Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.

Obesity-Associated Vitamin D Deficiency Correlates with Adipose Tissue DNA Hypomethylation, Inflammation, and Vascular Dysfunction.

Vitamin D (VD) deficiency is a hallmark of obesity and vascular dysfunction. We sought to test the hypothesis that VD deficiency may contribute to obesity-related vascular dysfunction by inducing adipokine hypomethylation and augmented expression. To this end, we collected blood and adipose tissues (ATs) from a cohort of 77 obese participants who were classified as having mild, moderate, or severe VD deficiency. The body composition, vascular reactivity, cardiometabolic profiles, and DNA methylation of 94 inflammation-related adipokines were measured. Our results show that higher degrees of VD deficiency were associated with lower DNA methylation and induced the expression of inflammatory adipokines such as B-cell lymphoma 6 (BCL6), C-X-C Motif Chemokine Ligand 8 (CXCL8), histone deacetylase 5 (HDAC5), interleukin 12A (IL12A), and nuclear factor κB (NFκB) in the ATs. They were also associated with higher BMI and total and visceral fat mass, impaired insulin sensitivity and lipid profiles, AT hypoxia, and higher concentrations of circulating inflammatory markers. Moderate and severe VD deficiency correlated with impaired vasoreactivity of the brachial artery and AT-isolated arterioles, reduced nitric oxide generation, and increased arterial stiffness. In a multivariate regression analysis, the VD deficiency level strongly predicted the adipokine methylation score, systemic inflammation, and microvascular dysfunction. In conclusion, our findings suggest that VD deficiency is a possible contributor to obesity-related adipokine hypomethylation, inflammation, and vascular dysfunction.

The Use of Time to Pregnancy for Estimating and Monitoring Human Fecundity From Demographic and Health Surveys.

BACKGROUND: Available studies on the prevalence of infertility have proved to have certain limitations, with a scarcity of population-based studies and inconsistent reporting from surveys in countries at all income levels. We wanted to test the applicability of the current duration approach to data from the important Demographic and Health Surveys (DHS) program, funded by USAID since its inception in 1985, https://dhsprogram.com/. METHODS: The current duration approach assumes that there is a well-defined time of initiation of attempts to get pregnant and defines the current duration of a still ongoing pregnancy attempt as the time interval from initiation to interview. The DHS interviews do not have an explicit question about initiation. We focused on nullipari and substituted date of "establishment of relationship with current partner" for initiation. Our study used the current duration approach on 15 datasets from DHS during 2002-2016 in eight different countries from sub-Saharan Africa, Asia, and Latin America. RESULTS: Well-established statistical techniques for current duration data yielded results that for some countries postulated surprisingly long median times to pregnancy and surprisingly high estimates of infertility prevalence. Further study of the data structures revealed serious deviations from expected patterns, in contrast to our earlier experience from surveys in France and the United States where participants were asked explicitly about time of initiation of attempts to become pregnant. CONCLUSIONS: Using cohabitation as a proxy for the initiation of attempts to get pregnant is too crude. Using the current duration approach with DHS data will require more explicit questions during the DHS interviews about initiation of pregnancy attempt.

Socioeconomic variations in risky sexual behavior among adolescents in 14 sub-Saharan Africa countries who report ever having had sex.

BACKGROUND: Equity is a guiding principle of the Global Strategy for Women, Children and Adolescents' Health (2016-2030) aimed at improving adolescent health and responding more effectively to adolescents' needs. We investigated the socioeconomic differentials in having multiple sexual partners and condom use among unmarried adolescents who reported ever having had sex aged 15-19 years in 14 sub-Saharan countries. METHODS: Using the most recent publicly available Demographic and Health Surveys conducted between 2011 and 2018, we calculated survey- and sex-specific proportions of two or more partners and condomless sex, both overall and by selected socioeconomic characteristics and we fitted logistic regression models to estimate the survey- and sex-specific adjusted odds ratios. The pooled adjusted odds ratios were estimated using multilevel logistic regression. RESULTS: In most countries, higher percentages of male adolescents than female adolescents reported having more than one partner in the last 12 months. Conversely, a lower percentage of young male reported having condomless sex when compared to young female: from 19.8% in Gabon to 84.5% in Sierra Leone among male adolescents and from 32.6% in Gabon to 93.2% in Sierra Leone among female adolescents. In the multilevel analyses, condomless sex was associated with place of residence, wealth and schooling for both female and male adolescents, while among male adolescents multiple partnerships was significantly associated with place of residence. CONCLUSION: Our findings on disparities in condomless sex associated with socioeconomic characteristics might reflect constraint choice and decision making. Results also suggest the need for educational programming and services and better access to barrier methods.

Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx.

The glycocalyx is crucial for normal endothelial function. It also tethers extracellular superoxide dismutase (SOD3), which protects the endothelium against oxidative damage. Proteolytic enzymes [matrix metalloproteinases (MMPs)] are capable of disrupting endothelial cell surface proteins, such as syndecans, resulting in derangements of the endothelial glycocalyx. We sought to test the role of MMPs in oxidative stress-mediated disruption of the endothelial glycocalyx and examine the effect of pharmacological inhibition of MMPs on mitigating this detrimental effect. We also examined the role of histone deacetylase (HDAC) in the oxidative stress-mediated MMP induction and glycocalyx remodeling. Oxidative stress was experimentally induced in human adipose microvascular endothelial cells using H2O2 and buthionine sulfoximine in the presence and absence of potent MMP and HDAC inhibitors. H2O2 and buthionine sulfoximine resulted in a notable loss of the endothelial glycocalyx; they also increased the expression and proteolytic activity of MMP-2 and MMP-9 and subsequently increased the shedding of syndecan-1 and SOD3 from the endothelial cell surface. MMP upregulation was accompanied by a decline in mRNA and protein levels of their inhibitors, tissue inhibitors of metalloproteinase (TIMPs; TIMP-1 and TIMP-3). Furthermore, oxidative stress induced HDAC activity. Inhibition of MMPs and HDAC reversed syndecan-1 and SOD3 shedding and maintained endothelial glycocalyx integrity. HDAC inhibition increased TIMP expression and reduced MMP expression and activity in endothelial cells. Our findings shed light on MMPs and HDAC as therapeutically targetable mechanisms in oxidative stress-induced glycocalyx remodeling. NEW & NOTEWORTHY Oxidative stress, a hallmark of many diseases, damages the endothelial glycocalyx, resulting in vascular dysfunction. Studying the mechanistic link between oxidative stress and endothelial glycocalyx derangements might help discover new therapeutic targets to preserve vascular function. In this study, we investigated the involvement of matrix metalloproteinases and histone deacetylase in oxidative stress-induced endothelial glycocalyx degradation.

Long term trends in behaviour to protect against adverse reproductive and sexual health outcomes among young single African women.

BACKGROUND: HIV and unintended pregnancy are major interrelated concerns in sub-Saharan Africa. Focussing on single women aged 15-24 years we assess trends in key behaviours that affect both outcomes. METHODS: We performed a secondary analysis of public-access data sets from 112 surveys from 36 countries in the region, conducted between 1991 and 2015. We examined trends over 20 years in primary abstinence (virginity), secondary abstinence (no sex in past 3 months) among sexually experienced women, current use of modern contraception and condom use at most recent coitus among sexually active women. RESULTS: Little change occurred in primary or secondary abstinence. Over the 20 year period, contraceptive use in the region rose from 14.7 to 33.4%, with significant increases observed in 18 of 30 countries with multiple surveys. Since 2001-2005, the proportion of contraceptive users reporting condoms as their method fell from 61.1 to 51.3%, while use of oral contraceptives or injectables rose from 19.9 to 24.0%. Between 1996 and 2000 and 2006-2010, condom use at last coitus rose from 21.3 to 40.5% but then plateaued. A strong correlation between condom use and national HIV prevalence was found. About half of condom users at last sex had earlier in interviews reported this method for pregnancy-prevention. CONCLUSIONS: Though condoms tend to be overlooked by both HIV and family planning agencies, their contribution to the health of single women remains central. Current efforts to promote non-barrier contraceptive methods may inadvertently increase HIV risk. Condom promotion for pregnancy-prevention should be re-invigorated by social marketing campaigns and other means.

Short-term regular aerobic exercise reduces oxidative stress produced by acute in the adipose microvasculature.

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm2) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to H2O2 Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature.NEW & NOTEWORTHY We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.

Personalised Medicine: Genome Maintenance Lessons Learned from Studies in Yeast as a Model Organism.

