Basal metabolic regulatory responses and rhythmic activity of mammalian heart to aqueous kola nut extracts

Preliminary investigation on the effect of aqueous extracts of three species of kola nut; Cola acuminata (P. Beav), C. nitida subsp. rubra and C. nitida subsp. alba (Vent), on the rhythmic activity of mammalian heart and metabolic rate was carried out using male albino rats, Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure.Keywords: Kolanut, extract, basal metabolic rate, mammalian hear

Utility of infrared thermography for screening febrile subjects

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Stroke types, risk factors, quality of care and outcomes at a Referral Hospital in Western Kenya

Background: The prevalence of stroke is increasing in sub-Saharan Africa due to increases in size of  aging population and stroke risk factors.We assessed risk factors, quality of care and outcomes of stroke to identify modifiable risk factors and areas of care that need improvement for better outcomes.Objectives: To describe the stroke types, risk factors, outcomes and stroke quality of care in a large academic medical centre hospital.Design: Hospital based retrospective study.Setting: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya.Subjects: All patients >18 years admitted with a diagnosis of stroke as per the WHO definition and with a supporting brain imaging (CT scan/ MRI )were included in the study. Data abstracted from the files included demographic details, stroke subtype, stroke risk factors, inpatient stroke care quality  indicators(based on US Joint Commission stroke quality indicator definitions) and in hospital stroke  outcomes. Descriptive statistics was used to summarise the data.Results: A total of 155 patients had stroke between January 2010 and December 2014 of whom 42% were male, the median age was 61 (IQR: 49-72) years. Majority (73%) had hypertension. The prevalence of diabetes was 4%. Left hemiplegia/hemiparesis was the predominant presentation (50%). Haemorrhagic strokes were frequent (52%) with anterior circulation stroke comprising 97% of all strokes. Assessment of quality of care indicators showed that overall, 84% of the patients had a brain CT scan on day one of admission,93% had a GCS documented at admission, 32% were on statins and 3% were screened for dysphagia before oral intake. Among patients with ischaemic strokes; none underwent thrombolysis, 24% received DVT prophylaxis, 54% received statins, and 73% received anti-thrombotic therapy by hospital day two. In hospital mortalityoccurred in 43(27%)with a higher rate among haemorrhagic strokes (31%) compared to ischaemic stroke (24%)(p=0.364).Conclusion: Haemorrhagic stroke was the most common type of stroke admitted, hypertension was the predominant risk factor and most strokes involved the anterior circulation. In-hospital mortality was 27%.There were several opportunities to improve evidence-based quality of care indicators

RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy.

Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR is an easy to use, open source R package that implements several published NIPT analysis methods. The input to RAPIDR is a set of sequence alignment files in the BAM format, and the outputs are calls for aneuploidy, including trisomies 13, 18, 21 and monosomy X as well as fetal sex. RAPIDR has been extensively tested with a large sample set as part of the RAPID project in the UK. The package contains quality control steps to make it robust for use in the clinical setting

Endometrial Cancer Risk Prediction According to Indication of Diagnostic Hysteroscopy in Post-Menopausal Women

We conducted a prospective observational study investigating the clinical relevance of endometrial thickness (ET) and abnormal uterine bleeding (AUB) on endometrial cancer (EC) risk in a cohort of postmenopausal patients undergoing diagnostic hysteroscopy and endometrial biopsy. Patients were divided into two groups according to the indication of diagnostic hysteroscopy: ET_Group (asymptomatic patients with endometrial thickness 4 mm) and AUB_Group (patients with a history of abnormal uterine bleeding). We further divided the AUB_Group into two subgroups based on endometrial thickness (AUB_Subgroup1: ET < 4 mm; AUB_Subgroup2: ET 4 mm). The primary outcome was the risk of endometrial cancer and atypical hyperplasia according to the indications of diagnostic hysteroscopy (AUB, ET 4 mm or both). The secondary outcome was to determine the best cut-o value of endometrial thickness to predict endometrial cancer in asymptomatic postmenopausal women. The prevalence of endometrial cancer and atypical hyperplasia in AUB_Group and ET_Group was 21% and 6.7% respectively. As well as for EC alone, higher prevalence of both conditions was observed in AUB_Subgroup2 (29.3%) in comparison to AUB_Subgroup1 (10.6%; p < 0.001). In asymptomatic patients the cut-o of endometrial thickness that showed the best sensitivity and specificity to diagnose endometrial cancer (100% and 80% respectively) was 11 mm (AUC of 91.4%; Exp : 1067; CI 95%). In conclusion, considering the high risk of neoplasia, diagnostic hysteroscopy with endometrial biopsy should be mandatory in cases of abnormal uterine bleeding in postmenopausal patients. Moreover, we want to emphasize the need for further evidence stating the clinical relevance of endometrial thickness value in asymptomatic patients and the impact of individual risk factors on endometrial cancer development

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Determination of Region of Influence Obtained by Aircraft Vertical Profiles Using the Density of Trajectories from the HYSPLIT Model

Aircraft atmospheric profiling is a valuable technique for determining greenhouse gas fluxes at regional scales (104–106 km2). Here, we describe a new, simple method for estimating the surface influence of air samples that uses backward trajectories based on the Lagrangian model Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). We determined “regions of influence” on a quarterly basis between 2010 and 2018 for four aircraft vertical profile sites: SAN and ALF in the eastern Amazon, and RBA and TAB or TEF in the western Amazon. We evaluated regions of influence in terms of their relative sensitivity to areas inside and outside the Amazon and their total area inside the Amazon. Regions of influence varied by quarter and less so by year. In the first and fourth quarters, the contribution of the region of influence inside the Amazon was 83–93% for all sites, while in the second and third quarters, it was 57–75%. The interquarter differences are more evident in the eastern than in the western Amazon. Our analysis indicates that atmospheric profiles from the western sites are sensitive to 42–52.2% of the Amazon. In contrast, eastern Amazon sites are sensitive to only 10.9–25.3%. These results may help to spatially resolve the response of greenhouse gas emissions to climate variability over Amazon

Venous pseudo-aneurysm as a late complication of short-term central venous catheterisation

Complications following central venous catheterisation abound in the medical literature. This reflects the under-estimated potential hazards associated with this procedure as well as an increase in the number of such procedures performed in high-risk patients. We report on a case where a venous pseudo-aneurysm developed four months after the removal of a short-term central venous catheter in a moderately high-risk patient

Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal non-invasive diagnosis (RAPID) protocol

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Non-invasive prenatal testing (NIPT) for aneuploidies is now available through commercial companies in many countries, including through private practice in the United Kingdom (UK). Thorough evaluation of service delivery requirements are needed to facilitate NIPT being offered more widely within state funded healthcare systems such as the UK's National Health Service (NHS). Successful implementation will require the development of laboratory standards, consideration of stakeholder views, an analysis of costs and development of patient and health professional educational materials. METHODS/DESIGN: NIPT will be offered in an NHS setting as a contingent screening test. Pregnant woman will be recruited through six maternity units in England and Scotland. Women eligible for Down's syndrome screening (DSS) will be informed about the study at the time of booking. Women that choose routine DSS will be offered NIPT if they have a screening risk ≥ 1:1000. NIPT results for trisomy 21, 18, 13 will be reported within 7-10 working days. Data on DSS, NIPT and invasive testing uptake, pregnancy outcomes and test efficacy will be collected. Additional data will be gathered though questionnaires to a) determine acceptability to patients and health professionals, b) evaluate patient and health professional education, c) assess informed choice in women accepting or declining testing and d) gauge family expenses. Qualitative interviews will also be conducted with a sub-set of participating women and health professionals. DISCUSSION: The results of this study will make a significant contribution to policy decisions around the implementation of NIPT for aneuploidies within the UK NHS. The laboratory standards for testing and reporting, education materials and counselling strategies developed as part of the study are likely to underpin the introduction of NIPT into NHS practice. NIHR PORTFOLIO NUMBER: 13865.This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-0707-10107) (the "RAPID" project). LSC is partially funded by the Great Ormond Street Hospital Children’s Charity and the NIHR Biomedical Research Centre at Great Ormond Street Hospital. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health