EVALUATION OF SAFETY PROFILES OF ANURADHA OIL-AN HERBAL WOUND HEALING FORMULATION IN LABORATORY ANIMALS

Objective: To investigate Acute, Sub-acute dermal toxicity, Mucus membrane irritation activity of Anuradha Oil's (AO and AO11) – An herbal formulation having wound healing potential.Methods: The formulations were derived from Curcuma longa Linn and Glycyrrhiza glabra Linn rhizhomes,  Hamiltonia suaveolens Roxb bark,  Typha angustifolia Linn flowers,  Azadirachta indica A. Juss leaves without/with pig fat (AO and AO11 respectively)mixed in certain proportion using Sesamum indicum Linn oil as a base, manufactured at a GMP certified facility. Acute, sub-acute dermal safety, mucus membrane irritation profiles were studied by OECD guidelines number 434, 410 and 405 in Wistar rats and New Zealand rabbits respectively. For acute study dermal application of 2000 mg/kg single dose and for sub-acute study limit dose protocol of 1000 mg/kg for 28 days was used. For mucus membrane irritation test 0.10 ml dose was used.Results: In an acute study no local reaction, behavioral changes and mortality was observed at 2000 mg/kg by dermal route till 14 days. In sub-acute study with dermal application of 1000 mg/kg for 28 days, there were no abnormal signs/symptoms at the application site, no difference in body weight, food consumption, hematology/enzyme profiles, urine analysis, relative organ weights and histopathological observations of vital organs in comparison to control animals. Mucus membrane of rabbits showed no evidence of irritation for both oils.Conclusion: Acute dermal LD50 cut off for AO and AO11was found to be>2000 mg/kg, safe for dermal application for 28 days using the dose of 1000 mg/kg and non-irritant. Â

Rate of change in longitudinal EMG indicates time course of an individual's neuromuscular adaptation in resistance-based muscle training

An individual's long-term neuromuscular adaptation can be measured through time-domain analyses of surface electromyograms (EMG) in regular resistance-based training. The perceived changes in recruitment, such as those measured during muscle fatigue, can subsequently prolong the recovery time in rehabilitation applications. Thus, by developing quantifiable methods for measuring neuromuscular adaptation, adjuvant treatments applied during neurorehabilitation can be improved to reduce recovery times and to increase patient quality of care. This study demonstrates a novel time-domain analysis of long-term changes in EMG captured neuromuscular activity that we aim to use to develop a quantified performance metric for muscle-based intervention training and optimization of an individual. We measure EMG of endurance and hypertrophy-based resistance exercises of healthy participants over 100 days to identify trends in long-term neuromuscular adaptation. Particularly, we show that the rate of EMG amplitude increase (motor recruitment) is dependent on the training modality of an individual. Particularly, EMG decreases over time with repetitive training – but the rate of decrease is different in hypertrophy, endurance, and control exercises. We found that the EMG peak contraction decreases across all subjects, on average, by 8.23 dB during hypertrophy exercise and 10.09 dB for endurance exercises over 100 days of training, while control participants showed negligible change. This represents approximately 2 dB difference EMG activity when comparing endurance and hypertrophy exercises, and >8 dB change when comparing to our control cases. As such, we show that the slope of the long-term EMG activity is related to the resistance-based exercise. We believe this can be used to identify person-specific performance metrics, and to create optimized interventions using a measured performance baseline of an individual

Use of Anti-Inflammatory Drugs and Lower Esophageal Sphincter-Relaxing Drugs and Risk of Esophageal and Gastric Cancers

Background & Aims: The incidence of esophageal and gastric cardia adenocarcinoma has increased in Western countries in recent decades for largely unknown reasons. We investigated whether use of LES-relaxing drugs was related to an increased risk of esophageal and gastric cardia adenocarcinoma, and whether use of NSAIDs was related to a reduced risk of esophageal and gastric cancers. Methods: We examined these associations by using administrative databases in a case-control study in 2 integrated health care delivery systems. Cases were incident esophageal adenocarcinomas (n = 163) and squamous cell carcinomas (n = 114) and gastric cardia (n = 176) and non-cardia adenocarcinomas (n = 320), diagnosed between 1980-2002 in one health system and between 1993-2002 in the other. Matched controls (n = 3996) were selected. Complete prescription information was available for the study period. Results: Prescription of corticosteroids was associated with a decreased risk of esophageal adenocarcinoma (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.9), esophageal squamous cell carcinoma (OR, 0.4; 95% CI, 0.2-0.6), and gastric non-cardia carcinoma (OR, 0.4, 95% CI, 0.3-0.6). Ever use of pharmacy-purchased aspirin was associated with 30%-60% decreased risks of the studied cancers. As a group, LES-relaxing drugs showed little evidence of association with increased risk of any esophageal or gastric cancer. Conclusions: Corticosteroid and aspirin use were associated with significantly decreased risks of esophageal and gastric cancer. LES-relaxing drugs as a group did not affect these risks, although we had limited power to assess individual drugs. The possibility that corticosteroids and aspirin might reduce esophageal cancer risk warrants further consideration

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke.</p> <p>Methods</p> <p>The study employed both a case-control and prospective follow-up design to study hospitalized adults with first – ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS).</p> <p>Results</p> <p>We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age ± SD of the cases was 58.8 ± 9.8 years, comparable to that of controls which was 58.3 ± 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 ± 38.8 hours, and mean admission NIHSS score was 10.1 ± 7.7. Total fasting Hcy in stroke patients was 10.2 ± 4.6 umol/L and did not differ significantly from controls (10.1 ± 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90^thpercentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 – 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001).</p> <p>Conclusion</p> <p>This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.</p

Local diversity in settlement, demography and subsistence across the southern Indian Neolithic-Iron Age transition: site growth and abandonment at Sanganakallu-Kupgal

The Southern Indian Neolithic-Iron Age transition demonstrates considerable regional variability in settlement location, density, and size. While researchers have shown that the region around the Tungabhadra and Krishna River basins displays significant subsistence and demographic continuity, and intensification, from the Neolithic into the Iron Age ca. 1200 cal. BC, archaeological and chronometric records in the Sanganakallu region point to hilltop village expansion during the Late Neolithic and ‘Megalithic’ transition period (ca. 1400–1200 cal. BC) prior to apparent abandonment ca. 1200 cal. BC, with little evidence for the introduction of iron technology into the region. We suggest that the difference in these settlement histories is a result of differential access to stable water resources during a period of weakening and fluctuating monsoon across a generally arid landscape. Here, we describe well-dated, integrated chronological, archaeobotanical, archaeozoological and archaeological survey datasets from the Sanganakallu-Kupgal site complex that together demonstrate an intensification of settlement, subsistence and craft production on local hilltops prior to almost complete abandonment ca. 1200 cal. BC. Although the southern Deccan region as a whole may have witnessed demographic increase, as well as subsistence and cultural continuity, at this time, this broader pattern of continuity and resilience is punctuated by local examples of abandonment and mobility driven by an increasing practical and political concern with water

Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution