Glucagon-like peptide-1(GLP-1) is an incretin hormone secreted primarily from the intestinal L-cells in response to meals. GLP-1 is a key regulator of energy metabolism and food intake. It has been proven that P9 protein from A. muciniphila could increase GLP-1 release and improve glucose homeostasis in HFD-induced mice. To obtain an engineered Lactococcus lactis which produced P9 protein，mature polypeptide chain of P9 was codon-optimized, fused with N-terminal signal peptide Usp45, and expressed in L. lactis NZ9000. Heterologous secretion of P9 by recombinant L. lactis NZP9 were successfully detected by SDS-PAGE and western blotting. Notably, the supernatant of L. lactis NZP9 stimulated GLP-1 production of NCI-H716 cells. The relative expression level of GLP-1 biosynthesis gene GCG and PCSK1 were upregulated by 1.63 and 1.53 folds, respectively. The engineered strain L. lactis NZP9 was more effective than A. muciniphila BAA-835 in stimulating the intestinal L cells to produce GLP-1. To our knowledge, this is the first report on the secretory expression of carboxyl-terminal processing protease P9 from A. muciniphila in L. lactis. Our results suggest that genetically engineered L. lactis which expressed P9 may have therapeutic potential for the treatment of diabetes, obesity and other metabolic disorders.

Pattern recall performance is associated with basic cognitive skills such as working memory (WM) that temporally stores information. The performance may also associate with expertise knowledge that utilizes long-term working memory (LTWM) to retrieve information in long-term memory. However, the role of WM and LTWM in pattern recall tasks are still not clarified. Also, the role of WM and LTWM in task demand and developmental differences of players remain unclear. Further, memory retrieval is associate with vagally-mediated heart rate variability (vmHRV) level. Thus, we examined the effect of WM and LTWM in pattern recall tasks by participants setting two phases separately represent WM and LTWM abilities. We situated varied task demand by situation complexities, taken investigation on the developmental difference by recruited adolescent (U15) and adult (U23) female soccer players. vmHRV was measured during all tasks. The results show the adult group performed better than adolescents in the radial error (RE) of LTWM phase. Moreover, RE of WM phase was predicted by age in low and medium complexity. RE of LTWM phase was predicted by soccer experience in all situation complexities and predicted by vmHRV in medium and high situation complexities. The results indicate that the LTWM phase of pattern recall has a stronger association with soccer experience and validity in distinguishing age groups than the WM phase. Additionally, vmHRV can serve as a score predictor in the LTWM phase, specifically in complex conditions, and plays an important role in pattern recall evaluation among female soccer players.

Objective: Scalp electroencephalogram (EEG) provides a substantial amount of data about information processing in the human brain. In the context of conventional event-related potential (ERP analysis), it is typically assumed that individual trials share similar properties and stem from comparable neural sources, especially when employing group-level methods (including cluster analysis). However, those group analyses can miss important information about the relevant neural process due to a rough estimation of the brain activities of individual subjects while selecting a fixed time window for all the subjects. Method: We designed a multi-set consensus clustering method to examine cognitive processes at the single-trial level. The obtained clusters for the trials were processed via consensus clustering at the individual subject level. The proposed method effectively identified the time window of interest for each individual subject. Results: The proposed method was applied to real EEG data from the active visual oddball task experiment to qualify the P3 component. Our early findings disclosed that the estimated time windows for individual subjects can provide more precise ERP identification than considering a fixed time window for all subjects. Moreover, based on standardized measurement error and established bootstrap for single-trial EEG, our assessments revealed suitable stability for the calculated scores for the identified P3 component. Significance: The new method provides a more realistic and information-driven understanding of the single trials’ contribution towards identifying the ERP of interest in individual ERP potential data.

In this text, we detail the rise in conjunctivitis cases reported in Karachi, Pakistan over the month of August 2023 and assess the potential contributing factors, that include the city’s humid weather, worsening air quality and less-than-expected rainfall in the ongoing Monsoon season. Additionally, the practice of hand hygiene which was implemented rigorously during the COVID-19 pandemic is recognized to have had a positive impact towards control of various infections that spread in a similar fashion as the virus, including conjunctivitis. Since a decrease in compliance with hand hygiene measures in the post-pandemic world, this rise in ‘pink-eye’ cases calls for initiation of ground-level research led by ophthalmologists to obtain a true prevalence of the condition. This review will also serve as the foundation for the initiation of policies dictating hygiene implementation and planning of awareness campaigns for the general public that can serve as effective preventative measures in order to curb the spread of this condition.

Aim: Worldwide climate-driven shifts in the distribution of species is of special concern when it involves habitat-forming species. In the coastal environment, large Laminarian algae – kelps – form key coastal ecosystems that support complex and diverse food webs. Among kelps, Macrocystis pyrifera is the most widely distributed habitat-forming species and provides essential ecosystem services. This study aimed to establish the main drivers of future distributional changes on a global scale and use them to predict both future habitat suitability. Location: Global Methods: Using species distribution models (SDM), we examined the changes in global distribution of M. pyrifera under different emission scenarios with a focus on the Southeastern Pacific shores. To constrain the drivers of our simulations to the most important factors controlling kelp forest distribution across spatial scales, we explored a suite of environmental variables and validated the predictions derived from the SDMs. Results: Minimum sea surface temperature was the single most important variable explaining the global distribution of suitable habitat for M. pyrifera. Under different climate change scenarios, we always observed a decrease of suitable habitat at low latitudes, while an increase was detected in other regions, mostly at high latitudes. Along the Southeast Pacific, we observed an upper range contraction of -17.08°S of latitude for 2100 under the RCP8.5 scenario, implying a loss of habitat suitability throughout the coast of Peru and poleward to -27.83°S in Chile. Along the area of Northern Chile where a complete habitat loss is predicted by our model, natural stands are under heavy exploitation. Main conclusions: The loss of habitat suitability will take place worldwide: significant impacts on marine biodiversity and ecosystem functioning are likely. Furthermore, changes in habitat suitability are a harbinger of massive impacts in the socio-ecological systems of the Southeastern Pacific.

Background: Alcohol Use Disorder (AUD) is a debilitating condition characterized by an individual’s inability to control their alcohol consumption despite adverse consequences. Understanding the neurological aspects of AUD is crucial for effective intervention. This review encompassed a comprehensive search of reputable databases, revealing key insights. Objective: To gain a better understanding of the neurological environment of alcoholism and to shed light on the role of various neurotransmitters in the phenomenon of alcoholism. Methods: A comprehensive search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar, was conducted to identify relevant articles. Results: Neurotransmitters such as dopamine, GABA, serotonin, and glutamate play pivotal roles in alcoholism. A disrupted balance of these neurotransmitters contributes to the development and maintenance of AUD. Genetic factors also heavily influence susceptibility to alcoholism, with ADH1B and ALDH2 genes displaying significant impacts on risk. Conclusion: This review will provide a detailed overview of the neurobiology of alcohol addiction, followed by recent studies published in the genetics of alcohol addiction, molecular mechanism and detailed information on the various acute and chronic neurological manifestations of alcoholism for the Future research.

Arachis pintoi (Fabaceae) is a common relative of the cultivated peanut, and folds its four leaflets up to look like one at night. The adaptive significance of this behavior (foliar nyctinasty) is unknown. To test the hypothesis that leaflet folding alone can deter herbivores, a leaf preference experiment was performed on Chromacris trogon grasshoppers. Small oval cutouts were made from leaves of the grasshopper’s preferred food source, Iochroma arborescens (Solanaceae), and were combined with small pieces of tape and dry grass to construct artificial leaves resembling the day and night form of A. pintoi. In the experiment, groups of three grasshoppers were starved for 24 hours and then placed in petri dishes containing one closed and one open artificial leaf. After 30 six-hour trials, the average herbivory of open leaves was 12.3%, while closed leaves was 5.2% (p = 0.00145), indicating a significant preference for open leaves. This suggests that the folded configuration of A. pintoi leaves can be a defense against herbivory.

Young Onset Ischemic Stroke due to Two Heterozygous Mutations: A Case Report

Successful treatment of a high-risk diabetic foot ulcer by ozone therapy and collagen powder: a case report

• BACKGROUND AND PURPOSE: The stem bark of Stereospermum kunthianum is used extensively in traditional medicine to treat wounds, inflammatory and other pain related health conditions in humans. The aim of this study was to evaluate the wound healing properties of the stem bark extract of S. kunthianum in alloxan-induced diabetic rats. • EXPERIMENTAL APPROACH: The aqueous methanol extract of S. kunthianum was analyzed for phytochemical constituents, acute toxicity tests in rats. The stem bark extract of S. kunthianum was evaluated for wound healing using excision and incision wound healing models in diabetic rats. • KEY RESULTS: The aqueous methanol extract of S. kunthianum revealed that saponins, terpenes, tannins and steroids were present. The acute toxicity study in rats up to 72 hrs. showed no observed toxicity sign up to the dose of 5000 mg/kg .The S. kunthianum stem bark extract (100, 200, 400 mg/kg, p.o) caused significant reduction of wound area. The excision wound contraction (%) in rats treated with S. kunthianum stem bark extract was most effective and had 100% wound contraction. In the incision wound studies, the S. kunthianum stem bark extract showed a progressive rate of wound repair with increasing doses of the extract. • CONCLUSION: The results corroborated the ethno-medicinal claims and have given the scientific justification for the use of S. kunthianum stem bark extract for wound healing. • IMPLICATION: The S. kunthianum stem bark extract therefore has the potential to be developed as a wound healing agent.

A document by Shyamolina Ghosh. Click on the document to view its contents.

Langerhans cells(LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling(YXL) is a representative herbal medicine formula for the treatment of psoriasis in South China. It was confirmed to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod(IMQ)-induced psoriasis-like C57BL/6 mouse model in vivo, and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL to regulate the differentiation, migration, mature and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections. Although there was not any effect on the proportion of total DCs in the skin draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 was significantly inhibited, and its migration to draining lymph nodes and maturation were also inhibited. Further data showed that the number of antigen-carrying LC in the epidermis increased, indicating that YXL could effectively inhibit the antigen presentation of LCs. YXL also significantly inhibited the differentiation of LC in vitro. Further data showed that YXL decreaded the relatve expression of TGFβmRNA and IL-23 mRNA. Thus, YXL allievates psoriasis by regualting differentiation, migration, maturation and antigen presentation via TGFβ/ PU.1/IL-23 signal axis.

Title: Can high flow nasal cannula cause subcutaneous emphysema, pneumomediastinum and pneumothorax? – a case report.Authors: JC Duarte1, S Ferreira1, M Valério1, C Giesta1, T Câmara1Serviço de Pneumologia, Centro Hospitalar do Médio Tejo, PortugalKeywords: high flow; emphysema; pneumothorax.

A document by Miles Weinberger. Click on the document to view its contents.

Falls are a widespread issue affecting people worldwide, regardless of their social status. Falls lead to physical, psychological, and economic consequences. Experts are developing solutions for this problem, given the high frequency of falls among the elderly. This study presents various ML models, which can predict human falls using signals of a wearable sensor located on the wrist or the waist. By extracting the mean, standard deviation, and range, we were able to train and evaluate various machine learning models considering accelerometers and gyroscopes as sensors. The combination of these characteristics and sensors resulted in the RF waist model achieving the most favorable metrics, achieving an accuracy rate of 97.22%.

Objective: This review aimed to identify if heterogeneity exists across outcomes measured and reported in treatment studies targeting perinatal individuals with Generalized Anxiety Disorder (GAD). Design: Scoping review. Setting: Existing literature that evaluates the effectiveness of interventions for GAD during the perinatal period (i.e., pregnant and postpartum). Methods: Studies were eligible if: 1) they were English from the years 2011 to 2021; 2) participants were in the perinatal period with a GAD diagnosis; and 3) the aim of the intervention was to treat GAD during the perinatal period. Three bibliographic databases were searched. Two reviewers independently screened studies for eligibility. Study characteristics and data (e.g., outcomes, OMIs used) were extracted. Main outcome measures: Outcome measures are not required for this type of study design. Results: Of the 4424 records identified, 4 studies were included. The outcomes from the four studies were mapped to one of five core areas in Dodd et al.’s (2018) research outcome framework. A total of 10 distinct outcomes were captured across the 4 studies. Anxiety symptoms, the most common outcome, employed three different OMIs. Notably, the majority of outcomes fell within the physiological/clinical core area, indicating a dearth of patient-centered outcomes in the literature. Conclusions: This review highlights outcome and OMI variations in perinatal GAD studies. To improve synthesis, reproducibility, and comparability among treatment studies, future research in perinatal GAD treatment should adopt standardized outcomes and OMIs. This standardization is essential for informing clinical practice guidelines and policies.

Objective: We aimed to investigate the incidence, prenatal factors, and outcomes of twin-to-twin transfusion (TTTS) with right ventricular outflow tract obstruction (RVOTO). Search Strategy: A systematic search was conducted to identify relevant studies published until February 2023 in English using the databases PubMed, Scopus, and Web of Science Selection Criteria: Studies reporting on pregnancies with TTTS and RVOTO were included. Primary outcome was survival including fetal demise, neonatal death, and 6-months survival. Secondary outcomes were incidence and prenatal risk factors. Data Collection and Analysis. The random-effect model pooled the mean differences or odds ratios (OR) and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. Results: 17 studies encompassing 4332 TTTS pregnancies of which 225 cases had RVOTO were included. Incidence of RVOTO at time of TTTS diagnosis was 6%. 134/197 (68%) had functional pulmonary stenosis (PS) and 62/197 (32%) had functional pulmonary atresia (PA). 27% resolved following laser and 55% persisted after birth. Of those persisting, 27% required cardiac valve procedures. Risk factors were TTTS stage III (53% vs 39% in no-RVOTO), stage IV TTTS (28% in RVOTO vs 12% in no-RVOTO), and DV reversed a-wave (60% in RVOTO vs 19% in no-RVOTO). GA at laser and GA at delivery were comparable between groups. Survival outcomes were also comparable between groups including fetal demise of 26%, neonatal death of 12%, and 6-months survival of 82% in RVOTO group. Findings were similar when subgroup analysis was done for studies including head-to-head analysis. Conclusions: RVOT occurs in about 6% of the recipient twins with TTTS, especially in stages III and IV and those with reversed DV a-wave. The findings from this systematic review support the need of a thorough cardiac assessment of pregnancies complicated by TTTS, both before and after laser in order to maximize perinatal outcome and the importance of early diagnosis of TTTS and timely management. Tweetable abstract: Meta-analysis shows that the incidence of right ventricular outflow tract obstruction among TTTS pregnancies is 6%, among which 68% had functional pulmonary stenosis and 32% had functional pulmonary atresia. Of these pregnancies, 27% resolved after laser therapy and 55% persisted after birth. Of cases persisting after birth, 27% required cardiac valve procedures. Significant risk factors were TTTS stage III-IV and ductus venosus a-wave reversal. Survival outcomes including fetal demise, neonatal death, and 6-months survival were similar compared to those without RVOTO.

Three-dimensional structure information, now available at the proteome scale, may facilitate the detection of remote evolutionary relationships in protein superfamilies. Here, we illustrate this with the identification of a novel family of protein domains related to the ferredoxin-like superfold, by combining (i) transitive sequence similarity searches, (ii) clustering approaches and (iii) the use of AlphaFold2 3D structure models. Domains of this family called CoBaHMA, were initially identified in relation with the intracellular biomineralization of calcium carbonates by Cyanobacteria. They are part of the large heavy-metal-associated (HMA) superfamily, departing from the latter by specific sequence and structural features. In particular, most CoBaHMA domains share conserved basic amino acids, forming a positively charged surface, which is likely to interact with anionic partners. CoBaHMA domains are found in diverse modular organizations in bacteria, existing in the form of monodomain proteins or as part of larger proteins, some of which are membrane proteins involved in transport or lipid metabolism. This suggests that the CoBaHMA domains may exert a regulatory function, involving interactions with anionic lipids. This hypothesis might have a particular resonance in the context of the compartmentalization observed for cyanobacterial intracellular calcium carbonates.

Introduction:Metronidazole is a bactericidal, amoebicidal, and trichomonacidal agent targeting anaerobic bacteria, certain amoebic and protozoal species. It is a nitroimidazole that inhibits nucleic acid synthesis by disrupting DNA resulting in strand breakage. Its bioavailability is more than 80% when taken orally. It is a usually well-tolerated antimicrobial but can cause gastrointestinal side effects like a gastric upset in the form of nausea, vomiting, abdominal cramps, diarrhea, or constipation [1]. It has also been associated with other adverse effects like dizziness, darkening of the urine, and joint pain. Disulfiram reaction has been reported, especially in those drinking ethanol. Neuro-ophthalmologic side effects such as peripheral neuropathy, ataxia, encephalopathy, and even seizures have been reported with metronidazole use[2]. Optic neuritis, an inflammation of the optic nerve, is an unrecognized side effect of Metronidazole and has been reported in association with metronidazole administration in a few case reports. The nerve damage induced by Metronidazole can be either temporary or permanent.Here, we are reporting a 30-year-old lady who had a bout of gastroenteritis and was given a dose of IV Metronidazole and one day after which she started noticing decreased right eye vision, which progressed to complete vision loss in her right eye. She was managed with IV Pulse steroids. She showed a slight improvement in her right eyesight.

