A Missense Pathogenic Variant in a Conserved Region of CNTNAP2 Is Associated with Obesity, Seizures, and Language Impairment in a Pakistani Family.

Introduction: In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood. Methods: By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T>A [p.Ile1124Asn]) in exon 20 of the CNTNAP2 gene was identified. Results: The pathogenic variant in this family is located within one of the laminin G-like 4 domains of CASPR2 and may cause loss of hydrophobic interactions of CASPR2 with its partner proteins. Single nucleotide and copy number variants in this gene have previously been related to Gilles de la Tourette syndrome, cortical dysplasia-focal epilepsy syndrome, schizophrenia, Pitt-Hopkins syndrome, and autism spectrum, attention deficit hyperactivity, and obsessive compulsive disorders. Yet, few studies described patients with CNTNAP2 variants showing diet-induced obesity. Conclusion: This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by documenting the clinical features and genetic findings of the patients.

Application of Machine Learning Techniques for Predicting Compressive, Splitting Tensile, and Flexural Strengths of Concrete with Metakaolin.

The mechanical properties of concrete are the important parameters in a design code. The amount of laboratory trial batches and experiments required to produce useful design data can be decreased by using robust prediction models for the mechanical properties of concrete, which can save time and money. Portland cement is frequently substituted with metakaolin (MK) because of its technical and environmental advantages. In this study, three mechanical properties of concrete with MK, i.e., compressive strength (f'c), splitting tensile strength (fst), and flexural strength (FS) were modelled by using four machine learning (ML) techniques: gene expression programming (GEP), artificial neural network (ANN), M5P model tree algorithm, and random forest (RF). For this purpose, a comprehensive database containing detail of concrete mixture proportions and values of f'c, fst, and FS at different ages was gathered from peer-reviewed published documents. Various statistical metrics were used to compare the predictive and generalization capability of the ML techniques. The comparative study of ML techniques revealed that RF has better predictive and generalization capability as compared with GEP, ANN, and M5P model tree algorithm. Moreover, the sensitivity and parametric analysis (PA) was carried out. The PA showed that the most suitable proportions of MK as partial cement replacement were 10% for FS and 15% for both f'c and fst.

Monotheca buxifolia Driven Synthesis of Zinc Oxide Nano Material Its Characterization and Biomedical Applications.

The current study demonstrates a sophisticated and environmentally friendly synthesis of zinc oxide nanoparticles (ZnO-NPs) for a range of biological and environmental applications using Monotheca buxifolia as a bio-source. At the nanometer scale, a simple aqueous extract from Monotheca buxifolia was used to convert Zn into stable elemental zinc (Zn0). With an average size of 45.8 nm and a spherical shape, the NPs were stable and pure. The nanoparticles studied here were tested in vitro for bactericide, fungicide, biocompatibility, leishmaniasis, anti-diabetic effect, antioxidant effect, and anti-Alzheimer's effect. According to our results, Monotheca buxifolia mediated ZnO-NPs are highly effective against spore-forming fungal strains and MDR bacterial strains. All examined bacterial isolates of UTI (urinary tract infection) were resistant to non-coated antibiotics; however, adding 1% of the produced ZnO-NPs to the treatments increased their bactericidal activity significantly. The NPs also showed dose-dependent cytotoxicity against Leishmania tropica parasites, with an LC50 of 248 µg/mL for promastigote parasites and 251 µg/mL for amastigote parasites. In addition, a significant inhibition of α-glucosidase, α-amylase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) was discovered, indicating anti-Alzheimer's and anti-diabetic effects. The biocompatibility of the particles with human red blood cells was also observed. Due to their environmentally friendly production, biological safety, and exceptional physicochemical properties, ZnO-NPs could be used as a new competitor for several biological and environmental applications.

In vitro examination of anti-parasitic, anti-Alzheimer, insecticidal and cytotoxic potential of Ajuga bracteosa Wallich leaves extracts.

This research study is mainly focused to evaluate the anti-parasitic, insecticidal, cytotoxic and anti-alzheimer potential of various leaf extracts of Ajuga bracteosa Wallich ex Bentham. 04 different extracts were prepared using solvent of different polarity to determine the best candidate for potent bioactivity i.e. n-hexane (NH), Ethyl acetate (EA), Ethanol (EL) and Chloroform (CH). Concentrations of each extracts were made specified for all activities. All extracts were exploited for broad range of biomedical applications including leishmaniasis, in vitro anti-Alzheimer, insecticidal and cytotoxic studies. Our results showed that A. bracteosa n-hexane extract was highly active against Leishmania Tropica with significant inhibition of 58 ± 1.61 for promastigote and 63 ± 2.29 for amastigote at 1000 µg/mL. Furthermore, promising anti-alzheimer activity acetylcholinesterase (AChE) 46 ± 0.83 and butrylcholineterase (BChE) 49 ± 1.17 was noted for n-hexane. The insecticidal potential of these extracts were test against five different insects (Rhyzopertha dominica, Trogoderma granarium, Tribolium castaneum, Sitophilus oryze, and Callosobruchus analis). The higest mortality rate of insecticidal activity was recorded by n-hexane followed by Ethyl acetate whereas ethanol extract was found to be less effective against all the test species. Significant cytotoxic potential of each plant sample against Artemia salina thus aware us for further detailed research to find out novel drugs. Based on our results we believe that Ajuga bracteosa could be used to develop as a potential botanical insecticide against different insect and pests, such as aphids as well as an excellent source for the compound isolation as anti-tumor agent.

Green Synthesis of Zinc Oxide (ZnO) Nanoparticles Using Aqueous Fruit Extracts of Myristica fragrans: Their Characterizations and Biological and Environmental Applications.

In the present work, bioaugmented zinc oxide nanoparticles (ZnO-NPs) were prepared from aqueous fruit extracts of Myristica fragrans. The ZnO-NPs were characterized by different techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and thermogravimetric analysis (TGA). The crystallites exhibited a mean size of 41.23 nm measured via XRD and were highly pure, while SEM and TEM analyses of synthesized NPs confirmed their spherical or elliptical shape. The functional groups responsible for stabilizing and capping of ZnO-NPs were confirmed using FTIR analysis. The ζ-size and ζ-potential of synthesized ZnO-NPs were reported as 66 nm and -22.1 mV, respectively, via the DLS technique can be considered as moderate stable colloidal solution. Synthesized NPs were used to evaluate for their possible antibacterial, antidiabetic, antioxidant, antiparasitic, and larvicidal properties. The NPs were found to be highly active against bacterial strains both coated with antibiotics and alone. Klebsiella pneumoniae was found to be the most sensitive strain against NPs (27 ± 1.73) and against NPs coated with imipinem (26 ± 1.5). ZnO-NPs displayed outstanding inhibitory potential against enzymes protein kinase (12.23 ± 0.42), α-amylase (73.23 ± 0.42), and α-glucosidase (65.21 ± 0.49). Overall, the synthesized NPs have shown significant larvicidal activity (77.3 ± 1.8) against Aedes aegypti, the mosquitoes involved in the transmission of dengue fever. Similarly, tremendous leishmanicidal activity was also observed against both the promastigote (71.50 ± 0.70) and amastigote (61.41 ± 0.71) forms of the parasite. The biosynthesized NPs were found to be excellent antioxidant and biocompatible nanomaterials. Biosynthesized ZnO-NPs were also used as photocatalytic agents, resulting in 88% degradation of methylene blue dye in 140 min. Owing to their eco-friendly synthesis, nontoxicity, and biocompatible nature, ZnO-NPs synthesized from M. fragrans can be exploited as potential candidates for biomedical and environmental applications.

Edible mushroom (Flammulina velutipes) as biosource for silver nanoparticles: from synthesis to diverse biomedical and environmental applications.

The current study reports advanced, ecofriendly and biosynthesized silver NPs for diverse biomedical and environmental applications using Flammulina velutipes as biosource. In the study, a simple aqueous extract of F. velutipes was utilized to reduce the AgNO3 into stable elemental silver (Ag0) at a nanometric scale. The NPs had average size of 21.4 nm, spherical morphology, and were highly stable and pure. The characterized nanoparticles were exploited for a broad range of biomedical applications including bacteriocidal, fungicidal, leishmanicidal, in vitro antialzheimer's, antioxidant, anti-diabetic and biocompatibility studies. Our findings showed that F. velutipes mediated AgNPs exhibited high activity against MDR bacterial strains and spore forming fungal strains. All the tested urinary tract infection bacterial isolates, were resistant to non-coated antibiotics but by applying 1% of the synthesized AgNPs, the bactericidal potential of the tested antibiotics enhanced manifolds. The NPs also exhibited dose-dependent cytotoxic potential against Leishmania tropica with significant LC50 of 248 µg ml-1 for promastigote and 251 µg ml-1 for amastigote forms of the parasite. Furthermore, promising antialzheimer and antidiabetic activities were observed as significant inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE) and butrylcholineterase (BChE) were noted. Moreover, remarkable biocompatible nature of the particles was found against human red blood cells. The biosynthesized AgNPs as photocatalyst, also resulted in 98.2% degradation of indigo carmine dye within 140 min. Owing to ecofriendly synthesis, biosafe nature and excellent physicochemical properties F. velutipes AgNPs can be exploited as novel candidates for multifaceted biomedical and environmental applications.

In Vitro Biomedical and Photo-Catalytic Application of Bio-Inspired Zingiber officinale Mediated Silver Nanoparticles.

