58; 95% confidence interval [95% CI], 0.43 to 0.77) and major bleeding (HR, 0.78; 95% CI, 0.62 to 0.98) in the intention-to-treat analysis over 6 months of follow-up. However, there was no difference between apixaban and warfarin in terms of risk of all-cause death (HR, 1.04; 95% CI, 0.94 to 1.16). Corresponding hazard ratios for the 6-month censored-at-drug-switch-or-discontinuation analysis and for corresponding analyses limited to a shorter (3-month) follow-up were all highly similar to the primary analysis.
In a large group of US patients on dialysis with recent venous thromboembolism, we observed that apixaban was associated with lower risk of recurrent venous thromboembolism and of major bleeding than warfarin. There was no observed difference in mortality.
In a large group of US patients on dialysis with recent venous thromboembolism, we observed that apixaban was associated with lower risk of recurrent venous thromboembolism and of major bleeding than warfarin. There was no observed difference in mortality.
The speed of vaccine development has been a singular achievement during the COVID-19 pandemic, although uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. We sought to explore the impact of mixing of vaccinated and unvaccinated populations on risk of SARS-CoV-2 infection among vaccinated people.
We constructed a simple susceptible-infectious-recovered compartmental model of a respiratory infectious disease with 2 connected subpopulations people who were vaccinated and those who were unvaccinated. check details We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to complete like-with-like mixing (complete assortativity), in which people have contact exclusively with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup and in the population as a whole.
We found that the risk of infection was markedly higher among unvaccinated people are unvaccinated, their choices affect risk of viral infection among those who are vaccinated in a manner that is disproportionate to the portion of unvaccinated people in the population.
Youth mental health is a global issue, with 75% of many serious mental health difficulties emerging before the age of 25. An increase in the popularity of online counselling for young people's mental health has been seen in recent years, due to their accessibility, cost-effectiveness and reduced stigmatising effects. Online synchronous chat counselling consists of real-time, text-based, one-to-one chats with a mental health professional and/or trained volunteer. Literature to date examining the effectiveness of these interventions has been limited, and little is known about their design features, their acceptance, effectiveness and the therapeutic processes that contribute to their working.
A mixed-methods systematic review of the literature will be conducted. PsycINFO MEDLINE, CINAHL, Web of Science and relevant grey literature will be searched for peer-reviewed, English language studies between January 1995 and June 2021. Backward and forward reference checking will be conducted. Quality of included articles will be examined using the Mixed Methods Appraisal Tool and a combination of the TIDieR checklist and a prepopulated data table will be used for extraction.
