Biotransformation of furanocoumarins by Cunninghamella elegans

AbstractBiotransformation of Furanocoumarins; psoralen (1), bergapten (2), xanthotoxin (3) and imperatorin (4) was explored by Cunninghamella elegans NRRL 1392, revealing the metabolism of psoralen (1) and bergapten (2) into bergaptol (5), while xanthotoxin (3) and imperatorin (4) were converted into xanthotoxol (6). On the other hand unexpected conversion of xanthotoxin (3) into 3,4 dihydroxanthotoxin (7) occurred. The structure of the isolated pure metabolites was established using physical and spectroscopic techniques including, melting points, IR, 1H NMR, 13C NMR and mass spectroscopy

Asthma remodeling: The pathogenic role of matrix metalloproteinase-9

AbstractBackgroundAsthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness and airflow obstruction. Pathological repair of the airways leads to these structural changes referred as airway remodeling. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in the remodeling process.Aim of the studyIs to study matrix metalloproteinase-9 in asthmatic patients, detecting its pathogenic role in airway remodeling.Subjects and methodsSamples of broncho-alveolar lavage (BAL) fluid and bronchoscopic biopsies from 30 asthmatic patients (10 mild, 10 moderate and 10 severe) and 10 healthy volunteers were assessed for the levels of matrix metalloproteinase-9 (MMP-9) total and differential cell count (in BAL fluid), histological airway remodeling changes and immunohistochemical expression of MMP-9 (in mucosal biopsies).ResultsBAL and tissue MMP-9 (going hand in hand with airway remodeling changes) were higher in asthmatic patients and it was significantly increased with increased severity. BAL total cell count is higher in asthmatic patients. BAL eosinophils, neutrophils, lymphocytes as well as MMP-9 positive cell count were higher in asthmatic patients and increased with severity. MMP-9 tissue expression was also strongly inversely correlated with the spirometric parameters in asthmatic patients.ConclusionsMMP-9 plays a role in airway inflammation and airway remodeling in asthma. MMP-9 is an important player in airway remodeling in bronchial asthma and may be the link between inflammation and remodeling processes

Open-array analysis of genetic variants in Egyptian patients with type 2 diabetes and obesity

Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants.Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 diabetes (T2D) and obesity susceptibility loci by GWAS in a sample of Egyptian patients to find out if there is shared genetic background underlying both disease entities.Methods: Genotyping was performed using OpenArray protocol on the QuantStudioTM 12K Flex Real- Time PCR System. In the present case control study a custom array was designed to facilitate costeffective analysis of selected SNPs related to glycolysis, gluconeogenesis, inflammation, insulin signalling, and immune function.Results: Seven gene variants showed significant association with the risk of T2D patients including FCGRA2, STAT4, CELSR2, PPARG, EXT2 rs3740878, GCKR, PTGS1. Factors that significantly affect T2D were obesity (p < 0.001) and GCKR (p = 0.001) and PTGS1 (p = 0.001) gene variants. Gene variants that showed significant or borderline effect on obesity were MTHFD1, EXT2 rs3740878, GCKR and PTGS1 (p = 0.03, 0.017, 0.059, 0.006) respectively.Conclusions/interpretation: Overlapping genetic aspects should be considered and the presence of risk alleles of different genes together could contribute to the risk of T2D or obesity or both. The MTHFD1 and EXT2rs3740878 gene variants significantly affect obesity and not shared with T2D. Gene variants that showed combined effect on both disease entities were GCKR and PTGS1. These findings provide a basis for future studies on a larger scale. More stress on the risk gene variants that have a combined impact on both diabetes and obesity is recommended to improve risk prediction and preventive strategies

Effects of water shortage on food legume crops

The clamor for agricultural resources is being pushed up by global climatic change and population growth. Such consequences are huge challenges to food security, wreaking havoc on the agroecosystem and causing biotic and abiotic stresses in plants, which in turn cause metabolic and physiological problems. Food legume crops contribute to food security in underdeveloped countries by playing an essential role in conservation farming methods. Drought has, nevertheless, exhibited a negative impact on productivity in many parts of the world. While water shortage is a significant abiotic barrier to legume crop output, drought impacts differ depending on drought timing, agro-climatic area, soil texture, and legume species. To resolve these concerns, we gathered data from the recent publications that revealed drought-induced changes in the production of monoculture legumes in field circumstances and examined it using meta-analysis approaches. Research findings revealed that the water cut’s quantity was strongly associated with a decrease in yield. However, the magnitude of the effect differed depending on the phenological stage of the drought and legume species. The legumes such as groundnut and lentil exhibited the lowest yield reductions (31.2% and 19.6% for groundnut and lentil, accordingly), however, the biggest yield drop (39.8%) facing the maximum water reduction was for faba bean

Healed Lesions of Human Cutaneous Leishmaniasis Caused By Leishmania major Do Not Shelter Persistent Residual Parasites

In human cutaneous leishmaniasis (HCL) caused by Leishmania (L.) major, the cutaneous lesions heal spontaneously and induce a Th1-type immunity that confers solid protection against reinfection. The same holds true for the experimental leishmaniasis induced by L. major in C57BL/6 mice where residual parasites persist after spontaneous clinical cure and induce sustainable memory immune responses and resistance to reinfection. Whether residual parasites also persist in scars of cured HCL caused by L. major is still unknown. Cutaneous scars from 53 volunteers with healed HCL caused by L. major were biopsied and the tissue sample homogenates were analyzed for residual parasites by four methods: i) microscope detection of amastigotes, ii) parasite culture by inoculation on biphasic medium, iii) inoculation of tissue exctracts to the footpad of BALB/c mice, an inbred strain highly susceptible to L. major, and iv) amplification of parasite kDNA by a highly sensitive real-time PCR (RT-PCR). Our results show that the scars of healed lesions of HCL caused by L. major do not contain detectable residual parasites, suggesting that this form likely induces a sterile cure at least within the scars. This feature contrasts with other Leishmania species causing chronic, diffuse, or recidivating forms of leishmaniasis where parasites do persist in healed lesions. The possibility that alternative mechanisms to parasite persistence are needed to boost and maintain long-term immunity to L. major, should be taken into consideration in vaccine development against L. major infection

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

Détection gravimétrique d'ions lourds métalliques par des dérivés de bisphénols. Corrélation entre résultats expérimentaux et modélisation par DFT

Water pollution by heavy metals has become a real ecological, societal and public healthproblem. Reliable and fast detection of very low concentrations of heavy ions requires the developmentand design of miniaturized analytical devices, which are none other than chemical sensors. In thiscontext, we have realized surface acoustic wave (SAW) sensors, functionalized with bisphenolderivatives, for lead ions detection.Six new molecules have been synthesized and tested in the framework of this work. Four possess thesame main chain of bisphenol S (BPS) and differ in their terminal groups, one or two phenyls (M1 andM2) and one or two anthracenes (M3 and M4). The two others, M5 and M6, have two anthraceneterminal groups and differ in their main chain consisting of bisphenol derivatives.Gravimetric measurements showed that the sensor functionalized with a molecule associating BPS andAN (M4) is the most sensitive one (its sensitivity was of the order of [7.2 ± 4.6] × 108 [ ° / M]) and thatit has the highest saturation value. The limit of detection of the designed M4/SAW was estimated at22 pM. The dissociation constant Kd, which is related to the affinity between M4 and lead ions, was oforder of (2.33 ± 0.27) 10-11 M. The use of appropriate ionic liquids has permitted to regenerate theM4 / SAW sensor about ten times, without altering the stability of the M4 molecule. In a complementaryway, calculations based on the density functional theory (DFT), made it possible to estimate the energiesof the complexes (Mi = 1-6 / Pb2+), to better apprehend the interaction between the different reagents. Itwas found that the interaction energy in solvated medium of the M4 / Pb2+ complex, of order of-290 KJ/mol, is higher than that of all the other synthesized molecules, in agreement with the gravimetricresults. An almost perfect correlation has thus been established between the theoretical calculations interms of energy and the experimental results in terms of sensitivity.La pollution des eaux par les métaux lourds est devenue un vrai problème écologique, sociétalet de santé publique. En détecter la présence à très faibles doses, voire à l’état de trace, de façon fiableet rapide requiert la mise au point et le design de nouveaux dispositifs analytiques miniaturisés : lescapteurs chimiques. C’est dans ce contexte que s’inscrit cette thèse dont l’objectif est de développer descapteurs à ondes acoustiques de surfaces (SAW pour Surface Acoustic Waves) fonctionnalisés avec desdérivés de bisphénol pour la détection des ions plomb.Six molécules ont été synthétisées et testées dans le cadre de ce travail. Quatre parmi elles sont forméesd’une même chaine principale en bisphénol S (BPS) et diffèrent par leurs groupements terminaux, un(M1) ou deux (M2) phényles et un (M3) ou deux (M4) anthracènes (AN) ; les deux autres, M5 et M6,possèdent deux groupements AN terminaux et diffèrent par leur chaine principale constituée de dérivésde bisphénol. Les résultats des mesures gravimétriques ont montré que c’est le capteur fonctionnaliséavec une molécule associant le BPS et l’AN (M4) qui présente la meilleure sensibilité (de l’ordre de[7,2 ± 4,6] × 108 [°/M]) et la plus grande valeur de saturation. La limite de détection a été estimée à22 pM. La constante de dissociation Kd, qui renseigne sur l’affinité entre M4 et les ions plomb, était del’ordre de (2.33±0.27) 10-11M. L’utilisation de liquides ioniques appropriés a permis de régénérer lecapteur M4/SAW une dizaine de fois sans altérer la stabilité de la molécules M4. De façoncomplémentaire, des calculs basés sur la théorie de la fonctionnelle de la densité (DFT), ont permisd’estimer les énergies des complexes (Mi = 1-6 / Pb2+), de mieux comprendre l’interaction entre lesdifférents réactifs. Il en est ressorti que l’énergie d’interaction en milieu solvaté du complexe M4/Pb2+,de l’ordre de -290 KJ/mol, est supérieure à celle de toutes les autres molécules synthétisées, en accordavec les résultats gravimétriques. Une corrélation quasi parfaite a ainsi pu être établie entre les calculsthéoriques en termes énergétiques et les résultats expérimentaux en termes de sensibilité