Concomitant Occurrence of Peripheral Neuropathy and Vision Loss Due to Multivitamin Deficiency After Bariatric Surgery.

Vitamin deficiencies, especially after Bariatric surgery, are common and, when not properly addressed, can lead to debilitating complications. Bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal; this alteration makes these patients more susceptible to developing nutritional deficiencies. Peripheral neuropathy is one of the complications that can arise from nutritional deficiencies, and it can cause severe functional impairment. Vision loss is a relatively uncommon complication after weight loss procedure. Changes in the retinal nerve fiber layer, choroidal thickness, and visual fields due to hypovitaminosis result in nutritional optic neuropathy and retinopathy. The main retinal complication is nyctalopia (night blindness), which is caused by vitamin A deficiency. We present a case of concomitant peripheral neuropathy and vision loss secondary to reduced levels of multiple vitamins following gastric bypass surgery. This case highlights the need for regular vitamin level monitoring and appropriate replenishment in patients after bariatric surgery to prevent significant morbidities.

Uterine artery embolization versus myomectomy: a systematic review and meta-analysis.

Introduction: Uterine fibroids are the commonest benign tumors of the reproductive tract in women of childbearing age. They are usually asymptomatic but can cause menorrhagia. Treatments include myomectomy and uterine artery embolization (UAE). The latter is a relatively new procedure, therefore of special interest. Objectives: We conducted a systematic review and meta-analysis of all published studies to provide a comprehensive outlook on the effectiveness of UAE by comparing its outcomes to those of myomectomy. Electronic databases (PubMed and Cochrane Central) were systematically searched from January 2000 to March 2022 for published randomized control trials, observational studies, and meta-analyses that compared UAE to myomectomy for at least one of the pre-specified outcomes, namely re-intervention rates, length of hospital stay, and complications. Methods: We shortlisted nine studies for the final analysis. For continuous outcomes, results from random-effects meta-analysis were presented as mean differences (MDs) and corresponding 95% confidence intervals (CIs). Risk ratios (RRs) for dichotomous outcomes were pooled using a random-effects model. Results: The final analysis consisted of nine studies. Factors like re-intervention, hospitalization, and complications, each with its unique follow-up duration were assessed. Pooled analysis demonstrated significant results for greater re-intervention rates with UAE as compared to myomectomy (RR: 2.16, 95% CI: (1.27-3.66), p-value 0.004, heterogeneity I2 = 85%). UAE holds a greater but statistically insignificant risk for major complications (RR: 0.62, 95% CI: (0.29-1.33), p-value 0.22, heterogeneity I2 = 0%) and myomectomy shows a statistically insignificant greater risk for minor complications (RR: 1.72, 95% CI: (0.92-3.22), p-value 0.09, heterogeneity I2 = 0%). UAE had a shorter but statistically insignificant duration of hospital stay (MD: -1.12, 95% CI: (-2.50 to 0.27), p-value 0.11, heterogeneity I2 = 96%) (p-value for subgroup differences = 0.005). Conclusion: Our meta-analysis of approximately 196,595 patients demonstrates that myomectomy results in a significant reduction in re-intervention rate compared to UAE.

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta-Analysis of Observational Studies and Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision-making, but data from randomized controlled trials often differ from real-world observational studies. METHODS AND RESULTS: A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10-5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57-4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03-3.25]), compared with non-ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28-7.39]). Stroke risk was not increased with use of ICIs in RCTs. CONCLUSIONS: We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.

Hydrogeochemical characteristics, stable isotopes, positive matrix factorization, source apportionment, and health risk of high fluoride groundwater in semiarid region.

Chronic exposure to high fluoride (F-) levels in groundwater causes community fluorosis and non-carcinogenic health concerns in local people. This study described occurrence, dental fluorosis, and origin of high F-groundwater using δ2H and δ18O isotopes at semiarid Gilgit, Pakistan. Therefore, groundwater (n = 85) was collected and analyzed for F- concentrations using ion-chromatography. The lowest F- concentration was 0.4 mg/L and the highest 6.8 mg/L. F- enrichment is linked with higher pH, NaHCO3, NaCl, δ18O, Na+, HCO3-, and depleted Ca+2 aquifers. The depleted δ2H and δ18O values indicated precipitation and higher values represented the evaporation effect. Thermodynamic considerations of fluorite minerals showed undersaturation, revealing that other F-bearing minerals viz. biotite and muscovite were essential in F- enrichment in groundwater. Positive matrix factorization (PMF) and principal component analysis multilinear regression (PCAMLR) models were used to determine four-factor solutions for groundwater contamination. The PMF model results were accurate and reliable compared with those of the PCAMLR model, which compiled the overlapping results. Therefore, 28.3% exceeded the WHO permissible limit of 1.5 mg/L F-. Photomicrographs of granite rocks showed enriched F-bearing minerals that trigger F- in groundwater. The community fluorosis index values were recorded at > 0.6, revealing community fluorosis and unsuitability of groundwater for drinking.

Cadmium and lead accumulation in important food crops due to wastewater irrigation: Pollution index and health risks assessment.

The contamination of farm soils with heavy metals (HMs) has raised significant concerns due to the increased bioavailability and accumulation of HMs in agricultural food crops. To address this issue, a survey experiment was conducted in the suburbs of Multan and Faisalabad to investigate the spatial distribution, bioaccumulation, translocation, and health risks of cadmium (Cd) and lead (Pb) in agricultural crops. The results show a considerable concentration of Cd and Pb in soils irrigated with wastewater, even though these levels were below the permissible limits in water and soil matrices. The pollution index for Cd was mostly greater than 1 at the selected sites, indicating its accumulation in soil over time due to wastewater irrigation. Conversely, the pollution index for Pb was below 1 at all sites. Among the plants, Zea mays accumulated the highest concentration of Cd and Pb. The translocation factor from soil to root was highest for Brassica olearecea (7.037 for Cd) and Zea mays (6.383 for Pb). The target hazard quotient (THQ) value of Cd exceeded the non-carcinogenic limit for most vegetables. The highest value was found in Allium cepa (5.256) and the lowest in Allium sativum (0.040). In contrast, the THQ level of Pb was below the non-carcinogenic limit for most vegetables, except for Allium cepa (1.479), Solanum lycopersicum (1.367), and Solanum tuberosum (1.326). The study highlights that Allium cepa poses the highest health risk for humans, while Medicago sativa poses the highest risk for animals due to Cd and Pb contamination. These results underscore the urgent need for effective measures to mitigate the health risks associated with HM contamination in crops and soils.

A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Geochemical control, water quality indexing, source distribution, and potential health risk of fluoride and arsenic in groundwater: Occurrence, sources apportionment, and positive matrix factorization model.

Fluoride (F-), and arsenic (As) in the groundwater cause health problems in developing countries, including Pakistan. We evaluated the occurrence, distribution, sources apportionment, and health hazards of F-, and As in the groundwater of Mardan, Pakistan. Therefore, groundwater samples (n = 130) were collected and then analyzed for F-, and As by ion-chromatography (IC) and Inductively-coupled plasma mass-spectrometry (ICP-MS). The F-, and As concentrations in groundwater were 0.7-14.4 mg/L and 0.5-11.2 µg/L. Relatively elevated F-, and As coexists with higher pH, Na+, HCO3-, SO4-2, and depleted Ca+2 due to fluoride, sulfide-bearing minerals, and anthropogenic inputs. Both F-, and/or As are transported in subsurface water through adsorption and desorption processes. Groundwater samples 45%, and 14.2% exceeded the WHO guidelines of 1.5 mg/L and 10 µg/L. Water quality indexing (WQI-model) declared that 35.7% samples are unfit for household purposes. Saturation and undersaturation of minerals showed precipitation and mineral dissolution. Groundwater contamination by PCA-MLR and PMF-model interpreted five factors. The fitting results and R2 values of PMF (0.52-0.99)>PCA-MLR (0.50-0.95) showed high accuracy of PMF-model. Human health risk assessment (HHRA-model) revealed high non-carcinogenic and carcinogenic risk for children than adults. The percentile recovery of F- and As was recorded 98%, and 95% with reproducibility ± 5% error.

Effect of storage on the nutritional and antioxidant properties of brown Basmati rice.

The purpose of the present study is to evaluate the effect of storage time and temperature on the nutritional and antioxidant values of different varieties of brown rice. PARB approved indigenous Basmati varieties (Basmati 86, Basmati 515, Basmati super, Basmati super fine and Basmati kainat) were procured and initially tested for physicochemical parameters, including moisture, ash, lipids, proteins, carbohydrates, and fibers from the brown rice powder. Similarly, antioxidant capacity of these brown rice samples was assessed in terms of total phenolic content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging potential. Samples of brown rice were stored for 3 and 6 months at 25 and 5°C. On increasing the storage time and temperature, antioxidant activity of rice decreases up to 50%. Nutritional parameters, such as minerals, carbohydrates, and fatty acids were characterized using UV/Vis spectrophotometer, ICP-OES, GC-MS, and HPLC, revealing significant changes in the chemical composition of brown rice. Observation indicates that storage at high temperatures leads to a rapid decrease in carbohydrate and moisture content than at lower temperatures. The protein and ash content remains controlled and integrate with the mineral composition found. Decrease in the glucose and fructose amount was observed in brown rice varieties except for Basmati super fine and Basmati kainat at 5°C. Regarding fatty acids, oleic and linoleic acids were prominent in oils extracted from the different brown rice varieties, and their content was reduced during the storage due to conversion to behenic, and erucic acids, respectively. From the present study, it can be concluded that low storage temperatures reduce the loss of nutrients, offering better nutritional quality for the consumer.

Chemical composition, antioxidant, and antimicrobial activities of P. roxburghii oleoresin essential oils extracted by steam distillation, superheated steam, and supercritical fluid CO2 extraction.

Pinus roxburghii is a rich source of high-quality oleoresin that is composed of resin acids and essential oil (EO). The present research work was planned to study and compare the yield, biological activities, and chemical profiling of P. roxburghii oleoresin EOs extracted through various green extraction methods. Steam distillation (SD), supercritical fluid extraction, and superheated SD (SHSD) at different temperatures (120, 140, and 160°C) were employed to extract EOs from P. roxburghii oleoresin. Antioxidant potential of EOs was determined by total antioxidant content/ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging activity (DPPH-FRSA), hydrogen peroxide scavenging assays, and percentage inhibition in linoleic acid. Antimicrobial activity of EOs was determined by resazurin microtiter-plate, disc diffusion, and micro-dilution broth susceptibility assays. Gas chromatography-mass spectrometry was used to determine the chemical composition of EOs. It was observed that extraction methods significantly affected the yield, biological activities, and chemical composition of EOs. The maximum yield (19.92%) was found in EO extracted by SHSD at 160°C. EO extracted by SHSD at 120°C showed the highest DPPH-FRSA (63.33% ± 0.47%), linoleic acid oxidation inhibition (96.55% ± 1.71%), hydrogen peroxide scavenging activity (59.42% ± 0.32%), and total antioxidant contents/FRAP (134.49% ± 1.34 mg/L of gallic acid equivalent). The antimicrobial activity results showed that superheated steam-extracted EO of 120°C revealed the highest antifungal and antibacterial activity. It is concluded that SHSD is an alternative and effective technique for the extraction of oleoresins EO that improves the EO yield and biological activities. Further research on optimization and experimental parameters for the extraction of P. roxburghii oleoresin EO by SHSD is required.

Divergent effects of cerium oxide nanoparticles alone and in combination with cadmium on nutrient acquisition and the growth of maize (Zea mays).

Introduction: The increasing use of cerium nanoparticles (CeO2-NPs) has made their influx in agroecosystems imminent through air and soil deposition or untreated wastewater irrigation. Another major pollutant associated with anthropogenic activities is Cd, which has adverse effects on plants, animals, and humans. The major source of the influx of Cd and Ce metals in the human food chain is contaminated food, making it an alarming issue; thus, there is a need to understand the factors that can reduce the potential damage of these heavy metals. Methods: The present investigation was conducted to evaluate the effect of CeO2-10-nm-NPs and Cd (alone and in combination) on Zea mays growth. A pot experiment (in sand) was conducted to check the effect of 0, 200, 400, 600, 1,000, and 2,000 mg of CeO2-10 nm-NPs/kg-1 dry sand alone and in combination with 0 and 0.5 mg Cd/kg-1 dry sand on maize seedlings grown in a partially controlled greenhouse environment, making a total of 12 treatments applied in four replicates under a factorial design. Maize seedling biomass, shoot and root growth, nutrient content, and root anatomy were measured. Results and discussion: The NPs were toxic to plant biomass (shoot and root dry weight), and growth at 2,000 ppm was the most toxic in Cd-0 sets. For Cd-0.5 sets, NPs applied at 1,000 ppm somewhat reverted Cd toxicity compared with the contaminated control (CC). Additionally, CeO2-NPs affected Cd translocation, and variable Ce uptake was observed in the presence of Cd compared with non-Cd applied sets. Furthermore, CeO2-NPs partially controlled the elemental content of roots and shoots (micronutrients such as B, Mn, Ni, Cu, Zn, Mo, and Fe and the elements Co and Si) and affected root anatomy.

Groundwater Quality, Health Risk Assessment, and Source Distribution of Heavy Metals Contamination around Chromite Mines: Application of GIS, Sustainable Groundwater Management, Geostatistics, PCAMLR, and PMF Receptor Model.

Groundwater contamination by heavy metals (HMs) released by weathering and mineral dissolution of granite, gneisses, ultramafic, and basaltic rock composition causes human health concerns worldwide. This paper evaluated the heavy metals (HMs) concentrations and physicochemical variables of groundwater around enriched chromite mines of Malakand, Pakistan, with particular emphasis on water quality, hydro-geochemistry, spatial distribution, geochemical speciation, and human health impacts. To better understand the groundwater hydrogeochemical profile and HMs enrichment, groundwater samples were collected from the mining region (n = 35), non-mining region (n = 20), and chromite mines water (n = 5) and then analyzed using ICPMS (Agilent 7500 ICPMS). The ranges of concentrations in the mining, non-mining, and chromite mines water were 0.02-4.5, 0.02-2.3, and 5.8-6.0 mg/L for CR, 0.4-3.8, 0.05-3.6, and 3.2-5.8 mg/L for Ni, and 0.05-0.8, 0.05-0.8, and 0.6-1.2 mg/L for Mn. Geochemical speciation of groundwater variables such as OH-, H+, Cr+2, Cr+3, Cr+6, Ni+2, Mn+2, and Mn+3 was assessed by atomic fluorescence spectrometry (AFS). Geochemical speciation determined the mobilization, reactivity, and toxicity of HMs in complex groundwater systems. Groundwater facies showed 45% CaHCO3, 30% NaHCO3, 23.4% NaCl, and 1.6% Ca-Mg-Cl water types. The noncarcinogenic and carcinogenic risk of HMs outlined via hazard quotient (HQ) and total hazard indices (THI) showed the following order: Ni > Cr > Mn. Thus, the HHRA model suggested that children are more vulnerable to HMs toxicity than adults. Hierarchical agglomerative cluster analysis (HACA) showed three distinct clusters, namely the least, moderately, and severely polluted clusters, which determined the severity of HMs contamination to be 66.67% overall. The PCAMLR and PMF receptor model suggested geogenic (minerals prospects), anthropogenic (industrial waste and chromite mining practices), and mixed (geogenic and anthropogenic) sources for groundwater contamination. The mineral phases of groundwater suggested saturation and undersaturation. Nemerow's pollution index (NPI) values determined the unsuitability of groundwater for domestic purposes. The EC, turbidity, PO4-3, Na+, Mg+2, Ca+2, Cr, Ni, and Mn exceeded the guidelines suggested by the World Health Organization (WHO). The HMs contamination and carcinogenic and non-carcinogenic health impacts of HMs showed that the groundwater is extremely unfit for drinking, agriculture, and domestic demands. Therefore, groundwater wells around the mining region need remedial measures. Thus, to overcome the enrichment of HMs in groundwater sources, sustainable management plans are needed to reduce health risks and ensure health safety.

Influence of ionic cerium and cerium oxide nanoparticles on Zea mays seedlings grown with and without cadmium.

Cerium (Ce4+) and cerium oxide nanoparticles (CeO2-NPs) have diversified reported effects on plants. Once dispersed in the environment their fate is not well understood, especially in co-existence with other pollutants like cadmium (Cd). The effect of co-application of Ce and Cd are reported in various studies, but the role of Ce source (ionic or bulk) and nanoparticle size is still unknown in cereal plants like maize (Zea mays). To better understand the synergistic effects of Ce and Cd, 500 mg kg-1 Ce coming from ionic (Ce4+ as CeSO4) and CeO2 nano sources (10 nm, 50 nm, and 100 nm) alone and in combination with 0.5 mg Cd kg-1 sand were applied to maize seedlings. Growth, physiology, root structure, anatomy, and ionic homeostasis in maize were measured. The results revealed that Ce4+ resulted in overall decrease in seedling growth, biomass and resulted in higher heavy metal (in control sets) and Cd (in Cd spiked sets) uptake in maize seedlings' root and shoot. The effects of CeO2-NPs were found to be dependent on particle size; in fact, under Cd-0 (non-Cd spiked sets) CeO2-100 nm showed beneficial effects compared to the control. While under co-application with Cd, CeO2-50 nm showed net beneficial effects on maize seedling growth parameters. The Ce alone, and in combination with Cd, altered the root suberin barrier formation. Both ionic and nano Ce sources alone and in co-existence with Cd behaved differently for tissue elemental concentrations (Ce, Cd, micronutrients like B, Mn, Ni, Cu, Zn, Mo, Fe and elements Co, Si) suggesting a strong influence of Cd-Ce coexistence on the element's uptake and translocation in maize.

Chemical composition and antimicrobial activity of Boswellia serrata oleo-gum-resin essential oil extracted by superheated steam.

Oleo-gum-resin is a complex mixture of essential oils, polysaccharides, and resin acids. The objectives of the present study were to evaluate the variation in chemical components and antimicrobial activity of essential oils extracted by superheated steam at various temperatures. The optimum essential oil yield was obtained at the highest superheated steam temperature (210 °C). In total, twenty-one compounds were quantified by GC-MS with α-pinene as the major compound, followed by α-thujene, trans-verbenol, ß-thujone, p-cymene, m-cymene, and sabinene. Antimicrobial activity was performed by disc diffusion, resazurin microtitre-plate and micro-dilution broth susceptibility assays in which essential oil extracted at 150 °C and 180 °C revealed the highest antibacterial and antifungal activity, respectively. It is concluded that superheated steam is an effective method for the isolation of essential oil from oleo-gum-resin that improves the recovery of essential oil as well as antimicrobial activity.

Effect of soil texture and zinc oxide nanoparticles on growth and accumulation of cadmium by wheat: a life cycle study.

Cadmium (Cd) is getting worldwide attention due to its continuous accumulation in agricultural soils which is due to anthropogenic activities and finally Cd enters in food chain mainly through edible plants. Cadmium free food production on contaminated soils is great challenge which requires some innovative measures for crop production on such soils. The current study evaluated the efficiency of zinc oxide nanoparticles (ZnONPs) (0, 150 and 300 mg/kg) on the growth of wheat in texturally different soils including clay loam (CL), sandy clay loam (SCL), and sandy loam (SL) which were contaminated with were contaminated with 25 mg/kg of Cd before crop growth. Results depicted that doses of ZnONPs and soil textures significantly affected the biological yields, Zn and Cd uptake in wheat plants. The application of 300 mg/kg ZnONPs caused maximum increase in dry weights of shoot (66.6%), roots (58.5%), husk (137.8%) and grains (137.8%) in CL soil. The AB-DTPA extractable Zn was increased while Cd was decreased with doses of NPs depending upon soil textures. The maximum decrease in AB-DTPA extractable Cd was recorded in 300 mg/kg of ZnONPs treatment which was 58.7% in CL, 33.2% in SCL and 12.1% in SL soil as compared to respective controls. Minimum Cd concentrations in roots, shoots, husk and grain were found in 300 mg/kg ZnONPs amended CL soil which was 58%, 76.7%, 58%, and 82.6%, respectively. The minimum bioaccumulation factor (0.14), translocation index (2.46) and health risk index (0.05) was found in CL soil with the highest dose of NPs. The results concluded that use of ZnONPs significantly decreased Cd concentration while increased Zn concentrations in plants depending upon doses of NPs and soil textures.

Geochemical Modeling Source Provenance, Public Health Exposure, and Evaluating Potentially Harmful Elements in Groundwater: Statistical and Human Health Risk Assessment (HHRA).

Groundwater contamination by potentially harmful elements (PHEs) originating from the weathering of granitic and gneissic rock dissolution poses a public health concern worldwide. This study investigated physicochemical variables and PHEs in the groundwater system and mine water of the Adenzai flood plain region, in Pakistan, emphasizing the fate distribution, source provenance, chemical speciation, and health hazard using the human health risk assessment HHRA-model. The average concentrations of the PHEs, viz., Ni, Mn, Cr, Cu, Cd, Pb, Co, Fe, and Zn 0.23, were 0.27, 0.07, 0.30, 0.07, 0.06, 0.08, 0.68, and 0.23 mg/L, respectively. The average values of chemical species in the groundwater system, viz., H+, OH−, Ni2+, Mn2+, Mn3+, Cr3+, Cr6+, Cu+, Cu2+, Cd2+, Pb2+, Pb4+, Co2+, Co3+, Fe2+, Fe3+, and Zn2+, were 1.0 × 10−4 ± 1.0 × 10−6, 1.0 × 10−4 ± 9.0 × 10−7, 2.0 × 10−1 ± 1.0 × 10−3, 3.0 × 10−1 ± 1.0 × 10−3, 1.0 × 10−22 ± 1.0 × 10−23, 4.0 × 10−6 ± 2.0 × 10−6, 4.0 × 10−11 ± 2.0 × 10−11, 9.0 × 10−3 ± 1.0 × 10−2, 2.0 × 10−1 ± 2.0 × 10−3, 7.0 × 10−2 ± 6.0 × 10−2, 5.0 × 10−2 ± 5.0 × 10−2, 2.0 × 10−2 ± 1.5 × 10−2, 6.0 × 10−2 ± 4.0 × 10−2, 8.0 × 10−31 ± 6.0 × 10−31, 3.0 × 10−1 ± 2.0 × 10−4, 4.0 × 10−10 ± 3.0 × 10−10, and 2.0 × 10−1 ± 1.0 × 10−1. The mineral compositions of PHEs, viz. Ni, were bunsenite, Ni(OH)2, and trevorite; Mn viz., birnessite, bixbyite, hausmannite, manganite, manganosite, pyrolusite, and todorokite; Cr viz., chromite and eskolaite; Cu viz., CuCr2O4, cuprite, delafossite, ferrite-Cu, and tenorite; Cd viz., monteponite; Pb viz, crocoite, litharge, massicot, minium, plattnerite, Co viz., spinel-Co; Fe viz., goethite, hematite, magnetite, wustite, and ferrite-Zn; and Zn viz., zincite, and ZnCr2O4 demarcated undersaturation and supersaturation. However, EC, Ca2+, K+, Na+, HCO3−, Cr, Cd, Pb, Co, and Fe had exceeded the WHO guideline. The Nemerow's pollution index (NPI) showed that EC, Ca2+, K+, Na+, HCO3−, Mn, Cd, Pb, Co, and Fe had worse water quality. Principal component analysis multilinear regression (PCAMLR) and cluster analysis (CA) revealed that 75% of the groundwater contamination originated from geogenic inputs and 18% mixed geogenic-anthropogenic and 7% anthropogenic sources. The HHRA-model suggested potential non-carcinogenic risks, except for Fe, and substantial carcinogenic risks for evaluated PHEs. The women and infants are extremely exposed to PHEs hazards. The non-carcinogenic and carcinogenic risks in children, males, and females had exceeded their desired level. The HHRA values of PHEs exhibited the following increasing pattern: Co > Cu > Mn > Zn > Fe, and Cd > Pb > Ni > Cr. The higher THI values of PHEs in children and adults suggested that the groundwater consumption in the entire region is unfit for drinking, domestic, and agricultural purposes. Thus, all groundwater sources need immediate remedial measures to secure health safety and public health concerns.

Hydrogeochemical assessment of carcinogenic and non-carcinogenic health risks of potentially toxic elements in aquifers of the Hindukush ranges, Pakistan: insights from groundwater pollution indexing, GIS-based, and multivariate statistical approaches.

Globally, potentially toxic elements (PTEs) and bacterial contamination pose health hazards, persistency, and genotoxicity in the groundwater aquifer. This study evaluates PTE concentration, carcinogenic and noncarcinogenic health hazards, groundwater quality indexing (GWQI-model), source provenance, and fate distribution in the groundwater of Hindukush ranges, Pakistan. The new estimates of USEPA equations record new research dimensions for carcinogenic and noncarcinogenic hazards. The principal component analysis (PCA), mineral phases, and spatial distribution determine groundwater contamination and its impacts. The average concentrations of PTEs, viz., Cd, Cu, Co, Fe, Pb, and Zn, were 0.06, 0.27, 0.07, 0.55, 0.05, and 0.19 mg/L, and E. coli, F. coli, and P. coli were 27.5, 24.0, and 19.0 CFU/100 ml. Moreover, the average values of basic minerals, viz., anhydrite, aragonite, calcite, dolomite, gypsum, halite, and hydroxyl apatite, were 0.4, 2.4, 2.6, 5.1, 0.6, and - 4.0, 11.2, and PTE minerals like monteponite, tenorite, cuprite, cuprous ferrite, cupric ferrite, ferrihydrite, goethite, hematite, lepidocrocite, maghemite, magnetite, massicot, minium, litharge, plattnerite, and zincite were - 5.5, 2.23, 4.65, 18.56, 20.0, 4.84, 7.54, 17.46, 6.66, 9.67, 22.72, - 3.36, 22.9, 3.16, - 18.0, and 1.46. The groundwater showed carcinogenic and non-carcinogenic health hazards for children and adults. The GWQI-model showed that 58.3% of samples revealed worse water quality. PCA revealed rock weathering, mineral dissolution, water-rock interaction, and industrial effluents as the dominant factors influencing groundwater chemistry. Carbonate weathering and ion exchange play vital roles in altering CaHCO3 type to NaHCO3 water. In this study, E. coli, F. coli, P. coli, EC, turbidity, TSS, PO43─, Na+, Mg+2, Ca+2, Cd, Co, Fe, and Pb have exceeded the World Health Organization (WHO) guidelines. The carcinogenic and non-carcinogenic impacts of PTEs and bacterial contamination declared that the groundwater is unfit for drinking and domestic purposes.

Heterozygous De Novo Truncating Mutation of Nucleolin in an ASD Individual Disrupts Its Nucleolar Localization.

Nucleolin (NCL/C23; OMIM: 164035) is a major nucleolar protein that plays a critical role in multiple processes, including ribosome assembly and maturation, chromatin decondensation, and pre-rRNA transcription. Due to its diverse functions, nucleolin has frequently been implicated in pathological processes, including cancer and viral infection. We recently identified a de novo frameshifting indel mutation of NCL, p.Gly664Glufs*70, through whole-exome sequencing of autism spectrum disorder trios. Through the transfection of constructs encoding either a wild-type human nucleolin or a mutant nucleolin with the same C-terminal sequence predicted for the autism proband, and by using co-localization with the nucleophosmin (NPM; B23) protein, we have shown that the nucleolin mutation leads to mislocalization of the NCL protein from the nucleolus to the nucleoplasm. Moreover, a construct with a nonsense mutation at the same residue, p.Gly664*, shows a very similar effect on the location of the NCL protein, thus confirming the presence of a predicted nucleolar location signal in this region of the NCL protein. Real-time fluorescence recovery experiments show significant changes in the kinetics and mobility of mutant NCL protein in the nucleoplasm of HEK293Tcells. Several other studies also report de novoNCL mutations in ASD or neurodevelopmental disorders. The altered mislocalization and dynamics of mutant NCL (p.G664Glufs*70/p.G664*) may have relevance to the etiopathlogy of NCL-related ASD and other neurodevelopmental phenotypes.

Residual effects of frequently available organic amendments on cadmium bioavailability and accumulation in wheat.

Wheat (Triticum aestivum L.) cultivation in cadmium (Cd) polluted soil is a core concern to food quality and food security all over the world. Cadmium toxicity is mainly associated with a Cd influx from contaminated soils to human via grain consumption. Organic amendments are widely used for Cd immobilization and enhancement in plant growth, but the residual effects of these amendments are mostly unknown. The present study addressed the long-term effects of organic amendments in contaminated soils by evaluating their residual effects on 3rd crop (wheat) in the sequence. Initially six organic amendments viz. rice husk biochar (RHB), wheat-straw biochar (WSB), cotton-stick biochar (CSB), poultry manure (PM), press mud (PrMd) and farm manure (FM) were applied once at a rate of 2% in Cd (50 mg kg-1) contaminated soil with wheat-rice rotation. After the harvest of wheat and rice crops, wheat (Var. Galaxy) was again grown in the same pots. Results revealed that plants grown under Cd stress (without any amendment) contain more tissue (root, shoot and grain) and soil AB-DTPA extractable Cd. The soil amended with RHB has shown lowest AB-DTPA extractable Cd (69% lower than control). Similarly, RHB application has significantly reduced wheat root, shoot and grain Cd concentrations compared to control and other amendments. Results have confirmed the effectiveness of RHB residual contents as an active amendment for restriction of Cd in non-bioavailable pool of soil and better growth and yield of wheat.

A Curious Case of Coronary Vasospasm with Cardiogenic Shock: Type 1 Kounis Syndrome Complicated by Eosinophilic Myocarditis.

Kounis syndrome is a rare but life-threatening form of coronary vasospasm, defined by the co-occurrence of acute coronary syndrome and hypersensitivity reaction. We present a case of refractory coronary vasospasm with aborted sudden cardiac arrest secondary to type 1 Kounis syndrome, which was complicated by eosinophilic myocarditis and cardiogenic shock. A 29-year-old Hispanic woman with history of vasospastic angina, presented with recurrent episodes of angina at rest. Initial evaluation revealed hyper-eosinophilia, elevated troponin and diffuse ST segment depression on electrocardiogram (ECG). Suddenly, she developed bradycardia and had a sudden cardiac arrest. An urgent coronary angiogram after resuscitation revealed severe multifocal vasospasm which resolved following high doses of intracoronary vasodilators. Type 1 Kounis syndrome was suspected and she was initiated on intravenous corticosteroids and anti-histamines. Subsequently, she developed cardiogenic shock, and a cardiac magnetic resonance imaging (cMRI) showed diffuse subendocardial late gadolinium enhancement (LGE) suggestive of eosinophilic myocarditis. She was diagnosed with type 1 Kounis syndrome associated with eosinophilic myocarditis. Kounis syndrome should be suspected in patients with refractory vasospastic angina. When indicated, coronary angiography should be performed with administration of intracoronary vasodilators for diagnostic and therapeutic purposes. Although, definite diagnosis of eosinophilic myocarditis requires endomyocardial biopsy, cMRI can be a crucial non-invasive method for establishing the diagnosis.