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Suresh Kumar Srinivasamurthy,1 Raghavendra Bhat,2 Abdalla Hamid Mohammed Omer Eladil2 1Department of Pharmacology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates; 2Department of Internal Medicine, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab EmiratesCorrespondence: Raghavendra Bhat, Professor of Internal Medicine and Chairperson, Department of Clinical Skills, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates, Email raghavendra@rakmhsu.ac.aeIntroduction: The post-pandemic era ignited the concepts of virtual learning, enhancing a strong need for a specific clinical case manual of commonly encountered scenarios in internal medicine. In this article, we describe the process for creating a clinical cases manual which can be followed for any other clinical science. Further, we report the participatory experience of students in the co-creation of manual.Methods: The hand-written notes of the teacher during the rotation of internal medicine were improvised, and created into a digital version. The editorial team which included mainly student volunteers participated in digitization and reviewing the content, diagrams and flowcharts. We describe the process of designing the clinical-cases manual for rotations in internal medicine, which includes handwritten notes, review of the notes, formation of editorial team, digitization of text and artwork, editing and book release. It can be replicated for any other clinical sciences in rotations. In addition, the online survey with both quantitative and qualitative type of questions was used to assess the students’ participatory experiences in co-creating manual.Results: The clinical-cases manual for rotations in internal medicine was released and received well. The online survey responses revealed that the participating students benefited in terms of professional and personal development. There was an inter-item statistical difference implying that all the participants were agreeing or strongly agreeing to survey questions. All participants agreed on the usefulness of the manual. The main themes identified through qualitative analysis were technical skills acquisition, lifelong learning and teaching, self-assessment, discipline, time management, teamwork and communication skills.Conclusion: The creation of a clinical case manual for rotation, specific to the local needs can be done through a systematic process, that can be enriched by involving students. Encouraging the participation of students in co-creation is an important academic exercise that contributes to professional and personal development.Keywords: clinical rotations, co-creation, students’ role, clinical learning, internal medicine teaching, internal medicine rotations

Timely access to healthcare is crucial in order to maintain a high standard of living. However, obtaining medical consultations can be difficult, especially for those living in remote areas or during a pandemic when face-to-face consultations are not always possible. The ability to accurately diagnose diseases is essential for effective treatment, and recent technological advancements offer a potential solution. Machine learning (ML) and Natural language processing (NLP) enables computer programs to understand human language and extract desired features from responses, allowing for human-like interaction with users. By leveraging these technologies, healthcare professionals can potentially provide more accessible and efficient medical consultations to individuals, regardless of their location. The concept is to establish an online platform where users can ask medical-related queries and receive responses from both medical professionals and fellow users. The platform would feature a Medical Chatbot, which employs advanced ML techniques to analyze user-provided symptoms and provide initial disease diagnosis and related information prior to consulting with a doctor. This disease prediction chatbot interacts dynamically with the users to enter the symptoms of the diseases and based on syntactic and semantic similarity response is given. In this work the threshold of similarity score is kept of 0.7. KNearest neighbors, Random forest, Support vector machine, Naive bayes and Logistic regression algorithms are used for prediction of disease based on symptoms which are faced by users. The syntactic similarity, fuzzy string matching and semantic similarity using all-MiniLM-L6-v2 model is used to improve the efficiency of the result. [ABSTRACT FROM AUTHOR]

Perennial plantation crops, such as coconut trees require the systematic addition of nutrients for sustained growth and productivity. This study aimed to understand plant and soil nutrient dynamics, root health and soil biological properties upon addition of specific nutrients in tropical land use systems. Field experiments in randomised block design were conducted in Agro-Ecological Unit-3 (AEU-3) and Agro-Ecological Unit-9 (AEU-9) from 2014 to 2020. Treatments were T1 (site-specific nutrient management practices (SSNM), T2 (SSNM without sodium chloride); T3 (SSNM without gypsum); T4 (SSNM along with the 50 g microbial formulation Kera Probio); T5 (Farming practice without any amendments or nutrients). Root health parameters, cumulative nut yield and nutrient dynamics in soil and leaf samples were estimated at the beginning and the end of the study. Systematic provision of all the essential nutrients resulted in significant increase content of N (1.39%), P (0.164%), K (1.71%), Ca (0.406%) and Mg (0.175%) in index leaves of coconut trees in sandy soils. Foliar nutrient levels of coconut trees grown in laterite soils were 1.21% N, 0.142% P, 1.27% K, 0.504% Ca and 0.146% Mg. In AEU-3, treatment that received all amendments and nutrients showed highest organic carbon content at the three depths as 6.79 g kg-1soil, 5.39 g kg-1 soil and 3.82 g kg-1,soil, respectively. In AEU-3, 61% increase in yield was observed, while in AEU-9,40% increase was recorded. Application of gypsum resulted in downward displacement of K and Mg indicating that gypsum is required for the amelioration of sub soil acidity in sandy soils. However, the displacement effect was less pronounced in laterite soils and beneficial effect of gypsum was evident with the enhancement of exchangeable Ca. Hence sandy soils require application of inputs as per T3 (T1 without gypsum), with external organic inputs and palm residues whereas in laterite soils application of treatments as per T1 is required with in situ palm residue recycling. [ABSTRACT FROM AUTHOR]

AbstractThis study proposes a novel therapeutic model for cancer treatment with radiation therapy by analyzing the interactions among cancer, immune and healthy cells through a system of three ordinary differential equations. In this model, the natural influx rate of mature immune cells is assumed constant and is denoted by, a. The overall effect of radiation therapy on cancer cells is represented by a parameter, s; which is the surviving fraction of cells as determined by the Linear Quadratic (LQ) model. Conditions for the stability of equilibria in the interaction model modified to include the surviving fraction, are systematically established in terms of the dose and model parameters. Numerical simulations are performed in Wolfram MATHEMATICA software, investigating a spectrum of initial cell population values irradiated with 60Co γ-ray Low-LET radiation and High-LET 165 keV/μm Ni-ion radiation to facilitate improved visualization and in-depth analysis. By analyzing the model, this study identifies threshold values for the absorbed dose D for particular values of the model and radiation parameters for both High Linear Energy Transfer (high-LET) and Low Linear Energy Transfer (low-LET) radiations that ensure either eradication or minimization of cancer cells from a patient’s body, providing valuable insights for designing effective cancer treatments. [ABSTRACT FROM AUTHOR]

Kyasanur forest disease (KFD) is an endemic flaviviral hemorrhagic fever in south India. We report seven cases of oral candidiasis in patients from Karnataka, India, who presented in March and April 2024 with the first phase of KFD. Except for lymphopenia, no other risk factors for oral candidiasis were identified in these patients. All patients were managed with antifungals and did well at the 28-day follow-up. We report this case series to highlight the possibility of transient immunosuppression and the occurrence of opportunistic infections in flaviviral infections such as KFD.

