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1.
Nat Immunol ; 23(6): 960-970, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35654851

RESUMO

The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate a large panel of human broadly neutralizing antibodies (bnAbs) to sarbecoviruses. Many of these bnAbs are remarkably effective in neutralizing a diversity of sarbecoviruses and against most SARS-CoV-2 VOCs, including the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor-binding domain (RBD). Consistent with targeting of conserved sites, select RBD bnAbs exhibited protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model in vivo. These bnAbs provide new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and provide a molecular basis for effective design of pan-sarbecovirus vaccines.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19/prevenção & controle , Humanos , Glicoproteína da Espícula de Coronavírus
2.
Mol Ecol ; 33(3): e17230, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38078558

RESUMO

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.


Assuntos
Animais Selvagens , Metagenômica , Animais , Humanos , População Urbana , Ecossistema , Sciuridae/genética
3.
J Rheumatol ; 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39486860

RESUMO

OBJECTIVE: Little is known about perceptions of aging among individuals living with systemic lupus erythematosus (SLE). Gaining this knowledge could help to identify targets for future behavioral interventions aimed at successful aging with SLE. This qualitative study sought to elicit the lived experiences, and essence, of aging from older adults with SLE. METHODS: We conducted semi-structured interviews with adults ≥65 years of age with SLE seen at a single tertiary center. Qualitative data were analyzed thematically using a phenomenological approach. We collected data on sociodemographic characteristics and disease features prior to each qualitative interview. RESULTS: Among 30 participants with mean age of 71.3 years and mean SLE duration of 26.3 years (range 5 to 62 years), four overarching themes emerged to describe the essence of aging with SLE: SLE and comorbid conditions, cumulative impact of SLE symptoms, SLE disease trajectory, and self-perceptions of aging. Older adults with SLE shared variable aging experiences, including perspectives on multimorbidity and disease trajectory and self-perceptions of aging. CONCLUSION: We identified both positive and negative self-perceptions of aging, often informed by participants' lived experiences of cumulative impact of SLE symptoms and SLE disease trajectory and underscoring the diversity of their experiences. Understanding self-perceptions of aging in this population could inform development of evidence-based strategies to empower older adults with SLE to harness their positivity and resilience and thus improve health-related outcomes, including health-related quality of life.

4.
J Natl Compr Canc Netw ; 22(7): 438-446, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39236750

RESUMO

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age at which to initiate screening in average-risk individuals and those with increased risk based on personal history of childhood, adolescent, and young adult cancer.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas
5.
Artigo em Inglês | MEDLINE | ID: mdl-39289141

RESUMO

OBJECTIVES: Approximately 5.5% of the population live with serious mental illnesses (SMI). Older adults with SMI experience a high burden of serious medical illnesses and disparities in advance care planning, symptom management, and caregiver support. The objectives of this study are to explore interdisciplinary clinician perspectives on the palliative care needs of older adults with SMI and serious medical illnesses. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study utilized thematic analysis of semi-structured interviews of interdisciplinary clinicians practicing palliative care, geriatrics, or geriatric/consultation-liaison psychiatry at four hospitals within an urban health system. MEASUREMENTS: Themes related to care of older adults with serious mental illness and serious medical illness with respect to clinician experiences, challenges in care, and opportunities to improve care. RESULTS: The authors interviewed 45 clinicians. Major themes identified were: (1) Current paradigms of palliative care do not meet the needs of patients with SMI; (2) Clinicians are motivated to care for this population but require more training and interdisciplinary practice; (3) There is a need for structural integration of psychiatric and palliative care services. CONCLUSIONS: The study underscores the inadequacy of current palliative care models in meeting the unique needs of older adults with SMI. Models of integrated psychiatric and serious illness care and enhanced training are needed to improve the delivery of palliative care. Integrated care models and workforce development at the interface of serious illness care and psychiatric have the potential to improve outcomes for this vulnerable population.

6.
Biol Lett ; 20(8): 20240033, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39140203

RESUMO

Characterizing the population density of species is a central interest in ecology. Eastern North America is the global hotspot for biodiversity of plethodontid salamanders, an inconspicuous component of terrestrial vertebrate communities, and among the most widespread is the eastern red-backed salamander, Plethodon cinereus. Previous work suggests population densities are high with significant geographic variation, but comparisons among locations are challenged by lack of standardization of methods and failure to accommodate imperfect detection. We present results from a large-scale research network that accounts for detection uncertainty using systematic survey protocols and robust statistical models. We analysed mark-recapture data from 18 study areas across much of the species range. Estimated salamander densities ranged from 1950 to 34 300 salamanders ha-1, with a median of 9965 salamanders ha-1. We compared these results to previous estimates for P. cinereus and other abundant terrestrial vertebrates. We demonstrate that overall the biomass of P. cinereus, a secondary consumer, is of similar or greater magnitude to widespread primary consumers such as white-tailed deer (Odocoileus virginianus) and Peromyscus mice, and two to three orders of magnitude greater than common secondary consumer species. Our results add empirical evidence that P. cinereus, and amphibians in general, are an outsized component of terrestrial vertebrate communities in temperate ecosystems.


Assuntos
Biomassa , Florestas , Densidade Demográfica , Urodelos , Animais , Urodelos/fisiologia , Biodiversidade , América do Norte
7.
J Geriatr Psychiatry Neurol ; 37(1): 3-13, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37161303

RESUMO

OBJECTIVES: Older adults with psychiatric illnesses often have medical comorbidities that require symptom management and impact prognosis. Geriatric psychiatrists are uniquely positioned to meet the palliative care needs of such patients. This study aims to characterize palliative care needs of geriatric psychiatry patients and utilization of primary palliative care skills and subspecialty referral among geriatric psychiatrists. METHODS: National, cross-sectional survey study of geriatrics psychiatrists in the United States. RESULTS: Respondents (n = 397) reported high palliative care needs among their patients (46-73% of patients). Respondents reported using all domains of palliative care in their clinical practice with varied comfort. In multivariate modeling, only frequency of skill use predicted comfort with skills. Respondents identified that a third of patients would benefit from referral to specialty palliative care. CONCLUSIONS: Geriatric psychiatrists identify high palliative care needs in their patients. They meet these needs by utilizing primary palliative care skills and when available referral to subspecialty palliative care.


Assuntos
Transtornos Mentais , Psiquiatria , Humanos , Estados Unidos , Idoso , Cuidados Paliativos/métodos , Cuidados Paliativos/psicologia , Estudos Transversais , Psiquiatria Geriátrica
8.
Med Teach ; : 1-5, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889448

RESUMO

Academic physicians are responsible for the education of medical students, residents, and other practicing physicians through clinical rotations lectures, seminars, research, and conferences. Therefore, the increasing need to recruit academic physicians holds immense value within the healthcare system. Academic Medicine Interest Group (AMIG) is a collective made up of students who share an interest in the growth and advancement of academic medicine. We present a guide and model on establishing an AMIG. We found that AMIG fostered professional growth by providing leadership, research, and teaching opportunities. Strategic planning, effective leadership, and group organization were all necessary for the success of the group.

9.
Angew Chem Int Ed Engl ; : e202413395, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166494

RESUMO

We report the development and applications of a computer vision based reaction monitoring method for parallel and high throughput experimentation (HTE). Whereas previous efforts reported methods to extract bulk kinetics of one reaction from one video, this new approach enables one video to capture bulk kinetics of multiple reactions running in parallel. Case studies, in and beyond well-plate high throughput settings, are described. Analysis of parallel dye-quenching hydroxylations, DMAP-catalysed esterification, solid-liquid sedimentation dynamics, metal catalyst degradation, and biologically-relevant sugar-mediated nitro reduction reactions have each provided insight into the scope and limitations of camera-enabled high throughput kinetics as a means of widening known analytical bottlenecks in HTE for reaction discovery, mechanistic understanding, and optimisation. It is envisaged that the nature of the multi-reaction time-resolved datasets made available by this analytical approach will later serve a broad range of downstream efforts in machine learning approaches to exploring chemical space.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37555816

RESUMO

OBJECTIVES: Frailty is a risk factor for adverse health in systemic lupus erythematosus (SLE). The Fried phenotype (FP) and the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) are common frailty metrics reflecting distinct approaches to frailty assessment. We aimed to 1) compare frailty prevalence according to both metrics in women with SLE and describe differences between frail and non-frail participants using each method and 2) evaluate for cross-sectional associations between each metric and self-report disability. METHODS: Women aged 18-70 years with SLE were enrolled. FP and SLICC-FI were measured, and agreement calculated using a kappa statistic. Physician-reported disease activity and damage, Patient Reported Outcome Measurement Information System (PROMIS) computerized adaptive tests, and Valued Life Activities (VLA) self-report disability were assessed. Differences between frail and non-frail participants were evaluated cross-sectionally, and the association of frailty with disability was determined for both metrics. RESULTS: Of 67 participants, 17.9% (FP) and 26.9% (SLICC-FI) were frail according to each metric (kappa = 0.41, p< 0.01). Compared with non-frail women, frail women had greater disease damage, worse PROMIS scores, and greater disability (all p< 0.01 for FP and SLICC-FI). After age adjustment, frailty remained associated with a greater odds of disability (FP: odds ratio [OR] 4.7, 95% confidence interval [CI] 1.2-18.8; SLICC-FI: OR 4.6, 95% CI 1.3-15.8). CONCLUSION: Frailty is present in 17.9-26.9% of women with SLE. These metrics identified a similar, but non-identical group of women as frail. Further studies are needed to explore which metric is most informative in this population.

11.
Psychosom Med ; 85(7): 612-618, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37010232

RESUMO

OBJECTIVES: Technology has substantial potential to transform and extend care for persons with chronic pain, a burdensome and costly condition. To catalyze the development of impactful applications of technology in this space, we developed the Pain Tech Landscape (PTL) model, which integrates pain care needs with characteristics of technological solutions. METHODS: Our interdisciplinary group representing experts in pain and human factors research developed PTL through iterative discussions. To demonstrate one potential use of the model, we apply data generated from a narrative review of selected pain and technology journals (2000-2020) in the form of heat map overlays, to reveal where pain tech research attention has focused to date. RESULTS: The PTL comprises three two-dimensional planes, with pain care needs on each x axis (measurement to management) and technology applications on the y axes according to a) user agency (user- to system-driven), b) usage time frame (temporary to lifelong), and c) collaboration (single-user to collaborative). Heat maps show that existing applications reside primarily in the "user-driven/management" quadrant (e.g., self-care apps). Examples of less developed areas include artificial intelligence and Internet of Things (i.e., Internet-linked household objects), and collaborative/social tools for pain management. CONCLUSIONS: Collaborative development between the pain and tech fields in early developmental stages using the PTL as a common language could yield impactful solutions for chronic pain management. The PTL could also be used to track developments in the field over time. We encourage periodic reassessment and refinement of the PTL model, which can also be adapted to other chronic conditions.


Assuntos
Dor Crônica , Humanos , Dor Crônica/terapia , Inteligência Artificial , Doença Crônica , Manejo da Dor , Tecnologia
12.
Nutr Cancer ; 75(10): 1900-1910, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791878

RESUMO

Studies of dietary inflammation potential and risks of colorectal cancer precursors are limited, particularly for sessile serrated lesions (SSLs). This study examines the association using the energy-adjusted dietary inflammatory index (E-DIITM), a measure of anti- and/or pro-inflammatory diet, in a large US colonoscopy-based case-control study of 3246 controls, 1530 adenoma cases, 472 hyperplastic polyp cases, and 180 SSL cases. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. Analyses were stratified by participant characteristics, and urinary prostaglandin E2 metabolite (PGE-M) and high-sensitivity plasma C-reactive protein (hs-CRP) levels, inflammation biomarkers. Highest E-DII™ intake was associated with significantly increased risks of colorectal adenomas (OR 1.36, 95% CI 1.11, 1.67), and hyperplastic polyps (OR 1.43, 95% CI 1.06, 1.98), compared with participants consuming the lowest E-DII™ quartile. A similar, but non-significant, increased risk was also observed for SSLs (OR 1.41, 95% CI 0.82, 2.41). The positive association was stronger in females (pinteraction <0.001), normal weight individuals (ptrend 0.01), and in individuals with lower inflammatory biomarkers (ptrend 0.02 and 0.01 for PGE-M and hs-CRP, respectively). A high E-DII™ is associated with colorectal polyp risk, therefore promoting an anti-inflammatory diet may aid in preventing colorectal polyps.


Assuntos
Adenoma , Pólipos Adenomatosos , Pólipos do Colo , Neoplasias Colorretais , Neoplasias Retais , Feminino , Humanos , Pólipos do Colo/patologia , Estudos de Casos e Controles , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Adenoma/etiologia , Colonoscopia , Dieta/efeitos adversos , Inflamação , Biomarcadores , Fatores de Risco
13.
J Int Neuropsychol Soc ; 29(6): 551-560, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36200831

RESUMO

OBJECTIVE: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel. METHOD: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates. RESULTS: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results. CONCLUSION: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.


Assuntos
Traumatismos por Explosões , Concussão Encefálica , Militares , Transtornos de Estresse Pós-Traumáticos , Humanos , Traumatismos por Explosões/complicações , Traumatismos por Explosões/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Cognição , Testes Neuropsicológicos , Guerra do Iraque 2003-2011 , Campanha Afegã de 2001-
14.
Ann Pharmacother ; 57(4): 397-407, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35950625

RESUMO

BACKGROUND: Agitation management is a principal challenge on inpatient psychiatric units. Overreliance on common prescribing strategies of pro re nata (PRN) medication administration is problematic, given the tendencies to have overlapping or unclear indications. OBJECTIVE: Piloted project to determine whether a standardized protocol for agitation intervention may reduce PRN medication administration. METHODS: The Birmingham Agitation Management (BAM) interdisciplinary team uniquely connected the Brøset Violence Checklist (BVC) for assessment of agitation severity to a standardized PRN medication order set. Nurses on the piloted unit were trained on how to score the BVC and administer medications. Patients were assessed by the BVC every 4 hours and, based on their score, would receive no medication, low-dose benzodiazepine, high-dose benzodiazepine, or high-dose benzodiazepine plus antipsychotic. The primary end point compared the number of PRNs administered after novel protocol implementation with a retrospective cohort. Secondary measures included analysis of medication-related effects, seclusion, and physical restraint rates. RESULTS: 377 patients were included in the final analyses (184 pre-BAM, 193 BAM intervention group). No significant differences were seen in patient characteristics between groups. The total number of PRNs administered decreased by 42.5%, with both the mean and median number of administrations decreasing significantly (95% confidence interval [CI] = [1.68-5.75]; P < 0.001). A trend was noted between the number of PRNs administered and seclusion rates, but did not reach statistical significance (95% CI = [-7.28 to 60.31]; P = 0.124). CONCLUSIONS: In seemingly the first initiative of its kind, we found that a standardized agitation management protocol can help decrease the total number of PRN administrations for agitation without worsening of restraint rates and may possibly reduce the risk of adverse effects. These results require validation in specific, larger populations.


Assuntos
Antipsicóticos , Ansiedade , Humanos , Estudos Retrospectivos , Preparações Farmacêuticas , Antipsicóticos/efeitos adversos , Benzodiazepinas/uso terapêutico
15.
Aging Ment Health ; 27(7): 1322-1328, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36068999

RESUMO

OBJECTIVES: Caregivers of individuals with Alzheimer's disease and related dementias experience significant burden and adverse outcomes. Enhancing caregiver self-efficacy has the potential to mitigate these negative impacts, yet little is known about its relationship with other aspects of caregiving. This study examined the relationship between self-efficacy and outcomes; identified factors associated with self-efficacy; examined the mediating role of self-efficacy; and analyzed whether there were racial/ethnic differences. METHODS: Data from caregivers (N = 243) were collected from the Caring for the Caregiver Network study. Participants' level of self-efficacy, depression, burden, and positive aspects of caregiving was assessed using validated measures. RESULTS: Two self-efficacy subscales predicted caregiver depression, burden, and positive aspects of caregiving. Being White, a spouse, or having a larger social network predicted lower self-efficacy for obtaining respite. Higher income and lower preparedness predicted lower self-efficacy for controlling upsetting thoughts and responding to disruptive behaviors. Self-efficacy for controlling upsetting thoughts mediated the relationship between preparedness and depression along with the relationship between preparedness and burden. Race/ethnicity did not improve model fit. CONCLUSION: Self-efficacy plays an important role in caregiver outcomes. These findings indicate that strategies to improve caregiver self-efficacy should be an integral component of caregiver interventions.

16.
Int J Mol Sci ; 24(14)2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37511584

RESUMO

Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Survivina/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Mama/metabolismo , Carcinoma Ductal de Mama/patologia
17.
Physiol Rev ; 95(3): 1025-109, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26133937

RESUMO

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca(2+) dysregulation is present through altered Ca(2+) homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.


Assuntos
Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Polineuropatias/fisiopatologia , Animais , Fenômenos Biomecânicos , Estado Terminal , Modelos Animais de Doenças , Metabolismo Energético , Acoplamento Excitação-Contração , Humanos , Mediadores da Inflamação/metabolismo , Unidades de Terapia Intensiva , Canais Iônicos/metabolismo , Mecanotransdução Celular , Proteínas Motores Moleculares/metabolismo , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Debilidade Muscular/metabolismo , Debilidade Muscular/terapia , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Doenças Musculares/metabolismo , Doenças Musculares/terapia , Polineuropatias/diagnóstico , Polineuropatias/etiologia , Polineuropatias/metabolismo , Polineuropatias/terapia , Valor Preditivo dos Testes , Fatores de Risco
18.
Pain Med ; 23(2): 280-287, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480572

RESUMO

OBJECTIVES: The COVID-19 pandemic and resulting shelter-in-place orders have profoundly changed the everyday social environment. This study examines the relationship between pain and psychological distress (depression, anxiety, and loneliness) among U.S. adults ages 54 and older during the pandemic. We also test whether use of technology for social purposes moderates the association between pain severity and psychological distress. METHODS: Using cross-sectional data on 1,014 adults ages 54 and older (pain free, n = 637; mild pain, n = 106; moderate pain, n = 227; and severe pain, n = 64) from the 2020 Health and Retirement Study COVID-19 Project (Early, Version 1.0), we conducted regression analyses to test the association between pain severity and psychological outcomes and to assess social technology use frequency as a moderator. RESULTS: Compared with their pain-free peers, participants with mild-to-moderate pain reported more depressive symptoms and greater loneliness; those with severe pain reported higher levels of depression, anxiety, and loneliness. Social technology use was associated with lower levels of depression and loneliness. However, interaction analyses show that social technology use predicted an increase in depression for individuals with pain but a decrease in depression among pain-free individuals. For anxiety and loneliness, no significant effects of social technology use were observed. CONCLUSION: Older adults with pain are at high risk of depression, anxiety, and loneliness during the pandemic. Although social technologies have become a common alternative to face-to-face interactions during the COVID-19 crisis, and overall they can provide mental health benefits, our results suggest that social technologies can be detrimental to psychological well-being among people with pain. These findings can inform technology-based interventions aiming to promote well-being among older adults with pain.


Assuntos
COVID-19 , Angústia Psicológica , Idoso , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Humanos , Pessoa de Meia-Idade , Dor/epidemiologia , Pandemias , SARS-CoV-2 , Tecnologia
19.
Pain Med ; 23(8): 1401-1408, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385109

RESUMO

OBJECTIVE: In this cross-sectional study of 237 older adults, we ascertained the importance of seven pain treatment goals and identified factors associated with their perceived importance. METHODS: Participants (mean age = 72 years) ranked each goal (e.g., pain reduction; finding a cure) on a 1 (not at all important) to 10 (extremely important) scale. We used general linear models to identify sociodemographic and pain factors independently associated with the perceived importance of each goal and repeated measures mixed models to examine their relative importance. RESULTS: The goal with the lowest adjusted score was "minimize harmful side effects from pain medications" with a mean (standard error [SE]) of 6.75 (0.239), while the highest ranked goals, "finding a cure," and "reducing my pain" had mean scores of 8.06 (0.237) and 7.89 (0.235), respectively. Pain reduction did not differ significantly from the average of the other 6 goals (P = .072) but was significantly different when compared with the goals of minimizing side effects (P < .0001) and finding a cause for the pain (P = .047), and different from the average of the five other goals excluding finding a cure (P = .021). We did not identify differences in the importance of the seven goals by gender or race/ethnicity. Age was inversely associated with the goals of minimizing harmful side effects and decreasing pain's effects on everyday activities. Pain reduction was rated more important than all other goals but finding a cure. CONCLUSIONS: Future research is needed to establish the benefits of eliciting treatment goals when delivering pain care to older adults.


Assuntos
Objetivos , Vida Independente , Idoso , Estudos Transversais , Humanos , Dor/complicações , Dor/tratamento farmacológico , Medição da Dor
20.
Aging Ment Health ; 26(1): 179-185, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33291958

RESUMO

OBJECTIVE: Despite recent concerns over the increase in opioid misuse among aging adults, little is known about the prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older patients with psychiatric disorders. This study aims to determine the lifetime prevalence of nonmedical opioid use among underserved, vulnerable U.S. adults aged ≥45 years with psychiatric disorders. METHOD: A nationally representative sample (n = 3,294) was obtained from the 2014 Health Center Patient Survey which collects data on psychiatric disorders, opioid use, and other health information from underserved, vulnerable U.S. primary care populations. Predictor variables included self-reported panic disorder, generalized anxiety disorder, schizophrenia, or bipolar disorder. The outcome variable was self-reported lifetime nonmedical opioid use. Frequencies, counts, and unadjusted and adjusted logistic regression models were conducted with the cross-sectional survey dataset. RESULTS: Patients with bipolar disorder had the highest lifetime nonmedical opioid use rate (20.8%), followed by schizophrenia (19.3%), panic disorder (16.5%), and generalized anxiety disorder (14.5%). Nonmedical opioid use was significantly associated with bipolar disorder (OR 3.46, 95% CI [1.33, 8.99]) and generalized anxiety disorder (OR 2.03 95% CI [1.08, 3.83]). CONCLUSION: Our findings demonstrate a high prevalence of lifetime nonmedical opioid use in underserved, vulnerable middle-aged and older health center patients with psychiatric disorders. Given the prevalence, health center professionals should monitor, prevent, and treat new or reoccurring signs and symptoms of nonmedical opioid use in this high-risk group of aging patients with psychiatric disorders.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Idoso , Transtornos de Ansiedade , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prevalência , Estados Unidos/epidemiologia
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