Explore the vast range of titles available.

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.

Background Hereditary Spastic Paraplegias (HSPs) and Hereditary Cerebellar Ataxias (HCAs) are progressive neurodegenerative disorders encompassing a spectrum of neurogenetic conditions with significant overlaps of clinical features. Spastic ataxias are a group of conditions that have features of both cerebellar ataxia and spasticity, and these conditions are frequently clinically challenging to distinguish. Accurate genetic diagnosis is crucial but challenging, particularly in resource-limited settings. This study aims to investigate the genetic basis of HSPs and HCAs in Pakistani families. Methods Families from Khyber Pakhtunkhwa with at least two members showing HSP or HCA phenotypes, and who had not previously been analyzed genetically, were included. Families were referred for genetic analysis by local neurologists based on the proband’s clinical features and signs of a potential genetic neurodegenerative disorder. Whole Exome Sequencing (WES) and Sanger sequencing were then used to identify and validate genetic variants, and to analyze variant segregation within families to determine inheritance patterns. The mean age of onset and standard deviation were calculated to assess variability among affected individuals, and the success rate was compared with literature reports using differences in proportions and Cohen’s h. Results Pathogenic variants associated with these conditions were identified in five of eight families, segregating according to autosomal recessive inheritance. These variants included previously reported SACS c.2182 C > T, p.(Arg728*), FA2H c.159_176del, p.(Arg53_Ile58del) and SPG11 c.2146 C > T, p.(Gln716*) variants, and two previously unreported variants in SACS c.2229del, p.(Phe743Leufs*8) and ZFYVE26 c.1926_1941del, p.(Tyr643Metfs*2). Additionally, FA2H and SPG11 variants were found to have recurrent occurrences, suggesting a potential founder effect within the Pakistani population. Onset age among affected individuals ranged from 1 to 14 years (M = 6.23, SD = 3.96). The diagnostic success rate was 62.5%, with moderate effect sizes compared to previous studies. Conclusions The findings of this study expand the genotypic and phenotypic spectrum of HSPs and HCAs in Pakistan and emphasize the importance of utilizing exome/genome sequencing for accurate diagnosis or support accurate differential diagnosis. This approach can improve genetic counseling and clinical management, addressing the challenges of diagnosing neurodegenerative disorders in resource-limited settings.

Background Hereditary motor and sensory neuropathy (HMSN) refers to a group of inherited progressive peripheral neuropathies characterized by reduced nerve conduction velocity with chronic segmental demyelination and/or axonal degeneration. HMSN is highly clinically and genetically heterogeneous with multiple inheritance patterns and phenotypic overlap with other inherited neuropathies and neurodegenerative diseases. Due to this high complexity and genetic heterogeneity, this study aimed to elucidate the genetic causes of HMSN in Pakistani families using Whole Exome Sequencing (WES) for variant identification and Sanger sequencing for validation and segregation analysis, facilitating accurate clinical diagnosis. Methods Families from Khyber Pakhtunkhwa with at least two members showing HMSN symptoms, who had not previously undergone genetic analysis, were included. Referrals for genetic investigations were based on clinical features suggestive of HMSN by local neurologists. WES was performed on affected individuals from each family, with Sanger sequencing used to validate and analyze the segregation of identified variants among family members. Clinical data including age of onset were assessed for variability among affected individuals, and the success rate of genetic diagnosis was compared with existing literature using proportional differences and Cohen’s h. Results WES identified homozygous pathogenic variants in GDAP1 (c.310 + 4 A > G, p.?), SETX (c.5948_5949del, p.(Asn1984Profs*30), IGHMBP2 (c.1591 C > A, p.(Pro531Thr) and NARS1 (c.1633 C > T, p.(Arg545Cys) as causative for HMSN in five out of nine families, consistent with an autosomal recessive inheritance pattern. Additionally, in families with HMSN, a SETX variant was found to cause cerebellar ataxia, while a NARS1 variant was linked to intellectual disability. Based on American College of Medical Genetics and Genomics criteria, the GDAP1 variant is classified as a variant of uncertain significance, while variants in SETX and IGHMBP2 are classified as pathogenic, and the NARS1 variant is classified as likely pathogenic. The age of onset ranged from 1 to 15 years (Mean = 5.13, SD = 3.61), and a genetic diagnosis was achieved in 55.56% of families with HMSN, with small effect sizes compared to previous studies. Conclusions This study expands the molecular genetic spectrum of HMSN and HMSN plus type neuropathies in Pakistan and facilitates accurate diagnosis, genetic counseling, and clinical management for affected families.

This study examined the effects of information literacy (IL) on entrepreneurial intention and entrepreneurial skills among business students in Sargodha, Pakistan. A quantitative research design was employed along with a survey method. The data were gathered using a structured and self-administered questionnaire to collect data from a sample of 277 students, recruited through a convenient sampling process. Data analysis involved the application of descriptive and inferential statistics in SPSS (Version 21). The results suggested that the business students’ IL levels were not optimal, with no significant differences noted based on age, gender, semester, and academic disciplines. However, IL skills showed a positive correlation with students’ CGPA. The results also showed that IL had a positive effect on entrepreneurial intentions and entrepreneurial skills. In essence, students with higher levels of IL tended to exhibit better entrepreneurial intention and skills compared to those with lower IL levels. These results inform educators and policymakers in shaping policies and practices for business education in general and entrepreneurial education in particular. This research would be a valuable addition to the existing body of knowledge on IL research in the context of academia in general and business and entrepreneurial education in particular, as a limited number of studies have appeared in the existing literature.

This study examined the impact of personality traits on the knowledge sharing behavior of academicians in the public sector. The data were collected from 237 respondents using a questionnaire. The results showed that the personality trait openness to experience had a significant and positive impact on the knowledge sharing behavior and its sub-dimensions such as written contributions, organizational communication, personal interactions, and communities of practice. Furthermore, the personality traits extraversion and agreeableness positively predicted the knowledge sharing behavior for the dimensions of communities of practice and organizational communication, respectively. The results of this study would be helpful for the administrative staff of universities to develop programs to promote a knowledge sharing culture in universities and improve collaborative learning, research, organizational effectiveness, and performance. It would also be a worthy contribution to the existing literature as only a limited number of studies have addressed the role of personality traits in the knowledge sharing behaviors in the academic environment of a non-western country.

IntroductionAt Sandwell General Hospital, there was no risk stratification tool or pathway for head injury (HI) patients presenting to the emergency department (ED). This resulted in significant delays in the assessment of HI patients, compromising patient safety and quality of care.AimsTo employ quality improvement methodology to design an effective adult HI pathway that: ensured >90% of high-risk HI patients being assessed by ED clinicians within 15 min of arrival, reduce CT turnaround times, and aiming to keep the final decision making <4 hours.MethodsSWOT analysis was performed; driver diagrams were used to set out the aims and objectives. Plan-Do-Study-Act cycle was used to facilitate the change and monitor the outcomes. Process map was designed to identify the areas for improvement. A new HI pathway was introduced, imaging and transporting the patients was modified, and early decisions were made to meet the standards.ResultsData were collected and monitored following the interventions. The new pathway improved the proportion of patients assessed by the ED doctors within 15 min from 31% to 63%. The average time to CT head scan was decreased from 69 min to 53 min. Average CT scan reporting time also improved from 98 min to 71 min. Overall, the average time to decision for admission or discharge decreased from 6 hours 48 min to 4 hours 24 min.ConclusionsFollowing implementation of the new HI pathway, an improvement in the patient safety and quality of care was noted. High-risk HI patients were picked up earlier, assessed quicker and had CT head scans performed sooner. Decision time for admission/discharge was improved. The HI pathway continues to be used and will be reviewed and re-audited between 3 and 6 months to ensure the sustained improvement.

Information literacy (IL) plays an essential role in digital inclusion as it enables people to make use of the information available in multiple mediums on the Internet through digital devices. This study intends to examine the effect of IL on lifelong learning (LL) through the mediating role of creativity among news reporters in Pakistan using a quantitative research approach. The survey was conducted using an online questionnaire from the registered news reporters of press clubs in the four provinces and the federal territory of Islamabad, Pakistan. A total of 758 responses were received and analyzed using PLS-SEM. The results indicated that the IL of news reporters positively influenced their lifelong learning through both direct and indirect pathways. Furthermore, the nexus between IL and LL was influenced by the mediation of creativity. These findings have practical implications for academia and the media industry, highlighting the invaluable role of IL in enhancing lifelong learning and creativity to attain a sustainable competitive advantage. These results may inform educational programs for journalism students and existing journalists to impart IL skills. This research contributes to the available literature on workplace IL, especially in the context of media professionals.

PurposeSeroprevalence surveys from different countries have reported SARS CoV-2 antibodies below 20% even in the most adversely affected areas and herd immunity cannot be predicted till more than half of the population gets the disease. The purpose of this survey was to estimate the magnitude of community-based spread of the infection, associated immunity, and the future prospects and proximity to a ‘herd community’.MethodsThe study was undertaken as a cluster randomized, cross-sectional countrywide survey. This largest community-based seroprevalence data of SARS-CoV-2 were collected between 15th and 31st July, 2020 from seven randomly selected cities belonging to the three most populous provinces of Pakistan. The FDA approved kit of ROCHE was used for detection of SARS-CoV-2 antibodies.ResultsSerum samples of 15,390 participants were tested for SARS CoV-2 antibodies with an overall seroprevalence of 42.4%. The seroprevalence ranged from 31.1% to 48.1% in different cities with the highest in Punjab province (44.5%). In univariable analysis, the odds of seropositivity was higher in men compared to women (OR: 1.10, 95% CI: 1.01–1.19, P < 0.05). In multivariable analysis, the risk of being seropositive was lower (OR 0.72, 95% CI: 0.60–0.87, P < 0.01) in younger group (≤ 20 years) than in those aged above 60 years.ConclusionThe study concluded that despite a reasonable seroprevalence, the country is yet to reach the base minimum of estimations for herd immunity. The durability of immunity though debated at the moment, has shown an evidenced informed shift towards longer side.

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.

Objective: To determine the diagnostic accuracy of Anti-Mullerian Hormone in Polycystic ovary syndrome detection, keeping Rotterdam criteria as a gold standard. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi and Rehman Medical Institute, (RMI)Peshawar, Pakistan from Jul 2018 to Jun 2019. Methodology: The study included one hundred and forty clinically suspected patients of polycystic ovary syndrome (PCOS) of 16-45 years of age. Blood samples were analyzed for serum Anti-Mullerian Hormone analysis on Architect ci 8200 System using the Chemiluminescent immunoassay technique. AMH was considered positive for Polycystic ovary syndrome at a threshold of 4.9ng/ml. In addition, AMH's diagnostic accuracy was evaluated, considering the Rotterdam criteria of PCOS as a gold standard. Results: The mean age and mean BMI of the study subjects were 26.73±5.07 years and 30.43±4.83kg/m2, respectively. The mean follicle-stimulating and Luteinizing hormones were 4.34±0.68mIU/ml and 5.24±1.43mIU/ml, respectively. The mean Anti-Mullerian hormone of all patients was 7.79±4.62ng/ml. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio of a positive test (LR+) and Likelihood ratio of a Negative Test (LR-) of AntiMullerian hormone were 91.8%, 74.7%, 73.7%, 92.2%, 3.63%, 0.11%, respectively and overall diagnostic accuracy was 82.1%. Conclusion: Anti-Mullerian hormone can effectively determine the existence of Polycystic ovary syndrome among women of reproductive age and serve as a sensitive diagnostic tool for Polycystic ovary syndrome.