Study of anaemia in pregnancy and low birth weight in fluoride endemic area of Western Rajasthan: a cohort study.

Background: Fluoride is a noxious element known to destroy gastrointestinal mucosa, leading to erythrocytes' destruction and causing anaemia. The birth weight of newborn babies is a significant indicator of a child's vulnerability to the risk of childhood diseases and chances of existence. Methods: This prospective cohort study was planned to find linkages between fluorosis and the low-birth weight of newborn babies with anaemic mothers. Antenatal mothers until the 20th week of gestation were followed up till delivery in the Antenatal Clinic of a District Hospital in one of the known fluoride-endemic districts (Nagaur) and the other not-so-endemic district (Jodhpur) of Western Rajasthan. Results: Around 19% of the newborn in Jodhpur and around 22% in Nagaur had low birth weight. Mean fluoride values in water samples were measured to be 0.57 (range from 0.0 to 2.7 PPM) in Jodhpur and 0.7 (range from 0.0 to 3.4 PPM) in Nagaur. Conclusions: Thus, in fluoride endemic areas, other factors should be included besides iron and folic acid supplementation for improving anaemia in pregnant women. This calls for assessing the effectiveness of de-fluoridation activities along with the area's most common indigenous food practices.

Circulatory GSK-3ß: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3ß and p53 accounts for tau hyperphosphorylation and the formation of amyloid-ß plaques. OBJECTIVE: Here, we explored GSK-3ß and p53 as blood-based biomarkers for early detection of AD. METHODS: The levels of GSK-3ß, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. RESULTS: GSK-3ß, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3ß and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. CONCLUSION: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

Neuroprotection by ethanolic extract of Syzygium aromaticum in Alzheimer's disease like pathology via maintaining oxidative balance through SIRT1 pathway.

The oxidative stress plays a key role in Alzheimer's disease (AD) and Sirtuin (SIRT1) is potential mediator of oxidative pathway. This study explored the role of Syzygium aromaticum on SIRT1 and oxidative balance in amyloid beta induced toxicity. Anti-oxidative capacity of Syzygium aromaticum was performed in Aß25-35 induced neurotoxicity in neuronal cells. Superoxide dismutase, Catalase and Glutathione enzyme activity were determined by the treatment of Syzygium aromaticum. Both recombinant and endogenous SIRT1 activity were performed in its presence. The expression of γ-secretase and SIRT1 were evaluated by western blot. Syzygium aromaticum was capable to scavenge ROS and elevate the percentage of anti-oxidant enzymes. It also activated and elevated the level of SIRT1 and downregulated γ-secretase level. These findings show a holistic approach towards the neurodegenerative disease management by Syzygium aromaticum which could lead to the formulation of new drug for AD. This Ayurvedic product can give a healthy aging with no side effects and also be cost effectives. It may meet unmet medical needs of current relevance.

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches.

Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment. These include blocking harmful inflammatory signaling in endothelial cells, microglia/macrophages, or Th17/γδ T cells with biologics, third generation epoxyeicosatrienoic acid (EET) analogs with extended half-life, and miRNA antagomirs. Complementary beneficial pathways may be enhanced by miRNA mimetics or hyperbaric oxygenation. These immunomodulatory approaches could be used to greatly expand the therapeutic window for thrombolytic treatment with tissue plasminogen activator (t-PA). Moreover, nanoparticle technology allows for the selective targeting of endothelial cells for delivery of DNA/RNA oligonucleotides and neuroprotective drugs. In addition, although likely detrimental to the progression of ischemic stroke by inducing inflammation, oxidative stress, and neuronal cell death, 20-HETE may also reduce susceptibility of onset of ischemic stroke by maintaining autoregulation of cerebral blood flow. Although the interaction between inflammation and stroke is multifaceted, a better understanding of the mechanisms behind the pro-inflammatory state at all stages will hopefully help in developing novel immunomodulatory approaches to improve mortality and functional outcome of those inflicted with ischemic stroke.

Emotional Processing in the First 2 Years of Life: A Review of Near-Infrared Spectroscopy Studies.

Emotional stimuli processing during childhood helps us to detect salient cues in our environment and prepares us for our social life. In early childhood, the emotional valences of auditory and visual input are salient and relevant cues of social aspects of the environment, and it is of special interest to understand how exactly the processing of emotional stimuli develops. Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool that has proven valuable in studying emotional processing in children. After conducting a systematic search of PubMed, Web of Science, and Embase databases, we examined 50 NIRS studies performed to study emotional stimuli processing in children in the first 2 years of age. We found that the majority of these studies are done in infants and the most commonly used stimuli are visual and auditory. Many of the reviewed studies suggest the involvement of bilateral temporal areas in emotional processing of visual and auditory stimuli. It is unclear which neural activation patterns reflect maturation and at what age the emotional encoding reaches those typically seen in adults. Our review provides an overview of the database on emotional processing in children up to 2 years of age. Furthermore, it demonstrates the need to include the less-studied age range of 1 to 2 years, and suggests the use of combined audio-visual stimuli and longitudinal studies for future research on emotional processing in children. Thus, NIRS might be a vital tool to study the associations between the early pattern of neural responses and socioemotional development later in life.

Longevity and healthy ageing genes FOXO3A and SIRT3: Serum protein marker and new road map to burst oxidative stress by Withania somnifera.

BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst. OBJECTIVES: In this study we quantified FOXO3A and SIRT3 proteins in human serum with increasing age and in-vitro assessment of modulation of their expression by the treatment of Withania somnifera (Ashwagandha). METHODOLOGY: Four hundred seventy three subjects were enrolled for the study and were divided into three groups according to increasing age [20-30years (young), 60-79years (old) and ≥80years (oldest)]. Serum levels of FOXO3A and SIRT3 proteins were estimated by Surface Plasmon Resonance (SPR) and validated by ELISA and Western blot. The statistical analysis was done with student's unpaired t-test, one way ANOVA by Stata9 and Graph pad prism5. The expression of these proteins were also analysed in stress induced HEK-293 cell line and level was observed by treatment with stress releasing compound Ashwagandha. RESULTS: In this cross sectional observational study, the serum concentration of FOXO3A and SIRT3 declined significantly (p<0.0001) with increasing age and even after adjustment with all geriatric co-morbidities the level remain downregulated with age. In the stress inducible cell line showed reduced level of proteins which gets upregulated by the treatment of Ashwagandha. CONCLUSION: This is the first report of inverse relation of age with human serum FOXO3A and SIRT3 and can be excellent marker for ageing with good therapeutic importance for maintaining healthy ageing.

Decompressive craniectomy for intracerebral hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) has a high mortality rate and leaves most survivors disabled. The dismal outcome is mostly due to the mass effect of hematoma plus edema. Major clinical trials show no benefit from surgical or medical treatment. Decompressive craniectomy has, however, proven beneficial for large ischemic brain infarction with massive swelling. We hypothesized that craniectomy can improve ICH outcome as well. METHODS: We used the model of autologous blood injection into the basal ganglia in rats. After induction of ICH and then magnetic resonance imaging, animals were randomly allocated to groups representing no craniectomy (n = 10) or to craniectomy at 1, 6, or 24 hours. A fifth group without ICH underwent craniectomy only. Neurological and behavioral outcomes were assessed on days 1, 3, and 7 after ICH induction. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were counted. RESULTS: After 7 days, compared with the ICH + no craniectomy group, all craniectomy groups had strikingly lower mortality (P < 0.01), much better neurological outcome (P < 0.001), and more favorable behavioral outcome. A trend occurred in the ICH + no craniectomy group toward more robust apoptosis. CONCLUSION: Decompressive craniectomy performed up to 24 hours improved outcome after experimental ICH, with earlier intervention of greater benefit.