Association of obesity with infertility among Pakistani men: A case control study

Background: The reported prevalence of infertility in Pakistan is 21% of which 35% is contributed by male factor. Male infertility has multifactorial etiologies ranging from modifiable to genetic risk factors. Among all the risk factors that may account for male infertility, obesity is one of the emerging public health problems. Therefore, the aim of the study was to determine the association of obesity with infertility in Pakistani men.Methods: We conducted a case control study. Cases were men with impaired semen parameters and controls did not have impaired semen parameters.Results: The final multivariable logistic regression model after adjusting for the effect of other variables revealed that with every 1 kg/m2 increase in BMI the odds of being infertile was 6% higher as compared to being fertile (aOR = 1.06; 95% CI = 1.01, 1.11). Moreover the odds of having education of higher secondary or above was 3 times greater among cases as compared with the controls (OR = 3.10; 95% CI = 1.66, 5.77). Furthermore the odds of having previous medical conditions increasing the risk of infertility was higher among cases as compared with the controls (OR = 3.07; 95% CI = 1.63, 5.79).Conclusion & recommendations: This study indicates that obesity is an important risk factor for male infertility. Moreover our findings also indicate that higher educational status and previous medical conditions are also associated with male infertility. Thus awareness can be raised through treating physicians and public health messages

Spectrum of cystic fibrosis conductance regulator gene mutations reported in Pakistani descent cystic fibrosis patients

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aims to determine the genotypic and phenotypic spectrum of the CFTR gene mutations reported in the literature for Pakistani-origin CF patients. Databases were searched for such studies from 1947-2019 for sample size, method of diagnosis, and CFTR gene mutations. The authors identified 12 studies reporting 33 CFTR gene mutations, both intronic as well as exonic in Pakistani origin patients. The most widely tested mutation was D508 with a frequency of 17%-60%. No hotspot zone was identified and not all reported mutations were causing disease. There is a need to identify common mutations in the Pakistani population to develop population-specific CFTR mutations panel. This will enable the researchers to perform phenotype-genotype correlation studies to improve the CF detection rate

Response to imatinib mesylate in patients with early chronic phase chronic myeloid leukemia and derivative chromosome 9 deletion or clonal evolution

Objectives: The significance of clonal evolution and derivative chromosome 9 in Philadelphia-positive CML is not fully characterized and studies have yielded conflicting results. After working on emergence of clonal evolution from our region, we continued to find out the response of Imatinib Mesylate on such cases of CML treated in our center. Materials and methods: We conducted a cross sectional, prospective analysis on response of Imatinib Mesylate on patients with Philadelphia positive chronic myeloid leukemia with clonal evolution treated from period of September 2007 till 2010. Patients were grouped on basis of cytogenetic analysis performed by conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques and followed for three years to see the response rate of imatinib mesylate. Results: We reported here the response rate in one hundred and two previously untreated cases of chronic myeloid leukemia (Philadelphia positive). Twelve patients (11.7%) exhibit derivative chromosome 9, three had trisomy 8, one with addition 15 and one had deletion 16. At follow-up of 30 months 78 cases were evaluable and 45% and 61% showed complete and major cytogenetic response respectively. There is no significant association of derivative chromosome 9 with the response of imatinib mesylate in our group. Conclusion: Imatinib mesylate is the first line therapy in chronic phase of CML but the role in patients with clonal evolution need to be established by larger group of patients

A cyclic lipopeptide from Fusarium graminearum targets plant membranes to promote virulence

Summary: Microbial plant pathogens deploy amphipathic cyclic lipopeptides to reduce surface tension in their environment. While plants can detect these molecules to activate cellular stress responses, the role of these lipopeptides or associated host responses in pathogenesis are not fully clear. The gramillin cyclic lipopeptide is produced by the Fusarium graminearum fungus and is a virulence factor and toxin in maize. Here, we show that gramillin promotes virulence and necrosis in both monocots and dicots by disrupting ion balance across membranes. Gramillin is a cation-conducting ionophore and causes plasma membrane depolarization. This disruption triggers cellular signaling, including a burst of reactive oxygen species (ROS), transcriptional reprogramming, and callose production. Gramillin-induced ROS depends on expression of host ILK1 and RBOHD genes, which promote fungal induction of virulence genes during infection and host susceptibility. We conclude that gramillin’s ionophore activity targets plant membranes to coordinate attack by the F. graminearum fungus