Background When unfolded proteins accumulate in the endoplasmic reticulum (ER), they cause ER stress and activate the pathways of unfolded protein response (UPR), constituted by a set of canonical ER stress transducing proteins. While the classical UPR is well-studied, the functions of non-canonical ER stress transducers are emerging. Findings The CREB3 (cyclic AMP responsive element binding protein 3) family, which contains five members including CREB3, CREB3L1, CREB3L2, CREB3L3, and CREB3L4, is the most important non-canonical ER stress response factor sensing and modulating unfolded protein homeostasis. As novel ER stress transducers, the CREB3 family plays important roles in regulating protein folding, modification, and secretion, contributing to biological events, including cell proliferation, differentiation, and migration in diverse contexts, especially in cancer. Conclusion This review summarized the roles of the CREB3 family in development and disease progression, with an aim to provide references for further research and clinical translation.

Background: Prostate cancer (PCa) is the common malignant disease in older men. Cancer-associated fibroblasts (CAFs) are a vital components of the TME and the major subpopulation of cells that promote tumor heterogeneity. However, there are still few studies on the correlation between PCa and CAFs. Thus, we predicted the prognosis of PCa by investigating CAFs characteristics in PCa and constructing a prognostic model with CAFs-related features. Methods: Firstly, we obtained the scRNA-seq and clinical data on PCa from the GEO and TCGA databases. We adopted a survival analysis to evaluate the impact of three distinct CAFs subtypes on the prognosis of PCa patients. Besides, we identified different CAFs by integrated univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis. Based on the CAFRGs, we built a prognostic model to exhibit PCa prognostic relevance and validated the prognostic signature. We also screened the drugs for PCa. Furthermore, we explored the correlation between malignant features and PCa. Results: We revealed that apCAFs and myCAFs were significantly correlated with PCa patient prognosis. 5 prognostic CAFRGs (SYNM, NR4A1, MSMB, HOPX, and GJC1) were screened by integrated analysis. We found that the low-risk group patients had significantly higher survival rates. And validation analyses targeting the prognostic model indicated that the high-risk group patients were more to exhibit higher BCR across external validation sets. The ssGSEA algorithm indicted that the majority of the immune cells had increased levels of infiltration and higher immune function scores in the high-risk group. Furthermore, the z-score algorithm results showed that CAFRG was closely connected angiogenesis, EMT, and cell cycle scores. Conclusion: In conclusion, we build a prognostic model with CAFs prognostic characteristics for PCa to offer further prediction of PCa prognosis and immunotherapy response, which ultimately guides the clinical management of PCa.

In July 1999, I took my final curtsey as an aspiring ballet dancer in London. At the time, I was devastated, having been ‘assessed out’ by the ballet school I’d attended the year after I finished high school in Ireland. I wish I knew then what I know now: there are no endings in a career, just different paths. It took a few more iterations for me to learn that lesson. I hope my experience can provide some reassurance for anyone out there grappling with their next career move.

Background: Anaphylaxis is increasing in recent years, with common triggers in infants being milk and eggs. Currently the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. This study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. Methods: Retrospective review of paediatric patients diagnosed with IgE-mediated milk and/or egg allergy between 2011-2021. Inclusion and exclusion criteria applied. Anaphylaxis defined as per the WAO amended criteria 2020. Data analysis utilised SPSS Version 28. Results: 1552 patient charts reviewed, 1094 excluded (n=458). 70 infants had anaphylaxis at diagnosis (milk n=36, egg n=34). 77.8%-85.2% with anaphylaxis successfully completed the ladder, 88.9-92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. 20.6-50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared to 17.3-40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. Conclusion: Milk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder, however these children are less likely to complete the ladder so parents should be educated in management of mild allergic reactions at home.

In the light of waste prevention in the conventional acrylic acid (AA) removal process uses a water washing tower, we report on an experimental evidence of a proof-of-concept alternative process using TiO2 ceramic membrane contactors. Experimental results allow us to estimate the mass transfer coefficient of the proposed membrane system, being 0.003 m3/m2h. Based on this value, we perform a techno-economic assessment (TEA) for the acrylate production process using membrane contactors for AA removal. The acrylate production cost is estimated with a focus on downstream processing. The results are benchmarked with the process using a water washing tower for AA removal. 2-ethylhexyl acrylate (2-EHA) is taken as the model product with a yield of 20,000 ton/year. We find that for the membrane contactors to be cost competitive with the water washing tower, the AA mass transfer coefficient needs to increase to 0.005 m3/m2h, keeping the other parameters constant.