Modified mesenchymal stromal cells by in vitro transcribed mRNA: a therapeutic strategy for hepatocellular carcinoma.

BACKGROUND: Mesenchymal stromal cells (MSCs) tropism for tumours allows their use as carriers of antitumoural factors and in vitro transcribed mRNA (IVT mRNA) is a promising tool for effective transient expression without insertional mutagenesis risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with antitumor properties by stimulating the specific immune response. The aim of this work was to generate modified MSCs by IVT mRNA transfection to overexpress GM-CSF and determine their therapeutic effect alone or in combination with doxorubicin (Dox) in a murine model of hepatocellular carcinoma (HCC). METHODS: DsRed or GM-CSF IVT mRNAs were generated from a cDNA template designed with specific primers followed by reverse transcription. Lipofectamine was used to transfect MSCs with DsRed (MSC/DsRed) or GM-CSF IVT mRNA (MSC/GM-CSF). Gene expression and cell surface markers were determined by flow cytometry. GM-CSF secretion was determined by ELISA. For in vitro experiments, the J774 macrophage line and bone marrow monocytes from mice were used to test GM-CSF function. An HCC model was developed by subcutaneous inoculation (s.c.) of Hepa129 cells into C3H/HeN mice. After s.c. injection of MSC/GM-CSF, Dox, or their combination, tumour size and mouse survival were evaluated. Tumour samples were collected for mRNA analysis and flow cytometry. RESULTS: DsRed expression by MSCs was observed from 2 h to 15 days after IVT mRNA transfection. Tumour growth remained unaltered after the administration of DsRed-expressing MSCs in a murine model of HCC and MSCs expressing GM-CSF maintained their phenotypic characteristic and migration capability. GM-CSF secreted by modified MSCs induced the differentiation of murine monocytes to dendritic cells and promoted a proinflammatory phenotype in the J774 macrophage cell line. In vivo, MSC/GM-CSF in combination with Dox strongly reduced HCC tumour growth in C3H/HeN mice and extended mouse survival in comparison with individual treatments. In addition, the tumours in the MSC/GM-CSF + Dox treated group exhibited elevated expression of proinflammatory genes and increased infiltration of CD8 + T cells and macrophages. CONCLUSIONS: Our results showed that IVT mRNA transfection is a suitable strategy for obtaining modified MSCs for therapeutic purposes. MSC/GM-CSF in combination with low doses of Dox led to a synergistic effect by increasing the proinflammatory tumour microenvironment, enhancing the antitumoural response in HCC.

Identification of functional enhancer variants associated with type I diabetes in CD4+ T cells.

Type I diabetes is an autoimmune disease mediated by T-cell destruction of ß cells in pancreatic islets. Currently, there is no known cure, and treatment consists of daily insulin injections. Genome-wide association studies and twin studies have indicated a strong genetic heritability for type I diabetes and implicated several genes. As most strongly associated variants are noncoding, there is still a lack of identification of functional and, therefore, likely causal variants. Given that many of these genetic variants reside in enhancer elements, we have tested 121 CD4+ T-cell enhancer variants associated with T1D. We found four to be functional through massively parallel reporter assays. Three of the enhancer variants weaken activity, while the fourth strengthens activity. We link these to their cognate genes using 3D genome architecture or eQTL data and validate them using CRISPR editing. Validated target genes include CLEC16A and SOCS1. While these genes have been previously implicated in type 1 diabetes and other autoimmune diseases, we show that enhancers controlling their expression harbor functional variants. These variants, therefore, may act as causal type 1 diabetic variants.

Placental glycosylation senses the anti-angiogenic milieu induced by human sFLT1 during pregnancy.

Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, -3 and -9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1high pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 high placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface.

Exercise improves respiratory function, body fluid and nitric oxide in hemodialysis patients.

Emerging evidence suggests that resistance training (RT) can mitigate respiratory muscle weakness in hemodialysis (HD) patients. However, the underlying mechanisms responsible for these beneficial effects remain unclear. The purpose of this study was to assess the impact of periodized RT on respiratory muscle strength and its relationship with handgrip strength (HGS), fat-free mass (FFM), nitric oxide (NO), and interdialytic weight gain (IWG) in HD patients. Thirty-three patients were randomly assigned to two groups: control (CTL; n=18) and RT (n=15). RT group did not perform any additional exercise training specific to the respiratory tract. Maximal inspiratory (MIP) and expiratory (MEP) pressures, peak expiratory flow (PEF), HGS, FFM, NO, and IWG were measured before and after the intervention period. Participants in the RT group engaged in a 24-week RT program, three times per week. RT resulted in significant improvements in MIP, MEP, PEF, as well as enhancements in HGS, FFM, NO, and IWG (p<0.05). Notably, inverse correlations were observed between MIP (r= -0.37, p=0.03) and PEF (r= -0.4, p=0.02) with IWG. Thus, the amelioration of HGS and FFM coincided with a reduction in respiratory muscle weakness among HD patients. Decreased IWG and increased circulating NO are plausible mechanisms contributing to these improvements.

Comparison between Injury Severity Score (ISS) and New Injury Severity Score (NISS) in predicting mortality of thoracic trauma in a tertiary hospital.

INTRODUCTION: measuring the severity of traumatic injuries is crucial for predicting clinical outcomes. Whereas the Injury Severity Score (ISS) has limitations in assigning scores to injuries at the same site, the New Injury Severity Score (NISS) corrects for this problem by taking into account the three most severe injuries regardless of the region of the body. This study seeks to comprehend the clinical and epidemiological profile of trauma patients while comparing the effectiveness of scales for predicting mortality. METHODS: a descriptive, observational and retrospective study using records of patients who underwent thoracotomy at the Hospital das Clínicas of the Federal University of Triângulo Mineiro between 2000 and 2019. Demographic data, mechanisms of injury, affected organs, length of stay and mortality were analyzed. Injury severity was assessed using the ISS and NISS, and statistical analyses were conducted using MedCalc and SigmaPlot. RESULTS: 101 patients were assessed, on average 29.6 years old, 86.13% of whom were men. The average duration of hospitalization was 10.9 days and the mortality rate was 28.7%. The ROC curve analysis revealed a sensitivity of 68.97%, specificity of 80.56% and area under the curve of 0.837 for the ISS, and 58.62%, 94.44% and 0.855 for the NISS, respectively. The Youden index was 0.49 for the ISS and 0.53 for the NISS. CONCLUSION: the study demonstrated comparable efficacy of NISS and ISS in predicting mortality. These findings hold significance in the hospital setting. Professionals must be familiar with these scales to utilize them competently for each patient.

Understanding the risks of co-exposures in a changing world: a case study of dual monitoring of the biotoxin domoic acid and Vibrio spp. in Pacific oyster.

Assessing the co-occurrence of multiple health risk factors in coastal ecosystems is challenging due to the complexity of multi-factor interactions and limited availability of simultaneously collected data. Understanding co-occurrence is particularly important for risk factors that may be associated with, or occur in similar environmental conditions. In marine ecosystems, the co-occurrence of harmful algal bloom toxins and bacterial pathogens within the genus Vibrio may impact both ecosystem and human health. This study examined the co-occurrence of Vibrio spp. and domoic acid (DA) produced by the harmful algae Pseudo-nitzschia by (1) analyzing existing California Department of Public Health monitoring data for V. parahaemolyticus and DA in oysters; and (2) conducting a 1-year seasonal monitoring of these risk factors across two Southern California embayments. Existing public health monitoring efforts in the state were robust for individual risk factors; however, it was difficult to evaluate the co-occurrence of these risk factors in oysters due to low number of co-monitoring instances between 2015 and 2020. Seasonal co-monitoring of DA and Vibrio spp. (V. vulnificus or V. parahaemolyticus) at two embayments revealed the co-occurrence of these health risk factors in 35% of sampled oysters in most seasons. Interestingly, both the overall detection frequency and co-occurrence of these risk factors were considerably less frequent in water samples. These findings may in part suggest the slow depuration of Vibrio spp. and DA in oysters as residual levels may be retained. This study expanded our understanding of the simultaneous presence of DA and Vibrio spp. in bivalves and demonstrates the feasibility of co-monitoring different risk factors from the same sample. Individual programs monitoring for different risk factors from the same sample matrix may consider combining efforts to reduce cost, streamline the process, and better understand the prevalence of co-occurring health risk factors.

Osteosarcoma cells exhibit functional interactions with stromal cells, fostering a lung microenvironment conducive to the establishment of metastatic tumor cells.

BACKGROUND: Osteosarcoma (OS) stands out as the most common bone tumor, with approximately 20% of the patients receiving a diagnosis of metastatic OS at their initial assessment. A significant challenge lies in the frequent existence of undetected metastases during the initial diagnosis. Mesenchymal stem cells (MSCs) possess unique abilities that facilitate tumor growth, and their interaction with OS cells is crucial for metastatic spread. METHODS AND RESULTS: We demonstrated that, in vitro, MSCs exhibited a heightened migration response toward the secretome of non-metastatic OS cells. When challenged to a secretome derived from lungs preloaded with OS cells, MSCs exhibited greater migration toward lungs colonized with metastatic OS cells. Moreover, in vivo, MSCs displayed preferential migratory and homing behavior toward lungs colonized by metastatic OS cells. Metastatic OS cells, in turn, demonstrated an increased migratory response to the MSCs' secretome. This behavior was associated with heightened cathepsin D (CTSD) expression and the release of active metalloproteinase 2 (MMP2) by metastatic OS cells. CONCLUSIONS: Our assessment focused on two complementary tumor capabilities crucial to metastatic spread, emphasizing the significance of inherent cell features. The findings underscore the pivotal role of signaling integration within the niche, with a complex interplay of migratory responses among established OS cells in the lungs, prometastatic OS cells in the primary tumor, and circulating MSCs. Pulmonary metastases continue to be a significant factor contributing to OS mortality. Understanding these mechanisms and identifying differentially expressed genes is essential for pinpointing markers and targets to manage metastatic spread and improve outcomes for patients with OS.

Heart Rate Variability, Deceleration Capacity of Heart Rate, and Death: A Veteran Twins Study.

BACKGROUND: Autonomic function can be measured noninvasively using heart rate variability (HRV), which indexes overall sympathovagal balance. Deceleration capacity (DC) of heart rate is a more specific metric of vagal modulation. Higher values of these measures have been associated with reduced mortality risk primarily in patients with cardiovascular disease, but their significance in community samples is less clear. METHODS AND RESULTS: This prospective twin study followed 501 members from the VET (Vietnam Era Twin) registry. At baseline, frequency domain HRV and DC were measured from 24-hour Holter ECGs. During an average 12-year follow-up, all-cause death was assessed via the National Death Index. Multivariable Cox frailty models with random effect for twin pair were used to examine the hazard ratios of death per 1-SD increase in log-transformed autonomic metrics. Both in the overall sample and comparing twins within pairs, higher values of low-frequency HRV and DC were significantly associated with lower hazards of all-cause death. In within-pair analysis, after adjusting for baseline factors, there was a 22% and 27% lower hazard of death per 1-SD increment in low-frequency HRV and DC, respectively. Higher low-frequency HRV and DC, measured during both daytime and nighttime, were associated with decreased hazard of death, but daytime measures showed numerically stronger associations. Results did not substantially vary by zygosity. CONCLUSIONS: Autonomic inflexibility, and especially vagal withdrawal, are important mechanistic pathways of general mortality risk, independent of familial and genetic factors.

ACTION APAC: Understanding perceptions, attitudes and behaviours in obesity and its management across south and Southeast Asia.

To identify perceptions and attitudes among people with obesity (PwO) and healthcare professionals (HCPs) toward obesity and its management in nine Asia-Pacific (APAC) countries, a cross-sectional online survey was conducted among adult PwO with self-reported body mass index of ≥25 kg/m2 (≥27 kg/m2, Singapore), and HCPs involved in direct patient care. In total, 10 429 PwO and 1901 HCPs completed the survey. Most PwO (68%) and HCPs (84%) agreed that obesity is a disease; however, a significant proportion of PwO (63%) and HCPs (41%) believed weight loss was the complete responsibility of PwO and only 43% of PwO discussed weight with an HCP in the prior 5 years. Most respondents acknowledged that weight loss would be extremely beneficial to PwO's overall health (PwO 76%, HCPs 85%), although nearly half (45%) of PwO misperceived themselves as overweight or of normal weight. Obesity was perceived by PwO (58%) and HCPs (53%) to negatively impact PwO forming romantic relationships. HCPs cited PwOs' lack of interest (41%) and poor motivation (37%) to lose weight as top reasons for not discussing weight. Most PwO (65%) preferred lifestyle changes over medications to lose weight. PwO and HCPs agreed that lack of exercise and unhealthy eating habits were the major barriers to weight loss. Our data highlights a discordance between the understanding of obesity as a disease and the actual behaviour and preferred approaches to manage it among PwO and HCPs. The study addresses a need to align these gaps to deliver optimal care for PwO.