To minimize the hazardous effect of physical and chemical synthesis of nanoparticles we focused on the green synthesis of nanoparticles. Nanotechnology is a research hotspot and catch great attention because of its versatile applications in medical, biosciences and engineering fields. Purpose of our recent study is to synthesize bio-inspired metallic silver NPs by root mediated Zingiber officianale extract. The synthesized Ag-NPs were further characterized by using UVVisible spectroscopy, XRD, EDX, SEM, TEM and DLS techniques. The extent of crystallites were confirmed by X-ray diffraction. SEM and TEM revealed the morphological features with size of nanoparticles between 17.3 and 41.2 nm. FTIR analysis confirmed the capping of nanoparticles by bio active constituents present in Zingiber officinale extract. Later EDX confirmed the elemental composition of nanoparticles. Zeta potential, PDI and hydrodynamic size of Ag-NPs were confirmed by DLS. The synthesize Ag-NPs possess eminent biological potency against bacterial and leishmanial strains. Moreover considerable anti-diabetic, anticancer, antioxidant and biocompatibility nature of Ag-NPs was elucidated. The highest antioxidant activity of 50.61± 1.12%, 38.22 ± 1.18% and 27.39 ± 0.92 at 200 g/mL for TAC, TRP DPPH and was observed respectively. Ag-NPs exhibit potent leishmanicidal activity of 80% ± 1.4 against promastigotes and 77% ± 1.6 against amastigotes cultures of L. tropica. Highest antidiabetic activity 30 ± 0.77% recorded at 200 µg/ml. Highest Brine shrimps cytotoxicity of Ag-NPs was 60 ± 1.18 at 200 g/ml. Maximum dye degradation for Ag-NPs was recorded as 94.1% at 140 minute. All UTI isolates were resistant to antibiotics not coated with Ag-NPs. By applying 1% of Ag-NPs highest activity was recorded as 25 ± 1.58 mm against K. pneumoniae. Maximum zone of inhibition for Ag-NPs coated with Imipenem antibiotics 26 ± 1.5 mm against K. pneumoniae and coated with Ciprofloxacin 26 ± 1.4 m against S. aureus were measured. Last but not least high biocompatible nature of Ag-NPs was observed against fresh RBCs making the ecofriendly biosynthesized silver NPs a multi-dimensional candidate in biomedical field.

COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus.

An epidemic of extreme respiratory deterrence, pneumonia and shortness of breath, the SARS-CoV-2 viral infection began in Wuhan, Hubei Province, China in December 2019, and rapidly spread across China and beyond, with human to human transmission. On February 12, 2020, World Health Organization officially named the new coronavirus disease as coronavirus disease 19 (COVID-19). Most COVID-19 patients were diagnosed with pneumonia and many were treated using Chinese medicines and other secondary therapies. As of April 22, 2020, the total figure of infected patients has crossed 2.6 million people worldwide with over 180,000 deaths and 700,000 patients that have recovered. Preliminary reports suggest that certain drugs, such as chloroquine and antiviral nucleotide analogues such as remdesivir, which inhibit viral replication, can target the new coronavirus, although their usefulness in the clinic is still under debate. An expert US committee developed the US NIH guidelines for COVID-19 treatment, which was just released and will be regularly updated. This manuscript reviews the epidemiology, etiology, mortality, COVID-19 clinical symptoms, and potential therapeutic drugs, while highlighting the seriousness and damage-induced by SARS-CoV-2.

The study of gene GJB2/DFNB1 causing deafness in humans by linkage analysis from district Peshawar.

Families with at least 2 or more individuals having hereditary hearing loss were enrolled from different areas of Khyber Pakhtoonkhwa, mainly from district Peshawar. Detailed history was taken from each family to minimize the presence of other abnormalities and environmental causes for deafness. Families were questioned about skin pigmentation, hair pigmentation, and problems relating to balance, vision, night blindness, thyroid, kidneys, heart, and infectious diseases like meningitis, antibiotic usage, injury, and typhoid. The pedigree structures were based upon interviews with multiple family members, and pedigrees of the enrolled families were drawn using Cyrillic program (version 2.1). All families showed recessive mode of inheritance. I studied 8 families of these 10. For linkage analyses, studies for DFNB1 locus, 3 STR markers (D13S175, D13S292, and D13S787) were genotyped using polyacrylamide gel electrophoresis (PAGE) and haplotypes were constructed to determined, linkage with DFNB1 locus. From a total of 8 families, a single family-10 showed linkage to DFNB1 locus.

Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis.

The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR) families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1). The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1)/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024) in vicinity of mental retardation (MR) locus (MRT1)/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.

Endotracheal spindle cell lipoma presenting as a chronic cough.

An elderly gentleman with a chronic cough was found to have a large midtracheal lesion on computed tomography scan. Endotracheal extirpation with an electrocautery snare successfully removed the lesion. Histologic and immunohistochemical analyses revealed the lesion to be a spindle cell lipoma. We provide herein the case presentation and management, the differential diagnosis, and an overview of spindle cell lipoma.