The influence of religious identity and socio-economic status on diet over time, an example from medieval France

In Southern France as in other parts of Europe, significant changes occurred in settlement patterns between the end of Antiquity and the beginning of the Middle Ages. Small communities gathered to form, by the tenth century, villages organized around a church. This development was the result of a new social and agrarian organization. Its impact on lifestyles and, more precisely, on diet is still poorly understood. The analysis of carbon and nitrogen isotopes in bone collagen from the inhabitants of the well-preserved medieval rural site Missignac-Saint Gilles le Vieux (fifth to thirteenth centuries, Gard, France) provides insight into their dietary practices and enables a discussion about its transformation over time. A sample of 152 adult individuals dated from 675 to 1175 AD (75 females, 77 males) and 75 specimens from 16 non-human species were analyzed. Results show the exploitation of freshwater, marine, and terrestrial ecosystems as well as various breeding practices specific to each species. The use of both C4 and halophyte plants for feeding domestic animals was also observed. Concerning human dietary practices, a change seemed to occur at the beginning of the tenth century with an increase of δ15N values and a decrease of δ13C values. This corresponds to the introduction of a significant amount of freshwater resources into the diet and could be related to the evolution of the Catholic doctrine. A concomitant diversification of access to individual food resources was also observed, probably linked to the increased diversity of practice inside a population otherwise perceived as one community

Diagnostic Accuracy of NS1 ELISA and Lateral Flow Rapid Tests for Dengue Sensitivity, Specificity and Relationship to Viraemia and Antibody Responses

Dengue is a viral infection of humans that is transmitted by mosquitoes. Dengue is a very important public health problem in many developing countries. Recently, new tests to help diagnose patients with dengue have been developed. Evaluating these tests to see how well they perform in different countries and in different health care settings is an important process that helps to guide health care policy on whether these assays are likely to be useful in making a diagnosis, and if so, when best to use them. Our hospital-based results, using two different types of NS1 tests for diagnosing dengue, indicates that these tests are most sensitive when used during the first 3 days of illness and are most likely to be positive if the patient has primary dengue. Our results also show that a positive NS1 test result is a reflection of the amount of virus in the blood, so that patients with high amounts of virus in the blood are more likely to be NS1 positive. Collectively, the results indicate these NS1 tests deserve inclusion in the diagnostic approach to dengue

A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese Adults

There is no available drug or vaccine against dengue, an acute viral disease that affects ∼50 million people annually in tropical and sub-tropical countries. Chloroquine (CQ), a cheap and well-tolerated drug, inhibits the growth of dengue viruses in the laboratory with concentrations achievable in the body. To measure the antiviral efficacy of CQ in dengue, we conducted a study involving 307 adults with suspected dengue. Patients received a 3-day oral dosage of placebo or CQ early in their illness. Unfortunately, we did not see an effect of CQ on the duration of viral infection. We did, however, observe that CQ had a modest anti-fever effect. In patients treated with CQ, we observed a trend towards a lower incidence of dengue hemorrhagic fever, a severe form of dengue. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. This trial provides valuable new information on how to perform trials of antiviral drugs for dengue

Global Analysis of Extracytoplasmic Stress Signaling in Escherichia coli

The Bae, Cpx, Psp, Rcs, and σE pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention