Early pregnancy biochemical markers of placentation for screening of gestational diabetes mellitus (GDM).

For the effective management and screening of patients with diabetes, lipid profile has been a useful mean. Here, we hypothesized that biochemical analyses of blood serum in pregnant women with GDM will develop an insight on the pathogenesis of the disease and possibly uncover new biomarkers. In order to test our hypothesis, antenatal pregnant women (n = 300) were selected for blood samples including 176 with positive clinical/family history and 124 with negative clinical/family history of GDM during the early second trimester (14-18 weeks of gestation). All the subjects were followed up to the early third trimester (24-28 weeks of gestation) for second sampling until the onset of GDM. Lipid profile data shows that mean values of triglycerides, total cholesterol, low density lipids and very low density lipids were significantly higher (p < 0.05) and mean HDL was significantly lower in early second trimester in those patients who subsequently developed GDM during late third trimester when compared with those who didn't develop GDM. Inflammatory biomarker such as High-sensitivity C-reactive protein (hs-CRP) levels were also found to be significantly higher by 69% increase in patients who developed GDM later in third trimester in comparison with those who didn't develop. About 32% patients who finally developed GDM belonged to positive clinical/family history group. The results of our study indicate that abnormal serum cholesterol; triglycerides, HDL, LDL, VLDL and hs-CRP play a vital in pathophysiology of gestational diabetes. Early diagnosis of GDM based on these biochemical markers will help decrease adverse neonatal and maternal outcomes.

Awareness and Attitudes of Research Students Toward Dual-use Research of Concern in Pakistan: A Cross-sectional Questionnaire.

Dual-use research poses a significant challenge for scientists in the biomedical field and for global health security in general. As the scientific knowledge and materials required for the development of biological agents become progressively more accessible and inexpensive, there is an increased need to understand and improve the governance of scientific research. Prevention of the misuse of facilities, equipment, agents, and scientific knowledge requires high levels of awareness of the concept of dual-use research, starting with early-career scientists and graduate students. In this study, the attitudes and level of awareness of postgraduate students in Pakistan toward the issues surrounding dual-use research were assessed through a survey containing both quantitative and qualitative questions in 32 universities in 4 provinces, federal area, and Azad Jammu and Kashmir regions of Pakistan; 933 students responded. Most (58.2%) had never heard of dual-use research of concern (DURC), while 18.5% had heard the term but were unsure of its meaning. Irrespective of prior knowledge, a higher percentage of students (68.6%) felt an obligation to report research misuse. Considering the need for DURC training, 94.1% of the respondents agreed that the principal investigator should take the responsibility to train students on DURC at the start of a research project. When experimental results having dual-use potential, 69.1% indicated they would publish with limited protocol, with 43.5% indicating they would publish the limited protocol only if there was a way for scientists to access their data. The survey results revealed limited DURC awareness among researchers across Pakistan. However, the respondents, although not formally educated about DURC, were quite aware of its impact. The information gained in this survey will be valuable in addressing country-specific awareness and training needs.

Formulation and in vitro evaluation of carbopol 934-based modified clotrimazole gel for topical application.

The aim of present study was to enhance topical permeation of clotrimazole gel preparation by using various permeability enhancers such as coconut oil, pistachio oil and sodium lauryl sulphate (SLS). Clotrimazole gel preparations were prepared and optimized by using three factor, five level central composite design. A second-order polynomial equation was generated in order to estimate the effect of independent variables i.e. coconut oil (X1), pistachio oil (X2) and sodium lauryl sulphate (X3) at various dependent variables i.e. flux (Y1), lag time (Y2), diffusion coefficient (Y3), permeability coefficient (Y4), and input rate (Y5) of clotrimazole gel formulations. Ex vivo skin permeation study was performed through rat skin by using modified Franz diffusion cell system. Optimized formulation F8 exhibited highest flux 2.17 µg/cm2/min, permeability coefficient 0.0019 cm/min and input rate 1.543 µg/cm2/min, along with moderate lag time 77.27 min and diffusion coefficient 0.063 cm2/min, which is further supported by anti-fungal activity that exhibited more prominent zone of inhibition against Candida albicans, Aspergillus niger and Mucor. Thus, it can be concluded that permeation of clotrimazole gel was enhanced by various combination of coconut oil, pistachio oil and sodium lauryl sulphate but optimized formulation F8 containing 0.4 ml pistachio oil, 0.8 ml coconut oil and 0.04 g of SLS exhibited more pronounced and promising effect through rat skin.

A cornucopia of screening and diagnostic techniques for human papillomavirus associated cervical carcinomas.

Cervical carcinoma is one of the major consequences of human papillomavirus (HPV) infections. Although HPV infections of cervix do not always progress to cancer, 90% cases of cervical cancer have been found associated with high risk HPV (hrHPV) infection. Usually, HPV infection is asymptomatic; however, this asymptomatic infection can cause abnormal changes in cervix ultimately leading to cancer development. These changes can be detected by the application of screening tests at regular time intervals. For this purpose, morphological, cytological, and DNA based techniques are available. Nevertheless, abnormal screening tests have only the predictive value for precancerous lesions and thus require further evaluation which is usually done by using diagnostic techniques. So far, colposcopy and histological examination alone were considered as the gold standards for cervical cancer diagnosis. Currently, some tests based on expression level of host cell biomarkers are also being used along with histology for diagnostic purpose. Albeit, these tests have significant specificity and sensitivity values but they are unable to suggest a particular viral genotype involved in infection. Diagnostic methods such as PCR, HPV genotyping assays, microarray, and mRNA based assays are useful to predict the genotypes as well as the quantity of viral load in a host cell. Similarly, these diagnostic procedures have high specificity and sensitivity ranges. However, only few of them are practiced commonly, as approval of these tests as routine diagnostic tests requires clinical validation and cost effectiveness.

Matrix-assisted refolding and purification of placenta-derived recombinant human interleukin-6 produced in Escherichia coli.

Biological activity of human interleukin-6 (IL-6) is associated with a vast number of diseases such as rheumatoid arthritis, sepsis, and severe inflammatory diseases. In this study, human IL-6 cDNA was isolated from a cDNA library that was constructed with mRNA derived from human placental tissues. Subsequently, the complete human IL-6 cDNA was cloned and expressed in BL21DE3 cells. The recombinant human IL-6 (rhIL-6) protein was expressed in a form of an insoluble inclusion body. Inclusion bodies were solubilized under denaturing conditions and purified by immobilized metal affinity chromatography with gradual on-column refolding by the gradient elution method (from 6 to 0 M urea). The protein was purified to apparent homogeneity of about 99% with a yield of 50 mg/L. The purity was assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion high-performance liquid chromatography, and Western blotting analysis. The bioactivity was assessed by proliferation assay of TF-1 cells in a dose-dependent manner. The present study confirms the expression of the placenta-derived IL-6 gene in a prokaryotic expression system and matrix-assisted on-column refolding and purification of rhIL-6 by immobilized metal affinity chromatography.

Sudden death and isolated right ventricular noncompaction cardiomyopathy: report of 2 autopsied adult cases.

A predominantly right ventricular variant of isolated noncompaction cardiomyopathy is a potentially lethal disease entity, which only recently has become recognized in the clinical and cardiac imaging literature. There are currently few established morphologic criteria for the diagnosis other than right ventricular dilation and presence of excessive regional trabeculation. To date, there have been no autopsy reports of cases following either clinical diagnosis or sudden death. We report 2 adult cases of sudden unexpected death in which unexplained right ventricular dilation and prominent apical hypertrabeculation were the principal findings. The gross and microscopic results suggest pathological similarities between, or coexistence of, right ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathies.

Myocbacterium-avium intracellulare associated inflammatory pseudotumor of the anterior nasal cavity.

In this case report, we describe an unusual case of mycobacterial associated inflammatory pseudotumor that occurred in a patient with a previous history of cocaine abuse. We discuss inflammatory pseudotumor (IPT) in general and emphasize the rare entity where an associated mycobacterial infection is seen. The histogenesis is not yet completely understood. The lesion can pose challenges for practicing pathologists and a misdiagnosis of malignancy can occur at multiple facets. A discussion about the differential diagnosis and clues to make the distinction is presented. In addition to spindle cell proliferation, the presence of a background of mixed inflammatory cell infiltrate and foamy macrophages are clues to make the diagnosis. In the case of mycobacteria associated IPT, Acid Fast Bacilli (AFB) stains will easily highlight the organisms confirming the diagnosis.