Hyperglycemia recognised in early pregnancy is phenotypically type 2 diabetes mellitus not gestational diabetes mellitus: a case control study

OBJECTIVE: Gestational diabetes mellitus is defined as "diabetes recognized in the second or third trimester that is not clearly overt diabetes". Evidence relating to women with hyperglycemia early in pregnancy is limited. We aimed to evaluate women diagnosed with hyperglycemia early in pregnancy (eGDM) and compared them to those with pregestational established type 2 diabetes mellitus (T2DM) and gestational diabetes diagnosed routinely at 24-28-week gestation (rtGDM) to determine if the length of exposure to hyperglycemia adversely affected outcomes. METHODS: Forty consecutive women with eGDM who attended a multidisciplinary antenatal clinic were reviewed. Two separate BMI-matched control groups were identified, recognized pregestational T2DM (n = 80) and rtGDM (n = 80). Baseline demographics and outcomes were compared. RESULTS: A higher proportion of women in the eGDM and T2DM group required insulin and the incidence of hypertensive disorders was similarly increased compared with the rtGDM group (88.6, 77.0 versus 8.1%, p < .001 and 42.5%, 37.5 versus 12.5% p < .001, respectively). The proportion of infants born small for gestational age varied (eGDM 11.1%, T2DM 13.0%, and rtGDM 2.5%, p=.049). Postpartum, 7.5% of eGDM women were diagnosed with T2DM versus 1.3% in the rtGDM group (p<.001). CONCLUSIONS: These novel data demonstrate that the length of exposure to glucose adversely affects materno-foetal outcomes independent of maternal adiposity

Proteomic Analysis of Chikungunya Virus Infected Microgial Cells

Chikungunya virus (CHIKV) is a recently re-emerged public health problem in many countries bordering the Indian Ocean and elsewhere. Chikungunya fever is a relatively self limiting febrile disease, but the consequences of chikungunya fever can include a long lasting, debilitating arthralgia, and occasional neurological involvement has been reported. Macrophages have been implicated as an important cell target of CHIKV with regards to both their role as an immune mediator, as well evidence pointing to long term viral persistence in these cells. Microglial cells are the resident brain macrophages, and so this study sought to define the proteomic changes in a human microglial cell line (CHME-5) in response to CHIKV infection. GeLC-MS/MS analysis of CHIKV infected and mock infected cells identified some 1455 individual proteins, of which 90 proteins, belonging to diverse cellular pathways, were significantly down regulated at a significance level of p<0.01. Analysis of the protein profile in response to infection did not support a global inhibition of either normal or IRES-mediated translation, but was consistent with the targeting of specific cellular pathways including those regulating innate antiviral mechanisms

Pregnant Women&rsquo;s Experiences with Midwifery-Led Antenatal Care Services in Peri-Urban Communities in Karachi, Pakistan

Nida Salman Yazdani,1 Kaniz Amna Haider,2 Amna Khan,2 Syed Ali Jaffar Zaidi,2 Akbar Rajani,1 Imran Nisar,2 Fyezah Jehan,2 Zahra Hoodbhoy2 1Research and Programs, VITAL Pakistan Trust, Karachi, Pakistan; 2Department of Paediatrics and Child Health, the Aga Khan University, Karachi, PakistanCorrespondence: Zahra Hoodbhoy, Aga Khan University, Stadium Road PO Box 3500, Karachi, 74800, Pakistan, Tel +92-3343481179, Email [email protected]: To understand pregnant women’s experience with midwifery-led antenatal care services using the Respectful Maternity Care charter in primary health centers in Karachi, Pakistan.Methods: This cross-sectional study was at Rehri Goth and Ibrahim Hyderi, two peri-urban communities in Karachi, Pakistan, where women receive antenatal care services. All pregnant women in their third trimester who consented during the study period were included. The participants were asked about access to care, antenatal care experience, person-centered approach, and general satisfaction with the facility using a pre-designed questionnaire. These themes were mapped onto the universal Respectful Maternity Care charter. Descriptive statistics were used to summarize the findings in each of these themes. Multivariable logistic regression techniques to determine the relationship between the dependent and independent variables.Results: There were 904 women who agreed to participate in this study during January to December 2021. Majority of the women (94%, n=854) were satisfied with the operating hours and cleanliness. More than 90% of the women reported positive experiences regarding privacy, respectful treatment by midwives, and non-discriminatory care. However, 40% (n=362) of the women reported not receiving adequate information and informed consent before a medical procedure, while 65% (n=587) reported poor counseling for birth preparedness. Maternal age, women’s occupation, women’s education, and parity were found to be significantly associated with respect provided, satisfaction with counseling and the consent process.Conclusion: This study reported satisfaction of pregnant women with the facility’s ambiance, respect, and care; however, poor communication skills regarding consent and antenatal counseling were reported. The findings suggest the need for more efficient strategies, such as regular respectful maternity care and technical training to strengthen midwife-patient interactions and enhance overall satisfaction, thus improving maternal and newborn outcomes.Keywords: antenatal care, patient satisfaction, Respectful Maternity Care, Pakista

The importance of male partner involvement for women's acceptability and adherence to female-initiated HIV prevention methods in Zimbabwe.

Enlisting male partner involvement is perceived as an important component of women's successful uptake of female-initiated HIV prevention methods. We conducted a longitudinal study among a cohort of 955 Zimbabwean women participating in a clinical trial of the effectiveness of a female-initiated HIV prevention method (the diaphragm and lubricant gel) to: (a) describe the extent to which women involved their male partners in the decision to use the study products, and (b) measure the effect perceived male partner support had on their acceptability and consistent use of these methods. Reported levels of male partner involvement in discussions and decisions regarding: joining the study, study activities, the outcome of HIV/STI test results, and product use were very high. In multivariate analyses, regular disclosure of study product use and partner approval for the diaphragm and gel were significantly associated with women's acceptability and consistent use of the products; an essential component for determining efficacy of investigational prevention methods. These results support the need for more sophisticated measurement of how couples interact to make decisions that impact study participation and investigational product use as well as more rigorous adaptations and evaluations of existing strategies to involve male partners in female-initiated HIV prevention trials

Prospects for bioreductive drug development

Bioreductive drugs are inactive prodrugs that are converted into potent cytotoxins under conditions of either low oxygen tension or in the presence of high levels of specific reductases. The biochemical basis for selectivity relies on the ability of oxygen to reverse the activation process and the presence of elevated reductase levels in some tumour types. Key criteria for an ideal bioreductive drug should include poor activity against aerobic cells, activation over a broad range of oxygen tensions and, penetration through the aerobic fraction of cells. In addition, the active drug should be capable of killing non-proliferating cells. Numerous compounds are currently at various stages of drug development but Mitomycin C, which is generally considered to be the prototype bioreductive drug, is the only one in clinical use today. Of the drugs currently being evaluated clinically, tirapazamine has definite clinical activity against a variety of solid tumours when used in combination with cisplatin. Other drugs, such as EO9 and various nitroimidazoles, have not been impressive in the clinic and further development is required to improve properties such as drug delivery in the case of indoloquinones. A novel approach to exploiting tumour hypoxia is the development of a gene-directed enzyme prodrug therapy (GDEPT) strategy, where a gene encoding for a prodrug activating enzyme has been placed under the control of a hypoxia responsive promoter sequence. It is generally recognised that bioreductive drugs must be directed towards patients whose tumours have hypoxic regions or have appropriate enzymological characteristics. In terms of identifying tumour hypoxia, there has been considerable progress in the development of nitroimidazole based hypoxia markers that can be detected either via non-invasive or invasive procedures. Another strategy currently undergoing preclinical evaluation is the use of agents that modulate tumour blood flow and synergistic effects have been reported between bioreductive drugs and photodynamic therapy or inhibitors of nitric oxide synthase for example. The development of clinically useful bioreductive drugs depends therefore on the expertise of scientists and clinicians with varying backgrounds. The purpose of this review is to describe and critically assess recent developments in this field, with particular emphasis being placed on drug development and strategies aimed at optimising bioreductive drug activity