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Background Almost two million stillbirths occur annually, most occurring in low- and middle-income countries. Nigeria is reported to have one of the highest stillbirth rates on the African continent. The aim was to identify sociodemographic, living environment, and health status factors associated with stillbirth and determine the associations between pregnancy and birth factors and stillbirth in the Murtala Mohammed Specialist Hospital, Kano, Nigeria. Methods A three-month single-site prospective observational feasibility study. Demographic and clinical data were collected. We fitted bivariable and multivariable models for stillbirth (yes/no) and three-category livebirth/macerated stillbirth/non-macerated stillbirth outcomes to explore their association with demographic and clinical factors. Findings 1,998 neonates and 1,926 mothers were enrolled. Higher odds of stillbirth were associated with low-levels of maternal education, a further distance to travel to the hospital, living in a shack, maternal hypertension, previous stillbirth, birthing complications, increased duration of labour, antepartum haemorrhage, prolonged or obstructed labour, vaginal breech delivery, emergency caesarean-section, and signs of trauma to the neonate following birth. Interpretation This work has obtained data on some factors influencing stillbirth. This in turn will facilitate the development of improved public health interventions to reduce preventable deaths and to progress maternal health within this site.

Inflammation is implicated in placental dysfunction leading to stillbirth, yet evidence of a systemic immune response during parturition remains unclear. Here, we present the first transcriptomic analysis of maternal systemic responses associated with stillbirth, using a minimally invasive finger-prick method for whole blood collection in labouring women in northern Nigeria. This approach facilitated participant recruitment with minimal disruption to care and provided high-quality RNA for transcriptomic profiling. Contrary to expectations, no major differences were observed in systemic immune states between propensity-matched live births and stillbirths. These findings suggest several possibilities, including the dominance of a parturition response masking an underlying immune state, physical protective barriers, or placental tolerance mechanisms. This study offers novel insights into maternal systemic immune health during stillbirth and highlights the need for further research. It also contributes to the broader “Stillbirths in Kano” initiative, aimed at reducing stillbirth rates through enhanced prenatal care.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for bla CTX-M-15 , bla NDM , bla KPC and bla OXA-48 -like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates’ rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers’ rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli , Klebsiella pneumoniae and Enterobacter cloacae / E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes. Analysis of gut microbiota of mothers and its neonates—as part of the BARNARDS study—reveals associations between β-lactamase gene carriage and neonatal sepsis risk in low-income settings.

Background A mirror placed in the mid-sagittal plane of the body has been used to reduce phantom limb pain and improve movement function in medical conditions characterised by asymmetrical movement control. The mirrored illusion of unimpaired limb movement during gait might enhance the effect, but a physical mirror is only capable of showing parallel movement of limbs in real time typically while sitting. We aimed to overcome the limitations of physical mirrors by developing and evaluating a Virtual Mirror Box which delays the mirrored image of limbs during gait to ensure temporal congruency with the impaired physical limb. Methods An application was developed in the CAREN system’s D-Flow software which mirrors selected limbs recorded by real-time motion capture to the contralateral side. To achieve phase shifted movement of limbs during gait, the mirrored virtual limbs are also delayed by a continuously calculated amount derived from past gait events. In order to accommodate non-normal proportions and offsets of pathological gait, the movements are morphed so that the physical and virtual contact events match on the mirrored side. Our method was tested with a trans-femoral amputee walking on a treadmill using his artificial limb. Joint angles of the elbow and knee were compared between the intact and mirrored side using cross correlation, root mean squared difference and correlation coefficients. Results The time delayed adaptive virtual mirror box produced a symmetrical looking gait of the avatar coupled with a reduction of the difference between the intact and virtual knee and elbow angles (10.86° and 5.34° reduced to 4.99° and 2.54° respectively). Dynamic morphing of the delay caused a non-significant change of toe-off events when compared to delaying by 50% of the previous gait cycle, as opposed to the initial contact events which showed a practically negligible but statistically significant increase (p < 0.05). Conclusions Adding an adaptive time delay to the Virtual Mirror Box has extended its use to treadmill gait, for the first time. Dynamic morphing resulted in a compromise between mirrored movement of the intact side and gait events of the virtual limbs matched with physical events of the impaired side. Asymmetrical but repeatable gait is expected to provide even more faithful mirroring.

To investigate the relationship between physical activity and lung cancer among smokers and whether this relationship differed according to physical activity intensity, smoking status, and gender. Meta-analysis. A computerized bibliographical search was conducted in five databases. Study inclusion criteria were: (i) the study population was not diagnosed with lung cancer at baseline; (ii) the study provided information concerning the effect size of physical activity on the risk of developing lung cancer in smokers; and (iii) the study distinguished different physical activity intensity levels. Two authors independently extracted data and assessed the methodological quality. Pooled rate ratios (RR) were calculated for all data, and for subgroups of physical activity intensity, smoking status, and gender. Pooled RRs of 7 cohort studies showed that physical activity was associated with a reduced risk of lung cancer in smokers (RR=0.82, 95% CI=0.77; 0.87). We did not find clear dose–response relationship regarding exercise or smoking intensity, i.e. high levels of physical activity did not show a higher risk reduction than moderate physical activity levels, and the association between physical activity and risk reduction did not differ between heavy and light smokers. The reduced risk associated with physical activity was greater in women than in men (p=0.03), but this finding was based on only one study that reported data on women. Results of this meta-analysis indicate that leisure time physical activity is associated with reduced risk of developing lung cancer among smokers. Future studies should provide insight into a potential dose–response relationship, and should use reliable and valid physical activity measurements.

Individuals with type 2 diabetes have increased fracture risk despite higher bone mineral density (BMD). Our aim was to examine the influence of glucose control on skeletal complications. Data of 4,135 participants of the Rotterdam Study, a prospective population-based cohort, were available (mean follow-up 12.2 years). At baseline, 420 participants with type 2 diabetes were classified by glucose control (according to HbA1c calculated from fructosamine), resulting in three comparison groups: adequately controlled diabetes (ACD; n = 203; HbA1c <7.5%), inadequately controlled diabetes (ICD; n = 217; HbA1c ≥ 7.5%), and no diabetes (n = 3,715). Models adjusted for sex, age, height, and weight (and femoral neck BMD) were used to test for differences in bone parameters and fracture risk (hazard ratio [HR] [95% CI]). The ICD group had 1.1-5.6% higher BMD, 4.6-5.6% thicker cortices, and -1.2 to -1.8% narrower femoral necks than ACD and ND, respectively. Participants with ICD had 47-62% higher fracture risk than individuals without diabetes (HR 1.47 [1.12-1.92]) and ACD (1.62 [1.09-2.40]), whereas those with ACD had a risk similar to those without diabetes (0.91 [0.67-1.23]). Poor glycemic control in type 2 diabetes is associated with fracture risk, high BMD, and thicker femoral cortices in narrower bones. We postulate that fragility in apparently \"strong\" bones in ICD can result from microcrack accumulation and/or cortical porosity, reflecting impaired bone repair.

Methane (CH 4 ) strongly contributes to observed global warming. As natural CH 4 emissions mainly originate from wet ecosystems, it is important to unravel how climate change may affect these emissions. This is especially true for ebullition (bubble flux from sediments), a pathway that has long been underestimated but generally dominates emissions. Here we show a remarkably strong relationship between CH 4 ebullition and temperature across a wide range of freshwater ecosystems on different continents using multi-seasonal CH 4 ebullition data from the literature. As these temperature–ebullition relationships may have been affected by seasonal variation in organic matter availability, we also conducted a controlled year-round mesocosm experiment. Here 4 °C warming led to 51% higher total annual CH 4 ebullition, while diffusion was not affected. Our combined findings suggest that global warming will strongly enhance freshwater CH 4 emissions through a disproportional increase in ebullition (6–20% per 1 °C increase), contributing to global warming. The impacts of climate change on natural methane (CH 4 ) emissions via ebullition are unclear. Here, using published and experimental multi-seasonal CH 4 ebullition data, the authors find a strong relationship between CH 4 ebullition and temperature across a wide range of freshwater ecosystems globally.

Humans have co-evolved with a dense community of microbial symbionts that inhabit the lower intestine. In the colon, secreted mucus creates a barrier that separates these microorganisms from the intestinal epithelium 1 . Some gut bacteria are able to utilize mucin glycoproteins, the main mucus component, as a nutrient source. However, it remains unclear which bacterial enzymes initiate degradation of the complex O -glycans found in mucins. In the distal colon, these glycans are heavily sulfated, but specific sulfatases that are active on colonic mucins have not been identified. Here we show that sulfatases are essential to the utilization of distal colonic mucin O -glycans by the human gut symbiont Bacteroides thetaiotaomicron . We characterized the activity of 12 different sulfatases produced by this species, showing that they are collectively active on all known sulfate linkages in O -glycans. Crystal structures of three enzymes provide mechanistic insight into the molecular basis of substrate specificity. Unexpectedly, we found that a single sulfatase is essential for utilization of sulfated O -glycans in vitro and also has a major role in vivo. Our results provide insight into the mechanisms of mucin degradation by a prominent group of gut bacteria, an important process for both normal microbial gut colonization 2 and diseases such as inflammatory bowel disease 3 . A single sulfatase produced by a bacterium found in the human colon is essential for degradation of sulfated O -glycans in secreted mucus.

The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)-associated cancer endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation.Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated malignancy endemic to southern China, southeast Asia and north Africa. The authors of this Review present a comprehensive overview of advances from the past three decades on the pathogenic role of EBV, and the genomic, epigenomic and immune landscape of NPC, which have led to the development of new biomarkers, therapeutic targets and improved treatment approaches for patients with NPC.

Gastric cancer is the second most frequent cause of cancer death worldwide, although much geographical variation in incidence exists. Prevention and personalised treatment are regarded as the best options to reduce gastric cancer mortality rates. Prevention strategies should be based on specific risk profiles, including Helicobacter pylori genotype, host gene polymorphisms, presence of precursor lesions, and environmental factors. Although adequate surgery remains the cornerstone of gastric cancer treatment, this single modality treatment seems to have reached its maximum achievable effect for local control and survival. Minimally invasive techniques can be used for treatment of early gastric cancers. Achievement of locoregional control for advanced disease remains very difficult. Extended resections that are standard practice in some Asian countries have not been shown to be as effective in other developed countries. We present an update of the incidence, causes, pathology, and treatment of gastric cancer, consisting of surgery, new strategies with neoadjuvant and adjuvant chemotherapy or radiotherapy, or both, novel treatment strategies using gene signatures, and the effect of caseload on patient outcomes.