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.     

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,...     

Immunological characterization and localization of the Na+/Ca2(+)-exchanger in bovine retina

The sodium/calcium exchanger was purified from bovine retinal rod outer segment membranes and used for the immunization of New Zealand White rabbits. A polyclonal antibody was produced which was found to bind specifically to the 230 kDa Na+/Ca2(+)-exchanger protein as assessed by Western blotting. The antibody did not bind to the high-molecular-weight "rim protein," thereby demonstrating that this protein is distinct from the rod outer segment of Na+/Ca2(+)-exchanger. We used the polyclonal antibody for immunohistochemically localizing the exchange protein in bovine retina. Fluorescent light microscopy revealed intensive immunolabeling of the photoreceptor outer segments, whereas other retinal cell layers exhibited minimal binding. Using the electron microscopic immunogold method, we found specific antibody binding to the extracellular side of rod outer segment plasma membrane. Rod disk membranes, rod inner segments, and cone photoreceptors displayed no significant labeling. We therefore conclude that the Na+/Ca2(+)-exchanger is localized primarily in the rod outer segment plasma membrane, the most appropriate localization considering its proposed role in the process of vertebrate phototransduction.     

Synthesis of substituted 7,12-dihydropyrido[3,2-b:5,4-b']diindoles: rigid planar benzodiazepine receptor ligands with inverse agonist/antagonist properties

A series of 1-, 2-, 3-, 4-, 5-, 6-, 7-, 10-, and 12-substituted pyridodiindoles were synthesized and screened in vitro against [3H]diazepam for activity at the benzodiazepine receptor (BzR). In vitro, the 2-substituted pyridodiindoles were found to be the most potent (IC50 less than 10 nM) of this new class of BzR ligands. In vivo, 2-methoxypyridodiindole 19a (IC50 = 8 nM) was found to be the most potent partial inverse agonist (proconvulsant) of the series. The parent compound 2 (IC50 = 4 nM) was only slightly less potent. In addition, 2-hydroxypyridodiindole 21a (IC50 = 6 nM) was found to exhibit potent proconvulsant activity when administered as a prodrug derivative, pivaloyl ester 22. 2-Chloropyridodiindole 16a (IC50 = 10 nM) was devoid of preconvulsant activity; however, 16a was found to be the most potent antagonist of the anticonvulsant effects of diazepam in this class of BzR ligands. From the in vivo data available, substitution on ring E of 2 with electron-withdrawing groups results in antagonists at BzR, while replacement of hydrogen at C-2 with electron-releasing groups provides enhanced inverse agonist activity. The pyridodiindoles were used as "templates" for the formulation of a model of the inverse agonist/antagonist active site of the BzR. The proposed model consists of a hydrogen bond acceptor site (A1) and a hydrogen bond donor site (D2) disposed 6.0-8.5 A from each other on the receptor protein. The hydrogen-bonding sites are believed to be located at the base of a narrow cleft. A large lipophilic pocket at the mouth of the narrow cleft serves to direct molecules into the binding site, while the presence of a small lipophilic pocket permits substitution only at position 2 of the pyridodiindole nucleus for maximum binding potency.