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Collectively, L. salivarius + L. agilis feeding in hens could improve intestinal microflora and metabolism profile, promote crypt's local energy metabolism and reactive oxygen species levels, and thus enhance Paneth cells and intestinal stem cells activity.Key points• Lactobacilli co-feeding could improve laying performance and egg nutrition.• Lactobacilli co-feeding could improve intestinal microflora and metabolism profile.• Lactobacilli co-feeding could enhance Paneth cells and intestinal stem cells activity.Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.Emerging trends in technological innovations, data analysis and practical applications have facilitated the measurement of cycling power output in the field, leading to improvements in training prescription, performance testing and race analysis. This review aimed to critically reflect on power profiling strategies in association with the power-duration relationship in cycling, to provide an updated view for applied researchers and practitioners. The authors elaborate on measuring power output followed by an outline of the methodological approaches to power profiling. Moreover, the deriving a power-duration relationship section presents existing concepts of power-duration models alongside exercise intensity domains. Combining laboratory and field testing discusses how traditional laboratory and field testing can be combined to inform and individualize the power profiling approach. Deriving the parameters of power-duration modelling suggests how these measures can be obtained from laboratory and field testing, including criteria for ensuring a high ecological validity (e.g. rider specialization, race demands). It is recommended that field testing should always be conducted in accordance with pre-established guidelines from the existing literature (e.g. set number of prediction trials, inter-trial recovery, road gradient and data analysis). It is also recommended to avoid single effort prediction trials, such as functional threshold power. Power-duration parameter estimates can be derived from the 2 parameter linear or non-linear critical power model P(t) = W'/t + CP (W'-work capacity above CP; t-time). Structured field testing should be included to obtain an accurate fingerprint of a cyclist's power profile.Secular changes in the incidence rate of hip fractures were estimated to vary by fracture type, i.e., femoral neck or trochanteric fractures, age, and sex, in urban or rural areas in Kyoto Prefecture, Japan from 2008 to 2017.

Our survey in Kyoto Prefecture from 2008 to 2017 showed that the incidence rate of femoral neck fractures is generally increasing. We investigated the differences between urban and rural areas in the changes of the incidence rate over time of femoral neck and trochanteric fractures during the same period.

Patients aged 65years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The ratio of sick beds for acute-term care at the investigated hospitals to total number of beds in the urban area was 16.5% (1863/11,158) and 30.6% (1863/5623) in the rural area. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015.

There were 3559 and 6474 hip fractures in the urban and rural areas, respectively. Femoral neck fractures were 1936 (54.4%) and 2813 (43.5%) in each area. The increase of the population-adjusted numbers was marked by neck fractures in males, in both areas. In women, there was a significant increase in femoral neck fractures in the urban area in those aged 85years and over. For trochanteric fractures, a significant increase was only found in women aged 65 to 74years in the rural area.

A regional difference in the secular changes in incidence rate of hip fractures was found in women, not in men, mostly because neck fractures in women increased in the over 85 group in the urban area.

A regional difference in the secular changes in incidence rate of hip fractures was found in women, not in men, mostly because neck fractures in women increased in the over 85 group in the urban area.Sodium fluorescein (NaFL) has been used to aid in the resection of primary and secondary lesions within the brain. Comparatively, there is limited research on clinical applications for lesions within the spinal cord. Fluorescein-guided microsurgery may increase the ability to localize and safely surgically treat spinal lesions. Twelve patients with spinal cord lesions received fluorescein sodium 10% (Alcon Laboratories INC, Fort Worth, TX, USA) at 3 mg/kg prior to surgical resection. Intraoperative visualization of fluorescence was performed using a Zeiss Pentero (Carl Zeiss AG, Oberkochen, Germany) microscope equipped with a Yellow560 filter or a Leica OH6 (Leica Microsystems, Wetzlar, Germany) equipped with a FL560 filter. Administration of NaFL resulted in lesional fluorescent contrast extravasation and facilitated surgical resection and localization in all twelve patients. In patients with a goal of complete resection, NaFL aided in complete resection of the spinal lesions in seven patients. In surgical resection patients, pathology was consistent with WHO grade I myxopapillary ependymoma in one patient, WHO grade II ependymoma in five patients, and nerve sheath tumor in one patient. In the other five patients, NaFL allowed for intraoperative tissue identification and successful tissue biopsy. In patients undergoing biopsy, tissue samples were positive for an intramedullary abscess, EBV-driven lymphoproliferative disease, and primary glial neoplasms. Fluorescein is a helpful microsurgical tool in guiding surgical resection and in the localization of intramedullary spinal lesions. Further research is necessary to explore fluorescein sodium applications in the resection of spinal cord lesions.

To conduct a systematic review and meta-analysis of the effects of antidepressant drug therapy (with or without physical exercise) on peripheral inflammatory markers in patients with major depressive disorder (MDD).

MEDLINE, PyscINFO, Embase, and Google Scholar databases were searched until May 2020. Randomized trials that measured at least one inflammatory biomarker and included adult outpatients with MDD under antidepressant drug therapy (any drug) with or without physical exercise (any modality) were eligible. FPR agonist Results were summarized using the standardized mean difference (SMD) with 95% confidence intervals (95% CI) under a random-effects model. The Cochrane risk of bias tool (2010) was used to evaluate the risk of bias in the included trials.

Sixty-three trials were identified, encompassing data from 3482 patients, and 20 investigated biomarkers. Trials had biases across multiple domains, rising concerns primarily to selection bias/performance bias/detection bias/attrition bias. SMDs between pre- and post-results indicated a significant reduction in the levels of IL-2 (SMD, - 0.25; 95% CI, - 0.41 to - 0.09, P = 0.002), IL-6 (SMD, - 0.19; 95% CI, - 0.35 to - 0.025, P = 0.024), IL-10 (SMD, - 0.32; 95% CI, - 0.57 to - 0.07, P = 0.011), and serum cortisol (SMD, - 0.35; 95% CI, - 0.58 to - 0.12, P = 0.002). Evidence supporting the influence of physical exercise combined with antidepressant drugs on peripheral inflammatory markers in MDD is sparse and heterogeneous.

There is some evidence that antidepressant drug therapy is associated with an overall positive reduction in inflammatory markers, but the evidence is heterogeneous. Further research linking how inflammatory biomarkers modulate physiology related to antidepressant response is required.

CRD42020220735.

CRD42020220735.

Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels. Although several cardiovascular outcome trials reported the effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence and synthesized incremental net benefit (INB) to quantify pooled cost-effectiveness.

We systematically searched for full economic evaluation studies reporting outcomes of PCSK9i compared with other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up to August 2021, adhering to preferred reporting items for systematic reviews and meta-analyses guidelines. We pooled INB in US$ with a 95% confidence interval using a random-effects model. We assessed heterogeneity using the Cochran Q test and I

statistics. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of selected studies.

Twenty-three studies were eligible, mainly from high-red to other lipid-lowering pharmacotherapies in HICs. Further, current pieces of evidence are predominantly from HICs with largely lacking evidence from other economies.

ID CRD42020206043.

ID CRD42020206043.Focal activation is believed to be an atrial fibrillation (AF) driver; however, little is known about whether all focal activations are necessary for AF persistence. The purpose of this study was to assess the electrical nature of focal activation and identify high-priority focal activations using a novel mapping system (CARTOFINDER). Thirty-five patients with persistent AF who underwent catheter ablation were assessed. Cycle length (CL) and CL standard deviation (CLSD) on unipolar recordings and voltage amplitude and electrogram morphologies on bipolar recordings were evaluated at all points of interest. The most frequent CL at each mapping site was defined as the dominant CL. We identified dominant focal activations (DFAs) that had a shorter dominant CL on the integrated CARTOFINDER map. The effect of elimination of DFAs on AF maintenance was assessed by the composite endpoint (termination to sinus rhythm, organization of the rhythm to atrial tachycardia, and AF CL slowing). In all, 450 focal activations were identified among 10,868 points, and 50.

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