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IntroductionOlder adults with higher needs are ideal candidates for social prescribing interventions, given the complex and intersectoral nature of their needs. This article describes findings from a developmental evaluation of 19 social prescribing programs for older adults at risk of frailty. MethodsAn evaluation of the programs was conducted from 2020 to 2023. We used data from three components of the evaluation: (1) initial evaluation data collected in 2020 and 2021; (2) program profiles developed in 2022; and (3) co-creation sessions conducted in 2023. ResultsFrom startup until March 2023, the programs served a total of 2544 older adults. The community connectors identified factors at the individual, interpersonal, institutional, community and policy levels that contributed to the successful implementation and delivery of their programs (e.g. physician champions, communities of practice, strong pre-existing relationships with the health care system), as well as challenges (e.g. limited capacity of family physicians, lack of community resources). There was strong agreement among community connectors that successful social prescribing programs should include the following core elements: (1) making connections to needed community resources; (2) co-creation of a wellness plan with long-term clients or clients who require intensive supports; (3) ongoing follow-up and check-ins for clients with wellness plans; and (4) an assessment and triaging process for the prioritization of clients. ConclusionTo leverage the full potential of social prescribing interventions, it is essential that programs engage with a range of health and social care providers, that community connectors are skilled and well supported, and that adequate investments are made in the nonprofit and voluntary sector.

IntroductionLes aînés ayant des besoins accrus sont des candidats idéaux pour les interventions de prescription sociale, compte tenu de la nature complexe et intersectorielle de leurs besoins. Cet article présente les résultats d’une évaluation de l’élaboration de 19 programmes de prescription sociale destinés aux aînés à risque de fragilité. MéthodologieNous avons effectué une évaluation des programmes pour la période 2020-2023. Nous avons utilisé les données de trois composantes de l’évaluation : 1) les données de l’évaluation initiale, recueillies en 2020 et en 2021, 2) les profils des programmes élaborés en 2022 et 3) les séances de cocréation tenues en 2023. RésultatsDe leur lancement jusqu’au mois de mars 2023, les programmes ont servi 2 544 aînés. Les agents de liaison communautaire ont cerné les facteurs au niveau individuel, au niveau interpersonnel, au niveau des établissements, au niveau de la collectivité et au niveau des politiques qui ont contribué à la mise en oeuvre et à la prestation de leurs programmes (médecins champions, communautés de pratique, solides relations préexistantes avec le système de santé, etc.), de même que les difficultés qui ont été rencontrées (capacité limitée des médecins de famille, manque de ressources communautaires, etc.). Les agents de liaison communautaire ont convenu qu’un programme de prescription sociale efficace devrait comprendre les éléments essentiels suivants : 1) établir des liens avec les ressources communautaires nécessaires, 2) prévoir la cocréation d’un plan de mieux-être avec les clients ayant besoin d’un soutien de longue durée ou intensif, 3) assurer un suivi et des vérifications de façon continuelle dans le cas des clients ayant des plans de mieux-être et 4) prévoir un processus d’évaluation et de triage pour la priorisation des clients. ConclusionPour tirer pleinement parti des possibilités offertes par les interventions de prescription sociale, il est essentiel que les programmes mobilisent un éventail de fournisseurs de soins de santé et de services sociaux, que les agents de liaison communautaire soient qualifiés et bien appuyés et que des investissements adéquats soient faits dans le secteur des organismes à but non lucratif et du bénévolat.

Abstract Introduction Frailty is a state of diminished physiological reserve and can be assessed using the frailty index. Early management of frailty is crucial for preventing adverse outcomes. Intended for assessing home‐living older adults, the initial release of the eFI‐CGA software was prior to the coronavirus disease 2019 (COVID‐19) pandemic. Methods In addressing the increased need of virtual assessment, the eFI‐CGA was upgraded to version 3.0. In this paper, we introduce the updated electronic frailty assessment tool, reporting the newly developed features and validating its use. Results End‐user experiences with the previous versions are discussed. The updated features include a search function to resume disrupted assessments. The improved user interface enabled clinicians to record care management details. Conclusion This study represents an example of software solutions in moving from disruption to transformation, benefiting healthcare for older adults during this challenging time.

Abstract Background Patient-level predictors of enrollment in pediatric biorepositories are poorly described. Especially in pandemic settings, understanding who is likely to enroll in a biorepository is critical to interpreting analyses conducted on biospecimens. We describe predictors of pediatric COVID-19 biorepository enrollment and biospecimen donation to identify gaps in COVID-19 research on pediatric biospecimens. Methods We compared data from enrollees and non-enrollees aged 0–25 years with suspected or confirmed COVID-19 infection who were approached for enrollment in the Massachusetts General Hospital pediatric COVID-19 biorepository between April 12, 2020, and May 28, 2020, from community or academic outpatient or inpatient settings. Demographic and clinical data at presentation to care were from automatic and manual chart extractions. Predictors of enrollment and biospecimen donation were assessed with Poisson regression models. Results Among 457 individuals approached, 214 (47%) enrolled in the biorepository. A COVID-19 epidemiologic risk factor was recorded for 53%, and 15% lived in a US Centers for Disease Control and Prevention-defined COVID-19 hotspot. Individuals living in a COVID-19 hotspot (relative risk (RR) 2.4 [95% confidence interval (CI): 1.8–3.2]), with symptoms at presentation (RR 1.8 [95% CI: 1.2–2.7]), or admitted to hospital (RR 1.8 [95% CI: 1.2–2.8]) were more likely to enroll. Seventy-nine percent of enrollees donated any biospecimen, including 97 nasopharyngeal swabs, 119 oropharyngeal swabs, and 105 blood, 16 urine, and 16 stool specimens, respectively. Age, sex, race, ethnicity, and neighborhood-level socioeconomic status based on zip code did not predict enrollment or biospecimen donation. Conclusions While fewer than half of individuals approached consented to participate in the pediatric biorepository, enrollment appeared to be representative of children affected by the pandemic. Living in a COVID-19 hotspot, symptoms at presentation to care and hospital admission predicted biorepository enrollment. Once enrolled, most individuals donated a biospecimen.

Abstract Background A crucial aspect of continued senior care is the early detection and management of frailty. Developing reliable and secure electronic frailty assessment tools can benefit virtual appointments, a need especially relevant in the context of the COVID-19 pandemic. An emerging effort has targeted web-based software applications to improve accessibility and usage. The objectives of this scoping review are to identify and evaluate web-based frailty assessment tools currently available and to identify challenges and opportunities for future development. Methods We conducted a review with literature (e.g., using MEDLINE databases) and Google searches (last updated on October 10, 2021). Each of the identified web applications were assessed based on eight featured categories and assigned a rating score accordingly. Results Twelve web-based frailty assessment applications were found, chiefly provided by the USA (50%) or European countries (41%) and focused on frailty grading and outcome prediction for specific patient groups (59%). Categories that scored well among the applications included the User Interface (2.8/3) and the Cost (2.7/3). Other categories had a mean score of 1.6/3 or lower. The least developed feature was Data Saving. Conclusions Web-based applications represent a viable option for remote frailty assessments and multidisciplinary integrated care of older adults. Despite the available web-based frailty assessments on the Internet, many missed certain needed features for professional use in healthcare settings. This situation calls for fully comprehensive web-based applications, taking into consideration a number of key functions linking graphical user interface and functionalities, and paying special attention to secure data management.

Integrated hepatitis B virus (HBV) DNA, found in more than 85% of HBV‐associated hepatocellular carcinomas (HBV‐HCCs), can play a significant role in HBV‐related liver disease progression. HBV‐host junction sequences (HBV‐JSs), created through integration events, have been used to determine HBV‐HCC clonality. Here, we investigate the feasibility of analyzing HBV integration in a noninvasive urine liquid biopsy. Using an HBV‐targeted next‐generation sequencing (NGS) assay, we first identified HBV‐JSs in eight HBV‐HCC tissues and designed short‐amplicon junction‐specific polymerase chain reaction assays to detect HBV‐JSs in matched urine. We detected and validated tissue‐derived junctions in five of eight matched urine samples. Next, we screened 32 urine samples collected from 25 patients infected with HBV (5 with hepatitis, 10 with cirrhosis, 4 with HCC, and 6 post‐HCC). Encouragingly, all 32 urine samples contained HBV‐JSs detectable by HBV‐targeted NGS. Of the 712 total HBV‐JSs detected in urine, 351 were in gene‐coding regions, 11 of which, including TERT (telomerase reverse transcriptase), had previously been reported as recurrent integration sites in HCC tissue and were found only in the urine patients with cirrhosis or HCC. The integration breakpoints of HBV DNA detected in urine were found predominantly (~70%) at a previously identified integration hotspot, HBV DR1‐2 (down‐regulator of transcription 1‐2). Conclusion: HBV viral–host junction DNA can be detected in urine of patients infected with HBV. This study demonstrates the potential for a noninvasive urine liquid biopsy of integrated HBV DNA to monitor patients infected with HBV for HBV‐associated liver diseases and the efficacy of antiviral therapy.

Abstract Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health‐related quality of life (HRQOL). The PAH‐symptoms and impact (PAH‐SYMPACT) questionnaire is a validated disease‐specific patient‐reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well‐being. We performed a single‐center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH‐SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1‐day version of the PAH‐SYMPACT questionnaire which consists of 22 Likert‐scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56–6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH‐SYMPACT questionnaire is both feasible and valuable. PAH‐SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.

Objective: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids. Methods: Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses. Results: Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver. Conclusions: Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.

Abstract Background Adopting a better understanding of how both older adults and health care providers view the community management of frailty is necessary for improving home health, especially facing the coronavirus disease 2019 (COVID‐19) pandemic. We conducted a qualitative focus group study to assess how both older adults and health care providers view frailty and virtual health care in home health. Methods Two focus groups enrolled home‐living older adults and health care professionals, respectively (n = 15). Questions targeting the use of virtual / telehealth technologies in‐home care for frail older adults were administered at audio‐recorded group interviews. Transcribed discussions were coded and analyzed using NVivo software. Results The older adult group emphasized the autonomy related to increasing frailty and social isolation and the need for transparent dissemination of health care planning. They were optimistic about remote technology‐based supports and suggested that telehealth / health‐monitoring/tracking were in high demand. Health care professionals emphasized the importance of a holistic biopsychosocial approach to frailty management. They highlighted the need for standardized early assessment and management of frailty. Conclusions The integrated perspectives provided an updated understanding of what older adults and practitioners value in home‐living supports. This knowledge is helpful to advancing virtual home care, providing better care for frail individuals with complex health care needs.

Abstract Background COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. Methods A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. Results Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. Conclusions Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

We present an atmospheric retrieval analysis of a pair of highly variable, ∼200 Myr old, early T type planetary-mass exoplanet analogs SIMP J01365662+0933473 and 2MASS J21392676+0220226 using the Brewster retrieval framework. Our analysis, which makes use of archival 1–15 μ m spectra, finds almost identical atmospheres for both objects. For both targets, we find that the data is best described by a patchy, high-altitude forsterite (Mg _2 SiO _4 ) cloud above a deeper, optically thick iron (Fe) cloud. Our model constrains the cloud properties well, including the cloud locations and cloud particle sizes. We find that the patchy forsterite slab cloud inferred from our retrieval may be responsible for the spectral behavior of the observed variability. Our retrieved cloud structure is consistent with the atmospheric structure previously inferred from spectroscopic variability measurements, but clarifies this picture significantly. We find consistent C/O ratios for both objects, which supports their formation within the same molecular cloud in the Carina-Near moving group. Finally, we note some differences in the constrained abundances of H _2 O and CO, which may be caused by data quality and/or astrophysical processes such as auroral activity and their differing rotation rates. The results presented in this work provide a promising preview of the detail with which we will characterize extrasolar atmospheres with JWST, which will yield higher-quality spectra across a wider wavelength range.

Introduction: Adolescent-onset cannabis use is rising in the era of marijuana legalization. Recent imaging studies have identified neuroanatomical differences between adult cannabis users and controls that are more prominent in early-onset users. Other studies point to sex-dependent effects of cannabis.Methods: A systematic review following PRISMA guidelines and subsequent effect-size seed-based d mapping (SDM) meta-analyses were conducted to investigate relationships between age (across the 12-to-21-year-old developmental window), sex, and gray matter volume (GMV) differences between cannabis using (CU) and typically developing (TD) youth.Results: Our search identified 1,326 citations, 24 of which were included in a qualitative analysis. A total of 6 whole-brain voxel-based morphometry (VBM) studies comparing regional GMV between 357 CU [mean (SD) age = 16.68 (1.28); 71% male] and 404 TD [mean (SD) age = 16.77 (1.36); 63% male] youth were included in the SDM-meta-analysis. Meta-analysis of whole-brain VBM studies identified no regions showing significant GMV difference between CU and TD youth. Meta-regressions showed divergent effects of age and sex on cortical GMV differences in CU vs. TD youth. Age effects were seen in the superior temporal gyrus (STG), with older-aged CU youth showing decreased and younger-aged CU youth showing increased STG GMV compared to age-matched TD youth. Parallel findings in the STG were also observed in relation to duration of CU (years) in supplemental meta-regressions. Regarding sex effects, a higher proportion of females in studies was associated with increased GMV in the middle occipital gyrus in CU vs. TD youth.Conclusions: These findings suggest that GMV differences between CU and TD youth, if present, are subtle, and may vary as a function of age, cumulative cannabis exposure, and sex in young people. Whether age- and sex-related GMV differences are attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrant further investigation.

Cancer patient navigation in Canada began in 2002 in Nova Scotia with oncology nurses providing support to patients from diagnosis up to and including end of life. This novel study was carried out to determine navigation frequency and palliative care contact rates, and variations in these rates among adults who were diagnosed with cancer, navigated, and then died between 2011 and 2014. Among the 2,532 study subjects, 56.7% were navigated for more than one month and 30.6% had palliative care contact reported. Variations were observed by geographic area, cancer stage, time from diagnosis to death, and whether the person died of cancer. Further study of the role of navigation is advised for persons at end of life.

Au Canada, la navigation des patients atteints de cancer a vu le jour en Nouvelle-Écosse, en 2002, à l’instigation d’infirmières en oncologie ayant décidé de soutenir les patients du diagnostic au décès. La présente étude voulait déterminer la fréquence (et la variation de fréquence) des services de navigation et de contacts pour soins palliatifs chez les adultes décédés entre 2011 et 2014 après avoir reçu un diagnostic de cancer ainsi que des services de navigation. Parmi les 2 532 sujets de l’étude, 56,7 % ont bénéficié de services de navigation pendant plus d’un mois et 30,6 % ont eu un contact pour soins palliatifs. Certaines variations ont été observées entre les régions géographiques, les stades de cancer, le temps écoulé entre le diagnostic et le décès, et la cause du décès (attribuable ou non au cancer). Il serait bon d’étudier plus en détail le rôle de la navigation pour les personnes en fin de vie.

Background: Adolescent cannabis use (CU) is associated with adverse health outcomes and may be increasing in response to changing cannabis laws. Recent imaging studies have identified differences in brain activity between adult CU and controls that are more prominent in early onset users. Whether these differences are present in adolescent CU and relate to age/developmental stage, sex, or cannabis exposure is unknown. Methods: A systematic review and subsequent effect-size seed-based d mapping (SDM) meta-analysis were conducted to examine differences in blood-oxygen-level-dependent (BOLD) response during fMRI studies between CU and non-using typically developing (TD) youth. Supplemental analyses investigated differences in BOLD signal in CU and TD youth as a function of sex, psychiatric comorbidity, and the dose and severity of cannabis exposure. Results: From 1371 citations, 45 fMRI studies were identified for inclusion in the SDM meta-analysis. These studies compared BOLD response contrasts in 1216 CU and 1486 non-using TD participants. In primary meta-analyses stratified by cognitive paradigms, CU (compared to TD) youth showed greater activation in the rostral medial prefrontal cortex (rmPFC) and decreased activation in the dorsal mPFC (dmPFC) and dorsal anterior cingulate cortex (dACC) during executive control and social cognition/emotion processing, respectively. In meta-regression analyses and subgroup meta-analyses, sex, cannabis use disorder (CUD) severity, and psychiatric comorbidity were correlated with brain activation differences between CU and TD youth in mPFC and insular cortical regions. Activation differences in the caudate, thalamus, insula, dmPFC/dACC, and precentral and postcentral gyri varied as a function of the length of abstinence. Conclusions: Using an SDM meta-analytic approach, this report identified differences in neuronal response between CU and TD youth during executive control, emotion processing, and reward processing in cortical and subcortical brain regions that varied as a function of sex, CUD severity, psychiatric comorbidity, and length of abstinence. Whether aberrant brain function in CU youth is attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrants further investigation.

Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6–8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.

Introduction: Abstinence from drinking represents the primary treatment target for alcohol use disorders (AUD) in youth, but few adolescents who engage in problematic drinking seek treatment. A reduction in World Health Organization (WHO) drinking risk level has been established as valid and reliable non-abstinent treatment target for AUD in adults but remains unstudied in youth. Methods: The present study used data from the NIDA-CTN-0028 trial to examine associations between reductions in WHO drinking risk level and changes in global functioning and attention-deficit hyperactivity disorder (ADHD) symptoms during treatment in a sample of adolescents (ages 13–18 years) with ADHD and comorbid substance use disorder (SUD) (n = 297, 61% with AUD) receiving a 16-week intervention that combined ADHD pharmacotherapy (OROS-methylphenidate vs. placebo) and drug-focused cognitive-behavioral therapy. Results: Shifts in drinking risk level during treatment were highly variable in adolescents treated for ADHD/SUD, and influenced by AUD diagnostic status. In the total sample, 15% of participants had a 2-level or greater reduction in WHO drinking risk level, with 59% and 24% showing no change or an increase in risk-level during treatment respectively. Achieving at least a 2-level change in WHO drinking risk level during treatment was associated with greater reduction in ADHD symptoms and better functional outcomes. Conclusions: These findings parallel the adult AUD literature and provide preliminary support for the use 2-level reductions in WHO risk levels for alcohol use as a clinically valid non-abstinent treatment outcome for youth with ADHD and comorbid AUD.

Background: Frailty is characterized by loss of biological reserves and is associated with an increased risk of adverse health outcomes. Frailty can be operationalized using a Frailty Index (FI) based on the accumulation of health deficits; items under health evaluation in the well-established Comprehensive Geriatric Assessment (CGA) have been used to generate an FI-CGA. Traditionally, constructing the FI-CGA has relied on paper-based recording and manual data processing. As this can be time-consuming and error-prone, it limits widespread uptake of this proven type of frailty assessment. Here, we report the development of an electronic tool, the eFI-CGA, for use on personal computers by frontline healthcare providers, to collect CGA data and automate FI-CFA calculation. The ultimate goal is to support early identification and management of frailty at points-of-care, and make uptake in Electronic Medical Records (EMR) feasible and transparent.Methods: An electronic CGA (eCGA) form was implemented to operate on Microsoft's WinForms platform and coded using C# programming language. Users complete the eCGA form, from which items under the CGA evaluation are automatically retrieved and processed to output an eFI-CGA score. A user-friendly interface and secured data saving methods were implemented. The software was debugged and tested using systematically designed simulation data, addressing different logic, syntax, and application errors, and then tested with clinical assessment. The user manual and manual scoring were used as ground truth to compare eFI-CGA input and automated eFI score calculations. Frontline health-provider user feedback was incorporated to improve the end-user experience.Results: The Standalone eFI-CGA software tool was developed and optimized for use on personal computers. The user interface adapted the design of paper-based CGA form to facilitate familiarity for clinical users. Compared to known scores, the software tool generated eFI-CGA scores with 100% accuracy to four decimal places. The eFI-CGA allowed secure data storage and retrieval of multiple types, including user input, completed eCGA form, coded items, and calculated eFI-CGA scores. It also permitted recording of actions requiring clinical follow-up, facilitating care planning. Application bugs were identified and resolved at various stages of the implementation, resulting in efficient system performance.Discussion: Accurate, robust, and reliable computerized frailty assessments are needed to promote effective frailty assessment and management, as a key tool in health care systems facing up to frailty. Our research has enabled the delivery of the standalone eFI-CGA software technology to empower effective frailty assessment and management by various healthcare providers at points-of-care, facilitating integrated care of older adults.

NAFLD has alarmingly increased, yet FDA-approved drugs are still lacking. An excessive intake of fructose, especially in liquid form, is a dietary risk factor of NAFLD. While fructose metabolism has been studied for decades, it is still controversial how fructose intake can cause NAFLD. It has long been believed that fructose metabolism solely happens in the liver and accordingly, numerous studies have investigated liver fructose metabolism using primary hepatocytes or liver cell lines in culture. While cultured cells are useful for studying detailed signaling pathways and metabolism in a cell-autonomous manner, it is equally important to understand fructose metabolism at the whole-body level in live organisms. In this regard, recent in vivo studies using genetically modified mice and stable isotope tracing have tremendously expanded our understanding of the complex interaction between fructose-catabolizing organs and gut microbiota. Here, we discuss how the aberrant distribution of fructose metabolism between organs and gut microbiota can contribute to NAFLD. We also address potential therapeutic interventions of fructose-elicited NAFLD.

HIV infection has been associated with increased diabetes risk, but prior work has mostly focused on insulin resistance, as opposed to beta cell effects, or included patients on antiretroviral therapies (ART) directly linked to metabolic toxicity. In this analysis, we measured markers of glucose homeostasis and beta cell function, stress, and death in fasting sera from a cross section of HIV+ individuals off ART (n = 43), HIV+ individuals on ART (n = 23), and HIV- controls (n = 39). Markers included glucose, HOMA%S, HOMA%B, proinsulin:C-peptide ratio (PI:C ratio), and circulating preproinsulin (INS) DNA. We performed multiple linear regressions with adjustments for age, sex, race, BMI, and smoking status. Compared to HIV- controls, HIV+ participants off ART exhibited similar beta cell function and insulin sensitivity, without increases in markers of beta cell stress or death. Specifically, in HIV+ participants with CD4 counts

Diffuse gastric adenocarcinoma or and ldquo;linitis plastica and rdquo; is characterized by a thickened and rigid stomach wall due to the diffuse infiltration of signet ring cells into the lower parts of the mucosa and submucosa of the stomach. This type of cancer is known to commonly metastasize to the liver, lungs, and ovaries, and metastasis to the gallbladder is extremely rare. We now report a case of a 79-year-old Caucasian female with diffuse gastric adenocarcinoma that metastasized to the gallbladder. The patient presented with symptoms mimicking acute cholecystitis. Histological analysis of the cholecystectomy specimen showed signet ring cells in the submucosa of the gallbladder wall. Further workup, which included esophagogastroduodenoscopy, revealed linitis plastic. This is the first case of gallbladder metastasis from diffuse gastric carcinoma reported in the United States. [Arch Clin Exp Surg 2012; 1(1.000): 54-57]

In a globally connected era due to developments in technology such as the Internet, video conferences, and electronic filing in the legal field, commercial mediation has also expanded itself from a strictly domestic realm. It is not uncommon to have mediation involving parties from different parts of the world who speak in different languages. These different "languages" in particular refer not only to the actual languages people speak but also to the particular negotiation styles the parties use because of their cultural background. As a result, although two parties may be negotiating in English or in another common language with the help of a translator, they will still likely be speaking in different "languages" of negotiation. Consequently, negotiators often doubt whether they want to do business with the opposing side because of the strange, insulting, or sometimes offending behaviors the prospective business partner exhibit during negotiations. [ABSTRACT FROM AUTHOR]

To determine whether the tumor necrosis factor α (TNFA) –308 guanine‐to‐adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA).The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease‐modifying antirheumatic drug treatment, and ≥2 sets of scored radiographs of the hands/wrists and forefeet. TNFA –308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA–DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score.Using a weighted least‐squares regression analysis, patients with the –308 TNFA AA plus AG genotypes (n = 49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n = 140). Presence of the SE (n = 137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n = 52). In a least‐squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C‐reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D′ = 0.84, r2 = 0.45, P < 0.001).This study showed an association between the TNFA –308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the –308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials. [ABSTRACT FROM AUTHOR]

To determine whether the RANKL and HLA–DRB1 “shared epitope” (SE) genotypes contribute to the development of rheumatoid arthritis (RA).We studied 237 patients with early RA (within 15 months of symptom onset) who were seropositive for rheumatoid factor. HLA–DRB1 genotyping was performed using the polymerase chain reaction (PCR)–based oligonucleotide probe assay. RANKL polymorphisms were analyzed using PCR pyrosequencing for SNP1 and fluorescence‐based PCR for the presence or absence of the TAAA insertion.The presence of SE‐containing DRB1*04 alleles was associated with an earlier age at RA onset (mean ± SD 47 ± 12.7 years versus 53 ± 12.5 years in SE– patients; P = 0.0004). The 2 novel RANKL polymorphisms were in strong linkage disequilibrium (P < 0.0001) and were associated with earlier ages at disease onset (e.g., for the CC versus CT/TT genotypes, 44 ± 13.5 years versus 51 ± 12.7 years; P = 0.0080). The mean age at disease onset in SE+ patients with the RANKL‐CC genotype (35 ± 7.2 years) was a mean of 18 years younger than in SE– patients with RANKL‐CT/TT (53 ± 12.5 years; P < 0.0001) and was 17 years younger than in SE– patients with RANKL‐CC (52 ± 13.2 years; P = 0.0005). The proportion of patients with both the SE and RANKL risk alleles was highest (23%) in those who developed RA during their third decade of life (ages 20–30 years), with a declining trend among those who developed RA during their fourth (16%), fifth (5%), and sixth or later (0%) decades. Interestingly, 92% of the patients diagnosed as having RA between ages 20 and 30 years carried at least 1 of the RA‐associated DRB1*04 alleles, suggesting a strong influence of the SE in the early onset of RA. The majority of patients who developed RA symptoms in their third to fifth decades (74 of 119 [62%]) carried at least 1 copy of the DRB1*04 alleles; in contrast, fewer than half of the patients who developed RA in their sixth decade or later (50 of 118 [42%]) had DRB1*04 alleles. RANKL genotypes were not associated with erosive disease at baseline or with the yearly progression rate of radiographic joint damage. This study provides the first evidence that novel RANKL polymorphisms were associated with an earlier age at RA onset in SE+, but not SE–, patients and that an interaction between SE‐containing HLA–DRB1 and RANKL polymorphisms increased the disease penetrance, resulting in a mean age at RA onset that was 18–20 years younger. Our results also suggested genetic differences between patients with early‐onset and those with late‐onset RA. [ABSTRACT FROM AUTHOR]

Objectives: In an earlier qualitative study we explored the attitudes of young men aged 15-19 (Group A) to mental health and, in particular, to engaging with the various mental health services available. We found that the participants perceived stigma in connection with mental ill health and they displayed particularly strong negative attitudes in relation to both doctors and medication. The investigation was then repeated with students who had been given a short (less than two-hour) programme called 'Beat the Blues' (BTB) about mental health (Group B) in order to assess the effect of that exposure by comparing the attitudes of the two groups of students. This present phase of the analysis is a quantitative examination of the written responses by both Groups A and B to an administered questionnaire., Methods: A total of 42 young men took part in eight focus groups held in boys-only Dublin secondary schools, described in Burke et al. A questionnaire, administered to each participant, examined the students' attitudes to depression and mental illness. The results were analysed by computer using SPSS to search for any trends and any contrasts between groups A and B and among the different socio-economic groups (SEGs) within the sample., Results: Almost no statistically significant differences were found between groups A and B. However, some differences were found among the SEGs. In particular, very significant differences (p < 0.01 in each case), were found in attitudes towards depression, with increasing support for statements such as "People with depression just need to snap out of it", "Drinking alcohol can help cure depression" and "Depression is only an excuse for laziness" found among the lower SEGs. A very high percentage of students indicated their desire to talk to someone in times of personal stress; this was almost always their best friend or their mother. However, most students said they would be uncomfortable if a friend raised such a topic., Conclusion: The main conclusion - that a single exposure to a positive programme about depression produces little or no effect - is hardly unexpected. Nonetheless, there are indications of a great willingness among older secondary students to learn about and discuss mental health issues. Furthermore, the highly negative attitudes among students from the lowest socio-economic group in this study would seem to indicate that the greatest need for education about mental health lies with working-class adolescents. Hence, it is recommended that a programme of multiple interventions be introduced into the senior cycle of secondary education.

Objectives: The rate of suicide among young men is rising. However, young men are reluctant to use mental health services. In this study we explored young men's attitudes towards mental illness and mental health services, as well as their willingness to use these services., Methods: Four focus groups were conducted in two Dublin schools. A total of 18 students participated in the study., Results: Students held negative views towards mental health services, particularly in respect to psychiatric hospitals and medication. Students were not well informed about whom to contact if they had depression and were very conscious about the stigma of going to see a 'professional'. Many students did not recognise depression as being a mental illness and could not differentiate between depression and feeling sad., Conclusions: This study shows that a lack of knowledge and understanding about mental illness, combined with prejudice against mental health professionals and fear of stigma, are important barriers to access of mental health services for young men.