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Ankle fracture is a common injury with a strong evidence base focused on effectiveness of treatments. However, there are no reporting guidelines on distal tibia and ankle fractures. This has led to heterogeneity in outcome reporting and consequently, restricted the contribution of evidence syntheses. Over the past decade, core outcome sets have been developed to address this issue and are available for several common fractures, including those of the hip, distal radius, and open tibial fractures. This protocol describes the process to co-produce-with patient partners and other key stakeholders-a multi-stakeholder derived Core Outcome Set for distal Tibia and Ankle fractures (COSTA). The scope of COSTA will be for clinical trials.

The study will have five-stages which will include the following (i) systematic reviews of existing qualitative studies and outcome reporting in randomised controlled trial studies to inform a developing list of potential outcome domains; (ii) qualitative interviews (including se interventions, potentially reducing reporting bias and research waste.

Hypothermia significantly affects mortality and morbidity of newborns. Literature about severe accidental hypothermia in neonates is limited. We report a case of a neonate suffering from severe accidental hypothermia. An understanding of the physiology of neonatal thermoregulation and hypothermia is important to decide on treatment.

A low-birth-weight newborn was found with severe accidental hypothermia (rectal temperature 25.7°C) due to prolonged exposure to low ambient temperature. The newborn presented bradycardic, bradypnoeic, lethargic, pale and cold. Bradycardia, bradypnea and impaired consciousness were interpreted in the context of the measured body temperature. Therefore, no reanimation or intubation was initiated. The newborn was closely monitored and successfully treated only with active and passive rewarming.

Clinical parameters such as heart frequency, blood pressure, respiration and consciousness must be interpreted in light of the measured body temperature. Medical treatment should be adapted to the clinical presentation. External rewarming can be a safe and effective measure in neonatal patients.

Clinical parameters such as heart frequency, blood pressure, respiration and consciousness must be interpreted in light of the measured body temperature. Medical treatment should be adapted to the clinical presentation. External rewarming can be a safe and effective measure in neonatal patients.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine.

The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1.

The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutarediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.Memory and long term potentiation require de novo protein synthesis. A key regulator of this process is mTORC1, a complex comprising the mTOR kinase. Growth factors activate mTORC1 via a pathway involving PI3-kinase, Akt, the TSC complex and the GTPase Rheb. In non-neuronal cells, translocation of mTORC1 to late endocytic compartments (LEs), where Rheb is enriched, is triggered by amino acids. However, the regulation of mTORC1 in neurons remains unclear. In mouse hippocampal neurons, we observed that BDNF and treatments activating NMDA receptors trigger a robust increase in mTORC1 activity. NMDA receptors activation induced a significant recruitment of mTOR onto lysosomes even in the absence of external amino acids, whereas mTORC1 was evenly distributed in neurons under resting conditions. NMDA receptor-induced mTOR translocation to LEs was partly dependent on the BDNF receptor TrkB, suggesting that BDNF contributes to the effect of NMDA receptors on mTORC1 translocation. In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR. To gain spatial and temporal control over mTOR localization, we designed an optogenetic module based on light-sensitive dimerizers able to recruit mTOR on LEs. In cells expressing this optogenetic tool, mTOR was translocated to LEs upon photoactivation. Pimasertib research buy In the absence of growth factor, this was not sufficient to activate mTORC1. In contrast, mTORC1 was potently activated by a combination of BDNF and photoactivation. The data demonstrate that two important triggers of synaptic plasticity, BDNF and NMDA receptors, synergistically power the two arms of the mTORC1 activation mechanism, i.e., mTORC1 translocation to LEs and Rheb activation. Moreover, they unmask a functional link between NMDA receptors and mTORC1 that could underlie the changes in the synaptic proteome associated with long-lasting changes in synaptic strength.

The prevalence of early initiation of breastfeeding and exclusive breastfeeding (EBF) at 6 months remain low in the Philippines. To help meet the 90% early initiation of breastfeeding target and to improve infant and young child feeding practices in the Philippines, the Millennium Development Goals - Fund 2030 Joint Programme (JP) on Ensuring Food Security and Nutrition for Children 0-24 months old was implemented. We aimed to determine the effectiveness of visits by peer counselors during pregnancy and after delivery, and membership in breastfeeding support groups in promoting these optimal breastfeeding practices.

We used data from the Endline Survey of the JPto study the effects of prenatal and postnatal peer counselor visits, and membership in breastfeeding support groups, and their possible interactions withinitiation of breastfeeding within 1 hour of birth among children aged 0 to 24 months and EBF at 6 months among children aged 6to 24 months, while adjusting for confounding. We used logistic regreing behaviors should be further reviewed. Our suggestion to integrate non-healthcare professionals to promote early initiation of breastfeeding and EBF could be tested in future intervention studies.

Our findings suggest breastfeeding support groups may be institutionalized to promote both early initiation of breastfeeding and EBF in the Philippines, while the role of peer counselors in promoting optimal breastfeeding behaviors should be further reviewed. Our suggestion to integrate non-healthcare professionals to promote early initiation of breastfeeding and EBF could be tested in future intervention studies.

To evaluate the ability of single heartbeat fast-strain encoded (SENC) cardiovascular magnetic resonance (CMR) derived myocardial strain to discriminate between different forms of left ventricular (LV) hypertrophy (LVH).

314 patients (228 with hypertensive heart disease (HHD), 45 with hypertrophic cardiomyopathy (HCM), 41 with amyloidosis, 22 competitive athletes, and 33 healthy controls) were systematically analysed. LV ejection fraction(LVEF), LV mass index and interventricular septal (IVS) thickness, T1 mapping and atypical late gadolinium enhancement (LGE) were assessed. In addition, the percentage of LV myocardial segments with strain ≤ -17% (%normal myocardium) was determined.

Patients with amyloidosis and HCM exhibited the highest IVS thickness (17.4 ± 3.3mm and 17.4 ± 6mm, respectively, p < 0.05 vs. all other groups), whereas patients with amyloidosis showed the highest LV mass index (95.1 ± 20.1g/m

, p < 0.05 vs all others) and lower LVEF compared to controls (50.5 ± 9.8% vs 59.2 ± 5.5%,etes vs. HHD. Combining strain and LGE data is useful for differentiating between HHD vs. HCM and HCM vs. cardiac amyloidosis.

The entry of PCR-based techniques into malaria diagnostics has improved the sensitivity and specificity of the detection of Plasmodium infections. It has been shown that humans are regularly infected by at least six different Plasmodium species. The MC004 real-time PCR assay for malaria diagnosis is a novel single-tube assay that has been developed for the purpose of simultaneously detecting all Plasmodium species known to infect humans, and discrimination between Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale wallikeri, Plasmodium ovale curtisi, Plasmodium knowlesi (including differentiation of three strains) and Plasmodium cynomolgi (including differentiation of three strains). Detection and identification of Plasmodium species relies on molecular beacon probe-based melting curve analysis. In addition, this assay might be used to quantify the parasitaemia of at least P. falciparum by calculating the level of parasitaemia directly from the Cq-value.

The samples used in thiudies.

Based upon the analytical performance characteristics that were determined, the MC004 assay showed performance suitable for use in clinical settings, as well as epidemiological studies.

Despite considerable institutional experimentation at national and international levels in response to calls for global health security reform, there is little research on organisational models that address outbreak preparedness and response. Created in the aftermath of the 2013-16 West AfricanEbola epidemic, the United Kingdom's Public Health Rapid Support Team (UK-PHRST) was designed to address critical gaps in outbreak response illuminated during the epidemic, while leveraging existing UK institutional strengths. The partnership between the government agency, Public Health England, and an academic consortium, led by the London School of Hygiene and Tropical Medicine, seeks to integrate outbreak response, operational research and capacity building. We explored the design, establishment and early experiences of the UK-PHRST as one of the first bodies of its kind globally, paying particular attention to governance decisions which enabled them to address their complex mission.

We conducted a qualitative caies reinforced theexisting global health architecture.

The UK-PHRST aims to enhance global outbreak response using an innovative and integrated model that capitalises on institutional strengths of the partnership. Insights suggest that despite adding complexity, integrating operational research through the government-academic collaboration contributed significant advantages. This promising model could be adopted and adapted by countries seeking to build similar outbreak response and research capacities.

The UK-PHRST aims to enhance global outbreak response using an innovative and integrated model that capitalises on institutional strengths of the partnership. Insights suggest that despite adding complexity, integrating operational research through the government-academic collaboration contributed significant advantages. This promising model could be adopted and adapted by countries seeking to build similar outbreak response and research capacities.

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