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

Aims: This study was aimed to monitor the asymptomatic carriage of coagulase-positive staphylococcal bacteria among university male students and detect the prevalence of virulence marker genes that encode methicillin resistance (mecA) and Panton-Valentine leukocidin (PVL) toxin among the isolates. Methodology and results: Single nasal swaps were collected from 144 participating students who resided at four different locations within Al-Madinah city. A total of 112 Gram-positive staphylococcal isolates were recovered from the 144 participants (carriage rate of 77.8%). Coagulase-positive staphylococci were differentiated using duplex PCR amplification of the 16S rRNA and nuc genes and accounted for 30 isolates (carriage rate of 20.8%). These isolates were most prevalent in the northern and southern parts of Al-Madinah city, while the lowest numbers of isolates were detected in students of the eastern part. Coagulase-positive isolates were further phenotypically characterized for methicillin resistance by the disc diffusion method. Uniplex PCR assays were conducted to screen for mecA- and PVL toxin-encoding genes. The mecA gene was amplified from all 15 (50%) methicillin-resistant coagulase-positive isolates, while the PVL toxin-encoding gene was detected in 19 isolates (63.3%), 10 (33.3%) of which contained the mecA gene. Lastly, PCR amplification of the NRPS gene from coagulase-positive isolates revealed the absence of Staphylococcus argenteus, the recently discovered genetically divergent lineage of Staphylococcus aureus. Conclusion, significance and impact of study An elevated prevalence of coagulase-positive isolates harboring mecA and PVL virulence genes was observed compared with previous investigations. This poses a potential threat if they spread among the population, resulting in outbreaks of community-acquired infections.

Background: Pediatric malignant bone tumors constitute an important subgroup of solid tumors and need comprehensive multidisciplinary care for optimal management. We aimed to review our local practice of managing malignant bone tumors and identify gaps to improve service. Methods: We retrospectively reviewed disease characteristics and management of twenty-five pediatric patients with malignant bone tumors from Jan 2000 to Dec 2020. Results: Median age at diagnosis was 8.75 years, male to female ratio of 0.8:1, and median follow-up was 3.6 years. Pain and swelling were the predominant symptoms at presentation, while lung was the most common metastatic site in Osteosarcoma (OS) and Ewing’s Sarcoma Family Tumors (ESFT). Metastatic disease was not associated with developing an event in OS (P=0.26) but was significantly associated with developing an event in the ESFT subgroup (P=0.002). There was no association of tumor necrosis of ＜90% or positive histological margins with developing an event in the entire cohort. The relapsed disease was associated with a mortality risk in the OS group (P=0.01). At the same time, it did not return significant results for this association in ESFT; however, a trend was noted for poor outcomes (P=0.09). Event-free survival and overall survival in OS were 54% and 69%, while in the ESFT group, they were 50% and 66%, respectively. Conclusion Metastatic disease was associated with developing relapsed disease in the ESFT cohort, while relapsed disease was associated with mortality in the OS cohort.Positive histological margins and ＜90% necrosis on resected tumor specimens did not result in poor survival. Multicenter collaboration at the national level is needed to improve the outcome of this disease group, which needs specialized multidisciplinary management.

Background: Pediatric malignant bone tumors constitute an important subgroup of solid tumors and need comprehensive multidisciplinary care for optimal management. We aimed to review our local practice of managing malignant bone tumors and identify gaps to improve service. Methods: We retrospectively reviewed disease characteristics and management of twenty-five pediatric patients with malignant bone tumors from Jan 2000 to Dec 2020. Results: Median age at diagnosis was 8.75 years, male to female ratio of 0.8:1, and median follow-up was 3.6 years. Pain and swelling were the predominant symptoms at presentation, while lung was the most common metastatic site in Osteosarcoma (OS) and Ewing’s Sarcoma Family Tumors (ESFT). Metastatic disease was not associated with developing an event in OS (P=0.26) but was significantly associated with developing an event in the ESFT subgroup (P=0.002). There was no association of tumor necrosis of ＜90% or positive histological margins with developing an event in the entire cohort. The relapsed disease was associated with a mortality risk in the OS group (P=0.01). At the same time, it did not return significant results for this association in ESFT; however, a trend was noted for poor outcomes (P=0.09). Event-free survival and overall survival in OS were 54% and 69%, while in the ESFT group, they were 50% and 66%, respectively. Conclusion Metastatic disease was associated with developing relapsed disease in the ESFT cohort, while relapsed disease was associated with mortality in the OS cohort.Positive histological margins and ＜90% necrosis on resected tumor specimens did not result in poor survival. Multicenter collaboration at the national level is needed to improve the outcome of this disease group, which needs specialized multidisciplinary management.

