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The proportion of children younger than 3 months at time of death was 17% in LMICs, 12% in UMICs, and 7% in HICs. We estimated that 3339 annual influenza-related in-hospital deaths occur in the first 3 months of life globally.

In our study, less than 20% of children is younger than 3 months at time of influenza-related death. Although maternal influenza vaccination may impact maternal and infant influenza disease burden, additional immunisation strategies are needed to prevent global influenza-related childhood mortality. read more The missing data, global coverage, and data quality in this study should be taken into consideration for further interpretation of the results.

Bill & Melinda Gates Foundation.

Bill & Melinda Gates Foundation.

There are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare.

Electronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A descriptive time series was conducted using data from five NHS trusts to examine patterns in referrals to services (1st January 2019 to 24th May 2020) and appointments (1st January 2020 to 24th May 2020) taking place.

The number of patients accessing mental health services dropped by an average of 55% in the early weeks after the March 2020 lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK, which gradually recovered to a 28% reduction by May. We found some evidence suggesting changes in the sociodemographic and clinical characteristics of referrals. Despite a reduction in access, the impact on appointments appeared limited with service providers shifting to remote delivery of care.

Services appeared to adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced, potentially placing a future burden on service. Despite the observational nature of the data, the present study can inform the planning of service provision and policy.

AD and TS were funded by Innovate UK (KTP #11,105).

AD and TS were funded by Innovate UK (KTP #11,105).

Individuals with Acute Rheumatic Fever (ARF) often report a family history of ARF or Rheumatic Heart Disease (RHD) however the degree of familial susceptibility to RHD is poorly defined. This study aimed to determine RHD prevalence among first degree relatives of ARF patients using echocardiography.

Children with ARF were recruited from Auckland, New Zealand. Parents and siblings ≥ 4years were offered echocardiography. Echocardiograms were reported according to World Heart Federation 2012 criteria. RHD prevalence in first degree relatives was compared to previously established population rates in the region.

In total, 70 index cases with ARF were recruited. Echocardiography was performed in 94 parents and 132 siblings. There were 3 siblings with definite RHD and 9 with borderline RHD. There were 4 parents with definite RHD. Overall prevalence of RHD (definite and borderline) in siblings was 90/1,000 (95% CI 45-143/1,000) compared to 36/1,000 (95% CI 30-42/1,000) in New Zealand children from high ARF incidence populations (p 0.001). Prevalence of definite RHD in parents was 42/1,000 (95% CI 7-87/1,000) compared to 22/1,000 (95% CI 9-36/1,000) in adults from a high ARF incidence New Zealand population (p 0.249).

RHD prevalence in siblings and parents of ARF cases is significantly greater than in comparable background populations. The contribution of hereditary versus environmental risk factors remains uncertain. We recommend targeted echocardiographic case-finding among siblings and parents of ARF/RHD cases in order to detect previously unrecognized latent RHD.

RHD prevalence in siblings and parents of ARF cases is significantly greater than in comparable background populations. The contribution of hereditary versus environmental risk factors remains uncertain. We recommend targeted echocardiographic case-finding among siblings and parents of ARF/RHD cases in order to detect previously unrecognized latent RHD.

While the effects of prolonged sleep deprivation (≥24h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management.

To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories.

Seizure probas with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.

Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria.

A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R

* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12h from medication. The study tical R

* without changing renal perfusion or blood flow. This suggests improved renal cortical oxygenation due to a reduced tubular transport workload in the proximal tubules. Such improved oxygenation may in part explain the long-term beneficial renal effects seen with SGLT2 inhibitors, but it remains to be determined whether the observed effects can be achieved with lower doses, with chronic treatment and if they occur in type 2 diabetes as well.

A single dose of 50 mg dapagliflozin acutely improved renal cortical R2* without changing renal perfusion or blood flow. This suggests improved renal cortical oxygenation due to a reduced tubular transport workload in the proximal tubules. Such improved oxygenation may in part explain the long-term beneficial renal effects seen with SGLT2 inhibitors, but it remains to be determined whether the observed effects can be achieved with lower doses, with chronic treatment and if they occur in type 2 diabetes as well.The capacity to distinguish comparable experiences is fundamental for the recall of similar memories and has been proposed to require pattern separation in the dentate gyrus (DG). However, the cellular mechanisms by which mature granule cells (GCs) of the DG accomplish this function are poorly characterized. Here, we show that Kv4.2 channels selectively modulate the excitability of medial dendrites of dentate GCs. These dendrites are targeted by the medial entorhinal cortex, the main source of spatial inputs to the DG. Accordingly, we found that the spatial pattern separation capability of animals lacking the Kv4.2 channel is significantly impaired. This points to the role of intrinsic excitability in supporting the mnemonic function of the dentate and to the Kv4.2 channel as a candidate substrate promoting spatial pattern separation.Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-Western diet, baboons, and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic polymerase chain reaction and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation.Signaling cascades converting the recognition of pathogens to efficient inflammatory responses by neutrophils are critical for host survival. SKAP2, an adaptor protein, is required for reactive oxygen species (ROS) generation following neutrophil stimulation by integrins, formyl peptide receptors, and for host defense against the Gram-negative bacterial pathogens, Klebsiella pneumoniae and Yersinia pseudotuberculosis. Using neutrophils from murine HoxB8-immortalized progenitors, we show that SKAP2 in neutrophils is crucial for maximal ROS response to purified C-type lectin receptor agonists and to the fungal pathogens, Candida glabrata and Candida albicans, and for robust killing of C. glabrata. Inside-out signaling to integrin and Syk phosphorylation occurred independently of SKAP2 after Candida infection. However, Pyk2, ERK1/2, and p38 phosphorylation were significantly reduced after infection with C. glabrata and K. pneumoniae in Skap2-/- neutrophils. These data demonstrate the importance of SKAP2 in ROS generation and host defense beyond antibacterial immunity to include CLRs and Candida species.Single traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Rodent studies suggested germline RNA as a mediator of effects of chronic environmental exposures to the progeny. The effects of an acute paternal stress exposure on the germline and their potential consequences on offspring remain to be seen. We find that acute administration of an agonist for the stress-sensitive Glucocorticoid receptor, using the common corticosteroid dexamethasone, affects the RNA payload of mature sperm as soon as 3 hr after exposure. It further impacts early embryonic transcriptional trajectories, as determined by single-embryo sequencing, and metabolism in the offspring. We show persistent regulation of tRNA fragments in sperm and descendant 2-cell embryos, suggesting transmission from sperm to embryo. Lastly, we unravel environmentally induced alterations in sperm circRNAs and their targets in the early embryo, highlighting this class as an additional candidate in RNA-mediated inheritance of disease risk.