From genes to therapy: A comprehensive exploration of congenital heart disease through the lens of genetics and emerging technologies.

Congenital heart disease (CHD) affects approximately 1 % of live births worldwide, making it the most common congenital anomaly in newborns. Recent advancements in genetics and genomics have significantly deepened our understanding of the genetics of CHDs. While the majority of CHD etiology remains unclear, evidence consistently indicates that genetics play a significant role in its development. CHD etiology holds promise for enhancing diagnosis and developing novel therapies to improve patient outcomes. In this review, we explore the contributions of both monogenic and polygenic factors of CHDs and highlight the transformative impact of emerging technologies on these fields. We also summarized the state-of-the-art techniques, including targeted next-generation sequencing (NGS), whole genome and whole exome sequencing (WGS, WES), single-cell RNA sequencing (scRNA-seq), human induced pluripotent stem cells (hiPSCs) and others, that have revolutionized our understanding of cardiovascular disease genetics both from diagnosis perspective and from disease mechanism perspective in children and young adults. These molecular diagnostic techniques have identified new genes and chromosomal regions involved in syndromic and non-syndromic CHD, enabling a more defined explanation of the underlying pathogenetic mechanisms. As our knowledge and technologies continue to evolve, they promise to enhance clinical outcomes and reduce the CHD burden worldwide.

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia.

BACKGROUND: Fetal hemoglobin (HbF) has been reported to be associated with disease severity and treatment response to HbF-inducing therapies like Hydroxyurea and thalidomide in patients suffering from transfusion-dependent beta-thalassemia (TDT). However, the role of hemoglobin A2 (HbA2) remains less clear in TDT, therefore this study aims to determine the impact of both HbF and HbA2 levels on disease severity and treatment response. METHODOLOGY: A prospective observational study was conducted at the Peshawar Institute of Medical Sciences and Fatimid Foundation Peshawar from May 2023 to October 2023. A total of 232 TDT-diagnosed patients were enrolled using a convenient sampling technique, whereas coinheritance of beta-thalassemia with other hemoglobinopathies was excluded. RESULT: This study reveals a significant impact of HbF on disease severity (p<0.05) but finds no substantial correlation (p>0.05) between HbA2 levels and disease severity. Additionally, HbF and HbA2 levels exhibit no association with treatment response categories in patients receiving HbF induction therapy, and various mutations do not significantly alter HbF and HbA2 levels or disease severity parameters in TDT patients. CONCLUSION: The study established a significant association between HbF and disease severity. However, regarding treatment response, neither HbF nor HbA2 levels impact response categories. Combinatorial treatment with hydroxyurea and thalidomide showed superior efficacy compared to monotherapy. A larger sample size and extended follow-up are recommended to further explore the impact of HbF, HbA2, and various mutations on disease severity and treatment response.

Seasonality of deaths with respect to age and cause in Chitral District Pakistan.

BACKGROUND: Seasonal variability in mortality has been studied in various regions globally. Proper evaluation of seasonally fluctuating mortality is important to establish effective public health measures. We investigated the overall, age-specific, and cause-specific seasonality of deaths in Chitral District in Pakistan. METHOD: Data on 2577 deaths were provided by the Agha Khan Health Support Program. Seasonal mortality patterns concerning age and causes were examined using the X-12 ARIMA pseudo-additive decomposition method. RESULTS: Of the total deceased, 59.6% were males. The proportion of deceased males was significantly higher than the female (40.4%, p< 0.001). The average age at death was 57.7 years (SD = 28.7). On average, approximately 43 deaths occurred each month. More than 10% of the deaths occurred in children less than 5-years-of-age. Among all the causes of death, the most frequent was cardiovascular disease (n = 666, 25.8%) followed by respiratory disease (n = 482, 18.7%). Significant seasonality in the overall deaths was evident, with a peak in winter. Deaths in people ≥ 55-years-of-age were significantly seasonal and peaked in winter. Deaths due to cardiovascular, respiratory, and kidney related diseases were also significantly seasonal with winter peaks. Further, deaths due to external causes were significantly seasonal with summer peak. CONCLUSION: In the winter season, all-cause, except external, and age-specific mortality peaks in Chitral District, Pakistan. Deaths due to external causes and cardiovascular, respiratory, and kidney related diseases were significant seasonal effects.

Trace Metal Accumulation in Trigonella foenum-graecum Irrigated with Wastewater and Human Health Risk of Metal Access Through the Consumption.

The aim of the present research was to determine the trace metal accumulations in Trigonella foenum-graecum irrigated with three different water regimes (ground water, canal water and sugar mill water). Also, transfer factors, pollution load indices, and health risk indices were assessed to evaluate metal transport and accumulation through the food chain. The analysis was conducted by Atomic Absorption Spectrophotometer (Shimadzu model AA-6300) to evaluate the concentration of metals in water, soil and vegetables. Trace metal concentrations in water samples ranged from 0.84 to 1.67, 0.42 to 0.72, 0.45 to 0.85, 2.51 to 9.99, 1.21 to 1.92, 1.82 to 9.98 and 0.64 to 0.91 mg/kg for Cd, Cr, Cu, Fe, Ni, Zn and Mn, respectively. The mean metal concentrations in soil samples were determined as 0.25, 0.86, 0.96, 3.37, 0.4, 0.44 and 2.31 mg/kg for Cd, Cr, Cu, Fe, Ni, Zn and Mn, respectively. Trace metal accumulations in T. foenum-graecum samples gathered from where soil samples were taken are as follows: The contents of Cd, Cr, Cu, Fe, Ni, Zn and Mn ranged from 0.48 to 1.06, 0.11 to 0.35, 0.15 to 0.29, 1.43 to 8.39, 0.39 to 0.54, 2.1 to 3.05 and 0.42 to 0.47 mg/kg, respectively. Statistical analyses showed that the treatments have non-significant effect (p > 0.05) on concentrations of metals in T. foenum-graecum samples collected from three sites for Ni, Cr, Cu, Zn and Mn and significant effect on Fe and Cd.

Evaluation of Potential Toxic Metals Accumulation in Wheat Irrigated with Wastewater.

The present study was carried out to ascertain the level of various metals in wheat variety (Chagi-4) irrigated with diverse doses of wastewater. The concentration of metals in soil, water and wheat grain samples was examined through an atomic absorption spectrophotometer. In wheat grains, the mean values of metals (mg/kg) varied from 0.06 to 0.2 for Pb, 1.2 to 1.6 for Cd, 0.6 to 0.9 for Ni, 0.8 to 1.6 for Fe, 0.4 to 1.0 for Mn, 0.7 to 1.4 for Cu, 0.3 to 0.5 for Cr, 0.1 to 0.9 for Zn and 0.03 to 0.2 for Co, correspondingly. Measured concentrations were found within the permissible limit given by FAO/WHO except for cadmium whose concentration exceeded an acceptable limit 0.2 mg/kg suggested by FAO/WHO. It might be due to high soil pH, which hinders the efficient transfer of metals between different mediums. Wastewater irrigated soil, wheat and water had high metal values, but the low rate of transfer was noticed from soil to grains. Higher bioconcentration factor was obtained for manganese and cadmium; cadmium had even higher pollution load index, which could indicate the contamination status of soil. Therefore, regular monitoring of wastewater is necessary to prevent the excessive build-up of metals.

Toxicological potential of cobalt in forage for ruminants grown in polluted soil: a health risk assessment from trace metal pollution for livestock.

The trace metal pollution in the environment is a highly concerned issue in these days. One of the important causes of trace metal pollution is the exhaust gases released from the vehicles on the roads. These dangerous gases pose life-threatening effects on the forage plants grown along the roadside as these plants are at direct risk to these trace metals. The aims of the present study were to determine the cobalt (Co) concentrations in soil, forages, and blood plasma of the buffaloes and to evaluate the Co deficiencies and toxicities in these samples. All samples were collected from six sites (Faisalabad roadside, Bhalwal roadside, Shaheenabad roadside, Mateela roadside, 50 Chak roadside, and Dera Saudi-control) of Sargodha city. The Co concentrations in these samples were determined by atomic absorption spectrophotometer (AA-6300 Shimadzu Japan). In soil samples, Co level ranged from 1.958 to 3.457 mg/kg in the six sampling sites. The highest Co level was observed at site 6 and the lowest at site 2. In forage samples, Co level ranged from 0.770 to 2.309 mg/kg in the six sampling sites. The highest Co level was observed at site 3 and the lowest at site 2. In blood plasma samples, Co level ranged from 2.644 to 4.927 mg/kg in the six sampling sites. The highest Co level was observed at site 1 and the lowest at site 3. The results showed higher Co values in the samples collected from the site IV while the bioconcentration factor for forage-soil was found highest in the samples collected from Site III. On the other hand, a correlation was found positively significant when soil and forage were correlated, and it was found negatively significant when blood and forage were correlated.

Improved adhesive strength and toughness of polyvinyl acetate glue on addition of small quantities of graphene.

We have prepared composites of polyvinyl acetate (PVAc) reinforced with solution exfoliated graphene. We observe a 50% increase in stiffness and a 100% increase in tensile strength on addition of 0.1 vol % graphene compared to the pristine polymer. As PVAc is commonly used commercially as a glue, we have tested such composites as adhesives. The adhesive strength and toughness of the composites were up to 4 and 7 times higher, respectively, than the pristine polymer.

Solvent-exfoliated graphene at extremely high concentration.

We describe three related methods to disperse graphene in solvents with concentrations from 2 to 63 mg/mL. Simply sonicating graphite in N-methyl-2-pyrrolidinone, followed by centrifugation, gives dispersed graphene at concentrations of up to 2 mg/mL. Filtration of a sonicated but uncentrifuged dispersion gives a partially exfoliated powder that can be redispersed at concentrations of up to 20 mg/mL. However, this process can be significantly improved by removing any unexfolaited graphite from the starting dispersion by centrifugation. The centrifuged dispersion can be filtered to give a powder of exfoliated few-layer graphene. This powder can be redispersed at concentrations of at least 63 mg/mL. The dispersed flakes are ~1 µm long and ~3 to 4 layers thick on average. Although some sedimentation occurs, ~26-28 mg/mL of the dispersed graphene appears to be indefinitely stable.

Estimation of bacteriological levels in surface water samples to evaluate their contamination profile.

The present work deals with the assessment of bacteriological contamination along with some physico-chemical parameters of water samples from Lahore canal. ANOVA showed that the observed p values of log-transformed viable plate counts, total suspended solids, turbidity, and biological oxygen demand are 0.000, 0.000, 0.000, and 0.000, respectively, which are < 0.05, while the p value of total coliforms, total fecal coliforms, and Escherichia coli are 0.728, 0.827, and 0.081, respectively which are > 0.05. Significant correlation was observed between log-transformed viable plate counts (CFU), biological oxygen demand, total suspended solids, and turbidity. Further regression analysis revealed that simple line regression model is fit for log-transformed viable plate counts and total suspended solids, log-transformed viable plate counts and turbidity, turbidity and total suspended solids, biological oxygen demand and total suspended solids, biological oxygen demand and log-transformed viable plate counts, and biological oxygen demand and turbidity.