Intracellular Concentrations of Borrelia burgdorferi Cyclic Di-AMP Are Not Changed by Altered Expression of the CdaA Synthase

The second messenger nucleotide cyclic diadenylate monophosphate (c-di-AMP) has been identified in several species of Gram positive bacteria and Chlamydia trachomatis. This molecule has been associated with bacterial cell division, cell wall biosynthesis and phosphate metabolism, and with induction of type I interferon responses by host cells. We demonstrate that B. burgdorferi produces a c-di-AMP synthase, which we designated CdaA. Both CdaA and c-di-AMP levels are very low in cultured B. burgdorferi, and no conditions were identified under which cdaA mRNA was differentially expressed. A mutant B. burgdorferi was produced that expresses high levels of CdaA, yet steady state borrelial c-di-AMP levels did not change, apparently due to degradation by the native DhhP phosphodiesterase. The function(s) of c-di-AMP in the Lyme disease spirochete remains enigmatic.     

Postpartum mental illness during the COVID-19 pandemic: a population-based,repeated cross-sectional study

BACKGROUND:It is unclear whether the clinical burden of postpartum mental illness has increased during the COVID-19 pandemic. We sought to compare physician visit rates for postpartum mental illness in Ontario, Canada, during the pandemic with rates expected based on prepandemic patterns.METHODS:In this population-based, repeated cross-sectional study using linked health administrative databases in Ontario, Canada, we used negative binomial regression to model expected visit rates per 1000 postpartum people for March–November 2020 based on prepandemic data (January 2016–February 2020). We compared observed visit rates to expected visit rates for each month of the pandemic period, generating absolute rate differences, incidence rate ratios (IRRs) and their 95% confidence intervals (CIs). The primary outcome was a visit to a primary care physician or a psychiatrist for any mental disorder. We stratified analyses by maternal sociodemographic characteristics.RESULTS:In March 2020, the visit rate was 43.5/1000, with a rate difference of 3.11/1000 (95% CI 1.25–4.89) and an IRR of 1.08 (95% CI 1.03–1.13) compared with the expected rate. In April, the rate difference (10.9/1000, 95% CI 9.14–12.6) and IRR (1.30, 95% CI 1.24–1.36) were higher; this level was generally sustained through November 2020. From April–November, we observed elevated visit rates across provider types and for diagnoses of anxiety, depressive and alcohol or substance use disorders. Observed increases from expected visit rates were greater for people 0–90 days postpartum compared with 91–365 days postpartum; increases were small among people living in low-income neighbourhoods. Public health units in the northern areas of the province did not see sustained elevations in visit rates after July; southern health units had elevated rates through to November.INTERPRETATION:Increased visits for mental health conditions among postpartum people during the first 9 months of the COVID-19 pandemic suggest an increased need for effective and accessible mental health care for this population as the pandemic progresses.

Postpartum mental illness affects as many as 1 in 5 mothers,¹ and can result in maternal suffering and diminished functioning.² Related impaired mother–infant interactions are linked to poor social, cognitive and behavioural outcomes in children across their lifespan.³ When mental illness becomes chronic and recurrent, its effects can extend to the entire family and across generations.⁴ With emergence of the novel coronavirus (SARS-CoV-2), the World Health Organization declared a global COVID-19 pandemic on Mar. 11, 2020. Globally, efforts to contain the virus have led to widespread travel restrictions, physical distancing and work limitations, causing broad social and financial disruption that has been associated with substantial mental health effects.^5,6During the COVID-19 pandemic, people have been reporting concerns about postpartum infection,⁷ and difficulty accessing the extended postpartum social support networks and key community programs that protect against mental illness, such as home visits from public health nurses, breastfeeding clinics and support groups, owing to public health measures.⁸ In Canadian surveys, about 50% of pregnant people reported psychological distress in spring 2020,⁹ and alcohol use increased among women, particularly among those with young children.¹⁰ Whether this represents an increased clinical burden of mental illness or need for care is unknown.Using routinely collected health care data from Ontario, Canada, (population of about 14.6 million), we aimed to examine whether rates of maternal visits to physicians for postpartum mental illness from March to November 2020 differed from expected visit rates based on pre-COVID-19 patterns, and to identify variation by provider type, clinical diagnosis, postpartum timing, parity, income, ethnicity and region of residence.     

Acute Biphasic Effects of Ayahuasca

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca''s compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it''s potential therapeutic effects is offered.     

Osteoporosis,falls, and age in fracture of the proximal femur.

The relative importance of osteoporosis and risk of falling in causing hip fracture is not known. Femoral neck bone mass was measured in 708 elderly people, all of whom had fallen and injured a hip. Below 75 years of age there was a steep increase in relative risk of fracture with reduced bone mass, measured by Singh grade. Above that age the increase in risk was small, and neuromuscular responses which protect the skeleton against trauma may be more important than bone mass.     

Exogenous GABA persistently opens Cl− channels in cultured embryonic rat thalamic neurons

We recorded whole-cell Cl^– currents in cultured embryonic rat thalamic neurons by brief applications of GABA or the structural analogue muscimol. In 17 of 141 neurons (12%) the Cl^– current persisted for a minute or more after the pipette was removed from the bath. Cl^– current never persisted after muscimol exposure even in those cells exhibiting persistent GABA-activated currents (PGC). The half decay times (T₅₀) of PGCs were exponentially and asymptotically related to the duration of GABA exposure and could be interrupted or completely aborted by low-pressure application of saline. PGCs were insensitive to membrane potential, to Tiagabine, a nipecotic acid analogue known to block GABA uptake, and persisted in Ca _o ²⁺ -free medium. Fluctuation analysis revealed that PGCs exhibited inferred Cl^– channel properties whose kinetic components and estimated average elementary conductance showed no significant difference from those estimated during GABA exposure. The relative contribution of low frequency components was consistently reduced and that of high frequency components modestly increased during PGC compared to those recorded during GABA exposure. Taken together, the results suggest the existence of a superficial compartment in these embryonic neurons that can momentarily accumulate and release exogenous GABA.We thank Dr. Wu Ma for advice in isolating thalamic neurons. Tiagabine is a kind gift from Novo Nordisk A/S, Denmark.