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Artificial intelligence (AI) development imitates the workings of the human brain to comprehend modern problems. The traditional approaches such as high throughput screening (HTS) and combinatorial chemistry are lengthy and expensive to the pharmaceutical industry as they can only handle a smaller dataset. Deep learning (DL) is a sophisticated AI method that uses a thorough comprehension of particular systems. The pharmaceutical industry is now adopting DL techniques to enhance the research and development process. Multi-oriented algorithms play a crucial role in the processing of QSAR analysis, de novo drug design, ADME evaluation, physicochemical analysis, preclinical development, followed by clinical trial data precision. In this study, we investigated the performance of several algorithms, including deep neural networks (DNN), convolutional neural networks (CNN) and multi-task learning (MTL), with the aim of generating high-quality, interpretable big and diverse databases for drug design and development. Studies have demonstrated that CNN, recurrent neural network and deep belief network are compatible, accurate and effective for the molecular description of pharmacodynamic properties. In Covid-19, existing pharmacological compounds has also been repurposed using DL models. In the absence of the Covid-19 vaccine, remdesivir and oseltamivir have been widely employed to treat severe SARS-CoV-2 infections. In conclusion, the results indicate the potential benefits of employing the DL strategies in the drug discovery process.Communicated by Ramaswamy H. Sarma.

In this work, authors used waste plastic bottle and aluminIum foil further modified with graphene oxide as triboelectric material to construct a triboelectric nanogenerator (TENG). The proposed device is based on a single electrode system. The operating mechanism involves the generation of energy by tapping the surfaces with hand or finger. TENG material provided good response and charge retaining capacity. The device is eco-friendly; provide easiness, and simplicity of process. The substrate material is of inertness nature so can be used in wet conditions as well. The results were conducted by measuring the open-circuit voltage, short circuit current, total charge density, and power density at different frequencies from 1Hz to 3Hz. The TENG generated approximate open-circuit voltage, short-circuit current, charge density, and maximum power density values of 1400 V, 45 µA, 120 nC/m2, and 300 μW/cm2, respectively by finger pressing and releasing. The application was run to charge 2 nF and 10 nF capacitor by TENG and successful results were obtained. This study provides an effective method for developing a cost-effective TENG without the use of complex surface micro-/nano-texturing.

Methemoglobinemia (MetHb, Fe3+) is a chronic disease arising from the unequal distribution of oxyhemoglobin (HbFe2+, OHb) in the blood circulatory system. The oxidation of standard oxyhemoglobin forms methemoglobin, causing cyanosis (skin bluish staining). Methemoglobin cannot bind the pulmonary gaseous ligands such as oxygen (O2) and carbon monoxide (CO). As an oxidizing agent, the biochemical approach (MetHb, Fe3+) is modified in vitro by sodium nitrite (NaNO2). The silver-doped iron zinc oxide (Ag@Fe3O4/ZnO) is hydrothermally synthesized and characterized by analytical and spectroscopic techniques for the electrochemical sensing of methemoglobin via cyclic voltammetry (CV). Detection parameters such as concentration, pH, scan rate, electrochemical active surface area (ECSA), and electrochemical impedance spectroscopy (EIS) are optimized. The linear limit of detection for Ag@Fe3O4/ZnO is 0.17 µM. The stability is determined by 100 cycles of CV and chronoamperometry for 40 h. The serum samples of anemia patients with different hemoglobin levels (Hb) are analyzed using Ag@Fe3O4/ZnO modified biosensor. The sensor's stability, selectivity, and response suggest its use in methemoglobinemia monitoring.

Perinatal depression and anxiety account for a high burden of perinatal morbidity and poor psychosocial functioning. There is a growing interest among mental health professionals, to devise interventions to prevent this condition. This review synthesizes evidence for the effectiveness of psychological and psychosocial interventions aimed at the prevention of perinatal depression and anxiety. We also explore qualitative evidence to understand the acceptability and feasibility of these interventions. Using a mixed-methods approach, data from a total of 21 studies were collated to inform the evidence for preventive interventions for perinatal depression and anxiety. Based on their theoretical orientations, these interventions were described by authors as cognitive-behavioral (n = 7); psychoeducational (n = 6); mindfulness (n = 2); and interpersonal psychotherapy (n = 2). These also included psychosocial approaches such as social support (n = 1) and multicomponent interventions (n = 3). For depressive symptoms, these interventions yielded moderate to strong effect sizes in favor of the intervention group [standardized mean difference (SMD) = −0.59; 95% confidence interval (CI) −0.95 to −0.23]. For anxiety symptoms, a strong effect size was estimated in favor of the intervention group (SMD = −1.43, 95% CI −2.22 to −0.65). Preventive interventions significantly reduce the severity of perinatal depressive and anxiety symptoms. These interventions are also acceptable and feasible in many settings.

Metformin (MET) is an anti-diabetic drug employed as the first-line therapy for patients of type II diabetes mellitus (T2DM). Overdosage of drugs leads to severe outcomes, and its monitoring in biofluids is vital. The present study develops cobalt-doped yttrium iron garnets and employs them as an electroactive material immobilized on a glassy carbon electrode (GCE) for the sensitive and selective detection of metformin via electroanalytical techniques. The fabrication procedure via the sol–gel method is facile and gives a good yield of nanoparticles. They are characterized by FTIR, UV, SEM, EDX, and XRD. Pristine yttrium iron garnet particles are also synthesized for comparison, where the electrochemical behaviors of varying electrodes are analyzed via cyclic voltammetry (CV). The activity of metformin at varying concentrations and pH is investigated via differential pulse voltammetry (DPV), and the sensor generates excellent results for metformin detection. Under optimum conditions and at a working potential of 0.85 V (vs. Ag/AgCl/3.0 M KCl), the linear range and limit of detection (LOD) obtained through the calibration curve are estimated as 0–60 μM and 0.04 μM, respectively. The fabricated sensor is selective for metformin and depicts a blind response toward interfering species. The optimized system is applied to directly measure MET in buffers and serum samples of T2DM patients.

Apo-H is a plasma glycoprotein. Nearly 19% of the molecular weight of this protein is composed of glycans. Up- and down-regulation and structural changes in protein glycans provide diagnostic value for disease detection. Here, an efficient, sensitive, and optimized method is developed for Apo-H N-glycans analysis by MALDI-TOF-MS in positive mode. This bioanalytical method includes sample preparation, sample purification, and detection. An Apo-H enrichment method is developed using standard proteins by anti-Apo-H beads followed by enrichment from plasma samples. SDS-PAGE confirms the Apo-H protein enrichment, which is further verified by LC-MS/MS analysis. The lower ionization efficiency of sialylated glycan hampers their analysis by MALDI-MS. For this, stabilization of sialic acids is done by selective derivatization of carboxyl groups to differentiate between α(2,3)- and α(2,6)-linked sialic acids. Glycans are further purified by HILIC-SPE and analyzed by MALDI-MS. Several branched bi- and tri-antennary glycans with fucosylation and sialylation are identified. The reproducibility of the developed method is tested by analyzing multiple replicates of human plasma, where the same glycans are consistently identified. This method could be applied for the Apo-H glycan profiling of large clinical cohorts for diagnostic purposes.

Background: Mucormycosis is a cause of fulminant necrotizing fungal infection in children with underlying immunocompromising condition. Rhino-orbito-cerebral infection is the most common form of mucormycosis in children with uncontrolled diabetes mellitus or diabetic ketoacidosis. Once considered a rare entity is now increasingly being reported especially in the diabetic population. The initial presentation can mimic a bacterial infection, thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality.Case report: We present a case of rhino-orbito-cerebral mucormycosis in two patients with diabetic ketoacidosis for the first time from Pakistan. Both the patients couldn’t survive due to late and extensive disease on presentation. Keywords: mucormycosis; rhino-orbito-cerebral mucormycosis; diabetic ketoacidosis; diabetes mellitus, pediatric; children

Background Rates of depression among Pakistani mothers are high, leading to poor developmental outcomes in their children. This study tested the effectiveness of a manualized integrated parenting program; Learning through Play Plus (LTP+) for maternal depression in Karachi, Pakistan. Methods A cluster randomized control trial conducted from January 2014 to December 2015 across 120 villages in Karachi. A total of 774 depressed mothers aged 18-44 years with children aged 0-30 months old, were included. Villages were randomized to receive LTP+ added to treatment as usual (TAU) or TAU alone. Primary outcomes were severity of maternal depression at 3 and 6 months measured by the Edinburgh Postnatal Depression Scale and child socio-emotional development at 6 months measured by the Ages and Stages Questionnaire (ASQ). Secondary outcomes included maternal anxiety, quality of life, social support, parenting competence, and knowledge about child development. Results Mothers in the LTP+ group reported significantly lower depression scores compared to those in the TAU group (6.6 vs. 13.8, effect size [ES]: -7.2; 95% confidence interval [CI]: -8.2, -6.1) at 3 and 6 months (7.2 vs. 12.00; ES: -4.6; 95% CI: -5.9, -3.4). Child socio-emotional development at 6 months was significantly better in the LTP+ group on all domains of the ASQ. There were also statistically significant improvements on all secondary outcomes at 3- and 6-month follow-up. Conclusion In low-resource settings like Pakistan, low-cost integrated parenting interventions delivered by lay health workers can provide effective treatment for depressed mothers, leading to improvements in child development.

IMPORTANCE: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. OBJECTIVE: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. DESIGN, SETTING, AND PARTICIPANTS: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. EXPOSURES: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. MAIN OUTCOMES AND MEASURES: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks. RESULTS: Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy. CONCLUSIONS AND RELEVANCE: In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.

In this study, we prepare a biocompatible and magnetic material coated with dopamine (Fe3O4/SiO2@DA) for drug delivery of doxorubicin. Doxorubicin is a commercially available drug for the treatment of several types of cancers such as metastatic breast carcinoma, blood, lungs, ovarian carcinoma, and sarcoma. Magnetic nanoparticles are synthesized by co-precipitation method and coated with dopamine. Characterization of materials is carried out by Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Magnetic properties of the particles are evaluated by magnetic moment measurements. Later, this material is applied to the targeted delivery of doxorubicin. Several experimental parameters such as loading time, release time, loading temperature, release temperature, desorption pH, amount of nanomaterial, salt concentration, and effect of solvent are optimized. Loading of a drug is maximum in basic pH while acidic pH (3.3) works best for the desorption process. With increasing the amount of material, loading of drug increase. Moreover, salt (NaCl) concentration does not affect the loading process. Loading of a drug is maximum at a lower temperature (room temperature) while the release is more efficient at a higher temperature (40–45 °C). This material showed superior efficiency (drug loading, drug release, and time) as compared to previously reported similar materials. These results indicate that Fe3O4/SiO2@DA has excellent potential to carry the drug and deliver to cancerous cells which have acidic pH and higher temperature as compared to normal healthy cells.

Resorcinol belongs to class of phenolic compounds with high medicinal importance due to antiseptic and disinfectant properties. In this research, cadmium–glutathione (Cd–GSH) complex has been synth...

In the present work, nonwoven cotton fabric was modified for antibacterial applications using low-cost and eco-friendly precursors. The treatment of fabric with alkali leads to the formation of active sites for surface modification, followed by dip coating with silver nanoparticles and chitosan. The surface was chlorinated in the next step to transform amide (N–H) groups in chitosan into N-halamine (N-Cl). The modified and unmodified surfaces of the nonwoven cotton fabric have been characterized by FTIR, SEM, and XRD. The active chlorine loading is measured with iodine/sodium thiosulphate. The antimicrobial activity and cell toxicity assay were carried out with and without modifications of nonwoven cotton fabric. The antimicrobial efficacies of loaded fabric were evaluated against four bacterial species (Micrococcus luteus, Staphylococcus aureus, Enterobacter aerogenes, and E.coli). It was found that modified fabric exhibited superior efficiency against gram-positive and gram-negative bacterial strains as compared to their bulk counterparts upon exposure without affecting strength and integrity of fabric. The overall process is economical for commercial purposes. The modified fabric can be used for antimicrobial, health, and food packaging industries, and in other biomedical applications.

Supplemental material, sj-docx-1-jef-10.1177_15589250221091265 for Eco-friendly bio-dyeing of bio-treated nylon fabric using Esfand (P. harmala) based yellow natural colorant by Shahid Adeel, Mahmood ul Hasan, Fatima Batool, Meral Ozomay, Mozhgan Hosseinnezhad, Nimra Amin and Muhammad Hussaan in Journal of Engineered Fibers and Fabrics

Postpartum depression and anxiety are highly prevalent worldwide. Fisher et al., estimated the prevalence of depression and anxiety at 15.6% during the antenatal and 19.8% during the postpartum period. Their impact on maternal and child health is well-recognized among the public health community, accounting for high societal costs. The public health impact of these conditions has highlighted the need to focus on the development and provision of effective prevention and treatment strategies.In recent decades, some advances have been made in the development of effective universal and targeted screening programmes for perinatal depression and anxiety disorders. Recent research has shown potential benefits of universal and targeted screening for perinatal depression, to identify and treat undiagnosed cases, and help thwart its deleterious consequences. Ethical implications, however, for these screening programmes, without the provision of treatment have often been emphasized.The present mixed-methods systematic review and meta-analysis was conducted to collate evidence for screening programmes for perinatal depression and anxiety. It aims to answer the following questions, in a global context: For women in the perinatal period, do screening programmes for perinatal depression and anxiety compared with no screening improve maternal mental health and infant outcomes?A series of meta-analyses reveal a reduction in perinatal depression and anxiety among perinatal women undergoing screening programmes. For the outcome of depressive disorder, meta-analysis indicates a positive impact in favour of the intervention group (OR = 0.55, 95% CI: 0.45 to 0.66, n = 9009), with moderate quality of evidence. A significant improvement (high quality) was also observed in symptoms of anxiety among perinatal women (SMD = − 0.18, 95% CI: − 0.25 to − 0.12, n = 3654).

The surface of matrix-assisted laser desorption/ionization mass spectrometry target is modified for improved signal strength and detection of analytes. The developed method includes on-target enrichment and detection of phosphopeptides/phospholipids using graphene oxide-lanthanide metal oxides (samarium, gadolinium, dysprosium, and erbium) nanocomposites. Enriched phosphopeptides are detected using material enhanced laser desorption/ionization mass spectrometry and phospholipids by laser desorption/ionization-mass spectrometry. Nanocomposites are prepared using graphene oxide with respective metal salts at high pH. They are characterized for nano-morphology, chemistry, porosity, composition, crystallinity, and thermal stability. Phosphopeptides enrichment protocol is developed and optimized for tryptic β-casein digest and that of phospholipids by phosphatidylcholine standard. Statistical analyses of phosphopeptides and phospholipids from milk show overlapping results for gadolinium, dysprosium, and erbium oxide nanocomposites. GO-Gd2 O3 has better enrichment efficiency and application as LDI material. Selectivity for GO-Dy2 O3 is 1:2500, for GO-Sm2 O3 is 1:3500, and 1:4000 for GO-Gd2 O3 . GO-Er2 O3 has a sensitivity of 25 fmol, whereas the highest sensitivity is down to 0.5 fmol for GO-Gd2 O3 . On-target enrichment is batch to batch reproducible with a standard deviation of

An electrochemical sensor based on an antimony/nitrogen-doped porous carbon (Sb/NPC) composite has been developed for the quantitative detection of albumin from hepatocellular carcinoma (HCC) patients. Sb/NPC is hydrothermally synthesized from Sn/NPC precursors. The synthesized precursor (Sn/NPC) and the product (Sb/NPC) are characterized by XRD, FTIR, TGA, UV/Vis, SEM, and AFM. Cyclic voltammetry, chronoamperometry, and electrochemical impedance studies are used to investigate the electrochemical performance of Sb/NPC-GCE. Sb/NPC-GCE detects albumin at physiological pH of 7.4 in the potential range 0.92 V and 0.09 V for oxidation and reduction, respectively. LOD and recovery of Sb/NPC-GCE for the determination of albumin are 0.13 ng.mL−1 and 66.6 ± 0.97–100 ± 2.73%, respectively. Chronoamperometry of the modified working electrode demonstrates its stability for 14 h, indicating its reusability and reproducibility. Sb/NPC-GCE is a selective sensor for albumin detection in the presence of interfering species. The electrode has been applied for albumin detection in human serum samples of HCC patients. A negative correlation of albumin with alpha-fetoprotein levels in HCC patients is observed by statistical analysis.

A three-step strategy is introduced to develop inherent iminodiaceticacid IDA functionalized nanopolymer. SEM micrographs show homogenous spherical beads with particle size of 500 nm. Further modification to COOH-functionalized 1,2-epoxy-5-hexene/DVB mesoporous nanopolymer enriches glycopeptides via hydrophilic interactions followed by their MS determination. Significantly high BET surface area 433.4336 m(2) g(−1) contributes to the improved surface hydrophilicity which is also shown by high concentration of ionizable carboxylic acids, 14.59 ± 0.25 mmol g(−1). Measured surface area is the highest among DVB based polymers and in general much higher in comparison to the previously reported BET surface areas of co-polymers, terpolymers, MOFs and graphene-based composites. Thirty-one, 19, and 16 N-glycopeptides are enriched/identified by nanopolymer beads from tryptic digests of immunoglobulin G, horseradish peroxidase and chicken avidin respectively without additional desalting steps. Material exhibits high selectivity (1:400 IgG: BSA), sensitivity (down to 0.1 fmol), regeneration ability up to three cycles and batch to batch reproducibility (RSD > 1%). Furthermore, from 1μL of digested human serum, 343 N-glycopeptides characteristics of 134 glycoproteins including 30 FDA approved serum biomarkers are identified via Nano-LC-MS/MS. The developed strategy to self-generate IDA on polymeric surface with improved surface area, porosity and ordered morphology is insignia of its potential as chromatographic tool contributing to future developments in large scale bio-medical glycoproteomics studies.

Nonwoven cotton fabric has been fabricated and designed for antibacterial applications using low cost and ecofriendly precursors. The treatment of fabric with alkali leads to formation of active sites. The surfaces were dip coated with silver nanaoparticles and chitosan. The surface was chlorinated in next step to transform amide (N-H) groups in chitosan into N-halamine (N-Cl). The modified and unmodified surfaces of the nonwoven cotton fabric have been characterized by FTIR, SEM, and XRD. The active chlorine loading is measured with iodine/ sodium thiosulphate. The antimicrobial activity and cell toxicity assay were carried out with and without modifications of nonwoven cotton fabric. The antimicrobial efficacies of loaded fabric were evaluated against four bacterial species (Micrococcus lutes, Staphylococcus aurea, Enterobacter aerogenes, and E.coli). It was found that modified fabric exhibited superior efficiency against gram-positive and gram-negative bacterial strains as compared to their bulk counterparts upon exposure without destroying and affecting fabric nature. The overall process is economical for commercial purposes. The modified fabric can be used for antimicrobial, health, and food packaging industries, and in other biomedical applications.

Creatinine is an indicator of hindrance in urination and renal insufficiency. Creatinine levels are the marker of the late stages of prostate cancer. Early and sensitive detection of creatinine can reduce deaths associated with prostate cancer. In this work, nitrogen-doped porous carbon antimony (Sb/NPC) nanoparticles are fabricated to be employed as a non-enzymatic biosensor. Sb/NPC has promising redox activity and is synthesized by a two-step reaction using low-cost precursors. Electrochemical sensing by Sb/NPC is conducted for standard creatinine solutions on a three-electrodes system. Cyclic voltammetry, amperometry, and electrochemical impedance spectroscopy are used to sense creatinine. LOD and LOQ of the Sb/NPC modified electrode are 0.74 µM and 2.4 µM, respectively. This electrode system analyzes creatinine in the serum of prostate cancer patients who have elevated PSA levels. More than 90% creatinine is recovered from a spiked serum sample of a prostate cancer patient. A direct relation is observed between PSA levels and creatinine levels in prostate cancer. The developed cyclic voltammetric setup detects trace concentrations of creatinine in serum.

Asthma is projected to be the third cause of death in all communities without age, gender, or race limits, along with Chronic Obstructive Pulmonary Disease (COPD). Patients treated with inhaled corticosteroids, intramuscular triamcinolone, omalizumab, mepolizumab, and dupilumab can live normal lives. Bronchiectasis is a chronic airway condition of epithelial and cartilage damage characterized by irritation, inflammation, sputum expectoration and dilatation of airway walls. Macrolides are medicines composed of twelve or more elements with a macrocyclic lactone ring. Because of their excellent tissue penetration and efficacy against respiratory pathogens, macrolides are the first-line drugs for respiratory infections. Bronchitis causes bronchial swelling and infection of bronchium. Bronchi walls bloat with extra sticky mucus. In- and out- lung circulation is partially blocked. Oral azole antifungal treatment is used for all types of aspergillosis, including allergic bronchopulmonary aspergillosis (ABPA). After myocardial infarction and stroke, pulmonary embolism (PE) is the third most common cause of death in the cardiovascular system. Inorganic nitrite decreases the matrix metalloproteinase-9 in acute PE. During acute PE, L-arginine, and NO donor diethylenetriamine/nonoate are inactive. As an inhaled medicine, ethyl nitrite can induce methemoglobin formation. Shortness of breath at rest, degenerate tachycardia with force, relative hypoxemia, and tachypnea are all symptoms of PE. Peribronchial cuffing (cardiac asthma) may induce wheezing. The treatment for cardiogenic PE has been intravenous morphine. In patients with hypertension and PE, angiogensin translating enzyme inhibitors should lower preload and afterload. Nesiritide raises CO levels while lowering vascular resistance and PCP levels.

The ineffectiveness of drugs against certain disease is termed as drug resistance. Drug resistance is a common phenomenon and a primary concern for health care professionals. Resistance to any particular drug(s) leads to the development of new therapies and vaccines. Drug resistance also exists in all types of reproductive system infections including bacterial infections, viral infections, and fungal infections. Bacterial resistance is found in Gonorrhea, Chlamydia, Syphilis, Chancroid, and Prostatitis. Viral resistance is associated with Genital herpes, Genital warts, and AIDS. Two main types of fungal infections (Candidiasis and Trichomoniasis) are also prone to drug resistance. The drug resistance ability of pathogens is different in regions, environments, and populations. Some pathogens are multi-drug resistant which cause problems in treatment. Each pathogen has its mechanism of action but most of these resistances are associated with genetic mutations caused during the interaction of drugs with targets. In this chapter, the effect of drug resistance on reproductive system diseases is discussed. Various aspects of resistance, possible alternatives, and future directions related to drug resistance are evaluated.

Cancer drug resistance is one of the obstacles in cancer treatment thus leading cause of death in cancer. Drug resistance in cancer means the evolution of tumor cells against therapeutic strategies. In each kind of resistance, every time there is a different pattern of resistivity. Two basic modes of resistance are found in the neoplastic cells that can be inherent or acquired. A large number of factors are influencing these two modes including mutations, efflux and influx variations, tumor cell heterogeneity, microenvironment of the cancer stem cells, microRNAs, long non-coding regions of RNAs, apoptotic failure, and many others. Evolution in tumor cells may be a result of increased ability of DNA repair, alteration in target molecules, involvement of kinase inhibitor, or topoisomerase inhibitors inactivity. It is the need of the hour to utilize other fields of science to avoid cancer drug resistance. Advanced knowledge of bioinformatics, genomics, proteomics, and nanotechnology is the way forward. Drugs with increased efficacy, decreased efflux pumps,high specificity, and targeted effects are required to be developed. Nanocarriers can play a role to avoid cancer drug resistance. Nano dosage of cancer drugs can prove more specific, lesstoxic, and can increase therapeutic effects.

The precise detection of hazardous 2,4,6-Trinitrophenol (TNP) is essential for the environment and human health. TNP is used as a precursor in whistling fireworks in ammunition, mining, agriculture and is a hazardous environmental pollutant generated from leather, chemical, and dye industries. Exploring rapid and low-cost approaches for the detection and quantification of TNP has attracted many scientists nowadays. The proposed chemosensor utilizes the concept of dispersive liquid-liquid micro-extraction coupled with a UV-visible spectrophotometer for its sensing at the ultra-trace level. Significant changes based on intramolecular interactions followed by a distinct color change to orange-red from yellow in the presence of TNP is an attractive feature for the present study. The successive addition of TNP shows ultra-trace sensitivity (3.9831 μA μM

The preservation of water and wastewater treatment has become a global challenge. The concentration of anions such as chlorides, fluorides, cyanides, and perchlorates above the permitted levels in water is harmful to human and aquatic life. Chlorfenapyr is an insecticide that contains the aforesaid anions and is abundantly present in industrial wastewater. This research is focused on the removal of these anions from wastewater by ethylene glycol functionalized benzyl dimethyl tetradecyl ammonium bromide immobilized on soluble polymer anion exchange membrane. The real wastewater samples rich in chlorfenapyr from two different sources (industrial and pond) were analyzed. Membrane efficiency was more than 50 ppm for each anion in a single fold. The double folds of membrane showed enhanced uptake and separation efficiency for chloride, fluoride, and cyanide from wastewater samples between 0.01 and 0.02 ppm down to lethal concenetrations values (LD 50). The membrane shows maximum separation efficiency between the pH ranges of 6–7. The interference effect on membrane separation efficiency showed that the replacement ability of sample anions was in the order of fluoride > chloride > perchlorate > cyanide. This high replacement efficiency of fluoride and chloride is attributed to the more chemical interactions of these anions with membrane.

A hydrophilic terpolymer MOF composite is designed with high surface area and porosity to enrich mono- and multi-glycosylated peptides facilitating a bottom-up approach. Terpolymer@ZIF-8 is synthesized using free radical polymerization followed by layer by layer ZIF-8 fabrication. Subsequent surface modification was made by aminophenylboronic acid (AMBA). The enrichment ability of terpolymer@ZIF-8@BA is evaluated by using tryptic digest of IgG and HRP to exemplify mono- and multi-glycosylated protein samples. Improved selectivity of 1:200 for spiked HRP in BSA digest and sensitivity down to 1 fmol μL−1 is achieved. Batch to batch reproducibility is better 1% RSD which favors the adoption of the developed method for routine N-linked glycopeptide/protein determination. Cost-effective nature of given approach is given by regeneration of the material up to four cycles. Total 318 N-linked glycopeptides have been identified from 1 μL human serum digest after subjecting the enriched and PNGase-treated deglycosylated peptides to LC-MS. Thus, terpolymer@ZIF-8@BA holds the potential both for mono- and multi-glycosylated peptides from complex biological sample.

A selective and cost-effective biosensor based on catalase immobilized antimonene quantum dots modified glassy carbon electrode (Cat@AMQDs-GCE) is designed for the first time to determine hydrogen peroxide (H

The study evaluates chemistry curriculum at the secondary level. Chemistry is the science subject which help in technological advancement. It deals with the study of composition, structure, properties, and different changes which take place in matter. There are different careers in chemistry such as in food processing, industries, health etc. The progress of any country depends on the achievement in the field of chemistry. The successes of these reforms are associated with chemistry curriculum. Therefore, this study re-examines the objectives of National Chemistry Curriculum 2006 and identifies the nature of implementation of chemistry curriculum. Questionnaire based data from 138 chemistry teachers (male and female) teaching at secondary level in District Haripur determined that modern teaching techniques are required in teaching chemistry. So, it is recommended to improve curriculum at regular intervals according to global standards.

Individuals having high interpersonal sensitivity are sensitive to relationships and self-deficits in comparison to others. Studies report that high interpersonal sensitivity can cause low self-esteem and feelings of insecurity. The objective of the study was to assess the interpersonal sensitivity in people with an at-risk mental state (ARMS) for psychosis compared to the individuals not at risk. A total sample of 50 individuals aged 18 to 35 years was recruited from Bahria University, Karwan- e-Hayat and Karachi Psychiatric Hospital: 25 with ARMS and 25 participants who were not ARMS, according to scores on Schizophrenia Proneness Inventory-Adult (SPI-A). All of the participants then responded to self-report questionnaire on Interpersonal Sensitivity Measure. Results showed a significant difference (p< .001), between both the groups where individuals screened positive for ARMS reported higher sensitivity to interpersonal relations compared to those who were not at risk. The findings of the present study indicate that increased sensitivity to social interactions is a manifestation of the potentially early phase of psychosis. Early intervention to those identified as sensitive to interpersonal relations can help avert serious disorders.

Hemoglobin is an important part of the biological system that is involved in the transportation of oxygen and carbon dioxide. Abnormal level of hemoglobin is associated with different diseases such as β-thalassemia and anemia. An electrochemical sensor based on graphene oxide-tellurium nanowires (TeNWs/GO) is developed for the first time for electrochemical sensing of hemoglobin (Hb). Sensing parameters such as concentration, pH, scan rate, and effect of interferences are optimized. Linearity, detection, and quantification limits for TeNWs/GO-GCE are 0.996, 0.29 μM, and 0.967 μM respectively. Stability is measured by cyclic voltammetry (100 cycles) and chronoamperometry (15 h). TeNWs/GO-GCE quantitatively determines hemoglobin from blood samples of β-thalassemia major patients. To evaluate the relationship between RBC’s count and hemoglobin β-thalassemia major patients with the level of HbA, HbA2, and HbF statistical analysis is carried out. Shapiro-Wilk analysis shows a non-normal distribution and the results are calculated by Spearman correlation analysis. The results show that thalassemia patients have low levels of hemoglobin due to mutations in globin chains of hemoglobin.

Maternal depression is a major public health problem. This may affect a mother's ability to provide adequate care for the child. The objective of this study was to evaluate the effectiveness of the Learning through Play Plus program (LTP Plus) - a parenting program integrated with Cognitive Behaviour Therapy (CBT).A total of 247 women with symptoms of depression in Karachi, Pakistan were assigned randomly to either LTP Plus or routine care (Clinical Trials Identifier: NCT00835016). Symptoms of maternal depression were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 3 and 6 months after baseline.At 3 months, there was a significant reduction in the EPDS scores in the intervention group compared to the routine group (adjusted mean difference [AMD] -3.65, 95% CI -6.14 to -1.15, p0.004). This effect was sustained at 6 months (AMD -2.62, 95% CI -4.43 to -0.81, p0.005). These women also reported less parental distress and disability. There was also a significant improvement in maternal knowledge about child development at 6 months.There was a significant reduction in depression among women who received the group parenting program LTP Plus. This intervention has the potential to be scaled up and integrated with mother and child health programs.

The issue of affordable housing in Karachi has been a concern as two third of Karachi population is considered poor. These low incomes earning people of Karachi have been striving hard for shelter for a long time but unable to do so because of their low disposable income. They have been caught in a dilemma between spending on high rentals or on other necessities such as education, nutrition etc. since many decades. As a result, they are forced to live in illegal settlements or slums where they are compelled to compromise on their social/ethical values and better upbringing of their children. It is estimated that around eighty thousand homes are required each year in Karachi and because of constantly increasing fiscal and budgetary deficits, Pakistan government is unable to cater to this demand. The purpose of this study is to offer a solution to fill up this wide gap between demand and supply situation of housing units in Karachi through creating a synergy between housing cooperative and waqf. Moreover, this paper attempts to identify two innovative waqf based financing tools to overcome the problem of lack of initial funding for the development of housing cooperatives.

High-density lipoproteins (HDLs) have anti-inflammatory and antioxidant properties and are potentially cardio-protective. Defective HDL function is caused by alterations in both the proteome and lipidome of HDL particles. As potential biomarkers, the development of analytical methods is necessary for the enrichment of HDLs. Therefore, a method for selective enrichment of HDLs using immobilized metal ion affinity chromatography (IMAC) and metal oxide affinity chromatography (MOAC) is presented. SPE-based isolation of HDLs from whole serum is adopted as an alternative to traditional ultracentrifugation methods followed by SDS-PAGE. The enrichment mechanism relies on isoelectric points of lipoproteins and metal oxide. Negatively charged lipoprotein particles interact with positively charged metal oxides and IMAC affinity, which acts as a cation. Identified proteins from HDL through MALDI-MS analysis are apo AI, AII, AIV, CI, CIII, E, J, M, H, serum amyloid A and other nonapoproteins that are part of HDL particles and perform cellular functions. This serum-based proteomics approach gives insight into the functional role of HDL. HDL-associated phospholipids have also been analyzed by LDI-MS. Results suggest that the adopted analytical strategy is a feasible idea to extract lipoproteins from serum. A comparative study of healthy and diseased samples using this approach will provide valuable information in future.

An anion exchange solid-phase sorbent is described. Chitosan coated magnetite nanoparticles were modified with polyethylenimine which is positively charged at pH 3 and therefore can be used for the magnet-supported enrichment of phosphopeptides which are negatively charged at this pH value. A 2-step strategy was used to synthesize the sorbent. The materials were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry and magnetic moment analysis. The anion exchanger was applied to extract phosphopeptides from a β-casein digest. Characteristic analytical figures include (a) a loading buffer of pH 3, (b) and elution buffer of pH 11, (c) a loading time of 5 min, (d) good selectivity (the β-casein to BSA ratio is 1:1000), and (e) excellent sensitivity (1 fmol). The optimized method was applied to egg yolk digest, non-fat milk digest, and diluted human serum. Graphical abstractSchematic representation of synthesis of PEI@chitosan@Fe

An agglomerative hierarchical clustering (AHC) framework and algorithm named HOSil based on a new linkage metric optimized by the average silhouette width (ASW) index is proposed. A conscientious investigation of various clustering methods and estimation indices is conducted across a diverse verities of data structures for three aims: a) clustering quality, b) clustering recovery, and c) estimation of number of clusters. HOSil has shown better clustering quality for a range of artificial and real world data structures as compared to k-means, PAM, single, complete, average, Ward, McQuitty, spectral, model-based, and several estimation methods. It can identify clusters of various shapes including spherical, elongated, relatively small sized clusters, clusters coming from different distributions including uniform, t, gamma and others. HOSil has shown good recovery for correct determination of the number of clusters. For some data structures only HOSil was able to identify the correct number of clusters., Comment: 43 pages, several figures

Genus Streptomyces has been a source of various clinically significant bioactive metabolites. Taxonomically, Streptomyces formicae KY5 is a new and different species. The complete genome sequences of S. formicae KY5 is available in the public DNA sequence databases for different analysis. The accessibility of the genomic sequence presents an excellent opportunity to explore the secondary metabolites potential of this distinct Streptomyces species. In this study, we employed the advance bioinformatics resources to annotate the total genome sequence of S. formicae KY5. Bioinformatics tools are applied to locate all the secondary metabolites hiding beneath their biosynthetic gene clusters (BGCs). The S. formicae KY5 is found to synthesis distinct and various secondary metabolites by undergoing the designated genomic encoding. Predictive analysis conveys that this strain has 34 gene clusters to encode potential secondary metabolites. For structural similarity with other drugs, we scanned the drug bank database, drug target and drug with the highest similarity was retrieved from PDB for molecular docking. Molecular docking analysis was carried out through molecular operating tool to evaluate drug-like potential of the chemical compounds. Three drugs like compounds were predicted from S.

A selective and cost-effective biosensor based on catalase immobilized antimonene quantum dots modified glassy carbon electrode (Cat@AMQDs-GCE) is designed for the first time to determine hydrogen peroxide (H2O2). Antimonene quantum dots (AMQDs) are synthesized by a single step method, characterized by various analytical techniques and applied to the electrochemical sensing of hydrogen peroxide. Catalase enzyme specific for H2O2 reduction is immobilized onto AMQDs to facilitate its detection by cyclic voltammetry and amperometry. Concentration, scan rate, pH, stability and selectivity are optimized. Linearity of Cat@AMQDs-GCE is determined as 0.989 with limit of detection as 4.4 μM. Amperometric measurements show recovery of 95 to 103.4% for H2O2 from human serum samples. Cat@AMQDs-GCE is electrochemically stable up to 30 cycles, reducing the cost of analysis. Cat@AMQDs-GCE shows good selectivity in presence of ascorbic acid, dopamine, leucine and glucose. Prepared electrode is also applied for the quantitative determination of H2O2 from ovarian cancer serum. CA 125 concentration is previously determined by Elecsys CA 125 II Assay. Results demonstrate that concentration of H2O2 increases with increasing levels of CA125 in serum.