Relevance of PNPLA3, TM6SF2, HSD17B13, and GCKR Variants to MASLD Severity in an Egyptian Population

\ua9 2024 by the authors.Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a frequent clinical condition globally. Single nucleotide polymorphisms (SNPs) associated with NAFLD have been proposed in the literature and based on bioinformatic screening. The association between NAFLD and genetic variants in Egyptians is still unclear. Hence, we sought to investigate the association of some genetic variants with NAFLD in Egyptians. Egyptians have been categorized into either the MASLD group (n = 205) or the healthy control group (n = 187). The severity of hepatic steatosis and liver fibrosis was assessed by a Fibroscan device. TaqMan-based genotyping assays were employed to explore the association of selected SNPs with MASLD. PNPLA3 rs738409 C>G variant is associated with the presence of MASLD with liver fibrosis, the severity of both hepatic steatosis and liver fibrosis, increased systolic and diastolic blood pressure and increased alanine aminotransferase (all p < 0.05), while the TM6SF2 rs58542926 C>T, HSD17B13 rs9992651 G>A, and GCKR rs1260326 T>C variants were not (all p > 0.05). The TM6SF2 rs58542926 T allele is associated with increased fasting blood glucose and a decreased waist circumference. The GCKR rs1260326 C allele is associated with decreased aspartate transaminase and diastolic blood pressure (all p < 0.05). Only after adjusting for the risk factors (age, sex, BMI, WC, HDL, TG, diabetes mellitus, and hypertension) F2 liver fibrosis score is negatively correlated with the HSD17B13 rs9992651 GA genotype. This study offers evidence for the association of the PNPLA3 rs738409 C>G variant with MASLD among Egyptians and for the association of the PNPLA3 rs738409 G allele, the TM6SF2 rs58542926 T allele, and the GCKR rs1260326 C allele with some parameters of cardiometabolic criteria

Landmark-based morphometric and meristic analysis in response to characterize the wild Bhagna, Labeo ariza populations for its conservation

The landmark-based morphometric and meristic analysis of three different stocks from the Atrai, the Jamuna and the Kangsha of Bhagna (Labeo ariza, Hamilton 1807) were examined from a phenotypical point of view to evaluate the population structure and to assess shape variation. A total of 90 Bhagna (L. ariza) were collected from three different water bodies: the Atrai, the Jamuna and the Kangsha of Bangladesh during January, 2017. Ten morphometric and nine meristic characters were analyzed along with twenty-two truss network measurements. One way ANOVA showed that all morphometric, meristic and truss network measurement were significantly different (P<0.001) among three different stock of the fish. For morphometric and landmark measurements, the first discriminant functions (DF) accounted for 98.6% and 97.9% and the second DF accounted for 1.4% and 2.1%, respectively among group variability, explaining 100% of total among groups variability. For the morphometric and truss network measurements, plotting discriminant functions showed a well-separated clusters of the stocks indicating that the measurement were significantly different among three stocks. The dendrogram based on morphometric and landmark distances data showed two major clusters; the Atrai and Jamuna stocks in one cluster and the Kangsha stock in another cluster. High degree of variation was observed in morphological characteristics among three different stocks (the Atrai, Jamuna and Kangsha) of L .ariza due to their environmental variation and separate geographical location. The results of this study are very useful for proper conservation and successful management of L. ariza and also for the scientific community for the further research

Enhanced heterogeneous activation of peroxymonosulfate by Ruddlesden-Popper-type La2CoO4+δ nanoparticles for bisphenol A degradation

The scalable synthesis of stable catalysts for environmental remediation applications remains challenging. Nonetheless, metal leaching is a serious environmental issue hindering the practical application of transition-metal based catalysts including Co-based catalysts. Herein, for the first time, we describe a facile one-step and scalable spray-flame synthesis of high surface area La2CoO4+δ nanoparticles containing excess oxygen interstitials (+δ) and use them as a stable and efficient catalyst for activating peroxymonosulfate (PMS) towards the degradation of bisphenol A. Importantly, the La2CoO4+δ catalyst exhibits higher catalytic degradation of bisphenol A (95% in 20 min) and stability than LaCoO3–x nanoparticles (60%) in the peroxymonosulfate activation system. The high content of Co2+ in the structure showed a strong impact on the catalytic performance of the La2CoO4+δ + PMS system. Despite its high specific surface area, our results showed a very low amount of leached cobalt (less than 0.04 mg/L in 30 min), distinguishing it as a material with high chemical stability. According to the radical quenching experiments and the electron paramagnetic resonance technology, SO4[rad]–, [rad]OH, and 1O2 were generated and SO4[rad]– played a dominant role in bisphenol A degradation. Moreover, the La2CoO4+δ + PMS system maintained conspicuous catalytic performance for the degradation of other organic pollutants including methyl orange, rhodamine B, and methylene blue. Overall, our results showed that we developed a new synthesis method for stable La2CoO4+δ nanoparticles that can be used as a highly active heterogeneous catalyst for PMS-assisted oxidation of organic pollutants

Numerical Study of Rosenau-KdV Equation Using Finite Element Method Based on Collocation Approach

In the present paper, a numerical method is proposed for the numerical solution of Rosenau-KdV equation with appropriate initial and boundary conditions by using collocation method with septic B-spline functions on the uniform mesh points. The method is shown to be unconditionally stable using von-Neumann technique. To check accuracy of the error norms L2 and L∞ are computed. Interaction of two and three solitary waves are used to discuss the effect of the behavior of the solitary waves during the interaction. Furthermore, evolution of solitons is illustrated by undular bore initial condition. These results show that the technique introduced here is suitable to investigate behaviors of shallow water waves

