Summary Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is ...affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.
Introduction
Peroral endoscopic myotomy (POEM) is a novel intervention for the treatment of achalasia, which combines the advantages of endoscopic access and myotomy. The purpose of this study was to ...perform a systematic review of the literature to evaluate the efficacy and safety of POEM.
Methods
The systematic review was conducted following the PRISMA guidelines. Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE (R) including in-process and non-indexed citations were searched for POEM studies using the keywords: esophageal achalasia, POEM, endoscopy, natural orifice surgery, laparoscopic Heller myotomy (LHM), and related terms. Eckardt score, lower esophageal sphincter (LES) pressure, and reported complications were the main outcomes. Two authors reviewed the search result independently. A third reviewer resolved all disagreements. Data abstraction was pilot-tested and approved by all authors. Data were examined for clinical, methodological, and statistical heterogeneity with the aim of determining whether evidence synthesis using meta- analysis was possible.
Results
The search strategy retrieved 2894 citations. After removing duplicates and applying the exclusion criteria, 54 studies were selected for full-text review of which a total of 19 studies were considered eligible for further analysis. There were 10 retrospective and 9 prospective studies, including 1299 POEM procedures. No randomized control trial (RCT) was identified. Overall, the pre- and post-POEM Eckardt scores and LES pressure were significantly different. The most frequently reported complications were mucosal perforation, subcutaneous emphysema, pneumoperitoneum, pneumothorax, pneumomediastinum, pleural effusion, and pneumonia. The median follow-up was 13 months (range 3–24).
Conclusion
POEM is a safe and effective alternative for the treatment of achalasia. However, only short-term follow-up data compared with LHM are available. RCTs and long-term follow-up studies are needed to establish the efficacy and safety of POEM in the management of patients with achalasia.
This paper describes the operation of the Coherent CAPTAIN-Mills (CCM) detector located at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. CCM is a 10-ton liquid argon ...detector located 20 meters from a high flux neutron/neutrino source and is designed to search for sterile neutrinos (νs’s) and light dark matter (LDM). An engineering run was performed in fall 2019 to study the characteristics of the CCM120 detector by searching for coherent scattering signals consistent with νs’s and LDM resulting from the production and decays of π+ and π0 in the tungsten target. New parameter space in a leptophobic dark matter (DM) model was excluded for DM masses between ~2.0 and 30 MeV. The lessons learned from this run have guided the development and construction of the new CCM200 detector that will begin operations in 2021 and significantly improve on these searches.
The MiniBooNE experiment at Fermilab reports a total excess of 638.0 ± 52.1 (stat .) ± 122.2 (syst.) electronlike events from a data sample corresponding to 18.75 × 10 20 protons-on-target in ...neutrino mode, which is a 46% increase in the data sample with respect to previously published results and 11.27 × 10 20 protons-on-target in antineutrino mode. The overall significance of the excess, 4.8σ, is limited by systematic uncertainties, assumed to be Gaussian, as the statistical significance of the excess is 12.2σ. The additional statistics allow several studies to address questions on the source of the excess. First, we provide two-dimensional plots in visible energy and the cosine of the angle of the outgoing lepton, which can provide valuable input to models for the event excess. Second, we test whether the excess may arise from photons that enter the detector from external events or photons exiting the detector from π 0 decays in two model independent ways. Beam timing information shows that almost all of the excess is in time with neutrinos that interact in the detector. The radius distribution shows that the excess is distributed throughout the volume, while tighter cuts on the fiducial volume increase the significance of the excess. The data likelihood ratio disfavors models that explain the event excess due to entering or exiting photons.
A search for sub-GeV dark matter produced from collisions of the Fermilab 8 GeV Booster protons with a steel beam dump was performed by the MiniBooNE-DM Collaboration using data from 1.86 × 1020 ...protons on target in a dedicated run. The MiniBooNE detector, consisting of 818 tons of mineral oil and located 490 meters downstream of the beam dump, is sensitive to a variety of dark matter initiated scattering reactions. Three dark matter interactions are considered for this analysis: elastic scattering off nucleons, inelastic neutral pion production, and elastic scattering off electrons. Multiple data sets were used to constrain flux and systematic errors, and time-of-flight information was employed to increase sensitivity to higher dark matter masses. No excess from the background predictions was observed, and 90% confidence level limits were set on the vector portal and leptophobic dark matter models. New parameter space is excluded in the vector portal dark matter model with a dark matter mass between 5 and 50 MeV c−2 . The reduced neutrino flux allowed to test if the MiniBooNE neutrino excess scales with the production of neutrinos. No excess of neutrino oscillation events were measured ruling out models that scale solely by number of protons on target independent of beam configuration at 4.6σ.
This study (EGF20009) assessed the efficacy and tolerability of two lapatinib administration schedules as first-line monotherapy in women with ErbB2-amplified locally advanced or metastatic breast ...cancer.
Patients with ErbB2-amplified, locally advanced or metastatic breast cancer previously untreated in the metastatic setting were randomly assigned to one of two lapatinib dose cohorts and received either 1,500 mg once daily or 500 mg twice daily. Clinical response was assessed at weeks 8 and 12 and every 12 weeks thereafter.
A total of 138 patients were treated with lapatinib for a median of 17.6 weeks. The overall response rate (complete response CR plus partial response PR) was 24% in the intent-to-treat population, and 31% of patients derived clinical benefit (CR, PR, or stable disease for >or= 24 weeks). The median time to response was 7.9 weeks, and the progression-free survival rates at 4 and 6 months were 63% and 43%, respectively. The most common lapatinib-related adverse events (AEs) were diarrhea, rash, pruritus, and nausea, and these events were primarily grade 1 or 2. There were no significant differences in clinical activity or the AE profile between the dosing schedules.
Lapatinib demonstrated clinical activity and was well tolerated as first-line therapy in ErbB2-amplified locally advanced or metastatic breast cancer. This study supports further evaluation of lapatinib in first-line and early-stage ErbB2-overexpressing breast cancer.
The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a ...steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01<m_{χ}<0.3 GeV in a vector portal model of dark matter. This is the best limit from a dedicated proton beam dump search in this mass and coupling range and extends below the mass range of direct dark matter searches. These results demonstrate a novel and powerful approach to dark matter searches with beam dump experiments.
Summary Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year ...assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2 , or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov , number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 SD 7·3 vs −1·9% 6·3; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark.
Display omitted
•Effect of various inoculum pretreatment on microbial community dynamics evaluated.•H2 yield was 70% higher for acid and alkali-treated inoculum than untreated.•The combined impact of ...heat and CO2 enriched > 90% spore-forming fermentative bacteria.•Clostridial-type fermentation dominated mesophilic H2 production from food waste.
This study systematically evaluated and compared different inoculum pretreatment methods to quickly select dark fermentative bacteria from anaerobic sludge for the bioconversion of food waste. The hydrogen (H2) production rate was found to be highest for 'heat + CO2′ treated inoculum at 140.75 ± 2.61 mL/L/h compared to control experiments (60.27 ± 2.61 mL/L/h). At the same time, H2 yield was found to be highest for alkali-treated inoculum at 157.25 ± 7.62 mL/g of volatile solids (VS) added compared to control experiments (91.61 ± 1.93 mL/g VS). Analysis of organic acids suggests a Clostridial-type fermentation with acetate (0.52 to 1.60 g/L) and butyrate (1.69 to 2.42 g/L) being the major by-products. The microbial data analysis showed that Firmicutes (63.64–90.39%), Bacteroidota (1.16–21.88%), and Proteobacteria (2.09–9.93%) were dominant at the phylum level, whereas genus-level classification showed Clostridium sensu stricto 1 (6.37–42.63%), Streptococcus (1.87–28.96%), Prevotella (0.57–16.59%), and Enterococcus (0.56–14.51%) dominated under different experimental conditions.
PDF
