Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.

BACKGROUND: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. METHODS: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. RESULTS: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. CONCLUSION: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

Microbes-assisted phytoremediation of lead and petroleum hydrocarbons contaminated water by water hyacinth.

An experiment was carried out to explore the impact of petroleum hydrocarbons (PHs)-degrading microbial consortium (MC) on phytoremediation ability and growth of water hyacinth (WH) plants in water contaminated with lead (Pb) and PHs. Buckets (12-L capacity) were filled with water and WH plants, PHs (2,400 mg L-1) and Pb (10 mg L-1) in respective buckets. Plants were harvested after 30 days of transplanting and results showed that PHs and Pb substantially reduced the agronomic (up to 62%) and physiological (up to 49%) attributes of WH plants. However, the application of MC resulted in a substantial increase in growth (38%) and physiology (22%) of WH plants over uninoculated contaminated control. The WH + MC were able to accumulate 93% Pb and degrade/accumulate 72% of PHs as compared to initial concentration. Furthermore, combined use of WH plants and MC in co-contamination of PHs and Pb, reduced Pb and PHs contents in water by 74% and 68%, respectively, than that of initially applied concentration. Our findings suggest that the WH in combination with PHs-degrading MC could be a suitable nature-based water remediation technology for organic and inorganic contaminants and in future it can be used for decontamination of mix pollutants from water bodies.

Phytoremediation by aquatic macrophytes is a promising technique for the cleanup of environmental toxins from wastewater. To our knowledge, this is the first study reporting the integrated use of water hyacinth (WH) plants and a newly developed multi-trait microbial consortium for the simultaneous remediation of organic (i.e., petroleum hydrocarbons) and inorganic (i.e., lead) pollutants from the contaminated water. Findings of this study provide the basic but important information on the combined use of WH and microbes for remediation of mix pollution from water bodies.

Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families.

BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically progressive retinal dystrophy associated with severe visual impairments and sometimes blindness, the most common syndromic form of which is Usher syndrome (USH). This study aimed to further increase understanding of the spectrum of RP in the Khyber Pakhtunkhwa region of Pakistan. METHODOLOGY: Four consanguineous families of Pashtun ethnic group were investigated which were referred by the local collaborating ophthalmologists. In total 42 individuals in four families were recruited and investigated using whole exome and dideoxy sequencing. Among them, 20 were affected individuals including 6 in both family 1 and 2, 5 in family 3 and 3 in family 4. RESULT: Pathogenic gene variants were identified in all four families, including two in cone dystrophy and RP genes in the same family (PDE6C; c.480delG, p.Asn161ThrfsTer33 and TULP1; c.238 C > T, p.Gln80Ter) with double-homozygous individuals presenting with more severe disease. Other pathogenic variants were identified in MERTK (c.2194C > T, p.Arg732Ter), RHO (c.448G > A, p.Glu150Lys) associated with non-syndromic RP, and MYO7A (c.487G > A, p.Gly163Arg) associated with USH. In addition, the reported variants were of clinical significance as the PDE6C variant was detected novel, whereas TULP1, MERTK, and MYO7A variants were detected rare and first time found segregating with retinal dystrophies in Pakistani consanguineous families. CONCLUSIONS: This study increases knowledge of the genetic basis of retinal dystrophies in families from Pakistan providing information important for genetic testing and diagnostic provision particularly from the Khyber Pakhtunkhwa region.

Multipath Detection and Mitigation of Random Noise Signals Propagated through Naturally Lossy Dispersive Media for Radar Applications.

This paper describes a methodological analysis of the Brillouin precursor formation to understand the impairments undergone by like-noise and random noise waveforms propagating through naturally dispersive media commonly found in radar applications. By means of a frequency-domain methodology based on considering the frequency response of the medium under study, the effect of these dispersive media on the evolution of an input signal can be seen as frequency filtering. The simulations were performed at a center frequency of 1.5 GHz and for a signal bandwidth of 3 GHz. Four random noise signals were considered: Barker codes, PRBS codes, Frank codes, Costas codes and additive white Gaussian noise. The experienced impairments were assessed in terms of cross-correlation function (CCF) degradation. The differences in the behavior of each type of phase and frequency coded signal to face the dispersive propagation have been demonstrated in terms of parameters used for information retrieval: peak amplitude decay, CCF secondary sidelobe level and multipath detectability. Finally, a frequency filtering approach is proposed to mitigate the impairments due to dispersive propagation under multipath conditions.

Evaluation of phytoremediation potential and resistance of Gladiolus grandiflora L. against cadmium stress.

Although irrigation water is a fundamental need for plant growth, it is also a source of pollutants if contaminated with harmful materials like cadmium (Cd). Irrigation water possessing abundant Cd causes damage to soil, plants, animals and ultimately human beings through the food chain. A pot experiment was conducted to evaluate the gladiolus (Gladiolus grandiflora L.) potential of Cd accumulation and the capability of the plant to be an economically beneficial choice in presence of high Cd irrigation water supply. Artificially prepared four levels of Cd irrigation water were applied to the plants viz., 30, 60, 90 and 120 mg L-1. The results revealed that 30 mg L-1 Cd had no difference in all growth-related parameters when compared to the control. Photosynthesis rate, stomatal conductance and transpiration rate along with plant height and spike length were reduced with high accumulation levels of Cd in plants. The main plant portion for Cd storage found in Gladiolus grandiflora L was corm where the amount of Cd was 10-12 times higher than the amount found in leaves, and 2-4 times more than the stem. This deportment was further established by the translocation factor (TF). In corm to shoot TF and corm to stem TF, the factor reduced with increasing Cd levels, while, in corm to leaves TF, Cd levels were statistically non-significant. From corm to shoot TF value of 0.68 and 0.43 in case of 30 and 60 mg L-1, Cd treatments indicates good phytoremediation potential of Gladiolus in low and moderate Cd-polluted environments. Conclusively, the study reveals the good capability of Gladiolus grandiflora L. to harvest Cd from the soil and water in reasonably good amount with sufficient potential to grow under irrigation-based Cd stress. Under revelations of the study, Gladiolus grandiflora L appeared as a Cd accumulator which could potentially be used as a sustainable approach for phytoremediation of Cd.

Geo-statistical analysis of climatic variability and trend detection in the Hindu Kush region, North Pakistan.

This paper is an effort of geo-statistical analysis of rainfall variability and trend detection in the eastern Hindu Kush region located in the north-west of Pakistan. The eastern section of the HK region lies in the western part of Pakistan. Exploring rainfall variability and quantifying its trend and magnitude is one of the key indicators among all climatic parameters. In the study area, Pakistan Meteorology Department (PMD) has established seven meteorological stations: Drosh, Chitral, Dir, Timergara, Saidu Sharif, Malam Jabba, and Kalam. Daily, mean monthly, and mean annual rainfall time series data for all the met stations were geo-statistically analyzed in the GIS environment for detecting monthly and annual variability in rainfall, variability, and trend detection. Mann-Kendall (MK) and Theil-Sen's slope (TSS) statistical tests were applied to rainfall data. Initially, the MK test was applied for detection of trends and TSS test was used to quantify the change in magnitude. The results indicate that the rainfall variability in intensity and trend pattern detection. The analysis confirms that an extremely significant rainfall trend in the case of mean annual rainfall was predicted at Dir and Malam Jabba meteorological stations. Opposite to this, at Kalam and Chitral stations, a less significant rainfall trend was noted. In a similar context, no prominent rainfall trend has been found at Drosh, Timergara, and Saidu Sharif meteorological stations. Likewise, using TSS, an extremely negative variation in the magnitude of rainfall was verified at Kalam and Malam Jabba. However, a noteworthy positive change in rainfall magnitude has been noted at Dir and Saidu Sharif meteorological stations. The findings of this research have the potential to assist the decision and policy makers and academicians to think truly and conduct more scientific research studies to mitigate climate change.