BIPV-Powered Smart Windows Utilizing Photovoltaic and Electrochromic Devices

A BIPV-powered smart window comprising a building-integrated photovoltaic (BIPV) panel and an all-solid-state electrochromic (EC) stack is proposed. In the proposed device, the output voltage of the BIPV panel varies in accordance with the intensity of the incident light and is modulated in such a way as to generate the EC stack voltage required to maintain the indoor illuminance within a specified range. Two different EC stacks are fabricated and characterized, namely one stack comprising ITO/WO3/Ta2O5/ITO and one stack comprising ITO/WO3/lithium-polymer electrolyte/ITO. It is shown that of the two stacks, the ITO/WO3/lithium-polymer electrolyte/ITO stack has a larger absorptance (i.e., approximately 99% at a driving voltage of 3.5 V). The experimental results show that the smart window incorporating an ITO/WO3/lithium-polymer electrolyte/ITO stack with an electrolyte thickness of 1.0 μm provides an indoor illuminance range of 750–1,500 Lux under typical summertime conditions in Taiwan

Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex

Overcoming limitations of current antiplatelet drugs: A concerted effort for more profitable strategies of intervention

Platelets play a central role in the pathophysiology of atherothrombosis, an inappropriate platelet activation leading to acute ischemic complications (acute myocardial infarction, ischemic stroke). In view of this, platelets are a major target for pharmacotherapy. Presently, the main classes of antiplatelet agents approved for the use in such complications are aspirin and fhienopyridines. Although antiplatelet treatment with these two types of drugs, alone or in combination, leads to a significant reduction of non-fatal myocardial infarction (−32%), non-fatal stroke (−25%), and of cardiovascular death (−17%), a residual risk persists

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

<p>Abstract</p> <p>Background</p> <p>Ionizing radiation-induced hematopoietic injury could occur either due to accidental exposure or due to diagnostic and therapeutic interventions. Currently there is no approved drug to mitigate radiation toxicity in hematopoietic cells. This study investigates the potential of ON 01210.Na, a chlorobenzylsulfone derivative, in ameliorating radiation-induced hematopoietic toxicity when administered after exposure to radiation. We also investigate the molecular mechanisms underlying this activity.</p> <p>Methods</p> <p>Male C3H/HeN mice (n = 5 mice per group; 6-8 weeks old) were exposed to a sub-lethal dose (5 Gy) of γ radiation using a ¹³⁷Cs source at a dose rate of 0.77 Gy/min. Two doses of ON 01210.Na (500 mg/kg body weight) were administered subcutaneously at 24 h and 36 h after radiation exposure. Mitigation of hematopoietic toxicity by ON 01210.Na was investigated by peripheral white blood cell (WBC) and platelet counts at 3, 7, 21, and 28 d after radiation exposure. Granulocyte macrophage colony forming unit (GM-CFU) assay was done using isolated bone marrow cells, and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) was performed on bone marrow sections at 7 d post-exposure. The DNA damage response pathway involving ataxia telangiectasia mutated (ATM) and p53 was investigated by Western blot in bone marrow cells at 7 d post-exposure.</p> <p>Results</p> <p>Compared to the vehicle, ON 01210.Na treated mice showed accelerated recovery of peripheral WBC and platelet counts. Post-irradiation treatment of mice with ON 01210.Na also resulted in higher GM-CFU counts. The mitigation effects were accompanied by attenuation of ATM-p53-dependent DNA damage response in the bone marrow cells of ON 01210.Na treated mice. Both phospho-ATM and phospho-p53 were significantly lower in the bone marrow cells of ON 01210.Na treated than in vehicle treated mice. Furthermore, the Bcl2:Bax ratio was higher in the drug treated mice than the vehicle treated groups.</p> <p>Conclusions</p> <p>ON 01210.Na treatment significantly mitigated the hematopoietic toxicity induced by a sub-lethal radiation dose. Mechanistically, attenuation of ATM-p53 mediated DNA damage response by ON 01210.Na is contributing to the mitigation of radiation-induced hematopoietic toxicity.</p

Knowledge and care seeking practices for ear infections among parents of under five children in Kigali, Rwanda : a cross-sectional study

Background: Infections affecting the middle ear are a common childhood occurrence. Some cases may present with ear discharge through a tympanic membrane perforation which may heal spontaneously. However, up to 5% or more cases of those affected have persistent ear discharge. A number of barriers contribute towards delayed presentation at health facilities for treatment of ear infections. We conducted a study to evaluate parents’ and caregivers’ knowledge and care seeking practices for ear infections in children under five in Gasabo district in Kigali, Rwanda. Methods: Parents/guardians (n = 810) were interviewed using a structured questionnaire to elicit their knowledge of ear infections in children under five and their attitude to seeking care for their children. Results: The mean age of the respondents was 31.27 years (SD = 7.88, range 17–83). Considering an average of knowledge parameters which included causes, symptoms, prevention, treatment and consequences of ear infections, we found that 76.6% (622) of respondents were knowledgeable about ear infections. We defined a positive practice as seeking medical treatment (community health workers or health facility) and this was found in 89.1% (722) respondents. Correlating knowledge with choice of seeking treatment, respondents were 33% less likely to practice medical pluralism (OR = 0.33, CI 0.11–0.97, P = 0.043) if they were familiar with infections. Moreover, urban dweller were 1.7 times more likely to know ear infections compared to rural dwellers (OR = 1.70, CI 1.22–2.38, P = 0.002). Conclusion: The majority of respondents had good knowledge and positive attitudes and practices about ear infection. However, medical pluralism was common. There is need to improve the community’s awareness and access to primary health care facilities for the care of ear infections especially in rural areas of Rwanda

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation