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7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRA; 53 (13.8%) patients maintained SROT, which was associated with TRA discontinuation in complete response (p less then 0.001). Very old age (≥75, 41.1%) was associated with more frequent TRAs start in persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in elderly ITP patients, with no fatal haemorrhages and with SROT in a significant portion of patients; in patients with thrombosis history caution is warranted and a careful risk/benefit balance should be carried out.Peroxiredoxin 3 (PRDX3) belongs to a superfamily of peroxidases that function as protective antioxidant enzymes. Among the six isoforms (PRDX1-PRDX6), PRDX3 is the only protein exclusively localized to the mitochondria, which are the main source of reactive oxygen species. Excessive levels of reactive oxygen species are harmful to cells, inducing mitochondrial dysfunction, DNA damage, lipid and protein oxidation and ultimately apoptosis. Neuronal cell damage induced by oxidative stress has been associated with numerous neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Leveraging the large aggregation of genomic ataxia datasets from the PREPARE (Preparing for Therapies in Autosomal Recessive Ataxias) network, we identified recessive mutations in PRDX3 as the genetic cause of cerebellar ataxia in five unrelated families, providing further evidence for oxidative stress in the pathogenesis of neurodegeneration. The clinical presentation of individuals with PRDX3 mutations consists of mild-to-moderate progressive cerebellar ataxia with concomitant hyper- and hypokinetic movement disorders, severe early-onset cerebellar atrophy, and in part olivary and brainstem degeneration. Patient fibroblasts showed a lack of PRDX3 protein, resulting in decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. Moreover, PRDX3 knockdown in cerebellar medulloblastoma cells resulted in significantly decreased cell viability, increased H2O2 levels and increased susceptibility to apoptosis triggered by reactive oxygen species. Pan-neuronal and pan-glial in vivo models of Drosophila revealed aberrant locomotor phenotypes and reduced survival times upon exposure to oxidative stress. Our findings reveal a central role for mitochondria and the implication of oxidative stress in PRDX3 disease pathogenesis and cerebellar vulnerability and suggest targets for future therapeutic approaches.

The management of perforated diverticular disease has changed in the past 10 years with a move towards less surgical intervention. This population-based cohort study aimed to define the risk of death and readmission following non-operative management of perforated diverticular disease.

Patients diagnosed with perforated diverticular disease and managed without surgery were identified from the linked Clinical Practice Research Datalink and Hospital Episode Statistics data from 2000 to 2013. The outcomes were 1-year case fatality, readmissions, and surgery at readmission.

In total, 880 patients with perforated diverticular disease were managed without surgery, comprising 523 women (59.4 per cent). The 1-year case fatality rate was 33.2 per cent (293 of 880). The majority of deaths occurred in the first 90 days after the index admission, with a 90-day case fatality rate of 28.8 per cent. The 90-day survival rate varied by age, and was 97.2 per cent among those aged less than 65 years, compared with 85.0 per cent for those aged between 65 and 74 years, and 47.7 per cent in those at least 75 years old. Of 767 patients discharged from hospital, 250 (32.6 per cent) were readmitted (47 elective, 6.1 per cent; 203 emergency, 26.5 per cent) during a median of 1.6 (i.q.r. 0.1-3.9) years of follow-up, with similar proportions in each age category. In the first year of follow-up, only 5.1 per cent of patients required surgery, of whom 16 of 767 (2.1 per cent) required elective and 23 (3.0 per cent) emergency operation.

Non-operative management of perforated diverticulitis in those aged less than 65 years is feasible and safe. Reintervention rates following conservative management were low across all age categories.

Non-operative management of perforated diverticulitis in those aged less than 65 years is feasible and safe. find more Reintervention rates following conservative management were low across all age categories.

Transanal total mesorectal excision (TaTME) is an innovative technique for distal rectal cancer dissection. It has been shown to have similar short-term outcomes to conventional open and laparoscopic total mesorectal excision (cTME), but recent studies have raised concern about increased morbidity and local recurrence rates. The aim of this study was to assess outcomes after TaTME versus cTME for rectal cancer.

TaTME was implemented in 2014 using IDEAL principles in a single institution. The institution maintains databases for all patients undergoing rectal cancer surgery. This retrospective review compared data collected from all patients who had TaTME with those from a propensity-matched cohort of patients who underwent cTME. The primary outcome was a composite pathological measure combining margin status and quality of total mesorectal excision (TME). Short-term clinical and survival outcomes were also measured.

Propensity matching created 109 matched pairs for analysis. Nine patients (8.3 per cent) undergoing TaTME had positive margins and/or incomplete TME, compared with 11 (10.5 per cent) undergoing cTME (P = 0.65). There were no significant differences in morbidity between the TaTME and cTME groups, including number of anastomotic leaks (13.8 versus 18.3 per cent; P = 0.37). The estimated 3-year local recurrence-free survival rate was 96.3 per cent in both groups (P = 0.39). Estimated 3-year overall (93.6 per cent for TaTME versus 94.5 per cent for cTME; P = 0.09) and disease-free (88.1 versus 76.1 per cent; P = 0.90) survival rates were similar.

TaTME provided similar outcomes to cTME for rectal cancer with the application of IDEAL principles.

TaTME provided similar outcomes to cTME for rectal cancer with the application of IDEAL principles.Conditions of impaired energy and nutrient homeostasis, such as diabetes and obesity, are associated with infertility. Hyperglycemia increases endoplasmic reticulum stress as well as oxidative stress and reduces embryo development and quality. Oxidative stress also causes deoxyribonucleic acid damage, which impairs embryo quality and development. The natural bile acid tauroursodeoxycholic acid reduces endoplasmic reticulum stress and rescues developmentally incompetent late-cleaving embryos, as well as embryos subjected to nuclear stress, suggesting the endoplasmic reticulum stress response, or unfolded protein response, and the genome damage response are linked. Tauroursodeoxycholic acid acts via the Takeda-G-protein-receptor-5 to alleviate nuclear stress in embryos. To evaluate the role of tauroursodeoxycholic acid/Takeda-G-protein-receptor-5 signaling in embryo unfolded protein response, we used a model of glucose-induced endoplasmic reticulum stress. Embryo development was impaired by direct injection of by nutrient excess-associated blastomere stress and embryo death.To examine the length of a hexanucleotide expansion in C9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterized C9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged the C9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Southern blotting (P = 5.0 × 10-4). Interestingly, we also detected a significant survival advantage for individuals with smaller expansions (P = 0.004). Additionally, we uncovered that smaller expansions were significantly associated with higher levels of C9orf72 transcripts containing intron 1b (P = 0.003), poly(GP) proteins (P = 1.3 × 10- 5), and poly(GA) proteins (P = 0.005). Thorough examination of the composition of the expansion revealed that its GC content was extremely high (median 100%) and that it was mainly composed of GGGGCC repeats (median 96%), suggesting that expanded C9orf72 repeats are quite pure. Taken together, our findings demonstrate that No-Amp sequencing is a powerful tool that enables the discovery of relevant clinicopathological associations, highlighting the important role played by the cerebellar size of the expanded repeat in C9orf72-linked diseases.Several international regulatory bodies and researchers have identified employees in the municipal refuse and recycling industry as potentially at risk of noise induced hearing loss. Whilst materials recycling facilities have been subject to research regarding the health effects of hazardous exposures, the roadside recycling collection aspects of the industry has been identified as requiring further investigation. The requirement for characterization of such risk has been increased in the European Union by legislation that has led to increased rates of municipal recycling in the waste disposal industry. In particular, the introduction of glass recycling collection rounds over recent years, alongside long-established refuse collection activities, has given rise to possible further increased levels of industrial noise exposure, beyond that of refuse collection alone. This cross-sectional study describes hearing threshold categorization in 201 male full-time refuse collection workers, most of whom had many years of employment in municipal refuse collection, and all of whom, in the 3-4 years preceding the study, had commenced a work pattern of alternating weeks of municipal glass recycling collection and refuse collection. During this period there was no compulsory use of personal hearing protective equipment. No excess of hearing loss was found in this group, irrespective of years in refuse collection duties or when compared with those studied with additional responsibilities as a driver of refuse wagons (a task not considered to lead to excessive noise exposure). Further research into hearing loss in such employees is merited, given the short time period of exposure to noise from glass collection, but the possible benefit of undertaking detailed full shift personal noise exposure in this group is proposed.We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6-23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if interictal epileptiform discharges occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate.