Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.

BACKGROUND AIMS: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. APPROACH RESULTS: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. CONCLUSIONS: Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

Decoding of Attentional State Using High-Frequency Local Field Potential Is As Accurate As Using Spikes.

Local field potentials (LFPs) in visual cortex are reliably modulated when the subject's focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spikes. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spikes was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found in rhesus monkeys that LFPs during neutral cueing were also intermediate between cued and uncued conditions. For a single electrode, attention was more discriminable using high frequency (>30 Hz) LFP power than spikes, which is expected because LFP represents a population signal and therefore is expected to be less noisy than spikes. However, previous studies have shown that when multiple electrodes are used, spikes can outperform LFPs. Surprisingly, in our study, spikes did not outperform LFPs when discriminability was computed using multiple electrodes, even though the LFP activity was highly correlated across electrodes compared with spikes. These results constrain the spatial scale over which attention operates and highlight the usefulness of LFPs in studying attention.

It Is Complex: Predicting Gastroschisis Outcomes Using Prenatal Imaging.

BACKGROUND: Gastroschisis occurs in one of 2000 births with survival rates partially contingent on intestinal complications and time to establishing feeding. Enhancements in prenatal imaging have given better insight into postnatal outcomes. The goal of this study was to examine the gastroschisis patient population at a single children's hospital in the modern era and to use prenatal ultrasound (US) to develop new prenatal prognostic indicators. METHODS: We performed a retrospective review of gastroschisis patients at a quaternary-care referral children's hospital from 2010 through 2018. We recorded demographics, prenatal data and imaging, early postnatal data, operative data, and patient outcomes. We compared patients within our cohort born with complex gastroschisis (bowel atresia/perforation) to uncomplicated gastroschisis patients. Second trimester and third trimester prenatal US were evaluated for changes in amniotic fluid level, amount of external bowel, bowel dilatation, and bowel wall edema to identify prognostic indicators of the status of the bowel at birth. For categorical variables, chi-square tests were used to assess for significance. Univariate and multivariable analyses were used to assess significance between categorical and continuous variables using medians and interquartile ranges or means. RESULTS: A total of 134 patients were included in the study: complex (n = 24), uncomplicated (n = 110). Compared with uncomplicated gastroschisis, complex patients required longer median days to feeding initiation (44 versus 10; P < 0.001), full feeding (80 versus 23; P < 0.001), length of stay (83 versus 33; P < 0.001), and total parenteral nutrition at discharge (P = 0.004). Full US data were available on 81% of patients, and partial data were identified on 19%. Prenatal US analysis showed significantly more complex patients had polyhydramnios on third trimester US (23.5%-4.3%; P = 0.018). US analysis showed these additional factors to be most associated with complex gastroschisis: large amount of external bowel on third trimester US, increase in bowel edema on third trimester US, and increase in external bowel dilation on third trimester US. Multivariable logistic regression analyses revealed amniotic fluid on third trimester US to be the most significant predictor of complex gastroschisis (P = 0.01). Polyhydramnios in combination with two-thirds of the other US factors had both sensitivity and positive predictive value for predicting complex gastroschisis of 75%. Patients with two or less of these positive US factors had high specificity (96.8%) and negative predictive value (87.5%), suggesting uncomplicated disease. There were no differences in perioperative or long-term complications in the complex group when compared with the group with uncomplicated gastroschisis. CONCLUSIONS: Polyhydramnios on third trimester prenatal US on babies with gastroschisis can predict complex gastroschisis at birth, whereas the absence of markers on prenatal US can suggest uncomplicated disease. Complex gastroschisis is associated with increased time to feeds and length of stay.

Time Series Forecasting of Univariate Agrometeorological Data: A Comparative Performance Evaluation via One-Step and Multi-Step Ahead Forecasting Strategies.

High-frequency monitoring of agrometeorological parameters is quintessential in the domain of Precision Agriculture (PA), where timeliness of collected observations and the ability to generate ahead-of-time predictions can substantially impact the crop yield. In this context, state-of-the-art internet-of-things (IoT)-based sensing platforms are often employed to generate, pre-process and assimilate real-time data from heterogeneous sensors and streaming data sources. Simultaneously, Time-Series Forecasting Algorithms (TSFAs) are responsible for generating reliable forecasts with a pre-defined forecast horizon and confidence. These TSFAs often rely on modelling the correlation between endogenous variables, the impact of exogenous variables on latent form and structural properties of data such as autocorrelation, periodicity, trend, pattern, and causality to approximate the model parameters. Traditionally, TSFAs such as the Holt-Winters (HW) and Autoregressive family of models (ARIMA) apply a linear and parametric approach towards model approximation, whilst models like Support Vector Regression (SVRs) and Neural Networks (NNs) adhere to a non-linear, non-parametric approach for modelling the historical data. Recently, Deep-Learning-based TSFAs such as Recurrent Neural Networks (RNNs), and Long-Short-Term-Memory (LSTMS) have gained popularity due to their capability to model long sequences of highly non-linear and stochastic data effectively. However, the evolution of TSFAs for predicting agrometeorological parameters pivots around one-step-ahead forecasting, which often overestimates the performance metrics defined for validating forecast capabilities of potential TSFAs. Hence, this paper attempts to evaluate and compare the performance of different machine learning (ML) and deep learning (DL) based TSFAs under one-step and multi-step-ahead forecast scenarios, thereby estimating the generalization capabilities of TSFA models over unseen data. The data used in this study are collected from an Automatic Weather Station (AWS), sampled at an interval of 15 min, and range over one month. Temperature (T) and Humidity (H) observations from the AWS are further converted into univariate, supervised time-series diurnal data profiles. Finally, walk-forward validation is used to evaluate recursive one-step-ahead forecasts until the desired prediction horizon is achieved. The results show that the Seasonal Auto-Regressive Integrated Moving Average (SARIMA) and SVR models outperform their DL-based counterparts in one-step and multi-step ahead settings with a fixed forecast horizon. This work aims to present a baseline comparison between different TSFAs to assist the process of model selection and facilitate rapid ahead-of-time forecasting for end-user applications.

Pancreatic stellate cell-potentiated insulin secretion from Min6 cells is independent of interleukin 6-mediated pathway.

Pancreatic stellate cells (PSCs) secrete various factors, which can influence the ß-cell function. The identification of stellate cell infiltration into the islets in pancreatic diseases suggests possible existence of cross-talk between these cells. To elucidate the influence of PSCs on ß-cell function, mouse PSCs were cocultured with Min6 cells using the Transwell inserts. Glucose-stimulated insulin secretion from Min6 cells in response to PSCs was quantified by enzyme-linked immunosorbent assay and insulin gene expression was measured by quantitative polymerase chain reaction. Upon cytometric identification of IL6 in PSC culture supernatants, Min6 cells were cultured with IL6 to assess its influence on the insulin secretion and gene expression. PLC-IP3 pathway inhibitors were added in the cocultures, to determine the influence of PSC-secreted IL6 on Glucose-stimulated insulin secretion from Min6 cells. Increased insulin secretion with a concomitant decrease in total insulin content was noticed in PSC-cocultured Min6 cells. Although increased GSIS was noted from IL6-treated Min6 cells, no change in the total insulin content was noted. Coculture of Min6 cells with PSCs or their exposure to IL6 did not alter either the expression of ß-cell-specific genes or that of miRNA-375. PSC-cocultured Min6 cells, in the presence of PLC-IP3 pathway inhibitors (U73122, Neomycin, and Xestospongin C), did not revoke the observed increase in GSIS. In conclusion, the obtained results indicate that augmented insulin secretion from Min6 cells in response to PSC secretions is independent of IL6-mediated PLC-IP3 pathway.

Is There a Correlation Between Airway Volume and Maximum Constriction Area Location in Different Dentofacial Deformities?

PURPOSE: The purpose of the present study was to correlate the airway volume and maximum constriction area (MCA) with the type of dentofacial deformity in patients who required orthognathic surgery. MATERIALS AND METHODS: The present retrospective cohort study included orthognathic surgery patients selected from the private practice of one of us. The selected cases were stratified into 5 different groups according to the clinical and cephalometric diagnosis of their dentofacial deformity. The preoperative airway volume and anatomic location of the MCA were calculated using the airway tool of the Dolphin Imaging software module (Dolphin Imaging and Management Solutions, Chatsworth, CA) and correlated with the diagnosed dentofacial deformity. Differences in the pretreatment airway volumes and MCA location were compared among the deformities. RESULTS: The MCA location was more often the nasopharynx for maxillary deficiency and the oropharynx for mandibular deficiency deformities. The nasopharynx volume was significantly smaller statistically (P < .005) for maxillary deficiency plus mandibular excess compared with mandibular deficiency. The hypopharynx volume was significantly smaller statistically (P < .005) for vertical maxillary excess plus mandibular deficiency than for both maxillary deficiency and maxillary deficiency plus mandibular excess. No statistically significant difference was found among the different deformity groups in relation to the mean airway volume (P > .005). CONCLUSIONS: The location of the airway MCA seems to have a strong correlation with the horizontal position of the maxilla and mandible. The MCA in maxillary deficiencies (isolated or combined) was in the nasopharynx, and the MCA in mandibular deficiencies (isolated or combined) was in the oropharynx. Clinicians should consider these anatomic findings when planning the location and magnitude of orthognathic surgery movements to optimize the outcomes.

A comparison of vaginal versus buccal misoprostol for cervical ripening in women for labor induction at term (the IMPROVE trial): a triple-masked randomized controlled trial.

BACKGROUND: Cervical ripening is commonly needed for labor induction. Finding an optimal route of misoprostol dosing for efficacy, safety, and patient satisfaction is important and not well studied for the buccal route. OBJECTIVE: To compare the efficacy and safety of vaginal and buccal misoprostol for women undergoing labor induction at term. STUDY DESIGN: The IMPROVE trial was an institutional review board-approved, triple-masked, placebo-controlled randomized noninferiority trial for women undergoing labor induction at term with a Bishop score ≤6. Enrolled women received 25 mcg (first dose), then 50 mcg (subsequent doses) of misoprostol by assigned route (vaginal or buccal) and a matching placebo tablet by the opposite route. The primary outcomes were time to delivery and the rate of cesarean delivery performed urgently for fetal nonreassurance. A sample size of 300 was planned to test the noninferiority hypothesis. RESULTS: The trial enrolled 319 women, with 300 available for analysis, 152 in the vaginal misoprostol group and 148 in the buccal. Groups had similar baseline characteristics. We were unable to demonstrate noninferiority. The time to vaginal delivery was lower for the vaginal misoprostol group (median [95% confidence interval] in hours: vaginal: 20.1 [18.2, 22.8] vs buccal: 28.1 [24.1, 31.4], log-rank test P = .006, Pnoninferiority = .663). The rate of cesarean deliveries for nonreassuring fetal status was 3.3% for the vaginal misoprostol group and 9.5% for the buccal misoprostol group (P = .033). The rate of vaginal delivery in <24 hours was higher in the vaginal group (58.6% vs 39.2%, P = .001). CONCLUSION: We were unable to demonstrate noninferiority. In leading to a higher rate of vaginal deliveries, more rapid vaginal delivery, and fewer cesareans for fetal issues, vaginal misoprostol may be superior to buccal misoprostol for cervical ripening at term.

Twin anemia-polycythemia sequence and routine monitoring practices amongst maternal-fetal medicine specialists in the United States: an initial investigation.

Background The purpose of this initial investigation was to begin to understand the routine twin anemia-polycythemia sequence (TAPS) monitoring practices of maternal-fetal medicine specialists (MFM specialists) in the United States in the absence of a formal guideline. Methods This study used an anonymous, online survey of 90 MFM specialists who were practicing in the United States. A $5 gift card to an online store was used to incentivize participants. Descriptive statistics were calculated. Results All MFM specialists reported at least some familiarity (100.00%) with TAPS. Most participants (92.94%) were familiar with methods for monitoring patients for TAPS and nearly all (97.50%) responded that they use 'Doppler MCA-PSV' to make a prenatal TAPS diagnosis. Nearly two-thirds of MFM specialists surveyed (65.06%) reported performing regular TAPS monitoring for patients with monochorionic-diamniotic (MCDA) pregnancies. Conclusion Despite no formal guidelines, the majority of American MFM specialists surveyed are using routine TAPS screening in their management of MCDA twin pregnancies, suggesting that the MFM specialists included in this study consider it a valuable diagnostic tool. Future research should further explore this possible trend toward routine TAPS monitoring amongst MFM specialists in the United States, as well as the potential value of routine TAPS monitoring in MCDA pregnancy.

Studies on Photocleavage, DNA Binding, Cytotoxicity, and Docking Studies of Ruthenium(II) Mixed Ligand Complexes.

This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.

Efficient pH dependent drug delivery to target cancer cells by gold nanoparticles capped with carboxymethyl chitosan.

Doxorubicin (DOX) was immobilized on gold nanoparticles (AuNPs) capped with carboxymethyl chitosan (CMC) for effective delivery to cancer cells. The carboxylic group of carboxymethyl chitosan interacts with the amino group of the doxorubicin (DOX) forming stable, non-covalent interactions on the surface of AuNPs. The carboxylic group ionizes at acidic pH, thereby releasing the drug effectively at acidic pH suitable to target cancer cells. The DOX loaded gold nanoparticles were effectively absorbed by cervical cancer cells compared to free DOX and their uptake was further increased at acidic conditions induced by nigericin, an ionophore that causes intracellular acidification. These results suggest that DOX loaded AuNPs with pH-triggered drug releasing properties is a novel nanotheraputic approach to overcome drug resistance in cancer.

Dissociation of attentional state and behavioral outcome using local field potentials.

Behavioral outcome (i.e., whether a target is detected or missed) depends on attentional state and potentially other factors related to decision-making, which could in turn modulate the power and phase of neuronal oscillations. Here we investigated whether attentional state (i.e., whether attention is inside or outside the receptive fields of neurons) and behavioral outcome are distinguishable using the power and phase of local field potential (LFP) recorded from electrode arrays in area V4 of two male rhesus monkeys performing an attentional task under different cuing conditions. Since attention also strongly modulates pairwise measures such as spike count correlation and phase consistency which are typically measured across trials, we developed novel methods to obtain single-trial estimates of these measures. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase, although single-trial gamma phase consistency provided good attentional discriminability. Our results provide a clear dissociation between the neural mechanisms that regulate attentional focus and those that govern behavioral outcome.

Dissociation of attentional state and behavioral outcome using local field potentials.

Successful behavior depends on attentional state and other factors related to decision-making, which may modulate neuronal activity differently. Here, we investigated whether attentional state and behavioral outcome (i.e., whether a target is detected or missed) are distinguishable using the power and phase of local field potential (LFP) recorded bilaterally from area V4 of two male rhesus monkeys performing a cued visual attention task. To link each trial's outcome to pairwise measures of attention that are typically averaged across trials, we used several methods to obtain single-trial estimates of spike count correlation and phase consistency. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase in attentional/behavioral discriminability, although single-trial gamma phase consistency provided reasonably high attentional discriminability. Our results suggest a dissociation between the neuronal mechanisms that regulate attentional focus and behavioral outcome.Significance statement Targets appearing at the attended location are detected more accurately than those at the unattended location. However, attention may not be the only factor regulating the behavioral outcome. We investigated whether the effects of behavioral outcome and attentional state could be differentiated using the local field potentials recorded from macaque visual area V4. We used various methods to obtain single-trial estimates of trial-wise measures like correlations and phase consistency. Remarkably, we found that while attentional location was most effectively discerned through gamma and high-gamma power, behavioral outcomes were better distinguished by alpha power and steady-state visually evoked potentials. These results suggest distinct mechanisms underlying attention and behavioral outcome, thus emphasizing the roles of additional factors in modulating the behavioral outcome.

Impact of toothbrush head configuration and dentifrice abrasivity on non-carious cervical lesions in-vitro.

OBJECTIVE: To investigate the effect of toothbrush head configuration and dentifrice slurry abrasivity on the development of simulated non-carious cervical lesions (NCCLs) in vitro. METHODS: Extracted premolars were randomly allocated into 15 groups (n = 16) generated by the association between toothbrush head configuration (flat-trimmed, rippled, cross-angled/multilevel/rubbers added, cross-angled/multilevel/flex head, feathered) and dentifrice slurry abrasivity (low/medium/high). Teeth were mounted on acrylic blocks and had their roots partially covered with acrylic resin, leaving 2-mm root surfaces exposed. Toothbrushing was performed for 35,000 and 65,000 double-strokes. Specimens were analyzed using non-contact profilometry for dental volume loss (mm3) and lesion morphology. Data was analyzed using ANOVA with pairwise comparisons and Kruskal-Wallis tests. RESULTS: The two-way interaction between toothbrush head configuration and slurry abrasivity was significant (p = 0.02). At 35,000 strokes, the flat-trimmed and cross-angled/multilevel/rubbers added toothbrushes caused the highest loss, when associated to the high-abrasive slurry (p<0.05); whereas cross-angled/multilevel/flex head showed the least loss, when associated to the low-abrasive (p<0.05). At 65,000, more dental loss was observed for all toothbrushes when associated to the high-abrasive slurry, with flat-trimmed causing the highest loss (p < 0.05). Lower dental loss rates were observed for cross-angled/multilevel/flex head associated to the low-abrasive slurry when compared to the other toothbrushes (p < 0.05), except to feathered (p = 0.14) and rippled (p = 0.08). Flat lesions (mean internal angle ± standard-deviation: 146.2°± 16.8) were mainly associated with low-abrasive slurry, while wedge-shaped lesions (85.8°± 18.8) were more frequent with medium- and high-abrasive slurries. CONCLUSION: The development, progression and morphology of simulated NCCLs were modulated by both toothbrush head configuration and dentifrice abrasivity. CLINICAL SIGNIFICANCE: Dental professionals should consider both the type of toothbrush and dentifrice abrasivity in the management plan of patients at risk of developing NCCLs.

Mechanistic insights into the early life stage microbiota of silver pompano (Trachinotus blochii).

Introduction: Deep investigations of host-associated microbiota can illuminate microbe-based solutions to improve production in an unprecedented manner. The poor larval survival represents the critical bottleneck in sustainable marine aquaculture practices. However, little is known about the microbiota profiles and their governing eco-evolutionary processes of the early life stages of marine teleost, impeding the development of suitable beneficial microbial management strategies. The study provides first-hand mechanistic insights into microbiota and its governing eco-evolutionary processes in early life stages of a tropical marine teleost model, Trachinotus blochii. Methods: The microbiota profiles and their dynamics from the first day of hatching till the end of metamorphosis and that of fingerling's gut during the routine hatchery production were studied using 16S rRNA amplicon-based high-throughput sequencing. Further, the relative contributions of various external factors (rearing water, live feed, microalgae, and formulated feed) to the microbiota profiles at different ontogenies was also analyzed. Results: A less diverse but abundant core microbial community (~58% and 54% in the whole microbiota and gut microbiota, respectively) was observed throughout the early life stages, supporting 'core microbiota' hypothesis. Surprisingly, there were two well-differentiated clusters in the whole microbiota profiles, ≤10 DPH (days post-hatching) and > 10 DPH samples. The levels of microbial taxonomic signatures of stress indicated increased stress in the early stages, a possible explanation for increased mortality during early life stages. Further, the results suggested an adaptive mechanism for establishing beneficial strains along the ontogenetic progression. Moreover, the highly transient microbiota in the early life stages became stable along the ontogenetic progression, hypothesizing that the earlier life stages will be the best window to influence the microbiota. The egg microbiota also crucially affected the microbial community. Noteworthily, both water and the feed microbiota significantly contributed to the early microbiota, with the feed microbiota having a more significant contribution to fish microbiota. The results illustrated that rotifer enrichment would be the optimal medium for the early larval microbiota manipulations. Conclusion: The present study highlighted the crucial foundations for the microbial ecology of T. blochii during early life stages with implications to develop suitable beneficial microbial management strategies for sustainable mariculture production.

[An abdominal wall bulging: consider a neurological cause]. / Een uitstulping van de buik.

A patient with a swelling of the abdominal wall is a regular occurrence in general practice and hospital. The diagnosis can often be made with a thorough history and physical examination. An abdominal wall hernia is characterized by an increase in swelling on standing physical examination and Valsalva maneuver, which is often reducible, and a hernia defect is palpable. If no interruption of the abdominal wall is palpable and there is hypoesthesia, there may be an abdominal wall paresis because of thoracic paramedian hernia nuclei pulposi (HNP). Where an abdominal wall hernia is treated surgically in case of symptoms, this is conservatively treated with an HNP.

Modulation of Nuclear Receptor 4A1 Expression Improves Insulin Secretion in a Mouse Model of Chronic Pancreatitis.

OBJECTIVES: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to lack of understanding on factor(s) triggering insulin secretory defects. Therefore, we aimed to delineate the molecular mechanism of ß-cell dysfunction in CP. MATERIALS AND METHODS: Transcriptomic analysis was conducted to identify endocrine-specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis of NR4A1-overexpressed (OE) MIN6 cells on NovaSeq6000 identified aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure, whereas downstream effect was examined by Fura2 AM-based fluorimetric and imaging studies. Mice with CP were treated with IFN-γ-neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion. RESULTS: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 µg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 µg/mg protein per minute, P = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ-neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold ( P = 0.03), showed improved insulin secretion (4.4 ± 0.2-fold, P = 0.01), and associated with increased Ca 2+ levels (2.39 ± 0.06-fold, P = 0.009). CONCLUSIONS: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.

Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Surgical resection is regarded as the only curative option for resectable oesophageal cancer, but pulmonary complications occurring in more than half of patients after open oesophagectomy are a great concern. We assessed whether minimally invasive oesophagectomy reduces morbidity compared with open oesophagectomy. METHODS: We did a multicentre, open-label, randomised controlled trial at five study centres in three countries between June 1, 2009, and March 31, 2011. Patients aged 18-75 years with resectable cancer of the oesophagus or gastro-oesophageal junction were randomly assigned via a computer-generated randomisation sequence to receive either open transthoracic or minimally invasive transthoracic oesophagectomy. Randomisation was stratified by centre. Patients, and investigators undertaking interventions, assessing outcomes, and analysing data, were not masked to group assignment. The primary outcome was pulmonary infection within the first 2 weeks after surgery and during the whole stay in hospital. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. FINDINGS: We randomly assigned 56 patients to the open oesophagectomy group and 59 to the minimally invasive oesophagectomy group. 16 (29%) patients in the open oesophagectomy group had pulmonary infection in the first 2 weeks compared with five (9%) in the minimally invasive group (relative risk [RR] 0·30, 95% CI 0·12-0·76; p=0·005). 19 (34%) patients in the open oesophagectomy group had pulmonary infection in-hospital compared with seven (12%) in the minimally invasive group (0·35, 0·16-0·78; p=0·005). For in-hospital mortality, one patient in the open oesophagectomy group died from anastomotic leakage and two in the minimally invasive group from aspiration and mediastinitis after anastomotic leakage. INTERPRETATION: These findings provide evidence for the short-term benefits of minimally invasive oesophagectomy for patients with resectable oesophageal cancer. FUNDING: Digestive Surgery Foundation of the Unit of Digestive Surgery of the VU University Medical Centre.

Lessons from neurolathyrism: a disease of the past & the future of Lathyrus sativus (Khesari dal).

Neurolathyrism is past history in India since Lathyrus sativus (khesari dal) is no longer used as a staple. A consensus has evolved that khesari dal is harmless as part of a normal diet. L-ODAP (ß-N-oxalyl-l-α-diamino propionic acid) the neurotoxic amino acid, from this pulse, is detoxified in humans but not in animals but still no laboratory animal is susceptible to it under acceptable feeding regimens. L-ODAP is an activator of protein kinase C and consequential crucial downstream effects such as stabilization of hypoxia inducible factor-1 (HIF-1) could be extremely conducive to humans under a variety of situations. ODAP is gradually finding a place in several patents for this reason. Homoarginine the second amino acid from L. sativus can be a better substrate for endogenous generation of nitric oxide, a crucial signaling molecule associated with the cardiovasculature and control of hypertension. These features could make L. sativus a prized commodity as a functional food for the general cardiovasculature and overcome hypoxic events and is set to change the entire perception of this pulse and neurolathyrism.

Formulation of herbal based hair colour from Phyllanthus reticulatus.

Synthetic oxidative hair dyes available in the market contain a combination of peroxide and ammonia. In addition, people who use synthetic dyes are at risk for skin burns, irritation to the eye and also lead to cancer. Hence, herbal-based hair dyes are safe to use. In the traditional system of medicine, different parts of Phyllanthus reticulatus were used for curing various ailments. The aqueous leaf extract showed the presence of phytochemical rich components. Herbal hair dye has been formulated by using P. reticulatus with various natural ingredients in the ratio of 5:1:1:1:1. The herbal hair dye was evaluated for its various parameters. It showed potent in vitro antimicrobial activity against various microorganisms and antioxidant activity. In the formulated product, the natural ingredients are known for their non-toxic properties and there are no added chemicals and preservatives. It offers a natural alternative, that can be used irrespective of any side effects.

Impact of Enhanced Recovery After Surgery pathway for cesarean delivery on postoperative pain.

BACKGROUND: Enhanced Recovery After Surgery pathways provide evidence-based recommendations to optimize perioperative care. OBJECTIVE: This study aimed to holistically investigate the effect of implementing an Enhanced Recovery After Surgery pathway for all cesarean deliveries on postoperative pain experience. STUDY DESIGN: This was a prepost study comparing subjective and objective measures of postoperative pain before and after the implementation of an Enhanced Recovery After Surgery pathway for cesarean delivery. The Enhanced Recovery After Surgery pathway was developed by a multidisciplinary team and included preoperative, intraoperative, and postoperative components, with emphasis on preoperative preparation, hemodynamic optimization, early mobilization, and multimodal analgesia. All individuals undergoing cesarean delivery, whether scheduled, urgent, or emergent, were included. Demographic, delivery, and inpatient pain management data were obtained through medical record review. Of note, 2 weeks after discharge, patients were surveyed about their delivery experience, analgesic usage, and complications. The primary outcome was inpatient opioid use. RESULTS: The study included 128 individuals, 56 in the preimplementation cohort and 72 in the Enhanced Recovery After Surgery cohort. Baseline characteristics between the 2 groups were similar. The survey response rate was 73% (94/128). Opioid use in the first 48 hours postoperatively was significantly lower in the Enhanced Recovery After Surgery group than the preimplementation group (9.4 vs 21.4 morphine milligram equivalents 0-24 hours after delivery [P<.001]; 14.1 vs 25.4 morphine milligram equivalents 24-48 hours after delivery [P<.001]) with no increase in either average or maximum postoperative pain scores. Individuals in the Enhanced Recovery After Surgery group used fewer opioid pills after discharge (10 vs 20; P<.001). Patient satisfaction and complication rates did not change after the implementation of an Enhanced Recovery After Surgery pathway. CONCLUSION: The implementation of an Enhanced Recovery After Surgery pathway for all cesarean deliveries decreased both inpatient and outpatient postpartum opioid use without increasing pain scores or decreasing patient satisfaction.