Use of follicular output rate to predict intracytoplasmic sperm injection outcome

Background: The measurement of follicular output rate (FORT) has been proposed as a good indicator for evaluating follicular response to the exogenous recombinant folliclestimulating hormone (rFSH). This places FORT as a promising qualitative marker for ovarian function. The objective of the study was to determine FORT as a predictor of oocyte competence, embryo quality and clinical pregnancy after intracytoplasmic sperm injection (ICSI).Materials and Methods: This prospective study was carried out on a group of infer- tile females (n=282) at Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2010 till August 2013. Downregulated females were stimulated in injection gonadotropins and on ovulation induction day, pre-ovulatory follicle count (PFC) was determined using transvaginal ultrasound scan (TVUS), and FORT was determined as a ratio of PFC to antral follicle count (AFC)*100. Group I consisted of females with a negative pregnancy test, while group II had a positive pregnancy test that was confirmed with the appearance of fetal cardiac activity. Linear regression analyses of categorical variables of clinical pregnancy along with other independent variables, including FORT, were performed using SPSS version 15.0.Results: Pregnancy occurred in 101/282 women who were tested, recording a clinical pregnancy rate of about 35.8%. FORT values were higher in group II as compared to group I females (P=0.0001). In multiple regression analysis, 97.7, 87.1, 78.2, and 83.4% variations were explained based on the number of retrieved oocytes per patients, number of metaphase II oocytes retrieved, number of fertilized oocytes, and number of cleaved embryos, respectively, indicating FORT as an independent predictor.Conclusion: FORT is a predictor of oocyte competence in terms of a number of retrieved, mature and fertilized oocytes. It also gives information about the number of cleaved embryos and clinical pregnancy rate

Suicide and deliberate self-harm in Pakistan: A scoping review

Background: Suicide is a major global public health problem with more than 800,000 incidents worldwide annually. Seventy-five percent of the global suicides occur in low and middle-income countries (LMICs). Pakistan is a LMIC where information on suicidal behavior is limited. The aim of the review is to map available literature on determinants, risk factors and other variables of suicidal behavior in Pakistan.Method: This study was based on Arksey and O\u27Malley\u27s methodological framework of scoping review, combining peer reviewed publications with grey literature. Ten databases including Applied Social Sciences Index and Abstracts (ASSIA), Cochrane Trials Register (CRG), Cumulative Index to Nursing and Allied Health (CINAHL), National Library of Medicine Gateway (NLMG), ExcerptaMedica (EMBASE), National Library of Medicine\u27s MEDLINE (PUBMED), PSYCHINFO, Social Science Citation Index and Science Citation Index (SCI) and Pakmedinet.com were searched from the beginning of their time frames until December 2016 using a combination of key terms. The inclusion criteria included studies of various study designs covering different aspects of suicidal behavior in English language.Results: Six hundred and twenty three articles were initially retrieved from all ten databases. Two independent reviewers screened the titles and abstracts for relevance. One hundred and eighteen articles were read in full, out of which 11 were excluded because they did not fit the eligibility criteria. One hundred and ten articles, including two student theses and one report, were included in the final review. Most studies were descriptive in nature, with only three that used a case-control design. Majority of the studies were from urban areas, and addressed determinants rather than risk factors. Gender differences and age were predominantly reported, with more males committing suicide. Suicidal behavior was more common among individuals younger than 30 years of age. The three most common methods for suicides were hanging, poisoning and use of firearms. Mental illness as a risk factor for suicides was mentioned in only three studies.Conclusions: This review is the first attempt to synthesize available literature on suicidal behavior in Pakistan. The evidence is limited, and calls for more robust analytical research designs, along with a focus on risk factors

The extracellular polysaccharide Pel makes the attachment of P. aeruginosa to surfaces symmetric and short-ranged

Biofilms are surface-mounted, multicellular communities of microbes. Biofilms are often associated with chronic infections that resist treatment, evade the immune system, and damage host tissue. An essential characteristic of the biofilm state is that constituent organisms are bound in a polymeric matrix. This matrix gives the system spatial structure and clusters bacteria near each other, facilitating intercellular interactions. The Pseudomonas aeruginosa strain PAO1 is widely studied as a model biofilm-forming organism. The polymeric matrix of PAO1 biofilms is dominated by two bacteria-produced extracellular polymers, Pel and Psl. We use a combination of optical and atomic force microscopy to examine the roles of these polymers in very early biofilm development. In agreement with other researchers, we find that Psl mediates strong attachment to a glass surface. We find that Pel alone can mediate some attachment, but not as permanent as that mediated by Psl. Unexpectedly, we find that Pel promotes symmetric attachment, in the form of rod-shaped bacteria lying down flat on the surface, and that the presence of Pel makes attachment forces more short-ranged than they are with Psl alone. We suggest that these effects may result from synergistic interactions of Pel with the Psl polymeric matrix

The Immune-related role of BRAF in melanoma

Background: The existence of a dichotomy between immunologically active and quiescent, tumor phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. BRAF and NRAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAF and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group. Methods: One-hundred-thirteen melanoma metastases underwent microarray analysis and BRAF and NRAS genotyping. Allele-specific PCR was also performed in order to exclude low-frequency mutations. Results: Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association was stronger in samples displaying low BRAF mRNA expression. However, when testing NRAS mutations, we were not able to find the same association. Conclusion: This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation.</br

Comparative trends in ischemic heart disease admissions, presentation and outcomes due to the COVID-19 pandemic: First insights from a tertiary medical center in Pakistan

Introduction: COVID-19 has manifested a striking disarray in healthcare access and provision, particularly amongst patients presenting with life-threatening ischemic heart disease (IHD). The paucity of data from low-middle income countries has limited our understanding of the consequential burden in the developing world. We aim to compare volumes, presentations, management strategies, and outcomes of IHD amongst patients presenting in the same calendar months before and during the COVID-19 pandemic.Methods: We conducted a retrospective cross-sectional analysis at the Aga Khan University Hospital, one of the premier tertiary care centres in Pakistan. Data were collected on all adult patients (\u3e18 years) who were admitted with IHD (acute coronary syndrome (ACS) and stable angina) from March 1 to June 30, 2019 (pre-COVID) and March 1 to June 30, 2020 (during-COVID), respectively. Group differences for continuous variables were evaluated using student t-test or Mann-Whitney U test. The chi-squared test or Fisher test was used for categorical variables. Values of p less than 0.05 were considered statistically significant. P-value trend calculation and graphical visualization were done using STATA (StataCorp, College Station, TX).Results: Data were assimilated on 1019 patients, with 706 (69.3%) and 313 (30.7%) patients presenting in each respective group (pre-COVID and during-COVID). Current smoking status (p=0.019), admission source (p\u3c0.001), month of admission (p\u3c0.001), proportions ACS (p\u3c0.001), non-ST-elevation-myocardial-infarction (NSTEMI; p\u3c0.001), unstable angina (p=0.025) and medical management (p=0.002) showed significant differences between the two groups, with a sharp decline in the during-COVID group. Monthly trend analysis of ACS patients showed the most significant differences in admissions (p=0.001), geographic region (intra-district vs intracity vs outside city) (p\u3c0.001), time of admission (p=0.038), NSTEMI (p=0.002) and medical management (p=0.001).Conclusion: These data showcase stark declines in ACS admissions, diagnostic procedures (angiography) and revascularization interventions (angioplasty and coronary artery bypass graft surgery, CABG) in a developing country where resources and research are already inadequate. This study paves the way for further investigations downstream on the short- and long-term consequences of untreated IHD and reluctance in health-seeking behaviour

Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Filarial nematodes are an important group of human pathogens, causing lymphatic filariasis and onchocerciasis, and infecting around 150 million people throughout the tropics with more than 1.5 billion at risk of infection. Control of filariasis currently relies on mass drug administration (MDA) programs using drugs which principally target the microfilarial life-cycle stage. These control programs are facing major challenges, including the absence of a drug with macrofilaricidal or permanent sterilizing activity, and the possibility of the development of drug-resistance against the drugs available. Cysteine proteases are essential enzymes which play important roles in a wide range of cellular processes, and the cathepsin-like cysteine proteases have been identified as potential targets for drug or vaccine development in many parasites. Here we have studied the function of several of the cathepsin-like enzymes in the filarial nematode, B. malayi, and demonstrate that these cysteine proteases are involved in the development of embryos, show similar functions to their counterparts in C. elegans, and therefore, provide an important target for future drug development targeted to eliminate filariasis

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Population Genetics of GYPB and Association Study between GYPB*S/s Polymorphism and Susceptibility to P. falciparum Infection in the Brazilian Amazon

Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil.Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection.GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity.Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population