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In this study, we evaluated the functional outcomes of nerve reconstruction for nerve gaps exceeding 7 cm, using sural nerve autografts. The cases primarily involved brachial plexus injuries and peripheral nerve injuries. The most frequent causes of these injuries were motorcycle accidents and workplace incidents, predominantly affecting young individuals. The best outcomes for nerve injuries are achieved through primary coaptation. All the patients in our study underwent delayed nerve reconstruction rather than primary repair for various reasons, resulting in outcomes that were not as favourable as those of primary repair. Despite using avascular nerve grafts to bridge long nerve gaps, many of our patients still experienced meaningful recovery. Motor function recovery outperformed sensory function recovery across all types of reconstructions. Hence, in situations where facilities and expertise for vascularized nerve grafts are unavailable, attempting reconstruction with an extended nerve graft for long nerve gap is justified. [ABSTRACT FROM AUTHOR]

The extensor apparatus is a complex muscle-tendon system that requires integrity or optimal reconstruction to preserve hand function. Extensor tendon injuries are common and they can lead decreased wrist and finger movements. Classification of extensor injuries into anatomical zones and the evaluation of the characteristics of the lesions are considered key points to select the appropriate management. In our retrospective observational study, we analyzed the demographic data, management & surgical outcomes of primary repair in 78 patients who presented with extensor tendon injuries in zone 6, according to Verdan's classification, to our institute from May 2021 to April 2022. 71 (91.02%) patients were males and 7 (8.98%) were female patients. The average age of patients were 34.6 years. Right hand was involved more than the left The most common etiology was work spot injury, mostly cutting machine injuries which accounted for 35 patients. The next most common cause was glass cut injuries seen in 23 patients. 15 patients had associated bony injuries. 55 patients had injury to multiple extensor tendons and 23 patients had injury to single extensor tendon. A total of 168 tendons were repaired. Functional outcomes were studied using Miller's criteria. The outcomes of the zone 6 extensor repair depends mainly on the severity of the tendon injury, injury to adjacent structures, strength of the repair and patient's compliance to physiotherapy [ABSTRACT FROM AUTHOR]

Summary: Recently, power system planners and operators are of interest to maximize distribution automation investments. Optimal operation of control centers of fully automated distribution systems enables it to control all switches as well as dispatching connected controllable apparatuses. Most previously enhanced distribution systems, which include additional enhancement apparatuses, such as distribution static VAr compensators, capacitor banks, and distributed generators, cannot take advantage of the features of these apparatuses because there is no efficient and reliable control. Accordingly, this article presents a robust and efficient technique using Manta ray foraging optimization algorithm (MRFOA) for optimal coordination and control of such apparatuses as well as distribution network reconfiguration simultaneously. The proposed procedure is employed for the dynamic operation of automated distribution systems, considering daily load variations, for losses minimization and emissions reduction with diverse cases of both the 33‐bus and 69‐bus distribution test systems. To manifest, these cases are developed to validate the proposed technique and to achieve optimum control and operation of the distribution systems. Despite the complexity of this problem, the proposed technique can achieve the optimal solution for the various considered cases. As well, the comparative assessment of the proposed MRFOA with relevant techniques demonstrates its effectiveness as an effective tool used in the control centers of modern automated distribution systems. One of the most complex challenges to distribution systems operators in the practical daily load variations is the control and optimal operation of the associated dispatchable enhancement apparatuses such as DGs and DSVCs. The DNR makes the utilization and control of such aforementioned enhancement apparatuses more feasible for distribution systems, but this is in return for increasing the complexity of the problem. Significant technical and environmental benefits have been achieved. Great power losses reduction (about 80%) and voltage enhancement are achieved using the MRFOA. In addition, the emission levels are kept at the lowest levels. [ABSTRACT FROM AUTHOR]

Introduction: The intention on vaccination of COVID-19 is influenced by demographic and psychological factors. An understanding of the factors that influence the intention of COVID-19 vaccination is important to achieve the successful vaccination programs. Objective: The objective of this study is to determine the critical factors affecting the intention of COVID-19 vaccination in Sri Lanka. Methodology: An online questionnaire was implemented amongst Sri Lankans to acquire the primary data. The questionnaire assessed the social demographic features, vaccination details, perception and intention about the vaccination, social norm, media exposure, and trust towards vaccines. Descriptive analysis was used to analyse the demographic characters and vaccination details. The structural equation model was used to analyse the relationship between the intention of COVID-19 vaccination and other relevant factors. Results: The results showed that the perception of vaccine, social norms and trust were significantly related with people’s intention towards vaccination, whereas media exposure showed an insignificant relationship with the intention towards vaccination. Meanwhile, perception about vaccine and media exposure had significant relationships between trust of the vaccines. Conclusion: It was conclusive that the intention of the COVID-19 vaccination was greatly influenced by the perception of vaccine, social norms and trust besides media exposure, which had an indirect effect on intention towards vaccination of COVID-19.

Ferroelectric negative capacitance materials have now been proposed for lowering electronics energy dissipation beyond basic limitations. In this paper, we presented the analysis on the performance of negative capacitance (NC) FinFET in comparison with conventional gate dielectrics by using a separation of variables approach, which is an optimal quasi-3D mathematical model. The result has been signified steeper surface potential (ψ), lower threshold voltage (Vth), 1.2 mA of on-state current (Ion), and enhanced immunity of negative capacitance FinFET against short channel effects (SCE’s) like 35.3 mV/V of drain-induced barrier lowering (DIBL), 60 mV/dec of subthreshold swing (SS) along with smallest off state current (Ioff) among another conventional gate dielectric. Hence, NC FinFET can be a potential candidate for low power and high-performance device.

The Rema-Kalenga Wildlife Sanctuary (RKWS) is a protected forest in Bangladesh that houses a variety of rare flora and fauna and supports the sustenance of 13 ethnic communities. This forest's indigenous and other inhabitants traditionally have a strong cultural connection to the plants, particularly medicinal plants. Due to modern allopathic medicine's rapid growth and commercial tree species prioritization, many medicinal plants are now on the verge of endangerment. Under such circumstances, it is crucial to explore how the local community perceives the importance of herbal treatments in contrast to allopathy, the underlying reasons for their perceptions, and the specific ailments for which they use the plants. The main objectives are: 1) to evaluate the perceptions of the local community towards allopathy and herbal medicine using Nussbaum's central capabilities approach, 2) to identify medicinal plant diversity, therapeutic usages, and quantitative indices, 3) to determine the factors that influence the use of medicinal plants. Repeated interviews and field surveys were conducted at the RKWS, interviewing 145 people, including the indigenous community (72.42 %) and traditional healers (8.27 %) from the surrounding seven villages. The study identified 51 medicinal plant species belonging to 39 families for their potent medicinal properties in treating various ailments. The predominant parts of the plants used in the treatments were leaves and roots. The uses were classified into 12 categories according to Nussbaum's central capabilities. The findings identified Aloe vera , Phyllanthus emblica, and Azadirachta indica as highly culturally important species. In contrast, Terminalia arjuna, Swertia chirata, and Azadirachta indica were found to have the highest relative importance. The underlying determinants influencing the preferences of individual users towards herbal medicine were income from agroforestry, beliefs, knowledge, and ethnicity, as revealed by the analysis of the ordinal logit model. The respondents viewed their strong inclination toward herbal medicine with many positive attitudes. Herbal medicine users held a negative perception of allopathy except for affiliation and practical reasons being viewed as the positive outcomes. Conversely, allopathic medicine users expressed mixed perceptions towards the treatment, with both positive and negative aspects being identified. Promoting the sustainable use of medicinal plants and their conservation efforts is imperative for the benefit of present and future generations in this region., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Romel Ahmed reports financial support was provided by the Social science Research Council (10.13039/100001345SSRC), Planning division of Planning Ministry, Government Republic of Bangladesh (Grant no. 20.00.0000.309.02.146.22–533)., (© 2024 The Authors.)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Excessive stimulation of the inositol (1,4,5)-trisphosphate (IP 3 ) signaling pathway has been linked to AF through abnormal calcium handling. However, little is known about the mechanisms involved in this process. We expressed the fluorescence resonance energy transfer (FRET)-based cytosolic cyclic adenosine monophosphate (cAMP) sensor EPAC-S H187 in neonatal rat atrial myocytes (NRAMs) and neonatal rat ventricular myocytes (NRVMs). In NRAMs, the addition of the α 1 -agonist, phenylephrine (PE, 3 µM), resulted in a FRET change of 21.20 ± 7.43%, and the addition of membrane-permeant IP 3 derivative 2,3,6-tri- O - butyryl -myo-IP 3 (1,4,5)-hexakis(acetoxymethyl)ester (IP 3 -AM, 20 μM) resulted in a peak of 20.31 ± 6.74%. These FRET changes imply an increase in cAMP. Prior application of IP 3 receptor (IP 3 R) inhibitors 2-aminoethyl diphenylborinate (2-APB, 2.5 μM) or Xestospongin-C (0.3 μM) significantly inhibited the change in FRET in NRAMs in response to PE. Xestospongin-C (0.3 μM) significantly inhibited the change in FRET in NRAMs in response to IP 3 -AM. The FRET change in response to PE in NRVMs was not inhibited by 2-APB or Xestospongin-C. Finally, the localization of cAMP signals was tested by expressing the FRET-based cAMP sensor, AKAP79-CUTie, which targets the intracellular surface of the plasmalemma. We found in NRAMs that PE led to FRET change corresponding to an increase in cAMP that was inhibited by 2-APB and Xestospongin-C. These data support further investigation of the proarrhythmic nature and components of IP 3 -induced cAMP signaling to identify potential pharmacological targets. NEW & NOTEWORTHY This study shows that indirect activation of the IP 3 pathway in atrial myocytes using phenylephrine and direct activation using IP 3 -AM leads to an increase in cAMP and is in part localized to the cell membrane. These changes can be pharmacologically inhibited using IP 3 R inhibitors. However, the cAMP rise in ventricular myocytes is independent of IP 3 R calcium release. Our data support further investigation into the proarrhythmic nature of IP 3 -induced cAMP signaling.

Polymeric graphitic carbon nitride (gCN) materials have received great attention in the fields of photo and electrocatalysis due to their distinct properties in metal-free systems with high physicochemical stability. Nevertheless, the activity of undoped gCN is limited due to its relatively low specific surface area, low conductivity, and poor dispersibility. Doping Gd atoms in a gCN matrix is an efficient strategy to fine-tune its catalytic activity and its electronic structure. Herein, the influence of various wt% of gadolinium (Gd) doped in melon-type carbon nitride was systematically investigated. Gadolinium-doped graphitic carbon nitride (GdgCN) was synthesized by adding gadolinium nitrate to dicyandiamide during polymerization. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) results revealed that the crystallinity and the morphological properties are influenced by the % of Gd doping. Furthermore, X-ray photoelectron spectroscopy (XPS) studies revealed that the gadolinium ions bonded with nitrogen atoms. Complementary density functional theory (DFT) calculations illustrate possible bonding configurations of Gd ions both in bulk material and on ultrathin melon layers and provide evidence for the corresponding bandgap modifications induced by gadolinium doping., Competing Interests: The authors declare that there is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: In context, the dengue virus causes dengue fever, which is spread by mosquito bites. About 22,000 people every year lose their lives as a direct result of it. Dengue fever has been on the rise recently, and its spread has alarmed health officials throughout the world., Discussion: Vaccination is essential for the prevention and management of dengue cases because there is currently no particular cure against dengue virus. The current dengue epidemic calls for urgent action in the form of immunization. However, there are serious drawbacks to using existing vaccines like Dengvaxia. Besides, the Qdenga vaccine has not yet been approved by the FDA in the United States. On the other hand, positive results from a phase II randomized and controlled clinical study of the TV005 tetravalent live-attenuated dengue vaccine were recently reported in Bangladesh. Only an effective vaccination can drastically lower dengue infection and mortality rates., Conclusion: The development of safe and effective vaccination, as well as their correct dissemination, is an essential requirement for the people of Bangladesh and the rest of the globe, and we concentrated on this critical problem in this article., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

A numerical investigation of a curved trapezoidal-corrugated channel with E-shaped baffles is conducted for thermal-hydraulic performance and flow behavior involving the use of single and hybrid nanofluids. This investigation introduces a unique integrated methodology for enhancing heat transfer efficiency by simultaneously combining geometric modifications and optimizing coolant utilization. To simulate turbulent, single-phase flow in three-dimensional corrugated channels, a computational model has been developed. The model considers a Reynolds number (Re) range of 5 × 10 3 ≤Re ≤ 35 × 10 3 and implies a uniform heat flux of 1000 W/m 2 . A commercial software, Ansys fluent was used in order to simulate the fluid flow by setting the inlet temperature at 300 K and velocity according to the Reynolds number. The continuity equation, momentum equation, and energy equations are discretized using a second-order upwind method. The equation's residual has been assigned a value of 1 × 10 6 for absolute criteria. The study evaluates the thermal-hydraulic performance of single nanofluids (Al 2 O 3 /water, CuO/water, SiO 2 /water) and hybrid nanofluids (Al 2 O 3 -Cu/water, TiO 2 -SiO 2 /EG-water) at varying volume fractions (1%≤φ ≤ 5%). Additionally, the investigation examines the effects of corrugations, baffles, and geometric parameter: blockage ratio (BR = 0.10, 0.15, 0.25). The findings demonstrate that the effects of baffles and corrugations can lead to the creation of vortex flow and greater turbulence, which can promote heat transfer enhancement. Various nanofluids demonstrated a significant rise in the Nusselt number, ranging from 35% to 60%, when compared to water in a curved corrugated channel. Additionally, a lower BR resulted in a smaller but still notable gain of 15%-19%. An effective heat exchanger that results in a significant energy dissipation is measured by the energy ratio (ER). The use of corrugated channels with narrow baffles has been found to consistently outperform smooth channels in terms of thermo-hydraulic parameters, leading to enhanced heat transfer. Using BR = 0.10 over 0.25 resulted in an increase in ΔP, HTC, and ER of 48.44%, 18.71%, and 45.86%, respectively. The implementation of a hybrid nanofluid consisting of 1% (20% TiO 2 -80% SiO 2 )/(60% Water-40% EG) volume fraction in a curved corrugated channel with baffles resulted in a significant improvement of 36.49% in thermal performance. This finding suggests that the aforementioned nanofluid composition and design parameter, characterized by a blockage ratio of 0.10, are the most effective in enhancing thermal performance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Human T-cell leukemia virus 1 (HTLV-1) associated lymphoma is a devastating malignancy triggered by HTLV-1 infections. We employeda comprehensive drug design and computational strategy in this work to explore the inhibitory activitiesof Astilbin derivatives against HTLV-1-associated lymphoma. We evaluated the stability, binding affinities, and various computational analysis of Astilbin derivatives against target proteins, such as HTLV-1 main protease and HTLV-1 capsid protein. The root mean square deviation (RMSD), root mean square fluctuation, radius of gyration, hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM) were applied to characterize these protein-ligand interactions further. Ligand-03 and ligand-04 exhibited notable binding affinity to HTLV-1 capsid protein, while ligand-05 displayed high binding affinity to HTLV-1 protease. MD simulation analysis revealed that ligand-03, bound to HTLV-1 capsid protein, demonstrated enhanced stability with lower RMSD values and fewer conformational changes, suggesting a promising binding orientation. Ligand-04, despite stable binding, exhibited increased structural deviations, making it less suitable. Ligand-05 demonstrated stable binding to HTLV-1 protease throughout the simulation period at 100 nanoseconds. Hydrogen bond analysis indicated that ligand-05 formed persistent hydrogen bonds with significantresidues, contributing to its stability. PCA highlighted ligand-03's more remarkable conformational changes, while DCCM showed ligand-05's distinct dynamics, indicating its different behavior in the complex. Furthermore, binding free energy calculations supported the favorable interactions of ligand-03 and ligand-04 with HTLV-1 capsid protein, while ligand-05 showed weaker interactions with HTLV-1 protease. Molecular electrostatic potential and frontier molecular orbital analyses provided insights into these compounds' charge distribution and stability. In conclusion, this research found Astilbin derivatives as potential inhibitors of HTLV-1-associated lymphoma. Future attempts at drug development will benefit from the steady interaction landscape provided by Ligand-03, Ligand-04 and Ligand-05, which showed the most attractive binding profile with the target protein. These results open up new opportunities for innovative drug development, and more experimental testing should be done between Astilbin derivatives and HTLV-1-associated lymphoma.Communicated by Ramaswamy H. Sarma.

The risk evaluation of natural disasters is an obstacle to ensuring healthcare services during catastrophic events worldwide. Therefore, timely and appropriate environmental health risk evaluation is essential. In this study, we incorporated the information from databases such as PubMed, Google Scholar, and Scopus. We performed this study to explore the feasibility of using artificial intelligence (AI) in disaster risk and emergency health management. Natural disasters have some phenomenon that is bound to happen. So, we can use AI to inform healthcare authorities about environmental health risks and emergency medical management. The recent innovations in technology have created novel opportunities for improving healthcare services across the world. AI technology would be the backbone of the fourth industrial revolution because we are entering an AI-based world this decade. Therefore, we suggest the authorities consider this positive aspect of AI technology to minimize the disastrous outcomes of any catastrophic events., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Multi-coloured and white-light emissions from pyrene-based hydrazones are described. They exhibit excitation wavelength-dependent emissions in solution due to the suppression of Kasha's rule. Interestingly, in dimethylformamide, 1-3 emit light that covers all the regions of primary colours as a function of excitation wavelength, and 1 and 2 emit white light ( λ ex = 420 nm) in isopropanol.

Objectives: Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown., Methods: In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes., Results: Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion ( p  < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four ( N  = 42, 9.5%) patients at 6-12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively., Conclusion: Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction Acute Appendicitis (AA) is the most common surgical emergency. Despite the use of various diagnostic parameters, the rate of negative appendectomy remains high (30%). Thus, through our retrospective study, we aim to analyse whether white blood cell (WBC) count or C-reactive protein (CRP) level is more indicative in the confirmation of AA. We also analysed imaging modalities ultrasonography (USG) and computed tomography (CT) of the abdomen to find out which is better for diagnosing AA. Methods Patients with suspected AA admitted for laparoscopic appendectomy in Saqr Hospital, Ras Al Khaimah, United Arab Emirates, during 2019-2020 were included in the study. Patients who had either or both WBC and CRP values were included in the study and their diagnosis was confirmed based on histological appendectomy findings. Data analysis was done using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States), receiver operating characteristic (ROC) curve, and chi-square test as required. p-value of <0.05 was considered statistically significant. Results Out of the 320 patients with suspected AA, WBC had a p-value of 0.8 (insignificant). A total of 228 patients who had elevated WBC had confirmed histological diagnosis of AA, and 152 patients who were tested for CRP and had elevated levels had confirmed histological diagnosis of AA. CRP had a p-value of 0.04 (significant). However, when the ROC curve was used as evidence to see which was a better test, WBC and CRP both had a low area under the curve (AUC), which proved that they were not the most accurate diagnostic marker in diagnosing AA. However, CRP was slightly better than WBC. A total of 266 patients underwent USG abdomen and it had a p-value of 0.4 (insignificant), while 118 patients underwent CT scan, which had a p-value of 0.01 (significant). CT abdomen was statistically proven as a better radiological investigation. Also, when the ROC curve was used to compare USG and CT abdomen, CT again proved to be a better radio diagnostic method for AA. Conclusions From our study, it can be concluded that CRP is better than WBC in ruling in appendicitis and CT abdomen is better than USG in diagnosing appendicitis, but CT abdomen is only next to histological diagnosis in confirming AA. Hence, we recommend doing CRP as the primary laboratory marker for suspected cases of AA. CT abdomen is the ideal imaging modality in cases of suspected AA where clinical examination, laboratory values, and ultrasound examination are inconclusive., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shahul Hameed et al.)

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered., (© 2023. Indian Society of Gastroenterology.)

Carbohydrate-binding proteins, known as lectins, play a wide range of vital roles in cellular and pathological processes. Mimicking lectins to achieve specific molecular recognition of carbohydrates in organic and aqueous media using artificial receptors is challenging due to the synthetic hurdles of receptors and structural similarities between sugars. Carbohydrate recognition using non-covalent interactions remains a vast topic. This review summarises the recognition of carbohydrates using metal-ligand assemblies, including metallosupramolecules, macrocycles, and cages. It also highlights the challenges and future directions in the field.

Background: Cigarette smoking increases the risk of cancer, cardiovascular diseases, and premature death. Aromatic amines (AA) are found in cigarette smoke and are well-established human bladder carcinogens., Methods: We measured and compared total urinary levels of 1-aminonaphthalene (1AMN), 2-aminonaphthalene (2AMN), and 4-aminobiphenyl (4ABP) in adults who smoked cigarettes exclusively and in adult nonusers of tobacco products from a nationally representative sample of non-institutionalized U.S. population in the 2013-2014 National Health and Nutrition Examination Survey., Results: Sample-weighted geometric mean concentrations of AAs in adults who smoked cigarettes exclusively compared with adult nonusers were 30 times higher for 1AMN and 4 to 6 times higher for 2AMN and 4ABP. We evaluated the association of tobacco-smoke exposure with urinary AAs using sample-weighted multiple linear regression models to control for age, sex, race/ethnicity, diet, and urinary creatinine. Secondhand smoke exposure status was categorized using serum cotinine (SCOT) among adult nonusers (SCOT ≤ 10 ng/mL). The exposure for adults who smoked cigarettes exclusively (SCOT > 10 ng/mL) was categorized on the basis of the average number of self-reported cigarettes smoked per day (CPD) in the five days prior to urine collection. The regression models show AAs concentration increased with increasing CPD (P < 0.001). Dietary-intake variables derived from the 24-hours recall questionnaire were not consistently significant predictors of urinary AAs., Conclusions: This is the first characterized total urinary AA concentrations of the U.S. adult non-institutionalized population. Our analyses show that smoking status is a major contributor to AA exposures., Impact: These data provide a crucial baseline for exposure to three AAs in U.S. non-institutionalized adults., (©2023 American Association for Cancer Research.)

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis (DC) patients with infection remain unknown., Methods: We conducted 16-srRNA sequencing on stool samples ( n =51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial diversity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events., Results: Genera associated with pathogenicity in conditions of immune exhaustion ( Corynebacterium , Lautropia ) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacteria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens ( Prevotella ), and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels >1,000 pg/dL. Pathogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission., Conclusions: Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based studies remain an unmet need., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Introduction: Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non-liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center., Methods: A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy., Results: Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in 'supposed' ultra-dilute formulations., Conclusion: Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not 'gentle placebos.', (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Severe alcohol-associated hepatitis (SAH) patients with infections have a high short-term mortality rate. Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH. Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation (FMT). Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature., Methods: From January 2019 to February 2021, retrospective analysis of a single hospital's records revealed 47 SAH patients undergoing FMT (100 mL/day via nasoduodenal tube for 7 days) and 25 matched patients receiving pentoxifylline (400 mg/8 h for 28 days). The primary end point was a 6-month survival rate. Secondary end points included incidence of ascites, hepatic encephalopathy, infections, acute kidney injury, and gut microbiota changes between post-therapy groups. Biomarker discovery and network analysis were also performed to identify significant taxa of gut microbiota in post-treatment groups in retrospectively stored stool samples., Results: All were males. The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline (83.0% vs 56.0%, P  =   0.012). At the end of 6-month follow-up, the incidences of clinically significant ascites (56.0% vs 25.5%, P  =   0.011), hepatic encephalopathy (40.0% vs 10.6%, P  =   0.003), and critical infections (52.0% vs 14.9%, P  <   0.001) in patients administered pentoxifylline were significantly higher than those in patients treated with FMT. At 3 months, biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group, respectively. At 6 months, Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable. Network analysis showed beneficial taxa ( Bifidobacterium ) as a central influencer in those undergoing FMT at 6 months., Conclusions: Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline. These clinical benefits were associated with favorable modulation of intestinal bacterial communities. Difficult-to-treat SAH patients may be safely bridged to transplantation using FMT. Controlled trials evaluating long-term outcomes are an unmet need., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: Healthy donor fecal microbiota transplantation (FMT) was preliminarily shown to have clinical benefits in hepatic encephalopathy (HE), severe alcohol-associated hepatitis (SAH), and alcohol use disorder. However, the long-term outcomes of FMT and the gut microbiota (GM) changes in patients with SAH are unknown., Methods: Patients with SAH who underwent FMT (N = 35) or standard of care (SoC, N = 26) from May 2017 to June 2018 were included, and their stored stool samples were analyzed prospectively. Clinical outcomes, including infections, hospitalizations, critical illness, alcohol relapse, and survival, were evaluated. Metagenomic analysis was undertaken to identify the relative abundances (Ras) and significant taxa at baseline and post-therapy (up to three years) among survivors between the two groups., Results: At follow-up, the incidences of ascites, HE, infections, and major hospitalizations were significantly higher in the SoC than in the FMT group ( P  < 0.05). Alcohol relapse was lower (28.6% versus 53.8%), and the time to relapse was higher in the FMT than in the SoC group ( P  = 0.04). Three-year survival was higher in the FMT than in the SoC group (65.7% versus 38.5%, P  = 0.052). Death due to sepsis was significantly higher in the SoC group (N = 13/16, 81.2%; P  = 0.008). GM analysis showed a significant increase in the RA of Bifidobacterium and a reduction in the RA of Acinetobacter in the FMT group. Beyond one to two years, the RA of Porphyromonas was significantly higher and that of Bifidobacterium was lower in the SoC than in the FMT group., Conclusions: In terms of treatment for patients with SAH, healthy donor FMT is associated with significantly lesser ascites, infections, encephalopathy, and alcohol relapse (with a trend toward higher survival rates) than SoC, associated with beneficial GM modulation. Larger controlled studies on FMT are an unmet need., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH., Methods: We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events., Results: All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI., Conclusions: Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area., (© 2021. Indian Society of Gastroenterology.)

Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Philips et al.)