Physical activity has a major impact on bone density and on osteoporosis prevention. Sclerostin is produced by osteocytes and inhibits bone formation. The impact of exercise on sclerostin secretion ...has not been studied so far. This pilot study aimed to explore circulating sclerostin levels immediately after acute exercise. Healthy young women practicing physical activity less than 120 min per week were enrolled. The exercise was a 45-min, low-speed, treadmill running test. Blood samples were taken at rest before exercise and within 5 min after the end of exercise. We assessed serum creatinine, 25-OH vitamin D, alkaline phosphatase, C-telopeptide of type I collagen, bone-specific alkaline phosphatase, and sclerostin. Sclerostin stability at rest was also validated over the same period of time among women fulfilling the same inclusion criteria. The study included 23 participants (mean ± SD age: 22.9 ± 1.5 years) for the exercise test and 9 participants for the resting test (26.1 ± 3.1 years). There was no difference in body mass index between the two groups. Sclerostin increased after exercise in comparison to baseline (mean ± SEM: 410 ± 27 vs. 290 ± 19 pg/mL;
p
< 0.001) corresponding to an increase of +44.3 ±5.5%. In the resting test, sclerostin remained stable (303 ± 20 vs. 294 ± 20 pg/mL,
p
= 0.76). There was a substantial increase in serum sclerostin in untrained healthy young women immediately after physical activity. These results suggest the existence of an acute release of systemic sclerostin in response to physical activity.
Text recognition in natural scene images is a challenging problem in computer vision. Different than the optical character recognition (OCR), text recognition in natural scene images is more complex ...due to variations in text size, colors, fonts, orientations, complex backgrounds, occlusion, illuminations and uneven lighting conditions. In this paper, we propose a segmentation-free method based on a deep convolutional recurrent neural network to solve the problem of cursive text recognition, particularly focusing on Urdu text in natural scenes. Compared to the non-cursive scripts, Urdu text recognition is more complex due to variations in the writing styles, several shapes of the same character, connected text, ligature overlapping, stretched, diagonal and condensed text. The proposed model gets a whole word image as an input without pre-segmenting into individual characters, and then transforms into the sequence of the relevant features. Our model is based on three components: a deep convolutional neural network (CNN) with shortcut connections to extract and encode the features, a recurrent neural network (RNN) to decode the convolutional features, and a connectionist temporal classification (CTC) to map the predicted sequences into the target labels. To increase the text recognition accuracy further, we explore deeper CNN architectures like VGG-16, VGG-19, ResNet-18 and ResNet-34 to extract more appropriate Urdu text features, and compare the recognition results. To conduct the experiments, a new large-scale benchmark dataset of cropped Urdu word images in natural scenes is developed. The experimental results show that the proposed deep CRNN network with shortcut connections outperform than other network architectures. The dataset is publicly available and can be downloaded from https://data.mendeley.com/datasets/k5fz57zd9z/1 .
Capsaicin 179 mg (8% weight per weight) cutaneous patch ("capsaicin patch") is a recommended topical treatment for peripheral neuropathic pain (PNP). In older patients, topical treatments may be ...preferred over systemic treatments, but data specific to the older population are scarce.
We conducted pooled analyses of multiple clinical trials to evaluate efficacy and safety of capsaicin patch in older patients. The analysis of efficacy included four randomized, double-blind, 12-week studies with similar trial design comparing a single treatment of capsaicin 179 mg cutaneous patch vs low-dose control patch in post-herpetic neuralgia. For the safety evaluation, data were pooled from 18 interventional studies in which capsaicin patch was used in PNP with varying etiologies.
Capsaicin patch had similar analgesic efficacy in elderly (n=582) and non-elderly patients (n=545) in terms of change from baseline to 2-12 weeks in the 11-point numeric pain rating scale (NPRS) score for average pain over the previous 24 hours. In both age groups, decrease in NPRS score was significantly greater with capsaicin patch vs control. Older patients treated with capsaicin patch were significantly more likely than those in the control group to achieve responder status (ie mean decrease in NPRS score from baseline to week 2-12 of at least 30% or ≥2 points): 36.1% vs 27.1% (odds ratio OR 95% CI 1.52 1.06, 2.18;
=0.0231) and 33.1% vs 20.9% (OR 95% CI 1.90 1.30, 2.78;
=0.0009) for active treatment vs control group, respectively. Similar proportions of non-elderly patients (n=2,311) and elderly patients (n=537) treated with capsaicin patch experienced treatment-emergent adverse events (TEAEs) (81.6% and 78.1%, respectively) and serious TEAEs (8.2% and 7.2%), with application-site reactions the most common TEAEs in both groups.
The capsaicin patch was equally efficacious and well tolerated in older patients as in younger patients.
Despite radiation forming the curative backbone of over 50% of malignancies, there are no genomically-driven radiosensitizers for clinical use. Herein we perform in vivo shRNA screening to identify ...targets generally associated with radiation response as well as those exhibiting a genomic dependency. This identifies the histone acetyltransferases CREBBP/EP300 as a target for radiosensitization in combination with radiation in cognate mutant tumors. Further in vitro and in vivo studies confirm this phenomenon to be due to repression of homologous recombination following DNA damage and reproducible using chemical inhibition of histone acetyltransferase (HAT), but not bromodomain function. Selected mutations in CREBBP lead to a hyperacetylated state that increases CBP and BRCA1 acetylation, representing a gain of function targeted by HAT inhibition. Additionally, mutations in CREBBP/EP300 are associated with recurrence following radiation in squamous cell carcinoma cohorts. These findings provide both a mechanism of resistance and the potential for genomically-driven treatment.
Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined ...magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress.
In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 Mg-vitamin B6; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl Mg; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs).
In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related.
These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.
Permafrost thaw is a major potential feedback source to climate change as it can drive the increased release of greenhouse gases carbon dioxide (CO2) and methane (CH4). This carbon release from the ...decomposition of thawing soil organic material can be mitigated by increased net primary productivity (NPP) caused by warming, increasing atmospheric CO2, and plant community transition. However, the net effect on C storage also depends on how these plant community changes alter plant litter quantity, quality, and decomposition rates. Predicting decomposition rates based on litter quality remains challenging, but a promising new way forward is to incorporate measures of the energetic favorability to soil microbes of plant biomass decomposition. We asked how the variation in one such measure, the nominal oxidation state of carbon (NOSC), interacts with changing quantities of plant material inputs to influence the net C balance of a thawing permafrost peatland. We found: (1) Plant productivity (NPP) increased post‐thaw, but instead of contributing to increased standing biomass, it increased plant biomass turnover via increased litter inputs to soil; (2) Plant litter thermodynamic favorability (NOSC) and decomposition rate both increased post‐thaw, despite limited changes in bulk C:N ratios; (3) these increases caused the higher NPP to cycle more rapidly through both plants and soil, contributing to higher CO2 and CH4 fluxes from decomposition. Thus, the increased C‐storage expected from higher productivity was limited and the high global warming potential of CH4 contributed a net positive warming effect. Although post‐thaw peatlands are currently C sinks due to high NPP offsetting high CO2 release, this status is very sensitive to the plant community's litter input rate and quality. Integration of novel bioavailability metrics based on litter chemistry, including NOSC, into studies of ecosystem dynamics, is needed to improve the understanding of controls on arctic C stocks under continued ecosystem transition.
Thawing permafrost in peat‐dominated ecosystems is a major potential feedback source to climate change as it can drive the increased release of greenhouse gases carbon dioxide (CO2) and methane (CH4). Although post‐thaw peatlands are currently C sinks because high plant productivity offsets high CO2 release from decomposition, this status is very sensitive to the plant community's litter input rate and quality. Integration of novel bioavailability metrics based on litter chemistry into studies of ecosystem dynamics, as introduced here, is needed to improve the understanding of controls on arctic C stocks under continued ecosystem transition.
Antimicrobial resistance (AMR) is a growing public health challenge that is expected to disproportionately burden lower- and middle-income countries (LMICs) in the coming decades. Although the ...contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil or food contaminated with human and animal faeces) has been given less attention as a global driver of AMR, especially in urban informal settlements in LMICs-commonly known as 'shanty towns' or 'slums'. These settlements may be unique hotspots for environmental AMR transmission given: (1) the high density of humans, livestock and vermin living in close proximity; (2) frequent antibiotic misuse; and (3) insufficient drinking water, drainage and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades.
The distinction between a specific factor inactivator and a non-specific inhibitor is important when confronted by a patient with a history of bleeding and abnormal in-vitro coagulation tests. We ...report on two patients who presented with bleeding and a prolonged activated partial thromboplastin time. Initial factor assays suggested combined deficiency of factors VIII and IX as a result of the presence of inactivators. The use of dilution studies, chromogenic assays, a novel in-house enzyme-linked-immunosorbent-assay-based technique and phospholipid neutralization, demonstrated that Case 1 had a genuine factor VIII inactivator resulting in factor VIII levels of less than 1 IU/dl but no factor IX deficiency. Case 2 had normal levels of factor VIII on further testing and no specific inactivator to either factor VIII or IX but a potent antiphospholipid antibody which had interfered with the phospholipid-dependent in-vitro assays. Care must be taken in the interpretation of laboratory assays in the presence of antiphospholipid antibodies to ensure that the correct diagnosis is made and inappropriate treatment avoided.
The increasing availability of remotely sensed data have offered unprecedented possibilities for monitoring and analysis of environmental variables, including boosting recent studies in the field of ...ecosystem resilience relying on indicators derived from timeseries analysis, such as the temporal autocorrelation of vegetation indices. A forest ecosystem with decreased resilience will be more susceptible to external drivers and their change and could shift into an alternative system configuration by crossing a tipping point. Nevertheless, remote sensing data quantifying vegetation and forests properties inherently carry information related to the climate as well, which has to be accounted for before performing any modelling exercise. In this paper, we aim to present the general workflow and the challenges encountered in processing and analysing the historical, high-frequency and high-resolution timeseries of vegetation and climatic data. The final aim is training a machine learning model (Random Forest) in order to model and explore the performance and importance of a set of climatic and environmental metrics in predicting an indicator of the resilience of forests. In this case, the resilience of forests is quantified through the temporal autocorrelation (TAC) of the kernel NDVI (kNDVI). Climatic and environmental predictors include 2-meter air temperature, total precipitation, vapour pressure deficit, surface solar radiation, forest cover and soil organic carbon content. Results show a good performance of the Random Forest model and the ranking in the importance of the predicting variables captured in terms of background climate and climate variability. This application allows to separate and identify the main drivers of the temporal autocorrelation of kNDVI.
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