Urdu translation and validation of the international consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS).

INTRODUCTION AND HYPOTHESIS: The International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) is a tool for the evaluation of lower urinary tract symptoms and their impact on the quality of life. The purpose of this research was the translation of ICIQ-FLUTS into the Urdu language and to determine its validity and reliability. METHODS: Two bilingual translators translated the ICIQ-FLUTS Questionnaire into the Urdu language. Three experts compared the Urdu ICIQ-FLUTS with the original version of ICIQ-FLUTS. Urdu version was translated back into English by two translators. The pre-final version was drafted after tracking the forward and backward translation differences. The final Urdu version was drafted after application to ten patients (pilot study). Final Urdu ICIQ-FLUTS was applied to 120 participants for validity and reliability. RESULTS: Urdu version was drafted after the consensus of the experts. The content validity index ranged between 0.81-0.93. The mean age of the participants was 45.2 ± 7.79 years. The test-retest reliability was analyzed through intraclass correlation coefficient (ICC) 0.972 and internal consistency by Cronbach's alpha 0.986. The concurrent validity was determined by correlating the ICIQ-FLUTS with ICIQ-UI SF (0.82) and UDI-6 (0.72). CONCLUSION: It was concluded that the Urdu version of ICIQ-FLUTS is an assessment questionnaire for the signs and symptoms of urinary incontinence. It has good content validity, concurrent validity, and test-retest reliability.

Rising surface temperatures lead to more frequent and longer burrow retreats in males of the fiddler crab, Minuca pugnax.

The fiddler crab Minuca pugnax occupies thermally unstable mudflat habitats along the eastern United States coastline, where it uses behavioral thermoregulation, including burrow retreats, to manage body temperature (Tb). We explored the relationship between frequency of burrow use and environmental conditions, including burrow and surface temperatures, relative tidal height, and time of day, by twenty male M. pugnax in breeding areas around Flax Pond, New York, USA. We found a highly significant positive correlation between burrow use and surface temperature, with a clear shift to longer times underground above 32 °C degrees. We also experimentally heated live crabs in the laboratory and allowed them to retreat into cooled artificial burrows while continuously measuring Tb. Laboratory data on cooling times were compared to field observations of burrow retreat durations. The median burrow duration in the field of 2.74 min was enough time for our laboratory crabs to capture over 70% of the cooling potential of artificial burrows 10 or 15 °C below Tb. Because crab bodies in burrows experience exponential declines in Tb due to Newton's law of cooling, there are diminishing returns to remaining in a burrow, and many crabs probably leave before coming to equilibrium. For M. pugnax, burrow retreats reduce time spent feeding and courting, activities that only occur on the surface. Current concerns about the impacts of climate change on animals include whether compensatory mechanisms, like more frequent and longer burrow retreats, will come at the cost of other behaviors necessary for survival and reproduction.

Mentha longifolia assisted nanostructures: An approach to obliterate microbial biofilms.

Microbes maneuver strategies to become incessant and biofilms perfectly play a role in scaling up virulence to cause long-lasting infections. The present study was designed to assess the use of an eco-friendly formulation of functionalized silver nanoparticles generated from Mentha longifolia leaf extract (MℓE) for the treatment of biofilm-producing microbes. Nanoparticles synthesized using MℓE as a reducing agent were optimized at different strengths of AgNO3 (1 mM, 2 mM, 3 mM, and 4 mM). Synthesis of M. longifolia silver nanoparticles (MℓAgNPs) was observed spectrophotometrically (450 nm) showing that MℓAgNPs (4 mM) had the highest absorbance. Various techniques e.g., Fourier transforms Infrared spectroscopy (FTIR), Dynamic light scattering (DLS), zeta potential (ZP), X-ray Diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to characterize MℓAgNPs. In the present study, the Kirby-Bauer method revealed 4mM was the most detrimental conc. of MℓAgNPs with MIC and MBC values of 0.62 µg/mL and 1.25 µg/mL, 0.03 µg/mL and 0.078 µg/mL, and 0.07 µg/mL and 0.15 µg/mL against previously isolated and identified clinical strains of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, respectively. Moreover, the MℓAgNP antibiofilm activity was examined via tissue culture plate (TCP) assay that revealed biofilm inhibition of up to 87.09%, 85.6%, 83.11%, and 75.09% against E. coli, P. aeruginosa, K. pneumonia, and S. aureus, respectively. Herbal synthesized silver nanoparticles (MℓAgNPs) tend to have excellent antibacterial and antibiofilm properties and are promising for other biomedical applications involving the extrication of irksome biofilms. For our best knowledge, it is the first study on the use of the green-synthesized silver nanoparticle MℓAgNP as an antibiofilm agent, suggesting that this material has antibiotic, therapeutic, and industrial applications.

Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy.

BACKGROUND: Adequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2. METHODS: Two suspected families - a multiplex Pakistani family (family A) with three affected siblings and a family of Moroccan origin (family B) with a single affected child who presented with seizures and reduced fasting blood glucose levels were genetically characterized. Whole exome sequencing (WES) was performed on the index patients, followed by Sanger sequencing-based segregation analyses on all available members of both families. RESULTS: The variant prioritization of WES and later Sanger sequencing confirmed three mutations in the GYS2 gene (12p12.1) consistent with an autosomal recessive pattern of inheritance. A homozygous splice acceptor site variant (NM_021957.3, c. 1646 -2A>G) segregated in family A. Two novel compound heterozygous variants (NM_021957.3: c.343G>A; p.Val115Met and NM_021957.3: c.875A>T; p.Glu292Val) were detected in family B, suggesting glycogen storage disorder. A special diet designed to avoid hypoglycemia, in addition to change of the anti-seizure medication led to reduction in seizure frequency. CONCLUSIONS: This study suggests that the seizures in patients initially diagnosed with epilepsy might be directly caused, or influenced by hypoglycemia due to pathogenic variants in the GYS2 gene.

Surface-enhanced Raman spectroscopy for characterization of filtrates of blood serum samples from patients with tuberculosis obtained by 50 kDa filtration devices.

The ability of surface-enhanced Raman spectroscopy (SERS) to generate spectroscopic fingerprints has made it an emerging tool for biomedical applications. The objective of this study is to confirm the potential use of Raman spectroscopy for early disease diagnosis based on blood serum. In this study, a total of sixty blood serum samples, consisting of forty from diseased patients and twenty (controls) from healthy individuals, was used. Because disease biomarkers, found in the lower molecular weight fraction, are suppressed by higher molecular weight proteins, 50 kDa Amicon ultrafiltration centrifugation devices were used to produce two fractions from whole blood serum consisting of a filtrate, which is a low molecular weight fraction, and a residue, which is a high molecular weight fraction. These fractions were then analyzed, and their SERS spectral data were compared with those of healthy fractions. The SERS technique was utilized on blood serum, filtrate and residue of patients with tuberculosis to identify characteristic SERS spectral features associated with the development of disease, which can be used to differentiate them from healthy samples using silver nanoparticles as a SERS substrate. For further analysis, the effective chemometric technique of principal component analysis (PCA) was used to qualitatively differentiate all the analyzed samples based on their SERS spectral features. Partial least squares discriminant analysis (PLS-DA) accurately classified the filtrate portions of healthy and tuberculosis samples with 97% accuracy, 97% specificity, 98% sensitivity, and an area under the receiver operating characteristic (AUROC) curve of 0.74.

Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families.

Progressive myoclonic epilepsies (PMEs) are a group of neurodegenerative disorders, predominantly affecting adolescents and, characterized by generalized worsening myoclonus epilepsies, ataxia, cognitive deficits, and dementia. To date, several genes, having implications in diverse phenotypic expressions associated with PMEs, have been identified. Genetic diagnosis is available for most of the adolescence-onset myoclonic epilepsies. This study aimed to elucidate the genetic basis of PMEs in three multiplex Pakistani families exhibiting clinically variable phenotypes. Causative variant(s) in the studied families, and mode of segregation were identified by Whole Exome Sequencing (WES) of the probands, followed by bi-directional Sanger sequencing for final validation. We identified homozygous recessive CLN6 missense variant c.768 C>G (p.Asp256Glu) in Family 1, and c.889 C>A (p.Pro297Thr) variant in Family 2. While in Family 3, we found a homozygous variant (c.316dup) that caused a frameshift mutation, leading to a premature stop codon in the CLN6 protein, resulting in a truncated protein (p.Arg106ProfsTer26). Though CLN6 is previously identified to underlie late infantile and adolescent onset neuronal ceroid lipofuscinosis, this study supports and expands the phenotypic spectrum of CLN6 mutations and signifies diagnositc potential CLN6 variants for PMEs. Diverse pathological effects of variant c .768 C>G were observed in Family 1, with same genotypes, suggesting clinical heterogeneity and/or variable expressivity that might be the implication of pleiotropic effects of the gene in these cases.

Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5-2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.

A systematic review of modeling approaches in green supply chain optimization.

Over the past decade, the significance of optimizing green supply chain management (GSCM) has gained unprecedented attention from both scholars and industry professionals. This surge in interest has led researchers to employ diverse modeling approaches in the pursuit of enhancing green supply chain networks. In this systematic review, we analyze 159 recent GSCM optimization papers published from 2017 to 2022 and identify the recent trends in mathematical modeling, multi-objective optimization, and the modeling/solver tools utilized. We find that the primary green focus is on minimizing carbon emissions (n = 44), reflecting the increasing concern for environmental sustainability. Among the modeling approaches employed, mixed-integer linear programming has emerged as the most popular choice (n = 51), followed by game theory-based modeling (n = 30). When it comes to multiobjective optimization, the ε-constraint approach is the most widely used. Evolutionary algorithms have emerged as the dominant meta-heuristic optimization approach. Additionally, the widely utilized solver in this domain is CPLEX with the most popular modeling/solver combination being GAMS/CPLEX. Moreover, the Journal of Cleaner Production was the leading outlet for research in this domain (n = 35). In addition to these findings, this study also discusses some other research trends and future research directions. Finally, we discuss the theoretical, managerial, and policy implications of this study. By providing GSCM researchers and practitioners with the latest trends in GSCM optimization approaches, this study contributes to the further advancement of the field.

CD34+ HSPCs-derived exosomes contain dynamic cargo and promote their migration through functional binding with the homing receptor E-selectin.

Exosomes are tiny vesicles released by cells that carry communications to local and distant locations. Emerging research has revealed the role played by integrins found on the surface of exosomes in delivering information once they reach their destination. But until now, little has been known on the initial upstream steps of the migration process. Using biochemical and imaging approaches, we show here that exosomes isolated from both leukemic and healthy hematopoietic stem/progenitor cells can navigate their way from the cell of origin due to the presence of sialyl Lewis X modifications surface glycoproteins. This, in turn, allows binding to E-selectin at distant sites so the exosomes can deliver their messages. We show that when leukemic exosomes were injected into NSG mice, they traveled to the spleen and spine, sites typical of leukemic cell engraftment. This process, however, was inhibited in mice pre-treated with blocking E-selectin antibodies. Significantly, our proteomic analysis found that among the proteins contained within exosomes are signaling proteins, suggesting that exosomes are trying to deliver active cues to recipient cells that potentially alter their physiology. Intriguingly, the work outlined here also suggests that protein cargo can dynamically change upon exosome binding to receptors such as E-selectin, which thereby could alter the impact it has to regulate the physiology of the recipient cells. Furthermore, as an example of how miRNAs contained in exosomes can influence RNA expression in recipient cells, our analysis showed that miRNAs found in KG1a-derived exosomes target tumor suppressing proteins such as PTEN.

Differential Treatment Responses in Pakistani Schizophrenia Samples: Correlation with Sociodemographic Parameters, Drug Addiction, Attitude to the Treatment and Antipsychotic Agents.

Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients' response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients. Methods: We conducted a retrospective study that included schizophrenia subjects (N = 200) belonging to different age groups, ethnicities, and regions from different outpatient and inpatient departments in psychiatric institutes located in different cities of Pakistan. These patients were assessed for their response to treatment therapies and categorized into four groups (non-responders (N-R), slow response (S-R), patients with relapse, and completely recovered patients (C-R)) according to their responses. Results: The final analysis included 200 subjects, of which 73.5% were males. Mean age was 34 ± 10 years. Percentage of N-R was 5%, S-R was 42%, patients with relapse were 24%, and C-R was 1.5%. The generalized linear regression model shows a significant association between medication response and age (p = 0.0231), age of onset (p = 0.0086), gender (p = 0.005), and marital status (p = 0.00169). Variability within the medication responses was a result of the treatment regime followed. Antipsychotic agents were significantly associated with the treatment response (p = 0.00258, F = 4.981) of the patients. Significant variation was also observed in the treatment response (p = 0.00128) of the patients that were given augmentation therapy as well as combination therapy. Conclusion: The data suggests proper monitoring of patients' behavior in response to treatment therapies to implement tailored interventions. Despite several genetic studies supporting the heritability of schizophrenia, an insignificant association between characteristic features and family history might have been due to the limited sample size, suggesting collaborative work with massive sample sizes.

The impact of financial development on CO2 emissions: new evidence from developed and emerging countries.

Taking into account the complicated and multidimensional nature of financial development, this study aims to investigate the impact of overall financial market development, institution development, and their sub-indices on CO2 emissions. To advance knowledge about the nexus between financial development and CO2 emissions, four financial market indices (overall financial market development, FM-access, FM-depth, and FM-efficiency) and four financial institution indices (overall financial institution development, FI-access, FI-depth, and FI-efficiency) are used. The study used two-stage system GMM and panel data of developed and emerging countries over the period 2000-2018. The empirical results reveal that the overall financial market development and its sub-indices (FM-access, FM-depth, and FM-efficiency) reduce CO2 emissions in developed and emerging countries. The results further show that the overall financial institution development and its sub-indices such as FI-access, FI-depth, and FI-efficiency foster the environment quality in developed economies, while these indices impede the environmental quality in emerging economies. The usage of renewable energy is found to be a viable solution to mitigate the CO2 emissions in both groups of countries. Additionally, policies related to sustainable development are also discussed in the paper.

Postpartum Insertion Of Intrauterine Contraceptive Device: A Safe And Effective Contraception.

Background: The incidence of maternal mortality and morbidity related to the termination of unwanted pregnancy in Pakistan is rising at an alarming rate. Instant Postpartum insertion of intrauterine contraceptive device (PPIUCD) is an effective contraceptive measure to reduce unexpected pregnancy and its associated complications in developing countries like Pakistan. Methods: The current study was conducted in a public sector hospital in Karachi with a total of 7314 pregnant women counselled for insertion of PPIUCD antenatally. Out of which 5682 women agreed to the insertion and 1632 refused the procedure, mostly due to unfamiliarity with PPIUCD insertion. PPIUCD was inserted within 48 hours of delivery in 1441 patients and they were followed for 6 months onwards. Results: Total postpartum insertions were 1441 which was found to be an effective measure with the continuation rate of 91% among 785 followed up cases. Postpartum IUCD insertion was found as an effective, satisfactory and convenient practice for the women of developing countries like Pakistan, to get an on-time appropriate contraceptive measure. Conclusion: : PPIUCD was found to have high retention and low expulsion rate and its efficacy can be improved further by proper training and skills of healthcare professionals. In this regard, appropriate strategies should be formulated and implemented at the statutory level by increasing social awareness and practice of using PPIUCD by health care providers to reduce undesired pregnancies.

The influence of stock market and financial institution development on carbon emissions with the importance of renewable energy consumption and foreign direct investment in G20 countries.

The present study aims to analyze the influence of stock market and financial institution development on carbon emissions by incorporating the role of renewable energy consumption and foreign direct investment in the function of carbon emissions on G20 member countries from 1981-217. Further, the empirical analysis is carried out on the full sample and sub-samples of developed and developing economies by employing panel econometric techniques. The findings confirm that the stock market development index reduces carbon emissions in the full sample and developed countries while increases carbon emissions in developing countries. However, the index of financial institution development increases carbon emissions in the full sample and developed countries but effect is found insignificant in the case of developing economies. The renewable energy consumption reduces the level of environmental degradation across the panels. Similarly, foreign direct investment increases environmental quality in the full sample and emerging economies while impede environmental quality in the developed economies. On the basis of empirical results, this study recommends policy implications.

Surface adsorption of nitrosourea on pristine and doped (Al, Ga and In) boron nitride nanosheets as anticancer drug carriers: the DFT and COSMO insights.

To minimize the side effects of chemotherapeutic drugs and enhance the effectiveness of cancer treatment, it is necessary to find a suitable drug delivery carrier for anticancer drugs. Recently nanomaterials are extensively being studied as drug vehicles and transport drugs in tumor cells. Using DFT calculations, the adsorption behavior with electronic sensitivity and reactivity of pristine and doped (Al, Ga and In)-BNNS towards the nitrosourea (NU) drug has been investigated in gas as well as water media. Our calculations showed that the NU drug is physically adsorbed on the pristine BNNS with -0.49 and -0.26 eV by transferring little amount of charge of about 0.033e and 0.046e in gas and water media in the most stable complex. But after replacing one of the central B atoms with an Al or Ga or In atom, the sensitivity of the doped BNNS remarkably enhances towards the NU drug molecules. The NU drug prefers to be chemically adsorbed on the BN(Al)NS, BN(Ga)NS and BN(In)NS by -1.28, -1.58 and -3.06 eV in the gas phase and -1.34, -1.23 and -3.65 eV in water media in the most stable complexes respectively. The large destabilization of LUMO energies after the adsorption of the NU drug on the BN(Al)NS, BN(Ga)NS and BN(In)NS significantly reduces their E g from 4.37 to 0.69, 4.37 to 1.04 and 4.33 to 0.66 eV in the S1 complex respectively. The reduction of E g of doped BNNS by the NU drug greatly enhances the electrical conductivity which can be converted to an electrical signal. Therefore, this doped BNNS can be used as a fascinating electronic sensor for the detection of NU drug molecules. Furthermore the work function of the doped BNNS was largely affected by the NU drug adsorption about 47.3%, 39.3% and 40.4% in the gas phase and 41.3%, 36.6% and 31.6% in water media in the S1 complex of NU/BN(Al)NS, NU/BN(Ga)NS and NU/BN(In)NS respectively. Thus, the doped BNNS may be used as a Ф type sensor for NU drug molecules.

Synthesis and Characterization of Organic-Inorganic Nanocomposite Poly-o-anisidine Sn(IV) Arsenophosphate: Its Analytical Applications as Pb(II) Ion-Selective Membrane Electrode.

Poly-o-anisidine Sn(IV) arsenophosphate is a newly synthesized nanocomposite material and has been characterized on the basis of its chemical composition, ion exchange capacity, TGA-DTA, FTIR, X-RAY, SEM, and TEM studies. On the basis of distribution studies, the exchanger was found to be highly selective for lead that is an environmental pollutant. For the detection of lead in water a heterogeneous precipitate based ion-selective membrane electrode was developed by means of this composite cation exchanger as electroactive material. The membrane electrode is mechanically stable, with a quick response time, and can be operated over a wide pH range. The selectivity coefficients were determined by mixed solution method and revealed that the electrode is sensitive for Pb(II) in presence of interfering cations. The practical utility of this membrane electrode has been established by employing it as an indicator electrode in the potentiometric titration of Pb(II).