Christensenpham8999

Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.

Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.

Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls ized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89546-559.

COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed.

To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19.

Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. GW3965 Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28days.

A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3±13.3; 69% men), and 104 steroids alone (age 54.06±13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10days. Patient's death was associated with hypertension (RR=3.5) and diabetes (RR=2.3). Mortality was 22 and 35% for CsA and control groups (P=0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P=0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P=0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P=0.0005) for CsA treatment in moderate to severe patients, and HR=1.95 (1.35-2.83, 95%CI, P=0.0003) for all patients.

CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Wild-type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.

To study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.

A total of 250 patients, aged 50-89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0-4. All patients with grade 3-4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT-proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.

Amyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3-4; all had fibril type A amentum flavum may be an early manifestation of systemic ATTR disease.

Whether the time from intravenous thrombolysis (IVT) to endovascular treatment (EVT) in patients with acute ischemic stroke has an effect on the functional outcome is unknown.

The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, multicenter, observational study that perform EVT in France. Data were analyzed from patients treated by IVT and EVT between October 2013 and December 2018 in 6 comprehensive stroke centers. In the primary analysis, we assessed the association of time from IVT administration to start of EVT with functional outcome (measured with the modified Rankin Scale [mRS]), by means of ordinal logistic regression. Secondary end points included angiographic and safety outcomes.

We analyzed 1,986 patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent IVT and EVT. An increased IVT to start of EVT time was associated with a worse functional outcome at 90 days (mRS = 0-2, adjusted odds ratio [OR] per 30 minutes increase in time = 0.91, 95% confidence interval [CI] = 0.86-0.96; mRS = 0-1, adjusted OR per 30 minutes increase in time = 0.89, 95% CI = 0.84-0.94), a lower chance of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b to 3 reperfusion (adjusted OR per 30 minutes increase in time = 0.93, 95% CI = 0.87-0.98), and an increased probability of symptomatic intracerebral hemorrhage (adjusted OR per 30 minutes increase in time = 1.09, 95% CI = 0.99-1.18).

These findings provide a basis for further studies to determine if the functional outcome of patients with stroke can be greatly improved by optimizing IVT to EVT times. ANN NEUROL 2021;89511-519.

These findings provide a basis for further studies to determine if the functional outcome of patients with stroke can be greatly improved by optimizing IVT to EVT times. ANN NEUROL 2021;89511-519.

Epidermolysis bullosa (EB) comprises a heterogeneous group of skin fragility disorders, classified in four major types based on skin cleavage level, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, and in more than 30 subtypes defined by the combination of laboratory and clinical data, including disease course.

Our aims were to address whether, in the age of genomics, electron microscopy (TEM) has still a role in diagnosing EB, and whether the genotype per se may be sufficient to sub-classify EB.

A thoroughly characterized single-centre EB case series was retrospectively evaluated to compare the power of TEM with immunofluorescence mapping (IFM) in establishing the EB type, and the ability of TEM, IFM and genetics to predict selected EB subtypes, i.e. severe dominant EBS (DEBS), severe JEB, severe recessive DEB (RDEB) and DEB self-improving, using genetic and final diagnosis, respectively, as gold standard.

The series consisted of 87 patients, including 44 newborns, with a nd complementary tools in the vast majority of EB cases.This study aimed to characterize an interactive and clinically applicable population pharmacokinetic-pharmacodynamic-pharmacodynamic (PK-PD-PD) model describing follicle-stimulating hormone (FSH)-inhibin B-oocyte relationship in women undergoing assisted reproduction with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The study was a prospective analysis of 25 healthy women undergoing IVF/ICSI using gonadotropin-releasing hormone (GnRH) antagonist protocol. The developed model used the FSH PK profiles to predict both inhibin B (first PD end point) and oocyte retrieval (second PD end point). The modeling framework involved 2 stages. First, the FSH-inhibin B model was developed by the simultaneous approach and applied to estimate the individual area under the inhibin B-time curve (AUCInhb ) at the end of stimulation cycles that varied in length in each woman. In the second stage, the estimated AUCInhb was introduced as a link covariate to predict oocyte retrieval and response category. The population FSH-inhibin B model was described as 3 submodels; PK (exogenous), endogenous, and inhibin B PD models. Weight was the main determinant of both endogenous and exogenous FSH exposures. GnRH antagonist therapy was a significant time-varying covariate when tested against the endogenous FSH production rate (P less then .001). AUCInhb could be predicted with women's age and weight. Log-transformed AUCInhb was a significant covariate when tested against oocyte retrieval (P less then .001). Simulations concluded a target AUCInhb of 144-303 ng·h/mL for optimal ovarian response. The GnRH antagonist was better started on day 7 of the cycle. Covariate-based dosing suggests lower recombinant follicle-stimulating hormone requirements in a thin and/or young population. An interactive web application "GonadGuide" was developed to facilitate the application in clinical practice.

Approximately 42-95% of working channels have been reported to show the presence of residual fluid despite endoscope reprocessing. The aim of this study was to design two novel protocols for cleaning residual simethicone and demonstrate its efficiency by evaluating the residual fluid and cleanliness in the working channels of patient-ready duodenoscopes.

The designed protocol for cleaning residual simethicone was implemented in manual cleaning and/or high-level disinfection (HLD). The residual fluid inside the working channels was estimated by visual inspection. Adenosine triphosphate (ATP) values were evaluated to determine cleanliness after manual cleaning.

Manual cleaning with novel simethicone cleaning protocol demonstrated a significant decrease in fluid droplets (14.6±29.9 vs 0±0, P<0.001) and ATP values (157±196 relative light units [RLUs] vs 52±41 RLUs, P=0.031). HLD with simethicone cleaning protocol, using either enzymatic detergent with effective for cleaning simethicone or cleaning time set in the automatic endoscope reprocessor program for 8min, demonstrated significant decrease in the number of fluid droplets. Follow-up after the implementation of the simethicone cleaning protocol showed a significant decrease in fluid droplets (37.4±41.0 vs 2.1±5.5, P=0.003) and ATP values (271±268 RLUs vs 82±136 RLUs, P=0.021).

Simethicone cleaning protocol is advantageous for significantly decreasing fluid droplets and ATP values within endoscope working channels. After manual cleaning with the simethicone cleaning protocol, in particular, no retained fluid droplet was observed in patient-ready duodenoscopes.

Simethicone cleaning protocol is advantageous for significantly decreasing fluid droplets and ATP values within endoscope working channels. After manual cleaning with the simethicone cleaning protocol, in particular, no retained fluid droplet was observed in patient-ready duodenoscopes.The plant-associated microbial community (microbiome) has an important role in plant-plant communications. Plants decipher their complex habitat situations by sensing the environmental stimuli and molecular patterns and associated with microbes, herbivores and dangers. Perception of these cues generates inter/intracellular signals that induce modifications of plant metabolism and physiology. Signals can also be transferred between plants via different mechanisms, which we classify as wired- and wireless communications. Wired communications involve direct signal transfers between plants mediated by mycorrhizal hyphae and parasitic plant stems. Wireless communications involve plant volatile emissions and root exudates elicited by microbes/insects, which enable inter-plant signalling without physical contact. These producer-plant signals induce microbiome adaptation in receiver plants via facilitative or competitive mechanisms. Receiver plants eavesdrop to anticipate responses to improve fitness against stresses.