Search

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. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes of side-to-side staple versus hand-sewn esophago-gastric anastomosis in esophagectomy patients with carcinoma of esophagus after subtotal esophagectomy along with gastric tube reconstruction. Study Design: Retrospective cross-sectional study. Place and Duration of Study: Lady Reading Hospital, Peshawar Pakistan, from July 2019 to June 2020. Methodology: After ethical approval, medical records of patients that underwent stapled/hand sewn gastro esophageal anastomosis due to carcinoma esophagus were included. Inoperable Ca esophagus and with thoracic anastomosis were excluded. Each anastomotic technique was applied on 50 patients randomly. The variables of study included demographic, anastomotic leak, anastomotic stricture, operative time, and other complications. All the cases were followed up for 1 year. SPSS version 26.0 was used for data analysis. Result: From 100 patients, 56 were males and 34 females. Age ranged from 15 to 80 years with mean age of 48.5 and 51.1 respectively in two groups. In 42 cases tumor was present in lower end, middle third in 30 and middle lower third of gastro esophageal junction in 28 cases. Histo-pathologically 58 cases were adenocarcinoma, 31 squamous cell carcinoma and 11 adeno squamous carcinoma. The anastomosis time in group I was 6.8±.22 minutes while in group II was 13.2±1.71 minutes (p0.04). None of the patients in group I, having stapled anastomosis were found to have anastomotic leakage or stricture formation after 1 year of follow up while 04 patients in group II were reported to have anastomotic leakage and 06 patients had anastomotic stricture formation (p-<0.01). Conclusion: Side by side stapled anastomosis technique was far superior to hand-sewn technique in terms of the time taken for anastomosis to be completed and patient outcomes (anastomotic leakage and stricture formation). [ABSTRACT FROM AUTHOR]

Study was conducted to assess the over prescription of antibiotics by Karachi dentists working in public and private sector. The sample size of the study was 500. A questionnaire was developed and distributed among the Registered Dental Practitioners. This study was spread over 6 months. Data entry and analysis was done on SPSS software version 20. Descriptive statistics were generated. The present study provides evidence of over prescription of antibiotics by dentists of Karachi, Pakistan. Therefore, appropriate guidelines should be provided by regulatory bodies. Local measures should be prioritized by removing the cause. It is necessary to take educational initiatives to encourage rational and correct use of antibiotics. [ABSTRACT FROM AUTHOR]

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&#95;176del, p.(Arg53&#95;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&#95;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., (© 2024. The Author(s).)

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&#95;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., (© 2024. The Author(s).)

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.

Background: Spiritual health forms the core of health and is associated with better physical and mental health. Spiritual health and wellbeing has been shown to be significantly associated with better mental outcomes, yet there's lack of understanding of the determinants of spiritual health. Religious practices have been shown to improve health and have been assumed to be associated with spirituality, yet there remains a gap between religious practices and spiritual health. It is therefore, crucial to understand the role of religious beliefs and practices in improving spiritual health., Purpose: To assess spiritual wellbeing between religious and non-religious professionals and assess how regional religious beliefs and practices are associated with spiritual wellbeing., Methods: We examined spiritual health among religious and non-religious professionals. A comparative cross sectional study was done with a sample size of 210. Differences of spiritual health and spiritual experiences, perceived spiritual traits and psychological parameters were observed., Results: Religious professionals were found to be more spiritually healthy than non-religious professionals (P < .05). Spiritual experiences weakly contribute to spiritual health (r = 0.39, P < .05). Perceived spiritual traits including frequency of prayer (β = 5.25, CI = 1.80-8.70, P < .01) and belief in the presence of Supreme Being (β = 1.001, CI = 0.120-1.883, P < .05) influenced spiritual wellbeing and spiritual wellbeing showed a negative association with psychological parameters including anger (OR = 0.95, CI = 0.929-0.987, P < .05)., Conclusion and Implications: The findings from this study show that religious professionals tend to be more spiritually healthy than non-religious professionals highlighting the importance of incorporating religious practices to ensure spiritual wellbeing. Improving spiritual wellbeing can provide an important tool for promoting holistic healing.

A survey was undertaken to assess the knowledge, attitude and practice of medical ethics among surgical residents and interns in three teaching hospitals of Karachi, Pakistan. 101 out of 120 completed responses were included in the study. Fifty-one respondents had heard about the Code of Ethics formulated by the Pakistan Medical and Dental Council. Forty-four had read the code. Seven had no knowledge about it. Forty-seven reported taking consent for procedures. Forty-two respondents gave correct answers on questions of confidentiality and knowledge of law pertaining to trauma victims. Only 11 reported having been taught ethics as students. Four did not feel the need of its teaching at an undergraduate level. Doctors graduating within the last 10 years gave fewer correct answers than those graduating earlier. Knowledge of medical ethics and its application on the surgical floors is extremely poor. The survey results support the view that medical ethics should be part of the undergraduate medical curriculum.