Biosocial and disease conditions are associated with good quality of life among older adults in rural eastern Nepal: Findings from a cross-sectional study

Background The ageing population in most low-and middle-income countries is accompanied by an increased risk of non-communicable diseases culminating in a poor quality of life (QOL). However, the factors accelerating this poor QOL have not been fully examined in Nepal. Therefore, this study examined the factors associated with the QOL of older adults residing in the rural setting of Nepal. Methods Data from a previous cross-sectional study conducted among older adults between January and April 2018 in in rural Nepal was used in this study. The analytical sample included 794 older adults aged ≥60 years, selected by a multi-stage cluster sampling approach. QOL was measured using the Older People’s Quality of Life tool; dichotomized as poor and good QOL. Other measures used included age, gender, ethnicity, religion, marital status, physical activity, and chronic diseases such as osteoarthritis, cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), and depression. The factors associated with QOL were examined using mixed-effects logistic regression. Results Seven in ten respondents (70.4%) reported a poor QOL. At the bivariate level, increasing age, unemployment, intake of alcohol, lack of physical activity as well as osteoarthritis, COPD and depression were significantly associated with a lower likelihood of a good QOL. The adjusted model showed that older age (AOR = 0.50, 95% CI: 0.28–0.90), the Christian religion (AOR = 0.38, 95% CI: 0.20–0.70), and of an Indigenous (AOR: 0.25; 95% CI: 0.14–0.47), Dalit (AOR: 0.23; 95% CI: 0.10–0.56), and Madheshi (AOR: 0.29; 95% CI: 0.14–0.60) ethnic background were associated with lower odds of good QOL. However, higher income of >NRs 10,000 (AOR = 3.34, 95% CI: 1.43–3.99), daily physical activity (AOR: 3.33; 95% CI: 2.55–4.34), and the absence of osteoarthritis (AOR: 1.9; 95% CI: 1.09–3.49) and depression (AOR: 3.34; 95% CI: 2.14–5.22) were associated with higher odds of good QOL. Conclusion The findings of this study reinforce the need of improving QOL of older adults through implementing programs aimed at addressing the identified biosocial and disease conditions that catalyse poor QOL in this older population residing in rural parts of Nepal

A novel approach towards therapeutic optimization of diclofenac

Con objeto de obtener compuestos con menor toxicidad gástrica que el diclofenaco, se sintetizaron yevaluaron cinco ésteres derivados aminoetílicos N,N-sustituidos derivados del diclofenaco. Estos ésteresse diseñaron para satisfacer el requisito estructural de disponer de una actividad anticolinérgica intactaantes de la separación. Además de bloquear el grupo carboxilo ácido mediante esterificación, estaactividad se incorporó a los ésteres sintetizados, con el beneficio adicional esperado de la reducción dela secreción de ácido gástrico y la consecuente eliminación de la irritación local mediante un mecanismodual. En este estudio se describen la síntesis, la cinética de la hidrólisis y la actividad biológica de estosésteres. Todos los derivados de éster permanecieron estables en tampones de pH 2,0 y 7,4 durante unperíodo de tiempo suficiente, lo que aseguró su absorción en estado intacto y la eliminación de lairritación gástrica local producida por el fármaco principal. Se observó una rápida hidrólisis enzimáticade todos los derivados en un 80% de suero humano combinado. Se descubrió que los ésteres sintetizadosposeían la actividad anticolinérgica propuesta. Se mantuvo la actividad antiinflamatoria en la mayoría delos compuestos y se logró una significativa reducción del potencial ulcerogénico en comparación con eldiclofenaco.In an effort for obtaining compounds with lower gastric toxicity than diclofenac, five different N,Ndisubstitutedaminoethylester derivatives of diclofenac were synthesized and evaluated. These esterswere designed so as to satisfy the structural requirement for them to possess the anticholinergic activityin intact form before cleavage. Besides blocking the acidic carboxyl group by esterification this activitywas incorporated into the synthesized esters with an expected additional benefit of having reduced gastricacid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes thesynthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives werefound to be stable in buffers (pH 2.0 and 7.4) for sufficient time period, assuring them to be absorbedintact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatichydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized esters werefound to possess the proposed anticholinergic activity. The anti-inflammatory activity for most of thecompounds was retained with a significant reduction in the ulcerogenic potential compared to diclofenac

Una nueva aproximación a la optimización terapéutica del diclofenaco

In an effort for obtaining compounds with lower gastric toxicity than diclofenac, five different N,Ndisubstitutedaminoethylester derivatives of diclofenac were synthesized and evaluated. These esterswere designed so as to satisfy the structural requirement for them to possess the anticholinergic activityin intact form before cleavage. Besides blocking the acidic carboxyl group by esterification this activitywas incorporated into the synthesized esters with an expected additional benefit of having reduced gastricacid secretion and thereby abolishing the local irritation by a dual mechanism. This report describes thesynthesis, hydrolysis kinetics and the biological activity of these esters. All the ester derivatives werefound to be stable in buffers (pH 2.0 and 7.4) for sufficient time period, assuring them to be absorbedintact and to successfully overcome the local gastric irritation of the parent drug. A fast enzymatichydrolysis was observed for all the derivatives in 80% pooled human serum. The synthesized esters werefound to possess the proposed anticholinergic activity. The anti-inflammatory activity for most of thecompounds was retained with a significant reduction in the ulcerogenic potential compared to diclofenac.Con objeto de obtener compuestos con menor toxicidad gástrica que el diclofenaco, se sintetizaron yevaluaron cinco ésteres derivados aminoetílicos N,N-sustituidos derivados del diclofenaco. Estos ésteresse diseñaron para satisfacer el requisito estructural de disponer de una actividad anticolinérgica intactaantes de la separación. Además de bloquear el grupo carboxilo ácido mediante esterificación, estaactividad se incorporó a los ésteres sintetizados, con el beneficio adicional esperado de la reducción dela secreción de ácido gástrico y la consecuente eliminación de la irritación local mediante un mecanismodual. En este estudio se describen la síntesis, la cinética de la hidrólisis y la actividad biológica de estosésteres. Todos los derivados de éster permanecieron estables en tampones de pH 2,0 y 7,4 durante unperíodo de tiempo suficiente, lo que aseguró su absorción en estado intacto y la eliminación de lairritación gástrica local producida por el fármaco principal. Se observó una rápida hidrólisis enzimáticade todos los derivados en un 80% de suero humano combinado. Se descubrió que los ésteres sintetizadosposeían la actividad anticolinérgica propuesta. Se mantuvo la actividad antiinflamatoria en la mayoría delos compuestos y se logró una significativa reducción del potencial ulcerogénico en comparación con eldiclofenaco

An overview of municipal solid waste management in Jaipur city, India - Current status, challenges and recommendations

In developing countries, urbanization and rapid population growth has resulted in a substantial increase in generation of Municipal Solid Waste (MSW). Safe collection, transportation and treatment of MSW are among the major issues for Indian cities. Poor MSW management practices have negative impact on public health, environment and climate change. India currently only treats 21% of MSW while the remainder disposed in unsanitary landfill sites with no recycling and treatment technologies. This paper reviews the existing MSW management practices, challenges and provides recommendations for improving MSW management for the city of Jaipur in Rajasthan, India. Despite being the state capital as well as the top tourist destination in northern part of India, there is no detailed study which reviews the waste management strategies of this city along with identifying the key challenges. The study reveals that the major challenges for MSW management in Jaipur include uncontrolled landfilling, inadequate public participation as well as failings of implementation of MSW legislation and waste conversion. Recommendations for improvement include public awareness campaigns, public-private partnership, investment in lined landfills, recycling and waste to energy techniques. Optimization models and life cycle assessment tools should be employed to minimize cost and the environmental impact of MSW management. This study will provide policy makers and private sector stakeholders to develop strategies for future planning, investment and execution of improved MSW management in Indian cities

Reduced haemodynamic response in the ageing visual cortex measured by absolute fNIRS

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Indigenous use and bio-efficacy of medicinal plants in the Rasuwa District, Central Nepal

<p>Abstract</p> <p>Background</p> <p>By revealing historical and present plant use, ethnobotany contributes to drug discovery and socioeconomic development. Nepal is a natural storehouse of medicinal plants. Although several ethnobotanical studies were conducted in the country, many areas remain unexplored. Furthermore, few studies have compared indigenous plant use with reported phytochemical and pharmacological properties.</p> <p>Methods</p> <p>Ethnopharmacological data was collected in the Rasuwa district of Central Nepal by conducting interviews and focus group discussions with local people. The informant consensus factor (F_IC) was calculated in order to estimate use variability of medicinal plants. Bio-efficacy was assessed by comparing indigenous plant use with phytochemical and pharmacological properties determined from a review of the available literature. Criteria were used to identify high priority medicinal plant species.</p> <p>Results</p> <p>A total of 60 medicinal formulations from 56 plant species were documented. Medicinal plants were used to treat various diseases and disorders, with the highest number of species being used for gastro-intestinal problems, followed by fever and headache. Herbs were the primary source of medicinal plants (57% of the species), followed by trees (23%). The average F_IC value for all ailment categories was 0.82, indicating a high level of informant agreement compared to similar studies conducted elsewhere. High F_ICvalues were obtained for ophthalmological problems, tooth ache, kidney problems, and menstrual disorders, indicating that the species traditionally used to treat these ailments are worth searching for bioactive compounds: <it>Astilbe rivularis</it>, <it>Berberis asiatica</it>, <it>Hippophae salicifolia, Juniperus recurva</it>, and <it>Swertia multicaulis</it>. A 90% correspondence was found between local plant use and reported plant chemical composition and pharmacological properties for the 30 species for which information was available. Sixteen medicinal plants were ranked as priority species, 13 of which having also been prioritized in a country-wide governmental classification.</p> <p>Conclusions</p> <p>The <it>Tamang </it>people possess rich ethnopharmacological knowledge. This study allowed to identify many high value and high priority medicinal plant species, indicating high potential for economic development through sustainable collection and trade.</p

Phosphorylation of SOS1 on tyrosine 1196 promotes its RAC GEF activity and contributes to BCR-ABL leukemogenesis

Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. Although the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro and for platelet-derived growth factor (PDGF) activation of RAC- and RAC-dependent actin remodeling and cell migration. SOS1 is also phosphorylated on Y1196 by BCR-ABL in chronic myelogenous leukemic cells. Importantly, in these cells, SOS1 is required for BCR-ABL-mediated activation of RAC, cell proliferation and transformation in vitro and in a xenograft mouse model. Finally, genetic removal of Sos1 in the bone marrow-derived cells (BMDCs) from Sos1fl/flmice and infected with BCR-ABL causes a significant delay in the onset of leukemogenesis once BMDCs are injected into recipient, lethally irradiated mice. Thus, SOS1 is required for full transformation and critically contribute to the leukemogenic potential of BCR-ABL

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide

Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models

Failure of remyelination of multiple sclerosis (MS) lesions contributes to neurodegeneration that correlates with chronic disability in patients. Currently, there are no available treatments to reduce neurodegeneration, but one therapeutic approach to fill this unmet need is to promote remyelination. As many demyelinated MS lesions contain plentiful oligodendrocyte precursor cells (OPCs), but no mature myelinating oligodendrocytes, research has previously concentrated on promoting OPC maturation. However, some MS lesions contain few OPCs, and therefore, remyelination failure may also be secondary to OPC recruitment failure. Here, in a series of MS samples, we determined how many lesions contained few OPCs, and correlated this to pathological subtype and expression of the chemotactic molecules Semaphorin (Sema) 3A and 3F. 37 % of MS lesions contained low numbers of OPCs, and these were mostly chronic active lesions, in which cells expressed Sema3A (chemorepellent). To test the hypothesis that differential Sema3 expression in demyelinated lesions alters OPC recruitment and the efficiency of subsequent remyelination, we used a focal myelinotoxic mouse model of demyelination. Adding recombinant (r)Sema3A (chemorepellent) to demyelinated lesions reduced OPC recruitment and remyelination, whereas the addition of rSema3F (chemoattractant), or use of transgenic mice with reduced Sema3A expression increased OPC recruitment and remyelination. We conclude that some MS lesions fail to remyelinate secondary to reduced OPC recruitment, and that chemotactic molecules are involved in the mechanism, providing a new group of drug targets to improve remyelination, with a specific target in the Sema3A receptor neuropilin-1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1112-y) contains supplementary material, which is available to authorized users