Evaluation of oxidative stress biomarkers and inflammation in pathogenesis of diabetes and diabetic nephropathy

This study aims to increase understanding of the association of oxidative stress and inflammation with type-2 diabetes and diabetic nephropathy to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of disease. Blood samples were collected from 498 West Indian individuals aged 42–72 years. Differences in the level of oxidative stress markers (MDA, GSH, SOD and CAT) and inflammation (TNF-α and IL1-α) was determined in patients (type 2 diabetic and diabetic nephropathy) and control participants. A significant decrease of SOD, GSH and significant increase of MDA and CAT activity were seen in patients with nephropathy compared to DM patients as well as controls. Significantly higher level of expression of TNF-α and IL1-α (P< 0.05) was observed in DM and DN patients as compared to controls. Oxidative stress and inflammation are triggered in patients of type 2 diabetes and diabetic nephropathy due to hyperglycemia

Raman and nuclear magnetic resonance investigation of alkali metal vapor interaction with alkene-based anti-relaxation coating

The use of anti-relaxation coatings in alkali vapor cells yields substantial performance improvements by reducing the probability of spin relaxation in wall collisions by several orders of magnitude. Some of the most effective anti-relaxation coating materials are alpha-olefins, which (as in the case of more traditional paraffin coatings) must undergo a curing period after cell manufacturing in order to achieve the desired behavior. Until now, however, it has been unclear what physicochemical processes occur during cell curing, and how they may affect relevant cell properties. We present the results of nondestructive Raman-spectroscopy and magnetic-resonance investigations of the influence of alkali metal vapor (Cs or K) on an alpha-olefin, 1-nonadecene coating the inner surface of a glass cell. It was found that during the curing process, the alkali metal catalyzes migration of the carbon-carbon double bond, yielding a mixture of cis- and trans-2-nonadecene.Comment: 5 pages, 6 figure

Assessment of efficacy and safety of artesunate plus sulfadoxine pyrimethamine combination for treatment of uncomplicated falciparum malaria

Background: Resistance of Plasmodium falciparum to antimalarial drugs is common in India. World Health Organization (WHO) recommends artemisinin‑based combination therapy (ACT) to counter the development of resistance in P. falciparum. WHO recommends that ideally antimalarial drug treatment policy or guidelines should be reviewed regularly and updated at least once every 24 months. In consideration to the above recommendation, we planned to conduct the following study. The objective was to determine the efficacy and safety of artesunate + sulphadoxine‑pyrimethamine (AS + SP) in patients with uncomplicated P. falciparum malaria.Methods: The study included 60 patients of uncomplicated P. falciparum. Each patient received AS + SP as per WHO guidelines. Diagnosis was confirmed by peripheral blood film. All patients were followed‑up on days 1, 3, 14, and 28 for detailed clinical and parasitological examination.Results: Of a total 60 patients, 55 patients were followed‑up for 28 days. Remaining 5 patients were lost in follow‑up. As per protocol analysis, 91% (50) of patients had demonstrated adequate clinical and parasitological response. Remaining 9% (5) had treatment failure in which 5.5% (3) had late parasitological failure and 3.6% (2) had late clinical failure. In our study, mean parasite clearance time was 45.2 ± 4.2 hrs.Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance

Prevalence of non-communicable chronic conditions, multimorbidity and its correlates among older adults in rural Nepal : a cross-sectional study

Objectives This study's objectives were to estimate the prevalence of major non-communicable conditions and multimorbidity among older adults in rural Nepal and examine the associated socioeconomic and behavioural risk factors. Design This was a community-based cross-sectional study conducted between January and April 2018. Setting Rural municipalities of Sunsari and Morang districts in eastern Nepal. Participants 794 older Nepalese adults, 60 years and older, were recruited using a multistage cluster sampling approach. Primary outcome measure(s) Prevalence of four major non-communicable chronic conditions (osteoarthritis, cardiovascular disease, diabetes and chronic obstructive pulmonary disease (COPD) and multimorbidity. Results Almost half (48.9%: men 45.3%; women 52.4%) of the participants had at least one of four non-communicable chronic conditions, and 14.6% (men 12.5%; women 16.8%) had two or more conditions. The prevalence of individual conditions included: osteoarthritis-41.7% (men 37.5%; women 45.9%), cardiovascular disease-2.4% (men 2.8%; women 2.0%), diabetes-5.3% (men 6.0%; women 4.6%) and COPD-15.4% (men 13.3%; women 17.5%). In the adjusted model, older adults aged 70-79 years (adjusted OR (AOR): 1.62; 95% CI: 1.04 to 2.54), those from Madhesi and other ethnic groups (AOR: 1.08; 95% CI: 1.02 to 1.72), without a history of alcohol drinking (AOR: 1.53; 95% CI: 1.18 to 2.01) and those physically inactive (AOR: 5.02; 95% CI: 1.47 to 17.17) had significantly higher odds of multimorbidity. Conclusions This study found one in seven study participants had multimorbidity. The prevalence of multimorbidity and associated socioeconomic and behavioural correlates need to be addressed by integrating social programmes with health prevention and management at multiple levels. Moreover, a longitudinal study is suggested to understand the temporal relationship between lifestyle predictors and multimorbidity among older Nepalese adults

Publisher’s Note: Adsorption Geometry Determination of Single Molecules by Atomic Force Microscopy [Phys. Rev. Lett. 111, 106103 (2013)]

We measured the adsorption geometry of single molecules with intramolecular resolution using noncontact atomic force microscopy with functionalized tips. The lateral adsorption position was determined with atomic resolution, adsorption height differences with a precision of 3 pm, and tilts of the molecular plane within 0.2°. The method was applied to five π-conjugated molecules, including three molecules from the olympicene family, adsorbed on Cu(111). For the olympicenes, we found that the substitution of a single atom leads to strong variations of the adsorption height, as predicted by state-of-the-art density-functional theory, including van der Waals interactions with collective substrate response effects

Effect of gabapentin on haloperidol induced inhibition of conditioned avoidance response in rat

Background: Haloperidol, an antipsychotic adversely affects acquisition and retention of a learned task. We decided to test the effect of Gabapentin, a new anti-epileptic drug using conditioned avoidance response model with cook’s pole climbing apparatus and haloperidol.Methods: Four groups of six rats were taken for this purpose. All the rats were first given drugs for five days and then trained for a period of 15 days. Gabapentin was given in a dose of 100mg/kg intra peritoneal, while haloperidol was given 0.5mg/kg intra peritoneal.Results: At the end of the training duration rats in the vehicle and gabapentin treated group achieved ≥85% acquisition responses. While the haloperidol and haloperidol + gabapentin group did not achieve the desired percentage of learning. A learning curve was plotted by using the percentage of conditioned responses in each group versus number of days. The mean ± SD percentage of conditioned responses of day 14 and 15 were for haloperidol group 26.19 ±11.90, for vehicle group 86.90 ± 4.29, for the gabapentin treated group 95.24 ± 2.38 and for the gabapentin + haloperidol group 46.42 ± 12.20. These figures and the learning curve suggest that gabapentin treated rats had a better acquisition response and haloperidol depressed learning.Conclusions: At the end of study duration we found that gabapentin significantly improved the acquisition response than the vehicle control group. Also haloperidol depressed the acquisition response. Gabapentin did not lead to reversal of haloperidol induced depression of acquisition process

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

BACKGROUND: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. METHODS: CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. RESULTS: Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). CONCLUSIONS: Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia

Assessment of the molecular mechanisms of action of novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one allosteric modulators at the M1 muscarinic acetylcholine receptors

Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer's disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism (Mistry et al., 2016), but their molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, BQCA, in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human M1 mAChR. Interactions between the orthosteric agonists and the novel PAMs or BQCA suggested their allosteric effects were solely governed by modulation of agonist affinity. The greatest degree of positive co-operativity was observed with higher efficacy agonists, whereas minimal potentiation was observed when the modulators were tested against the lower efficacy agonist, xanomeline. Each PAM was investigated for its effects on the endogenous agonist, ACh, on three different signalling pathways, (ERK1/2 phosphorylation, IP1 accumulation and β-arrestin-2 recruitment), revealing that the allosteric potentiation generally tracked with the efficiency of stimulus-response coupling and that there was little pathway bias in the allosteric effects. Thus, despite the identification of novel allosteric scaffolds targeting the M1 mAChR, the molecular mechanism of action of these compounds is largely consistent with a model of allostery previously described for BQCA, suggesting that this may be a more generalized mechanism for M1 mAChR PAM effects than previously appreciated

A qualitative study to understand drivers of psychoactive substance use among Nepalese youth

Background Psychoactive substance use among youth is an emerging public health issue in Nepal. This exploratory study aimed to better understand the drivers of psychoactive substance use among Nepalese youth in Rupandehi district of Nepal. Materials and methods This study used a qualitative approach for data collection. Both in-depth interviews (IDI, seven participants) and focus group discussions (FGD, 13 participants) were conducted among study participants who self-reported as psychoactive substance users or had history of psychoactive substance use. Participants for IDI were aged between 11 and 24 years and between 18 and 35 years old for FGDs. Semi-structured interview guides were prepared separately for IDIs and FDGs. Interviews were conducted in Nepali language and were audio recorded, which were there transcribed and translated into English for coding and analyses. In addition, interviews notes were taken by two research assistants. An inductive thematic analysis was used to analyze the data. Results This study identified a range of drivers of psychoactive substances use among Nepalese youths. Themes included (i) socio-cultural factors, (ii) individual factors, (iii) academic environment, (iv) physical environment and the (v) influence of media. The socio-cultural factors were categorized into sub-themes of family relationships, ethnic identity and psychoactive substance use and lack of social acceptance. Individual factors included peer pressure, stress relief and coping with financial challenges. Accessibility and availability of psychoactive substances in the surrounding environment and lack of monitoring and reinforcement of rules/ law and regulations were other drivers to psychoactive substance use among this Nepalese youth cohort. Conclusion Our study identified several important drivers of psychoactive substance use among youth in the Rupandehi district of Nepal. Future works are anticipated to further explore youth initiation and use of psychoactive substances and support the design of interventions that address these risk factors to reduce and prevent subsequent harms