Search

AIMS: Current risk scores for undiagnosed diabetes are additive in structure. We sought to derive a globally applicable screening model based on established non-invasive risk factors for diabetes but with a more flexible structure. METHODS: Data from the DETECT-2 study were used, including 102,058 participants from 38 studies covering 8 geographical regions worldwide. A global screening model for undiagnosed diabetes was identified through tree-structured regression analysis. The performance of the global screening model was evaluated in each of the geographical regions by receiver operating characteristic (ROC) analysis. RESULTS: The global screening model included age, height, body mass index, waist circumference and systolic- and diastolic blood pressure. Area under the ROC curve ranged between 0.64 in North America and 0.76 in Australia and New Zealand. Overall, to identify 75% of the undiagnosed diabetes cases, 49% required further diagnostic testing. CONCLUSIONS: We identified a globally applicable screening model to detect individuals at high risk of undiagnosed diabetes. The model performed well in most geographical regions, is simple and requires no calculations. This global screening model may be particularly helpful in developing countries with no population based data with which to develop own screening models. [ABSTRACT FROM AUTHOR]

AIMS: To estimate the population attributable fraction (PAF) of elevated body mass index (BMI) for diabetes mortality by country, sex and age group, for the Western Pacific and South-East Asia regions. METHODS: Published data on nationally representative mean BMI (since year 2000) and age-specific hazard ratios for death due to diabetes for a unit increase in BMI were used to calculate PAFs using the methodology of the WHO Global Burden of Disease project, taking a BMI of 21kg/m(2) as the ideal. RESULTS: Data were available for 15 countries in the Western Pacific and South East Asia regions. This included data from 330,374 individuals. Age-standardized male PAFs ranged from 11% for India to 98% for American Samoa. Age-standardized female PAFs ranged from 9% in India to 95% in American Samoa. For males, several countries had PAFs at or below 30% - these were India, Indonesia and Japan; whereas, India and Indonesia were the only two countries with PAFs below approximately 30% for females. CONCLUSION: Although this study is not a trial and thus not able to definitively state the proportions of diabetes deaths that could be averted by reducing mean BMI, this paper demonstrates that theoretically between 9% and 98% of deaths from diabetes could be prevented by tackling obesity in the Asia Pacific region. Preventing these deaths is likely to have an enormous positive social and economic impact, particularly in this region consisting of many low and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: It is commonly believed that the quality of health care decreases during trainee changeovers at the end of the academic year.Purpose: To systematically review studies describing the effects of trainee changeover on patient outcomes.Data Sources: Electronic literature search of PubMed, Educational Research Information Center (ERIC), EMBASE, and the Cochrane Library for English-language studies published between 1989 and July 2010.Study Selection: Title and abstract review followed by full-text review to identify studies that assessed the effect of the changeover on patient outcomes and that used a control group or period as a comparator.Data Extraction: Using a standardized form, 2 authors independently abstracted data on outcomes, study setting and design, and statistical methods. Differences between reviewers were reconciled by consensus. Studies were then categorized according to methodological quality, sample size, and outcomes reported.Data Synthesis: Of the 39 included studies, 27 (69%) reported mortality, 19 (49%) reported efficiency (length of stay, duration of procedure, hospital charges), 23 (59%) reported morbidity, and 6 (15%) reported medical error outcomes; all studies focused on inpatient settings. Most studies were conducted in the United States. Thirteen (33%) were of higher quality. Studies with higher-quality designs and larger sample sizes more often showed increased mortality and decreased efficiency at time of changeover. Studies examining morbidity and medical error outcomes were of lower quality and produced inconsistent results.Limitations: The review was limited to English-language reports. No study focused on the effect of changeovers in ambulatory care settings. The definition of changeover, resident role in patient care, and supervision structure varied considerably among studies. Most studies did not control for time trends or level of supervision or use methods appropriate for hierarchical data.Conclusion: Mortality increases and efficiency decreases in hospitals because of year-end changeovers, although heterogeneity in the existing literature does not permit firm conclusions about the degree of risk posed, how changeover affects morbidity and rates of medical errors, or whether particular models are more or less problematic.Primary Funding Source: National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes is an incurable chronic autoimmune disease. Although transplantation of pancreatic islets may serve as a surrogate source of insulin, recipients are subjected to a life of immunosuppression. Interleukin (IL)-21 is necessary for type 1 diabetes in NOD mice. We examined the efficacy of an IL-21-targeted therapy on prevention of diabetes in NOD mice, in combination with syngeneic islet transplantation. In addition, we assessed the role of IL-21 responsiveness in islet allograft rejection in mouse animal models.Research Design and Methods: NOD mice were treated with IL-21R/Fc, an IL-21-neutralizing chimeric protein. This procedure was combined with syngeneic islet transplantation to treat diabetic NOD mice. Survival of allogeneic islet grafts in IL-21R-deficient mice was also assessed.Results: Evidence is provided that IL-21 is continually required by the autoimmune infiltrate, such that insulitis was reduced and reversed and diabetes inhibited by neutralization of IL-21 at a late preclinical stage. Recovery from autoimmune diabetes was achieved by combining neutralization of IL-21 with islet transplantation. Furthermore, IL-21-responsiveness by CD8+ T-cells was sufficient to mediate islet allograft rejection.Conclusions: Neutralization of IL-21 in NOD mice can inhibit diabetes, and when paired with islet transplantation, this therapeutic approach restored normoglycemia. The influence of IL-21 on a graft-mounted immune response was robust, since the absence of IL-21 signaling prevented islet allograft rejection. These findings suggest that therapeutic manipulation of IL-21 may serve as a suitable treatment for patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To re-evaluate the relationship between glycemia and diabetic retinopathy.Research Design and Methods: We conducted a data-pooling analysis of nine studies from five countries with 44,623 participants aged 20-79 years with gradable retinal photographs. The relationship between diabetes-specific retinopathy (defined as moderate or more severe retinopathy) and three glycemic measures (fasting plasma glucose [FPG; n = 41,411], 2-h post oral glucose load plasma glucose [2-h PG; n = 21,334], and A1C [n = 28,010]) was examined.Results: When diabetes-specific retinopathy was plotted against continuous glycemic measures, a curvilinear relationship was observed for FPG and A1C. Diabetes-specific retinopathy prevalence was low for FPG <6.0 mmol/l and A1C <6.0% but increased above these levels. Based on vigintile (20 groups with equal numbers) distributions, glycemic thresholds for diabetes-specific retinopathy were observed over the range of 6.4-6.8 mmol/l for FPG, 9.8-10.6 mmol/l for 2-h PG, and 6.3-6.7% for A1C. Thresholds for diabetes-specific retinopathy from receiver-operating characteristic curve analyses were 6.6 mmol/l for FPG, 13.0 mmol/l for 2-h PG, and 6.4% for A1C.Conclusions: This study broadens the evidence based on diabetes diagnostic criteria. A narrow threshold range for diabetes-specific retinopathy was identified for FPG and A1C but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/l and that an A1C of 6.5% is a suitable alternative diagnostic criterion. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the influence of two different bar diameters on neuromuscular activation and strength. The bar diameters used reflected a standard Olympic bar (28 mm (1.1 inch); THIN) and a larger fat bar (51 mm [2 inch]; THICK). Eighteen healthy men (age 25.0 +/- 1 years) were assessed for their maximal voluntary contraction (MVC) during a unilateral isometric bench press exercise with the 2 bar types at 2 different joint angles (angle 1 and angle 2; elbow joint at approximately 45 and 90 degrees , respectively). Additionally, on a separate day, subjects performed three 10-second isometric repetitions at an intensity of 80% MVC using the 2 different bars at angle 1 and angle 2. Electromyographic recordings were collected in the pectoralis major and the muscles of the forearm flexor region at a sampling rate of 1000 Hz during the second day of testing. Analysis of variance was used to examine differences in MVC between bars and also examine between bar differences in electromyographic activity for each muscle group at each joint angle. A significance level of 0.05 was used for all tests. MVC was not different between bar types, although there was a main effect of joint angle on MVC such that it was greater at angle 2. There was a main effect of bar at both angles for the forearm muscles and at angle 1 for the pectoralis such that electromyographic activity was greater with THIN. Our data do not support the hypothesis that bar diameter influences performance during an isometric bench press exercise. However, higher electromyographic activity with THIN suggests greater neuromuscular activation with a standard Olympic bar as opposed to a larger diameter 'fat' bar. Although our data do not support the use of a fat bar for increasing neuromuscular activation, these findings should be confirmed in other resistance training exercises. [ABSTRACT FROM AUTHOR]

