Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form of asthenoteratozoospermia, characterized by morphological abnormalities and reduced motility of sperm, causing male infertility. Although approximately 60% of MMAF cases can be explained genetically, the etiology of the remaining cases is unclear. Here, we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families using whole-exome sequencing (WES), including one compound heterozygous mutation ( DNAH10 : c.9409C>A [p.P3137T]; c.12946G>C [p.D4316H]) in family 1 and another compound heterozygous mutation ( DNAH10 : c.8849G>A [p.G2950D]; c.11509C>T [p.R3687W]) in family 2. All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools. Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance. Hematoxylin and eosin (H&E) staining revealed MMAF, including sperm head abnormalities, in the patients. In addition, immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella. These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.
Adult ; Humans ; Male ; Alleles ; Asthenozoospermia/pathology* ; Axonemal Dyneins/genetics* ; Dyneins/genetics* ; Exome Sequencing ; Infertility, Male/pathology* ; Mutation ; Pakistan ; Pedigree ; Sperm Tail/pathology*

PURPOSEFirearm injuries impose a continuous economic burden on society and hospital resources. The aim of this study was to assess the pattern of bony injuries among victims of gunshots.

METHODSA retrospective study was conducted in the Department of Orthopedics, Dow University of Health Sciences and Civil Hospital Karachi from January 2011 to December 2012. Patients with isolated bony injuries were included while patients with other systemic injuries were excluded.

RESULTSThere were 90 cases and the majority of them were male (84.4%). Mean age was (32.52 ± 10.27) years. Most of the patients (72.2%) belong to the younger age group. A low velocity weapon was used in 61 (67.8%) cases and a high velocity weapon was used in 29 (32.2%) cases. Armed robbery (64.4%) was the cause of conflict in more than half of the cases. Lower limb was involved in 72.2%. Fifty eight (64.4%) patients remained hospitalized for 15-20 days and others for more than 20 days. Internal fixation with intramedullary nailing was done in 35 patients while K-wire was used in 5 patients. Fifty patients were managed with external fixation, either uniplanar or multiplanar ilizarov. Deep wound infection and nonunion were observed more often in high velocity injuries.

CONCLUSIONArmed robbery was the leading cause of gunshot bony injuries in our hospital. Young males were victimized in a majority of cases. High velocity injuries were associated with more complications.

Adolescent ; Adult ; Bone and Bones ; injuries ; Female ; Fracture Fixation, Intramedullary ; Humans ; Male ; Middle Aged ; Pakistan ; epidemiology ; Retrospective Studies ; Tertiary Healthcare ; Wounds, Gunshot ; epidemiology

Objective: Present study was conducted to investigate in liver of rats from 8-12 weeks old to 20 weeks old, the age dependent changes, carbon tetrachloride mediated changes, and the hepatoprotective effect shown by the seeds of Vitis vinifera L. Method: The hepatoprotective activity was studied by observing the effect of 100 mg/kg dose of ethanolic extract of grape seeds on carbon tetrachloride induced hepatotoxicity in albino rats and results were compared with those of the aged group results. Results: 100 mg/kg b.w. of ethanolic extract of Vitis vinifera seeds produced highly significant decrease in AST, ALT, ALP, bilirubin, albumin levels and significant decrease in the TSP levels compared to the toxic group levels. The levels of AST, ALT, ALP, bilirubin and albumin in aged control rats were found to be significantly higher than the levels in young control animals. MDA levels were slightly higher while GSH levels were lower in aged control rats as compared to young control rats. MDA levels in the toxic group showed highly significant increase compared to the young control levels. Ethanolic extract of seeds of Vitis vinifera significantly lowered the MDA levels. Histopathology results reveal that 100mg/kg/day dose of ethanolic extract of seeds of Vitis vinifera L. cured the hepatic damage to a great extent which was induced by CCl4. Conclusions: Aging leads to the changes in the hepatic structure which are comparable to the changes induced by low doses of a hepatotoxin and the ethanolic extract of seeds of Vitis vinifera L. was effective in bringing about functional improvement of hepatocytes exposed to free radical attack, which was confirmed by biochemical and histological observations.