The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We ...investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria.
We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed.
At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 0.73) than in the control (9.77 0.41, P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2).
The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
So far, solar energy has been viewed as only a minor contributor in the energy mixture of the US due to cost and intermittency constraints. However, recent drastic cost reductions in the production ...of photovoltaics (PV) pave the way for enabling this technology to become cost competitive with fossil fuel energy generation. We show that with the right incentives, cost competitiveness with grid prices in the US (e.g., 6–10
US¢/kWh) can be attained by 2020. The intermittency problem is solved by integrating PV with compressed air energy storage (CAES) and by extending the thermal storage capability in concentrated solar power (CSP). We used hourly load data for the entire US and 45-year solar irradiation data from the southwest region of the US, to simulate the CAES storage requirements, under worst weather conditions. Based on expected improvements of established, commercially available PV, CSP, and CAES technologies, we show that solar energy has the technical, geographical, and economic potential to supply 69% of the total electricity needs and 35% of the total (electricity and fuel) energy needs of the US by 2050. When we extend our scenario to 2100, solar energy supplies over 90%, and together with other renewables, 100% of the total US energy demand with a corresponding 92% reduction in energy-related carbon dioxide emissions compared to the 2005 levels.
Lithium users are offered routine renal monitoring but few studies have quantified the risk to renal health. The aim of this study was to assess the association between use of lithium carbonate and ...incidence of renal failure in patients with bipolar disorder.
This was a retrospective cohort study using the General Practice Research Database (GPRD) and a nested validation study of lithium exposure and renal failure. A cohort of 6360 participants aged over 18 years had a first recorded diagnosis of bipolar disorder between January 1, 1990 and December 31, 2007. Data were examined from electronic primary care records from 418 general practices across the UK. The primary outcome was the hazard ratio for renal failure in participants exposed to lithium carbonate as compared with non-users of lithium, adjusting for age, gender, co-morbidities, and poly-pharmacy.
Ever use of lithium was associated with a hazard ratio for renal failure of 2.5 (95% confidence interval 1.6 to 4.0) adjusted for known renal risk factors. Absolute risk was age dependent, with patients of 50 years or older at particular risk of renal failure: Number Needed to Harm (NNH) was 44 (21 to 150).
Lithium is associated with an increased risk of renal failure, particularly among the older age group. The absolute risk of renal failure associated with lithium use remains small.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accurate optical characterisation and removal of small adenomas (<10 mm) at colonoscopy would allow hyperplastic polyps to be left in situ and surveillance intervals to be determined without the need ...for histopathology. Although accurate in specialist practice the performance of narrow band imaging (NBI), colonoscopy in routine clinical practice is poorly understood.
NBI-assisted optical diagnosis was compared with reference standard histopathological findings in a prospective, blinded study, which recruited adults undergoing routine colonoscopy in six general hospitals in the UK. Participating colonoscopists (N=28) were trained using the NBI International Colorectal Endoscopic (NICE) classification (relating to colour, vessel structure and surface pattern). By comparing the optical and histological findings in patients with only small polyps, test sensitivity was determined at the patient level using two thresholds: presence of adenoma and need for surveillance. Accuracy of identifying adenomatous polyps <10 mm was compared at the polyp level using hierarchical models, allowing determinants of accuracy to be explored.
Of 1688 patients recruited, 722 (42.8%) had polyps <10 mm with 567 (78.5%) having only polyps <10 mm. Test sensitivity (presence of adenoma, N=499 patients) by NBI optical diagnosis was 83.4% (95% CI 79.6% to 86.9%), significantly less than the 95% sensitivity (p<0.001) this study was powered to detect. Test sensitivity (need for surveillance) was 73.0% (95% CI 66.5% to 79.9%). Analysed at the polyp level, test sensitivity (presence of adenoma, N=1620 polyps) was 76.1% (95% CI 72.8% to 79.1%). In fully adjusted analyses, test sensitivity was 99.4% (95% CI 98.2% to 99.8%) if two or more NICE adenoma characteristics were identified. Neither colonoscopist expertise, confidence in diagnosis nor use of high definition colonoscopy independently improved test accuracy.
This large multicentre study demonstrates that NBI optical diagnosis cannot currently be recommended for application in routine clinical practice. Further work is required to evaluate whether variation in test accuracy is related to polyp characteristics or colonoscopist training.
The study was registered with clinicaltrials.gov (NCT01603927).
The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape ...after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade.
We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT.
Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.
This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.
Abstract Purpose Cognitive load, specifically extraneous load (EL) reflective of distractions, may provide evidence of a lack of focus, potentially making additional work unsafe. The assessment of ...trainees performing inpatient consultations provides a helpful model for examining this question. The goal of this study was to provide useful information to clinical and educational leaders to optimize inpatient consultation services and rotations and mitigate potential patient safety risk. Method In 2019, using the Consult Cognitive Load instrument, the authors obtained EL data from inpatient consultations performed by internal medicine fellows and psychiatry residents across 5 University of California hospitals. In 2023, the authors constructed a Wright map to compare the participants’ EL data with the number of prior initial consultations performed during the shift. Results Of 326 trainees contacted, 139 (43%) completed the EL survey items. The Wright map shows that trainees were estimated to agree that interruptions were already distracting at the first consultation of the shift. After 4 consultations, trainees were estimated to strongly agree that interruptions were distracting and to agree that emotions, extraneous information, and technology were distracting. Conclusions The authors propose a quantitative, empirically driven, mean safety limit of 4 new inpatient consultations per shift for trainees to avoid cognitive overload, thereby potentially supporting patient safety. Clinical and educational leaders can adjust this limit to fit the unique needs of their practice setting. A similar approach using cognitive load and item response theory could be used to conduct patient safety research in other domains.
Flea beetles (Coleoptera: Chrysomelidae) of the genus Phyllotreta are major pests of cole crops, canola, and related crops in the mustard family (Brassicaceae). Adults may damage seedlings or larger ...crop plants, impairing crop growth, rendering crops unmarketable, or killing seedlings outright. The two major North American crucifer pest species, Phyllotreta striolata (F.) and Phyllotreta cruciferae (Goeze), have male-produced pheromones attractive to both female and male adults. We tested the racemic synthetic pheromones, himachaladiene and hydroxyhimachalanone, as well as the host-plant-produced allyl isothiocyanate, alone and in combination, with experimental trapping in Maryland, Virginia, and North Dakota, using clear and yellow sticky traps and the ground-based ‘rocket’ trap (modified from boll weevil trap). Phyllotreta striolata was consistently attracted to the hydroxyketone, and captures were often enhanced by allyl isothiocyanate (AITC), but its response to pheromones, AITC, and trap color were variable from state to state. Phyllotreta cruciferae was strongly attracted to AITC, but its response to pheromone components varied by state, and this species was found rarely at the Maryland site. Phyllotreta bipustulata (F.) was attracted to the diene component, a new finding for this species. Several other genera of flea beetles were captured, some showing response to the semiochemicals and/or color. Results will be helpful in monitoring and possibly population suppression; however, further research is necessary to develop more efficient syntheses, optimal lure loadings, combinations, and controlled release methods.
Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom ...comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care.
The tumor microenvironment is crucial in the initiation and progression of cancers. The interplay between cancer cells and the surrounding stroma shapes the tumor biology and dictates the response to ...cancer therapies. Consequently, a better understanding of the interactions between cancer cells and different components of the tumor microenvironment will drive progress in developing novel, effective, treatment strategies. Co-cultures can be used to study various aspects of these interactions in detail. This includes studies of paracrine relationships between cancer cells and stromal cells such as fibroblasts, endothelial cells, and immune cells, as well as the influence of physical and mechanical interactions with the extracellular matrix of the tumor microenvironment. The development of novel co-culture models to study the tumor microenvironment has progressed rapidly over recent years. Many of these models have already been shown to be powerful tools for further understanding of the pathophysiological role of the stroma and provide mechanistic insights into tumor-stromal interactions. Here we give a structured overview of different co-culture models that have been established to study tumor-stromal interactions and what we have learnt from these models. We also introduce a set of guidelines for generating and reporting co-culture experiments to facilitate experimental robustness and reproducibility.
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