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INTRODUCTION: Recent expansion of cannabis legalization in multiple states calls for reexamination of the prevalence of cannabis use, cannabis use disorder (CUD), and the associations between CUD severity and substance use treatment. We used Andersen's behavioral model of healthcare use as the conceptual/analytic framework for examining treatment use. METHODS: We used data from the 2022 National Survey on Drug Use and Health (NSDUH; N = 47,100, age 18+) to describe the prevalence of past-year cannabis use, CUD and CUD severity, other substance use disorders, and substance use treatment. We compared sociodemographic, mental health, healthcare use, and cannabis and other substance use characteristics by CUD severity. Finally, we used logistic regression models to examine the associations between CUD severity and substance use treatment. RESULTS: Of the U.S. adult population, 23.0 % used cannabis in the past year; 7.0 % had a CUD (3.9 % mild, 1.9 % moderate, and 1.2 % severe CUD); and 4.7 % received substance use treatment. Of past-year cannabis users, 30.3 % had CUD (16.9 % mild, 8.4 % moderate, and 5.0 % severe CUD), and 9.6 % received substance use treatment. Cannabis users had 3-4 times higher rates of other substance use disorders than nonusers. Of those with CUD, 38.4 % had moderate/severe mental illness, 52.4 % had other substance use disorders, and 16.5 % received substance use treatment. Among all cannabis users, moderate (aOR [adjusted odds ratios] = 1.48, 95 % CI = 1.03-2.13) and severe (aOR = 2.57, 95 % CI = 1.60-4.11) CUDs were associated with greater odds of substance use treatment. Among cannabis users without nicotine dependence and alcohol, opioid, tranquilizer/sedative, and stimulant use disorders, only severe CUD (aOR = 6.03, 95 % CI = 3.37-10.78) was associated with greater odds of substance use treatment. CONCLUSIONS: This study shows increased prevalence of cannabis use and CUD among U.S. adults, and with or without other substance use disorders, CUD was associated with greater odds of substance use treatment. However, the overall low rate of treatment use among those with CUD is concerning. Healthcare providers need to provide education for both medical and recreational users on the development of tolerance and dependence. Harm reduction strategies to minimize the negative consequences of CUD are also needed.

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Given diversified cannabis products, we examined associations between cannabis consumption methods and cannabis risk perception of smoking cannabis 1-2 times a week. Using the 2022 U.S. National Survey on Drug Use and Health data (N = 12,796 past-year adult cannabis users; M = 6127 and F = 6669), we used multinomial and binary logistic regression models. Smoking was the most prevalent method, followed by eating/drinking, vaping, and dabbing. One-half of cannabis users reported no perceived risk of smoking cannabis 1-2 times a week, 37.5% perceived slight risk, 9.2% moderate risk, and 2.9% great risk. Those with moderate or great risk perception had a lower likelihood of using 4+ methods of consumption (e.g., RRR = 0.40, 95% CI = 0.20, 0.77 for great risk perception). Any perceived risk was associated with higher odds of edibles/drinks only (e.g., aOR = 2.81, 95% CI = 1.43, 5.54 for great risk perception). Along with medical use and CUD, sociodemographic factors, mental illness, and other substance use were also significant correlates of cannabis consumption methods. Understanding the varying risk perceptions associated with different consumption methods is needed for harm reduction initiatives. More research is needed on cannabis products, particularly edibles/drinks and dabs/concentrates, to better understand the potential risks associated with them.

Asunto(s)

Fumar Marihuana , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Persona de Mediana Edad , Fumar Marihuana/epidemiología , Adolescente , Estados Unidos/epidemiología , Cannabis , Percepción , Uso de la Marihuana/epidemiología , Riesgo

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Despite the high prevalence of alcohol use and binge drinking among older adults, little research has been conducted on the association between their alcohol risk perception and alcohol use patterns. Using data on past-year alcohol users aged 50 and older (N = 6693) in the 2022 National Survey on Drug Use and Health, we examined the (1) associations between risk perception of binge alcohol use 1-2 times a week and alcohol use frequency, binge use frequency, and alcohol use disorder (AUD), and (2) the association between alcohol treatment use and risk perception. About 40% of past-year alcohol users perceived great risk of binge alcohol use 1-2 times a week, and 27% of past-year users had binge drinking in the past month. Multivariable analyses showed the negative association between great risk perception and alcohol use frequency (IRR = 0.60, 95%CI = 0.48-0.74 for daily use) and past-month binge alcohol use (IRR = 0.33, 95%CI = 0.19-0.57 for 6-19 days of binge use). The odds of great risk perception were also lower among those with mild AUD. Risk perception was not significantly associated with alcohol treatment. The lower likelihood of risk perception among problematic alcohol users and low treatment use is concerning. Education and interventions to reduce harm from alcohol are needed.

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Alcoholismo , Consumo Excesivo de Bebidas Alcohólicas , Humanos , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Alcoholismo/epidemiología , Percepción , Consumo de Bebidas Alcohólicas/epidemiología , Anciano de 80 o más Años

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ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

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Adenosina Desaminasa , Receptores ErbB , Hepatocitos , Helicasa Inducida por Interferón IFIH1 , Hígado , Macrófagos , Ratones Noqueados , Progranulinas , Animales , Adenosina Desaminasa/metabolismo , Adenosina Desaminasa/genética , Receptores ErbB/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Progranulinas/metabolismo , Progranulinas/genética , Hígado/metabolismo , Hígado/inmunología , Hígado/patología , Hepatocitos/metabolismo , Ratones , Helicasa Inducida por Interferón IFIH1/metabolismo , Helicasa Inducida por Interferón IFIH1/genética , Transducción de Señal , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones Endogámicos C57BL , ARN Bicatenario/metabolismo , Edición de ARN

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OBJECTIVE: To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). METHODS: Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS4) ≤75) were enrolled. Primary outcome was KOOS4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded. RESULTS: 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. CONCLUSION: CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975.

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Análisis Costo-Beneficio , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Rodilla/rehabilitación , Persona de Mediana Edad , Anciano , Técnicos Medios en Salud , Método Simple Ciego , Ortopedia , Calidad de Vida , Grupo de Atención al Paciente , Terapia por Ejercicio/métodos

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INTRODUCTION: Despite known contraindications, benzodiazepines are frequently prescribed for older adults. This study utilizes poison control center data on benzodiazepine-involved cases aged 50 and above to compare the characteristics of suspected suicide attempt with other intentional misuse cases. We also examined associations of major medical outcomes (major effect/death) with demographic characteristics and other co-used substances in each group. METHODS: The study employed data from the America's Poison Center National Poison Data System from 2015-2022. Descriptive statistics and binary logistic regression models were used. RESULTS: Of the benzodiazepine-poisoning cases of intentional misuse (n = 93,245), 85 percent were suicide attempts and 15 percent were other intentional misuses. Reports to poisons centers showed a decline from 2019-2022 when compared to 2015-2016. However, the likelihood of a reported suicide attempt, compared to other intentional misuse, was greater in 2019-2022 compared to 2015-2016 and among those who co-used antidepressants, anxiolytics, atypical antipsychotics, other benzodiazepines, other analgesics, anticonvulsants, and alcohol. The odds of major effect/death in both groups were also greater in 2019-2022, with suicide attempt cases in advanced ages showing higher odds. The co-use of antidepressants, prescription opioids, atypical antipsychotics, anticonvulsants, and other analgesics were associated with a higher likelihood of major effect/death in both exposure groups. For instance, adjusted odds ratios for co-used prescription opioids were 2.20 (95 percent confidence intervals: 2.09-2.31) among suicide attempt cases and 3.51 (95 percent confidence intervals: 3.10-3.97) among other intentional misuse cases. DISCUSSION: Healthcare providers need to screen for suicidal ideation among benzodiazepine users, with special attention to an increased risk of suicide attempt among those who co-use antidepressants and opioids and to decreasing adverse outcomes in all misuse cases. Assessments of underlying mental health and substance use problems and medication regimens to minimize polypharmacy and drug interactions are needed to reduce adverse outcomes. CONCLUSIONS: Though the numbers of benzodiazepine-involved suicide attempt and other intentional misuse cases reported to United States poison centers decreased in recent years, the likelihood of major medical effect/death among these cases have increased.

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Benzodiazepinas , Centros de Control de Intoxicaciones , Intento de Suicidio , Humanos , Benzodiazepinas/envenenamiento , Centros de Control de Intoxicaciones/estadística & datos numéricos , Masculino , Femenino , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Intento de Suicidio/estadística & datos numéricos , Anciano de 80 o más Años , Sobredosis de Droga/epidemiología , Intoxicación/epidemiología

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In this study, based on the 2022 National Health and Aging Trend Study (N = 5,593, age 65+), we examined direct associations between moderate and vigorous physical exercise (PE) and depressive/anxiety symptoms as well as bothersome pain and sleep problems. We then examined if the association between PE and depressive/anxiety symptoms would be partially mediated by the effects of PE on bothersome pain and sleep problems. Results from a path model showed that controlling for sociodemographic and health statuses, PE was negatively associated with depressive/anxiety symptoms and bothersome pain, but it was not significantly associated with sleep problems. The mediation analysis showed that 10% of the total effects of PE on depressive/anxiety symptoms was indirect effects of PE on bothersome pain. This study is important as it examined the associations among PE, pain, sleep, and depression/anxiety in community-dwelling older adults in their natural environments. Healthcare and social service providers for older adults need to emphasize the importance and benefits of PE for older adults' physical and mental health. Easy access to venues for PE is also important.

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Using the 2018-2021 National Health Interview Survey data, we examined the associations between healthcare cost burden and depressive/anxious feelings in older adults. Nearly12% reported healthcare cost burden and 18% daily/weekly depressive/anxious feelings. Healthcare cost burden was higher among women, racial/ethnic minorities, those with chronic illnesses, mobility impairment, and those with Medicare Part D, but lower among individuals with Medicare-Medicaid dual eligibility, Medicare Advantage, VA/military insurance, and private insurance. Daily/weekly depressive/anxious feelings was higher among healthcare cost burden reporters. The COVID-19 pandemic-related medical care access problems were also associated with a higher risk of reporting healthcare cost burden and depression/anxiety.

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Medicare , Pandemias , Humanos , Femenino , Anciano , Estados Unidos/epidemiología , Autoinforme , Costos de la Atención en Salud

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Analyzing the 2021 National Survey on Drug Use and Health data with generalized linear models, we examined: (1) COVID pandemic-related and other correlates of mental health treatment use and unmet perceived treatment need among U.S. adults who experienced serious suicidal thoughts (N = 3,177); and (2) correlates of self-reported reasons for not receiving treatment. We found that 61% used any mental health treatment, and 48% of users and 37% of nonusers reported perceived treatment need. Significant correlates of treatment use were demographic factors, insurance, major depressive disorder, and illicit drug use disorder. Significant correlates of perceived treatment need were age 18-34, some college education, and major depressive episode. Perceived negative effect of the COVID pandemic on mental health was a significant factor for both treatment use and perceived need. The most frequent reasons for not getting treatment were the cost of treatment or lack of insurance and stigma-related concerns.

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COVID-19 , Servicios de Salud Mental , Ideación Suicida , Humanos , COVID-19/psicología , COVID-19/epidemiología , Adulto , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Adulto Joven , Adolescente , Servicios de Salud Mental/estadística & datos numéricos , SARS-CoV-2 , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Pandemias , Necesidades y Demandas de Servicios de Salud , Anciano , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología

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OBJECTIVES: To examine correlates of the changes in technology use among older adults and the associations of depression/anxiety symptoms with technology use changes. METHODS: We used the 2019-2021 U.S. National Health and Aging Trends Study (N = 3,063; age 70+). We fitted multinomial logistic regression models to examine: (1) correlates of never use and discontinued use versus use of email/texting and the internet during the 3-year study period; and (2) associations of past-month depression/anxiety symptoms in 2021 with use and discontinued use versus never use of email/texting and social network site (SNS). RESULTS: The findings show age, socioeconomic, and health barriers to technology use. Email/texting and SNS use in 2021, compared to never use in all 3 years, was associated with a lower likelihood of moderate/severe depression/anxiety symptoms in 2021 (RRR = 0.54, 95% CI = 0.37-0.81 for email/texting use; RRR = 0.56, 95% CI = 0.33-0.97 for SNS use). Video calls with family/friends were not associated with depression/anxiety symptoms. CONCLUSIONS: The findings expand the existing knowledge base regarding potential impact of technology use on mental health beyond the early months of the COVID-19 pandemic. CLINICAL IMPLICATIONS: More concerted efforts are warranted to help older adults' technology uptake and continued use and to promote mental health benefits of technology use.

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BACKGROUND: A significant portion of suicides are precipitated by interpersonal relationship problems. AIMS: To examine demographic and clinical correlates of any intimate partner conflicts (IPC) and other interpersonal conflicts (OPC) as suicide precipitants. METHODS: We analyzed data on 92,805 (72,628 male; 20,177 female) adult suicide decedents from the 2017 to 2019 U.S. National Violent Death Reporting System, using multinomial and binary logistic regression models. We included case examples from coroners/medical examiner (CME) and law enforcement (LE) agency reports. RESULTS: Of all decedents, 23.6% had IPC and 8.0% had OPC as a suicide precipitant. Compared to those without any relationship conflict, those who had IPC or OPC were younger and more likely to have had previous suicide attempt(s), alcohol/other substance use problems, and job/finance/housing and legal problems. Compared to those with OPC, those with IPC were more likely to be male and Hispanic and had higher odds of previous suicide attempt, depression diagnosis, alcohol problems, and more acute crises. CME/LE reports showed distress of divorce/break-up, other life stressors, prior suicide attempt(s), alcohol/other substance involvement, and/or loss of family support. CONCLUSIONS: Access to behavioral health treatment for those at risk of suicide in the face of IPC or OPC is essential for suicide prevention.

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Homicidio , Violencia , Adulto , Humanos , Masculino , Femenino , Estados Unidos , Causas de Muerte , Intento de Suicidio , Prevención del Suicidio

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RNA epigenetics, or epitranscriptome, is a growing group of RNA modifications historically classified into two categories: RNA editing and RNA modification. RNA editing is usually understood as post-transcriptional RNA processing (except capping, splicing and polyadenylation) that changes the RNA nucleotide sequence encoded by the genome. This processing can be achieved through the insertion or deletion of nucleotides or deamination of nucleobases, generating either standard nucleotides such as uridine (U) or the rare nucleotide inosine (I). Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent type of RNA modification in mammals and is catalyzed by adenosine deaminase acting on the RNA (ADAR) family of enzymes that recognize double-stranded RNAs (dsRNAs). Inosine mimics guanosine (G) in base pairing with cytidine (C), thereby A-to-I RNA editing alters dsRNA secondary structure. Inosine is also recognized as guanosine by the splicing and translation machineries, resulting in mRNA alternative splicing and protein recoding. Therefore, A-to-I RNA editing is an important mechanism that causes and regulates "RNA mutations" in both normal physiology and diseases including cancer. In this chapter, we reviewed current paradigms and developments in the field of A-to-I RNA editing in the context of cancer.

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Neoplasias , ARN , Animales , Humanos , ARN/genética , ARN/metabolismo , Edición de ARN , Neoplasias/genética , Nucleótidos/metabolismo , Inosina/genética , Inosina/metabolismo , Adenosina/genética , Adenosina/metabolismo , Guanosina/metabolismo , Mamíferos/genética , Mamíferos/metabolismo

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Background and aims: A majority of older adult suicide decedents used firearms. In this study, we focused on suicide decedents age 75+ who disclosed their suicidal intent within a month of their injury/death to examine demographic and clinical characteristics associated with firearm use and firearm access restriction attempts by their family members. Methods: The 2017-2019 U.S. National Violent Death Reporting System provided data (N = 1,734 suicidal intent disclosers; 1,476 males and 258 females; 21.4% of decedents age 75+). Generalized linear model (GLM) for a Poisson distribution with a log link was used to examine firearm use risk factors. Firearm access restriction attempts by decedents' family members were examined based on coroner/medical examiner and law enforcement (CME/LE) reports. Results: Nearly three quarters of disclosers disclosed their intent to family members, and 82.9% of males and 27.5% of females used firearms. GLM results showed males, non-Hispanic white people, and residents in the South and West regions had higher likelihood of firearm use. CME/LE reports of 140 out of 1,294 firearm decedents included narratives related to firearm restriction attempts or lack thereof. Firearm access restrictions were not attempted in 65 cases because family members did not take suicidal intent disclosure seriously or because decedents promised no self-harm. Partial or complete removal of firearms in 75 cases were not effective as decedents had hidden a firearm or purchased a new one. Others used different lethal methods. Implications: The findings indicate a need for: (a) training family members of older adults who are at risk of suicide in effective means safety/access restriction and strategies to prevent means substitution; (b) more comprehensive legislative reforms reducing access to firearms by those at risk of suicide; and (c) more comfort and palliative care and counseling for psychosocial risk factors.

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Armas de Fuego , Suicidio , Masculino , Femenino , Humanos , Anciano , Ideación Suicida , Suicidio/psicología , Factores de Riesgo , Violencia

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CONTEXT: Despite a rapidly growing number of older cocaine users, the link between cocaine use and suicide attempt in older adults has not been examined. We examined associations between co-used other substances and (1) suspected suicide attempts versus other intentional misuse, and (2) major medical outcomes (major effect or death) of suspected suicide attempts and other intentional misuse. METHODS: We used the 2015-2021 United States National Poison Data System (N = 5,191 cases age 50 and older). Descriptive statistics and generalized linear models for a Poisson distribution with a log link function were used to examine the study questions. RESULTS: Cocaine exposures steadily increased from 2015 through 2021. Over the seven years, 52.3% and 47.7% were suicide attempts and other intentional misuse cases, respectively. Co-use of alcohol (incidence rate ratios = 1.24, 95% confidence interval = 1.14-1.35) and psychotropic (e.g., antidepressants: incidence rate ratios = 1.37, 95% confidence interval = 1.24-1.53) and cardiovascular medications were associated with a higher likelihood of suicide attempt, but co-use of prescription opioids, heroin, or other illicit drugs was associated with a lower likelihood of suicide attempt compared to other intentional misuse. Prescription opioids and amfetamine were associated with a higher likelihood of major effect or death in both suicide attempts and intentional misuse and heroin use and injection use were associated with a higher likelihood of major effect/death among intentional misuse cases. CONCLUSIONS: These findings show that significant proportions of older cocaine users who attempted suicide also used psychotropic and cardiovascular medications. We suggest that healthcare providers screen for suicidal ideation among cocaine users, with special attention to an increased risk of suicide attempts among those who co-use cocaine with alcohol and psychotropic and other prescription medications.

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Cocaína , Mal Uso de Medicamentos de Venta con Receta , Humanos , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Intento de Suicidio , Heroína , Ideación Suicida , Analgésicos Opioides , Etanol

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Background and Objectives: Physical health problems are a significant late-life suicide precipitant. This study's purpose was to examine differences in (i) other suicide precipitants and psychiatric/substance use problems, and (ii) suicide methods (firearms, hanging/suffocation, and poisoning) in 3 age groups (55-64, 65-74, and 75+) of older suicide decedents who had physical health problems as a suicide precipitant. Research Design and Methods: Data came from the 2017-2019 U.S. National Violent Death Reporting System (N = 34,912; 27,761 males [79.5%] and 7,151 females [20.5%]). Generalized linear models for a Poisson distribution with a log link were used to examine the study questions. Results: Physical health problems were a suicide precipitant for 25.8%, 41.9%, and 57.7% of the 55-64, 65-74, and 75+ age groups, respectively, and were associated with a higher likelihood of having had depressed mood (IRR = 1.38, 95% CI: 1.33-1.43) and other substance use problems (IRR = 1.22, 95% CI: 1.13-1.31). Interaction effects showed that when job/finance/housing problems, depressed mood, or any psychiatric disorders were co-present with physical health problems, the age group differences in the predicted rates of physical health problems were diminished. Physical health problems were also positively associated with firearm and poisoning use, but negatively associated with hanging/suffocation. Interaction effects indicated that the predicted rates of firearm and poisoning use significantly increased among those aged 55-64 with than without physical health problems. Discussion and Implications: In all 3 age groups of older suicide decedents, physical health problems were the predominant suicide precipitant, and those with physical health problems had elevated depressed mood. Assessment of suicide risk, affordable and accessible health, and mental health services, restriction of access to lethal suicide methods, and policy-based suicide prevention approaches for older adults with physical health problems are needed.

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OBJECTIVE: To evaluate the neurodevelopmental outcomes at 5.5 years of age in children who were previously randomized to cow milk-based infant formula (control) or similar formula (milk fat globule membrane + lactoferrin) with added sources of bovine milk fat globule membrane and bovine lactoferrin through 12 months of age. DESIGN: Children who completed study feeding were invited to participate in follow-up assessments: cognitive development across multiple domains (primary outcome; Wechsler Preschool & Primary Scale of Intelligence, 4th Edition), inhibitory control/rule learning (Stroop Task), flexibility/rule learning (Dimensional Change Card Sort), and behavior/emotion (Child Behavior Checklist). RESULTS: Of 292 eligible participants (control: 148, milk fat globule membrane + lactoferrin: 144), 116 enrolled and completed assessments (control: 59, milk fat globule membrane + LF: 57). There were no group demographic differences except family income (milk fat globule membrane + lactoferrin significantly higher). Wechsler Preschool & Primary Scale of Intelligence, 4th Edition composite scores (mean ± standard error) for Visual Spatial (100.6 ± 1.7 vs 95.3 ± 1.7; P = .027), Processing Speed (107.1 ± 1.4 vs 100.0 ± 1.4; P < .001), and Full-Scale IQ (98.7 ± 1.4 vs 93.5 ± 1.5; P = .012) were significantly higher for milk fat globule membrane + lactoferrin versus control, even after controlling for demographic/socioeconomic factors. Stroop Task scores were significantly higher in milk fat globule membrane + lactoferrin versus control (P < .001). Higher Dimensional Change Card Sort scores (P = .013) in the border phase (most complex/challenging) were detected, and more children passed the border phase (32% vs 12%; P = .039) for milk fat globule membrane versus control. No group differences in Child Behavior Checklist score were detected. CONCLUSIONS: Children who received infant formula to 12 months of age with added bovine milk fat globule membrane and bovine lactoferrin versus standard formula demonstrated improved cognitive outcomes in multiple domains at 5.5 years of age, including measures of intelligence and executive function. TRIAL REGISTRATION: Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT04442477.

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Fórmulas Infantiles , Lactoferrina , Niño , Preescolar , Femenino , Humanos , Lactante , Glucolípidos , Glicoproteínas , Lactoferrina/farmacología

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CONTEXT: Cocaine and metamfetamine use and overdose deaths among United States adults have been increasing in recent years. We examined associations of medical outcomes with co-used opioids and other substances among cocaine, and metamfetamine exposures in people age ≥50 years (N = 9300) reported to the National Poison Data System, 2015-2021. METHODS: We first described increases in these exposures over time. We fitted generalized linear models for a Poisson distribution with a log link, one for cocaine exposures and the other for metamfetamine exposures, to examine associations of medical outcomes (major effects/death versus all others) with co-used other substances, controlling for exposure year and demographics. RESULTS: The number of exposures increased steadily during the seven years, but metamfetamine exposures increased more rapidly starting in 2018. One-fifth of cocaine and one-sixth of metamfetamine exposures suffered major effects/death. Co-use of prescription opioids (incident risk ratio = 2.00, 95% CI = 1.76-2.28 for cocaine; incident risk ratio = 1.62, 95% CI = 1.27-2.07 for metamfetamine), illicit fentanyl (incident risk ratio =1.88, 95% CI = 1.08-3.27 for cocaine; incident risk ratio = 2.05, 95% CI = 1.04-4.06 for metamfetamine), heroin (incident risk ratio =1.62, 95% CI = 1.37-1.90 for cocaine), or amfetamine (incident risk ratio =1.73, 95% CI = 1.28-2.33 for cocaine) was associated with a higher likelihood of major effects/death. DISCUSSION: Increases in the number of cocaine and metamfetamine exposures among older adults reported to poison centers are of concern, and so is the increased risk of major effects/death from polysubstance use, especially prescription and illicit opioids, among these illicit psychostimulant users. CONCLUSIONS: Healthcare provider screening of individuals at risk of cocaine and/or metamfetamine use and psychoeducation about the dangers of these substance use are needed.

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Cocaína , Metanfetamina , Venenos , Trastornos Relacionados con Sustancias , Humanos , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Analgésicos Opioides , Trastornos Relacionados con Sustancias/epidemiología , Centros de Control de Intoxicaciones

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TIR (Toll/interlukin-1 receptor) domains are found in archaea, bacteria and eukaryotes, featured in proteins generally associated with immune functions. In plants, they are found in a large group of NLRs (nucleotide-binding leucine-rich repeat receptors), NLR-like proteins and TIR-only proteins. They are also present in effector proteins from phytopathogenic bacteria that are associated with suppression of host immunity. TIR domains from plants and bacteria are enzymes that cleave NAD+ (nicotinamide adenine dinucleotide, oxidized form) and other nucleotides. In dicot plants, TIR-derived signalling molecules activate downstream immune signalling proteins, the EDS1 (enhanced disease susceptibility 1) family proteins, and in turn helper NLRs. Recent work has brought major advances in understanding how TIR domains work, how they produce signalling molecules and how these products signal.

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Nucleótidos , Inmunidad de la Planta , Inmunidad de la Planta/genética , Plantas/genética , Plantas/metabolismo , Dominios Proteicos , Proteínas NLR/genética , Bacterias/metabolismo , Enfermedades de las Plantas

RESUMEN

OBJECTIVES: To examine the changes in the frequency of going outside among U.S. older adults between 2020 and 2021 (post-COVID vaccine) and correlates of those changes. METHODS: We used the 2019-2021 National Health and Aging Trend Study (NHATS) (N = 3,063, age 70+) and multinomial logistic regression to analyze associations of increased and decreased frequencies in going outside with physical, psychosocial, and cognitive health, environmental (COVID concerns and transportation) factors, and social media use as the independent variables. RESULTS: In 2021 compared to 2020, 13% and 16% of those age 70+ reported increased and decreased frequencies, respectively. Increased frequency was associated with social media use. Decreased frequency was associated with poor physical health, depression/anxiety, and perceived memory decline. COVID concerns and transportation problems, as well as female gender, age 90+, and being non-Hispanic Black, were also significant correlates of decreased frequency. CONCLUSIONS: Most U.S. adults age 70+ appear to have resumed their 2019 level of frequency of going outside in 2021 after the COVID vaccines became available; however, 16% reported decreased frequency of going outside in 2021 compared to 2020. CLINICAL IMPLICATIONS: Older adults with physical, mental, and cognitive health challenges need help to increase their frequency of going outside.

Asunto(s)

Vacunas contra la COVID-19 , Estado de Salud , Humanos , Femenino , Anciano , Anciano de 80 o más Años

RESUMEN

We used the 2019-2021 U.S. National Health and Aging Trend Study (N = 3,063, age 70+) and multinomial logistic regression and generalized linear models with Poisson and log link to identify correlates of (1) recurrent falls (2 + falls) over 3 years (2019-2021); and (2) any subsequent fall among those who had a fall in 2019. We also examined the associations between falls and hospitalization in 2021. Results show that those with recurrent falls had greater physical/functional and psychological health problems in 2019, while single fallers over the 3 years were not significantly different from those without a fall. Exercise was associated with a lower likelihood of a subsequent fall among those who fell in 2019. Both a single fall and recurrent falls over the 3 years were associated with a higher risk of hospitalization in 2021. Multifactorial fall preventions including exercise and depression/anxiety treatment are needed to mitigate recurrent fall risks.

Asunto(s)

Envejecimiento , Hospitalización , Humanos , Anciano , Tiempo de Internación , Envejecimiento/psicología , Estado de Salud , Factores de Riesgo