The Impact of Colorectal Conditions on Psychosocial Well Being of Caregivers and Patients Presenting to A Tertiary Care Hospital

Colorectal conditions such as Hirschsprung disease, anorectal malformation, fecal incontinence and spinal condition cause a significant stress among patients and their caregivers. Managing such disorders requires not only a one-time definitive surgery but a significant number of follow up visits, dietary modifications and long-term medication. The aim of this study was to estimate the psychosocial wellbeing of caregivers and patients suffering from these conditions

Genus Primula and its role in phytomedicine; a systematic review

Background: Primula is one of the prevalent and complex genus of family Primulaceae. Plants of Genus Primula are used in traditional medicine for treating various ailments. These plants are mostly growing in soggy meadows to alpine slopes. Various species are distributed in Pakistan, India, Indonesia, Ethiopia and South America. Purpose: This review is presented to provides up-to-date research progress in, phytochemistry, pharmacology of Genus Primula. It provides a strong basis for future scientific research in phytomedicine. Method: The relevant literature on Genus Primula was collected by resources i.e., scientific databases including Pubmed, Google Scholar, Google, ACS, Sci hub, Web of science, Science Direct databases and Encyclopedia. Results: Traditionally plants are used to treat eye aliments, respiratory tract infections, headache, epileptic seizures, insomnia, skin problems, ulcers, urinary disorders, expectorant and wound healing process etc. Alkaloids, flavonoids, flavones, glycosides, saponins, sapogenins, tannins, quinolones, terpenes, polysaccharides, volatile oils, coumarins, fatty acid, fatty alcohols, phytosterols, sugar alcohol, miconidin, fatty acid ester and unsaturated higher fatty acids are the medicinally important phytoconstituents of genus species of Primula. Pharmacological studies have shown their prominent biological activities such as antibacterial, antioxidant, antidiabetic, antiviral, antileishmanial, antiepileptic, anticancer, cardioprotactive, antiproliferative, anxiolytic, and contraceptive. Conclusion: Species of genus Primula are widely employed in traditional medicine system. It contains potential phytoconstituents which are being used in modern pharmacological research area. This review revealed that primulas are important medicinal plants and have pivotal role in phytomedicine

A Novel Homozygous Nonsense Variant in BICD2 Underlies Hereditary Spastic Paraplegia Complex Type

Hereditary spastic paraplegia (HSP) are a group of genetically and clinically diverse neurodegenerative ailments with distinguishing feature of lower limbs spasticity and upper motor neuron degeneration. BICD2 is an adaptor protein which regulates the cellular trafficking of cargo molecules crucial for motor neuron growth and maturation. In present study, a Pakistani family of HSP penetrating in autosomal recessive pattern was ascertained. Patients presented spasticity and stiffness of upper and lower limbs, severe microcephaly, dysphagia, no speech, hearing loss and seizures. Genome wide linkage analysis and whole exome sequencing revealed a novel homozygous nonsense mutation (c.204T>G) in BICD2 gene which was predicted to yield a truncated protein product (p. Glu68*). This is first nonsense mutation being reported causing HSP with complex clinical features and early onset. Further, functional exploration will be required for genotype phenotype correlation

An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan

Background: Primary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion of brain. Mutations in 25 genes have been reported to cause this disorder. Although majority of these genes were discovered in the Pakistani population, still a significant proportion of these families remains uninvestigated. Methods: We studied a cohort of 32 MCPH families from different regions of Pakistan. For disease gene identification, genome-wide linkage analysis, Sanger sequencing, gene panel, and whole-exome sequencing were performed. Results: By employing these techniques individually or in combination, we were able to discern relevant disease-causing DNA variants. Collectively, 15 novel mutations were observed in five different MCPH genes; ASPM (10), WDR62 (1), CDK5RAP2 (1), STIL (2), and CEP135 (1). In addition, 16 known mutations were also verified. We reviewed the literature and documented the published mutations in six MCPH genes. Intriguingly, our cohort also revealed a recurrent mutation, c.7782_7783delGA;p.(Lys2595Serfs*6), of ASPM reported worldwide. Drawing from this collective data, we propose two founder mutations, ASPM:c.9557C>G;p. (Ser3186*) and CENPJ:c.18delC;p.(Ser7Profs*2), in the Pakistani population. Conclusions: We discovered novel DNA variants, impairing the function of genes indispensable to build a proper functioning brain. Our study expands the mutational spectra of known MCPH genes and also provides supporting evidence to the pathogenicity of previously reported mutations. These novel DNA variants will be helpful for the clinicians and geneticists for establishing reliable diagnostic strategies for MCPH families