Endothelial γ-protocadherins inhibit KLF2 and KLF4 to promote atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Laminar shear stress from blood flow, sensed by vascular endothelial cells, protects from ASCVD by upregulating the transcription factors KLF2 and KLF4, which induces an anti-inflammatory program that promotes vascular resilience. Here we identify clustered γ-protocadherins as therapeutically targetable, potent KLF2 and KLF4 suppressors whose upregulation contributes to ASCVD. Mechanistic studies show that γ-protocadherin cleavage results in translocation of the conserved intracellular domain to the nucleus where it physically associates with and suppresses signaling by the Notch intracellular domain. γ-Protocadherins are elevated in human ASCVD endothelium; their genetic deletion or antibody blockade protects from ASCVD in mice without detectably compromising host defense against bacterial or viral infection. These results elucidate a fundamental mechanism of vascular inflammation and reveal a method to target the endothelium rather than the immune system as a protective strategy in ASCVD.

Loss of TGFß-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis.

BACKGROUND: TGF (transforming growth factor)-ß pathway is central to blood-brain barrier development as it regulates cross talk between pericytes and endothelial cells. Murine embryos lacking TGFß receptor Alk5 (activin receptor-like kinase 5) in brain pericytes (mutants) display endothelial cell hyperproliferation, abnormal vessel morphology, and gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH), leading to perinatal lethality. Mechanisms underlying how ALK5 signaling in pericytes noncell autonomously regulates endothelial cell behavior remain elusive. METHODS: Transcriptomic analysis of human brain pericytes with ALK5 silencing identified differential gene expression. Brain vascular cells isolated from mutant embryonic mice with GMH-IVH and preterm human IVH brain samples were utilized for target validation. Finally, pharmacological and genetic inhibition was used to study the therapeutic effects on GMH-IVH pathology. RESULTS: Herein, we establish that the TGFß/ALK5 pathway robustly represses ANGPT2 (angiopoietin-2) in pericytes via epigenetic remodeling. TGFß-driven SMAD (suppressor of mothers against decapentaplegic) 3/4 associates with TGIF1 (TGFß-induced factor homeobox 1) and HDAC (histone deacetylase) 5 to form a corepressor complex at the Angpt2 promoter, resulting in promoter deacetylation and gene repression. Moreover, murine and human germinal matrix vessels display increased ANGPT2 expression during GMH-IVH. Isolation of vascular cells from murine germinal matrix identifies pericytes as a cellular source of excessive ANGPT2. In addition, mutant endothelial cells exhibit higher phosphorylated TIE2 (tyrosine protein kinase receptor). Pharmacological or genetic inhibition of ANGPT2 in mutants improves germinal matrix vessel morphology and attenuates GMH pathogenesis. Importantly, genetic ablation of Angpt2 in mutant pericytes prevents perinatal lethality, prolonging survival. CONCLUSIONS: This study demonstrates that TGFß-mediated ANGPT2 repression in pericytes is critical for maintaining blood-brain barrier integrity and identifies pericyte-derived ANGPT2 as an important pathological target for GMH-IVH.

Phytosomes Nanocarrier with Insight Towards the Future in Cancer Therapy: A Mini-Review.

Cancer is classified as having one of the highest mortality rates on a global scale, presenting a significant challenge in its treatment, especially when conventional chemotherapy methodologies are used. Conversely, there is a growing interest in utilizing herbal medicine as an alternative to the treatment of cancer because of its lack of adverse effects compared to contemporary medical strategies. The incorporation of nanotechnology into therapy has attracted attention owing to its efficacy in the treatment of various illnesses. Phytosomes play a crucial role in the treatment of cancer by enhancing the characteristics of drugs and nanostructures within carriers to enable targeted drug delivery. The establishment of chemical bonds between phospholipid molecules and bioactive compounds from plants ensures the stability of phytosomes, thus establishing them as an innovative mechanism for drug delivery systems that transport plant-derived constituents to specific areas. This mini-overview discusses the potential phytosome complexes, uses, drawbacks, patents, challenges, and prospects of phytosomes in cancer treatment. Thus, numerous phytosomal formulations incorporating plant-derived components have exhibited promising anticancer properties, with several formulations currently undergoing clinical trials.

The change in handgrip strength, after physical exercise, is moderated by digit ratio (2D:4D): A study among the young adults in Poland.

BACKGROUND: The digit ratio (2D:4D), the ratio of the lengths of second (2D) to the fourth (4D) fingers, is a proxy indicator of prenatal androgen exposure. On average, males display lower 2D:4D than females. Previous studies have shown that lower 2D:4D ratios were associated with better sports and physical abilities. AIM: To assess whether a challenge condition, imposed by intense exercise, could increase handgrip strength (HGS) associated with 2D:4D. METHODS: This cross-sectional experimental study included 90 healthy young Polish adults (40 males, 50 females). They underwent intense physical exercise, before (7 days) and after which they were measured for HGS and 2D:4D. Height and weight were also measured. Analyses of Covariance were employed to delineate associations. RESULTS: 2D:4D had significant predictive effects on the differences in HGS (DHGS) measured in two occasions, without and after, physical exercises. The lower was the 2D:4D, the higher the DHGS, particularly, for the left hand. CONCLUSION: The results reconfirmed that the link between prenatal testosterone exposure (indicated by 2D:4D) and physical strength depends on the context, such as a challenged condition.

Redox-signalling and Redox Biomarkers in Cardiovascular Health and Disease.

Overproduction of reactive nitrogen and oxygen species (RNS and ROS) has been linked to the pathogenesis of diabetes, hypertension, hyperlipidemia, stroke, angina, and other cardiovascular diseases. These species are produced in part by the mitochondrial respiratory chain, NADPH oxidase, and xanthine oxidase. RNS and ROS both contribute to oxidative stress, which is necessary for the development of cardiovascular disorders. In addition to ROS species like hydroxyl ion, hydrogen peroxide, and superoxide anion, RNS species like nitric oxide, peroxynitrous acid, peroxynitrite, and nitrogen dioxide radicals have also been linked to a number of cardiovascular conditions. They promote endothelial dysfunction, vascular inflammation, lipid peroxidation, and oxidative damage, all of which contribute to the development of cardiovascular pathologies. It's crucial to understand the mechanisms that result in the production of RNS and ROS in order to identify potential therapeutic targets. Redox biomarkers serve as indicators of oxidative stress, making them crucial tools for diagnosing and predicting cardiovascular states. The advancements in proteomics, metabolomics, genomics, and transcriptomics have made the identification and detection of these small molecules possible. The following redox biomarkers are notable examples: 3-nitrotyrosine, 4-hydroxy-2-nonenal, 8- iso-prostaglandin F2, 8-hydroxy-2-deoxyguanosine, malondialdehyde, Diacron reactive oxygen metabolites, total thiol, and specific microRNAs (e.g. miRNA199, miRNA21, miRNA1254, miRNA1306-5p, miRNA26b-5p, and miRNA660-5p) are examples. Although redox biomarkers have great potential, their clinical applicability faces challenges. Redox biomarkers frequently have a short half-life and exist in small quantities in the blood, making them challenging to identify and measure. The interpretation of biomarker data may also be influenced by confounding factors and the complex interplay of various oxidative stress pathways. Therefore, in-depth validation studies and the development of sensitive and precise detection methods are needed to address these problems. In the search for redox biomarkers, cutting-edge techniques like mass spectrometry, immunoassays, and molecular diagnostics are applied. New platforms and technologies have made it possible to accurately detect and monitor redox biomarkers, which facilitates their use in clinical settings. Our expanding knowledge of RNS and ROS involvement in cardiovascular disorders has made it possible to develop redox biomarkers as diagnostic and prognostic tools. Overcoming the challenges associated with their utility and utilizing advanced detection techniques, which will improve their clinical applicability, will ultimately benefit the management and treatment of cardiovascular conditions.

VEGF counteracts shear stress-determined arterial fate specification during capillary remodeling.

A key feature of arteriogenesis is capillary-to-arterial endothelial cell fate transition. Although a number of studies in the past two decades suggested this process is driven by VEGF activation of Notch signaling, how arteriogenesis is regulated remains poorly understood. Here we report that arterial specification is mediated by fluid shear stress (FSS) independent of VEGFR2 signaling and that a decline in VEGFR2 signaling is required for arteriogenesis to fully take place. VEGF does not induce arterial fate in capillary ECs and, instead, counteracts FSS-driven capillary-to-arterial cell fate transition. Mechanistically, FSS-driven arterial program involves both Notch-dependent and Notch-independent events. Sox17 is the key mediator of the FSS-induced arterial specification and a target of VEGF-FSS competition. These findings suggest a new paradigm of VEGF-FSS crosstalk coordinating angiogenesis, arteriogenesis and capillary maintenance.

Gamma protocadherins in vascular endothelial cells inhibit Klf2/4 to promote atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide1. Laminar shear stress (LSS) from blood flow in straight regions of arteries protects against ASCVD by upregulating the Klf2/4 anti-inflammatory program in endothelial cells (ECs)2-8. Conversely, disturbed shear stress (DSS) at curves or branches predisposes these regions to plaque formation9,10. We previously reported a whole genome CRISPR knockout screen11 that identified novel inducers of Klf2/4. Here we report suppressors of Klf2/4 and characterize one candidate, protocadherin gamma A9 (Pcdhga9), a member of the clustered protocadherin gene family12. Pcdhg deletion increases Klf2/4 levels in vitro and in vivo and suppresses inflammatory activation of ECs. Pcdhg suppresses Klf2/4 by inhibiting the Notch pathway via physical interaction of cleaved Notch1 intracellular domain (NICD Val1744) with nuclear Pcdhg C-terminal constant domain (CCD). Pcdhg inhibition by EC knockout (KO) or blocking antibody protects from atherosclerosis. Pcdhg is elevated in the arteries of human atherosclerosis. This study identifies a novel fundamental mechanism of EC resilience and therapeutic target for treating inflammatory vascular disease.

TNFα increases the degradation of pyruvate dehydrogenase kinase 4 by the Lon protease to support proinflammatory genes.

The endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism; however, the function and regulation of elevated mitochondrial metabolism in EC in response to proinflammatory cytokines remain unclear. Studies using high-resolution metabolomics and 13C-glucose and 13C-glutamine labeling flux techniques showed that pyruvate dehydrogenase activity (PDH) and oxidative tricarboxylic acid cycle (TCA) flux are elevated in human umbilical vein ECs in response to overnight (16 h) treatment with TNFα (10 ng/mL). Mechanistic studies indicated that TNFα mediated these metabolic changes via mitochondrial-specific protein degradation of pyruvate dehydrogenase kinase 4 (PDK4, inhibitor of PDH) by the Lon protease via an NF-κB-dependent mechanism. Using RNA sequencing following siRNA-mediated knockdown of the catalytically active subunit of PDH, PDHE1α (PDHA1 gene), we show that PDH flux controls the transcription of approximately one-third of the genes that are up-regulated by TNFα stimulation. Notably, TNFα-induced PDH flux regulates a unique signature of proinflammatory mediators (cytokines and chemokines) but not inducible adhesion molecules. Metabolomics and ChIP sequencing for acetylated modification on lysine 27 of histone 3 (H3K27ac) showed that TNFα-induced PDH flux promotes histone acetylation of specific gene loci via citrate accumulation and ATP-citrate lyase-mediated generation of acetyl CoA. Together, these results uncover a mechanism by which TNFα signaling increases oxidative TCA flux of glucose to support TNFα-induced gene transcription through extramitochondrial acetyl CoA generation and histone acetylation.

Pyro-Phototronic Effect in All-Inorganic Two-Dimensional Ruddlesden-Popper Ferroelectric Perovskite Thin-films and Photodetection.

Ferroelectric perovskites, where ferroelectricity is embedded in the structure, are being considered for different device applications. In this study, we introduce Cs2PbI2Cl2, an all-inorganic 2D Ruddlesden-Popper (RP) halide perovskite, as a ferroelectric material suitable for pyro-phototronic applications. Thin-films of the all-inorganic perovskite are successfully cast, and they demonstrate ferroelectric properties. Unlike hybrid materials, the ferroelectricity in Cs2PbI2Cl2 does not rely on the organic moiety possessing an electric dipole moment. Instead, the 2D-layer-forming octahedra are twisted and tilted due to a distortion in the bond lengths, leading to the emergence of spontaneous electric polarization. Based on the properties, we fabricate p-i-n heterojunctions by integrating the perovskite with carrier-transport layers. To determine the band-energies of the materials, scanning tunneling spectroscopy and Kelvin probe force microscopy are employed. The band-edges evidence a type-II band-alignment at both interfaces, enabling the material to exhibit both photovoltaic and pyroelectric behaviors when subjected to pulsed illumination. The devices based on the all-inorganic RP perovskite developed in this study exhibit pyro-phototronic effects and serve as self-powered photodetectors without any need for an external bias.

Profiling of Polyphenolic Compounds, Antioxidant, Antidyslipidemic and Cardiac Risk Preventive Effect of Keteki Joha and Kola Joha Rice Cultivars Grown in Assam, India: A Comparative Study.

BACKGROUND: Food grains' ability to promote health is widely recognized as a result of their rich nutritional profile and presence of antioxidants. AIM: The present study aimed to investigate the antioxidant, antidyslipidemic, and cardiac risk preventive effects of unpolished whole rice extracts of Keteki and Kola Joha of Assam, India, and to profile the polyphenolic compounds present. METHODS: Whole unpolished rice samples were extracted with ethanol and the efficacy of the extract of both rice cultivars was evaluated against high-fat and high-sugar induced hyperlipidemia in rats. The effects of extracts on lipid profile, hepatic enzyme, endogenous antioxidants, lipid peroxidation, creatine kinase-NAC, lactate dehydrogenase, C-reactive protein and lipoprotein(s) were evaluated. Atherogenic indices were calculated to find the effect of the extract on cardiac risk. HPLC analysis of whole unpolished rice samples was also carried out to profile the polyphenolics present. RESULTS: HPLC analysis revealed the presence of gallic acid, vanillic acid, caffeic acid, sinapic acid, o-coumaric acid, t-coumaric acid, rosamarinic acid, chlorogenic acid, phytic acid in both rice samples. Protocatechuic acid, syringic acid, and p-coumaric acid were detected in keteki joha, and ferulic acid was detected in kola joha only. Ethanol extracts (200 and 400 mg/kg) of both rice varieties for 30 days significantly averted dyslipidemia, preserved the level of endogenous antioxidants, and prevented lipid peroxidation. Levels of creatine kinase-NAC, lactate dehydrogenase, Creactive protein, and lipoprotein (a) were significantly (P < 0.01) less in the extract-treated group compared to the disease-control group. Extract treatment enhanced ApoA1 level while the reduced level of ApoB. ApoB/ApoA1 ratio was found more in the disease control group, which was significantly reduced in the extract-treated group. The atherogenic index, atherogenic coefficient, and cardiac risk ratio were reduced, while the cardioprotective index was enhanced in treatment groups. CONCLUSION: This paper profiled polyphenolic compounds for the first time. Keteki joha exhibited better results than Kola joha. Observations offer novel insights into the hypothesis for the first time that unpolished Keteki and Kola Joha rice can be beneficial in averting hyperlipidemia and its associated coronary events.

Is 2D:4D digit ratio related to avowed religion? A study among Mongolian young males from Ulaanbaatar.

BACKGROUND: The ratio of the second- (2D) to fourth (4D) digit lengths of hand (2D:4D) is a proxy marker of the relative testosterone and estrogen concentration during a relatively narrow period of fetal development that might affect behavioral and personality characteristics. AIM: To estimate the differences in 2D:4D between different religious groups among a sample of young adult males in Mongolia. METHODS: Two hundred and sixty-five Mongolian male students with mean age of 20.5 (SD = 1.7) years from different universities in Ulan Bator, were included in the study. Information on age, religious affiliation, marital status and parental education were obtained directly from each study participant. Digit lengths were measured from scanned images by using the ImageJ software 1.53 K. One-way analysis of variance was employed to evaluate whether they were significant differences in 2D:4D ratio between groups, along with Scheffe's post hoc comparison. RESULTS: Study participants significantly differed in 2D:4D across religion. Left 2D:4D, but not the right, showed a significant difference between religions, with Muslims exhibiting the highest 2D:4D mean and the lowest DR-L . CONCLUSION: Our study suggests that the 2D:4D ratio is related to the participants' religion. However, the distinctiveness of the Muslim students from study participants belonging to other religious groups in this study could also be related to ethnic differences, given that the students were Kazakhs. This is, to our knowledge, the only study looking at the relationship between the 2D:4D ratio and religious affiliation and, thus, further research is needed to confirm its results.

Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability.

The role of serum response factor (Srf), a central mediator of actin dynamics and mechanical signaling, in cell identity regulation is debated to be either a stabilizer or a destabilizer. We investigated the role of Srf in cell fate stability using mouse pluripotent stem cells. Despite the fact that serum-containing cultures yield heterogeneous gene expression, deletion of Srf in mouse pluripotent stem cells leads to further exacerbated cell state heterogeneity. The exaggerated heterogeneity is detectible not only as increased lineage priming but also as the developmentally earlier 2C-like cell state. Thus, pluripotent cells explore more variety of cellular states in both directions of development surrounding naïve pluripotency, a behavior that is constrained by Srf. These results support that Srf functions as a cell state stabilizer, providing rationale for its functional modulation in cell fate intervention and engineering.

