Alternative strategies to prevent malaria in pregnancy are needed. The prevention of all malaria infections by providing sustained exposure to effective concentrations of antimalarial drugs is key to reducing the adverse effects of malaria in pregnancy.Older adults with diabetes are heterogeneous in their medical, functional, and cognitive status, and require careful individualisation of their treatment regimens. However, in the absence of detailed information from clinical trials involving older people with varying characteristics, there is little evidence-based guidance, which is a notable limitation of current approaches to care. It is important to recognise that older people with diabetes might vary in their profiles according to age category, functional health, presence of frailty, and comorbidity profiles. In addition, all older adults with diabetes require an individualised approach to care, ranging from robust individuals to those residing in care homes with a short life expectancy, those requiring palliative care, or those requiring end-of-life management. In this Review, our multidisciplinary team of experts describes the current evidence in several important areas in geriatric diabetes, and outlines key research gaps and research questions in each of these areas with the aim to develop evidence-based recommendations to improve the outcomes of interest in older adults. The DEPICT-1 and DEPICT-2 studies showed that dapagliflozin as an adjunct to insulin in individuals with inadequately controlled type 1 diabetes improved glycaemic control and bodyweight, without increase in risk of hypoglycaemia. We aimed to determine the effect of dapagliflozin on urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) using pooled data from the DEPICT studies. In this post-hoc analysis, we used data pooled from both DEPICT studies (DEPICT-1 ran from Nov 11, 2014, to Aug 25, 2017; DEPICT-2 ran from July 8, 2015, to April 18, 2018), in which participants were aged 18-75 years, with inadequately controlled type 1 diabetes and with a baseline UACR of at least 30 mg/g. In the DEPICT studies, participants were randomly assigned (111) to receive dapagliflozin (5 mg or 10 mg) or placebo all plus insulin, for 24 weeks, with a 28-week long-term extension (ie, 52 weeks in total). In this post-hoc analysis, we assessed the percentage change from baseline in UACR seline was seen in eGFR, with a mean difference in change from baseline versus placebo of 3·27 mL/min per 1·73 m (95% CI -0·92 to 7·45) for dapagliflozin 5 mg and 2·12 mL/min per 1·73 m (-2·03 to 6·27) for dapagliflozin 10 mg. Similar proportions of participants in each treatment group had adverse events and serious adverse events, including hypoglycaemia and diabetic ketoacidosis; no new safety signals were identified in this population. Treatment with dapagliflozin resulted in UACR reduction, which might provide renoprotective benefits in individuals with type 1 diabetes and albuminuria. Dedicated prospective studies are needed to confirm these findings as prespecified endpoints. AstraZeneca.AstraZeneca. Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m or ≥30 kg/m ) in a ratio of 11 using random block sizes of 4 and 6. Baxdrostat cell line Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 daysutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.In response to skeletal muscle contraction during exercise, paracrine factors coordinate tissue remodeling, which underlies this healthy adaptation. Here we describe a pH-sensing metabolite signal that initiates muscle remodeling upon exercise. In mice and humans, exercising skeletal muscle releases the mitochondrial metabolite succinate into the local interstitium and circulation. Selective secretion of succinate is facilitated by its transient protonation, which occurs upon muscle cell acidification. In the protonated monocarboxylic form, succinate is rendered a transport substrate for monocarboxylate transporter 1, which facilitates pH-gated release. Upon secretion, succinate signals via its cognate receptor SUCNR1 in non-myofibrillar cells in muscle tissue to control muscle-remodeling transcriptional programs. This succinate-SUCNR1 signaling is required for paracrine regulation of muscle innervation, muscle matrix remodeling, and muscle strength in response to exercise training. In sum, we define a bioenergetic sensor in muscle that utilizes intracellular pH and succinate to coordinate tissue adaptation to exercise.Every day we make decisions critical for adaptation and survival. We repeat actions with known consequences. But we also draw on loosely related events to infer and imagine the outcome of entirely novel choices. These inferential decisions are thought to engage a number of brain regions; however, the underlying neuronal computation remains unknown. Here, we use a multi-day cross-species approach in humans and mice to report the functional anatomy and neuronal computation underlying inferential decisions. We show that during successful inference, the mammalian brain uses a hippocampal prospective code to forecast temporally structured learned associations. Moreover, during resting behavior, coactivation of hippocampal cells in sharp-wave/ripples represent inferred relationships that include reward, thereby "joining-the-dots" between events that have not been observed together but lead to profitable outcomes. Computing mnemonic links in this manner may provide an important mechanism to build a cognitive map that stretches beyond direct experience, thus supporting flexible behavior.