In homoeostasis, the shape and sessility of untransformed epithelial cells are intricately linked together. Variations of this relationship in migrating cancer cells as they encounter different microenvironments are as yet ill-understood. Here, we explore the interdependency of such traits in two morphologically distinct invasive ovarian cancer cell lines (OVCAR-3 and SK-OV-3) under mechanically variant contexts. We first established a metric toolkit that assessed traits associated with cell motion and shape, and rigorously measured their dynamical variation across trajectories of migration using a Shannon entropic distribution. Two stiffness conditions on polymerized Collagen I with Young's moduli of 0.5 kPa (soft) and 20 kPa (stiff) were chosen. Both the epithelioid OVCAR-3 and mesenchymal SK-OV-3 cells on soft substrata exhibited slow and undirected migration. On stiff substrata, SK-OV-3 showed faster persistent directed motion. Surprisingly, OVCAR-3 cells on stiffer substrata moved even faster than SK-OV-3 cells but showed a distinct angular motion. The polarity of SK-OV-3 cells on stiff substrata was well-correlated with their movement, whereas for OVCAR-3, we observed an unusual 'slip' behavior, wherein the axes of cell shape and movement were poorly correlated. While SK-OV-3 and OVCAR-3 showed greater mean deformation on stiffer substrata, the latter was anti-correlated with variation in angular motion or the mean deviation between shape and motility axis for SK-OV-3 but poorly correlated for OVCAR-3. Moreover, on softer substrata OVCAR-3 and SK-OV-3 were relatively rigid but showed greater shape variation (with OVCAR-3 showing a higher fold change) on stiffer substrata. Our findings suggest that greater deformability on stiffer milieu allow epithelioid cells to overcome constraints on the congruence in axis of shape and motion seen for mesenchymal cells and display distinct motile behaviors across this phenotypic spectrum., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Objective: Women with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or Caribbean women not affected by SCD and whether there were differences between SCD individuals with the haemoglobin SS (HbSS) or haemoglobin SC (HbSC) genotypes. Furthermore, we wished to determine if any differences related to deprivation., Design: A matched cohort study., Setting: Tertiary perinatal centre in London PATIENTS: 4964 African or Caribbean women without SCD and 148 with SCD., Main Outcome Measures: Mode of delivery, maternal exchange transfusion, birthweight, neonatal unit admission, neonatal death and deprivation indices RESULTS: SCD women were more likely to be delivered by caesarean section (p<0.001) and had babies of lower birthweight (p<0.001). Their infants were no more likely to be admitted to neonatal intensive care unit or suffer a neonatal death. There were no significant differences between the SCD women and those without SCD in their deprivation index or deprivation decile. The women with the HbSS genotype compared to those with the HbSC genotype were more anaemic (p<0.02), required more exchange transfusions (p<0.001) and were more likely to be delivered by caesarean section (p=0.008). The infant outcomes did not differ significantly between the genotypes., Conclusions: Although, the SCD women, particularly those with the HbSS genotype, had greater morbidity, infant morbidity, and mortality was similar in mothers with the HbSS or HbSC genotypes and those without SCD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The downstream processability of Hot Melt Extrusion (HME) Amorphous Solid Dispersions (ASD), an underexplored topic of importance, was assessed through a multi-faceted particle engineering approach. Extrudates, comprised of griseofulvin (GF), a model poorly water-soluble drug, and hydroxypropyl cellulose (HPC), were prepared at four drug concentrations and three HME temperature profiles to yield cases with and without residual crystallinity and subsequently milled to five sieve cuts ranging from < 45 μm to 355 - 500 μm. Solid state characterization was performed with XRPD, FT-IR, and TGA. Particle scale properties of the milled extrudates were evaluated including particle size, density, surface energy, and morphologies imaged via SEM. It was observed that regardless of sieve cut size, drug concentration and HME conditions impacted the flowability trends, quantified via Flow Function Coefficient (FFC) and bulk density. As a novelty, the effects of various process parameters and drug loadings were consolidated into a dimensionless interparticle cohesion measure, granular Bond Number (Bo g ), to better correlate them with bulk powder properties. The significant contrast in particle morphologies, particle size, and densities among selected cases demonstrated that particle size alone should not be the sole consideration when correlating particle scale to bulk powder scale properties of milled extrudates. Instead, the HME temperature profile and ASD drug loading may be more suitable parameters affecting the bulk powder properties of the milled extrudates., 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.)

The crowded milieu of a biological cell significantly impacts protein aggregation and interactions. Understanding the effects of macromolecular crowding on the aggregation and fibrillation of amyloidogenic proteins is crucial for the treatment of many amyloid-related disorders. Most in vitro studies of protein amyloid formation and its inhibition by small molecules are conducted in dilute buffers, which do not mimic the complexity of the cellular environment. In this study, we used PEGs to simulate macromolecular crowding and examined the inhibitory effects of flavones DHF, baicalein, and luteolin on human lysozyme (HuL) aggregation at pH 2. Naturally occurring flavones have been effective inhibitors of amyloid formation in some proteins. Our findings indicate that while flavones inhibit HuL aggregation and fibrillation in dilute buffer solutions, complete inhibition is observed with a combination of flavones and PEGs, as shown by ThT fluorescence, light scattering, TEM, and AFM studies. The species formed in the presence of PEG 8000 and flavones were less hydrophobic, less toxic, and α-helix-rich compared to control samples, which were hydrophobic and β-sheet-rich, as demonstrated by ANS hydrophobicity, MTT assay, and CD spectroscopy. Fluorescence titration studies of flavones with HuL showed a significant increase in binding constant values under crowding conditions. These findings highlight the importance of macromolecular crowding in modulating protein aggregation and amyloid inhibition. Further studies using disease-causing mutants of HuL and other amyloidogenic proteins are needed to explore the role of macromolecular crowding in small-molecule-mediated modulation and inhibition of protein aggregation and amyloid formation.

Acute febrile illnesses (AFI) such as dengue, leptospirosis, and scrub typhus start with fever, but some patients can deteriorate rapidly. Identifying these patients at risk is necessary to ensure early referral. The study's objective was to assess the utility of serum adrenomedullin (ADM) as a biomarker in predicting outcomes in adult AFI patients presenting to the emergency department (ED). In this prospective observational study, all consecutive patients admitted with AFI through the ED between June 2023 and February 2024 were assessed for eligibility. Clinical and laboratory findings were noted. The serum samples sent routinely for biochemical tests were used to calculate ADM levels at admission and 48 hours later (whenever possible). Clinically relevant outcome variables were collected for all patients. The utility of ADM in predicting 7-day mortality was evaluated for primary outcome analysis using a stepwise binary logistic regression. A total of 181 patients were recruited, with dengue (n = 91, 50%) being the most common diagnosis. The median sequential organ failure assessment score at admission was 5 (IQR: 3-10). The 7-day mortality was 26 (14%, 95% CI: 9.3-19.5). The median admission ADM levels and difference in ADM levels at 48 hours were significantly higher in those who died by day 7. Adrenomedullin levels at admission were found to be an independent predictor of 7-day mortality (adjusted odds ratio: 1.002, 95% CI: 1.001-1.004, P = 0.005). High ADM levels can be used for early referral in patients with tropical AFI. There is a need to explore the utility of antibodies targeting ADM in clinical studies.

Background: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications., Methods: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications., Results: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported., Conclusions: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively., Levels of Evidence: Level II, retrospective study., Competing Interests: Conflicts of interest None of the authors have financial disclosures related to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings., Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment., Results: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings., Conclusions: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities., Trial Registration: NCT05714644., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Folasade P. May: Exact Sciences: Advisory Board Sapna Syngal: inventor of the PREMM model (the intellectual property of which is owned by Dana-Farber Cancer Institute); research funding by Exact Sciences, Biological Dynamics, Inc.; consultant for Natera, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Septic melioidosis is associated with high mortality in resource-limited settings. The current study aims to find 28-d all-cause mortality predictors within 24 h of admission in melioidosis patients presenting to an emergency department., Methods: This retrospective cohort study (2018-2022) included melioidosis patients divided into two groups based on their primary outcomes (28-d mortality). All the clinically relevant factors significant in univariate analysis were selected for binary logistic regression analysis. Those factors significant in logistic regression analysis were considered independent predictors of mortality., Results: Of the 53 patients with melioidosis, the 28-d mortality of melioidosis patients admitted to the emergency department was 51% (n=27). Respiratory involvement, renal dysfunction, haemodynamic instability, elevated aspartate transaminase, elevated activated partial thromboplastin time, elevated CRP, elevated procalcitonin, decreased albumin, decreased absolute neutrophil count, decreased absolute lymphocyte count and use of piperacillin-tazobactam or azithromycin were significant predictors of mortality on univariate analysis. Vasopressor requirement (p=0.03) and low serum albumin level (0.041) at presentation were independent predictors of mortality., Conclusion: Vasopressor requirement and low albumin levels at presentation in the emergency department are independent predictors of mortality. There is a need to create awareness among primary care physicians to enable early diagnosis and prompt initiation of treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Few studies have prospectively evaluated the incidence and outcomes in children with provoked venous thromboembolism (VTE) and transient or persistent antiphospholipid antibodies (aPL). We compared outcomes of patients <21 years old with a first-episode acute provoked VTE and positive aPL at diagnosis enrolled in the Kids-DOTT trial. aPL were tested at enrollment and, when positive, repeated at 6 weeks post-VTE. Subsequent testing was performed at discretion of the treating hematologist. Of 524 patients, 116 (22%) had positive aPL at enrollment. At follow-up, 70 (60%) had transient (n=66) or low titer aPL (n=4), 11 (10%) had persistent aPL meeting criteria for antiphospholipid syndrome (APS), and 35 (30%) had no repeat testing. Patients with APS were older (15.8 vs. 9.9 years, p=.014), and had a statistically significant higher risk of symptomatic recurrent VTE (18% vs. 1%, OR: 12.2 [1.4 - 108], p= .025), and a statistically non-significant but clinically meaningful difference in the risk of anticoagulant-related clinically-relevant bleeding (9% vs. 0%, OR: 20.1 [0.7 - 558], p=0.077) compared to those in the transient or low titer aPL group. In conclusion, aPL are common in young patients with acute provoked VTE and are mostly transitory and clinically insignificant. Patients with APS and provoked VTE appear to have an increased risk of recurrent VTE compared to patients with transitory or low titer aPL. Future collaborative studies should investigate the optimal VTE management of children with provoked VTE who meet criteria for APS., (Copyright © 2024 American Society of Hematology.)

Objectives . The role of race in late preterm respiratory morbidity has not been adequately described. We aimed to determine whether neonatal respiratory morbidity differs between Black and White late preterm infants. Methods . Single-centre retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK of infants born at 34 to <37 weeks of gestational age. The incidence of invasive ventilation was used as the main outcome. Results . In the study period 354 Black and 673 White late preterm infants were admitted. Black, compared to white infants, had a lower incidence of invasive ventilation (19% vs 27%, P  < .001) and a lower incidence of non-invasive ventilation (22% vs 34%, P  < .001). Black infants had a shorter duration and cost of stay compared to White infants ( P  = .011 and <0.001 respectively). Conclusion . Black late preterm infants needed less frequently invasive and non-invasive ventilation and had a shorter duration and cost of stay compared to White late preterm infants., 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) 2024.)

Objectives: To assess the impact of oral dextrose gel (ODG) treatment on NICU admission rates for hypoglycemic infants in a well-baby nursery., Study Design: We retrospectively compared newborn infants at risk for hypoglycemia born during the intervention period (n = 3775) with historical controls (n = 655). We also compared the rates of the primary outcome (NICU admission) and secondary outcomes (exclusive breastfeeding and hospital costs) between the two periods., Results: Following the implementation of ODG supplementation, the NICU admissions rates dropped from 4% to 2%, p < 0.05, for at-risk infants and from 15% to 7%, p < 0.05, for hypoglycemic infants in the baseline and intervention periods, respectively, with an adjusted OR (95% CI) of 0.39 (0.24-0.64), p < 0.001. Additionally, the ODG protocol sustained rates of exclusive breastfeeding in contrast to the institutional protocol., Conclusion: The adoption of an ODG protocol fosters a more nurturing and baby-friendly environment through reduced NICU transfers, support for exclusive breastfeeding, and decreased hospital costs., (© 2024. The Author(s).)

Generalised pustular psoriasis (GPP) is a chronic, multisystemic, autoinflammatory disease with predominantly cutaneous manifestations, characterised by recurrent episodes of widespread, macroscopic and aseptic pustules. It has a highly unpredictable, heterogeneous and unstable clinical course. There are no consensus guidelines in India for the management of GPP. The objective of this Delphi panel study was to achieve consensus on problem areas in the understanding and management of GPP. Based on the inputs from an expert panel, 19 topics across six domains were identified as being important regarding the understanding and management of GPP. Statements were developed for these 19 topics, and consensus for the statements was sought using the modified Delphi method. Twelve experts evaluated the statements, indicating their agreement or disagreement. Consensus was considered to be reached when ≥80% of experts agreed with a statement. After two rounds of discussion, consensus was reached for 17 out of 19 (89%) statements and no consensus was achieved for two (11%) statements. We have presented the statements along with the respective degrees of consensus. Wherever relevant, clarifications or additional comments by experts are provided in the document.

The terminology "Financially Palliative" is a pseudonym and refers to a unique challenge faced in countries where public healthcare insurance coverage is not robust and the percentage of out-of-pocket health expenditure continues to be high. Emergency and critical care healthcare expenditures in such circumstances usually pose additional burden as they are unforeseen expenses, disproportionately high, for which most people are unprepared. Such situations may lead into a vicious cycle that initiates with expenditure hesitancy and delay in definitive care, which in turn leads to deterioration in the patient's condition and delay-related complications. This further fuels expenditure hesitancy due to uncertain prognosis and outcomes. The future threats posed by this issue are manifold, which are not only restricted to poor patient outcomes and diminishing physician morale but also hinder progress in science by influencing research outcomes/endpoints in areas where it is highly prevalent. Identifying and defining the problem with terminology is only the first step in working towards solutions. The issue needs to be addressed and mitigated before it spreads its roots deeper into our healthcare system., How to Cite This Article: Bhat R, Ramaswami A. "Financially Palliative": The Need to Address a Perplexing Financial Conundrum in Emergency and Critical Care. Indian J Crit Care Med 2024;28(9):820-822., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Introduction: To evaluate the impact of the updated United States Preventive Services Task Force colorectal cancer (CRC) screening recommendations on screening rates in a large health system., Methods: We reviewed Massachusetts General Brigham electronic health record data for individuals eligible for CRC screening between January 3, 2020, and January 5, 2023, and calculated whether age-eligible individuals were up-to-date with CRC screening., Results: There were large declines in the percentage of individuals who were up-to-date with CRC screening for all racial/ethnic groups, with non-Hispanic Asians being largest (-13.5%)., Discussion: Health systems should implement culturally tailored strategies to reach and screen newly eligible individuals for CRC screening to prevent worsening disparities in CRC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia., Methods: Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia-Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory., Results: Data from 271 dermatologists were included for analysis. About one-third (31.7%) reported that they referred to the Hanifin and Rajka criteria during diagnosis. The majority of dermatologists used clinical impression when assessing AD severity and treatment response. Reduction of eczema and pruritus was the primary treatment objective when managing both acute (98.1%) and chronic (69.1%) AD. More than half of dermatologists preferred adding systemic anti-inflammatory medication for patients who did not respond to maximized topical treatment, while 43.6% would switch to another systemic medication for those failing to respond to maximized systemic treatment. Topical corticosteroids were frequently selected by dermatologists. For systemic therapies, oral corticosteroids were most frequently used, followed by cyclosporin and dupilumab. Narrow-band ultraviolet B was the most common phototherapy reported (84.9%). There was considerable variation in estimated average and maximum durations of therapies used to treat AD., Conclusion: This study has provided insights on the real-world management of moderate-to-severe AD in the Asia-Pacific region. The diverse approaches in diagnosis and treatment highlight the multifactorial nature of AD, reliance on clinical judgement, and importance of personalized care. To improve outcomes in patients with AD, it will be crucial to develop biomarkers for diagnosis, reduce subjectivity in assessment, as well as promote access to newer and effective therapies., (© 2024. The Author(s).)

Objectives: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants., Design: A 3-round Delphi study., Setting and Participants: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries., Methods: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms., Results: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth., Conclusions and Implications: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs., Competing Interests: Disclosure B.E.M. is supported by a postgraduate research scholarship funded by Monash University. A.J.C. is supported by an NHMRC Emerging Leadership 1 grant (APP2009633). C.M.B. is supported by a National Institute on Aging Grant (R24AG064025). A.J.C. has received grant funding or consulting funds from the Medical Research Future Fund and Pharmaceutical Society of Australia. J.S.B. has received grant funding or consulting funds from the National Health and Medical Research Council (NHMRC), Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution. M.A.S. receives royalties from UpToDate and honoraria from the American Geriatrics Society. All other co-authors have no real or perceived conflicts of interest to declare., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. All rights reserved.)

Introduction: The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs., Methods: Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory., Results: Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2%) and oral steroids (58.7%) were frequently prescribed to manage AD. Common atopic comorbidities were allergic urticaria (64.2%), allergic rhinitis (61.8%), and allergic conjunctivitis (51.5%). Median DLQI score was 13.0 (IQR 11.0), while median EQ-5D-5L (based on China value set) score was 0.8 (IQR 0.4); 87.2% and 77.2% of patients reported pain/discomfort and anxiety/depression on the EQ-5D-5L domains, respectively. Median total annual costs associated with AD were USD 10,128.52 (IQR 12,963.26) per patient, with indirect costs being the largest component. Findings from WPAI indicated that presenteeism is a major contributor to productivity loss., Conclusion: This multinational survey study showed that AD is associated with substantial QoL impairment and economic burden among Asian adult patients with moderate-to-severe AD. To alleviate burden of AD, clinicians should be more proactive in managing other concomitant conditions including psychological issues, and advocate for increased reimbursement for AD treatments., (© 2024. The Author(s).)

Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA-5 Ab) is associated with amyopathic dermatomyositis (DM). These patients are particularly at high-risk for developing acute and rapidly progressive interstitial lung disease (ILD). Given the lack of muscle-related symptoms, along with its sudden onset and rapid clinical progression, the diagnosis of anti-MDA-5 Ab + ILD represents a challenge for clinicians. Even after the diagnosis is established, prognosis remains dismal owing to a hyperinflammatory state, mimicking cytokine storm, commonly refractory to potent immunosuppressive therapy. Hence, we present an elderly African American man who developed acute and rapidly progressive ILD in the setting of positive anti-MDA5 Ab, in whom lung histopathology was consistent with organizing phase of diffuse alveolar damage. Despite receiving combined immunosuppression with corticosteroids, cyclosporine, and cyclophosphamide, he developed irreversible lung injury within a month and was eventually referred for lung transplant evaluation., 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.

Direct sound printing (DSP), an alternative additive manufacturing process driven by sonochemical polymerization, has traditionally been confined to a single acoustic focal region, resulting in a voxel-by-voxel printing approach. To overcome this limitation, we introduce holographic direct sound printing (HDSP), where acoustic holograms, storing cross-sectional images of the desired parts, pattern acoustic waves to induce regional cavitation bubbles and on-demand regional polymerization. HDSP outperforms DSP in terms of printing speed by one order of magnitude and yields layerless printed structures. In our HDSP implementation, the hologram remains stationary while the printing platform moves along a three-dimensional path using a robotic arm. We present sono-chemiluminescence and high-speed imaging experiments to thoroughly investigate HDSP and demonstrate its versatility in applications such as remote ex-vivo in-body printing and complex robot trajectory planning. We showcase multi-object and multi-material printing and provide a comprehensive process characterization, including the effects of hologram design and manufacturing on the HDSP process, polymerization progression tracking, porosity tuning, and robotic trajectory computation. Our HDSP method establishes the integration of acoustic holography in DSP and related applications., (© 2024. The Author(s).)

This comprehensive review deals with the multifaceted aspects of electronic cigarettes (e-cigarettes), examining their composition, health implications, regulatory challenges, and market dynamics. E-cigarettes, also known as vaping devices, function by warming a solution of liquid containing flavors, nicotine, and various other compounds to produce an aerosol for users to inhale. This review underscores the evolution and widespread adoption of e-cigarettes since their introduction in 2003, highlighting their appeal as alternatives to traditional tobacco smoking. The essential parts of e-cigarettes are the battery, heating element, e-liquid (or e-juice), and mouthpiece. Propylene glycol and vegetable glycerin are common ingredients in e-liquids, along with nicotine and other flavors. Concerns over the health impacts of e-cigarettes have grown, particularly in light of incidents like the e-cigarette or vaping-associated lung injury outbreak in 2019 linked to vaping-associated lung injuries. Evidence suggests that while e-cigarettes may pose fewer risks than conventional cigarettes, they are not without health consequences, including potential respiratory and cardiovascular effects. Regulatory efforts worldwide have struggled to keep pace with the rapid evolution of e-cigarettes, exacerbated by their diverse flavors and marketing strategies that appeal to youth. The review discusses global regulatory responses, including bans and restrictions, to curb youth uptake and address public health concerns. Furthermore, the rise of a black market for e-cigarettes poses additional challenges to effective regulation and tobacco control efforts. In conclusion, while e-cigarettes offer potential harm reduction benefits for adult smokers seeking alternatives to traditional tobacco products, their widespread availability and evolving landscape necessitate vigilant regulatory oversight to protect public health, especially among youth. Future research should continue to explore the long-term health impacts and efficacy of e-cigarettes as smoking elimination aids, informing evidence-based policies and interventions., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ghuman et al.)

Hsp90 is a molecular chaperone that acts on its clients through an ATP-dependent and conformationally dynamic functional cycle. The cochaperone Accelerator of Hsp90 ATPase, or Ahsa1, is the most potent stimulator of Hsp90 ATPase activity. Ahsa1 stimulates the rate of Hsp90 ATPase activity through a conserved motif, NxNNWHW. Metazoan Ahsa1, but not yeast, possesses an additional 20 amino acid peptide preceding the NxNNWHW motif that we have called the intrinsic chaperone domain (ICD). The ICD of Ahsa1 diminishes Hsp90 ATPase stimulation by interfering with the function of the NxNNWHW motif. Furthermore, the NxNNWHW modulates Hsp90's apparent affinity to Ahsa1 and ATP. Lastly, the ICD controls the regulated recruitment of Hsp90 in cells and its deletion results in the loss of interaction with Hsp90 and the glucocorticoid receptor. This work provides clues to how Ahsa1 conserved regions modulate Hsp90 kinetics and how they may be coupled to client folding status., (© 2024. The Author(s).)

Introduction: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia., Methods: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Patients and dermatologists completed separate surveys designed to elicit their expectations regarding AD management, and their perceived level of patient-clinician communication. Patients were also asked about their treatment satisfaction and whether they prefer additional treatment beyond what was prescribed. Demographic information and responses were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory, and all participants provided informed consent., Results: A total of 1103 patients and 271 dermatologists completed the surveys. Both patients and dermatologists were largely aligned in their top treatment goals in AD management. However, greater proportions of patients prioritized the prevention of exacerbation (78.0% versus 47.2%), minimization of treatment adverse effects (46.4% versus 9.1%), and improvement in mental health (16.0% versus 4.9%), compared with dermatologists. Although patient-clinician communication was observed to be generally good, 10.9% of patients reported dissatisfaction with communication in AD management. The majority of patients were either "very satisfied" or "satisfied" with their latest acute AD treatment, but 65.5% of patients still desired additional treatment., Conclusions: This multinational study has provided insights on the perspectives of Asian patients and dermatologists in treatment goals, AD management, and communication. In general, both patients and dermatologists were aligned in treatment goals and there was satisfactory patient-clinician communication in most aspects. However, potential areas of improvement have been identified to further enhance patient-centered care., (© 2024. The Author(s).)

Aim: The aim of our study was to explore the effect of nomination-based social-media campaign and CPR-skill-booth on change in knowledge as well as hands-only CPR skills among young adults., Methods: A quasi-experimental study was conducted in two non-healthcare-stream colleges, one intervention and other control arm. After baseline evaluation of CPR knowledge in both colleges, a 4-week nomination-based social media campaign '#CPR challenge' was rolled out in the intervention arm which included a CPR-skill-booth that was setup for one hour every day to train interested participants in CPR. The participants were encouraged to share the same on their social media handles and data of self-reported metrics were collected. A post-intervention assessment was conducted in both arms, to assess knowledge and its translation to hands-only-CPR skills using qCPR mannequin and qCPR app® for objective assessment., Results: A total of 690 assessments were done; Intervention arm (pre-intervention-214, post intervention -155) and control arm (pre-intervention -157, post-intervention -134). The baseline knowledge scores were comparable in both groups. Knowledge score doubled in the intervention arm, (p < 0.001) from a median value of 29% (IQR:14 - 43) in the pre-intervention-cohort to 57% (IQR:29 - 71) in the post-intervention-cohort. Median CPR-skill-score was higher in the intervention arm 67.5(IQR:39-92) in comparison to control arm 21 (IQR:1-53) (p < 0.001). In terms of social media engagement, 50% of participants had watched the videos and 40.6% attended the CPR-skill-booth., Conclusion: Strategies such as a nomination-based social media campaign can improve the awareness, knowledge and also skills regarding hand-only CPR., 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 Author(s).)

Background: We investigated the associations of micronutrients and lipids with prediabetes, glycemic parameters, and glycemic indices among the adolescent girls of the DERVAN (aDolescent and prEconception health peRspectiVe of Adult Non-communicable diseases) cohort study from rural India., Methods: We recruited 1,520 adolescent girls aged 16-18 years. We measured glycemic parameters (glucose, insulin and HbA 1 C), lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides), and micronutrients (vitamin B 12 , folate, and vitamin D). Prediabetes was defined using American Diabetes Association criteria (fasting glucose ≥100 mg/dL or HbA1C ≥5.7%). Glycemic indices (insulin resistance, insulin sensitivity, and β cell function) were calculated using the homeostasis model. Associations of prediabetes, glycemic parameters and glycemic indices with micronutrients and lipids were analyzed by multiple logistic regressions., Results: The median age and Body Mass Index (BMI) were 16.6 years and 17.6 kg/m 2 , respectively. Overall, 58% of girls had a low BMI. Median vitamin B 12 , folate, and vitamin D concentrations were 249.0 pg/mL, 6.1 ng/mL, and 14.2 ng/mL, respectively. The deficiencies observed were 32.1% for vitamin B 12 , 11.8% for folate, and 33.0% for vitamin D. Median total cholesterol, LDL, HDL, and triglyceride concentrations were 148.0 mg/dL, 81.5 mg/dL, 50.8 mg/dL, and 61.5 mg/dL, respectively. Elevated total cholesterol, LDL, and triglycerides were observed in 4.8, 4.0, and 3.8%, respectively, while low HDL was observed in 12.8%. Prediabetes was observed in 39.7% of the girls. Among lipids, total cholesterol and LDL were higher in girls with prediabetes ( p  < 0.01 for both). In a multivariate model containing cholesterol and vitamin B 12 /folate/vitamin D, prediabetes was associated with high cholesterol. Prediabetes was also associated with high LDL, independent of folate and vitamin D. Poor insulin secretion was high in those with low vitamin B 12 . Elevated insulin resistance was associated with low HDL. The likelihood of high insulin sensitivity was reduced in those with high triglycerides. The likelihood of poor β cell function was high in those with high LDL. Statistical interactions between micronutrients and lipids for prediabetes and glycemic outcomes were not significant., Conclusion: There was a substantial deficiency of micronutrients and an absence of dyslipidemia. Our results indicate the need for lipid and micronutrient-based interventions in adolescence to improve glycemic outcomes. Maintaining adequate storage of not only micronutrients but also lipids in adolescent girls is likely to reduce diabetes risk in adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Patil, Dervankar, Hardikar-Bhat, Joglekar, Bhat, Patil and Yadav.)

(1) Background: Preterm premature rupture of membranes (PPROM) has been associated with increased perinatal morbidity, but the effect of PPROM on respiratory disease has not been previously quantified. We hypothesised that PPROM would be associated with a higher incidence of invasive ventilation. (2) Methods: A retrospective cohort study at the Neonatal Unit at King's College Hospital NHS Foundation Trust, London, UK, was conducted on infants born before 37 weeks of gestation. PPROM was defined as the rupture of membranes for >48 h. (3) Results: We reviewed 1901 infants (434 with PPROM) with a median (IQR) gestational age of 32.4 (28.7-35.0) weeks. The median (IQR) duration of rupture of membranes in the infants with PPROM was 129 (78-293) h. The incidence of invasive ventilation was 56% in the infants with PPROM and 46% in the infants without PPROM ( p < 0.001). Following regression analysis, PPROM was significantly related to a higher incidence of invasive ventilation (odds ratio: 1.48; 95% CI: 1.13-1.92, adjusted p = 0.004) after adjusting for birth weight [odds ratio = 0.34; 95% CI: 0.33-0.43, adjusted p < 0.001], Apgar score at 10 min [odds ratio =0.61; 95% CI: 0.56-0.66, adjusted p < 0.001] and antenatal corticosteroid use (adjusted p = 0.939). (4) Conclusions: PPROM was associated with a 1.48-fold higher risk of needing invasive ventilation.

In this study, the use of an Unscented Kalman Filter as an indicator in predictive current control (PCC) for a wind energy conversion system (WECS) that employs a permanent magnetic synchronous generator (PMSG) and a superconducting magnetic energy storage (SMES) system connected to the main power grid is presented. The suggested UKF indication in the hybrid WECS-SMES arrangement is in charge of estimating vital metrics such as stator currents, electromagnetic torque, rotor angle, and rotor angular speed. To optimize control strategies, PCCs use these projected properties rather than direct observations. To control the unpredictable wind energy's nature, SMES must be regulated to minimize fluctuations in the DC-link voltage and power output to the main grid. Fractional order-PI (FOPI) controllers are used in a novel control structure for the SMES system to regulate the output power and DC-link voltage. An artificial bee colony optimization approach is employed to optimize the FOPI controllers. Three commonly utilized indicators, including sliding-mode, EKF, and Luenberger, were evaluated using "MATLAB" to evaluate the performance of the UKF estimate. Assessment criteria such as mean absolute percentage error and root mean squared error were used to gauge the accuracy of the estimates. Simulation findings showed the efficiency of fractional order-PI controllers for SMES and the proposed UKF indication for predictive current control, especially in the presence of measurement noise and over a variety of wind speeds. An improvement in estimation accuracy of up to 99.9 % was demonstrated by the UKF indicator. Moreover, the stability of the suggested UKF-based PCC control for the hybrid WECS-SMES combination was confirmed using Lyapunov stability criteria.", 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 Published by Elsevier Ltd.)

With the rising prevalence of diabetes and its association with cognitive impairment, interest in the use of dietary alkaloids and other natural products has grown significantly. Understanding how these compounds manage diabetic cognitive dysfunction (DCD) is crucial. This comprehensive review explores the etiology of DCD and the effects of alkaloids in foods and dietary supplements that have been investigated as DCD therapies. Data on how dietary alkaloids like berberine, trigonelline, caffeine, capsaicin, 1-deoxynojirimycin, nuciferine, neferine, aegeline, tetramethylpyrazine, piperine, and others regulate cognition in diabetic disorders were collected from PubMed, Research Gate, Web of Science, Science Direct, and other relevant databases. Dietary alkaloids could improve memory in behavioral models and modulate the mechanisms underlying the cognitive benefits of these compounds, including their effects on glucose metabolism, gut microbiota, vasculopathy, neuroinflammation, and oxidative stress. Evidence suggests that dietary alkaloids hold promise for improving cognition in diabetic patients and could open exciting avenues for future research in diabetes management., (© 2024 International Union of Biochemistry and Molecular Biology.)

Sellar-suprasellar masses, with diverse origins ranging from infiltrative to neoplastic processes, are frequently encountered in endocrinology clinics. Evaluation involves a detailed history, hormone analysis, and imaging of the hypothalamic-pituitary axis. However, overlapping hormonal and imaging features can complicate diagnosis, often necessitating confirmation through tissue biopsy. Pituicytoma, a rare sellar tumor mimicking other masses biochemically and radiologically, exemplifies this challenge. These are benign intracranial neoplasms with characteristic bipolar spindle-shaped astrocytic cells organized in fascicular or storiform patterns with specific immunohistochemistry. The current case is of an elderly postmenopausal woman with a history of hypertension who presented with recurrent headaches and transient vision loss in the left eye. Imaging studies revealed a suprasellar mass, which was biopsied and diagnosed on histopathological examination as a pituicytoma. This case highlights the importance of considering less common etiologies when encountering such presentations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bhat et al.)

