Voxel-wise body composition analysis using image registration of a three-slice CT imaging protocol: methodology and proof-of-concept studies.

BACKGROUND: Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data. METHODS: The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies. RESULTS: Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information. CONCLUSION: The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors.

Does Researcher Allegiance Bias Outcomes in Psychotherapy Research? A Quasi-Experimental Secondary Analysis.

Researchers who conduct studies comparing the efficacy of two treatments often find that their preferred treatment outperforms the comparison treatment. This finding has been labelled the allegiance association. Although this association is robust, it is unclear whether it reflects an allegiance bias on the part of the researchers or whether it is noncausal, with researchers being allied to the more effective treatments. This study applied a quasi-experimental method proposed by a previous study to 19 pairs of treatment comparison studies. Each member of a pair had used the same two psychotherapies to treat clients with the same disorder, but the researchers in each of the two studies had opposing allegiances. If the authors of one study in the pair concluded that their preferred treatment was superior and the authors of the other study concluded that their preferred treatment was superior or that the two treatments were equivalent, these patterns would suggest allegiance bias. In 10 of the 19 pairs, the patterns were consistent with the operation of an allegiance bias, indicating that although allegiance biases are not inevitable, they are ubiquitous. Practitioners and other psychotherapy research consumers should use caution when interpreting the findings from treatment comparison studies.

The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov.

Introduction: Psilocybin, a tryptamine psychedelic, has been touted in the media both historically and recently as a potential game-changing mental health therapeutic. ClinicalTrials.gov has over one hundred and thirty psilocybin clinical trials listed covering the last twenty years. The single most important aspect of any therapeutic is to gain approval for marketing and thus enter the real-world phase of development. A typical new chemical entity progresses from inception to US Food and Drug Administration (FDA) approval in approximately 12 years and seeks approval for a single indication. Methods: An observational study was conducted with the available information on the ClinicalTrials.gov site to observe the extent of progress made demonstrating the clinical utility of psilocybin. Results: The results showed 134 psilocybin trials typically unblinded studies of 10-20 participants, recruited over years at a single site. Additionally, there have been only three advanced trials (1 Phase 2/3 and 2 Phase 3) submitted, and only in the last two years. Discussion: The hundreds of psilocybin clinical trials initiated over the past twenty years comprising a myriad of potential indications may actually be slowing this potential game-changing mental health therapeutic agent's approval and is costing excessive amounts of capital. To fully evaluate the actual potential of psilocybin, purposeful clinical trials need to be designed well, executed efficiently, and analyzed utilizing sequential and statistically valid processes for each potential indication. This will require a change from the current exploratory forays to defined, well-funded, sequential pharmaceutical development practices, including adequate and appropriate blinding of studies, statistical design to determine the number of participants and more importantly, professional expertise in conducting multicenter trials. Unfortunately, these results demonstrate little real progress towards FDA approval of psilocybin and a field with no clear direction forward.

[Effects on cognitive processes of dual-task training in people with Parkinson's disease: a systematic review]. / Efectos sobre los procesos cognitivos del entrenamiento basado en doble tarea en personas con enfermedad de Parkinson: una revisión sistemática.

INTRODUCTION: Dual-tasking is a non-pharmacological intervention in people with neurodegenerative conditions, and is used in Parkinson's disease (PD), primarily to enhance motor performance. The aim of this review is to compile the current evidence on how dual-task training affects cognitive processes in people with PD. MATERIAL AND METHODS: A systematic review was undertaken, applying PRISMA guidelines, which included articles obtained from the PubMed, Web of Science, Science Direct and Springer Link databases. Methodological quality was assessed using PEDro and ROBINS-I. RESULTS: Twelve articles met the inclusion and exclusion criteria: nine of them were randomized controlled trials, and the remaining three were non-randomized studies. Improvements in attention and executive functions were identified, although the diversity of approaches and duration means that reaching definitive conclusions is difficult. CONCLUSIONS: Increased research and standardized intervention programmes are essential. Longitudinal and randomized controlled studies in representative samples which provide conclusions that are applicable to other contexts are also important.

TITLE: Efectos sobre los procesos cognitivos del entrenamiento basado en doble tarea en personas con enfermedad de Parkinson: una revisión sistemática.Introducción. La doble tarea es una intervención no farmacológica en personas con condiciones neurodegenerativas, utilizada en la enfermedad de Parkinson (EP), principalmente para favorecer el desempeño motor. El objetivo de esta revisión es reunir la evidencia actual sobre cómo el entrenamiento de doble tarea afecta a los procesos cognitivos en personas que presenten EP. Material y métodos. Se desarrolló una revisión sistemática, aplicando las directrices de PRISMA, incluyendo artículos obtenidos en las bases de datos de PubMed, Web of Science, Science Direct y Springer Link. La calidad metodológica se evaluó mediante PEDro y ROBINS-I. Resultados. Doce artículos cumplieron con los criterios de inclusión y exclusión: nueve de ellos corresponden a ensayos controlados aleatorizados y los tres restantes fueron estudios no aleatorizados. Se identificaron mejoras en la atención y las funciones ejecutivas, aunque la diversidad en enfoques y duración dificulta llegar a conclusiones definitivas. Conclusiones. Es crucial expandir la investigación, estandarizando los programas de intervención. Del mismo modo, es importante llevar a cabo estudios longitudinales y controlados aleatorizados en muestras representativas que permitan llegar a conclusiones aplicables a otros contextos.

An experimental framework to assess biomolecular condensates in bacteria.

High-resolution imaging of biomolecular condensates in living cells is essential for correlating their properties to those observed through in vitro assays. However, such experiments are limited in bacteria due to resolution limitations. Here we present an experimental framework that probes the formation, reversibility, and dynamics of condensate-forming proteins in Escherichia coli as a means to determine the nature of biomolecular condensates in bacteria. We demonstrate that condensates form after passing a threshold concentration, maintain a soluble fraction, dissolve upon shifts in temperature and concentration, and exhibit dynamics consistent with internal rearrangement and exchange between condensed and soluble fractions. We also discover that an established marker for insoluble protein aggregates, IbpA, has different colocalization patterns with bacterial condensates and aggregates, demonstrating its potential applicability as a reporter to differentiate the two in vivo. Overall, this framework provides a generalizable, accessible, and rigorous set of experiments to probe the nature of biomolecular condensates on the sub-micron scale in bacterial cells.

Assessing Laboratory Method Validations for Informing Inference Across Survey Cycles in the National Health and Nutrition Examination Survey.

Background and objectives Laboratory tests conducted on survey respondents' biological specimens are a major component of the National Health and Nutrition Examination Survey. The National Center for Health Statistics' Division of Health and Nutrition Examination Surveys performs internal analytic method validation studies whenever laboratories undergo instrumental or methodological changes, or when contract laboratories change. These studies assess agreement between methods to evaluate how methodological changes could affect data inference or compromise consistency of measurements across survey cycles. When systematic differences between methods are observed, adjustment equations are released with the data documentation for analysts planning to combine survey cycles or conduct a trend analysis. Adjustment equations help ensure that observed differences from methodological changes are not misinterpreted as population changes. This report assesses the reliability of statistical methods used by the Division of Health and Nutrition Examination Surveys when conducting method validation studies to address concerns that adjustment equations are being overproduced (recommended too frequently). Methods Public-use 2017-2018 National Health and Nutrition Examination Survey laboratory data were used to simulate "new" measurements for 120 analytic method validation studies. Blinded studies were analyzed to determine the final adjustment recommendation for each study using difference plots, descriptive statistics, t-tests, and Deming regressions. Final recommendations were compared with simulated difference types to assess how often spurious results were observed. Concordance estimates (concordance, misclassification, sensitivity, specificity, and positive and negative predictive values) informed assessments. Results Adjustment equations were appropriately recommended for 75.0% of the studies, over-recommended for 5.8%, under-recommended for 15.8%, and recommended with an inappropriate technique for 3.3%. Across simulated difference types, sensitivity ranged from 65.9% to 84.4% and specificity from 74.7% to 97.5%. Conclusions Findings from this report suggest that the current methodology used by the Division of Health and Nutrition Examination Surveys performs moderately well. Based on these data and analyses, underadjustment was more prevalent than overadjustment, suggesting that the current methodology is conservative.

Methodological quality of systematic reviews on atopic dermatitis treatments: a cross-sectional study.

BACKGROUND: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019-2022. We extracted SRs' bibliographical data and appraised SRs' methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. RESULTS: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. CONCLUSIONS: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users.

Health-related quality of life and associated factors among health care providers in the northwest of Ethiopia: a multicenter cross-sectional study, 2023.

Background: The diminished quality of life among healthcare providers (HCPs) could impact both their personal well-being and their ability to effectively fulfill healthcare needs and provide necessary facilities to the public. Furthermore, this decline in quality of life may also significantly influence the overall health of HCPs, regardless of their professional training and duties. Objectives: The aim of this study was to assess the health-related quality of life (HRQoL) and associated factors among healthcare providers at comprehensive specialized hospitals in the Northwest Ethiopia. Method: A cross-sectional study was conducted among 412 healthcare providers at comprehensive specialized hospitals in Northwest Ethiopia from June to July 2023. Study participants were enrolled using simple random sampling. Health-related quality of life (HRQoL) was measured using the World Health Organization Quality of Life Scale-Bref Version. Data entry and analysis were performed using Epi-data version 4.6.1 and SPSS version 24, respectively. Binary logistic regression was employed to assess the association between quality of life and independent variables. Variables with a p-value <0.05 at a 95% confidence interval were considered statistically significant. Result: Out of the 422 study participants approached, 412 respondents were included in the final analysis. Poor quality of life was observed in 54.6% of participants. Factors such as working hours per day (AOR = 1.85, 95% CI: 1.12; 3.05), working experience (AOR = 1.95, 95% CI: 1.04; 3.65), and the presence of chronic disease (AOR = 2.11, 95% CI: 1.18; 3.75) were significantly associated with poor quality of life. Conclusion: This study revealed that more than half of the participants experienced poor quality of life. Specific attention is needed for healthcare providers working for more than 8 h per day, those with less work experience, and those with chronic illnesses in order to improve their quality of life.

60 Years of the 3Rs symposium: Lessons learned and the road ahead.

When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory - and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Bal-timore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John "Jack" R. Fowle III, and the Society of Toxicology (SoT). Fourteen pres-entations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life - science, government, and industry - work toward a common goal.

William Russell and Rex Burch published their book The Principles of Humane Experimental Technique in 1959. The book encouraged researchers to replace animal experiments where it was possible, to refine experiments with animals in order to reduce their suffering, and to reduce the number of animals that had to be used for experiments to the minimum. Sixty years later, a group of pioneering and leading scientists and researchers in the field gathered to share how the publi­cation came about and how the vision inspired international collaborations and successes on many different levels including new laws. The paper includes an overview of important milestones in the history of alternatives to animal experimentation.

Comparing the Effectiveness of a Clinical Decision Support Tool in Reducing Pediatric Opioid Dose Calculation Errors: PediPain App vs. Traditional Calculators - A Simulation-Based Randomised Controlled Study.

Wrong dose calculation medication errors are widespread in pediatric patients mainly due to weight-based dosing. PediPain app is a clinical decision support tool that provides weight- and age- based dosages for various analgesics. We hypothesized that the use of a clinical decision support tool, the PediPain app versus pocket calculators for calculating pain medication dosages in children reduces the incidence of wrong dosage calculations and shortens the time taken for calculations. The study was a randomised controlled trial comparing the PediPain app vs. pocket calculator for performing eight weight-based calculations for opioids and other analgesics. Participants were healthcare providers routinely administering opioids and other analgesics in their practice. The primary outcome was the incidence of wrong dose calculations. Secondary outcomes were the incidence of wrong dose calculations in simple versus complex calculations; time taken to complete calculations; the occurrence of tenfold; hundredfold errors; and wrong-key presses. A total of 140 residents, fellows and nurses were recruited between June 2018 and November 2019; 70 participants were randomized to control group (pocket calculator) and 70 to the intervention group (PediPain App). After randomization two participants assigned to PediPain group completed the simulation in the control group by mistake. Analysis was by intention-to-treat (PediPain app = 68 participants, pocket calculator = 72 participants). The overall incidence of wrong dose calculation was 178/576 (30.9%) for the control and 23/544 (4.23%) for PediPain App, P < 0·001. The risk difference was - 32.8% [-38.7%, -26.9%] for complex and - 20.5% [-26.3%, -14.8%] for simple calculations. Calculations took longer within control group (median of 69 Sects. [50, 96]) compared to PediPain app group, (median 48 Sects. [38, 63]), P < 0.001. There were no differences in other secondary outcomes. A weight-based clinical decision support tool, the PediPain app reduced the incidence of wrong doses calculation. Clinical decision support tools calculating medications may be valuable instruments for reducing medication errors, especially in the pediatric population.

Comparison of Full-Field Stimulus Threshold Measurements in Patients With Retinitis Pigmentosa and Healthy Subjects With Dilated and Nondilated Pupil.

Purpose: The common protocol of full-field stimulus threshold (FST) testing recommends pupil dilation. The aim of this study is to investigate the difference between FST measurements with dilated and nondilated pupils in healthy subjects and patients with retinitis pigmentosa (RP). Methods: Twenty healthy subjects and 20 RP patients were selected. One pupil of each subject was dilated; the other eye was measured in physiological width of the pupil. The FST was conducted using Diagnosys Espion E2/E3 with white, blue, and red stimuli. Statistical analysis was conducted with a mixed-model analysis of variance and a paired t-test. Results: The statistical analysis revealed a significant difference between measurements of dilated and nondilated pupils with the following: blue stimuli for all subjects and groups except those with highly progressed RP; white stimuli for all tested subjects in total, for RP patients with better-preserved visual field (VF), and rod-mediated FST response; and red stimuli for RP patients with better-preserved VF and rod-mediated FST response. On average, the difference between the FST values for RP patients were -3.2 ± 3 dB for blue, -2.3 ± 2.9 dB for white, and -0.83 ± 3 dB for red stimuli. The correlation between the FST values of dilated and nondilated pupils with all three stimuli was linear. Conclusions: Current recommendations are to perform FST with dilated pupils. However, based on this study's findings, pupil dilation can be omitted for clinical diagnostics or rough follow-ups. Translational Relevance: Our data provide useful information for the clinical use of FST.

Digital Interventions for Recreational Cannabis Use Among Young Adults: Systematic Review, Meta-Analysis, and Behavior Change Technique Analysis of Randomized Controlled Studies.

BACKGROUND: The high prevalence of cannabis use among young adults poses substantial global health concerns due to the associated acute and long-term health and psychosocial risks. Digital modalities, including websites, digital platforms, and mobile apps, have emerged as promising tools to enhance the accessibility and availability of evidence-based interventions for young adults for cannabis use. However, existing reviews do not consider young adults specifically, combine cannabis-related outcomes with those of many other substances in their meta-analytical results, and do not solely target interventions for cannabis use. OBJECTIVE: We aimed to evaluate the effectiveness and active ingredients of digital interventions designed specifically for cannabis use among young adults living in the community. METHODS: We conducted a systematic search of 7 databases for empirical studies published between database inception and February 13, 2023, assessing the following outcomes: cannabis use (frequency, quantity, or both) and cannabis-related negative consequences. The reference lists of included studies were consulted, and forward citation searching was also conducted. We included randomized studies assessing web- or mobile-based interventions that included a comparator or control group. Studies were excluded if they targeted other substance use (eg, alcohol), did not report cannabis use separately as an outcome, did not include young adults (aged 16-35 y), had unpublished data, were delivered via teleconference through mobile phones and computers or in a hospital-based setting, or involved people with mental health disorders or substance use disorders or dependence. Data were independently extracted by 2 reviewers using a pilot-tested extraction form. Authors were contacted to clarify study details and obtain additional data. The characteristics of the included studies, study participants, digital interventions, and their comparators were summarized. Meta-analysis results were combined using a random-effects model and pooled as standardized mean differences. RESULTS: Of 6606 unique records, 19 (0.29%) were included (n=6710 participants). Half (9/19, 47%) of these articles reported an intervention effect on cannabis use frequency. The digital interventions included in the review were mostly web-based. A total of 184 behavior change techniques were identified across the interventions (range 5-19), and feedback on behavior was the most frequently used (17/19, 89%). Digital interventions for young adults reduced cannabis use frequency at the 3-month follow-up compared to control conditions (including passive and active controls) by -6.79 days of use in the previous month (95% CI -9.59 to -4.00; P<.001). CONCLUSIONS: Our results indicate the potential of digital interventions to reduce cannabis use in young adults but raise important questions about what optimal exposure dose could be more effective, both in terms of intervention duration and frequency. Further high-quality research is still needed to investigate the effects of digital interventions on cannabis use among young adults. TRIAL REGISTRATION: PROSPERO CRD42020196959; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=196959.

Multiomics-Based Feature Extraction and Selection for the Prediction of Lung Cancer Survival.

Lung cancer is a global health challenge, hindered by delayed diagnosis and the disease's complex molecular landscape. Accurate patient survival prediction is critical, motivating the exploration of various -omics datasets using machine learning methods. Leveraging multi-omics data, this study seeks to enhance the accuracy of survival prediction by proposing new feature extraction techniques combined with unbiased feature selection. Two lung adenocarcinoma multi-omics datasets, originating from the TCGA and CPTAC-3 projects, were employed for this purpose, emphasizing gene expression, methylation, and mutations as the most relevant data sources that provide features for the survival prediction models. Additionally, gene set aggregation was shown to be the most effective feature extraction method for mutation and copy number variation data. Using the TCGA dataset, we identified 32 molecular features that allowed the construction of a 2-year survival prediction model with an AUC of 0.839. The selected features were additionally tested on an independent CPTAC-3 dataset, achieving an AUC of 0.815 in nested cross-validation, which confirmed the robustness of the identified features.

Applications of Flow Cytometry in Drug Discovery and Translational Research.

Flow cytometry is a mainstay technique in cell biology research, where it is used for phenotypic analysis of mixed cell populations. Quantitative approaches have unlocked a deeper value of flow cytometry in drug discovery research. As the number of drug modalities and druggable mechanisms increases, there is an increasing drive to identify meaningful biomarkers, evaluate the relationship between pharmacokinetics and pharmacodynamics (PK/PD), and translate these insights into the evaluation of patients enrolled in early clinical trials. In this review, we discuss emerging roles for flow cytometry in the translational setting that supports the transition and evaluation of novel compounds in the clinic.

Daily Duration of Eating for Children and Adolescents: A Systematic Review and Meta-Analysis.

Time-limited eating is a dietary intervention whereby eating is limited to a specific window of time during the day. The usual eating windows of adults, and how these can be manipulated for dietary interventions, is well documented. However, there is a paucity of data on eating windows of young people, the manipulation of which may be a useful intervention for reducing obesity. This paper reviewed the existing literature on the eating windows of children and adolescents, aged 5-18 years, plus clock times of first and last intakes and variations by subgroup. Two databases (Medline and Embase) were searched for eligible papers published between February 2013 and February 2023, with forward searching of the citation network of included studies on Web of Science. Articles were screened, and data extracted, in duplicate by two independent reviewers. Ten studies were included, with both observational and experimental designs. Narrative synthesis showed large variations in eating windows with average values ranging from 9.7 h to 16.4 h. Meta-analysis, of five studies, showed a pooled mean daily eating window of 11.3 h (95% CI 11.0, 11.7). Large variations in eating windows exist across different study populations; however, the pooled data suggest that it may be possible to design time-limited eating interventions in paediatric populations aimed at reducing eating windows. Further high-quality research, investigating eating windows and subsequent associations with health outcomes, is needed.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Marijuana use among community-dwelling older adults: A population-based study.

OBJECTIVES: There is a paucity of population-level data on marijuana use and mental health and functioning in older adults. METHODS: We analyzed cross-sectional data (n = 910) from a well-characterized cohort, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age-stratified random sample of the population age 65 years and older from a small-town in the USA. Half the sample was female and half were over 75 (Mean age = 77). Most participants were non-Hispanic White. Marijuana use was assessed by self-report and symptoms of mood disorders were screened using the modified Centers for Epidemiological Studies-Depression Scale and the Generalized Anxiety Disorder screener. Cognition was assessed by the Mini-Mental State Examination and a neuropsychological test battery; functioning using the OARS Activities of Daily Living and Instrumental Activities of Daily Living; and overall assessment using the Clinical Dementia Rating (CDR®). RESULTS: One in five MYHAT participants had a history of marijuana use and 5% reported recent use, primarily for pain (41%) and recreation/relaxation (37%). Recent use was associated with cigarette and alcohol use, symptoms of depression or anxiety, and impairments in attention. CONCLUSIONS: Twenty-percent of community-dwelling older adults living in a US state where recreational marijuana use is illegal had a history of marijuana use. Recent marijuana use was less common but, consistent with prior research, associated with other substance use and poorer mental health.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometry strategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.

The Effect of Inflammatory Bowel Disease and Irritable Bowel Syndrome on Pravastatin Oral Bioavailability: In vivo and in silico evaluation using bottom-up wbPBPK modeling.

The common disorders irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) can modify the drugs' pharmacokinetics via their induced pathophysiological changes. This work aimed to investigate the impact of these two diseases on pravastatin oral bioavailability. Rat models for IBS and IBD were used to experimentally test the effects of IBS and IBD on pravastatin pharmacokinetics. Then, the observations made in rats were extrapolated to humans using a mechanistic whole-body physiologically-based pharmacokinetic (wbPBPK) model. The rat in vivo studies done herein showed that IBS and IBD decreased serum albumin (> 11% for both), decreased PRV binding in plasma, and increased pravastatin absolute oral bioavailability (0.17 and 0.53 compared to 0.01) which increased plasma, muscle, and liver exposure. However, the wbPBPK model predicted muscle concentration was much lower than the pravastatin toxicity thresholds for myotoxicity and rhabdomyolysis. Overall, IBS and IBD can significantly increase pravastatin oral bioavailability which can be due to a combination of increased pravastatin intestinal permeability and decreased pravastatin gastric degradation resulting in higher exposure. This is the first study in the literature investigating the effects of IBS and IBD on pravastatin pharmacokinetics. The high interpatient variability in pravastatin concentrations as induced by IBD and IBS can be reduced by oral administration of pravastatin using enteric-coated tablets. Such disease (IBS and IBD)-drug interaction can have more drastic consequences for narrow therapeutic index drugs prone to gastric degradation, especially for drugs with low intestinal permeability.

Palliative care needs of people and/or their families with serious and/or chronic health conditions in low- or middle-income country (LMIC) humanitarian settings-a systematic scoping review protocol.

BACKGROUND: Palliative care in low- or middle-income country (LMIC) humanitarian settings is a new area, experiencing a degree of increased momentum over recent years. The review contributes to this growing body of knowledge, in addition to identifying gaps for future research. The overall aim is to systematically explore the evidence on palliative care needs of patients and/or their families in LMIC humanitarian settings. METHODS: Arksey and O'Malley's (Int J Soc Res Methodol. 8:19-32, 2005) scoping review framework forms the basis of the study design, following further guidance from Levac et al. (Implement Sci 5:1-9, 2010), the Joanna Briggs Institute (JBI) Peters et al. (JBI Reviewer's Manual JBI: 406-452, 2020), and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) from Tricco et al. (Ann Intern Med 169:467-73, 2018). This incorporates a five-step approach and the population, concept, and context (PCC) framework. Using already identified key words/terms, searches for both published research and gray literature from January 2012 to October 2022 will be undertaken using databases (likely to include Cumulative Index of Nursing and Allied Health (CINAHL), MEDLINE, Embase, Global Health, Scopus, Applied Social Science Index and Abstracts (ASSIA), Web of Science, Policy Commons, JSTOR, Library Network International Monetary Fund and World Bank, Google Advanced Search, and Google Scholar) in addition to selected pre-print sites and websites. Data selection will be undertaken based on the inclusion and exclusion criteria and will be reviewed at each stage by two reviewers, with a third to resolve any differences. Extracted data will be charted in a table. Ethical approval is not required for this review. DISCUSSION: Findings will be presented in tables and diagrams/charts, followed by a narrative description. The review will run from late October 2022 to early 2023. This is the first systematic scoping review specifically exploring the palliative care needs of patients and/or their family, in LMIC humanitarian settings. The paper from the review findings will be submitted for publication in 2023.