Miracle-dz/UniFAR-FTUs huggingface dataset:
Rural centres do not have a higher prevalence of post‐operative complications than urban centres: a retrospective analysis of a mortality audit

The trend towards centralization of surgical care from rural to high‐volume centres is based on studies showing better outcomes for patients requiring complex surgical procedures. However, evidence that this also applies to less complex procedures is lacking. This study therefore aimed to determine whether there was a relationship between geographic location (rural versus urban) of surgical procedures of varying complexity and post‐operative complications.
Retention of tocilizumab with and without methotrexate during maintenance therapy for rheumatoid arthritis: the ACTRA-RI cohort study

Abstract Objectives To compare retention of tocilizumab (TCZ) as monotherapy vs combination therapy with MTX in RA patients achieving clinical improvements during the first year. Methods We performed a multicentre cohort study using a real-life registry containing RA patients who had begun TCZ with or without MTX between April 2008 and November 2016. Among patients with ≥50% improvement of clinical disease activity index (CDAI) during the first year (CDAI50 responders), we evaluated whether MTX use may have affected TCZ discontinuation during the second and subsequent years (maintenance therapy). Results Among 510 patients with high or moderate CDAI, 328 (64.3%) were CDAI50 responders. The rate of MTX use was 53.0% among responders and 54.4% among non-responders. During maintenance therapy (mean follow-up 30.7 months), 43.9% of CDAI50 responders discontinued TCZ. The most common cause was efficacy loss followed by adverse events. Kaplan-Meier estimates for TCZ retention were 48.3 months (95% CI 42.0, 54.5) for monotherapy and 50.0 months (95% CI 45.9, 54.0) for combination therapy. According to Gray’s test, there was no significant impact of MTX use on cumulative incidence of efficacy loss or adverse events. In the Fine-Gray competing risk regression model, CDAI >10 at the start of maintenance therapy and age were predictive factors for TCZ discontinuation due to efficacy loss (hazard ratio 2.58, 95% CI 1.41, 4.72) and adverse events (hazard ratio 1.04, 95% CI 1.01, 1.08), respectively. Conclusion There was no significant difference in TCZ retention between monotherapy and combination therapy with MTX.
Is There a Difference in Infection Risk Between Single and Multiple Doses of Prophylactic Antibiotics? A Meta-analysis.

BACKGROUND The prevention of surgical site infection guidelines issued by the Centers for Disease Control and Prevention (CDC) recently recommended that only a single dose of preoperative antibiotics be administered to patients undergoing clean-contaminated procedures based on data from a variety of surgical disciplines. For orthopaedic procedures, where postoperative infections can have significant consequences, the existing evidence for this recommendation is widely debated. QUESTIONS/PURPOSES Is there a difference in postoperative infection risk when utilizing a single dose of preoperative antibiotics compared with multiple doses of perioperative antibiotics for orthopaedic procedures where implants are placed? METHODS MEDLINE, EMBASE, Google Scholar, and Cochrane were systematically reviewed for randomized controlled trials (RCTs) of a single dose of preoperative antibiotics compared with pre- and postoperative prophylaxis from 1980 to 2017 for all orthopaedic procedures where implants were being placed. Infection (both superficial and deep) as a primary outcome through all available followup was required for inclusion. Fourteen RCTs detailing 9691 orthopaedic procedures were included for analysis, including seven arthroplasty, one spine, and six general orthopaedic trials (two specific to hip fracture fixation). Pooled infection outcomes were analyzed with random-effects modeling in light of study heterogeneity. Bias was evaluated using the Cochrane risk of bias tool as well as a funnel plot for publication bias, and quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Bias was largely uncertain; however, a high risk of bias was noted in four studies. No significant overall publication bias was noted. The quality of evidence was determined to be very low based on the GRADE tool, downgraded based on risk of bias, inconsistency, and imprecision. Despite the quality of evidence, the data were pooled in light of the current recommendations from the CDC to critically evaluate the recommendation that a single dose of antibiotics be utilized. RESULTS There were no differences in infection risk between single- versus multiple-dose groups (single: 83 of 4263 [2%], multiple: 101 of 5428 [2%]; odds ratio, 0.92 [95% confidence interval, 0.56-1.51]; p = 0.740, I = 36% for statistical heterogeneity). CONCLUSIONS There is no difference in infection risk between a single dose and multiple doses of perioperative antibiotics for orthopaedic procedures where implants are utilized, consistent with recent recommendations. However, the quality of evidence for orthopaedic procedures is low, and a randomized study with a sufficient sample size is needed to examine the issue before universal adoption of a single antibiotic dose. LEVEL OF EVIDENCE Level I, therapeutic study.
Biomass segregation between biofilm and flocs improves the control of nitrite-oxidizing bacteria in mainstream partial nitritation and anammox processes

The control of nitrite-oxidizing bacteria (NOB) challenges the implementation of partial nitritation and anammox (PN/A) processes under mainstream conditions. The aim of the present study was to understand how operating conditions impact microbial competition and the control of NOB in hybrid PN/A systems, where biofilm and flocs coexist. A hybrid PN/A moving-bed biofilm reactor (MBBR; also referred to as integrated fixed film activated sludge or IFAS) was operated at 15 °C on aerobically pre-treated municipal wastewater (23 mgNH4-N·L−1). Ammonium-oxidizing bacteria (AOB) and NOB were enriched primarily in the flocs, and anammox bacteria (AMX) in the biofilm. After decreasing the dissolved oxygen concentration (DO) from 1.2 to 0.17 mgO2·L−1 - with all other operating conditions unchanged - washout of NOB from the flocs was observed. The activity of the minor NOB fraction remaining in the biofilm was suppressed at low DO. As a result, low effluent NO3− concentrations (0.5 mgN·L−1) were consistently achieved at aerobic nitrogen removal rates (80 mgN·L−1·d−1) comparable to those of conventional treatment plants. A simple dynamic mathematical model, assuming perfect biomass segregation with AOB and NOB in the flocs and AMX in the biofilm, was able to qualitatively reproduce the selective washout of NOB from the flocs in response to the decrease in DO-setpoint. Similarly, numerical simulations indicated that flocs removal is an effective operational strategy to achieve the selective washout of NOB. The direct competition for NO2− between NOB and AMX - the latter retained in the biofilm and acting as a “NO2-sink” - was identified by the model as key mechanism leading to a difference in the actual growth rates of AOB and NOB (i.e., μNOB < μAOB in flocs) and allowing for the selective NOB washout. Experimental results and model predictions demonstrate the increased operational flexibility, in terms of variables that can be easily controlled by operators, offered by hybrid systems as compared to solely biofilm systems for the control of NOB in mainstream PN/A applications. Highlights Hybrid PN/A systems provide increased operational flexibility for NOB control AOB and NOB enrich primarily in the flocs, and AMX in the biofilm (“NO2-sink”) AMX use NO2− allowing to differentiate AOB and NOB growth rates A decrease in DO or an increase in floc removal leads to selective NOB washout from flocs The activity of the minor NOB fraction in the biofilm is suppressed at limiting DO
Periodontal Disease in Pregnancy: The Influence of General Factors and Inflammatory Mediators.

PURPOSE To determine the influence of plaque and progesterone on periodontitis in pregnant women and their relationship with inflammatory mediators. MATERIALS AND METHODS A longitudinal observational study of 60 pregnant women was undertaken in two observation periods. During the third trimester, plaque Index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed, and the basal levels of progesterone, CRP, IL-6 and TNF-α in plasma were measured. The second observation phase was carried out 6 weeks after childbirth, when periodontal indices, progesterone and serum levels of CRP were again evaluated. RESULTS Periodontal disease was moderate in 18.3%. PI and toothbrushing proved to have a correlation with the severity of periodontitis. High levels of CRP were significantly correlated (p < 0.05), with a greater BOP (r = 0.360) and PPD (r = 0.321). There was no correlation between IL-6 or TNF-α with periodontal parameters. After childbirth, progesterone was drastically reduced, BOP and PPD improved and CRP showed a significant reduction of 2.63 mg/l (p < 0.05). CONCLUSIONS Periodontal disease is prevalent during pregnancy. PI and frequency of toothbrushing are correlated with the severity of periodontitis in pregnant women. Pregnancy showed an increased in the level of CRP, which was positively correlated with BOP and PPD. All periodontal indices and CRP level statistically significantly decreased after childbirth, together with a marked reduction of progesterone and without changes in PI.
Psychosocial factors and behavioral medicine interventions in asthma.

OBJECTIVE This review examines the evidence for psychosocial influences in asthma and behavioral medicine approaches to its treatment. METHOD We conducted a systematic review of the literature on psychosocial influences and the evidence for behavioral interventions in asthma with a focus on research in the past 10 years and clinical trials. Additional attention was directed at promising new developments in the field. RESULTS Psychosocial factors can influence the pathogenesis and pathophysiology of asthma, either directly through autonomic, endocrine, immunological, and central nervous system mechanisms or indirectly through lifestyle factors, health behaviors, illness cognitions, and disease management, including medication adherence and trigger avoidance. The recent decade has witnessed surging interest in behavioral interventions that target the various pathways of influence. Among these, self-management training, breathing training, and exercise or physical activation programs have proved particularly useful, whereas other essential or promising interventions, such as smoking cessation, dietary programs, perception and biofeedback training, and suggestive or expressive psychotherapy, require further, more rigorous evaluation. Given the high comorbidity with anxiety and mood disorders, further evaluation of illness-specific cognitive behavior therapy is of particular importance. Progress has also been made in devising community-based and culturally tailored intervention programs. CONCLUSION In concert with an essential medication treatment, behavioral medicine treatment of asthma is moving closer toward an integrated biopsychosocial approach to disease management.
Toxicity of CeO2 nanoparticles on a freshwater experimental trophic chain: A study in environmentally relevant conditions through the use of mesocosms

Abstract The toxicity of CeO2 NPs on an experimental freshwater ecosystem was studied in mesocosm, with a focus being placed on the higher trophic level, i.e. the carnivorous amphibian species Pleurodeles waltl. The system comprised species at three trophic levels: (i) bacteria, fungi and diatoms, (ii) Chironomus riparius larvae as primary consumers and (iii) Pleurodeles larvae as secondary consumers. NP contamination consisted of repeated additions of CeO2 NPs over 4 weeks, to obtain a final concentration of 1 mg/L. NPs were found to settle and accumulate in the sediment. No effects were observed on litter decomposition or associated fungal biomass. Changes in bacterial communities were observed from the third week of NP contamination. Morphological changes in CeO2 NPs were observed at the end of the experiment. No toxicity was recorded in chironomids, despite substantial NP accumulation (265.8 ± 14.1 mg Ce/kg). Mortality (35.3 ± 6.8%) and a mean Ce concentration of 13.5 ± 3.9 mg/kg were reported for Pleurodeles. Parallel experiments were performed on Pleurodeles to determine toxicity pathways: no toxicity was observed by direct or dietary exposures, although Ce concentrations almost reached 100 mg/kg. In view of these results, various toxicity mechanisms are proposed and discussed. The toxicity observed on Pleurodeles in mesocosm may be indirect, due to microorganism’s interaction with CeO2 NPs, or NP dissolution could have occurred in mesocosm due to the structural complexity of the biological environment, resulting in toxicity to Pleurodeles. This study strongly supports the importance of ecotoxicological assessment of NPs under environmentally relevant conditions, using complex biological systems.
Effects of SRSF1 on subnuclear localization of topoisomerase I

Subnuclear localization of topoisomerase I (top I) is determined by its DNA relaxation activity and a net of its interactions with in majority unidentified nucleolar and nucleoplasmic elements. Here, we recognized SR protein SRSF1 (Serine/arginine‐rich splicing factor 1, previously known as SF2/ASF) as a new element of the net. In HeLa cells, overexpression of SRSF1 recruited top I to the nucleoplasm whereas its silencing concentrated it in the nucleolus. Effect of SRSF1 was independent of top I relaxation activity and was the best pronounced for the mutant inactive in relaxation reaction. In HCT116 cells where top I was not released from the nucleolus upon halting relaxation activity, it was also not relocated by elevated level of SRSF1. Out of remaining SR proteins, SRSF5, SRSF7, and SRSF9 did not influence the localization of top I in HeLa cells whereas overexpression of SRSF2, SRSF3, SRSF6, and partly SRSF4 concentrated top I in the nucleolus, most possibly due to the reduction of the SRSF1 accessibility. Specific effect of SRSF1 was exerted because of its distinct RS domain. Silencing of SRSF1 compensated the deletion of the top I N‐terminal region, individually responsible for nucleoplasmic localization of the mutant, and restored the wild‐type phenotype of deletion mutant localization. SRSF1 was essential for the camptothecin‐induced clearance from the nucleolus. These results suggest a possible role of SRSF1 in establishing partition of top I between the nucleolus and the nucleoplasm in some cell types with distinct combinations of SR proteins levels.
Cryopreservation of UVC pathogen‐inactivated platelets

Extending the platelet (PLT) shelf life and enhancing product safety may be achieved by combining cryopreservation and pathogen inactivation (PI). Although studied individually, limited investigations into combining these treatments has been performed. The aim of this study was to investigate the effect of PI treating PLTs before cryopreservation on in vitro PLT quality and function.
On the use of oxygenic photosynthesis for the sustainable production of commodity chemicals

A sustainable society will have to largely refrain from the use of fossil carbon deposits. In such a regime, renewable electricity can be harvested as a primary source of energy. However, as for the synthesis of carbon‐based materials from bulk chemicals, an alternative is required. A sustainable approach towards this is the synthesis of commodity chemicals from CO2, water and sunlight. Multiple paths to achieve this have been designed and tested in the domains of chemistry and biology. In the latter, the use of both chemotrophic and phototrophic organisms has been advocated. ‘Direct conversion’ of CO2 and H2O, catalyzed by an oxyphototroph, has excellent prospects to become the most economically competitive of these transformations, because of the relative ease of scale‐up of this process. Significantly, for a wide range of energy and commodity products, a proof of principle via engineering of the corresponding production organism has been provided. In the optimization of a cyanobacterial production organism, a wide range of aspects has to be addressed. Of these, here we will put our focus on: (1) optimizing the (carbon) flux to the desired product; (2) increasing the genetic stability of the producing organism and (3) maximizing its energy conversion efficiency. Significant advances have been made on all these three aspects during the past 2 years and these will be discussed: (1) increasing the carbon partitioning to >50%; (2) aligning product formation with the growth of the cells and (3) expanding the photosynthetically active radiation region for oxygenic photosynthesis.
EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow–Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction

Background: Clinical trials of bone marrow cell–based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific bone marrow cell–derived secreted proteins may provide an alternative biological approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in bone marrow cells from patients with acute MI and discovered a poorly characterized secreted protein, EMC10 (endoplasmic reticulum membrane protein complex subunit 10), showing activity in an angiogenic screen. Methods: We investigated the angiogenic potential of EMC10 and its mouse homolog (Emc10) in cultured endothelial cells and infarcted heart explants. We defined the cellular sources and function of Emc10 after MI using wild-type, Emc10-deficient, and Emc10 bone marrow–chimeric mice subjected to transient coronary artery ligation. Furthermore, we explored the therapeutic potential of recombinant Emc10 delivered by osmotic minipumps after MI in heart failure–prone FVB/N mice. Results: Emc10 signaled through small GTPases, p21-activated kinase, and the p38 mitogen-activated protein kinase (MAPK)–MAPK-activated protein kinase 2 (MK2) pathway to promote actin polymerization and endothelial cell migration. Confirming the importance of these signaling events in the context of acute MI, Emc10 stimulated endothelial cell outgrowth from infarcted mouse heart explants via p38 MAPK-MK2. Emc10 protein abundance was increased in the infarcted region of the left ventricle and in the circulation of wild-type mice after MI. Emc10 expression was also increased in left ventricular tissue samples from patients with acute MI. Bone marrow–derived monocytes and macrophages were the predominant sources of Emc10 in the infarcted murine heart. Emc10 KO mice showed no cardiovascular phenotype at baseline. After MI, however, capillarization of the infarct border zone was impaired in KO mice, and the animals developed larger infarct scars and more pronounced left ventricular remodeling compared with wild-type mice. Transplanting KO mice with wild-type bone marrow cells rescued the angiogenic defect and ameliorated left ventricular remodeling. Treating FVB/N mice with recombinant Emc10 enhanced infarct border-zone capillarization and exerted a sustained beneficial effect on left ventricular remodeling. Conclusions: We have identified Emc10 as a previously unknown angiogenic growth factor that is produced by bone marrow–derived monocytes and macrophages as part of an endogenous adaptive response that can be enhanced therapeutically to repair the heart after MI.
Indoxyl Sulfate Downregulates Renal Expression of Klotho through Production of ROS and Activation of Nuclear Factor-ĸB

Background/Aim: Klotho, an anti-aging gene, is expressed in the kidneys, and its renal expression is decreased in chronic kidney disease (CKD). The present study aimed to examine whether renal expression of Klotho is regulated by indoxyl sulfate, a uremic toxin, using rat kidneys and human proximal tubular cells (HK-2). Methods: The effect of indoxyl sulfate on renal expression of Klotho was examined using (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH+IS). The effects of indoxyl sulfate, inhibitors of nuclear factor-ĸB (NF-ĸB) and an antioxidant on the expression of Klotho in HK-2 cells were examined. Results: DH+IS and DN+IS rats showed decreased expression of Klotho mRNA in the kidneys as compared with DH and DN rats, respectively. Indoxyl sulfate suppressed the expression of Klotho mRNA and protein in HK-2 cells, whereas an antioxidant, N-acetylcysteine, and NF-ĸB inhibitors, pyrrolidine dithiocarbamate and isohelenin, alleviated these effects. Conclusions: Indoxyl sulfate downregulates Klotho expression in kidneys through production of reactive oxygen species and activation of NF-ĸB in proximal tubular cells. Indoxyl sulfate may be involved in reduced renal expression of Klotho in CKD.
Fate of Enteropathogens Inoculated onto Chopped Ham 1.

A survey of 36 pairs of new (< 10 days from manufacture) and old (pull date) samples of vacuum-packaged, sliced chopped ham were analyzed for total microbial load, specific pathogen count and pH. Results indicated a wide range of microbial loads, absence of pathogenic bacteria at the levels tested, and presumptive group D streptococci generally < 100/g except for 22% of new samples and 44% of old samples, which had presumptive group D counts > 100 but < 106/g. The survey results also indicated marked differences in pH between products from different manufacturers. Product from two manufacturers was selected for inoculation studies. Chopped ham sandwiches were inoculated with a mixture of five enteropathogenic bacteria and held at 30, 21 and 4 C for up to 24 h. Bacillus cereus , Escherichia coli , Salmonella typhimurium and Staphylococcus aureus , but not Clostridium petfringens , grew in low competition product under the severely abusive holding temperature of 30 C in < 24 h, at 21 C in > 24 h. Product from one manufacturer inhibited the gram negative pathogens. Results indicated that chopped ham in sandwiches required almost unrealistic mishandling to develop a food poisoning potential by enterotoxigenic bacteria, but infective pathogens survived well.