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BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Abstract Background Celiac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. Methods This is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI). Discussion In this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting. Trial registration {2} ClinicalTrials.gov NCT 06178315. Registered on December 21, 2023

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been shown to provide effective cardiorenal protection, reducing mortality in conditions such as heart failure and chronic kidney disease. While several mechanisms have been identified, recent research has shed light on the drug’s ability to attenuate sympathetic nervous system (SNS) activity. Controversy exists on whether this is due to the extra-renal effects of the drug, or simply due to its renoprotective effects. However, recent trials have highlighted the persistent efficacy of SGLT2i despite declining renal function. Therefore, investigating the ability of SGLT2i to attenuate the SNS independently of the kidney could lead to more insight into its mechanism of action. So far, there has been limited research done on investigating the extra-renal effects of SGLT2i in human subjects on dialysis where the glycosuric renal effects of SGLT2i are negligible. This current study therefore aims to investigate the effects of SGLT2i on the SNS in anuric haemodialysis patients. Methods: We developed a protocol for a mechanistic study to investigate the extra-renal effects of SGLT2i on the SNS. The study will be an investigator-led, open-label, prospective study involving 20 adult (aged ≥18 years) haemodialysis patients with a residual urine output of ≤250 mL/day. Participants will be administered empagliflozin 25 mg/day for 6 weeks. Baseline SNS activity will be measured before and after administration by microneurography to assess central SNS outflow. Secondary outcomes such as changes from baseline in SNS stressor response, heart rate variability, and endothelial function will also be examined. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive in anuric haemodialysis patients. Discussion: This will be the first study evaluating the effects of SGLT2i on the SNS in haemodialysis subjects. This study aims to enhance our understanding of the potential role of SGLT2i-induced SNS reduction in the setting of markedly reduced renal function. The study has received ethics approval from the Royal Perth Hospital Human Research Ethics Committee (RGS0000003840) (Australian New Zealand Clinical Trials Registry [ANZCTR] ID: ACTRN12623001237673).

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Abstract The broad mite, Polyphagotarsonemus latus (Tarsonemidae: Acari) is a highly polyphagous species that damage plant species spread across 57 different families. This pest has developed high levels of resistance to some commonly used acaricides. In the present investigation, we deciphered the genome information of P. latus by PacBio HiFi sequencing. P. latus is the third smallest arthropod genome sequenced so far with a size of 49.1 Mb. The entire genome was assembled into two contigs. A set of 9,286 protein-coding genes were annotated. Its compact genome size could be credited with multiple features such as very low repeat content (5.1%) due to the lack of proliferation of transposable elements, high gene density (189.1/Mb), more intronless genes (20.3%) and low microsatellite density (0.63%).

Background and study aims Endoscopist techniques affect biliary cannulation success and the risk of adverse events during endoscopic retrograde cholangiopancreatography (ERCP). This survey study aims to understand the current practice of biliary cannulation techniques among endoscopists. Methods Practicing endoscopists were sent an anonymous 28-question electronic survey on biliary cannulation techniques and intraprocedural pancreatitis prophylactic strategies. Results The survey was completed by 692 endoscopists (6.2% females). A wire-guided cannulation technique (WGT) was the preferred initial biliary cannulation approach (95%). The preferred secondary approaches were a double-wire (DWT) (65.8%), precut needle-knife technique (NKT) (25.7%), transpancreatic sphincterotomy (5.9%) or other (2.6%). Overall, 18.1% of respondents were not comfortable with NKTs. In the setting of pancreatic duct (PD) access, 81.9% and 97% reported a threshold of three or more wire passes or contrast injections into the PD, respectively, before changing strategy, 34% reported placement of a prophylactic PD stent 200 ERCPs per year) were associated with comfort with precut NKTs and likelihood of prophylactic PD stent ( P

Abstract Background Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). Methods Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. Results After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. Conclusion miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. Systematic review registration PROSPERO (CRD42022302729).

ABSTRACTThis study aimed to synthesize silver nanoparticles (VJ@AgNPs) using Valeriana jatamansi root extract and assess their antibacterial, antioxidant, and antibiofilm properties against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. Various chemical and physical characterization methods were employed to analyze the synthesized VJ@AgNPs. UV-Visible spectroscopy confirmed the presence of VJ@AgNPs with a peak absorption at 426 nm, while FT-IR results indicated the involvement of phyto-compounds from V. jatamansi in the reduction and stabilization of these nanoparticles. High-resolution transmission electron microscopy revealed well-dispersed spherical nature with an average size of 29.1 ± 2.06 nm, and X-ray diffraction confirmed their crystalline structure. The biosynthesized VJ@AgNPs exhibited significant antibacterial activity against all tested pathogens, with substantial inhibition zones at 50 and 100 μg/mL concentrations. Additionally, VJ@AgNPs displayed potent antibiofilm activity and antioxidant capacity in scavenging assays. Furthermore, these VJ@AgNPs showed promise in photocatalytic degradation, effectively removing 95% of RhB dye within 75 minutes under solar light irradiation, following pseudo-first-order kinetics. This suggests their potential application in wastewater treatment for organic dye removal. The biocompatible and environmentally friendly nature of VJ@AgNPs underscores their potential as therapeutic agents against bacterial infections and oxidative stress-related diseases.

ABSTRACTClonostachys rosea is a biocontrol agent against a wide range of pests and diseases. In the present study, an in-vitro nematicidal activity of C. rosea has been documented by observing the behavioural response of Meloidogyne incognita (Mi) towards the culture filtrate of C. rosea. Eleven different biomolecules observed in GC-MS analysis were tested against seven potential target proteins of Mi through molecular modelling using PyRx 0.8 software. Among the biomolecules tested, Dihydro-4-hydroxy-2(3H)-furanone had the highest binding affinity for Acetylcholine esterase (AchE) (−7.5 kcal/mol), Cytochrome c oxidase subunit 1 (COX) (−7.8 kcal/mol), Heat shock protein (Hsp90) (−8.4 kcal/mol), Odorant response gene 1 (ODR 3) (−6.5 kcal/mol), Neuropeptide G-protein coupled receptor (nGPCR) (−7.6 kcal/mol) and Cathepsin L-protease (cpl-1) (−6.8 kcal/mol) protein targets compared to synthetic pesticide, carbofuran. The biomolecule 2,3-dihydroxypropanal has shown the highest binding affinity for Odorant response gene 1 (ODR 1) (−6.6 kcal/mol). Understanding the interactions between the target protein-ligands docked complexes displayed additional contacts such as hydrophobic interactions, van der Waals, pi-pi stacking, alkyl and pi-alkyl. The present investigation demonstrated that C. rosea is a hub of potential biomolecules that could be explored for nematicidal activities.

Key Clinical Message Pyroglutamic acidosis (PGA) or 5‐Oxoprolinuria is an uncommon and often overlooked cause of high anion gap metabolic acidosis (HAGMA). This case highlights the importance of systematically approaching HAGMA, and to consider PGA as a differential diagnosis when medications that disrupt the γ‐glutamyl cycle such as flucloxacillin and paracetamol are present.

Background: Streptococcus pyogenes is one of the major public health concerns causing human infections ranging from skin and throat infections to acute rheumatic fever and post streptococcal glomerulonephritis. Moreover, nowadays drug-resistant strains of S. pyogenes are emerging and can be transmitted through apparently healthy carriers to susceptible individuals. Objective: To assess the prevalence, antimicrobial susceptibility pattern and associated factors S. pyogenes among apparently healthy school children in Mekelle city primary schools, Northern Ethiopia. Methods: A cross-sectional study was conducted among 504 apparently healthy school children from February to May 2018. We used structured questionnaire to collect socio-demographic data. Throat specimens were collected using sterile cotton Swab and transported for culture, antimicrobial susceptibility and identification of S. pyogenes according to standard operating procedures. Data were analyzed using Stata 13 for descriptive statistics, bivariate and multivariate logistic regression. P-value

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches.