Signature precursor and mature microRNAs in cervical ripening during gestational diabetes mellitus lead to pre-term labor and other impediments in future.

Gestational diabetes mellitus (GDM) is a pathological condition in which the placenta releases a hormone called human placental lactogen that prevents maternal insulin uptake. GDM is characterised by varying degrees of carbohydrate intolerance and is first identified during pregnancy. Around 5-17% of pregnancies are GDM pregnancies. Older or obese women have a higher risk of developing GDM during gestation. Hyperglycemia is a classic manifestation of GDM and leads to alterations in eNOS and iNOS expression and subsequently causes ROS and RNS overproduction. ROS and RNS play an important role in maintaining normal physiology, when present in low concentrations. Increased concentrations of ROS is harmful and can cause cellular and tissue damage. Oxidative stress is defined as an imbalance between pro-oxidant and antioxidant molecules that manifests due to hyperglycemia. miRNAs are short, non-coding RNAs that play a critical role in regulating gene expression. Studies have shown that the placenta expresses more than 500 miRNAs, which play a crucial role in trophoblast division, movement, and apoptosis. Latest research has revealed that hyperglycemic conditions and increased oxidative stress, characteristic of GDM, can lead to the dysregulation of miRNAs. The placenta also releases miRNAs into the maternal circulation. The secreted miRNAs are encapsulated in exosomes or vesicles. These exosomes interact with tissues and organs at distant sites, releasing their cargo intracellularly. This crosstalk between hyperglycemia, ROS and miRNA expression in GDM has detrimental effects on both foetal and maternal health. One of the complications of GDM is preterm labour. GDM induced iNOS expression has been implicated in cervical ripening, which in turn causes preterm birth. This article focuses on the speculations of oxidative and nitrative stress markers that lead to detrimental effects in GDM. We have also envisaged the role of non-coding miRNA interactions in regulating gene expression for oxidative damage. Graphical Abstract: Holistic view of miRNA in GDM. I)(A) Placenta as a metabolic organ that provides the foetus with nutrients, oxygen and hormones to maintain pregnancy. Human placental lactogen (hPL) is one such hormone that is released into maternal circulation. hPL is known to induce insulin resistance. (B) ß-cell dysfunction leads to reduced glucose sensing and insulin production. Insulin resistance, a characteristic of GDM, exacerbates insulin ß cell dysfunction leading to maternal hyperglycemia. Hyperglycemia leads to increased ROS and RNS production through several mechanisms. Consequently, GDM is characterised by increased oxidative and nitrative stress.II)Exposure to maternal hyperglycemia causes increased ROS and RNS production in trophoblast cells. Oxidative stress caused by hyperglycemia may lead to eNOS uncoupling, causing eNOS to behave as a superoxide producing enzyme. iNOS expression in trophoblast cells leads to increased NO production. iNOS-derived NO reacts with ROS to produce RNS, thereby increasing nitrosative stress. Expression of antioxidant defences are reduced. Hyperglycemia and oxidative stress may alter the expression of some miRNAs. Some miRNAs are upregulated while others are downregulated. Some miRNAs are secreted into maternal circulation in the form of exosomes. Oxidative stress markers, nitrative stress markers and circulating miRNAs are found to be increased in maternal circulation.

Cross-talk between insulin resistance and nitrogen species in hypoxia leads to deterioration of tissue and homeostasis.

Hypoxia has been linked with insulin resistance as it produces changes in the metabolism of the cell; in which the adipocytes impede the insulin receptor tyrosine, phosphorylation, directing at decreased levels of transport of glucose. At this juncture, we are focusing on cross-talk between insulin resistance and nitrogen species in hypoxia, leading to the deterioration of tissue and homeostasis. Physiological levels of nitric oxide play a very crucial role in acting as a priority effector and signaling molecule, arbitrating the body's responses to hypoxia. Both ROS and RNS are associated with a reduction in IRS1 phosphorylation in tyrosine, which leads to reduced levels of IRS1 content and insulin response, which further leads to insulin resistance. Cellular hypoxia is a trigger to inflammatory mediators which signal tissue impairment and initiate survival requirements. But, hypoxia-mediated inflammation act as a protective role by an immune response and promotes wound healing during infection. In this review, we abridge the crosstalk between the inflammation and highlight the dysregulation in physiological consequences due to diabetes mellitus. Finally, we review various treatments available for its related physiological complications.

Prospective dietary radical scavengers: Boon in Pharmacokinetics, overcome insulin obstruction via signaling cascade for absorption during impediments in metabolic disorder like Diabetic Mellitus.

Diabetes mellitus is a metabolic disorder which is characterized based on the blood glucose level. This can be due to the lack of efficiency of utilizing insulin or lack of production of insulin. There are numerous therapies and medications which are available for the treatment of this disease which can reduce the risk of diabetes. But there is no permanent cure found. Nutritional antioxidants show a foremost role in sustaining the homeostasis of the oxidative equilibrium. They have imparted their electron donor efficacy in preventing aging and in cancer. Vitamin C, E, ß-carotene, carotenoids, polyphenols and selenium have been appraised as antioxidant constituents in the human diet nourishment. This paper emphasizes on the role of antioxidants which help in reducing or maintaining the level of glucose in the body. Antioxidants are substances that reduces the damages to the cells caused by free radicals. The available treatment and medications and how the supplementation of antioxidants is different from them is also discussed. Different type of antioxidants and their treatment in curing the disease is further focused in this paper.

Dysregulation of nitric oxide synthases during early and late pathophysiological conditions of diabetes mellitus leads to amassing of microvascular impedement.

Diabetes is a major killer worldwide and its unprecedented rise poses a serious threat to mankind. According to recent estimation, 387 million people worldwide are affected from the disease with a prevalence rate of 8.3 and 46.3 % still remains undiagnosed. Important characteristics of diabetes are abnormalities of the physiological signalling functions of reactive oxygen species and reactive nitrogen species. Increased oxidative stress contributes to the activation of stress-sensitive intracellular signalling pathways and the development of gene products that trigger cellular damage and contribute to the vascular complications of diabetes. Growing evidence from studies into many diseases suggests that the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure are correlated with oxidative stress. This leads to cell metabolism and cell-cell homeostasis to be complexly dysregulated. This review focuses to investigate the status of oxidative stress, nitric oxide and reactive species in early and diabetes. Significance of nitric oxide synthases Evidences has accumulated indicating that the generation of reactive oxygen species (oxidative stress) may play an important role in the etiology of diabetic complications thus attention was given on the reactive oxygen and reactive nitrogen species and their potential role in pathogenesis. Additionally, the therapeutic advances in diabetes management are included. Nanotechnology, statins and stem cell technology are some techniques which can be considered to have a possible future in the treatment sector of diabetes.

Estimating the Sizes of Populations At Risk of HIV Infection From Multiple Data Sources Using a Bayesian Hierarchical Model.

In most countries in the world outside of sub-Saharan Africa, HIV is largely concentrated in sub-populations whose behavior puts them at higher risk of contracting and transmitting HIV, such as people who inject drugs, sex workers and men who have sex with men. Estimating the size of these sub-populations is important for assessing overall HIV prevalence and designing effective interventions. We present a Bayesian hierarchical model for estimating the sizes of local and national HIV key affected populations. The model incorporates multiple commonly used data sources including mapping data, surveys, interventions, capture-recapture data, estimates or guesstimates from organizations, and expert opinion. The proposed model is used to estimate the numbers of people who inject drugs in Bangladesh.

Estimating the size of key populations at higher risk of HIV infection: a summary of experiences and lessons presented during a technical meeting on size estimation among key populations in Asian countries.

PROBLEM: Size estimates of key populations at higher risk of HIV exposure are recognized as critical for understanding the trajectory of the HIV epidemic and planning and monitoring an effective response, especially for countries with concentrated and low epidemics such as those in Asia. CONTEXT: To help countries estimate population sizes of key populations, global guidelines were updated in 2011 to reflect new technical developments and recent field experiences in applying these methods. ACTION: In September 2013, a meeting of programme managers and experts experienced with population size estimates (PSE) for key populations was held for 13 Asian countries. This article summarizes the key results presented, shares practical lessons learnt and reviews the methodological approaches from implementing PSE in 13 countries. LESSONS LEARNT: It is important to build capacity to collect, analyse and use PSE data; establish a technical review group; and implement a transparent, well documented process. Countries should adapt global PSE guidelines and maintain operational definitions that are more relevant and useable for country programmes. Development of methods for non-venue-based key populations requires more investment and collaborative efforts between countries and among partners.

Estimating the size of key populations at higher risk of HIV infection: a summary of experiences and lessons presented during a technical meeting on size estimation among key populations in Asian countries

Problem:Size estimates of key populations at higher risk of HIV exposure are recognized as critical for understanding the trajectory of the HIV epidemic and planning and monitoring an effective response, especially for countries with concentrated and low epidemics such as those in Asia. Context:To help countries estimate population sizes of key populations, global guidelines were updated in 2011 to reflect new technical developments and recent field experiences in applying these methods. Action:In September 2013, a meeting of programme managers and experts experienced with population size estimates (PSE) for key populations was held for 13 Asian countries. This article summarizes the key results presented, shares practical lessons learnt and reviews the methodological approaches from implementing PSE in 13 countries. Lessons learnt:It is important to build capacity to collect, analyse and use PSE data; establish a technical review group; and implement a transparent, well documented process. Countries should adapt global PSE guidelines and maintain operational definitions that are more relevant and useable for country programmes. Development of methods for non-venue-based key populations requires more investment and collaborative efforts between countries and among partners.

HIV surveillance systems in the Asia Pacific region.

In 2011, the United Nations Joint Programme on HIV/AIDS (UNAIDS) Regional Support Team for Asia-Pacific conducted a stock-taking process of available strategic information in the Asia Pacific region. This paper summarizes the progress of HIV surveillance for 20 countries in the region, covering population size estimates of key populations at higher risk, HIV case reporting, HIV sentinel surveillance and probability surveys of behavioural and biological markers. Information on surveillance activities was obtained from publically available surveillance reports and protocols, supplemented by personal communication with the UNAIDS monitoring and evaluation advisers and surveillance experts in country. Key findings include substantial efforts in broadening the number and types of HIV surveillance components included in national HIV surveillance systems and adopting approaches to make surveillance more cost-efficient, such as integrating routine programme monitoring data and passive surveillance case reporting systems. More investment in regularly analysing and applying surveillance data to programme strengthening at the subnational level is needed but will require additional capacity-building and resources. The ability to triangulate multiple sources of surveillance data into a more comprehensive view of the HIV epidemic will be enhanced if more investment is made in better documentation and dissemination of surveillance activities and findings.

HIV surveillance systems in the Asia Pacific region

In 2011, the United Nations Joint Programme on HIV/AIDS (UNAIDS) Regional Support Team for Asia-Pacific conducted a stock-taking process of available strategic information in the Asia Pacific region. This paper summarizes the progress of HIV surveillance for 20 countries in the region, covering population size estimates of key populations at higher risk, HIV case reporting, HIV sentinel surveillance and probability surveys of behavioural and biological markers. Information on surveillance activities was obtained from publically available surveillance reports and protocols, supplemented by personal communication with the UNAIDS monitoring and evaluation advisers and surveillance experts in country. Key findings include substantial efforts in broadening the number and types of HIV surveillance components included in national HIV surveillance systems and adopting approaches to make surveillance more cost-efficient, such as integrating routine programme monitoring data and passive surveillance case reporting systems. More investment in regularly analysing and applying surveillance data to programme strengthening at the subnational level is needed but will require additional capacity-building and resources. The ability to triangulate multiple sources of surveillance data into a more comprehensive view of the HIV epidemic will be enhanced if more investment is made in better documentation and dissemination of surveillance activities and findings.

HIV and AIDS Data Hub for Asia Pacific: a regional tool to support strategic information needs

The 2011 global commitments towards controlling HIV made by Asia-Pacific countries require considerable improvement in strategic information and response tracking. The HIV and AIDS Data Hub can serve as an important tool for stakeholders with its regional database of subnational indicators, web site and data synthesis capacity.

HIV transmission in Bangladesh: an analysis of IDU programme coverage.

BACKGROUND: Sentinel Surveillance found HIV had increased to 7% among street-based injection drug users (IDUs) in Central Bangladesh in 2006-2007, indicating the urgent need to increase prevention. In 2004, size estimation of groups vulnerable to HIV was done by an expert committee under the National AIDS/STD Programme, making programme coverage estimates possible for the first time. METHODS: Appropriate multipliers were applied to size information to estimate a total of 20,000-40,000 IDUs throughout the country. Data from 2003 onwards from the major needle-exchange programmes (NEPs) and detoxification services were analysed to estimate programme coverage as the proportion of the total IDU population reached by interventions, and to assess the proportion of safe injections. RESULTS: An estimated 31-61% of the upper and lower national size estimates of IDUs, respectively, were in contact with any HIV prevention effort by 2006, with an increasing trend evident over the years. Of these, 24-49% were enrolled at NEPs, and 8-16% had been through detoxification. Although there was a marked improvement over the years, it appears NEPs only provided 160 days of safe injections for every IDU reached in 2006 in the North and Southeast, and 50 days in the South and Southwest, assuming IDU inject twice daily with new needles. If all IDUs reached by programmes in the North and Southeast injected every day, 44% of injections were covered by new needles, and 14% in the South and Southwest. CONCLUSION: Within the context of an HIV epidemic among some IDU, and high levels of needle-sharing and risky sexual behaviour, the implications of the low level of programme coverage are alarming, and it is clear Bangladesh needs to take action to improve it in order to control the spread of HIV.