Exogenous melatonin mitigates chromium toxicity in maize seedlings by modulating antioxidant system and suppresses chromium uptake and oxidative stress.

Melatonin, being an endogenous signaling molecule plays important role in plant growth and stress alleviation. The present study was conducted to evaluate the ameliorative role of melatonin against Cr toxicity in maize seedlings. The Cr toxicity (50, 100 and 200 µM) severely affected hydroponically grown seedlings growth in a dose-dependent manner; however, the melatonin (0.5 and 1.0 µM) application markedly restored toxicity-induced growth retardation. Higher dose of melatonin (1.0 µM) was more effective in case of lower Cr toxicity (50 and 100 µM). Exposure of 200 µM Cr caused 45% and 43% reduction in shoot and root lengths and more than 80% reduction in biomass. In case of 200 µM Cr toxicity, application of 1.0 µM MT effectively restored shoot and root lengths reduction (from 45 to 30%) and biomass decline (from 80 to around 60%). Biomass restoration by 1.0 µM melatonin under 50 and 100 µM Cr was even more pronounced bringing it near to control plants having no Cr exposure. Further, both melatonin levels also improved root tips, root diameter, root volume and root surface area that had been damaged by Cr exposure. The melatonin also alleviated Cr-induced chlorophyll and carotenoids inhibition, improved relative water content, and markedly lowered proline and MDA content in shoots. Lower accumulation of MDA and proline, and greater membrane stability indices indicate that the melatonin conferred better plant growth by playing the role of antioxidant and detoxifying oxidative stress creating substances. Although antioxidant enzymes viz. SOD, POD, CAT and APX activities were also elevated by MT, this increase was not significantly different in the most of cases. No significant difference in NPK contents of shoot was observed by Cr and melatonin application indicating the growth retardation being caused directly by Cr intrinsic toxicity and not by nutrients deficiency. The melatonin-based amelioration of Cr toxicity in maize seedlings seems as the result of its nature as antioxidant, and not by activation/elevation of antioxidative enzymatic system.

Effects of mirror and coloured balls as environmental enrichment tools on performance, welfare and meat quality traits of commercial broiler.

This study evaluated the effect of environmental enrichment on the performance, behaviour and welfare aspects; blood biochemistry; carcass and meat quality traits of broiler chickens. A total of 450 straight run broiler chicks (Ross-308) were divided into 5 treatment groups having 6 replicates of 15 birds each under a completely randomised design. Treatments were environmental enrichment (EE) tools and consisted of C = control group; R = red ball for EE; G = green ball for EE; B = blue ball for EE and M = mirror for EE. These environmental enrichment tools were provided throughout the experimental period (0 to 35 days). Mean feed intake per bird was higher in all treatment groups except the blue balls group; weight gain and feed conversion ratio were better in the green and blue ball groups. Broiler chickens reared under different environmental enrichment were more active and they exhibited maintenance behaviour (preening, dust bathing and wing stretching, or scratching) more frequently. Regarding welfare traits, lower incidence of toe damage, footpad dermatitis and hock burn was observed in birds having different environmental enrichment tools as compared to the control group. The birds reared with red balls as environmental enrichment showed the lowest values for glucose, cholesterol, total protein, albumin and globulin amongst all the treatment groups. Birds reared with green balls had the highest body weight at slaughter, dressed weight, carcass yield and liver weight. Breast meat of environmentally enriched treated groups was lighter and had lower ultimate pH. It was concluded that the addition of environmental enrichment tools (visual, structural and plastic) motivates the birds for physical activities and improves the performance of broiler chickens.

Rotavirus gastroenteritis in Pakistan, 2018: updated disease burden.

OBJECTIVE: Rotavirus A (RVA) is a significant cause of severe diarrheal illness and one of the common causes of death in children under the age of five. This study was aimed at detecting the prevalence of RVA in Pakistan after rotavirus vaccines were introduced. Fecal samples were obtained from 813 children from different hospitals in Rawalpindi and Islamabad, Pakistan, from January 2018 to December 2018. To obtain additional information from the parents / guardians of the children, a standard questionnaire was used. RESULTS: Using an enzyme-linked immunosorbent assay kit (ELISA), rotavirus antigen was detected and ELISA positive samples were subjected to reverse transcription PCR (RT-PCR). The findings showed 22% prevalence of RVA in children with acute gastroenteritis (AGE) via ELISA and 21% prevalence via RT-PCR in children with AGE. There was no statistically significant difference between gender, age and RVA infections. The winter, spring and fall/autumn seasons were statistically significant for RVA prevalence. CONCLUSION: The present study will provide post vaccine prevalence data for the health policy makers. The implementation of rotavirus vaccines, along with adequate nutrition for babies, clean water supply and maternal hygienic activities during infant feeding, is recommended. Furthermore, continuous surveillance is mandatory in the whole country to calculate the disease burden caused by RVA.

Exogenous melatonin regulates chromium stress-induced feedback inhibition of photosynthesis and antioxidative protection in Brassica napus cultivars.

KEY MESSAGE: Melatonin is an early player in chromium stress response in canola plants; it promotes ROS scavenging and chlorophyll stability, modulates PSII stability and regulates feedback inhibition of photosynthesis conferring chromium tolerance. The development of heavy metals, especially chromium (Cr)-tolerant cultivars is mainly constrained due to poor knowledge of the mechanism behind Cr stress tolerance. In the present study, two Brassica napus contrasting cultivars Ac-Excel and DGL were studied for Cr stress tolerance by using chlorophyll a fluorescence technique and biochemical attributes with and without melatonin (MT) treatments. Cr stress significantly reduced the PSII and PSI efficiency, biomass accumulation, proline content and antioxidant enzymes in both the cultivars. The application of MT minimized the oxidative stress, as revealed via a lower level of reactive oxygen species (ROS) synthesis (H2O2 and OH-). Enhanced enzymatic activities of important antioxidants (SOD, APX, CAT, POD), proline and total soluble protein contents under MT application play an effective role in the regulation of multiple transcriptional pathways involved in oxidative stress responses. Higher NPQ and Y(NPQ) observed in Cr stress tolerant cv Ac-Excel, indicating that the MT-treated tolerant cultivar had better ability to protect PSII under Cr stress by increasing heat dissipation as photo-protective component of NPQ. Reduced PSI efficiency along with increased donor end limitation of PSI in both canola cultivars further confirmed the lower PSII activity and electron transport from PSII. The Cr content was higher in cv. DGL as compared to (that in Ac-Excel). The application of MT significantly decreased the Cr content in leaves of both cultivars. Overall, MT-induced Cr stress tolerance in canola cultivars can be related to improved PSII activity, Y(NPQ), and antioxidant potential and these physiological attributes can effectively be used to select cultivars for Cr stress tolerance.

USH2A gene variants cause Keratoconus and Usher syndrome phenotypes in Pakistani families.

BACKGROUND: Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, affecting approximately 1 in 4000 individuals worldwide. The most common form of syndromic RP is Usher syndrome (USH) accounting for approximately 20-30 % of RP cases. Mutations in the USH2A gene cause a significant proportion of recessive non-syndromic RP and USH type II (USH2). This study aimed to determine the causative role of the USH2A gene in autosomal recessive inherited ocular diseases and to establish genotype-phenotype correlation associated with USH2A variants. METHODS: We performed direct Sanger sequencing and co-segregation analysis of the USH2A gene to identify disease causing variants in a non-syndromic RP family, two USH2 families and two Keratoconus (KC) families. RESULTS: Disease causing variants in the USH2A gene were identified in two families displayed KC and USH2 phenotypes. A novel variant c.4029T > G, p.Asn1343Lys in the USH2A gene was detected in a Pakistani family with KC phenotype. In addition, a missense variant (c.7334 C > T, p. Ser2445Phe) in the USH2A gene was found segregating in another Pakistani family with USH2 phenotype. Homozygosity of identified missense USH2A variants was found associated with autosomal recessive inherited KC and USH2 phenotypes in investigated families. These variants were not detected in ethnically matched healthy controls. Moreover, the USH2A variants were predicted to be deleterious or potentially disease causing by PolyPhen-2, PROVEAN and SIFT. CONCLUSIONS: This study provided first evidence for association of a novel USH2A variant with KC phenotype in a Pakistani family as well as established the phenotype-genotype correlation of a USH2A variant (c.7334 C > T, p. Ser2445Phe) with USH2 phenotype in another Pakistani family. The phenotype-genotype correlations established in present study may improve clinical diagnosis of affected individuals for better management and counseling.

Variations in phytoremediation potential and phytoavailability of heavy metals in different Salix genotypes subjected to seasonal flooding.

Climate-related flooding poses a potential challenge to phytoremediation of metal polluted areas. In the present study, uptake, translocation and accumulation of heavy metals (Cd, Zn and Cu), and their phytoavailability in six flood-tolerant Salix genotypes were investigated under simulated seasonal flooding conditions (non-flooding conditions were kept as the control). Plants were cultivated in a greenhouse with open windows using the soil polluted with Cd, Zn and Cu for 110 days. All the control (non-flooded) genotypes did not exhibit visible toxic symptoms, whereas the flooded genotypes showed leaf chlorosis and developed both lenticels and adventitious roots. Biomass production and metal accumulation in tissues varied with Salix genotypes. The flooded genotypes dramatically decreased aerial biomass production compared with corresponding non-flooded genotypes. All the control Salix genotypes showed relatively high accumulation for Cd, Zn and Cu in aerial parts due to high EDTA-extractable metals in the rhizosphere, exhibiting phytoextraction features. In contrast, the flooded genotypes drastically decreased uptake, translocation, accumulation, and extraction capacities for Cd, Zn and Cu in aerial parts, differing with genotypes, and tended to phyto-stabilize them in roots, especially Cu. This study indicated that flooding is a leading factor on phytoremediation efficiency for contaminated sites with willows.

Hydrogen sulfide alleviates chromium stress on cauliflower by restricting its uptake and enhancing antioxidative system.

The present study evaluated the physiological and biochemical mechanisms through which exogenous sodium hydrosulfide (H2 S donor) mitigates chromium (Cr) stress in cauliflower. The different levels of Cr included 0, 10, 100 and 200 µM. Results reported that Cr exposure reduced growth and biomass, chlorophyll (Chl) contents, gas exchange parameters and enzymatic antioxidants. Chromium stress enhanced the production of electrolyte leakage (EL), hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA) contents and increased Cr content in the roots, stem, leaf and flowers. Exogenous H2 S improved the physiological and biochemical attributes of Cr-stressed cauliflower. Hydrogen sulfide decreased Cr content in different parts of Cr-stressed plants, whereas it increased the Chl contents and gas exchange attributes. H2 S reduced the EL, H2 O2 and MDA concentrations, enhancing the antioxidant enzymes activities in Cr-stressed roots and leaves compared to the Cr treatments alone. Collectively, our results provide an insight into the protective role of H2 S in Cr-stressed cauliflower and suggest H2 S as a potential candidate in reducing Cr toxicity in cauliflower and other crops.

Baseline characteristics of infected foot ulcers in patients with diabetes at a tertiary care hospital in Pakistan.

OBJECTIVE:: Studies on diabetic foot ulcers (DFU) involving a representative sample of patients in Pakistan are scarce. This study aimed to determine baseline characteristics of infected DFUs in patients hospitalised at the Pakistan Institute of Medical Sciences Islamabad. METHOD:: In this cross-sectional study, carried out during May 2015 and June 2016, foot ulcer characteristics of patients with DFUs were investigated and documented. From infected DFUs, aerobic bacterial pathogens were isolated, identified and evaluated for antimicrobial susceptibility. RESULTS:: A total of 214 patients were recruited to the study, 62.6% of which were male, 90.2% were aged ≥40 years, 76.2% had type 1 diabetes and 78.5% had poor glycaemic control at time of presentation to hospital. Most patients had grade 3/moderate ulceration (based on the Wagner and International Working Group on the Diabetic Foot/Infectious Diseases Society of America criteria). Over half of the DFUs (57.9%) were of ≤3 months' duration and 70.1% were ≥3 cm2. Of the patients with deep infection grade ulcers, 26.6% underwent amputation, accounting for their prolonged hospital stay (≥20 days). Significant differences were observed between patients with type 1 and type 2 diabetes with DFUs in relation to gender (p≤0.0001), ulcer size (p=0.0421) and duration of hospital stay (p=0.0253). The most significant predictors for lower extremity amputation were osteomyelitis (p=0.0114), retinopathy (p=0.0001) and neuropathy (p=0.0001. Piperacillin/tazobactam was found to be an effective antibiotic against the most commonly isolated Staphylococcus non-aureus (35.48%), Pseudomonas aeruginosa (22.26%), and Staphylococcus aureus (20.96%) species indentified in the DFU infections. CONCLUSION:: The findings of this study may be helpful in the optimal management and appropriate treatment of patients with infected DFUs.

SynCLay: Interactive synthesis of histology images from bespoke cellular layouts.

Automated synthesis of histology images has several potential applications in computational pathology. However, no existing method can generate realistic tissue images with a bespoke cellular layout or user-defined histology parameters. In this work, we propose a novel framework called SynCLay (Synthesis from Cellular Layouts) that can construct realistic and high-quality histology images from user-defined cellular layouts along with annotated cellular boundaries. Tissue image generation based on bespoke cellular layouts through the proposed framework allows users to generate different histological patterns from arbitrary topological arrangement of different types of cells (e.g., neutrophils, lymphocytes, epithelial cells and others). SynCLay generated synthetic images can be helpful in studying the role of different types of cells present in the tumor microenvironment. Additionally, they can assist in balancing the distribution of cellular counts in tissue images for designing accurate cellular composition predictors by minimizing the effects of data imbalance. We train SynCLay in an adversarial manner and integrate a nuclear segmentation and classification model in its training to refine nuclear structures and generate nuclear masks in conjunction with synthetic images. During inference, we combine the model with another parametric model for generating colon images and associated cellular counts as annotations given the grade of differentiation and cellularities (cell densities) of different cells. We assess the generated images quantitatively using the Frechet Inception Distance and report on feedback from trained pathologists who assigned realism scores to a set of images generated by the framework. The average realism score across all pathologists for synthetic images was as high as that for the real images. Moreover, with the assistance from pathologists, we showcase the ability of the generated images to accurately differentiate between benign and malignant tumors, thus reinforcing their reliability. We demonstrate that the proposed framework can be used to add new cells to a tissue images and alter cellular positions. We also show that augmenting limited real data with the synthetic data generated by our framework can significantly boost prediction performance of the cellular composition prediction task. The implementation of the proposed SynCLay framework is available at https://github.com/Srijay/SynCLay-Framework.

Evaluation of stroke in pregnant and non-pregnant women of reproductive years: A multicenter ambispective cohort study in a low- to middle-income country.

Objective: Early recognition of stroke symptoms and risk factors is important for timely intervention to improve outcomes. This study aimed to investigate differences in stroke frequency, risk factors, and presentation in pregnant and non-pregnant women of reproductive years. Methods: This multicenter ambispective cohort study, conducted from 4th August 2021 to 4th March 2023, examined strokes in women of reproductive years at the neurology outpatient/emergency department of five busiest/referred neuro-medical facilities in Karachi, Pakistan, where patients from across the nation are assessed. In all, 1210 patients were enrolled via consecutive or convenient sampling retrospectively from January 2017 to August 2021 and prospectively from August 2021 to March 2023. Pregnancy-related and non-pregnancy-related stroke occurrence and characteristics were compared using the chi-square/Fischer's exact test. Results: 56% were non-pregnancy-related strokes and 44% were pregnancy-related strokes with non-pregnancy-related strokes approximately equal throughout the reproductive years (15-24 years = 34%, 25-34 years = 25%, 35-45 years = 41%) and pregnancy-related stroke between 15 and 35 years (82%). In the non-pregnancy-related stroke, arterial stroke dominated (96.4%); while in pregnancy-related stroke, arterial stroke accounted for 61.4% and venous stroke for 38.6% of cases. Middle cerebral artery was a typical stroke site (66%). Infarction was the most significant CT/MRI finding (PRS = 89%, NPRS = 66%), with pregnancy-related stroke hemorrhagic stroke occurring in only 11% of cases and non-pregnancy-related stroke comprising one-third (34%). The most prevalent etiologies were eclampsia in pregnancy-related stroke (32%), hypertension in non-pregnancy-related stroke (40%), and cardiac problems among both groups (25%:33%). Weakness and headache were the common clinical manifestations among both groups. In the pregnancy-related and non-pregnancy-related stroke groups, the initial presentation of stroke resulted in severe disability for 91% and 75%, respectively. With timely treatment, the outcome improved significantly. The mortality rate was 7% for the pregnancy-related stroke group and 4% for the non-pregnancy-related stroke group. Conclusions: Our findings show that stroke is prevalent among reproductive-year women, posing a significant mortality risk if not adequately recognized and treated. Awareness, research, and screening of stroke risk factors and their often-overlooked early presentation (i.e., headache and weakness) in reproductive years are essential to reducing stroke occurrence among reproductive-year women.

Intelligent model for the detection and classification of encrypted network traffic in cloud infrastructure.

This article explores detecting and categorizing network traffic data using machine-learning (ML) methods, specifically focusing on the Domain Name Server (DNS) protocol. DNS has long been susceptible to various security flaws, frequently exploited over time, making DNS abuse a major concern in cybersecurity. Despite advanced attack, tactics employed by attackers to steal data in real-time, ensuring security and privacy for DNS queries and answers remains challenging. The evolving landscape of internet services has allowed attackers to launch cyber-attacks on computer networks. However, implementing Secure Socket Layer (SSL)-encrypted Hyper Text Transfer Protocol (HTTP) transmission, known as HTTPS, has significantly reduced DNS-based assaults. To further enhance security and mitigate threats like man-in-the-middle attacks, the security community has developed the concept of DNS over HTTPS (DoH). DoH aims to combat the eavesdropping and tampering of DNS data during communication. This study employs a ML-based classification approach on a dataset for traffic analysis. The AdaBoost model effectively classified Malicious and Non-DoH traffic, with accuracies of 75% and 73% for DoH traffic. The support vector classification model with a Radial Basis Function (SVC-RBF) achieved a 76% accuracy in classifying between malicious and non-DoH traffic. The quadratic discriminant analysis (QDA) model achieved 99% accuracy in classifying malicious traffic and 98% in classifying non-DoH traffic.

Incidence and characteristics of ligamentous knee injuries accompanying a femur shaft fracture and their association with injury mechanism and fracture characteristics: A prospective-observational study in a low-middle-income country.

Objective: This study aims to elaborate the incidence, types, and characteristics of ligamentous knee injuries accompanying femoral-shaft fractures and their association with demographic data, fracture characteristics, and injury mechanism. Methods: This multi-center-prospective-observational study examined patients in the Shaheed Mohtarma Benazir Bhutto Institute of Trauma and Civil Hospital orthopedic wards. Using the consecutive sampling technique, 146 patients with femoral-shaft fractures were recruited, and scrutinized to determine the presence of ligamentous knee injury, through an evaluation form encompassing patients' demographic data, fracture characteristics, knee examinations, and confirmed through magnetic resonance imaging. Knee injuries were detected intra-operatively under regional/general anesthesia and post-operatively utilizing diagnostic maneuvers (varus/valgus stress, Lachman, anterior/posterior drawer, external rotation recurvatum, and McMurray tests) by 2-3 surgeons and confirmed through magnetic resonance imaging. Magnetic resonance imaging was exclusively employed in suspected false positive/negative cases, and when a titanium implant was utilized, that is, 131 cases (89.7%). Chi-square test was used to assess the relationship between incidence and type of ligamentous knee injury with demographic data, injury mechanism, and fracture characteristics. Results: Among the 146 patients with femoral-shaft fractures, 78% and 22% were males and females, with 37% experiencing associated ligamentous knee injury. Medial collateral ligament and anterior cruciate ligament were the commonest types of ligamentous injuries accompanying femoral-shaft fractures, at 44% and 33%. The Chi-square revealed a statistically significant association between the incidence of ligamentous knee injury accompanying femoral-shaft fracture with demographic data, injury mechanism, and fracture characteristics (p-value < 0.05), and was noted to be higher among males (55.6%), participants aged 18-25 years (66.7%), involved in a road traffic accident (88.9%), resulting in a complex (77.8%) and close fracture (88.9%). A similar association was seen between medial collateral ligament and anterior cruciate ligament injuries with age, injury mechanism, and fracture characteristics (p-value < 0.05). Conclusion: Our study revealed the unaddressed fact that Pakistan has a significant incidence of ligamentous knee injuries accompanying femoral-shaft fractures. These insights can empower clinicians/surgeons to understand and manage this condition effectively.

Gender Inequity in Clinical Clerkships and its Influence on Career Selection: A Cross-Sectional Survey.

Objective: The aim of this study was to identify the frequency, form, and underlying factors contributing to gender inequity experienced by medical undergraduates and assess its influence on their career choices. Method: This was a cross-sectional, retrospective survey with a 100% response rate. This survey was distributed among medical students of clinical years in Karachi's private and government medical colleges from September 10th, 2021-March 30th, 2022. 430 participants were enrolled using a simple-random-sampling-technique. Chi-square/Fisher's Exact tests are employed to assess the relationships between gender and gender-based inequity in various specialties, including their characteristics, influence on career choices, adverse psychological effects, and potential mitigation strategies. Results: Among 430 respondents, 28.6% were male, and 71.4% were female. 89.1% reported gender inequity, evenly distributed in government (80.4%) and private institutions (88.1%). The general surgery and gynecology disciplines stood out, each with a 56% prevalence. In gynecology and surgery clinical-clerkships, both genders experienced similar rates, with females at 54.5% and 42.3%, and males at 56.7% and 61.6%, respectively (P-value = .000*). Disrespect from staff/professors/patients (48.8%) was the most common manifestation, driven by factors like preferences (73.7%), gender superiority (62.6%), societal attitudes (54%), and cultural norms (50.9%). Furthermore, 82.6% of students reported that gender inequity had a negative impact on their career decision (Male = 82.9%;Female = 82.4%, P-value = .899). Additionally, gender inequity also caused demotivation (78.1%), poor self-esteem (67.2%), helplessness/hopelessness (48.6%), and frustration (45.8%). Conclusions: Gender inequity is widely prevalent in the clinical-clerkships, affecting medical students' career decisions and mental health, stressing the need to prioritize and implement solutions at the undergraduate clinical-clerkship level.

Cancer drug sensitivity prediction from routine histology images.

Drug sensitivity prediction models can aid in personalising cancer therapy, biomarker discovery, and drug design. Such models require survival data from randomised controlled trials which can be time consuming and expensive. In this proof-of-concept study, we demonstrate for the first time that deep learning can link histological patterns in whole slide images (WSIs) of Haematoxylin & Eosin (H&E) stained breast cancer sections with drug sensitivities inferred from cell lines. We employ patient-wise drug sensitivities imputed from gene expression-based mapping of drug effects on cancer cell lines to train a deep learning model that predicts patients' sensitivity to multiple drugs from WSIs. We show that it is possible to use routine WSIs to predict the drug sensitivity profile of a cancer patient for a number of approved and experimental drugs. We also show that the proposed approach can identify cellular and histological patterns associated with drug sensitivity profiles of cancer patients.