Purpose-The purpose of this empirical study is to investigate the use of, and perception of, weblogs in the Irish library and information profession, in order to ascertain the extent weblog technology is used by Irish librarians, and what factors promote or discourage the use of weblogs.Design/methodology/approach-The research questions answered in the study were: 'What types of library/librarian weblogs exist in the Irish library community?'; 'Does the Irish librarian community use weblogs and other social communication technologies?'; 'What factors affect the uptake of blogging technologies by Irish librarians?'. The methodology employed in the study combined quantitative and qualitative techniques, and involved content analysis of existing Irish library and librarian weblogs; a survey of Irish librarians concerning weblogs and other social communication technologies; and interviews with Irish librarians who maintain weblogs.Findings-The study found that a high proportion of Irish librarians read weblogs, but weblogs are not extensively used as an information resource or communication method, and e-mail and websites are preferred. The professional use of weblogs was found to be associated with simplicity of use, and a proactive attitude to technology and to library users. Constraining factors included time concerns, fear of misuse of the weblog, the limitations of the linear nature of weblogs and the newness of the technology. Interest in weblog technology is growing and its uptake will ultimately depend on the interest of the librarian and the perceived and actual needs of the library users.Originality/value-This study analyzes, for the first time, the Irish biblioblogosphere and contributes to the emergent body of knowledge concerning librarians' use of weblogs. [ABSTRACT FROM AUTHOR]

Background. Previously, we reported that there was an outbreak of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The objectives of the present study were to conduct a molecular epidemiological analysis and to characterize the full-length genome of the Taiwanese CRF07_BC.Methods. Three hundred and fifty-eight patients with HIV-1/AIDS from hospitals and 133 HIV-1-infected inmates from detention centers were recruited. DNA sequencing and phylogenetic analysis were conducted to determine subtypes and evolutionary relationships. Recombination breakpoints of 2 full-length CRF07_BC strains were elucidated using a bootscanning method.Results. Of 206 HIV-1-infected patients who received a diagnosis in 2004, 44.7% were infected with subtype B, 53.4% with CRF07_BC, and 1.5% with CRF01_AE. Ninety-eight percent (109/111) of IDUs were infected with CRF07_BC. Deletions of 7-11 amino acids in both p6(gag) and p6(pol) proteins were noted among the Taiwanese CRF07_BC strains. The CRF_07BC strains belonged to 2 phylogenetic clusters, and the first cluster contained only CRF07_BC strains from the southern part of Taiwan.Conclusions. The Taiwanese CRF07_BC strains had 97% full-length sequence homology with the prototype from mainland China. CRF07_BC was first introduced into the southern region in 2002 and then spread to other regions in Taiwan in 2004. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

PURPOSE: To examine cardiac autonomic modulation, via heart rate variability (HRV), after exercise bouts at 50% (LO) and 80% (HI) of VO2 reserve (VO2R). METHODS: Thirteen male volunteers (age: 25.7+/-3 yr) exercised on a treadmill at either LO or HI (randomly assigned) on separate days, expending 300 kcal during each bout. During each visit, electrocardiogram (ECG) recordings were obtained during a supine 5-min period before exercise (PRE) and during 30 min of postexercise supine recovery (POST). The last 25 min of POST was divided into five 5-min segments to closely examine postexercise HRV. ECG segments were analyzed for the standard deviation of RR intervals (SDNN), whereas total- (lnTP), low- (lnLF), and high-frequency (lnHF) power were obtained via spectral analysis. LF and HF were further normalized (LFNU and HFNU) to better quantify autonomic balance. RESULTS: There were main effects of time and intensity on SDNN such that it was lower than PRE until 15 min POST, and lower after HI. There were significant intensity x time interactions on lnTP, lnLF, lnHF, LFNU, HFNU, and lnLF/lnHF. Post hoc analysis revealed that lnTP and lnLF were lower than PRE up to 20 min POST after HI. lnHF was lower than PRE for 25 min POST for HI, and for 10 min POST for LO. LFNU and lnLF/lnHF were greater, whereas HFNU was lower, compared with PRE up to 15 min POST, and from 20-25 min POST for HI only. CONCLUSION: Exercise at 50% VO2R caused less of a shift in the cardiac autonomic balance, with a quicker restoration of vagal modulation than exercise at 80% VO2R. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the influence of 2 wk (eight sessions) of endurance training on cardiac autonomic modulation, as measured by heart rate variability (HRV). METHODS: Twenty-four males (mean age: 23.1 yr) were randomized to an exercise (EX; N = 12) or control group (CT; N = 12). EX trained for eight sessions (4x wk-1, 40 min, 80-85% HRreserve) on a cycle ergometer. ECG tracings were collected during 5 min of paced breathing (12 breaths x min-1 (PB)), 5 min of spontaneous breathing (SB1), 5 min of 70 degrees head-up tilt (TILT), and a second 5-min period of spontaneous breathing (SB2). Data were collected before (test 1), during (tests 2-4), and 48 h after (test 5) the 2-wk period. HRV was reported as the standard deviation of RR intervals, and as natural logarithm of the normalized units (NU) of high- and low-frequency power (lnHF and lnLF). RESULTS: EX exhibited a significant increase in peak oxygen consumption (8%). During PB and TILT conditions, ANOVA revealed a group x time interaction such that EX exhibited lower lnLFNU and lnLF/lnHF during test 5 compared with test 1. CONCLUSION: These data suggest that eight endurance exercise-training sessions performed over 2 wk enhance the relative vagal modulation of the heart during PB and TILT, but not during SB. [ABSTRACT FROM AUTHOR]

BACKGROUND: attention-demanding tasks cause changes in the autonomic modulation of cardiac function. Heart rate variability, an index of autonomic modulation of heart rate, decreases with age. OBJECTIVE: to examine heart rate variability in elderly and young participants at rest and during an attention-demanding task. METHODS: we assessed 16 old participants (ages 72-91) and 16 college-age (ages 20-25) participants for short-term (5 min) heart rate variability at rest and during a simple-reaction time task. We report heart rate variability as the standard deviation of all interbeat intervals, and as the relative contribution of changes occurring at low- and high-frequencies. RESULTS: there were no group differences in resting heart rate. A 2x2 mixed model ANOVA suggested a main effect of age on standard deviation of all interbeat intervals (P<0.05) which was significantly lower for the older group than their younger counterparts. There was also a significant effect of the test condition on standard deviation of all interbeat intervals and spectral measures of heart rate variability (P<0.05) in that standard deviation of all interbeat intervals dropped during the simple reaction time as did high-frequencies, while normalized low frequency power increased. CONCLUSION: cardiac autonomic modulation during provocative stress show similar physiologic responses in young and older adults. [ABSTRACT FROM AUTHOR]

This article aims to assess whether a detachable functional focused rigidity cast can be used as a one-off definitive treatment for proximal 5th metatarsal fractures. A prospective trial was carried out over a 2-year period. Forty-one patients with proximal 5th metatarsal fractures (tuberosity and Jones) were recruited and treated with a detachable focused rigidity cast after appropriate consent. Of the 39 patients with follow-up, six had a Jones fracture and 33 had tuberosity fractures. All 33 patients with tuberosity fractures achieved clinical union within 4-5weeks (mean of 4.2weeks). Four of the six patients with Jones fractures achieved clinical union in 8-12weeks. One achieved union in 14weeks and one underwent open reduction and internal fixation for delayed union. There were no complications related to the cast. The results support the use of a detachable focused rigidity cast as a one-off definitive treatment of tuberosity fractures of the 5th metatarsal. However, all the Jones fractures and the diaphyseal fractures should be referred to an orthopaedic team for further management. [ABSTRACT FROM AUTHOR]

It is well established that college students have high rates of alcohol use and misuse and suffer the negative consequences of this behavior. Research evaluating the results of brief interventions with high-risk college students has shown these approaches to be successful in reducing alcohol consumption and/or related consequences. Several screening tools have been developed to detect the presence of problematic alcohol use and associated disorders, and some are designed specifically for use in a college student population. College campuses offer several opportunities to implement screening and interventions, including universal or large-scale assessments; health services, counseling centers, or local emergency rooms; or via established judicial or grievance systems set up to deal with students who violate campus alcohol policies. Issues to consider when implementing screening and brief interventions in college populations include who should deliver the interventions--peer or professional counselors--and how students should be encouraged to participate in the interventions. Regardless of how the measures are implemented, the content and process of the brief interventions should be based on the available scientific evidence regarding established efficacious interventions. [ABSTRACT FROM AUTHOR]

Objective: Little work has evaluated the relationship between injunctive norms and marijuana use. This study sought to establish whether misperceptions exist between perceived injunctive norms of typical college students and the actual approval level of the students. We also examined respondents' perceptions of which groups (typical student, close friends, and parents) were the most and least approving of marijuana. These variables were then applied to an explanatory model to assess their relationships with marijuana use.Method: Participants were 3,753 students (61% female) randomly recruited from two West Coast campuses. Participants were asked about their own marijuana use and their own approval toward marijuana. Injunctive norms were assessed by asking respondents about their perceptions of how much other reference groups approved of marijuana.Results: Students overestimated the extent to which the typical student approves of marijuana use. A path model showed that perceived approval of both close friends and parents predicted actual/self-approval, which in turn was most predictive of personal marijuana use. Perceptions of typical-student and close friends' approval also directly predicted one's own use, whereas the path from parental approval to marijuana use was fully mediated by one's own approval.Conclusions: Findings suggest that perceived injunctive norms may function differently with respect to marijuana use than they do with respect to alcohol use and raise questions about how to incorporate social-normative information into marijuana interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE/AIM: Hepatocellular carcinoma (HCC) surveillance is a common practice for patients with liver cirrhosis. The aims of the study were to assess impacts of surveillance and therapeutic options on survival of patients with HCC. METHODS: A total of 1436 cirrhotic patients with newly diagnosed HCC were enrolled between January 2002 and December 2004. Patients with HCC detected within periodic surveillance were the surveillance group (n=318, 22.1%). The other patients with HCC incidentally detected were the non-surveillance group (n=1118, 77.95%). Initial treatment options were recorded and overall survival was analysed. RESULTS: Compared with patients in the non-surveillance group, larger proportions of patients in the surveillance group possessed small tumours, at an early stage without vascular invasion or metastases, and afforded more curative treatment options including surgical resection, radiofrequency ablation and percutaneous ethanol injection. The overall survival was better for patients in surveillance (3-year survival rate: 59.1% versus 29.3%, p<0.001), early stages by Barcelona Clinic Liver Cancer (BCLC) staging or curative treatment options. Multivariate analysis demonstrated surveillance, hepatitis aetiology, alpha-fetoprotein, tumour gross type, tumour stage and treatment options were associated factors for patients' survival. Moreover, surveillance patients in curative BCLC stage following the treatment guideline for HCC proposed by the American association for the study of liver disease (AASLD) had a significantly better 3-year survival rate (77.1% versus 55.2%, p<0.001). CONCLUSIONS: HCC surveillance for cirrhotic patients could detect HCC at early and curative stages. However, appropriate treatment options following AASLD guideline further improve the survival for patients in early stage. [ABSTRACT FROM AUTHOR]

The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification and treatment allocation for hepatocellular carcinoma (HCC). We conducted this retrospective study to assess the efficacy of different treatment options for patients with initial HCC diagnosis. Survival rate and median survival times associated with different treatment options in each stage of BCLC classification were compared using the Kaplan-Meier method and log-rank test. A total of 3892 patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at 5 years. The median survival times decreased from 57.7 months in very early stage to 1.6 months in terminal stage. Surgical resection offered the best survival benefit for patients in very early, early and even intermediate stages. Transarterial embolisation and conformal radiotherapy offered survival benefits for selected patients in advanced and terminal stages. In conclusion, following the treatment schedules allocated by BCLC staging had survival benefits for HCC patients. [ABSTRACT FROM AUTHOR]

Aim: The term MetALD has been introduced to describe individuals who have metabolic dysfunction-associated steatotic liver disease (MASLD) with greater alcohol consumption, according to the new nomenclature for steatotic liver disease (SLD). This study aims to evaluate the prevalence and clinical characteristics of MetALD in the general population., Methods: This study is a retrospective, cross-sectional analysis that utilizes the population-based data from the Korea National Health and Nutrition Examination Survey (KNHANES) undertaken between 2019 and 2021. A total of 16 521 participants aged over 18 years were included in the analysis. The presence of hepatic steatosis was determined based on a hepatic steatosis index of 36 or higher., Results: The prevalence of MetALD was 2.8% (95% confidence interval, 2.5-3.2). Individuals with MetALD were predominantly men (85.4%) and tended to be younger compared to those with MASLD. They showed a higher prevalence of hypertension and had significantly higher levels of fasting glucose, triglycerides, high-density lipoprotein cholesterol, and creatinine compared to individuals with MASLD. The average daily total energy intake was higher in the MetALD group. In addition, the MetALD group had a lower proportion of unemployment with higher income compared to the MASLD group., Conclusion: Patients with MetALD showed distinct clinical characteristics from those with MASLD. The characteristics of MetALD were similar to those with alcohol-related liver disease. Further analysis of MetALD across various regions and ethnic groups would be needed., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

The objective of our study is to measure perirenal fat thickness using MRI in individuals with steatotic liver disease and investigate the relationship between perirenal fat thickness and metabolic syndrome. This retrospective study included consecutive patients with steatotic liver disease who underwent magnetic resonance imaging-proton density fat fraction from October 2018 to February 2020. Among them, patients with crossed fused kidneys or who underwent nephrectomy were excluded. The metabolic abnormalities were reviewed; presence of hypertension, type 2 diabetes, abdominal circumference, triglyceride, and high-density lipoprotein. Perirenal fat was measured in four directions in both kidneys and the total sum of them was calculated. A total of 250 patients (140 males and 110 females) were included. Perirenal fat thickness showed a moderate correlation with waist circumference, creatinine, and hepatic fat fraction (all p < 0.001). Perirenal fat thickness was significantly higher in patients with metabolic syndrome than in patients without (76.8 mm vs. 65.1 mm, p = 0.004). In multivariable regression analysis, the group with high perirenal fat thickness had as significantly higher odd ratio of 2.71 compared to the low group. The perirenal fat thickness is independently associated with metabolic syndrome in patients with steatotic liver disease., (© 2024. The Author(s).)

Background: Despite intervention efforts, negative alcohol-related consequences continue to impact young adults. Most alcohol interventions focus on reducing alcohol consumption; however, previous research indicates that focusing solely on alcohol use may not decrease consequences. Additionally, many alcohol interventions have diminishing engagement, and few are designed with young adults involved in the development process. Drawing on user-centered design, this study sought to understand young adult perceptions, preferences, and needs for electronic interventions specifically aimed at reducing alcohol consequences., Methods: Using semi-structured qualitative interviews, 21 young adult drinkers (ages 18-24; 57.1% female) shared their opinions regarding the need for electronic interventions (i.e., mobile or web-delivered) to reduce alcohol consequences as well as their preferences for content, features, and ways to increase engagement. Interviews were coded and analyzed using a multi-step thematic analysis approach., Results: As part of our discovery phase of intervention development, content coding revealed four main themes. Participants perceived several benefits of interventions focused on alcohol consequences, such as promoting mindful alcohol use and reducing alcohol-related harms. Participants also discussed perceived limitations of such programs, including believing consequences from drinking are unavoidable, necessary for learning, and associated with peer pressure. Preferences for features included real-time tracking, personalized feedback, and psychoeducation along with preferences for design including non-judgmental framing, interactive content, and a user-friendly platform., Conclusions: Engaging end users early in the development process is a valuable approach to increase intervention relevancy with the target population. This can also inform intervention content and design to maximize engagement and satisfaction (e.g., framing, features, and interactivity) while also reducing barriers identified early on (e.g., peer pressure)., (© 2024 Research Society on Alcohol.)

Background: Simultaneous alcohol and cannabis use is associated with riskier daily drinking. However, little research has tested momentary mechanisms through which simultaneous use predicts continued drinking during acute drinking episodes. The current study tested whether simultaneous use moments predicted within-episode increases in subjective responses, craving, and continued drinking, and whether these relations were potentiated in social versus solitary settings., Methods: Emerging adults who co-use alcohol and cannabis (N = 85) completed 21 days of ecological momentary assessment with event-contingent reports during drinking episodes. Three-level multilevel models tested whether simultaneous (vs. alcohol-only) use moments indirectly predicted subsequent, continued drinking through subjective responses (i.e., high-arousal positive/stimulant, high-arousal negative/aggression, low-arousal positive/relaxation, low-arousal negative/impairment) and alcohol craving, and whether relations differed by social versus solitary contexts., Results: Within drinking episodes, simultaneous (vs. alcohol-only) use moments were associated with increased stimulation, which was indirectly associated with continued drinking through increased alcohol craving. Additionally, the relation between simultaneous (vs. alcohol-only) use and stimulating effects was potentiated during solitary drinking moments, whereas the relation between stimulating effects and craving was potentiated during social drinking moments. However, stimulating effects were higher in social contexts across all moments. Finally, simultaneous (vs. alcohol-only) use moments were associated with increased relaxation, which was indirectly associated with a lower likelihood of continued drinking through lesser craving., Conclusions: Simultaneous use predicted both continued within-episode drinking and cessation of drinking, with acute subjective effects and craving as mechanisms, dependent upon context. Just-in-time interventions should consider targeting affect, craving, and context in event-specific interventions., (© 2024 Research Society on Alcohol.)

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage "eat me" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders., (Copyright © 2024 by The American Association of Immunologists, Inc.)