Background: Pediatric malignant bone tumors constitute an important subgroup of solid tumors and need comprehensive multidisciplinary care for optimal management. We aimed to review our local practice of managing malignant bone tumors and identify gaps to improve service. Methods: We retrospectively reviewed disease characteristics and management of twenty-five pediatric patients with malignant bone tumors from Jan 2000 to Dec 2020. Results: Median age at diagnosis was 8.75 years, male to female ratio of 0.8:1, and median follow-up was 3.6 years. Pain and swelling were the predominant symptoms at presentation, while lung was the most common metastatic site in Osteosarcoma (OS) and Ewing’s Sarcoma Family Tumors (ESFT). Metastatic disease was not associated with developing an event in OS (P=0.26) but was significantly associated with developing an event in the ESFT subgroup (P=0.002). There was no association of tumor necrosis of ＜90% or positive histological margins with developing an event in the entire cohort. The relapsed disease was associated with a mortality risk in the OS group (P=0.01). At the same time, it did not return significant results for this association in ESFT; however, a trend was noted for poor outcomes (P=0.09). Event-free survival and overall survival in OS were 54% and 69%, while in the ESFT group, they were 50% and 66%, respectively. Conclusion Metastatic disease was associated with developing relapsed disease in the ESFT cohort, while relapsed disease was associated with mortality in the OS cohort.Positive histological margins and ＜90% necrosis on resected tumor specimens did not result in poor survival. Multicenter collaboration at the national level is needed to improve the outcome of this disease group, which needs specialized multidisciplinary management.

Background: Pediatric malignant bone tumors constitute an important subgroup of solid tumors and need comprehensive multidisciplinary care for optimal management. We aimed to review our local practice of managing malignant bone tumors and identify gaps to improve service. Methods: We retrospectively reviewed disease characteristics and management of twenty-five pediatric patients with malignant bone tumors from Jan 2000 to Dec 2020. Results: Median age at diagnosis was 8.75 years, male to female ratio of 0.8:1, and median follow-up was 3.6 years. Pain and swelling were the predominant symptoms at presentation, while lung was the most common metastatic site in Osteosarcoma (OS) and Ewing’s Sarcoma Family Tumors (ESFT). Metastatic disease was not associated with developing an event in OS (P=0.26) but was significantly associated with developing an event in the ESFT subgroup (P=0.002). There was no association of tumor necrosis of ＜90% or positive histological margins with developing an event in the entire cohort. The relapsed disease was associated with a mortality risk in the OS group (P=0.01). At the same time, it did not return significant results for this association in ESFT; however, a trend was noted for poor outcomes (P=0.09). Event-free survival and overall survival in OS were 54% and 69%, while in the ESFT group, they were 50% and 66%, respectively. Conclusion Metastatic disease was associated with developing relapsed disease in the ESFT cohort, while relapsed disease was associated with mortality in the OS cohort.Positive histological margins and ＜90% necrosis on resected tumor specimens did not result in poor survival. Multicenter collaboration at the national level is needed to improve the outcome of this disease group, which needs specialized multidisciplinary management.

The coronavirus disease (COVID-19) pandemic has led to an alarming increase in domestic violence against women owing to lockdown measures and limited access to support services. This article provides insights into the global prevalence of domestic violence, barriers to seeking help, its impact on women and children, and the best practices implemented worldwide. Domestic violence encompasses various forms of abuse; many young women experience partner violence. Barriers to seeking help include fear, financial constraints, lack of awareness of available services, and distrust among stakeholders. The consequences of domestic violence affect the mental health of both mothers and children. Countries have increased shelter funding and developed innovative protocols to reach survivors and address this issue. However, the healthcare sector’s involvement in addressing domestic violence has been limited. This review advocates collaboration among healthcare institutions and government bodies. Key recommendations include utilizing telehealth services, implementing comprehensive training programs, establishing effective referral systems, enhancing health education, developing a domestic violence registry, improving the responses of law enforcement and justice systems through healthcare integration, promoting data sharing, and conducting further research. Healthcare systems should recognize domestic violence as a public health concern and detect, prevent, and intervene in cases to support survivors.

Background: In patients with suspected pulmonary embolism (PE), the literature suggests the overuse of computerized tomography pulmonary angiography (CTPA) and underuse of clinical decision rules before imaging request. This study determined the potential for avoidable CTPA using the modified Wells score (mWS) and D-dimer assay in patients with suspected PE. Methods: This hospital-based retrospective study analyzed the clinical data of 661 consecutive patients with suspected PE who underwent CTPA in the emergency department of a tertiary hospital for the use of a clinical prediction rule (mWS) and D-dimer assay. The score was calculated retrospectively from the available data in the files of patients who did not have a documented clinical prediction rule. Overuse (avoidable) CTPA was defined as D-dimer negativity and PE unlikely for this study. Results: Of 661 patients’ data examined, clinical prediction rules were documented in 15 (2.3%).In total, 422 patients (63.8%) had required information on modified Wells criteria and D-dimer assays and were included for further analysis. PE on CTPA was present in 22 (5.21%) of PE unlikely (mWS ≤4) and 1 (0.24%) of D-dimer negative patients. Thirty patients (7.11%) met the avoidable CTPA (DD negative+PE unlikely) criteria, and it was significantly associated with dyspnea. The value of sensitivity of avoidable CTPA was 100%, whereas the positive predictive value was 90.3%. Conclusion Underutilization of clinical prediction rules before prescribing CTPA is common in emergency departments. Therefore, a mandatory policy should be implemented regarding the evaluation of avoidable CTPA imaging to reduce CTPA overuse.

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