Fine and gross motor skills in 7-10 years old Indian children exposed to a natural disaster during early development.

Fetal life and infancy are extremely sensitive to adverse environmental conditions. This study aimed to assess the effect of exposure to a natural disaster (cyclone Aila) in utero or during infancy on fine and gross motor functions in preadolescent Indian children. The study was conducted in West Bengal, India, and included approximately 700 children (7-10 years old) who were prenatally or postnatally exposed to cyclone Aila and a nonaffected group. Anthropometric measures included height, weight, and birthweight. Socioeconomic status was based on parental education, family size, and income. Motor functions were assessed using the short form of Bruininks-Oseretsky Test of Motor Proficiency (BOT-2). Statistical analyses included, for example, generalized linear models. There were no differences in motor functions relative to the timing of the exposure (trimester) during pregnancy. Compared to the controls, prenatal Aila exposure resulted in poorer performance in all BOT-2 subtests, except for fine motor precision, strength, and balance (the last in boys), while postnatal Aila exposure, compared to the controls, resulted in poorer performance in manual dexterity, bilateral coordination, balance (girls only), and speed and agility. Early life exposure to a natural disaster has long-term adverse effect on motor proficiency in children. By inference, the welfare of pregnant women and infants should be of particular concern for emergency and health services during an environmental cataclysm.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19.

Metabolic associated fatty liver disorder (MAFLD) characterizes the contributing etiologies (i.e., type 2 diabetes mellitus, metabolic syndrome, overweight) of individuals with fatty liver disease that affects 1/3rd of the world population. In 2020, the coronavirus disease 2019 (COVID-19) crisis was unprecedented, and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2. MAFLD patients are frequently obese with added metabolic menace like diabetes, hypertension, and dyslipidemia leading to greater jeopardy of COVID-19. MAFLD patients are 4 to 6-fold more prone towards infections. COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin. Hence, MAFLD in COVID-19 patients worsens the condition significantly. The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission. Direct hepatic injury, enhanced levels of inflammatory cytokines, declined hepatic mitochondrial activity, and compromised immunity are considered as some underlying mechanisms. The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients. The review systematically analyzes the effect of striking two worldwide pandemics (MAFLD and COVID-19) together in the present era.

The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques.

Aging is the predominant risk factor for atherosclerosis, the leading cause of death. Rare smooth muscle cell (SMC) progenitors clonally expand giving rise to up to ~70% of atherosclerotic plaque cells; however, the effect of age on SMC clonality is not known. Our results indicate that aged bone marrow (BM)-derived cells non-cell autonomously induce SMC polyclonality and worsen atherosclerosis. Indeed, in myeloid cells from aged mice and humans, TET2 levels are reduced which epigenetically silences integrin ß3 resulting in increased tumor necrosis factor [TNF]-α signaling. TNFα signals through TNF receptor 1 on SMCs to promote proliferation and induces recruitment and expansion of multiple SMC progenitors into the atherosclerotic plaque. Notably, integrin ß3 overexpression in aged BM preserves dominance of the lineage of a single SMC progenitor and attenuates plaque burden. Our results demonstrate a molecular mechanism of aged macrophage-induced SMC polyclonality and atherogenesis and suggest novel therapeutic strategies.

Citric acid esterified Glutinous Assam bora rice starch enhances disintegration and dissolution efficiency of model drug.

The current work was designed to study the starch's physicochemical attributes, tablet disintegration and dissolution efficiency and its derivatives obtained from the glutinous Assam bora rice (G-ABR) variety of Assam, Northeast India. Starch was isolated by a simple protein denaturation method, and a starch derivative was prepared through citric acid modification. G-ABRS and citrated G-ABRS were characterized through FTIR, DSC, XRD and SEM. The rate of consolidation, consolidation index, angle of internal friction, packing rearrangement and cohesive properties were determined to investigate their applications as functional excipients in pharmaceutical industries. G-ABRS and citrated G-ABRS exhibited better packing rearrangement and cohesive properties than standard corn starch. Furthermore, immediate release of API from the tablet compact was observed when the starch concentration increased from 1 to 5 %, indicating facilitation of the tablet compact disintegration. Therefore, G-ABRS and citrated G-ABRS are potentially functional and sustainable materials for pharmaceutical industries.

Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets.

Diabetes mellitus is a chronic metabolic disorder resulting in an increased blood glucose level and prolonged hyperglycemia, causes long term health conse-quences. Chronic wound is frequently occurring in diabetes patients due to compromised wound healing capability. Management of wounds in diabetic patients remains a clinical challenge despite many advancements in the field of science and technology. Increasing evidence indicates that alteration of the biochemical milieu resulting from alteration in inflammatory cytokines and matrix metalloproteinase, decrease in fibroblast and keratinocyte functioning, neuropathy, altered leukocyte functioning, infection, etc., plays a significant role in impaired wound healing in diabetic people. Apart from the current pharmacotherapy, different other approaches like the use of conventional drugs, antidiabetic medication, antibiotics, debridement, offloading, platelet-rich plasma, growth factor, oxygen therapy, negative pressure wound therapy, low-level laser, extracorporeal shock wave bioengineered substitute can be considered in the management of diabetic wounds. Drugs/therapeutic strategy that induce angiogenesis and collagen synthesis, inhibition of MMPs, reduction of oxidative stress, controlling hyperglycemia, increase growth factors, regulate inflammatory cytokines, cause NO induction, induce fibroblast and keratinocyte proliferation, control microbial infections are considered important in controlling diabetic wound. Further, medicinal plants and/or phytoconstituents also offer a viable alternative in the treatment of diabetic wound. The focus of the present review is to highlight the molecular and cellular mechanisms, and discuss the drug targets and treatment strategies involved in the diabetic wound.

Prenatal and early postnatal exposure to a natural disaster and Attention-Deficit/Hyperactivity Disorder symptoms in Indian children.

The aim of this study was to assess the relation between early exposure to stressful events and symptoms of the Attention-Deficit/Hyperactivity Disorder (ADHD) in children, based on the outcomes from a natural experiment. It was hypothesized that children pre- and postnatally exposed to cyclone Aila have increased ADHD symptoms compared to the control group, and the effect depends on the timing of the exposure. Indian children (8-11 years) prenatally (N = 336) and early postnatally (N = 216) exposed to cyclone Aila were compared to a non-exposed control peer group (N = 285). ADHD symptoms were assessed using the Conner's Teacher Rating Scale Revised. The main effect of exposure to the cyclone on the total ADHD symptoms' score, ADHD index, Hyperactivity and Oppositional symptoms was significant and independent to covariates: age and sex of children, gestational age and birth weight, maternal stress during the year before the study and the socioeconomic status of a family. The timing of exposure and sex of the children were found to be a significant moderator of the relation between early exposure to the natural disaster and ADHD symptoms. The prenatal, but also early postnatal exposure to stressful experiences such as a natural disaster, may disturb the development of cognitive functions and behavioural control, thus increasing the risk of ADHD in children.

Relative Body Fat Distribution in Preadolescent Indian Children Exposed to a Natural Disaster during Early Development.

Fetal life and infancy are critical periods when adverse environmental conditions, such as natural disasters, may alter a developing organism, leading to life-lasting unfavorable health outcomes, such as central body fat distribution. Therefore, the aim of this study was to assess the effect of the exposure to cyclone Aila in utero or during infancy on the relative subcutaneous adiposity distribution in preadolescent Indian children. The study included children prenatally (N = 336) or postnatally (during infancy, N = 212) exposed to Aila and a non-affected group (N = 284). Anthropometric indices involved, i.e., subscapular, suprailiac, triceps, and biceps skinfolds. The relative adiposity distribution (PC1) and socioeconomic status (SES) were assessed using principal component analysis. An analysis of covariance and Tukey's post hoc test for unequal samples were performed to assess the effect of exposure to a natural disaster on the PC1, controlling for age, sex, Z-BMI, and SES. Prenatally and postnatally Aila-exposed children revealed a significantly more central-oriented pattern of relative subcutaneous fat distribution compared to the controls (p < 0.05). Early-life exposure to a natural disaster was related to an adverse pattern of relative adipose tissue distribution in preadolescent children.

Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification.

Expression of a neuropilin-like protein, DCBLD2, is reduced in human calcific aortic valve disease (CAVD). DCBLD2-deficient mice develop bicuspid aortic valve (BAV) and CAVD, which is more severe in BAV mice compared with tricuspid littermates. In vivo and in vitro studies link this observation to up-regulated bone morphogenic protein (BMP)2 expression in the presence of DCBLD2 down-regulation, and enhanced BMP2 signaling in BAV, indicating that a combination of genetics and BAV promotes aortic valve calcification and stenosis. This pathway may be a therapeutic target to prevent CAVD progression in BAV.