Rapid discrimination of four Salmonella enterica serovars: A performance comparison between benchtop and handheld Raman spectrometers.

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.

Estrogen increases the expression of BKCa and impairs the contraction of colon smooth muscle via upregulation of sphingosine kinase 1.

Estrogen (E2) may impair the contraction of colonic smooth muscle (SM) leading to constipation. Large conductance Ca2+ -activated K+ channels (BKCa ) are widely expressed in the smooth muscle cells (SMCs) contributing to hyperpolarization and relaxation of SMCs. Sphingosine kinase 1 (SphK1) is known to influence the expression of BKCa . We aimed to elucidate the potential underlying molecular mechanism of BKCa and SphK1 that may influence E2-induced colonic dysmotility. In ovariectomized rats, SM contraction and expression of BKCa , SphK1, sphingosine-1-phosphate receptor (S1PR) were analyzed after the treatment with vehicle, BSA-E2, E2, and E2 receptor antagonist. The role of BKCa , SphK1, and S1PR in E2-induced SM dysmotility was investigated in rat colonic SMCs. The effect of SphK1 on SM contraction as well as on the expression of BKCa and S1PR was analyzed in SphK1 knock-out mutant mice and wild-type (WT) mice treated with or without E2. The E2-treated group exhibited a weak contraction of colonic SM and a delayed colonic transit. The treatment with E2 significantly upregulated the expression of BKCa , SphK1, S1PR1, and S1PR2, but not S1PR3, in colon SM and SMCs. Inhibition of BKCa , SphK1, S1PR1, and S1PR2 expression attenuated the effect of E2 on Ca2+ mobilization in rat colon SMCs. WT mice treated with E2 showed impaired gastrointestinal motility and enhanced expression of BKCa , S1PR1, and S1PR2 compared with those without E2 treatment. Conversely, in SphK1 knock-out mice treated with E2, these effects were partially reversed. E2 increased the release of S1P which in turn could have activated S1PR1 and S1PR2. Loss of SphK1 attenuated the effect of E2 on the upregulation of S1PR1 and S1PR2 expression. These findings indicated that E2 impaired the contraction of colon SM through activation of BKCa via the upregulation of SphK1 and the release of S1P. In the E2-induced BKCa upregulation, S1PR1 and S1PR2 might also be involved. These results may provide further insights into a therapeutic target and optional treatment approaches for patients with constipation.

Retro-Aza-Piancatelli Rearrangement Triggered Cascade Reaction of Methyl Furylacrylates with Anilines to Access Cyclopenta[b]pyrrolidinones.

A novel aza-Piancatelli rearrangement triggered cascade reaction has been developed by utilizing methyl furylacrylates as a new type of functionalized furanoxonium ion precursor, permitting rapid and flexible construction of diverse cyclopenta[b]pyrrolidinone derivatives. The unprecedented and highly efficient bicyclic γ-lactam product formation is originated from an unusual retro-aza-Piancatelli rearrangement of the major cis-fused multifunctionalized cyclopentenone to the minor trans-fused one followed by a lactamization reaction.

Association Between Gastroesophageal Flap Valve and Endoscopically Diagnosed Gastroesophageal Reflux Disease According to Lyon Consensus: A Meta-analysis of Asian Studies.

BACKGROUND: Lyon Consensus altered the previous understanding of endoscopic gastroesophageal reflux disease (GERD) and pointed out that only high-grade reflux esophagitis (RE) [Los Angeles (LA) grades C or D], Barrett's esophagus or peptic stricturing were considered confirmatory evidence for GERD but low-grade RE (LA grades A or B) was regarded as suspected GERD. We aimed to summarize the possible relationship between gastroesophageal flap valve (GEFV) and endoscopic GERD according to Lyon Consensus using meta-analysis of studies done in Asia. MATERIALS AND METHODS: Comprehensive searches of PubMed, WOS, Embase, SinoMed, and CNKI databases were completed to identify eligible studies published before September 22, 2019. A total of 237 articles have been reviewed and 2 reviewers independently evaluated the eligibility for inclusion, extracted, and analyzed the statistical data. The pooled risk ratios (RRs) with 95% confidence intervals (CI) were measured for the association. Random-effects models were used when observing significant heterogeneity. RESULTS: A total of 15 studies were included and we found that abnormal GEFV (III and IV) could be associated with RE and the correlation become stronger as the grade increases (RE-A vs. controls-RR: 2.186, 95% CI: 1.560-3.064, P<0.001; RE-B vs. RE-A-RR: 1.268, 95% CI: 1.128-1.425, P<0.001; RE-C vs. RE-B-RR: 1.181, 95% CI: 1.000-1.395, P=0.049; RE-D vs. RE-C-RR: 1.471, 95% CI: 1.151-1.879, P=0.002). Both suspected GERD (RR: 2.400, 95% CI: 1.761-3.271, P<0.001) and endoscopic GERD (RR: 1.388, 95% CI: 1.127-1.711, P=0.002) were related to abnormal GEFV. CONCLUSION: Abnormal GEFV could provide useful information for reflux conditions, but it could not distinguish confirmatory GERD from low-grade RE under the upper endoscopy.

Clinical value of positive BET and pelvic floor dyssynergia in Chinese patients with functional defecation disorder.

BACKGROUND: Functional defecation disorder (FDD) is a common subtype of functional constipation (FC). Balloon expulsion test (BET) and high resolution anorectal manometry (HR-ARM) are significant tools but their results are not always consistent. AIMS: To investigate the characteristics of patients with positive BET and pelvic floor dyssynergia (PFD) and explore the value of both positive results in FDD diagnosis. METHODS: We retrospectively diagnosed FC subtypes and enrolled FDD patients based on Rome-IV criteria. They underwent HR-ARM, BET and CTT tests. Then they were classified to two groups and further stratified by FDD subtypes. Validated questionnaires were applied to investigate patients' constipation, anxiety/depression and quality of life. RESULTS: 335 FDD patients were finally enrolled. They were classified into two groups according to whether BET and PFD were both positive (consistent or not). 84.48% showed consistent results. These patients had significantly higher anal residual pressure, lower anal relaxation rate, manometric defecation index (MDI) and a more negative rectoanal pressure gradient (RAPG) (Ps < .05). The specific distribution of FDD phenotypes in two groups showed significant difference (p = .021). Males suffered a more negative RAPG (p < .001) and age was correlated with anal relaxation rate (p < .001). A subset (177 individuals) was investigated with validated questionnaires. Scores for Defecation Symptoms, Physical Discomfort and GAD-7 score were significantly high in Consistent Group (Ps < .05). GAD-7 score was associated with Defecation Symptoms (p < .001) while anal residual pressure, GAD-7 and Defecation Symptoms score were linked to Physical Discomfort (Ps < .05). The diagnostic specificity and PPV for FDD rose significantly with positive BET and PFD. CONCLUSION: FDD patients with positive BET and PFD suffered from severe defecation symptoms, anxiety and impaired QOL. Positive BET and PFD could be an ideal tool for screening FDD.

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds.

A visible light-mediated heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile has been established using K-modified carbon nitride (CN-K) as a recyclable semiconductor photocatalyst. This protocol, employing readily accessible alkyl N-hydroxyphthalimide (NHPI) ester as a radical initiator, allows the efficient construction of a broad array of structural diverse nitrogenous heterocyclic compounds including indolines, oxindoles, isoquinolinones, and isoquinolinediones.

Quantitative Proteomics Reveals the Mechanism of Silver Nanoparticles against Multidrug-Resistant Pseudomonas aeruginosa Biofilms.

The decline of clinically effective antibiotics has made it necessary to develop more effective antimicrobial agents, especially for refractory biofilm-related infections. Silver nanoparticles (AgNPs) are a new type of antimicrobial agent that can eradicate biofilms and reduce bacterial resistance, but its anti-biofilm mechanism has not been elucidated. In this study, we investigated the molecular mechanism of AgNPs against multidrug-resistant Pseudomonas aeruginosa by means of anti-biofilm tests, scanning electron microscopy (SEM), and tandem mass tag (TMT)-labeled quantitative proteomics. The results of anti-biofilm tests demonstrated that AgNPs inhibited the formation of P. aeruginosa biofilm and disrupted its preformed biofilm. SEM showed that when exposed to AgNPs, the structure of the P. aeruginosa biofilm was destroyed, along with significant reduction of its biomass. TMT-labeled quantitative proteomic analysis revealed that AgNPs could defeat the P. aeruginosa biofilm in multiple ways by inhibiting its adhesion and motility, stimulating strong oxidative stress response, destroying iron homeostasis, blocking aerobic and anaerobic respiration, and affecting quorum sensing systems. Our findings offer a new insight into clarifying the mechanism of AgNPs against biofilms, thus providing a theoretical basis for its clinical application.

Spirulina platensis alleviates chronic inflammation with modulation of gut microbiota and intestinal permeability in rats fed a high-fat diet.

Recent research suggested that taking a high-fat diet (HFD) may lead to a gut microbiota imbalance and colon tissue damage. This would lead to increased intestinal permeability and consequent constant circulation of low-grade inflammatory cytokines. Spirulina platensis can protect against HFD-induced metabolic inflammation and can stimulate the growth of beneficial bacteria in in vitro stool cultures. However, it is unknown whether this beneficial effect acts on intestinal tissues. In this study, rats were fed a high-fat diet fed with 3% S platensis for 14 weeks. We analysed endotoxin, the composition of the microbiota, inflammation and gut permeability. We found that S platensis decreased the bodyweight and visceral fat pads weight of the HFD-fed rats. In addition, it lowered the levels of lipopolysaccharide and pro-inflammatory cytokines in serum. Our results showed that S platensis could largely reduce the relative amount of Proteobacteria and the Firmicutes/Bacteroidetes ratio in faecal samples from HFD-fed rats. S platensis significantly reduced intestinal inflammation, as shown by decreased expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4), NF-κB (p65) and inflammatory cytokines. S platensis also ameliorated the increased permeability and decreased expression of tight junction proteins in the intestinal mucosa, such as ZO-1, Occludin and Claudin-1. Therefore, in HFD-induced gut dysbiosis rats, S platensis benefits health by inhibiting chronic inflammation and gut dysbiosis, and modulating gut permeability.

Clinical Characteristics of Different Primary Constipation Subtypes in a Chinese Population.

GOAL: To investigate the clinical characteristics of different primary constipation subtypes, including symptom clusters, psychological problems, quality of life (QOL), and to explore the role of constipation symptoms and the mental state in the QOL of constipation subtypes. BACKGROUND: Patients with chronic constipation (CC) may be unsatisfied with their therapy and suffer recurrent symptoms. Different constipation subtypes require different treatments; therefore, it is important to identify the features of different constipation subtypes. STUDY: CC patients (n=206) visiting our gastroenterology clinic were studied. CC subtypes were diagnosed using the Rome-IV criteria. We used validated questionnaires to investigate the symptom severity, mental state, and QOL of patients. QOL was assessed with the Patient Assessment of Constipation Quality of Life (PAC-QOL) and SF-36 questionnaire. Results of symptom, mental and QOL scores are expressed as means with 95% confidence interval. RESULTS: Three groups of CC patients differed in their constipation scoring system and the Patient Assessment of Constipation Symptoms (PAC-SYM) total scores, and both were significantly higher in the functional defecation disorder (FDD) group compared with that in the normal transit constipation (NTC) group. FDD patients tended to have more severe "abdominal symptoms," "rectal symptoms" than NTC group. No significant difference in General Anxiety Disorder 7-item or Patient Health Questionnaire-9 results was found among the 3 groups. Significantly more patients with FDD suffered more "physical discomfort" and had poorer QOL in the "physical function" dimension of SF-36. FDD and NTC patients mainly showed associations between CC-related QOL and constipation severity, while slow transit constipation patients' QOL was significantly associated with anxiety and depression. CONCLUSION: Patients with FDD suffer more severe constipation symptoms and have a lower QOL than patients in other CC subgroups. FDD and NTC patients' QOL is mainly linked to constipation symptoms, while that of slow transit constipation is mainly related to mental states such as anxiety and depression.

Association of ADAM17 Expression Levels in Patients with Interstitial Lung Disease.

A disintegrin and metalloproteinases (ADAMs) are believed to be involved in the pathogenesis of many fibrosis-related diseases. However, little is known regarding the significance of ADAM17 as a biomarker for interstitial lung disease (ILD). In this study, by using the RT-PCR, western blotting and ELISA, we detected the expression level of ADAM17 in peripheral blood mononuclear cells and serum from idiopathic pulmonary fibrosis (IPF) patients, connective tissue disease associated ILD (CTD-ILD) patients and healthy controls, and correlations between clinical and laboratory parameters were also analyzed. We found that IPF patients and CTD-ILD patients showed higher levels of ADAM17 than healthy controls. Moreover, ADAM17 in IPF patients with acute exacerbation (AE-IPF) was significantly higher than that in stable IPF (S-IPF) patients. Expression of ADAM17 was positively correlated with disease duration and CRP but negatively correlated with diffusing capacity of carbon monoxide (DLCO) and total lung capacity (TLC). Among the CTD-ILD patients, SSc-ILD patients had the highest serum levels of ADAM17 compared with the RA-ILD, SS-ILD and IIM-ILD groups and ADAM17 expression levels were correlated with image grading. In conclusion, this study showed that ADAM17 is highly expressed in ILD patients and is associated with disease activity and severity. Additionally, ADAM17 expression is not only related to the primary CTDs, but also to image grading. ADAM17 may serve as a new biomarker for ILD.

Reference intervals for thyroid-stimulating hormone and thyroid hormones using the access TSH 3rd IS method in China.

BACKGROUND: To calculate the reference intervals for thyroid-stimulating hormone (TSH) and thyroid hormones using the Access TSH 3rd IS method and evaluate the differences between age and genders in Chinese populations. METHODS: This study collected 349 serum samples of healthy subjects were from Shengli Oilfield Central Hospital in China. Subjects who tested positive for thyroid peroxidase antibody or thyroglobulin antibody were excluded. Accordingly, 313 subjects were included for establishing reference intervals for the thyroid hormones. The serum concentrations of TSH, total and free thyroxine (TT4 and FT4), and total and free triiodothyronine (TT3 and FT3) were measured using the Access TSH 3rd IS method. The 2.5th and 97.5th percentiles or mean with standard deviation were calculated as the reference interval as appropriate. RESULTS: The reference intervals for TSH, FT4, FT3, TT4, and TT3 calculated in present study were 0.61-4.16 mIU/L, 0.67-1.11 ng/dL, 2.63-4.33 pg/mL, 5.56-11.33 µg/dL, and 0.72-1.32 ng/mL, respectively. The FT3, TT4, and TT3 levels in males were significantly higher than in females (P < .05), while TSH levels in males were significantly lower than in females (P < .05). The levels of FT3 in subjects with the age of less than 30 years were significantly higher than other groups (P < .05). CONCLUSION: The present study provided a valid basis for the reference intervals for TSH, FT4, FT3, TT4, and TT3 in Chinese populations. In addition, this present study indicated that age and gender should be considered in diagnostic evaluation of thyroid diseases.

A triple-channel sensing array for protein discrimination based on multi-photoresponsive g-C3N4.

Graphitic carbon nitride (g-C3N4) as an outstanding photoresponsive nanomaterial has been widely used in biosensing. Other than the conventional single channel sensing mode, a triple-channel sensing array was developed for high discrimination of proteins based on the photoresponsive g-C3N4. Besides the photoluminescence and Rayleigh light scattering features of g-C3N4, we exploit the new photosensitive colorimetry of g-C3N4 as the third channel optical input. The triple-channel optical behavior of g-C3N4 can be synchronously changed after interaction with the protein, resulting in the distinct response patterns related to each specific protein. Such a triple-channel sensing array is demonstrated for highly discriminative and precise identification of nine proteins (hemoglobin, trypsin, lysozyme, cytochrome c, horseradish peroxidase, transferrin, human serum albumin, pepsin, and myoglobin) at 1 µM concentration levels with 100% accuracy. It also can discriminate proteins being present at different concentration and protein mixtures with different content ratios. The practicability of this sensor array is validated by high accuracy identification of nine proteins in human urine samples. This indicates that the array has a great potential in terms of analyzing biological fluids. Graphic abstract .

Enhanced Photochemical Vapor Generation for the Determination of Bismuth by Inductively Coupled Plasma Mass Spectrometry.

An enhanced photochemical vapor generation (PVG) sample introduction procedure is developed for the determination of trace Bi with inductively coupled plasma mass spectrometry (ICP MS) by the addition of iron. Gas chromatography mass spectrometry (GC-MS) reveals that (CH3)3Bi is the major component of the volatile Bi species formed in the presence of 20% (v/v) acetic acid, 5% (v/v) formic acid, and 60 µg mL-1 Fe3+ under UV irradiation. The addition of Fe3+ not only largely increases the PVG efficiency of Bi3+ but also accelerates the reaction kinetics of photochemical reduction of Bi3+. The analytical sensitivity was enhanced 30-fold using PVG for sample introduction compared to that for direct solution nebulization detection by ICP MS detection. Furthermore, the proposed method shows much better tolerance of interference from Cu2+ and Ni2+ than that from conventional hydride generation (HG). Under the optimized conditions, a detection limit of 0.3 ng L-1 was obtained for Bi by ICP MS determination. The relative standard deviation (RSD) was 2.5% for seven replicate measurements of 0.5 ng mL-1 Bi3+ standard solution. The proposed method has been successfully applied for the determination of Bi in environmental samples, including water samples, and certified reference material of soil (GSS-1) and sediments (GSD-5a and GSD-10) with satisfying results.

LncRNA MALAT1 is up-regulated in diabetic gastroparesis and involved in high-glucose-induced cellular processes in human gastric smooth muscle cells.

Recent years, widespread long non-coding RNAs (lncRNAs) were identified and known as regulator of gene expression. Diabetic gastroparesis (DGP) is one of the most common chronic complications of diabetes mellitus. There was no research reported the role of lncRNAs in DGP. In this study, we firstly established a rat model of DGP by STZ injection. Then, we detected the expression of MALAT1 and found that expression of MALAT1 was up-regulated in rat model of DGP, comparing to the control group (P < .01). Furthermore, we revealed that MALAT1 expression was increased in the samples from diabetic patients with DGP symptoms, in comparison with the control. In addition, we demonstrated that the inhibition of MALAT1 increased the expression of α-SMA and SM myosin heavy chains, reduced the cell viability, inhibited the potential of cell migration and induced cell apoptosis in human gastric smooth muscle cells (SMCs). Ultimately, we found that the regulation of MALAT1 expression modulated the function of high-glucose stimulation in human gastric SMCs. Therefore, our study firstly indicated that MALAT1 was up-regulated in DGP and played an important role in the pathogenesis of DGP.

Advanced Glycation End Products Impair Ca2+ Mobilization and Sensitization in Colonic Smooth Muscle Cells via the CAMP/PKA Pathway.

BACKGROUND/AIMS: Excessive production of advanced glycation end products (AGEs) has been implicated in diabetes-related complications. This study aimed to investigate the mechanism by which AGEs potentially contribute to diabetes-associated colonic dysmotility. METHODS: Control and streptozotocin (STZ)-induced diabetic groups were treated with aminoguanidine (AG). The colonic transit time and contractility of circular muscle strips was measured. ELISA, immunohistochemistry and western blotting were used to measure Nε-carboxymethyl-lysine (CML) levels. Primary cultured colonic smooth muscle cells (SMCs) were used in complementary in vitro studies. RESULTS: Diabetic rats showed prolonged colonic transit time, weak contractility of colonic smooth muscle strips, and elevated levels of AGEs in the serum and colon tissues. cAMP levels, protein kinase-A (PKA) activities, and inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) phosphorylation were increased in the colon muscle tissues of diabetic rats, whereas RhoA/Rho kinase activity and myosin phosphatase target subunit 1 (MYPT1) phosphorylation were reduced. The inhibition of the production of AGEs (AG treatment) reduced these effects. In cultured colonic SMCs, AGE-BSA treatment increased IP3R3 phosphorylation and reduced intracellular Ca2+ concentration, myosin light chain (MLC) phosphorylation, RhoA/Rho kinase activity, and MYPT1 phosphorylation. The PKA inhibitor H-89 and anti-RAGE antibody inhibited the AGE-BSA-induced impairment of Ca2+ signaling and cAMP/PKA activation. CONCLUSION: AGEs/RAGE participate in diabetes-associated colonic dysmotility by interfering with Ca2+ signaling in colonic SMCs through targeting IP3R3-mediated Ca2+ mobilization and RhoA/Rho kinase-mediated Ca2+ sensitization via the cAMP/PKA pathway.

Rate matrix estimation from site frequency data.

A procedure is described for estimating evolutionary rate matrices from observed site frequency data. The procedure assumes (1) that the data are obtained from a constant size population evolving according to a stationary Wright-Fisher or decoupled Moran model; (2) that the data consist of a multiple alignment of a moderate number of sequenced genomes drawn randomly from the population; and (3) that within the genome a large number of independent, neutral sites evolving with a common mutation rate matrix can be identified. No restrictions are imposed on the scaled rate matrix other than that the off-diagonal elements are positive, their sum is ≪1, and that the rows of the matrix sum to zero. In particular the rate matrix is not assumed to be reversible. The key to the method is an approximate stationary solution to the diffusion limit, forward Kolmogorov equation for neutral evolution in the limit of low mutation rates.

Plasma miR-122 as a potential diagnostic and prognostic indicator in human glioma.

Gliomas are the most common and aggressive brain tumors, and a poor prognosis is correlated with its World Health Organization (WHO) grade. MicroRNAs (miRNAs) may serve as diagnostic and prognostic biomarkers in gliomas. In the present study, we collected plasma samples from patients with gliomas to evaluate the expression of miR-122 and analyzed the role of miR-122 in the diagnosis and prognosis of gliomas. We found that the expression of miR-122 in the plasma of patients with gliomas was significantly down-regulated compared to that in healthy individuals. In addition, the expression of miR-122, which was significantly correlated with WHO grade, decreased along with the development of gliomas. A receiver operating characteristic curve analysis showed high sensitivity and specificity of miR-122 for diagnosing gliomas (sensitivity 91.9%; specificity 81.1%; area under the curve 0.939). Finally, we found that lower expression of miR-122 was correlated with poor prognosis, and miR-122 was an independent prognostic parameter indicating poor prognosis for gliomas. In conclusion, our results showed that plasma miR-122 expression might act as a diagnostic and prognostic biomarker for gliomas.

An approximate stationary solution for multi-allele neutral diffusion with low mutation rates.

We address the problem of determining the stationary distribution of the multi-allelic, neutral-evolution Wright-Fisher model in the diffusion limit. A full solution to this problem for an arbitrary K×K mutation rate matrix involves solving for the stationary solution of a forward Kolmogorov equation over a (K-1)-dimensional simplex, and remains intractable. In most practical situations mutations rates are slow on the scale of the diffusion limit and the solution is heavily concentrated on the corners and edges of the simplex. In this paper we present a practical approximate solution for slow mutation rates in the form of a set of line densities along the edges of the simplex. The method of solution relies on parameterising the general non-reversible rate matrix as the sum of a reversible part and a set of (K-1)(K-2)/2 independent terms corresponding to fluxes of probability along closed paths around faces of the simplex. The solution is potentially a first step in estimating non-reversible evolutionary rate matrices from observed allele frequency spectra.

High-resolution Anorectal Manometry in Parkinson Disease With Defecation Disorder: A Comparison With Functional Defecation Disorder.

GOAL: To investigate the characteristics of high-resolution anorectal manometry (HR-ARM) in Parkinson disease (PD) patients with defecation disorder (DD) compared with patients with functional defecation disorder (FDD). BACKGROUND: DD is a common gastrointestinal symptom in PD. HR-ARM is a relatively new and reliable method for detecting DD. STUDY: A cohort of PD patients with DD was matched with FDD patients. Defecatory symptoms were investigated by questionnaire. Anorectal motility and sensation were evaluated by HR-ARM. Differences in defecatory symptoms, sensorimotor parameters, and DD type were analyzed. Defecatory symptoms and manometric variables obtained in early-stage PD were compared with advanced stage, and relationships between manometric parameters and evacuatory symptoms explored. RESULTS: Straining and sensation of blockage was experienced significantly more in PD than FDD, and stool consistency more severely affected. Maximum squeeze and intrarectal pressure during defecation in PD was lower than in FDD. Anal resting and residual pressures, duration of sustained squeeze, threshold volumes for first sensation, urgency, and maximum discomfort were similar between groups. PD patients presented predominantly with inadequate propulsive forces, whereas FDD patients showed dyssynergic defecation. Defecatory symptoms and manometric parameters did not differ between stages of PD. CONCLUSIONS: PD patients with DD experienced more straining and sensation of blockage than FDD patients, possibly related to inadequate anorectal motility and paradoxical anal contraction of pelvic floor. Impaired squeeze response and inadequate propulsive forces are specific to anorectal function of PD patients with DD, compared with FDD, with abnormalities unchanged between early and advanced PD.

Catalytic Asymmetric Piancatelli Rearrangement: Brønsted Acid Catalyzed 4π†Electrocyclization for the Synthesis of Multisubstituted Cyclopentenones.

The first catalytic asymmetric Piancatelli reaction is reported. Catalyzed by a chiral Brønsted acid, the rearrangement of a wide range of furylcarbinols with a series of aniline derivatives provides valuable aminocyclopentenones in high yields as well as excellent enantioselectivities and diastereoselectivities. The high value of the aza-Piancatelli rearrangement was demonstrated by the synthesis of a cyclopentane-based hNK1 antagonist analogue.