Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

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*

Background and Objectives: Monosyllable words are the most common speech recognition stimuli since they test auditory perception and are used to assess speech recognition. However, there is a lack of resources available for the Urdu-speaking Pakistani population. This study aims to develop and psychometrically evaluate a digitally recorded Urdu monosyllabic word list for Word Recognition Score (WRS) testing. Subjects and Methods: A total of 135 monosyllabic words were selected from a previous study. These words were digitally recorded by a native female Urdu speaker in a studio. The recordings were psychometrically assessed by 30 native Urdu speakers with normal hearing. The 100 most familiar words were selected and organized into two lists, each further divided into four halves to ensure that the words were relatively homogeneous in terms of audibility. Results: The average psychometric slope between 20% and 80% for the full list was 4.78%/dB±0.22%/dB, while it was 4.81%/dB±0.35%/dB for the half list. No statistically significant difference in p-values was observed between the full and half lists. The mean psychometric slope for 50% intelligibility was 6.04%/dB for both the full list (SD=0.44) and the half lists (SD=0.40). Conclusions Digitally recorded Urdu monosyllabic word lists are valid for assessing speech recognition in native Urdu speakers with normal hearing.

Male infertility is a worldwide health issue, affecting 8%-12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.848C>A, p.A283E) in the coiled-coil domain-containing 34 gene (CCDC34) in a consanguineous Pakistani family. This rare mutation was predicted to be deleterious and to affect the protein stability. Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms. These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms, thus expanding the phenotypic spectrum of CCDC34 missense mutations.
Humans ; Male ; Mutation, Missense/genetics* ; Pakistan ; Consanguinity ; Asthenozoospermia/genetics* ; Pedigree ; Infertility, Male/genetics* ; Adult ; Oligospermia/genetics* ; Exome Sequencing ; Axoneme/ultrastructure* ; Spermatozoa/ultrastructure*

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
Humans ; Male ; Consanguinity ; Pakistan ; Infertility, Male/metabolism* ; Semen/metabolism* ; Sperm Tail/metabolism* ; Spermatozoa/metabolism* ; Flagella/pathology* ; Mutation

Background: and Purpose Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. Methods: We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. Results: Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60–187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.07), male sex (OR, 0.44; 95% CI, 0.24–0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29–0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. Conclusion Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.