Collective cell invasion (CCI), a canon of most invasive solid tumors, is an emergent property of the interactions between cancer cells and their surrounding extracellular matrix (ECM). However, tumor populations invariably consist of cells expressing variable levels of adhesive proteins that mediate such interactions, disallowing an intuitive understanding of how tumor invasiveness at a multicellular scale is influenced by spatial heterogeneity of cell-cell and cell-ECM adhesion. Here, we have used a Cellular Potts model-based multiscale computational framework that is constructed on the histopathological principles of glandular cancers. In earlier efforts on homogenous cancer cell populations, this framework revealed the relative ranges of interactions, including cell-cell and cell-ECM adhesion that drove collective, dispersed, and mixed multimodal invasion. Here, we constitute a tumor core of two separate cell subsets showing distinct intra- and inter-subset cell-cell or cell-ECM adhesion strengths. These two subsets of cells are arranged to varying extents of spatial intermingling, which we call the heterogeneity index (HI). We observe that low and high inter-subset cell adhesion favors invasion of high-HI and low-HI intermingled populations with distinct intra-subset cell-cell adhesion strengths, respectively. In addition, for explored values of cell-ECM adhesion strengths, populations with high HI values collectively invade better than those with lower HI values. We then asked how spatial invasion is regulated by progressively intermingled cellular subsets that are epithelial, i.e., showed high cell-cell but poor cell-ECM adhesion, and mesenchymal, i.e., with reversed adhesion strengths to the former. Here too, inter-subset adhesion plays an important role in contextualizing the proportionate relationship between HI and invasion. An exception to this relationship is seen for cases of heterogeneous cell-ECM adhesion where sub-maximal HI patterns with higher outer localization of cells with stronger ECM adhesion collectively invade better than their relatively higher-HI counterparts. Our simulations also reveal how adhesion heterogeneity qualifies collective invasion, when either cell-cell or cell-ECM adhesion type is varied but results in an invasive dispersion when both adhesion types are simultaneously altered., Competing Interests: Declaration of interests The authors do not declare any conflicts of interest., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Background: Pulpitis primarily arises from the pulp space infection by oral microbiota. Vital pulp therapy is a minimally invasive approach that relies on assessing the severity of pulpal inflammation to facilitate repair. However, the current evaluation methods prescribed by the American Association of Endodontics are subjective, leading to ambiguity in assessment. Therefore, this review aims to explore molecular strategies for evaluating the severity of pulpal inflammation to accurately predict the success of pulp vitality preservation in clinical settings., Methodology: This review was conducted by searching relevant keywords, such as irreversible pulpitis, pulpitis biomarkers, molecular diagnosis, inflammation, and genomic strategies, in databases such as PubMed, Web of Science, and Scopus to address the subjective nature of diagnosis. The data included in this review were collected up to April 2023. The literature search revealed well-documented limitations in clinically assessing the pulp inflammatory. Molecular approaches that aid in clinical differentiation between irreversible and reversible pulpitis may potentially enhance favorable outcomes in vital pulp therapy. Non-invasive diagnostic methods for pulpal assessment would also be valuable for determining whether the inflamed pulp is reversible, irreversible, or necrotic., Conclusion: The present review examines the various molecular diagnostic approaches that have revolutionized the medical field and are considered the most promising empirical methodologies for the proactive detection of pulpal diseases. It also provides comprehensive insights into the current diagnostic methods, associated challenges, next-generation strategies, and future directions for diagnosing the severity of pulp inflammation., Competing Interests: Declaration of competing interest Revolutionizing the diagnosis of Irreversible Pulpitis – Current Strategies and Future Directions, All authors are required to disclose any COI within the period of 12 months prior to the submission of any manuscript in the subject matter of which any company, entity, or organization has an interest. - Nil, The corresponding author is required to complete this form with information from all the authors listed in the manuscript., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity of underlying molecular processes in the kidney thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within kidney disease drivers we analyzed publicly available transcriptomic data from kidney biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network machine-learning algorithm was used to stratify a total of 369 patients with CKD and 46 living kidney donors as healthy controls. Unbiased stratification of the discovery cohort resulted in identification of four novel molecular categories of disease termed CKD-Blue, CKD-Gold, CKD-Olive, CKD-Plum that were replicated in independent CKD and diabetic kidney disease datasets and can be further tested on any external data at kidneyclass.org. Each molecular category spanned across CKD stages and histopathological diagnoses and represented transcriptional activation of distinct biological pathways. Disease progression rates were highly significantly different between the molecular categories. CKD-Gold displayed rapid progression, with significant eGFR-adjusted Cox regression hazard ratio of 5.6 [1.01-31.3] for kidney failure and hazard ratio of 4.7 [1.3-16.5] for composite of kidney failure or a 40% or more eGFR decline. Urine proteomics revealed distinct patterns between the molecular categories, and a 25-protein signature was identified to distinguish CKD-Gold from other molecular categories. Thus, patient stratification based on kidney tissue omics offers a gateway to non-invasive biomarker-driven categorization and the potential for future clinical implementation, as a key step towards precision medicine in CKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Although suppressed cAMP levels have been linked to cancer for nearly five decades, the molecular basis remains uncertain. Here, we identify endosomal pH as a novel regulator of cytosolic cAMP homeostasis and a promoter of transformed phenotypic traits in colorectal cancer. Combining experiments and computational analysis, we show that the Na+/H+ exchanger NHE9 contributes to proton leak and causes luminal alkalinization, which induces resting [Ca2+], and in consequence, represses cAMP levels, creating a feedback loop that echoes nutrient deprivation or hypoxia. Higher NHE9 expression in cancer epithelia is associated with a hybrid epithelial-mesenchymal (E/M) state, poor prognosis, tumor budding, and invasive growth in vitro and in vivo. These findings point to NHE9-mediated cAMP suppression as a pseudostarvation-induced invasion state and potential therapeutic vulnerability in colorectal cancer. Our observations lay the groundwork for future research into the complexities of endosome-driven metabolic reprogramming and phenotype switching and the biology of cancer progression., Implications: Endosomal pH regulator NHE9 actively controls cytosolic Ca2+ levels to downregulate the adenylate cyclase-cAMP system, enabling colorectal cancer cells to acquire hybrid E/M characteristics and promoting metastatic progression., (©2024 American Association for Cancer Research.)

Olive mill waste (OMW) is a promising source of valuable compounds such as polyphenols, terpenes, sterols, and other bioactive compounds, which are of interest to the pharmaceuticals and cosmeceutical industries. This review examines the potential of OMW extracts for health and beauty applications based on evidence reports from human clinical trials. The results achieved to date indicate health-enhancing properties, but little is known about the underlying mechanisms of action, dose-response relationships, and long-term impacts. Therefore, while olive by-products, extracted using eco-friendly methods, present opportunities for the development of high-value health and cosmetic products, further studies are necessary to determine the full range of their effects and establish specific therapeutic strategies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Parkinson's disease arises from protein misfolding, aggregation, and fibrillation and is characterized by LB (Lewy body) deposits, which contain the protein α-synuclein (α-syn) as their major component. Another synuclein, γ-synuclein (γ-syn), coexists with α-syn in Lewy bodies and is also implicated in various types of cancers, especially breast cancer. It is known to seed α-syn fibrillation after its oxidation at methionine residue, thereby contributing in synucleinopathy. Despite its involvement in synucleinopathy, the search for small molecule inhibitors and modulators of γ-syn fibrillation remains largely unexplored. This work reveals the modulatory properties of cyclic-nordihydroguaiaretic acid (cNDGA), a natural polyphenol, on the structural and aggregational properties of human γ-syn employing various biophysical and structural tools, namely, thioflavin T (ThT) fluorescence, Rayleigh light scattering, 8-anilinonaphthalene-1-sulfonic acid binding, far-UV circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR) spectroscopy, atomic force microscopy, ITC, molecular docking, and MTT-toxicity assay. cNDGA was observed to modulate the fibrillation of γ-syn to form off-pathway amorphous species that are nontoxic in nature at as low as 75 μM concentration. The modulation is dependent on oxidizing conditions, with cNDGA weakly interacting ( K d ∼10 -5 M) with the residues at the N-terminal of γ-syn protein as investigated by isothermal titration calorimetry and molecular docking, respectively. Increasing cNDGA concentration results in an increased recovery of monomeric γ-syn as shown by sodium dodecyl sulfate and native-polyacrylamide gel electrophoresis. The retention of native structural properties of γ-syn in the presence of cNDGA was further confirmed by far-UV CD and FTIR. In addition, cNDGA is most effective in suppression of fibrillation when added at the beginning of the fibrillation kinetics and is also capable of disintegrating the preformed mature fibrils. These findings could, therefore, pave the ways for further exploring cNDGA as a potential therapeutic against γ-synucleinopathies.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular involvement, which is among the leading causes of morbidity and mortality worldwide. Echocardiography (ECHO) could be a reliable, non-invasive tool for predicting the risk of cardiovascular modalities in patients with COPD. Combining the ECHO parameters with highly selective cardiac troponin could predict the severity and outcome of patients with COPD., Methods: This prospective observational study was conducted at a tertiary care hospital in South India. All patients who met the criteria were included. Patients with other concomitant chronic lung diseases were excluded. An echocardiographic examination was performed, and blood samples for hs-Tnt were taken on admission for patients admitted with COPD. Categorical variables were analyzed using Pearson's Chi-square test, and the T-test was used to compare the means. One-way analysis of variance (ANOVA) followed by the Bonferroni multiple comparison tests was done to compare different echo parameters concerning COPD severity., Results: The mean tricuspid annulus plane systolic excursion (TAPSE) and right ventricle (RV) fraction area change (FAC) values were lower with the increase in the disease severity (P < 0.001). There was a significant increase in the mean systolic pressures in the right atrium and ventricle in patients with severe COPD (P < 0.001). The mean hs-TnT values were significantly higher in patients with severe COPD (18.86 ± 18.12) and correlated well with the increase in the severity of the disease (P < 0.001). Changes in the echo parameters, such as mean TAPSE and RV FAC values, negatively correlated with COPD severity. There was an increase in systolic pressure in both atria and ventricles with the progression of COPD. Troponin helped predict mortality during hospitalization., Conclusion: Comprehensive echocardiographic parameters, such as TAPSE and RV FAC, help assess the disease's severity, predict mortality, and evaluate whether the proper ventricular function is reliable. Troponin is a valuable adjunct that is an independent and strong predictor of overall mortality in patients with COPD., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

The synthesis and absorption of Vitamin D play crucial roles in numerous bodily functions, yet deficiencies persist due to factors like insufficient sunlight exposure and dietary inadequacy. Research underscores the significance of lifestyle elements such as diet, sun exposure, and physical activity in maintaining optimal Vitamin D levels. Strategies aimed at tackling deficiencies emphasize supplementation alongside lifestyle adjustments, especially in regions with abundant sunlight like the Middle East and North Africa (MENA). Despite the abundance of sunshine in the Arab world, there remains a prevalent issue of Vitamin D deficiency. This problem arises from various factors, including cultural practices such as traditional clothing covering most skin areas, which limit sun exposure, and environmental factors like air pollution that reduce UV penetration. Dietary habits and lifestyle choices also contribute to this deficiency. Dealing with the ongoing pandemic requires a focused effort to enhance awareness. While some individuals may recognize common diseases caused by Vitamin D deficiency, such as rickets and osteomalacia, many remain unaware of the broader health risks associated with the condition, including non-skeletal manifestations. Additionally, there is a lack of understanding regarding the numerous hidden benefits of this hormone. Therefore, prioritizing educational initiatives that delve into these aspects is essential to effectively combat the current health crisis. This literature review aims to report both skeletal and extraskeletal consequences of hypovitaminosis and briefly discuss the cause of paradoxical vitamin D deficiency in sunny regions like the MENA. This was done by reviewing pertinent articles published between January 2000 and January 2024, sourced from databases such as PubMed, UpToDate, Scopus, and CINAHL, focusing exclusively on English language literature and using keywords such as "Vitamin D deficiency" and "Extraskeletal manifestations.", Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Qureshi et al.)

Outcome measurement and feedback are key to quality improvement in healthcare. Goal attainment scaling (GAS) is a tool that could be used to measure outcomes of mental health services delivering recovery-oriented care. The objective of this prospective study was to evaluate the effectiveness of tailored, interprofessional, multilevel and adaptable GAS training on clinician views, learning, competence, performance and confidence in the use of GAS. Thematic analysis of eight clinician participant views was done using the method proposed by Braun and Clarke (Thematic analysis: a practical guide to understanding and doing, 2022). Four main themes were generated: clinicians found that this type of training is useful, GAS influenced the way they thought about their roles in goal setting and recovery-oriented care and COVID-19 pandemic impacts. Furthermore, clinicians' skills to set scalable GAS goals with consumers and clinician confidence in using GAS improved. The results of this study show a positive impact of tailored, interprofessional, multilevel and adaptable training supporting development of clinician skills in the GAS process. The training design had a favourable effect on clinician views, learning, competence, performance and confidence of GAS as a recovery-oriented outcome measure. The approach to GAS training and use of GAS as a recovery-oriented outcome measure should be considered in response to mental health service reform., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Peripheral arterial disease is one of the leading complications of type 2 diabetes mellitus. The primary symptom of peripheral arterial disease is claudication pain. Exercise is known to improve the claudication pain, thereby improving the quality of life., Methods: A total of 74 participants were recruited in each group and a detailed demographic assessment was done for all the participants. The study group received a comprehensive structured exercise program and standard care whereas the control group received only the standard care. Progression of the exercise was made at the 6th week of the protocol. All the outcome measures were reassessed after the 12th weeks for both study and control group., Results: The mean age of participants was 60.78 ± 11.29 (years) and 59.98 ± 11.42 (years) for the study and control group, respectively. There was a statistically significant difference in toe brachial index ( p  < 0.001), ankle brachial index ( p  < 0.001), 6-minute walk distance ( p  < 0.001), WHO-BREF quality of life questionnaire ( p  < 0.001), and walking ability (( p  < 0.001) in the study group in comparison to the control group., Conclusion: In the present study we found that comprehensive structured exercise program improves the arterial indices, quality of life, walking ability and reduces claudication pain in type 2 diabetes mellitus with peripheral arterial disease., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01426-2., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)