Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism.

Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with "protein glycosylation" and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.

A Systematic Review of the Impact of the First Year of COVID-19 on Obesity Risk Factors: A Pandemic Fueling a Pandemic?

Obesity is increasingly prevalent worldwide. Associated risk factors, including depression, socioeconomic stress, poor diet, and lack of physical activity, have all been impacted by the coronavirus disease 2019 (COVID-19) pandemic. This systematic review aims to explore the indirect effects of the first year of COVID-19 on obesity and its risk factors. A literature search of PubMed and EMBASE was performed from 1 January 2020 to 31 December 2020 to identify relevant studies pertaining to the first year of the COVID-19 pandemic (PROSPERO; CRD42020219433). All English-language studies on weight change and key obesity risk factors (psychosocial and socioeconomic health) during the COVID-19 pandemic were considered for inclusion. Of 805 full-text articles that were reviewed, 87 were included for analysis. The included studies observed increased food and alcohol consumption, increased sedentary time, worsening depressive symptoms, and increased financial stress. Overall, these results suggest that COVID-19 has exacerbated the current risk factors for obesity and is likely to worsen obesity rates in the near future. Future studies, and policy makers, will need to carefully consider their interdependency to develop effective interventions able to mitigate the obesity pandemic.

Iatrogenic Complications of Compulsory Treatment in a Patient Presenting with an Emotionally Unstable Personality Disorder and Self-Harm.

Attempted suicide and deliberate self-harm are common and challenging presentations in the emergency department. A proportion of these patients refuse interventions and this presents the clinical, legal, and ethical dilemma as to whether treatment should be provided against their will. Multiple factors influence this decision. It is difficult to foresee the multitude and magnitude of complications that can arise once it has been decided to treat individuals who do not consent. This case illustrates a particularly complex chain of events that occurred after treating someone against their will who presented with self-harm and suicidal ideation. These consequences are contrasted with those of not intervening when similar situations arose with the same patient.

Generation COVID-19 - Should the foetus be worried?

AIM: The aim of this narrative review was to evaluate the risks, both direct and indirect, to the foetus from the COVID-19 pandemic. METHODS: Direct and indirect risks were defined as (a) vertical infection (congenital or intrapartum), (b) maternal infection and its sequelae, and (c) sources of maternal stress during lockdown, including social isolation and altered healthcare provision. RESULTS: Early studies suggest that vertical viral transmission is low; however, there may be an important effect of maternal infection on foetal growth and development. The impact of various degrees of lockdown on prospective mothers' health, habits and healthcare provision is of concern. In particular, increased maternal stress has been shown to have a significant effect on foetal brain development increasing the risk of mental health, and cognitive and behavioural disorders in later life. CONCLUSION: From the evidence available to date, direct risks to the foetus from the SARS-CoV-2 virus are low. Indirect effects of the pandemic, particularly resulting from the effect of maternal stress on the developing brain, can have lifelong detrimental impacts for this generation of children.

Severe Aplastic Anemia Presenting as Neutropenic Sepsis.

A 40-year-old female with aplastic anemia presented with a gum abscess deteriorating into neutropenic sepsis. Infection is an incredibly rare initial manifestation of aplastic anemia even on a background of significant neutropenia, hence the uniqueness of this case. The patient's initial complaints were of a subacute history of heavy vaginal bleeding and unexplained bruising, however on examination in the emergency department the patient was also noted to be pyrexial with gingival hyperplasia and a left sided submandibular lymphadenopathy. Initial blood results were phoned through from the lab reporting pancytopenia, confirming clinical suspicion of neutropenic sepsis. Antibiotic therapy was commenced and maxillofacial review for her unrelenting jaw pain revealed a gum abscess ultimately requiring tooth extraction. The patient underwent bone marrow biopsy showing hypocellular marrow with erythroid-dominant, dysplastic hematopoiesis. A thorough panel of investigations to rule out secondary causes led to the diagnosis of aplastic anemia, for which the patient is currently being managed with oral ciclosporin plus eltrombopag-bridging therapy, plus counselling for the potential requirement for stem cell transplant.

Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus.

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.