Yeast research has been tremendously contributing to the understanding of a variety of molecular pathways due to the ease of its genetic manipulation, fast doubling time as well as being cost-effective. The understanding of these pathways did not only help scientists learn more about the cellular functions but also assisted in deciphering the genetic and cellular defects behind multiple diseases. Hence, yeast research not only opened the doors for transforming basic research into applied research, but also paved the roads for improving diagnosis and innovating personalized therapy of different diseases. In this chapter, we discuss how yeast research has contributed to understanding major genome maintenance pathways such as the S-phase checkpoint activation pathways, repair via homologous recombination and non-homologous end joining as well as topoisomerases-induced protein linked DNA breaks repair. Defects in these pathways lead to neurodegenerative diseases and cancer. Thus, the understanding of the exact genetic defects underlying these diseases allowed the development of personalized medicine, improving the diagnosis and treatment and overcoming the detriments of current conventional therapies such as the side effects, toxicity as well as drug resistance.

Fructose-asparagine is a primary nutrient during growth of Salmonella in the inflamed intestine.

Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10-/- mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1- SPI2- or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.

Uptake and predictors of contraceptive use in Afghan women.

BACKGROUND: Afghanistan has one of the world's highest fertility rates and, related to this, an infant mortality rate far higher than its South Asian neighbors. Contraception enhances family spacing, improves women's safety in child birth and, as a result, reduces infant and child mortality. Until recently, there has been a paucity of information on the comparative rates of contraceptive practices in the country and socioeconomic correlates of uptake. We aimed to elucidate the factors influencing the use of contraception in Afghanistan using recent, robust national data. METHODS: Using Afghanistan Mortality Survey (AMS) 2010 data, the distribution of Contraceptive Prevalence Rate (CPR) and correlates of contraceptive use among currently married women aged 15-49 years were explored. We initially summarised descriptive data on 25,743 married women and then derived predictors of the use of any form of contraception using a multiple logistic regression model. RESULTS: The prevalence of self-reported current use of any contraceptive method was 21.8% (95% CI: 20.4-23.4) at the national level though there was a wide variation in practice between provinces. Herat province in the West region had a highest contraceptive prevalence rate of 49.4% while Paktika in the Southeast region had the lowest CPR of 2%. Multiple logistic regression analysis showed that a family size of greater than 6 living children strongly predicted contraceptive use (AOR 7.4 (95% CI:6.1-9.0)). Other independent predictors included: secondary or high level of education (AOR 2.1 (95% CI: 1.8-2.5)) and being in the wealthiest stratum (OR 2.1 (95% CI 1.5-3.0)). Rural residence predicted a lower use of contraception (AOR, 0.72; 95% CI: 0.56-0.92). CONCLUSION: Contraceptive uptake rate was low overall with wide inter provincial variation. Strengthening female education, targeting married women in rural area and women with no education may enhance the effectiveness of National Family planning program in Afghanistan.

P selectin and T cell profiles provide verification to understand the pathogenesis of liver cirrhosis in HCV and Schistosoma mansoni infections.

Hepatitis C virus (HCV) and Schistosoma mansoni are two major causes of chronic liver disease (CLD). Both immune alteration and thrombocytopenia are common complications in the majority of cirrhotic patients. The current study aimed to monitor the effect of T cell profile and platelets activation on the pathogenesis of liver cirrhosis in patients suffered from single or concomitant schistosomiasis and HCV infections. The subjects were divided into 4 groups: Group I, patients infected with schistosomiasis; Group II, patients infected with HCV; Group III, patients with combined liver diseases and Group IV: healthy individuals. All groups were subjected to full clinical evaluation as well as laboratory examination including ELISA anti-HCV antibodies screening, parasitological examination, and complete blood picture as well as flow cytometry for CD41, CD42, CD62P (P selectin), CD63, CD4 and CD8. The platelets count was significantly decreased in HCV and/or schistosoma infected patients compared to controls. The percentage of the total T-lymphocytes and T-helper was significantly reduced in all infected groups, while the percentage of T-cytotoxic was increased. The patients possessed a significantly higher percentage of the platelets activation markers than control group. There were considerable correlations between the platelets counts and P selectin and MFI. Thrombocytopenia was a common finding in patients with CLD. Patients with CLD showed increased platelets activation which may contribute to the occurrence of thrombocytopenia and play a role in the pathogenesis of CLD. Infected patient showed reduction in the cell-mediated-immunity as evidenced by low T -helper cells.

Interatrial septum motion but not Doppler assessment predicts elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery.

BACKGROUND: Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. METHODS: In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). RESULTS: Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e' and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e' ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥ 17, and 0.98 for ≥ 18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥ 17, and 0.78 for ≥ 18 mmHg). CONCLUSION: Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

Massage therapy restores peripheral vascular function after exertion.

OBJECTIVE: To determine if lower extremity exercise-induced muscle injury reduces vascular endothelial function of the upper extremity and if massage therapy (MT) improves peripheral vascular function after exertion-induced muscle injury. DESIGN: Randomized, blinded trial with evaluations at 90 minutes, 24 hours, 48 hours, and 72 hours. SETTING: Clinical research center. PARTICIPANTS: Sedentary young adults (N=36) were randomly assigned to 1 of 3 groups: (1) exertion-induced muscle injury and MT (n=15; mean age ± SE, 26.6 ± 0.3); (2) exertion-induced muscle injury only (n=10; mean age ± SE, 23.6 ± 0.4), and (3) MT only (n=11; mean age ± SE, 25.5 ± 0.4). INTERVENTION: Participants were assigned to exertion-induced muscle injury only (a single bout of bilateral, eccentric leg press exercise), MT only (30-min lower extremity massage using Swedish technique), or exertion-induced muscle injury and MT. MAIN OUTCOME MEASURES: Brachial artery flow-mediated dilation (FMD) was determined by ultrasound at each time point. Nitroglycerin (NTG)-induced dilation was also assessed (0.4 mg). RESULTS: Brachial FMD increased from baseline in the exertion-induced muscle injury and MT group and the MT only group (7.38%±.18% to 9.02%±.28%, P<.05 and 7.77%±.25% to 10.2%±.22%, P<.05, respectively) at 90 minutes and remained elevated until 72 hours. In the exertion-induced muscle injury only group, FMD was reduced from baseline at 24 and 48 hours (7.78%±.14% to 6.75%±.11%, P<.05 and 6.53%±.11%, P<.05, respectively) and returned to baseline after 72 hours. Dilations of NTG were similar over time. CONCLUSIONS: Our results suggest that MT attenuates impairment of upper extremity endothelial function resulting from lower extremity exertion-induced muscle injury in sedentary young adults.

Genetic Potential of Newly Developed Maize Hybrids under Different Water-Availability Conditions in an Arid Environment.

Drought is a crucial environmental stress that tremendously impacts maize production, particularly under abrupt climate changes. Consequently, breeding drought-tolerant and high-yielding maize hybrids has become decisive in sustaining its production and ensuring global food security under the global fast-growing population. The present study aimed to explore drought tolerance and agronomic performance of newly developed maize inbred lines and their hybrids. Ten newly developed maize inbred lines were crossed with two high-yielding testers using a line × tester mating design. The developed twenty hybrids alongside two high-yielding commercial hybrids were evaluated under water-deficit (5411 m3/ha) and well-watered (7990 m3/ha) conditions in dry summer climate conditions. Highly significant variations were detected among the evaluated hybrids for all studied agronomic traits under well-watered and water-deficit conditions. The inbred lines L10 and L6 were particularly notable, demonstrating the most significant negative general combining ability (GCA) effects for earliness, which is crucial for stress avoidance in both environmental settings. Inbred lines L11, L7, L6, and L1 also showed the highest positive and most significant GCA effects for key yield traits, indicating their potential as parents in breeding programs. The crosses L-10×T-1 and L-6×T-2 were outstanding for their heterotic effects on earliness in days to tasseling and silking. Similarly, the crosses L-4×T-2 and L-1×T-1 excelled in plant and ear heights under both irrigation regimes. The hybrids L-1×T-2 and L-7×T-1 demonstrated superior heterosis for chlorophyll content, number of rows per ear, and overall grain yield. Additionally, hybrids L-11×T-1 and L-11×T-2 exhibited remarkable heterotic effects for the number of grains per row, number of rows per ear, 100-kernel weight, and grain yield, highlighting their potential in breeding for productivity. Based on drought tolerance indices and cluster analysis, the cross combinations L-11×T-1, L-11×T-2, L-7×T-1, and L-1×T-2 were classified as the most drought-tolerant crosses. The principal component analysis highlighted traits such as days to tasseling, days to silking, chlorophyll content, plant height, ear height, number of grains per row, number of rows per ear, and 100-kernel weight can be taken as selection criteria for improving grain yield in maize breeding programs under limited water conditions. Based on the summarized results, the identified genetic materials could be considered promising under both conditions and hold potential for future breeding programs.

A 3-O-sulfated heparan sulfate binding peptide preferentially targets herpes simplex virus 2-infected cells.

Herpes simplex virus 2 (HSV-2) is the primary cause of genital herpes, which is one of the most common sexually transmitted viral infections worldwide and a major cofactor for human immunodeficiency virus infection. The lack of an effective vaccine or treatment and the emergence of drug-resistant strains highlight the need for developing new antivirals for HSV-2. Here, we demonstrate that a low-molecular-weight peptide isolated against 3-O-sulfated heparan sulfate (3-OS HS) can efficiently block HSV-2 infection. Treatment with the peptide inhibited viral entry and cell-to-cell spread both in vitro and in vivo using a mouse model of genital HSV-2 infection. Quite interestingly, the peptide showed a preferential binding to HSV-2-infected cells, with more than 200% increased binding compared to uninfected cells. Our additional results show that heparan sulfate expression is upregulated by 25% upon HSV-2 infection, which is a significant new finding that could be exploited for designing new diagnostic tests and treatment strategies against HSV-2-infected cells. In addition, our results also raise the possibility that 3-OS HS modifications within HS may be upregulated even more to accommodate for a significantly higher increase in the peptide binding to the infected cells.

Measuring stillbirth and perinatal mortality rates through household surveys: a population-based analysis using an integrated approach to data quality assessment and adjustment with 157 surveys from 53 countries.

BACKGROUND: In most low-income and middle-income countries (LMICs), national surveys are the main data source for stillbirths and perinatal mortality. Data quality issues such as under-reporting and misreporting have greatly limited the usefulness of such data. We aimed to enhance the use of mortality data in surveys by proposing data quality metrics and exploring adjustment procedures to obtain the best possible measure of perinatal mortality. METHODS: We performed a population-based analysis of data from 157 demographic and health surveys (DHSs) from 1990 to 2020, with reproductive calendar and birth history data from 53 LMICs. Pregnancies terminated before 7 months' gestation were excluded. We examined data quality and compared survey values with reference values obtained from a literature review to assess misreporting of the age at early neonatal death, omission and transference of stillbirths, and very early neonatal deaths. Real cohort life-table rates of stillbirth, early neonatal, and perinatal mortality per 1000 births were calculated. The underlying risks of stillbirth and daily deaths were modelled using modified Gompertz-Makeham models. FINDINGS: Data for 2 008 807 pregnancies of ≥7 months' gestational age were extracted from the reproductive calendar for the analysis period. Age heaping at day 7 occurred in most surveys. The median value for the heaping index of deaths at day 7 was 2·05 (IQR 1·36-2·87). The median ratio of stillbirths to deaths on days 0-1 was 1·15 (0·86-1·51). Of the 157 surveys, 23 (15%) were considered to have plausible ratios, 71 (45%) had probable ratios, and 63 (40%) had improbable ratios. The ratio of deaths on days 0-1 to deaths on days 2-6 varied considerably between surveys and 119 surveys (76%) had ratios of less than 2·4, indicative of under-reporting of very early neonatal deaths in most surveys. The fully adjusted model increased the median stillbirth rates from 12·2 (9·4-15·9) to 25·6 (18·0-33·4) per 1000 births, with a median relative increase of 95·0% (56·6-136·6). The median perinatal mortality rate also increased from 32·6 (23·6-38·3) to 44·8 (32·8-58·0) per 1000 births, with a median relative increase of 47·8% (6·9-61·0). INTERPRETATION: A simultaneous focus on stillbirths and early neonatal mortality facilitates a comprehensive assessment of inaccurate reporting in household surveys and allows for better use of surveys in planning and monitoring of efforts to reduce stillbirths and early neonatal mortality. FUNDING: None.

The risk of perinatal mortality following short inter-pregnancy intervals-insights from 692 402 pregnancies in 113 Demographic and Health Surveys from 46 countries: a population-based analysis.

BACKGROUND: Inter-pregnancy interval has been identified as a potentially modifiable risk factor to improve perinatal outcomes. We examined the WHO recommended interval of at least 24 months after a livebirth to next pregnancy, and its recommendation of waiting for at least 6 months after a pregnancy loss to improve subsequent pregnancy outcomes. We aimed to estimate the association between inter-pregnancy interval and perinatal mortality using the Demographic and Health Survey reproductive and contraceptive calendar. METHODS: For this population-based analysis, we extracted data for pregnancies with gestational age and pregnancy outcomes from 113 publicly available Demographic and Health Surveys conducted between 2000 and 2022 in 46 countries that included a reproductive or contraceptive calendar module. The primary outcome was perinatal mortality (stillbirth and early neonatal death) while the inter-pregnancy interval was the exposure of interest, grouped into categories of less than 6 months, 6-11 months, 12-17 months, 18-23 months, and 24-59 months. The analysis was stratified by preceding pregnancy outcome (livebirths, stillbirths, or abortions). The Kaplan-Meier method and Cox proportional hazard model were used to calculate the cumulative probability of perinatal mortality and the hazard ratios (HRs). FINDINGS: The analysis sample comprised of 692 402 pregnancies contributed by 570 145 women with a mean age of 28·4 years (SD 5·96). The overall HR of perinatal death was 2·72 (95% CI 2·52-2·93) times higher for an inter-pregnancy interval of less than 6 months compared with the WHO recommended optimal waiting time of 18-23 months following a livebirth. Overall HRs followed a context-related pattern, with the highest ratio of 2·95 (95% CI 2·67-3·25) in sub-Saharan Africa and the lowest of 1·98 (1·47-2·66) in north Africa, west Asia, and Europe. Inter-pregnancy intervals of less than 3 months, 6 months, and 12 months following stillbirth or abortion (spontaneous or induced) do not pose a higher risk for perinatal death in subsequent pregnancy. INTERPRETATION: Our study reaffirms the WHO recommendation on optimal interval between the last livebirth and the next pregnancy of at least 24 months and avoiding pregnancy before 18 months. However, our analysis does not support the WHO recommendation of delaying the next pregnancy for at least 6 months after a pregnancy loss for improved perinatal survival. FUNDING: None.

Ultrasound-Guided Techniques for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy: Erector Spinae Plane Block vs. Quadratus Lumborum Block.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a common bariatric surgery. Regional anesthetic techniques decrease postoperative pain, narcotic analgesic requirements, and opioid-related adverse effects in patients scheduled for bariatric surgery. OBJECTIVES: The research team conducted this clinical trial to assess the effects of bilateral ultrasound (US)-guided erector spinae plane block (ESPB) on postoperative pain scores and postoperative analgesics consumption compared with bilateral US-guided quadratus lumborum block (QLB) in the first 24 hours following LSG. STUDY DESIGN: A randomized, double-blind, prospective, single-center study. SETTING: Ain-Shams University Hospitals. METHODS: Patients: One hundred twenty morbidly obese patients were scheduled for LSG. INTERVENTION: Were randomly assigned to 3 groups (40 each): bilateral US-guided ESPB, bilateral US-guided QLB, or control (C) group. MEASUREMENTS: The time to first rescue analgesia (ketorolac) was considered as a primary outcome. The time to perform the block, the duration of anesthesia, the time to first ambulation, the visual analog scale (VAS) at rest, VAS at movement, the total nalbuphine consumption (mg), the total requirements of rescue analgesia (ketorolac) over the first 24 hours after surgery and the study safety profile were considered as secondary outcomes. RESULTS: The time to perform the block and the duration of anesthesia were higher in the QLB group compared to other groups, with significant differences between ESPB and C groups (P < 0.001, P < 0.001, respectively). The ESPB and QLB groups were superior to the C group as regards the time to first rescue analgesia, the total dose of rescue analgesia, and the total nalbuphine consumption (P < 0.001, P < 0.001, P < 0.001, respectively). In the C group, VAS-R and VAS-M readings were higher in the first 18 hours after surgery (P < 0.001, P < 0.001, respectively). In the rest 6 hours of 24 hours after surgery, the QLB group had lower VAS-R and VAS-M readings than the C group (P < 0.001, P < 0.001, respectively). More patients in the C group had higher incidences of nausea and vomiting (P = 0.011, P = 0.002, respectively). In the C group, the time to first ambulation, the length of PACU stay, and the hospital stay were higher in comparison to the ESPB and QLB groups (P < 0.001, P < 0.001, P < 0.001, respectively). More patients in the ESPB and QLB groups were satisfied with postoperative pain management protocol (P < 0.001). LIMITATIONS: The lack of postoperative respiratory assessment (e.g., spirometry) precluded the identification of either ESPB or QLB effects on pulmonary functions in such patients. CONCLUSION: Bilateral ultrasound-guided erector spinae plane block and bilateral ultrasound-guided quadratus lumborum block provided adequate postoperative pain control and reduced postoperative analgesic requirements for morbidly obese patients scheduled for laparoscopic sleeve gastrectomy with priority to bilateral erector spinae plane block.