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ense reproductive behavior. Genotyping might be a useful procedure for identifying the correct and rational use of rams in modern sheep farming.Dairy farms face many challenges and changes. With increasing herd sizes and fewer farmers or employees per cow, new strategies to maintain or improve reproductive management are required. One of the major challenges is to detect cows in estrus and to estimate the perfect time for artificial insemination (AI). Several estrus and ovulation synchronization programs with timed AI as well as estrus detection aids, e.g., tail-paint, pedometer, accelerometer, and others are available. A combination of ovulation synchronization programs and technical solutions, however, has rarely been tested. This study was designed to gain insights into behavioral patterns of cows subjected to an Ovsynch program and to test if behavioral data could be used to optimize the timing of insemination within an Ovsynch program. In this study, we used an ear-tag based 3D-accelerometer system (SMARTBOW, Smartbow GmbH, Weibern, Austria) to generate data of behavioral patterns, i.e., rumination and activity. In Part 1 of this study, behavioral patterns during the peri-estrus period were compared between cows with physiological estrus and cows subjected to an Ovsynch protocol. On the day before estrus and on the day of estrus/AI, cows with natural estrus showed a clear drop in rumination and "inactivity" and an increase in "high activity", based on an algorithm of the accelerometer system, whereas, cows in the Ovsynch protocol showed only minor changes in behavioral patterns. In Part 2, we analyzed behavioral patterns between synchronized cows that became pregnant after AI and synchronized cows that remained open. As a result, no differences were detected between these two Ovsynch groups before AI. see more Thus, in this study we found no evidence that behavioral patterns can be used to improve conception rates within an Ovsynch protocol.

PARP inhibitors are active in various tumour types beyond BRCA-mutant cancers, but their activity and molecular correlates in colorectal cancer (CRC) are not well studied.

Mutations and genome-wide mutational patterns associated with homologous recombination deficiency (HRD) were investigated in 255 primary CRCs with whole-exome sequencing and/or DNA copy number data. Efficacy of five PARP inhibitors and their molecular correlates were evaluated in 93 CRC cell lines partly annotated with mutational-, DNA copy number-, and/or gene expression profiles. Post-treatment gene expression profiling and specific protein expression analyses were performed in two pairs of PARP inhibitor sensitive and resistant cell lines.

A subset of microsatellite stable (MSS) CRCs had truncating mutations in homologous recombination-related genes, but these were not associated with genomic signatures of HRD. Eight CRC cell lines (9%) were sensitive to PARP inhibition, but sensitivity was not predicted by HRD-related genomic and transcriptomic signatures. In contrast, drug sensitivity in MSS cell lines was strongly associated with TP53 wild-type status (odds ratio 15.7, p=0.023) and TP53-related expression signatures. link2 Increased downstream TP53 activity was among the primary response mechanisms, and TP53 inhibition antagonized the effect of PARP inhibitors. Wild-type TP53-mediated suppression of RAD51 was identified as a possible mechanism of action for sensitivity to PARP inhibition.

PARP inhibitors are active in a subset of CRC cell lines and preserved TP53 function may increase the likelihood of response.

PARP inhibitors are active in a subset of CRC cell lines and preserved TP53 function may increase the likelihood of response.

The epidemiology of multiple sclerosis (MS) is important for planning disease modifying therapy (DMT). Secular changes in the use of DMT in MS can guide future service development.

A population study of the prevalence of multiple sclerosis was completed in the west of Northern Ireland - a defined geographic area making up the Western Health and Social Care Trust (WHSCT). The use, category and cost of DMT for the MS population in the WHSCT were measured over 11 years.

The WHSCT had a recorded prevalence of MS of 238.4/100,000 (95%CI 221.5-256.5) in 2018. DMT use increased over threefold in 11 years. Four hundred and nine (57%) of 720 MS patients were taking a DMT by 2018. The annual expenditure of DMT drugs had increased sixfold over ten years to £5,301,198 in 2018 (using 2018 prices), reflecting both an increase in DMT use and a switch to more intensive DMTs. Younger MS patients were more likely to be taking a DMT (P<0.001).

DMT use and cost have been increasing among the MS population in the Northern Ireland. There has been a temporal switch to more efficacious DMTs. Future research should monitor the cost-effectiveness and equity of treatment of MS patients.

DMT use and cost have been increasing among the MS population in the Northern Ireland. There has been a temporal switch to more efficacious DMTs. Future research should monitor the cost-effectiveness and equity of treatment of MS patients.

This study aimed to map the outcome measures of clinical efficacy reported in Randomized Controlled Trials (RCT) to evaluate disease-modifying therapies (DMT) in patients with relapsing forms of multiple sclerosis (RMS).

A systematic scoping review was performed to identify RCT that assessed the efficacy of DMT in adult patients with RMS. Searches were conducted in PubMed, Scopus, and The Cochrane Controlled Register of Trials and complemented by manual search. A descriptive-quantitative analysis of the clinical efficacy outcomes with their respective definitions was performed.

Of the 5,476 records identified, 226 were included. Among the included studies, 89% reported clinical efficacy outcomes, with 77 different outcomes identified, including five composite outcomes. A total of 36 different definitions for 'relapse' were identified. 'Annualized relapse rate' was the most prevalent single outcome (n=56 studies). At the same time, the 'Proportion of patients with no evidence of radiological and clinic disease activity' was the most prevalent composite outcome (n=14 studies) although with six different definitions.

An absence of consensus on the clinical efficacy outcomes reported in RCT associated with a wide heterogeneity of definitions were identified. The mapped results of this research can be used as a basis for the definition of a core outcome set for clinical efficacy outcomes in adults with RMS.

An absence of consensus on the clinical efficacy outcomes reported in RCT associated with a wide heterogeneity of definitions were identified. The mapped results of this research can be used as a basis for the definition of a core outcome set for clinical efficacy outcomes in adults with RMS.

A wide range of risk factors, from genetic to environmental, have been identified to play role in the etiology of multiple sclerosis. However, the role of trace element remains mostly unknown. We sought to combine all available evidence to assess the association between copper concentration and multiple sclerosis.

This systematic review and meta-analysis was conducted based on PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science were searched since inception till July 2020. Observational studies that assessed copper as exposure in serum, plasma, whole blood, and cerebrospinal fluid were included. Standardized mean differences (SMD), comparing the mean of copper concentration in multiple sclerosis patients versus healthy controls, were considered as the measure of association. The fixed-effect model with inverse variance weighting was used to combine the findings.

Twenty studies inclusive of 797 multiple sclerosis cases and 875 healthy controls were included in the meta-analysis (all case-control studies). The combined SMDs were 1.25 (95% confidence interval [CI] 0.95 to 1.55, number of included studies [n]=4) in plasma, 0.45 (CI 0.22 to 0.68, n=4) in whole blood, 0.19 (CI 0.06 to 0.33, n=12) in blood serum and 1.23 (CI 0.83 to 1.64, n=4) in cerebrospinal fluid.

We found a higher concentration of copper in multiple sclerosis patients than healthy controls. The possible causal nature of the observed associations warrants further investigation with prospective data.

We found a higher concentration of copper in multiple sclerosis patients than healthy controls. The possible causal nature of the observed associations warrants further investigation with prospective data.

The epidemiology of multiple sclerosis (MS) and neuromyelitis optica (NMO) remains to be clarified or updated in many parts of Asia. This study aims to investigate the epidemiology and comorbidities of MS and NMO during 2001-2015 in Taiwan.

We conducted a retrospective nationwide population-based study using data from Taiwan's National Health Insurance Research Database. Cases of MS and NMO aged 20 years or above during 2001-2015 were enrolled. The incidence, prevalence, demographic features, and comorbidities were investigated.

We identified 4627 MS and 861 NMO incident cases aged 20 or above during 2003-2015. The incidence of MS was relatively stationary, while that of NMO apparently rose steeply during the study period. The age-standardized incidence rate of MS and NMO in 2015 were 1.34 and 0.61 per 100,000 person-years, respectively. The age-standardized prevalence rate of MS and NMO in 2015 were 6.69 and 1.47 per 100,000 persons, respectively. The female preponderance was evident for both MS and NMO. Except for diabetes mellitus, the most common autoimmune comorbidities for MS and NMO were Sjogren syndrome and systemic sclerosis, and Sjogren syndrome and systemic lupus erythematosus, respectively.

Taiwan has transitioned from low- to medium-risk zone during 2001-2015 in terms of MS prevalence, although its incidence remained stationary. The apparent upsurge of NMO over the period probably reflects increased awareness of this clinical entity. Comorbid autoimmune disorders were relatively common, and overlapping but differential autoimmune comorbidity profiles were noted for MS and NMO.

Taiwan has transitioned from low- to medium-risk zone during 2001-2015 in terms of MS prevalence, although its incidence remained stationary. The apparent upsurge of NMO over the period probably reflects increased awareness of this clinical entity. Comorbid autoimmune disorders were relatively common, and overlapping but differential autoimmune comorbidity profiles were noted for MS and NMO.While the abundance of photobacteria has previously been exclusively associated with marine environments and spoilage of seafood, several recent studies have demonstrated their status as pervasive constituents of the microbiota on packaged meats. Since their ubiquitous nature has been revealed, detection of their presence on meat, their entry route into meat processing environments and prevention of their growth is a novel emerging challenge for the food industry. In this study, we have developed a highly sensitive and specific loop-mediated isothermal amplification (LAMP) assay for the detection of relevant species of photobacteria on foods, and tested its efficacy on meats. The gene encoding trimethylamine-N-oxide reductase (torA) was chosen as the target for this assay. Designed primers based on the gene sequence proved their specificity by testing 67 isolates of 5 species of photobacteria (positive) as well as 63 strains of 16 species of other common meat spoilers (negative). link3 The optimized assay takes 2 h including sample preparation and has a detection limit of only 10-11 copies (50 fg/reaction) of the average Photobacterium (P.