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Purpose of Review: This review examines the unphysiological nature of conventional intermittent hemodialysis (IHD) and explores alternative dialysis modalities that more closely mimic natural kidney function. As cardiovascular complications remain a leading cause of morbidity and mortality in dialysis patients, understanding and addressing the limitations of IHD is crucial for improving outcomes., Recent Findings: IHD's intermittent nature leads to significant fluctuations in metabolites, electrolytes, and fluid status, contributing to hemodynamic instability and increased cardiovascular risk. More frequent dialysis modalities, such as short daily hemodialysis and nocturnal hemodialysis have numerous benefits including reduced left ventricular hypertrophy, improved blood pressure control, and potentially decreasing mortality. Peritoneal dialysis offers a more continuous approach to treatment, which may provide cardiovascular benefits through gentler fluid removal and residual kidney function preservation., Summary: Conventional thrice weekly intermittent hemodialysis offers a fundamentally unphysiologic equilibrium of uremic solutes. Alternate approaches have demonstrated cardiovascular benefits., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A new set of metal-organic frameworks was designed by functionalizing g-C 3 N 4 with benzoic acid and using them as structure-directing ligands during the metal-organic framework (MOF) formation. One such MOF exhibited dual emissions, both metal- and ligand-centered, enabling ratiometric sensing of the carcinogenic industrial solvent dioxane. The fabricated MOFs possessed a unique fluffy spherical morphology that enabled atomic level resolution in transmission electron microscopy-a rarity in MOFs due to the 'Knock-on' effect. Sensor experiments showed a rapid response within 5 s of analyte introduction and achieved a low limit of detection (LOD) of 0.026 ppm, well below the FDA-approved level of 10 ppm. In addition, the sensor exhibited exceptional selectivity, discriminating 1,4-dioxane from a pool of 16 solvents. This increased sensing capability was attributed to the formation of complexes and precise alignment of energy levels between the host and analyte, facilitating photoinduced electron transfer (PET). This material is equally efficient for colorimetric detection of the same solvent under excitation of UV light as well as gas phase detection of this volatile organic compound through I - V characteristics. Density functional theory (DFT) analysis supported the crucial role of Eu and the ligand system in efficiently detecting 1,4-dioxane by fluorescence spectroscopy, as shown in the energy level diagram. Future research could focus on optimizing these metal-organic frameworks for enhanced industrial applications in the detection of dioxane and exploring their potential applications in real-world environmental monitoring and public health safety.

Biopharmaceutical Classification Systems (BCS) class II drugs show poor solubility and high permeability in the body. Fenofibrate (FF) is a classic example of a BCS class II drug, used to treat high cholesterol and triglyceride (fat-like substances) levels in the blood. Atomic layer coating (ALC) is a surface engineering technology adapted from the semiconductor industry, where metal oxides are coated one atomic layer at a time over the active pharmaceutical ingredients (API) particles. ALC coating was proven to improve the processability, alter the hydrophilicity, improve the stability, and fine-tune the release of drugs. Herein, we report the intervention of ALC coating in enhancing the bioavailability of a poorly water-soluble drug (fenofibrate) in the animal model. The physical properties of uncoated fenofibrate were compared with those of zinc oxide-coated and silicon oxide-coated fenofibrate. Following the application of the coatings, the structural integrity (both chemical stability and solid-state stability) of the active pharmaceutical ingredient (API) remained uncompromised, as corroborated by 1 H NMR and powder X-ray diffraction analyses. Notably, zinc oxide-coated fenofibrate exhibited favorable flow characteristics, whereas no discernible enhancement in flow behavior was observed for silicon oxide-coated fenofibrate. The results from contact angle measurements suggest that the silicon oxide-coated fenofibrate exhibits superior wetting behavior, as indicated by a contact angle nearing 0°. The application of ALC demonstrates an enhanced dissolution rate when compared to the uncoated active pharmaceutical ingredient (API) while leaving its equilibrium solubility unaffected. Coating the API with silicon oxide improves particle hydrophilicity and wetting properties, whereas zinc oxide coating aids in particle de-agglomeration, thereby enhancing their interaction with an aqueous medium. In vivo bioavailability studies conducted on rodents and larger animal (dog) models indicate a substantial increase in bioavailability (approximately 2 times) for the silicon oxide-coated API in comparison to the uncoated API, as determined by the area under the curve (AUC). Furthermore, the C max values for the silicon oxide-coated API also demonstrate a significant increase (approximately 3 times) over the uncoated API. Notably, an oral subacute toxicity study of ALC silicon-coated fenofibrate revealed no toxic effects attributable to the coating. This study underscores the potential of ALC in augmenting the bioavailability of BCS(II) drugs., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier Inc.)

Housing is a critical social determinant of children's health. While individual pathways between housing and health are well evidenced, there has been less attention on the co-occurrence of housing disadvantages. We aim to identify typologies of children's housing disadvantage and describe the health inequities they generate. A cross-sectional latent class analysis (LCA) was conducted on 4355 Australian children aged 4 to 5 years who participated in the Longitudinal Study of Australian Children. Nine binary indicators-dwelling tenure, external condition, affordability, stability, crowding, cleanliness, fuel poverty, and noise exposure-were used to generate latent housing typologies. Generalized linear models with robust standard errors described disparities in quality of life, injury, disability, and health service use across these housing typologies. Four distinct housing typologies were identified in this cohort: "good condition, affordable, and secure" (60%); "insecure" (11%); "crowded" (24%); and "unsuitable" (5%). Unsuitable housing, characterized by crowding, poor external conditions, and noise exposure, was more likely to be occupied by single-parent families, low-income households, and be headed by parents with low levels of education. Children in unsuitable housing lagged on quality of life indicators at preschool age (e.g., by 8.0 points on emotional functioning, 95% CI - 10.6, - 5.5), and underutilized primary healthcare services (e.g., prevalence ratio 0.76 for GP services, 95% CI 0.67, 0.87), compared to children in good quality housing. This finding supports the case for early intervention strategies that account for children's housing circumstances., (© 2024. The Author(s).)

The Bioconcentration Factor (BCF) is used to evaluate the bioaccumulation potential of chemical substances in reference organisms, and it directly correlates with ecotoxicity. Traditional in vivo BCF estimation methods are costly, time-consuming, and involve animal sacrifice. Many in silico technologies are used to avoid the problems associated with in vivo testing. This study aims to develop a quantitative read across structure-property relationship (q-RASPR) model using a structurally diverse dataset consisting of 1303 compounds by combining quantitative structure-property relationship (QSPR) and read-across (RA) algorithms. The model incorporates simple, interpretable, and reproducible 2D molecular descriptors along with RASAR descriptors. The PLS-based q-RASPR model demonstrated robust performance with internal validation metrics ( R 2 = 0.727 and Q 2 (LOO) = 0.723) and external validation metrics ( Q 2 F1 = 0.739, Q 2 F2 = 0.739, and CCC = 0.858). These results indicate that the q-RASPR model is statistically superior to the corresponding QSPR model. Furthermore, screening of 1694 compounds from the Pesticide Properties Database (PPDB) was performed using the PLS-based q-RASPR model for assessing the eco-toxicological bioaccumulative potential of various compounds, ensuring the external predictability of the developed model and confirming the real-world application of the developed model. This model offers a reliable tool for predicting the BCF of new or untested compounds, thereby helping to develop safe and environment-friendly chemicals.

Electrocaloric (EC) cooling presents a promising approach to efficient and compact solid-state heat pumps. However, reported EC coolers have complex architectures and limited cooling temperature lift. In this work, we introduce a self-regenerative heat pump (SRHP) using a cascade of EC polymer film stacks, which have electrostrictive actuations in response to an electric field that are directed to realize efficient heat transfer, eliminating the need for additional transportive or regenerative mechanisms. The SRHP demonstrates a cooling of 8.8 kelvin below ambient temperature in 30 seconds and delivers a maximum specific cooling power of 1.52 watts per gram. The temperature lift of the SRHP is 14.2 kelvin. These results underscore the potential of the compact solid-state cooling mechanism to address the increasing need for localized thermal management.

Organic polymers have found diverse applications in the industrial and scientific world. One such application is using chitosan-based electrochemical sensors, which have gained rapid popularity due to their unique properties. To further enhance the material's porosity and adsorption capacity, the incorporation of a surfactant into the film has been explored. This study focuses on a rarely investigated combination of fungi-derived chitosan and cationic surfactant N-Cetyl-N, N, N-trimethyl-ammonium bromide (CTAB). The resultant composite was transformed into a thin film on the surface of a graphite electrode, by drop casting method, followed by curing at 65 °C hot air. The low-cost sensor thus obtained was characterized by electrochemical studies, and surface study techniques including AFM, SEM, and XPS. The results showed the properties of the film were strongly governed by the ratio of components in the composite. Under optimal conditions, the affinity for composite film increased 3 to 4 folds for Pb and Cd. The developed electrochemical sensors had a limit of detection of 0.317 μM and 0.572 μM for Pb and Cd respectively. The linear range of detection was found to be 1 × 10 -6  M to 1.2 × 10 -4  M for Pb (II) and 2 × 10 -6  M to 1.4 × 10 -4  M for Cd (II)., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This report describes two brothers from India and a Chinese patient with somatic reversion of an inherited deleterious mutation in the WAS gene. Both the Indian siblings had inherited a single nucleotide deletion causing a frameshift mutation (c.1190del, p.Pro397Argfs*48) (variant 1: marked in blue) from the mother. Another variant (variant 2: marked in red), a 12-nucleotide deletion at position 1188-1199 (c.1188_1199del, p.P401_P404del) was also found, which resulted in restoration of the frame and subsequent rescue of the protein sequence. DNA sequencing from buccal mucosal cells revealed only the inherited variant (variant 1), while no reversion mutation was identified in the mucosal cells. Similarly, the Chinese patient was found to have a novel germline 14-base duplication (ACGAAAATGCTTGG) c.120_132 + 1dup (variant 1). This resulted in abolishment of the original splice junction coupled with the creation of a new junction 14 bases 3' and a frameshift mutation with predicted protein truncation p. Thr45Aspfs*. DNA from the patient's PBMC showed co-existence of wild-type and mutated sequences, but only the mutant was present in the buccal cells. Genomic and mRNA analysis of the isolated CD3+ T lymphocytes, CD3- mononuclear cells, and EBV-transformed B lymphocytes indicated that the reverant variant (germline variant was restored to wild-type sequence) were selectively found in CD3+ T lymphocytes., (© 2024 The Scandinavian Foundation for Immunology.)

Tranexamic acid (TXA) is acknowledged for reducing blood loss and transfusion requirements in various surgical specialties, yet its role in orthognathic procedures is less defined. Our study seeks to fill this knowledge gap by reviewing the available data and summarising the efficacy and clinical outcomes of TXA in orthognathic surgery. We performed a systematic review and meta-analysis, searching five databases for studies until 16 April, 2023. Our key outcome measures were intraoperative blood loss, postoperative bleeding, and transfusion rate. Previous weaknesses in systematic review and meta-analyses (SRMA) were identified using Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). The risk of bias was evaluated with the RoB-2 tool. A total of 15 studies were included, involving a combined total of 1060 patients. Compared with the control, the TXA group demonstrated significant reductions in intraoperative blood loss (mean difference -135.60 mL; p < 0.00001; 95% CI, -177.51 to -93.70 mL), Hb level drop (mean difference: 2.67 [-0.63, 5.98]), and improved surgical field visibility [p < 0.00001. (MD -0.99) (CI -1.11 to -0.86)]. No significant differences were observed in postoperative haematocrit levels (mean difference: -0.42 [-2.19, 1.35]; p = 0.003; I 2  = 75%), operation duration (p = 0.21), or duration of hospital stay (p = 0.63) between TXA and control groups. In orthognathic surgery, TXA effectively minimises blood loss, demonstrating both safety and efficiency. Well-designed, larger studies and comparisons with other haemostatic agents could solidify TXA evidence., (Copyright © 2024 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aims: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe., Methods and Results: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy., Conclusion: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility., (© 2024 John Wiley & Sons Ltd.)

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT. We demonstrated that a two-compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non-ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2-fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring., (© 2024, The American College of Clinical Pharmacology.)

Background: Abdominal wall reconstruction (AWR) is a treatment option for structural defects of the abdominal wall. The most frequently cited publications related to AWR have not been quantitatively or qualitatively assessed. This bibliometric analysis characterizes and assesses the most frequently cited AWR publications, to identify trends, gaps, and guide future efforts for the international research community., Methods: The 100 most cited publications in AWR were identified on Web of Science, across all available journal years (from May 1964 to December 2023). Study details, including the citation count, main content focus, and outcome measures, were extracted and tabulated from each publication. Oxford Centre for Evidence-Based Medicine levels of evidence (LOE) of each study were also assessed., Results: The 100 most cited publications in AWR were cited by a total of 9674 publications. Citations per publication ranged from 43 to 414 (mean 96.7 ± 52.48). Most publications were LOE 3 (n = 60), representative of the large number of retrospective cohort studies. The number of publications for LOE 5, 4, 3, 2, and 1 was 21, 2, 60, 2, and 12, respectively. The main content focus was surgical technique in 44 publications followed by outcomes in 38 publications. Patient-reported outcome measures were used in 3 publications, and no publications reported validated esthetic outcome measures., Conclusions: Overall, 3 was the LOE for most frequently cited AWR publications, with more publications below LOE 3 than above LOE 3. Validated outcome measures and patient-reported outcome measures were infrequently incorporated in the studies evaluated., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Inborn errors of immunity (IEI) are a group of genetically heterogeneous disorders with a wide-ranging clinical phenotype, varying from increased predisposition to infections to dysregulation of the immune system, including autoimmune phenomena, autoinflammatory disorders, lymphoproliferation, and malignancy. Lymphoproliferative disorder (LPD) in IEI refers to the nodal or extra-nodal and persistent or recurrent clonal or non-clonal proliferation of lymphoid cells in the clinical context of an inherited immunodeficiency or immune dysregulation. The Epstein-Barr virus (EBV) plays a significant role in the etiopathogenesis of LPD in IEIs. In patients with specific IEIs, lack of immune surveillance can lead to an uninhibited proliferation of EBV-infected cells that may result in chronic active EBV infection, hemophagocytic lymphohistiocytosis, and LPD, particularly lymphomas., Areas Covered: We intend to discuss the pathogenesis, diagnosis, and treatment modalities directed toward EBV-associated LPD in patients with distinct IEIs., Expert Opinion: EBV-driven lymphoproliferation in IEIs presents a diagnostic and therapeutic problem that necessitates a comprehensive understanding of host-pathogen interactions, immune dysregulation, and personalized treatment approaches. A multidisciplinary approach involving immunologists, hematologists, infectious disease specialists, and geneticists is paramount to addressing the diagnostic and therapeutic challenges posed by this intriguing yet formidable clinical entity.

Monitoring the genetic diversity and emerging mutations in SARS-CoV-2 remains crucial for understanding its evolution, given the virus's persistence in India. This study analyzes lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. The predominant variants identified were alpha, beta, delta, and omicron, with delta and omicron making up 76.05 % of sequenced genomes. The B.1.617.2 lineage of the delta variant was the major contributor to COVID-19 cases before the rise of omicron. Mutation screening of non-structural proteins (NSPs) and spike proteins revealed distinct profiles for each VOC. Co-mutation patterns were analyzed, showing structural and energetic alterations. Phylogenetic analysis indicated that nsp1, nsp3, nsp4, nsp13, and nsp14 were strongly associated with increased mutation load. The study also highlighted that nsp14 and spike have similar mutability patterns, underscoring nsp14's critical role in SARS-CoV-2 infectivity and persistence. This research provides a comprehensive view of SARS-CoV-2's evolution and persistence in India., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ankur Chaudhuri reports financial support was provided by ICMR for postdoctoral Research fellowship. Subhrangshu Das reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology., (Copyright © 2024. Published by Elsevier B.V.)

Objective: There are varying anatomical and mechanical demands of stent placement in the iliofemoral venous segment; the Duo Venous Stent System is designed to address these issues. The purpose of the VIVID (Venous stent for the Iliofemoral Vein Investigational clinical trial using the Duo Venous Stent System) study was to investigate the safety and efficacy of the Duo Venous Stent System for the treatment of patients with non-malignant iliofemoral venous obstructive disease., Methods: This was an international, prospective, multi-center, single-arm study that enrolled patients with symptomatic non-thrombotic (NT), post-thrombotic (PTS), or acute deep vein thrombotic (aDVT) iliofemoral venous outflow obstruction. The primary safety endpoint was freedom from major adverse events at 30 days post-index procedure. The primary efficacy endpoint was primary patency of stent-bearing segments at 12 months. Secondary and observational endpoints included symptom relief, primary assisted patency, secondary patency, and device success. Patients remain in follow-up for 36 months., Results: A total of 162 patients were enrolled at 30 sites in the United States and Poland. The primary safety endpoint was achieved in 98.7% of patients against a predefined performance goal of 89.0% (P<0.0001). The primary safety endpoint was achieved in 100%, 95.0%, and 100% of the NT, PTS, and aDVT cohorts, respectively. The primary efficacy endpoint was met in 90.2% compared with the performance goal of 77.3% (P=0.0002). Primary patency was observed in 95.2% of patients with NT disease, 79.4% of those with PTS, and 86.7% of those with aDVT. No stent fracture, migration, or embolization occurred through 12 months. Patient reported outcomes showed improvements in Venous Clinical Severity Score, Villalta, EQ-5D-3L, and VEINES-QoL/Sym scores from baseline through 6 and 12 months., Conclusions: Through 12 months, the Duo Venous Stent System is safe and effective for the treatment of non-malignant iliofemoral venous obstructive disease., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this paper, the phototransistor behavior is investigated in the germanium-on-insulator (GeOI)-based junctionless nanowire (JL-NW) transistor under various light conditions. High responsivity and photosensitivity are attributed in the fully depleted regime within the visible and near-infrared bands. The impact of light is also investigated in detail on the electronic and transfer characteristics such as energy bandgap, carrier distribution, electrostatic potential, electric field, and generation and recombination rates. Further, the channel doping and thickness are tuned to optimize the optical responsivity. The significant tunability of responsivity is observed with increasing channel thickness. The device exhibits fast optical switching performance, which is further enhanced at higher input light power. Overall, at the nanoscale dimension, our proposed phototransistor demonstrates better detectivity with a significantly smaller illumination area. Thus, the GeOI-based JL-NW phototransistors can be used for imaging (visible wavelength range) and bioimaging (near-infrared wavelength range) applications in advanced technology nodes., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Numerous studies proposed methods to detect Parkinson's disease (PD) via speech analysis. However, existing corpora often lack prodromal recordings, have small sample sizes, and lack longitudinal data. Speech samples from celebrities who publicly disclosed their PD diagnosis provide longitudinal data, allowing the creation of a new corpus, ParkCeleb. We collected videos from 40 subjects with PD and 40 controls and analyzed evolving speech features from 10 years before to 20 years after diagnosis. Our longitudinal analysis, focused on 15 subjects with PD and 15 controls, revealed features like pitch variability, pause duration, speech rate, and syllable duration, indicating PD progression. Early dysarthria patterns were detectable in the prodromal phase, with the best classifiers achieving AUCs of 0.72 and 0.75 for data collected ten and five years before diagnosis, respectively, and 0.93 post-diagnosis. This study highlights the potential for early detection methods, aiding treatment response identification and screening in clinical trials., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a leading cause of cognitive decline in the aging population, presenting a critical need for early diagnosis and effective prognostic tools. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have emerged as promising biomarkers for AD due to their roles in regulating gene expression and potential for reversibility. This review examines the current landscape of epigenetic biomarkers in AD, emphasizing their diagnostic and prognostic relevance. DNA methylation patterns in genes such as APP, PSEN1, and PSEN2 are highlighted for their strong associations with AD pathology. Alterations in DNA methylation at specific CpG sites have been consistently observed in AD patients, suggesting their utility in early detection. Histone modifications, such as acetylation and methylation, also play a crucial role in chromatin remodelling and gene expression regulation in AD. Dysregulated histone acetylation and methylation have been linked to AD progression, making these modifications valuable biomarkers. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), further contribute to the epigenetic regulation in AD. miRNAs can modulate gene expression post-transcriptionally and have been found in altered levels in AD, while lncRNAs can influence chromatin structure and gene expression. The presence of these non-coding RNAs in biofluids like blood and cerebrospinal fluid positions them as accessible and minimally invasive biomarkers. Technological advancements in detecting and quantifying epigenetic modifications have propelled the field forward. Techniques such as next-generation sequencing, bisulfite sequencing, and chromatin immunoprecipitation assays offer high sensitivity and specificity, enabling the detailed analysis of epigenetic changes in clinical samples. These tools are instrumental in translating epigenetic research into clinical practice. This review underscores the potential of epigenetic biomarkers to enhance the early diagnosis and prognosis of AD, paving the way for personalized therapeutic strategies and improved patient outcomes. The integration of these biomarkers into clinical workflows promises to revolutionize AD management, offering hope for better disease monitoring and intervention., Competing Interests: Declaration of Competing Interest None Declared, (Copyright © 2024. Published by Elsevier B.V.)

Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30 y). The tumor size ranged from 4​​​​​​ to 15 cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10 mo). Four patients died of metastatic disease (range: 5 to 16 mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In the realm of arterial disease interventions, drug-eluting stents (DES) have become a vital therapeutic choice in preventing atherosclerotic plaque formation and restenosis and facilitating vessel healing. Sirolimus-encapsulated poly Lactic-co-Glycolic acid (PLGA) Microparticles (MPs) were developed using solvent evaporation. MPs were freeze-dried with a cryoprotectant and coated on the stent surface using an efficient and reproducible nitrogen-assisted spray coating technique. The MPs displayed a uniform distribution particle size of 4.38 ± 1.1 μm, span value of 0.88 ± 0.02, coating mass transfer efficiency of 13.45 ± 1.1 % on the stent, and a coating time of ≤ 2 min per stent. Post sterilization, the particle size and morphology of the coated stents remained unchanged. Accelerated in vitro drug release profiles were evaluated under different conditions, indicating significant influences based on dissolution methods ranging from 28.2 %±4.3 %, 42.5 %±5.3 %, 76.6 %±4.7 %, and 84.25 %±3.1 % for dialysis bag (DB), vessel simulating flow-through cell (vFTC), flow-through cell (FTC), and sample and separate (SS) technique respectively for 48 h. The drug release mechanism from the coated stents is governed by the combination of the Korsmeyer Peppas and Higuchi models. The developed dissolution method exhibited discriminative effectiveness when evaluated with critical formulation attributes and process parameter variations. The 48 h accelerated drug release studies correlated well with the 6-month real-time release rate with an R 2 value of 0.9142 and Pearson's R2 of 0.9561. Ex-vivo studies demonstrated the permeation of MPs into artery tissues. Stability studies confirmed that MPs coated stents maintained desired properties at 4 °C and 30 °C/65 % RH for 6 months. Overall, these findings contribute to advancing stent technology, suggesting the potential for improvement of arterial interventions and enhanced patient outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Sarika Jadhav reports financial support was provided by Sahajanand Medical Technologies Pvt Ltd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Repository corticotropin injection (RCI) has been suggested to exert immunomodulatory and anti-inflammatory effects in ocular inflammation. The index retrospective study aimed to evaluate the efficacy and tolerability of subcutaneous RCI in patients with active scleritis or uveitis., Main Body: Medical records of patients who were diagnosed with different types of active scleritis or uveitis and received RCI for more than six months at a tertiary eye center were reviewed. Patient characteristics including age, sex, comorbidities, clinical findings, treatment details, and adverse events were recorded. A total of 17 eyes of 17 patients were included. Median age was 43 years old and 53% of patients were male. Mean treatment duration was 25.4 ± 15.5 months. Indications for RCI therapy were scleritis (7 anterior and 1 posterior) (47.8%), panuveitis (17.4%), retinal vasculitis (17.4%), chronic/recurrent anterior uveitis (13%), and posterior uveitis (4.35%). RCI was initiated at a dose of 40 to 80 units 3 times weekly. Given the adequate control of inflammation, RCI was successfully discontinued in four patients (23.5%). Prior to RCI therapy, 14 (82.3%) patients were on oral prednisone at an average of 10 mg daily (range 2.5-40 mg), and two (11.7%) patients discontinued prednisone immediately before initiating RCI due to side effects. After six months of therapy, the prednisone dose was reduced in four (23.5%) patients to an average of 3 mg daily (range 1-5 mg) and was stopped in eight (53%) patients. Concomitant immunomodulatory therapies (IMTs) included mycophenolate mofetil (23.5%) and methotrexate (23.5%), and adalimumab (23.5%). Ten patients were on IMTs prior to using RCI, and during the course of treatment, IMT was stopped in two patients and reduced in one. Side effects included insomnia (23%), hypertension (11.7%), lower extremity edema (11.7%), hyperglycemia (11.7%), weight gain (11.7%), and infection (5.8%)., Conclusion: RCI may be considered as a potential therapy with acceptable tolerability for patients with non-infectious scleritis or uveitis., (© 2024. The Author(s).)

Background and Aims: Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD., Methods: This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD., Results: PD was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups., Conclusion: Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative "pro-inflammatory" microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory-axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: The feasibility of implementing genome sequencing as an adjunct to traditional newborn screening (NBS) in newborns of different racial and ethnic groups is not well understood., Objective: To report interim results of acceptability, feasibility, and outcomes of an ongoing genomic NBS study in a diverse population in New York City within the context of the New York State Department of Health Newborn Screening Program., Design, Setting, and Participants: The Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study was a multisite, single-group, prospective, observational investigation of supplemental newborn genome screening with a planned enrollment of 100 000 participants. Parent-reported race and ethnicity were recorded at the time of recruitment. Results of the first 4000 newborns enrolled in 6 New York City hospitals between September 2022 and July 2023 are reported here as part of a prespecified interim analysis., Exposure: Sequencing of 156 early-onset genetic conditions with established interventions selected by the investigators were screened in all participants and 99 neurodevelopmental disorders associated with seizures were optional., Main Outcomes and Measures: The primary outcome was screen-positive rate. Additional outcomes included enrollment rate and successful completion of sequencing., Results: Over 11 months, 5555 families were approached and 4000 (72.0%) consented to participate. Enrolled participants reflected a diverse group by parent-reported race (American Indian or Alaska Native, 0.5%; Asian, 16.5%; Black, 25.1%; Native Hawaiian or Other Pacific Islander, 0.1%; White, 44.7%; 2 or more races, 13.0%) and ethnicity (Hispanic, 44.0%; not Hispanic, 56.0%). The majority of families consented to screening of both groups of conditions (both groups, 90.6%; disorders with established interventions only, 9.4%). Testing was successfully completed for 99.6% of cases. The screen-positive rate was 3.7%, including treatable conditions that are not currently included in NBS., Conclusions and Relevance: These interim findings demonstrate the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in a population of different racial and ethnic groups. DNA sequencing offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots. Additional studies are required to understand if these findings are generalizable to populations of different racial and ethnic groups and whether introduction of sequencing leads to changes in management and improved health outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT05990179.

Despite the availability of effective treatment and vaccines for hepatitis B virus (HBV) and C virus (HCV), many people are still infected and remain unaware of their infection. The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT), a computer-based search tool, was introduced in 60 general practices (GPs) in April 2014 to support identification, testing and treatment of individuals at high risk for blood-borne viruses (BBVs). CIVHIT searched electronic medical records (EMRs), flagging all those with codes linked to risk factors or medical conditions associated with BBVs. CIVHIT was associated with a 78.5% increase in BBV tests in primary care in both boroughs. This translated to a 55.8% rise in new diagnoses. HBV testing saw the largest increase resulting in twice as many people diagnosed. Only 23.2% of HBV and 14.9% of HCV-positive tests were referred to secondary care. In an index practice, the most common flag was a history of STIs (477/719, 66.3%). Individuals with previous or current drug use and those with a known hepatitis contact were more likely to be offered a test compared to those flagged due to a history of STI. HIV and HBV testing was lower in males following a test offer. There was an increased likelihood of testing for HBV and HCV with increasing age. Additionally, individuals with previous or current drug use and individuals with a known hepatitis contact were more likely to test for HCV compared to individuals flagged due to STI history. CIVHIT shows promise to assist with the elimination of BBVs., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Tetrahedral carbon is a well-accepted structural motif. Theory has paved the way for many rule-breaking planar tetracoordinate carbon structures. Herein, we have explored the possibility of phosphorous supported carbon cluster C(P 4 ) 2+ to locate a planar tetracoordinate carbon centre (ptC). Our calculations revealed a penta-atomic planar tetracoordinate carbon (ptC) atom as a local minimum with a significant barrier for interconversion into the lowest energy isomer. The proposed species is kinetically stable and is a probable candidate for experimental detection. The stabilization of the planar structure arises due to delocalization of the p-electrons of the central carbon atom to the surrounding P 4 skeleton and significant electrostatic attraction.

Fibroblast growth factor (FGF) signaling elicits multiple downstream pathways, most notably the Ras/MAPK cascade facilitated by the adaptor protein Grb2. However, the mechanism by which Grb2 is recruited to the FGF signaling complex remains unresolved. Here we showed that genetic ablation of FGF signaling prevented lens induction by disrupting transcriptional regulation and actin cytoskeletal arrangements, which could be reproduced by deleting the juxtamembrane region of the FGF receptor and rescued by Kras activation. Conversely, mutations affecting the Frs2-binding site on the FGF receptor or the deletion of Frs2 and Shp2 primarily impact later stages of lens vesicle development involving lens fiber cell differentiation. Our study further revealed that the loss of Grb2 abolished MAPK signaling, resulting in a profound arrest of lens development. However, disrupting the Grb2 binding site on Shp2 or abrogating Shp2 phosphatase activity only modestly influenced FGF signaling, whereas mutating the presumed Shp2 dephosphorylation site on Grb2 did not impede MAPK signaling in lens development, indicating that Shp2 is only partially responsible for Grb2 recruitment. In contrast, we observed that FGF signaling is required for the phosphorylation of the Grb2-binding sites on Shc1 and the deletion of Shc1 exacerbates the lens vesicle defect caused by Frs2 and Shp2 deletion. These results reveal that Shc1 collaborates with Frs2 and Shp2 to target Grb2 in FGF signaling.

Natural transformation (NT) represents one of the major modes of horizontal gene transfer in bacterial species. During NT, cells can take up free DNA from the environment and integrate it into their genome by homologous recombination. While NT has been studied for >90 years, the molecular details underlying this recombination remain poorly understood. Recent work has demonstrated that ComM is an NT-specific hexameric helicase that promotes recombinational branch migration in Gram-negative bacteria. How ComM is loaded onto the post-synaptic recombination intermediate during NT, however, remains unclear. Another NT-specific recombination mediator protein that is ubiquitously conserved in both Gram-positive and Gram-negative bacteria is DprA. Here, we uncover that DprA homologs in Gram-negative species contain a C-terminal winged helix domain that is predicted to interact with ComM by AlphaFold. Using Helicobacter pylori and Vibrio cholerae as model systems, we demonstrate that ComM directly interacts with the DprA winged-helix domain, and that this interaction is critical for DprA to recruit ComM to the recombination site to promote branch migration during NT. These results advance our molecular understanding of recombination during this conserved mode of horizontal gene transfer. Furthermore, they demonstrate how structural modeling can help uncover unexpected interactions between well-studied proteins to provide deep mechanistic insight into the molecular coordination required for their activity., Significance Statement: Bacteria can acquire novel traits like antibiotic resistance and virulence through horizontal gene transfer by natural transformation. During this process, cells take up free DNA from the environment and integrate it into their genome by homologous recombination. Many of the molecular details underlying this process, however, remain incompletely understood. In this study, we identify a new protein-protein interaction between ComM and DprA, two factors that promote homologous recombination during natural transformation in Gram-negative species. Through a combination of bioinformatics, structural modeling, cell biological assays, and complementary genetic approaches, we demonstrate that this interaction is required for DprA to recruit ComM to the site of homologous recombination.

Objectives: The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology., Methods: A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded., Results: The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%., Conclusions: Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The optofluidic microreactor, a convergence of optics and microfluidics, offers advanced functionalities that can be pivotal in the rapid assessment of nanocatalysts for tackling environmental contamination issues. This article presents an efficient approach for degrading Methylene blue (MB) dye, commonly used in the textile industry, within a cost-effective polydimethylsiloxane (PDMS) based continuous flow optofluidic microreactor. This microreactor combines graphene quantum dots (QDs) and NH 2 -MIL-125 (MOF(Ti)) as a highly effective photocatalyst coating within its microchannels. By directly incorporating graphene QDs@MOF(Ti) into the microchannels, the photocatalytic medium is brought into close proximity with the flowing MB dye solutions, thereby reducing the necessary interaction time and enhancing purification efficiency. Furthermore, the findings demonstrate an impressive degradation efficiency of ∼99% for MB dye at a flow rate of 50 μL min -1 under visible light irradiation, achieved in a single pass. Additionally, the microfluidic reactor exhibits prolonged stability of the photocatalyst, enabling its reuse without significant efficiency loss. In addition, a comparative analysis highlights the advantages of microreactor-based photocatalysis over traditional methods. These advancements in the features of the graphene QDs@MOF(Ti) nanocomposite substantiate their demonstrated superiority in degradation efficiency., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Humans receive around 50% of natural radiation dose due to 222 Rn (radon), 220 Rn (thoron) and their decay products. Several field campaigns measuring these gases and the decay products in different regions of India have been conducted in the recent past. Some of these studies measured indoor activity concentration and/or dose due to these gases and the associated decay products. This work compares the fraction of 222 Rn and decay products and 220 Rn and decay products in inhalation dose for 10 studies conducted in Uttarakhand state. It is seen that AEDT (annual effective dose due to 220 Rn and decay products) for these regions varies between 21 and 48% and it is significantly higher than the averaged worldwide reference value of 6%. Based on elaborative measurements performed in the Bageshwar district (present work), Almora and Nainital districts (our previous campaigns); the reasons for this high value have been explored. It was observed that a higher source term for mud houses could be the main reason for the high AEDT range. Interestingly, preliminary analysis revealed that the fraction is higher for the dwellings situated at higher altitudes thus indicating the role of the unavailability of modern building construction materials at remote locations. The study highlights the significant contribution of thoron in the Indian Himalayas., (© 2024. The Author(s).)

Tacticity is long known as a significant contributor in changing the chemical and mechanical properties of the polymers drastically. This study explores mechanism of bandgap formation in elastic mechanical metastructures designed with a focus on tacticity. We introduce metabeams, comprising a primary slender beam embedded with short secondary beams featuring end masses at their tips. The investigation delves into the numerically simulated vibration characteristics of metabeams using finite element analysis, with a subsequent comparison to experimental results for fabricated metabeams. Employing a unit-cell design approach that manipulates spatial and physical parameters, we explore a wide range of uniform and non-uniform metabeam configurations based on the distance between secondary beams and distribution of local resonators as per tacticity. Hence, drawing inspiration from tacticity, we extend our investigation to isotactic and syndiotactic metabeams, altering physical parameters (mass) within the unit cell for both configurations. The strategic distribution of end masses on attached secondary beams introduces unique characteristics to isotactic and syndiotactic metabeams, allowing for the modulation of bandgaps without altering the natural frequencies of the resonators in symmetric and anti-symmetric metabeam designs. Our research demonstrates, incorporating tacticity in metabeam design offers a novel and unconventional approach to modulate the bandgap formation mechanism., (© 2024. The Author(s).)

Purpose: Repair of type C esophageal atresia with tracheo-esophageal fistula (EA/TEF) may be complicated by esophageal anastomotic leak. Risk factors associated with leak and the impact of leak on inpatient outcomes remains uncertain. Our objectives are to estimate the associations between clinical factors and esophageal anastomotic leak and quantify the association of leak with length of stay (LOS) in infants who underwent repair of type C EA/TEF., Methods: Using the Children's Hospitals Neonatal Database (CHND), we identified infants with type C EA/TEF from 2021 to 2023. The main outcomes were anastomotic leak and LOS. Multivariable associations between patient and clinical factors and these outcomes were quantified using logistic regression (leak) and Cox proportional hazards modelling (LOS)., Results: Among 365 infants at 36 centers, anastomotic leak occurred in 55 (15.1 %) infants, and thoracoscopic approach, lower birthweight, small for gestational age less than 10th percentile, male sex, staged repair, ventricular septal defect, and center were independently associated with leak (area under receiver operating curve = 0.853). Also, LOS was increased in infants with leak compared to those without [hazard ratio (HR): 0.655, 95 % CI = 0.431-0.996, p = 0.044], independent of birth weight, surgical approach, male sex, or VSD. The adjusted LOS demonstrated a 11-fold inter-center variation (p = 0.034)., Conclusions: Several clinical and operative factors are associated with esophageal anastomotic leak in infants after type C EA/TEF repair. Leak significantly prolongs LOS. The magnitude of inter-center variability in LOS also suggests that identifying best practices could aid in improving patient care in this patient population., Type of Study: Retrospective Comparative Study., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Key Clinical Message: Early recognition and management of familial hypercholesterolemia (FH) are crucial, especially in patients with extensive xanthomas and premature coronary artery disease. Prompt diagnosis and aggressive lipid-lowering therapy can significantly reduce morbidity and mortality rates. Careful clinical assessment in resource-limited settings is essential for optimal outcomes., Abstract: Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder that causes chronically elevated levels of low-density lipoprotein (LDL) cholesterol. Based on LDL levels, FH can be heterozygous or homozygous, further established through clinical features, laboratory findings, and genetic analysis. Elevated cholesterol levels cause atherosclerosis, coronary artery disease, myocardial infarction, and sudden death. Xanthomas are a clinical manifestation of FH that reveal the underlying systemic genetic disease. We present the case of a 47-year-old male with triple vessel coronary artery disease and widespread xanthomas, diagnosed with homozygous FH based on "The Dutch Lipid Clinic Network Diagnostic Criteria for Familial Hypercholesterolemia." Lifelong therapy with lipid-lowering medications and lifestyle changes is necessary in such cases., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Competing Interests: Nil.

Our systematic review aims to synthesise the evidence on interventions targeting improvement in patient adherence to psychological treatments for common mental disorders. A search was conducted on six electronic databases using search terms under the following concepts: common mental disorders, adherence, psychological treatments and controlled trial study design. Due to the heterogeneity in intervention content and outcomes evaluated in the included studies, a narrative synthesis was conducted. Risk of bias was assessed using the Cochrane Risk of Bias Version 2 tool for randomised controlled trials and the Cochrane ROBINS-I tool for non-randomised controlled trials. The search yielded 23 distinct studies with a total sample size of 2,779 participants. All studies were conducted in high-income or upper-middle-income countries. Interventions to improve patient adherence to psychological treatments included reminders and between-session engagement (e.g., text messages), motivational interviewing, therapy orientation (e.g., expectation-setting) and overcoming structural barriers (e.g., case management). Interventions from 18 out of 23 studies were successful in improving at least one primary adherence outcome of interest (e.g., session attendance). Some studies also reported an improvement in secondary outcomes - six studies reported an improvement in at least one clinical outcome (e.g., depression), and three studies reported improvements in at least one measure of well-being or disability (e.g., days spent in in-patient treatment). By incorporating these interventions into psychological treatment services, therapists can better engage with and support their patients, potentially leading to improved mental health outcomes and overall well-being., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s) 2024.)

Objectives: This study aims to determine the usage pattern, effectiveness and safety of oral tramadol 75 mg and dexketoprofen trometamol 25 mg fixed-dose combination (TRAM/DKP FDC) in the short-term treatment of moderate-to-severe acute pain in real-world clinical practice in Asia., Design: Real-world, prospective, multicentre, observational, phase IV study., Setting: 13 tertiary-care hospital sites across the Philippines, Thailand, Malaysia and Singapore., Participants: Adult patients aged 18-80 years prescribed TRAM/DKP FDC for the short-term (up to 5 days) treatment of moderate-to-severe acute pain., Main Outcome Measures: Primary endpoints were the proportion of patients prescribed TRAM/DKP FDC with different types of postsurgical and non-surgical treatments, and the average dosing frequency and duration of TRAM/DKP FDC treatment. Secondary endpoints were the proportion of patients achieving ≥30% pain reduction at 8 hours post the first dose (pain severity was assessed using the 11-point Numeric Pain Rating Scale); patient satisfaction at the end of treatment (based on a 5-point Patient Global Evaluation Scale (PGE)) and safety including the incidence of adverse drug reactions (ADRs)., Results: Among 599 patients (median age 44 years, 61.3% female) enrolled in this study, 68.61% (n=411) were postsurgical and 31.39% (n=188) were non-surgical patients. TRAM/DKP FDC was prescribed in a diverse group of postsurgical patients (eg, orthopaedic, general and cancer surgery) as well as in non-surgical conditions (eg, lower back pain and musculoskeletal pain). In the majority of patients, TRAM/DKP FDC was prescribed every 8 hours (65.94%) and for 5 days (78.80%). There was a significant reduction in pain intensity throughout the study and 65% of patients achieved ≥30% pain reduction from baseline at 8 hours post the first dose of TRAM/DKP FDC on day 1. 95.69% of patients were satisfied with the treatment (rated good, very good and excellent on the PGE scale). Overall, 13.9% of patients reported ADRs; most were mild to moderate in severity. The most common ADRs were nausea, vomiting and dizziness., Conclusion: This study showed that TRAM/DKP FDC was used in diverse types of postsurgical and non-surgical patients in the real-world setting in Asia. It effectively reduced pain and was well tolerated with a high level of patient satisfaction., Competing Interests: Competing interests: BG, AG and DN are employees of A. Menarini Asia-Pacific Holdings Pte. Ltd., Singapore. All other authors report receiving investigator fees for this study from the sponsor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite decades of a call to action to engage men in reproductive health, men are often left out of programs and interventions. In India, where half of pregnancies are reported as unintended, patriarchal gender norms and still dominant patterns of arranged marriages make engaging men in family planning and strengthening couples communication critical in increasing reproductive autonomy and helping young couples meet their reproductive goals. This study explores the feasibility and acceptability from the men's perspective of the pilot of a gender transformative intervention for newly married couples in India., Methods: A pilot study was conducted of TARANG, a 4 month intervention for newly married women, with light touch engagement of husbands (4 sessions). A total of 41 husbands participated in the pilot, and we collected baseline knowledge and endline feasibility and acceptability data from them, along with in depth qualitative interviews with 13 men. The study was conducted in June 2023-January 2024., Results: Men had low levels of knowledge about biology, family planning, with the majority of men reporting that no one had provided them information about these topics. Most men wanted to delay the first birth by at least 2 years, yet less than a quarter had discussed childbearing plans with their partner or engaged in family planning methods. While all men reported high acceptability (satisfaction and usefulness), feasibility (participation) was low, with only 43% attending 2 or more sessions. Main barriers to participation included commitments due to work and migration. Men reported that the intervention led to improvements in their relationships with their wives, gave them a sense of empowerment, and led them to become resources for other men in their community., Conclusions: Men in these rural communities are not receiving the information that they need to meet their reproductive goals, however, they greatly desire this information and ways to improve relationships with their new wives. Such an intervention appears to have the potential to help change norms and spread information in the community and provide men with positive, life affirming feelings. Providing information through technology could address barriers to in-person engagement. TRIAL REGISTRATION CLINICALTRIALS.GOV : 03/13/24.NCT06320964., (© 2024. The Author(s).)

Purpose: Maxillofacial reconstruction with dental implants in microvascular tissue flaps aims to improve mastication. However, the quality of life (QoL) impact of this intervention is yet to be determined. This systematic review assessed the QoL impact of maxillofacial reconstruction with implant-supported teeth compared to no dental rehabilitation, removable dentures, and obturator (modified denture). Additionally, we examined instruments applied to measure QoL in maxillofacial reconstruction., Methods: Databases Ovid Medline and Embase, Scopus, Web of Science and Handle on QoL were searched. Cohort, case-control and randomized controlled trials (RCT) were narratively synthesized for QoL captured through validated instruments. Study methodological quality was assessed using Cochrane Risk of Bias 2 and Risk of Bias in Non-randomized studies of Exposure. Instruments underwent COSMIN content validity analysis., Results: Of a total of 2735 studies screened, the three included studies (two cohort and one RCT) showed improved QoL with maxillofacial reconstruction compared to obturator and no dental rehabilitation. However, these studies have high risk of bias due to confounding. None of the instruments achieved a sufficient relevance rating for maxillofacial reconstruction, having been designed for other target populations and there is no evidence on their content validity for this population, but the EORTC QLQ30 H&N35 satisfied more COSMIN criteria than the UW-QOL and OHIP-14., Conclusion: Although studies showed favourable QoL with maxillofacial reconstruction involving dental implants, these have high risk of bias and further studies are needed to establish the impact. Existing QoL instruments lack content validity and tailored instruments are needed for QoL evaluation in maxillofacial reconstruction., (© 2024. The Author(s).)

Background: Newly married young women face increased susceptibility to adverse health outcomes, social isolation, and disempowerment, yet interventions targeting this vulnerable group remain limited. We examined the feasibility and acceptability of TARANG, a life skills and reproductive health empowerment intervention, developed for and with young newly married women. Methods: We recruited 42 newly married women as participants in our study. We conducted a convergent mixed-methods, single-group cluster pilot study to the intervention in which 41 participants (retention rate=97.6%) completed both baseline and endline surveys in July 2023 and January 2024, respectively. We assessed three primary outcomes--feasibility using proportion of participants who completed at least 50% sessions, acceptability using proportion completely satisfied/somewhat satisfied with TARANG and usefulness using proportion who found TARANG useful/somewhat useful. We conducted in-depth interviews with a purposive sample of 12 participants to understand intervention acceptance and usefulness of the intervention and 6 program staff and moderators to understand barriers to implementing the intervention. We analyzed the quantitative data with descriptive statistics and qualitative data using thematic analysis. We triangulated data from monitoring data filled by moderators, quantitative surveys with participants, and qualitative data. Results: In the pilot study, 35/42 participants had completed at least one session. Overall, 82% participants attended at least 50% of the sessions. Among those who attended at least 1 session,97% were satisfied/somewhat satisfied with the intervention and 100% of participants found the intervention to be useful/somewhat useful. Qualitative findings reveal participants' appreciation for open discussions on sensitive topics, such as family planning, and highlight the intervention's role in filling knowledge gaps and fostering social connections, better sense of agency and improved relationships with mothers-in-law and husbands. While barriers to consistent participation were identified, feedback informed refinements to the intervention for the main trial, including session modifications, increased engagement strategies, and integration of educational videos. Conclusion: Our community-based participatory approach, developed with input from end users, demonstrated not only high acceptability and feasibility but also had many benefits for newly married women in rural/tribal Rajasthan. Our findings also led to adaptations that may enhance delivery of, and satisfaction with TARANG intervention, which will be tested with a larger sample in a rigorous cluster randomized controlled trial in Rajasthan, India. ClinicalTrials.gov : The study is registered at ClinicalTrials.gov (NCT06320964). Registered retrospectively on 13 March 2024, https://clinicaltrials.gov/study/NCT06320964.

Background: In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment., Method: Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024., Results: Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes., Conclusions: This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In robotic donor hepatectomy (RDH), hepatic duct division (HDD) and its stump closure technique are of paramount importance in avoiding postoperative biliary complications in both donors and recipients. We describe our novel triple C ("clip-clamp-cut") technique of HDD. Methods: Out of 4016 living donor liver transplant (LDLT) (2004-October 2023), we have performed 208 RDH cases since December 2019. This study is a retrospective analysis of the first 160 RDH cases. After excluding the first 20 RDH cases (learning curve) and 3 left-sided RDH cases, 137 cases with no exclusion criteria were included. We divided these 137 donors into the "cut and suture" (CS) group ( n  = 33) and the "triple C" technique group ( n  = 104). We compared intraoperative details and postoperative outcomes. Results: All 137 robotic donors and 128/137 recipients are currently well. Donor biliary leak rate was significantly lower among the triple C group ( n  = 3, 2.9%) compared to the CS group ( n  = 5, 15.2%) ( p =0.009). No other differences in postdonation morbidity were observed among the two groups. Recipient biliary complication rate was lower in the triple C group than in the CS group although not statistically significant (10.6% vs. 15.1%; p =0.537), despite more multiple biliary anastomoses in the former. No significant differences in post-transplant recipient morbidity and mortality were observed. Conclusions: Our simple yet novel triple C technique enables clean, precise, bloodless HDD resulting in lower donor and potentially recipient biliary complication rates. The ease and reproducibility make it ideal for widespread adoption., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Arvinder S. Soin et al.)

Purpose: To report the detailed histopathology of two enucleated eyes from two patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and to propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis (HORV)., Design: Case series., Subjects: Two enucleated eyes from two patients treated with intravitreal pegcetacoplan., Methods: Retrospective, multicenter consecutive clinical-pathologic analysis., Main Outcome Measures: Histopathologic review and immunophenotypic characterization., Results: Both patients presented with inflammation and significant vision loss nine days following the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient one at 4 months post-injection and patient two at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and variably the optic nerve, episclera, and muscle tendons composed of predominantly of T-cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, one eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve., Conclusion: Drug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication following pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings due to compensatory changes in the eyes over time (prior to enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as mechanism of initial injury., (Copyright © 2024. Published by Elsevier Inc.)

Particle tracking (PT) is a popular technique in microscopy, microfluidics and colloidal transport studies, where image analysis is used to reconstruct trajectories from bright spots in a video. The performance of many PT algorithms has been rigorously tested for directed and Brownian motion in open media. However, PT is frequently used to track particles in porous media where complex geometries and viscous flows generate particles with high velocity variability over time. Here, we present an evaluation of four PT algorithms for a simulated dispersion of particles in porous media across a range of particle speeds and densities. Of special note, we introduce a new velocity-based PT linking algorithm (V-TrackMat) that achieves high accuracy relative to the other PT algorithms. Our findings underscore that traditional statistics, which revolve around detection and linking proficiency, fall short in providing a holistic comparison of PT codes because they tend to underpenalize aggressive linking techniques. We further elucidate that all codes analyzed show a decrease in performance due to high speeds, particle densities, and trajectory noise. However, linking algorithms designed to harness velocity data show superior performance, especially in the case of high-speed advective motion. Lastly, we emphasize how PT error can influence transport analysis., (© 2024. The Author(s).)