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Summary: Background: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods. Our objective was therefore to study the prospective association between the nutritional quality of diet characterized by the uNS-NPS and the risk of cardiovascular diseases in a large European population. Methods: Our analyses included 345,533 participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC, 1992–2010, 7 European countries). Food intakes were assessed at baseline using country-specific dietary questionnaires. The uNS-NPS was calculated as a continuous scale for each food, based on its 100 g content of energy, sugars, saturated fatty acids, salt, fibre, and protein and percentage content of fruit, vegetables, and pulses. A dietary index was derived at the individual level (uNS-NPS DI: energy-weighted mean of uNS-NPS scores of all foods consumed by a participant). Cardiovascular events during follow-up were retrieved using country-specific methods (self-report, registry data). Multi-adjusted Cox models were computed. Findings: Overall, 16,214 first cardiovascular events were reported (median follow-up: 12.3 years; 4,103,133 person-years). The consumption of foods with a higher uNS-NPS score (reflecting a lower overall nutritional quality of diet) was associated with higher risks of total cardiovascular events (Hazards Ratio (HR) for an increment of 1 standard deviation: 1.03 (95% Confidence Interval 1.01–1.05)), especially myocardial infarction (HR = 1.03 (1.01–1.07)), and stroke (HR = 1.04 (1.01–1.07)). Interpretation: In this large prospective study among European adults, a higher risk of cardiovascular diseases (total and several subtypes) was observed in individuals consuming a diet with a lower nutritional value, as graded by the uNS-NPS score. This brings new evidence on the relevance of the updated nutrient profile underlying the Nutri-Score to characterize foods with a healthier nutrient profile. Funding: EPIC-CVD was supported by EU FP7, ERC, UK MRC, British Heart Foundation, and UK NIHR.

Atherosclerotic plaque formation is a leading cause of arterial thrombosis that significantly impacts global health by instigating major adverse cardiovascular events (MACE) like myocardial infarction (MI) and stroke. Platelets are central to this process, leading to the development of antiplatelet therapies, to mitigate MACE risks. The combination of aspirin with a potent P2Y12 inhibitor known as dual antiplatelet therapy (DAPT) is the standard for post-percutaneous coronary intervention (PCI) aimed at reducing ischemic events. However, DAPT’s associated bleeding risks, particularly in high bleeding risk (HBR) patients, require a balanced approach to optimize therapeutic outcomes. Recent advancements have led to the exploration of ticagrelor monotherapy as a promising strategy after short-term DAPT to reduce bleeding risks while preserving ischemic protection. This review manuscript focuses on ticagrelor monotherapy for HBR patients with discussion on optimal timing, patient selection, and treatment duration. It highlights ticagrelor’s broad efficacy in diverse patient sub-groups and outlines its superiority over aspirin (ASA) and clopidogrel monotherapies. Trials such as TICO, TWILIGHT, GLOBAL LEADERS, and ULTIMATE-DAPT as well as literature meta-analyses validate ticagrelor monotherapy’s role in lowering mortality and clinical adverse events versus conventional DAPT. The review endorses a personalized treatment regimen, beginning with DAPT before moving to ticagrelor monotherapy, as a balanced method for managing both bleeding and ischemic risks in post-PCI acute coronary syndrome (ACS) patients, especially those facing higher bleeding threats.

Stress exposure during the sensitive period of early development has been shown to program the brain and increases the risk to develop cognitive deficits later in life. We have shown earlier that early-life stress (ES) leads to cognitive decline at an adult age, associated with changes in adult hippocampal neurogenesis and neuroinflammation. In particular, ES has been shown to affect neurogenesis rate and the survival of newborn cells later in life as well as microglia, modulating their response to immune or metabolic challenges later in life. Both of these processes possibly contribute to the ES-induced cognitive deficits. Emerging evidence by us and others indicates that early nutritional interventions can protect against these ES-induced effects through nutritional programming. Based on human metabolomics studies, we identified various coffee-related metabolites to be part of a protective molecular signature against cognitive decline in humans. Caffeic and chlorogenic acids are coffee-polyphenols and have been described to have potent anti-oxidant and anti-inflammatory actions. Therefore, we here aimed to test whether supplementing caffeic and chlorogenic acids to the early diet could also protect against ES-induced cognitive deficits. We induced ES via the limited nesting and bedding paradigm in mice from postnatal(P) day 2–9. On P2, mice received a diet to which 0.02% chlorogenic acid (5-O-caffeoylquinic acid) + 0.02% caffeic acid (3′,4′-dihydroxycinnamic acid) were added, or a control diet up until P42. At 4 months of age, all mice were subjected to a behavioral test battery and their brains were stained for markers for microglia and neurogenesis. We found that coffee polyphenols supplemented early in life protected against ES-induced cognitive deficits, potentially this is mediated by the survival of neurons or microglia, but possibly other mechanisms not studied here are mediating the effects. This study provides additional support for the potential of early nutritional interventions and highlights polyphenols as nutrients that can protect against cognitive decline, in particular for vulnerable populations exposed to ES.

Greater Cairo, the largest megacity of the Middle East North Africa (MENA) region, is currently suffering from major aerosol pollution, posing a significant threat to public health. However, the main sources of pollution remain insufficiently characterized due to limited atmospheric observations. To bridge this knowledge gap, we conducted a continuous 2-month field study during the winter of 2019–2020 at an urban background site, documenting for the first time the chemical and physical properties of submicron (PM1) aerosols. Crustal material from both desert dust and road traffic dust resuspension contributed as much as 24 % of the total PM1 mass (rising to 66 % during desert dust events), a figure not commonly observed in urban environments. Our observations showed significant decreases in black carbon concentrations and ammonium sulfate compared to data from 15 years ago, indicating an important reduction in both local and regional emissions as a result of effective mitigation measures. The diurnal variability of carbonaceous aerosols was attributed to emissions emanating from local traffic at rush hours and nighttime open biomass burning. Surprisingly, semi-volatile ammonium chloride (NH4Cl) originating from local open biomass and waste burning was found to be the main chemical species in PM1 over Cairo. Its nighttime formation contributed to aerosol water uptake during morning hours, thereby playing a major role in the build-up of urban haze. While our results confirm the persistence of a significant dust reservoir over Cairo, they also unveil an additional source of highly hygroscopic (semi-volatile) inorganic salts, leading to a unique type of urban haze. This haze, with dominant contributors present in both submicron (primarily as NH4Cl) and supermicron (largely as dust) modes, underscores the potential implications of heterogeneous chemical transformation of air pollutants in urban environments.

This prospective observational study aimed to determine the proportion of mechanical complications in patients with acute STEMI and assess the associated outcomes. The study was conducted between June’21 and May’22, including 1307 patients. Mechanical complications were evaluated using 2D-Echo. Among the STEMI patients, 17 individuals (1.3 %) experienced mechanical complications. The most prevalent complication was FWR (n = 9), followed by VSR(n = 7) and PMR (n = 1). However, despite their low incidence, mechanical complications carry a significant mortality burden. Mortality rates were higher in older age and female patients.

Objective: Type 2 diabetes mellitus (T2DM) is known to be associated with development of left ventricular (LV) dysfunction and heart failure (HF). The study aimed to determine the prevalence of LV dysfunction and HF in unselected out-patients with T2DM with no previous cardiac history and to correlate LV dysfunction and HF with demographic and comorbid characteristics. Methods: This cross-sectional study conducted at 27 centers in India captured demographic and clinical data through electronic case record forms. B-type natriuretic peptide of >105 pg/mL was used to diagnose HF and two-dimensional echocardiography was used to assess LV dysfunction. Results: Of the 615 patients, 54.3 % (n = 334) were males; mean age was 57.4 ± 10.48 years. More than one-third of the patients had T2DM duration of >10 years (n = 238; 38.7 %), with hypertension as the most prevalent comorbidity (n = 372, 78.6 %). Approximately 61.3 % of the patients had LV hypertrophy. The mean LV mass was 135.0 ± 56.16 g (95 % CI 130.28, 139.70). The prevalence of any type of LV dysfunction, including systolic or diastolic dysfunction and HF was 55 % (95 % CI 51.0, 59.0) and 10 % (95 % CI 7.0, 12.0), respectively. A negligible but statistically significant correlation was observed between LV dysfunction and T2DM duration (p = 0.011), alongside HF and age (p

Problems considered: Global challenges posed by obesity, type 2 diabetes mellitus (T2DM), hypertension, and related metabolic diseases necessitate effective interventions. Pharmacotherapy often falls short, leading to a demand for innovative approaches. This study delves into the effects of an organized diet featuring a readily available food substitute blend over an eight-week span. Methods: The study implemented a low-calorie diet (800–830 calories), comprising three shakes, non-starchy vegetables, soups, reduced buttermilk, and limited fat. Assessments covered NCDs like T2DM, hypertension, dyslipidemia, and non-alcoholic fatty liver disease. WHO STEPS protocol guided anthropometric measures and blood pressure readings, while INBODY 230 Analyser determined body composition. SPSS 16 software facilitated analysis of baseline and two-month follow-up data. Results: Participants with an average baseline BMI of 31.9 kg/m2 witnessed substantial improvements. Weight, BMI, waist and hip circumferences, neck, arm, and thigh circumferences, and body fat percentage registered significant decreases. Positive changes were observed in diabetes indicators, including reduced HbA1c (7.2%–6.1%) and fasting/post-prandial blood glucose (p

This study aims at estimating which pesticide active substances (ASs) are the best candidates to study potential further degradation of the AS above 120°C. To achieve this, a prioritisation list was built following five consecutive criteria. This first includes substances that are anthropogenic, have a carbon backbone structure, are authorized in the European Union, and have a defined maximum residue limit (MRL). Then, substances were selected according to their physicochemical and structural properties, MRL in main food commodities, standard price and degradation in hydrolysis studies below 120°C. The results showed that out of the initial 1 478 substances reported in the European pesticide database, 24 ASs were selected as the best candidates to test the assumption of degradation above 120°C. This prioritisation list could be useful for future research studies to build their own list and save time in selecting suitable candidates according to their criteria.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Agriculture is a backbone of global economy and most of the population relies on this sector for their livelihood. Chitosan as a biodegradable material thus can be explored for in various fields in its nano form to replace non-biodegradable and toxic compounds. The chitosan has appealing properties like biocompatibility, non-toxicity, biodegradability, and low allergenic, making it useful in several applications including in agriculture sector. Because of their unique properties, chitosan nanoparticles (ChNPs) are extensively applied as a bioagent in various biological and biomedical processes, including wastewater treatment, plant growth promoter, fungicidal agent, wound healing, and scaffold for tissue engineering.Furthermore, the biocompatibility of chitosan nanoparticles (ChNPs) is reported to have other biological properties such as anti-cancerous, antifungal, antioxidant activities, even induces an immune response in the plant, and helps manage biotic and abiotic stresses. Chitosan can also find its application in wastewater treatment, hydrating agents in cosmetics, the food industry, paper, and the textile industry as adhesive, drug-delivering agent in medical as well as for bioimaging. Since chitosan has low toxicity, the nano-formulation of chitosan can be used for the controlled release of fertilizers, pesticides, and plant growth promoters in agriculture fields. The ChNPs applications in precision farming being a novel approach in recent developments. Here we have comprehensively reviewed the major points in this review are; the synthesis of ChNPs by biological resources, their modification and formulation for increasing its applicability, their modified types, and the different agricultural applications of ChNPs.

The potential of arbuscular mycorrhizal fungi in augmenting arsenic (As) tolerance in wheat is well recognized; however, its effect on mineral profile of grains under As stress is not known. The study was performed to assess the effectiveness of Rhizophagus intraradices on acquisition, translocation, and accumulation of minerals in grains of wheat grown in three As levels (0, 25, and 50 mg As kg−1 soil). Inoculation of R. intraradices decreased As accumulation, increased macronutrients uptake, and ensured higher accumulation of N, P, K, Ca, and Mg in grains. However, its influence was non-significant on S concentration in grains. Presence of As in soil reduced Zn, Ni, and Se and augmented Fe, Na, and Mn concentrations in wheat roots. Conversely, translocation of Fe, Na, and Mn to grains declined significantly and concentrations of Fe, Na, Zn, Mn, Ni, and Se reduced in grains with increasing As level in soil. Regardless of lower concentration of Fe and Mn in roots, mycorrhizal (M)-plants maintained higher concentrations of Zn, Mn, Fe, Ni, Se, and Mo in grains than non-inoculated (NI)-plants. Although, mycorrhizal status of plant had non-significant effect on grain phytic acid concentration, R. intraradices significantly increased the bioavailability of Fe and Zn in grains, which was primarily due to enhanced accumulation of Fe and Zn. While bioavailability of Zn improved from poor to moderate, bioavailability of Fe in M-plants, although higher than NI-plants, remained below the desired level.Overall, the study advocates that in addition to limiting As accumulation in grains, AMF could also provide augmented levels of P, N, K, Mg, Ca, Fe, Zn, Mn, Ni, and Se in grains, thus can aid in overcoming the mineral deficiencies for populations consuming wheat-based diets especially in As contaminated areas.

The development of social robots has the potential to address significant societal concerns, however, most people have limited experience of such technology. The present research investigated whether techniques borrowed from the psychology of intergroup relations – namely direct and extended contact – affect people's attitudes towards robots. Participants were provided with either direct contact with a social robot or extended contact (these participants watched a video recorded by a friend who had met the robot) before their explicit and implicit attitudes towards robots were measured. Results indicated that direct contact affected both explicit and implicit attitudes, while extended contact affected implicit attitudes. The implication of these findings is that contact with a robot, direct or indirect, can change attitudes; much as previous research has shown that contact with a person who is a member of an out-group can change attitudes towards that group. We conclude that methods and theories from the study of human intergroup relationships can be usefully applied to understand attitudes toward social robots.

Background: Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level. Methods: We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314). Findings: Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample. Interpretation: These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline. Funding: The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.

Hydrological variability (HA) in the river due to damming is well explored but there is a dearth of research about the HA on the riparian wetland. Time series data scarcity perhaps withstands against such research. The present work intended to measure the degree of HA of the river using flow data of gauge station and riparian wetland using time-series remote sensing data derived wetland indices as a proxy of water depth. For the first time, it is attempted to measure the degree of HA of wetland at pixel levels multi-analytical approaches like image-based hydrological attributes integration (HAI) approach, Histogram comparison approach (HCA), and Range of variability approach (RVA). The result has demonstrated that both river and wetlands have experienced significant HA after damming over the Atreyee river basin of India and Bangladesh. The degree of HA of the river in pre-monsoon and post-monsoon seasons respectively are 35.73% and 20.90% as per HCA and 27% and 28% as per RVA. In the wetland, this degree is quite higher (>66%) as per HCA and

A total diet study (TDS) was undertaken to estimate the chronic dietary exposure to pesticide residues and health risks for the French infants and young children below 3 years old. As a whole, 516 pesticides and metabolites were analysed in 309 food composite samples including 219 manufactured baby foods and 90 common foods, which cover 97% of infants and young children's diet. These composite samples were prepared using 5,484 food products purchased during all seasons from 2011 to 2012 and processed as consumed. Pesticide residues were detected in 67% of the samples and quantified in 27% of the baby food samples and in 60% of the common foods. Seventy-eight different pesticides were detected and 37 of these quantified at levels ranging from 0.02 to 594 µg/kg. The most frequently detected pesticides (greater than 5% samples) were (1) the fungicides 2-phenylphenol, azoxystrobin, boscalid, captan and its metabolite tetrahydrophthalimide, carbendazim, cyprodinil, difenoconazole, dodine, imazalil, metalaxyl, tebuconazole, thiabendazole, (2) the insecticides acetamiprid, pirimiphos-methyl and thiacloprid, (3) the herbicide metribuzin and (4) the synergist piperonyl butoxide. Dietary intakes were estimated for each of the 705 individuals studied and for 431 pesticides incl. 281 with a toxicological reference value (TRV). In the lower-bound scenario, which tends to underestimate the exposure, the TRV were never exceeded. In the upper-bound scenario that overestimates exposure, the estimated intakes exceeded the TRV for dieldrin and lindane (two persistent organic pollutants) and propylene thiourea, a metabolite of propineb. For these three substances, more sensitive analyses are needed to refine the assessment. For 17 other detected and/or prioritised pesticides, the risk could not be characterised due to the lack of a valid TRV, of certain food analyses or the absence of analytical standards for their metabolites. Keywords: Food safety, Infants and young children, Pesticide residues, Total diet study, Exposure assessment, Risk characterization

A rare case of biventricular thrombi complicating acute myocardial infarction detected during echocardiography is described.

Background:: Angelman syndrome (AS) is a severe neurodevelopmental disorder with electroencephalographic (EEG) abnormalities and sleep disturbances. It results from lack of the functional maternal allele of UBE3A, which encodes a ubiquitin–protein ligase. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity; the majority of cases of AS are due to a de novo maternal deletion of the 15q11–q13 region. Methods:: Ube3a maternal-deficient mice (Ube3a m−/p+) were generated in a C57Bl/6J background. This study compares cortical EEG and architecture of the sleep–waking cycle in adult Ube3a m−/p+ mice compared with those of age-matched WT (m+/p+) mice, under baseline conditions or after 4-h sleep deprivation (SD). Results:: Ube3a m−/p+ mice exhibited: reduced slow-wave sleep (SWS) amount with increase waking (W) at the dark/light transitions; increased SWS and W episode numbers; and deterioration of paradoxical sleep (PS) over 24 h [amount: −44%; episode duration: −46%; episode number: −40%; theta peak frequency (TPF) acceleration: 7.6 Hz vs. 7.0 Hz in WT mice]. Characteristic paroxysmal EEG discharges are observed during W and SWS associated with synchronous muscle bursting activity during hypoactive W. During the recovery period following SD, Ube3a m−/p+ mice exhibited no rebound either in slow-wave activity (+89% in WT) or in δ-power spectra but a slight rebound in PS amount (+20%). Conclusions:: These data validate the mouse model produced by null mutation of the maternal Ube3a gene and provide useful results to investigate and better understand the molecular basis of sleep disturbances in AS patients.

Sleep–wake homeostasis is crucial for behavioral performances and memory both in the general population and in patients with learning disability, among whom were Down syndrome (DS) patients. We investigated, in mouse models of DS, cortical EEG and sleep–wake architecture under baseline conditions and after a 4-h sleep deprivation (SD). Young hemizygous mice (hSODwt/+) transgenic for the human CuZn superoxide dismutase (hSOD1) or for the human amyloid precursor protein (HuAPP695; hAPPwt/+) were obtained on the same FVB/N inbred background. Baseline records for slow wave sleep (SWS) and wake (W) parameters were unchanged, whereas paradoxical sleep (PS) episode numbers were decreased and PS latency increased after lights off in hSODwt/+ mice versus controls. hSODwt/+ mice did not experience SWS or PS rebounds after SD but EEG activity in the delta-SWS activity (SWA) was enhanced. hAPPwt/+ mice exhibited no change in PS but an increase in W and a decrease in SWS before light transition as well as an increase in theta-power in PS and W. After SD, hAPPwt/+ mice exhibited SWS and PS rebounds as well as enhancement of SWA. We investigated also the nitrite/nitrate levels in all mice and found an increase in the brainstem of hSODwt/+ mice only versus control ones. These preliminary data provide useful results to investigate other genetically manipulated mice and to better understand the biochemical basis of sleep disorders in DS patients.

Δ6- and Δ5-desaturase activities were studied in human fetal liver microsomes obtained after legally approved therapeutic abortion. Enzyme activities were measured by a radiochemical method using reverse-phase high performance liquid chromatography (HPLC). Free and phospholipid fatty acids were assessed in each liver sample by a combination of thin-layer chromatography (TLC) and gas–liquid chromatography (GLC) procedures. The kinetic measurements showed higher Δ6-desaturase activity for the n–3 series than for the n–6 series. Apparent Km of 6.5, 3.9, and 24.5 μm and Vm of 7.5, 9.1, and 24.4 pmol·min-1·mg-1 were obtained, respectively, for 18:2n–6 Δ6-, 20:3n–6 Δ5-, and 18:3n–3 Δ6-desaturases. Beyond 30, 20, and 60 μm of 18:2n–6, 20:3n–6, and 18:3n–3 concentration, respectively, the enzyme activity deviated from Michaelis-Menten kinetics, suggesting an inhibition by excess substrate which is unlikely to occur in vivo as endogenous substrate concentration is much lower. We observed a breakdown in linearity between desaturase activity and microsomal protein concentration beyond 4–5 mg microsomal protein, whatever the enzyme or substrate. Both this phenomenon and the inhibition due to excess substrate should be taken into account in the determination of Δ6- and Δ5-desaturase activities. Comparison of concentrations of the respective endogenous substrates and the kinetic constants of each enzyme suggested that the higher Δ6-desaturase activity observed for the n–3 series than for the n–6 series is not physiologically relevant in human fetal liver.—Rodriguez, A., P. Sarda, C. Nessmann, P. Boulot, C. L. Leger, and B. Descomps. Δ6- and Δ5-desaturase activities in the human fetal liver: kinetic aspects.

A protein, molecular weight 70,000 that inhibits pancreatic lipase has been isolated from soybean seeds. Inhibition is not reversed by colipase unless bile salts are added to the assay system. Inhibitory properties of the purified protein are very similar to those of serum albumin or alpha-lactoglobulin. It has been confirmed that, during intestinal lipolysis of dietary fats, bile salts play an essential role for the activation of the lipase-colipase system in the presence of inhibitory proteins. The purified soybean lipase inhibitory protein was shown to be highly surface-active and able to penetrate monomolecular films of various glycerides and phospholipids at high surface pressure. Inhibition of pancreatic lipase by proteins is related to their capacity to interact with lipids and to modify the quality of the substrate-water interface. The protein isolated from soybeans inhibits pancreatic and Rh. delemar lipase in contrast to the Rh. arrhizus enzyme.

Pancreatic lipase requires colipase, a protein cofactor, to counteract the in vitro inhibition by bile salt. Lipase activity is inhibited by nonsteroidic detergents regardless of their charge and structure. Detergent-inhibited lipase is reactivated by colipase but in all cases activation is limited to a narrow range of detergent concentration. Complementary studies on the bile salt and detergent effect on lipase activity and on interfacial tension at the substrate-water interface show that inhibition is not related to the interfacial surface tension. It is hypothesized that absorption of amphiphilic compounds to the substrate surface modifies the distribution of the enzyme between the lipid surface and the aqueous phase. The activity of detergent-inhibited lipase is fully restored by adding bile salt to the reaction system. Bile salt might play a critical role during in vivo lipolysis by desorbing surface-active substances from the lipid-water interface thus allowing lipase and colipase to interact with substrate.

This prospective observational study aimed to determine the proportion of mechanical complications in patients with acute STEMI and assess the associated outcomes. The study was conducted between June'21 and May'22, including 1307 patients. Mechanical complications were evaluated using 2D-Echo. Among the STEMI patients, 17 individuals (1.3 %) experienced mechanical complications. The most prevalent complication was FWR (n = 9), followed by VSR(n = 7) and PMR (n = 1). However, despite their low incidence, mechanical complications carry a significant mortality burden. Mortality rates were higher in older age and female patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Purpose: To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify new CA genes., Methods: Singleton -exome sequencing on these 20 well-clinically characterized CA patients. We first checked for rare homozygous pathogenic variants, then, for variants from a list of genes known to be associated with CA or very early-onset ataxia, regardless of their mode of inheritance. Our replication cohort of 180 CA patients was used to validate the new CA genes., Results: We identified a causal gene in 16/20 families: six known CA genes (7 patients); four genes previously implicated in another neurological phenotype (7 patients); two new candidate genes (2 patients). Despite the consanguinity, 4/20 patients harbored a heterozygous de novo pathogenic variant., Conclusion: Singleton exome sequencing in 20 consanguineous CA families led to molecular diagnosis in 80% of cases. This study confirms the genetic heterogeneity of CA and identifies two new candidate genes (PIGS and SKOR2). Our work illustrates the diversity of the pathophysiological pathways in CA, and highlights the pathogenic link between some CA and early infantile epileptic encephalopathies related to the same genes (STXBP1, BRAT1, CACNA1A and CACNA2D2).

A rare case of biventricular thrombi complicating acute myocardial infarction detected during echocardiography is described., (Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Purpose: Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C., Methods: We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene., Results: We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature., Conclusion: Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.

Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies., (Copyright © 2015. Published by Elsevier Masson SAS.)

Kabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Autism Spectrum Disorders (ASD) are a group of developmental disorders caused by environmental and genetic factors. Diagnosis is based on behavioral and developmental signs detected before 3 years of age with no reliable biological marker. The purpose of this study was to evaluate the potential use of a 2D NMR-based approach to express the global biochemical signature of autistic individuals compared to normal controls. This technique has greater spectral resolution than to 1D (1)H NMR spectroscopy, which is limited by overlapping signals. The urinary metabolic profiles of 30 autistic and 28 matched healthy children were obtained using a (1)H-(13)C NMR-based approach. The data acquired were processed by multivariate orthogonal partial least-squares discriminant analysis (OPLS-DA). Some discriminating metabolites were identified: β-alanine, glycine, taurine and succinate concentrations were significatively higher, and creatine and 3-methylhistidine concentrations were lower in autistic children than in controls. We also noted differences in several other metabolites that were unidentified but characterized by a cross peak correlation in (1)H-(13)C HSQC. Statistical models of (1)H and (1)H-(13)C analyses were compared and only 2D spectra allowed the characterization of statistically relevant changes [R(2)Y(cum)=0.78 and Q(2)(cum)=0.60] in the low abundance metabolites. This method has the potential to contribute to the diagnosis of neurodevelopment disorders but needs to be validated on larger cohorts and on other developmental disorders to define its specificity., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Distal biceps tendon rupture is not a very common injury and the literature remains scarce, mainly limited to case series. While surgical repair has become popular, it is not universally accepted and there are insufficient data regarding patient satisfaction following repair. The purpose of this study was to assess the results of anatomical reinsertion according to objective muscle strength testing and patient-reported outcome measures., Patients and Methods: Twenty-four patients underwent surgical repair over the last 10 years. All patients underwent clinical assessment using the Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH) score and Oxford Elbow score. Measurement of range of motion, supination and flexion strength testing was done using a Biodex isokinetic dynamometer., Results: Ninety-five percent of the patients had good or excellent results following surgery as defined by Mayo and Oxford Elbow scores. The average DASH score following surgery was 7.1, nearly the same as the score of 6.2 in the normal population. The mean elbow flexion arc was 134° ± 10.8 (range, 125-150°; 95% confidence interval (CI) 129.6-137.8) with no flexion contractures in the operated side compared with the unaffected elbow. The range of pronation-supination was also comparable in both sides. The average torque in flexion improved by 19.8% (p = 0.25) while supination torque was reduced by 4% (p = 0.12) when compared to the uninjured side. There was 8% incidence of persistent neuropraxia of the antebrachial cutaneous nerve of the forearm and 4% incidence of asymptomatic heterotopic ossification., Conclusion: Surgical repair of distal biceps ruptures provides consistently good results in terms of patient-scored outcomes. Objective muscle strength testing does not reveal statistical difference between the injured and the opposite side., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Genetic syndromes that mimic congenital infections must be recognized because of the associated risk of recurrence. We describe a male infant who was born with the association of intra-uterine growth retardation, microcephaly, intracranial calcifications, white matter abnormalities, microphtalmy, bilateral cataract, and hearing loss. Congenital cytomegalovirus (CMV) infection was suspected, but serologic CMV markers were not decisive (IgG+/IgM-). His half-sister (same father) presented a similar phenotype. Therefore, the diagnosis of congenital CMV infection was questioned and a genetic hypothesis was suggested. In 1983, Baraitser et al. first described two brothers with microcephaly and intracranial calcifications and negative TORCH analysis. Later, a number of authors reported children in whom detailed investigation failed to objectively confirm an intra-uterine infective agent. Clinical features include severe postnatal microcephaly, seizures, and pronounced developmental arrest. These cases have been considered to define a distinct autosomal recessive disorder first named pseudo-Torch syndrome. The family described herein is different from the cases previously described with a suspected autosomal dominant inheritance, severe ophtalmological abnormalities, and unusual brain imaging., (Copyright © 2011. Published by Elsevier SAS.)

Background/aims: The aim of this study was to identify human liver proteins that are associated with different stages of liver development., Methods: We collected liver samples from 14 fetuses between 14 and 41 weeks of development, one child and four adults. Proteins which exhibited consistent and significant variations during development by two-dimensional differential in gel electrophoresis (2D-DIGE) were subjected to peptide mass fingerprint analysis by MALDI-TOF mass spectrometry. Real-time PCR analysis confirmed, at the transcriptional level, the data obtained by the proteomic approach., Results: Among a total of 80 protein spots showing differential expression, we identified 42 different proteins or polypeptide chains, of which 26 were upregulated and 16 downregulated in developing in comparison to adult liver. These proteins could be classified in specific groups according to their function. By comparing their temporal expression profiles, we identified protein groups that were associated with different developmental stages of human fetal liver and suggest that the changes in protein expression observed during the 20- to 36-week time window play a pivotal role in liver development., Conclusions: The identification of these proteins may represent good markers of human liver and stem cells differentiation.

In this report, we present updated spectrum and frequency of mutations of the CFTR gene that are responsible for cystic fibrosis (CF) in Languedoc-Roussillon (L-R), the southwestern part of France. A total of 75 different mutations were identified by DGGE in 215 families, accounting for 97.6% of CF genes and generating 88 different mutational genotypes. The frequency of p.F508del was 60.23% in L-R versus 67.18% in the whole country and only five other mutations (p.G542X, p.N1303K, p.R334W, c.1717-1G>A, c.711+1G>T) had a frequency higher than 1%. The mutations were scattered over 20 exons or their border. This sample representing only 5.7% of French CF patients contributed to 24% of CFTR mutations reported in France. This is one of the highest molecular allelic heterogeneity reported so far in CF. We also present the result of a neonatal screening program based on a two-tiered approach "IRT/20 mutations/IRT" analysis on blood spots, implemented in France with the aim to improve survival and quality of life of patients diagnosed before clinical onset. This 18-month pilot project showed an unexpected low incidence of CF (1/8885) in South of France, with only six CF children detected among 43,489 neonates born in L-R, and 13 among 125,339 neonates born in Provence-Alpes-Côte-d'Azur (PACA).

In view to prepare Mars human exploration, it is necessary to promote and lead, at the international level, a highly interdisciplinary program, involving specialists of geochemistry, geophysics, atmospheric science, space weather, and biology. The goal of this program will be to elaborate concepts of individual instruments, then of integrated instrumental packages, able to collect exhaustive data sets of environmental parameters from future landers and rovers of Mars, and to favour the conditions of their implementation. Such a program is one of the most urgent need for preparing human exploration, in order to develop mitigation strategies aimed at ensuring the safety of human explorers, and minimizing risk for surface operations. A few main areas of investigation may be listed: particle and radiation environment, chemical composition of atmosphere, meteorology, chemical composition of dust, surface and subsurface material, water in the subsurface, physical properties of the soil, search for an hypothesized microbial activity, characterization of radio-electric properties of the Martian ionosphere. Scientists at the origin of the present paper, already involved at a high degree of responsibility in several Mars missions, and actively preparing in situ instrumentation for future landed platforms (Netlander--now cancelled, MSL-09), express their readiness to participate in both ESA/AURORA and NASA programs of Mars human exploration. They think that the formation of a Mars Environment working group at ESA, in the course of the AURORA definition phase, could act positively in favour of the program, by increasing its scientific cross-section and making it still more focused on human exploration., (c2004 Published by Elsevier Ltd on behalf of COSPAR.)

Gorlin syndrome or nevoid basal cell carcinoma syndrome is an autosomal dominant disease characterized by developmental abnormalities and a predisposition to cancers. The responsible gene for this syndrome is the PTCH tumor suppressor gene encoding for the Sonic Hedgehog receptor. We screened for PTCH mutations in 65 French Gorlin syndrome families or sporadic cases for the first time. Nineteen novel mutations and five new polymorphisms were identified in this group of patients. One microdeletion without frameshift underlines the importance of one amino acid for Ptc receptor function. Although no mutation hot-spot was described, we identified a recurrent mutation.

Objective: The aim of the study was to characterize n-3 and n-6 fatty acid delta5- and delta6-desaturase activities and their time course variations in human fetal liver between the 17th and 36th gestational week., Study Design: Twenty-one biologic samples were obtained after legally approved medical abortion, according to French law. The desaturase activities were measured in the 21 liver samples by a radiochemical method by means of reverse-phase high-performance liquid chromatography. The fatty acid composition (percentage by weight) of liver phospholipids was assessed in 16 samples by gas-liquid chromatographic analysis., Results: Both delta5- and delta6-desaturase activities were significantly expressed between the 17th and 36th gestational weeks. During the second trimester n-6 fatty acid delta5- and delta6-desaturase activities showed opposite patterns of variation; both then remained stable between the 25th and 36th weeks. Delta6-desaturation was higher in n-3 than n-6 fatty acids and peaked at the 18th gestational week. The percentages of linoleic and docosahexaenoic acids in liver microsomes were positively correlated with the gestation age (P < .01), whereas arachidonic acid remained stable., Conclusion: Significant n-3 and n-6 delta5- and delta6-desaturase activities are expressed in human fetal liver as early as the 17th gestational week and are stable throughout the third trimester. Their theoretic capacity evaluated from in vitro measurements appears lower than polyunsaturated fatty acid requirements and is not directly related to liver microsomal membrane fatty acid composition.

Delta6- and delta5-desaturase activities were studied in human fetal liver microsomes obtained after legally approved therapeutic abortion. Enzyme activities were measured by a radiochemical method using reverse-phase high performance liquid chromatography (HPLC). Free and phospholipid fatty acids were assessed in each liver sample by a combination of thin-layer chromatography (TLC) and gas-liquid chromatography (GLC) procedures. The kinetic measurements showed higher delta6-desaturase activity for the n-3 series than for the n-6 series. Apparent Km of 6.5, 3.9, and 24.5 microM and Vm of 7.5, 9.1, and 24.4 pmol x min(-1) x mg(-1) were obtained, respectively, for 18:2n-6 delta6-, 20:3n-6 delta5-, and 18:3n-3 delta6-desaturases. Beyond 30, 20, and 60 microM of 18:2n-6, 20:3n-6, and 18:3n-3 concentration, respectively, the enzyme activity deviated from Michaelis-Menten kinetics, suggesting an inhibition by excess substrate which is unlikely to occur in vivo as endogenous substrate concentration is much lower. We observed a breakdown in linearity between desaturase activity and microsomal protein concentration beyond 4-5 mg microsomal protein, whatever the enzyme or substrate. Both this phenomenon and the inhibition due to excess substrate should be taken into account in the determination of delta6- and delta5-desaturase activities. Comparison of concentrations of the respective endogenous substrates and the kinetic constants of each enzyme suggested that the higher delta6-desaturase activity observed for the n-3 series than for the n-6 series is not physiologically relevant in human fetal liver.

Objective: This study was performed in order to evaluate indications, techniques and maternal risks of medical abortions, and technical difficulties encountered in these procedures., Type of the Study: A monocentric, descriptive and retrospective study., Materials and Methods: Four hundred seventeen medical abortions (MA) were performed in our fetal medicine Unit between 1986 and 1994, including 117 (28%) performed for maternal reasons and 300 (72%) for fetal reasons. Each indication was discussed in a collegial system and varied protocols of labor induction were used, mainly prostaglandins, RU 486, or feticide. MAIN PARAMETERS MEASURED: They were duration of the labor, maternal accidents, number of the fetal post-mortem examinations, counselling given to the couples. We considered that a MA is correctly managed when the intervention corresponded to the following criteria: expulsion by natural route without uterine damage, an examinable fetus and examination by a foetopathologist., Main Results: Mean rate of MA satisfying our definition was about 45% in 1988 and reached to 74% in 1994. Our results show that the procedure is rarely complicated and that vaginal expulsion can be obtained. The foetopathologist examination rate increased regularly over the period. The mean gestational age of MA due to maternal indications was 14.5 weeks vs 23.9 weeks when dealing with fetal indications. The infection rate is about 6.2%, hemorrhage rate following expulsion was about 5.9% and the rate of uterine rupture was about 0.48%., Conclusions: These data suggest that medical abortion need to be evaluated regularly.

We observed a plurifocal cystic adenomatoid malformation of the lung, Stocker class II, in a 21-week gestation fetus in association with polycystosis of a solitary medial kidney. There was no other notable abnormally. The caryotype could not be obtained. The association of these two congenital malformations is exceptional, only three similar cases have been reported in the literature. Two other cases of pulmonary adenomatoid malformations associated with nephromegaly with renal hyperlobulation have also been described. Whether this is a fortuitous association or not remains to be determined.

Linkage analysis was performed in a three generation family with three males affected by the recently delineated X-linked form of alpha-thalassemia/mental retardation syndrome (ATR-X). Results are in agreement with the linkage study reported by Gibbons et al in 1992 and further confirm that the ATR-X gene is located in proximal Xq. Positive LOD scores were obtained for several markers situated in the pericentromeric region. A maximum LOD score of 2.09 at a recombination fraction of 0 was obtained for DXS453 located at the boundary q12-q13.1. The nearest flanking loci demonstrating recombination with the disease locus were AR at Xq11.2-q12 on the centromeric side and DXS72 at Xq21.1 on the telomeric side. Consequently the authors were able to reduce the previously defined candidate region for the gene location. Their results are compatible with a distal boundary at Xq21.1 instead of q21.31.

Three male patients with X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome in a large French family are reported. Diagnosis was suspected on particular craniofacial dysmorphism associated with severe mental retardation and X-linked transmission. Hematological investigations, and in particular presence of Hb H inclusions in two of the boys, confirmed diagnosis. The clinical, hematological and radiological features are discussed in order to better define what appears to be a characteristic phenotype.

It has been suggested that partial distal 2p2----2pter duplication causes a relatively well defined clinical syndrome, mostly as regards craniofacial dysmorphism, musculoskeletal and genitalia anomalies. Duplications covering a larger portion of 2p i.e. 2p12 or 2p13----2pter are however less documented. The authors report a new case of partial 2p13----2pter duplication which supplies further evidence for short life expectancy due to the large number of malformations in these partial duplications.

The effects on plasma lipoproteins of four fat-modified diets were assessed in 11 nuns in a contemplative order in the Mediterranean region of Spain. Diet 1 [high polyunsaturated fatty acid (PUFA), low monounsaturated fatty acid (MUFA), low ratio of PUFAs to saturated fatty acids (P:S)] and diet 3 (low PUFA, high MUFA, low P:S) induced significant, directly comparable reductions in total plasma (12% and 13%, respectively) and low-density-lipoprotein (LDL) cholesterol (24% and 19%, respectively). Diet 2 [high PUFA, high MUFA, low saturated fatty acid (SFA), high P:S] induced greater decrements (23% and 30% in total plasma and LDL cholesterol, respectively). Diet 4 (low PUFA, low MUFA, high SFA, low P:S) induced a significant increase in LDL cholesterol of 11%. No significant changes in high-density-lipoprotein cholesterol were observed with these diets. Because the effects of PUFAs and MUFAs are comparable, no recommendations on modifying the habitual, high-MUFA-containing Mediterranean diet need be made other than, perhaps, a reduction in the overall intake of SFAs.

The CHARGE association includes a group of several malformations, and always a coloboma and/or choanal atresia. We present 8 cases of this syndrome, 5 complete and 3 incomplete forms. Prognosis at term seems severe, considering the visceral malformations (namely cardiac) and the cerebral handicap often associated. In most cases the CHARGE association is a sporadic event; however, one cannot exclude the possibility that certain forms follow a Mendelian pattern of inheritance. The mechanisms leading to this association have not yet been elucidated: it is probably due to migration abnormalities of the neural crests as in the VATER association of Di George syndrome.

The authors report a case of post natal hernia with group B beta hemolytic streptococcus infection. The frequency of such an association compared to the rarity of delayed onset congenital diaphragmatic hernia may constitute a reflexion subject. The literature is reviewed and a concept of pathogenesis is discussed.