The nuclear/mitotic apparatus protein NuMA is a component of the somatodendritic microtubule arrays of the neuron

Neurons are terminally post-mitotic cells that utilize their microrubule arrays for the growth and maintenance of axons and dendrites rather than for the formation of mitotic spindles. Recent studies from our laboratory suggest that the mechanisms that organize the axonal and dendritic microtubule arrays may be variations on the same mechanisms that organize the mitotic spindle in dividing cells. In particular, we have identified molecular motor proteins that serve analogous functions in the establishment of these seemingly very different microtubule arrays. In the present study, we have sought to determine whether a non-motor protein termed NuMA is also a component of both systems. NuMA is a ~230 kDa structural protein that is present exclusively in the nucleus during interphase. During mitosis, NuMA forms aggregates that interact with microtubules and certain motor proteins. As a result of these interactions, NuMA is thought to draw together the minus-ends of microtubules, thereby helping to organize them into a bipolar spindle. In contrast to mitotic cells, post-mitotic neurons display NuMA both in the nucleus and in the cytoplasm. NuMA appears as multiple small particles within the somatodendritic compartment of the neuron, where its levels increase during early dendritic differentation. A partial but not complete colocalization with minus-ends of microtubules is suggested by the distribution of the particles during development and during drug treatments that alter the microtubule array. These observations provide an initial set of clues regarding a potentially important function of NuMA in the organization of microtubules within the somatodendritic compartment of the neuron.     

Anti-progesterones and the law

Antiprogesterone drugs such a RU 486 can be used as an occasional contraceptive when administered in the luteal phase, as a last-chance contraceptive when administered before completion of implantation, as an abortifacient when administered after completion of implantation, or as a cervical primer for diagnostic purposes or to ease the expulsion of a dead fetus. A critical legal question raised by these agents is: when does contraception end and abortion begin? Completion of implantation represents the beginning of legal pregnancy in many jurisdictions. The legal event necessary to establish criminal liability for abortion is evidence that a health worker believed that implantation had occurred. If it is known to be biologically unlikely that implantation has occurred, it will be more credible that a health worker's intent is contraceptive-based. The prosecuting attorney still bears the burden of establishing a high level of evidence of what a defendant actually knew. An aid to use of RU 486 taken as a last chance contraceptive would be a presumption of contraceptive intention when it is used with the longest possible interval between a woman's last menstrual period and completion of implantation. A presumption of contraceptive intent up to 35 days after the last menstrual period is consistent with both traditional law and modern public policy.     

Atraumatic osteolysis of the distal clavicle: histologic evidence of synovial pathogenesis. A case report

Osteolysis of the distal clavicle was diagnosed in a young male athlete following many years as a baseball pitcher with a supplementary weightlifting program. There was no history of ligamentous injuries, contusions, fractures or separation of the acromioclavicular joint. As such, this case was categorized as "atraumatic" osteolysis. Non-decalcified histologic sections from the resected clavicle suggest that the pathogenesis of this atraumatic osteolysis arose from the synovium.     

Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.     

The effect of respiratory activity,non-invasive respiratory support and facemasks on aerosol generation and its relevance to COVID-19

Respirable aerosols (< 5 µm in diameter) present a high risk of SARS-CoV-2 transmission. Guidelines recommend using aerosol precautions during aerosol-generating procedures, and droplet (> 5 µm) precautions at other times. However, emerging evidence indicates respiratory activities may be a more important source of aerosols than clinical procedures such as tracheal intubation. We aimed to measure the size, total number and volume of all human aerosols exhaled during respiratory activities and therapies. We used a novel chamber with an optical particle counter sampling at 100 l.min^-1 to count and size-fractionate close to all exhaled particles (0.5–25 µm). We compared emissions from ten healthy subjects during six respiratory activities (quiet breathing; talking; shouting; forced expiratory manoeuvres; exercise; and coughing) with three respiratory therapies (high-flow nasal oxygen and single or dual circuit non-invasive positive pressure ventilation). Activities were repeated while wearing facemasks. When compared with quiet breathing, exertional respiratory activities increased particle counts 34.6-fold during talking and 370.8-fold during coughing (p < 0.001). High-flow nasal oxygen 60 at l.min^-1 increased particle counts 2.3-fold (p = 0.031) during quiet breathing. Single and dual circuit non-invasive respiratory therapy at 25/10 cm.H₂O with quiet breathing increased counts by 2.6-fold and 7.8-fold, respectively (both p < 0.001). During exertional activities, respiratory therapies and facemasks reduced emissions compared with activities alone. Respiratory activities (including exertional breathing and coughing) which mimic respiratory patterns during illness generate substantially more aerosols than non-invasive respiratory therapies, which conversely can reduce total emissions. We argue the risk of aerosol exposure is underappreciated and warrants widespread, targeted interventions.     

Impact of vaccination by priority group on UK deaths,hospital admissions and intensive care admissions from COVID-19

National (and global) vaccination provides an opportunity to control the COVID-19 pandemic, which disease suppression by societal lockdown and individual behavioural changes will not. We modelled how vaccination through the UK’s vaccine priority groups impacts deaths, hospital and ICU admissions from COVID-19. We used the UK COVID-19 vaccines delivery plan and publicly available data to estimate UK population by age group and vaccination priority group, including frontline health and social care workers and individuals deemed ‘extreme clinical vulnerable’ or ‘high risk’. Using published data on numbers and distributions of COVID-19-related hospital and ICU admissions and deaths, we modelled the impact of vaccination by age group. We then modified the model to account for hospital and ICU admission, and death among health and social care workers and the population with extreme clinical vulnerability and high risk. Our model closely matches the government’s estimates for mortality after vaccination of priority groups 1–4 and groups 1–9. The model shows vaccination will have a much slower impact on hospital and ICU admissions than on deaths. The early prioritisation of healthcare staff and clinically vulnerable patients increases the impact of vaccination on admissions and also protects the healthcare service. An inflection point, when 50% of the adult population has been vaccinated – with deaths reduced by 95% and hospital admissions by 80% – may be a useful point for re-evaluating vaccine prioritisation. Our model suggests substantial reductions in hospital and ICU admissions will not occur until late March and into April 2021.     

Findings From a Community Survey of Individuals Who Engage in Pup Play

Archives of Sexual Behavior - This study presents findings from a community survey on pup play. Pup play is a kink activity and a form of role play that is growing in popularity internationally,...     

Analysis of time‐to‐event for observational studies: Guidance to the use of intensity models

This paper provides guidance for researchers with some mathematical background on the conduct of time‐to‐event analysis in observational studies based on intensity (hazard) models. Discussions of basic concepts like time axis, event definition and censoring are given. Hazard models are introduced, with special emphasis on the Cox proportional hazards regression model. We provide check lists that may be useful both when fitting the model and assessing its goodness of fit and when interpreting the results. Special attention is paid to how to avoid problems with immortal time bias by introducing time‐dependent covariates. We discuss prediction based on hazard models and difficulties when attempting to draw proper causal conclusions from such models. Finally, we present a series of examples where the methods and check lists are exemplified. Computational details and implementation using the freely available R software are documented in Supplementary Material. The paper was prepared as part of the STRATOS initiative.