Psychological Distress and the Risk of Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease.

BACKGROUND: Psychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear. OBJECTIVES: The purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction. METHODS: Pooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years. RESULTS: In both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved. CONCLUSIONS: Among patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

Acute psychological stress-induced progenitor cell mobilization and cardiovascular events.

OBJECTIVE: Certain brain activation responses to psychological stress are associated with worse outcomes in CVD patients. We hypothesized that elevated acute psychological stress, manifesting as greater activity within neural centers for emotional regulation, mobilizes CPC from the bone marrow to the peripheral blood and predicts future cardiovascular events. METHODS: In 427 patients with stable CAD undergoing a laboratory-based mental stress (MS) test, CPCs were enumerated using flow cytometry as CD34-expressing mononuclear cells (CD34+) before and 45 min after stress. Changes in brain regional blood flow with MS were measured using high resolution-positron emission tomography (HR-PET). Association between the change in CPC with MS and the risk of cardiovascular death or myocardial infarction (MI) during a 5-year follow-up period was analyzed. RESULTS: MS increased CPC counts by a mean of 150 [630] cells/mL (15%), P < 0.001. Greater limbic lobe activity, indicative of activation of emotion-regulating centers, was associated with greater CPC mobilization (P < 0.005). Using Fine and Gray models after adjustment for demographioc, clinical risk factors and medications use, greater CPC mobilization was associated with a higher adjusted risk of adverse events; a rise of 1000 cells/mL was associated with a 50% higher risk of cardiovascular death/MI [hazards ratio, 1.5, 95% confidence interval, 1.1-2.2). CONCLUSION: Greater limbic lobe activity, brain areas involved in emotional regulation, is associated with MS-induced CPC mobilization. This mobilization isindependently associated with cardiovascular events. These findings provide novel insights into mechanisms through which psychological stressors modulate cardiovascular risk.

Variable-coefficient parabolic theory as a high-dimensional limit of elliptic theory.

This paper continues the study initiated in Davey (Arch Ration Mech Anal 228:159-196, 2018), where a high-dimensional limiting technique was developed and used to prove certain parabolic theorems from their elliptic counterparts. In this article, we extend these ideas to the variable-coefficient setting. This generalized technique is demonstrated through new proofs of three important theorems for variable-coefficient heat operators, one of which establishes a result that is, to the best of our knowledge, also new. Specifically, we give new proofs of L2→L2 Carleman estimates and the monotonicity of Almgren-type frequency functions, and we prove a new monotonicity of Alt-Caffarelli-Friedman-type functions. The proofs in this article rely only on their related elliptic theorems and a limiting argument. That is, each parabolic theorem is proved by taking a high-dimensional limit of a related elliptic result.

Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Pilot Evaluation of the Family Bridge Program: A Communication- and Culture-Focused Inpatient Patient Navigation Program.

OBJECTIVE: Children with low income and minority race and ethnicity have worse hospital outcomes due partly to systemic and interpersonal racism causing communication and system barriers. We tested the feasibility and acceptability of a novel inpatient communication-focused navigation program. METHODS: Multilingual design workshops with parents, providers, and staff created the Family Bridge Program. Delivered by a trained navigator, it included 1) hospital orientation; 2) social needs screening and response; 3) communication preference assessment; 4) communication coaching; 5) emotional support; and 6) a post-discharge phone call. We enrolled families of hospitalized children with public or no insurance, minority race or ethnicity, and preferred language of English, Spanish, or Somali in a single-arm trial. We surveyed parents at enrollment and 2 to 4 weeks post-discharge, and providers 2 to 3 days post-discharge. Survey measures were analyzed with paired t tests. RESULTS: Of 60 families enrolled, 57 (95%) completed the follow-up survey. Most parents were born outside the United States (60%) with a high school degree or less (60%). Also, 63% preferred English, 33% Spanish, and 3% Somali. The program was feasible: families received an average of 5.3 of 6 components; all received >2. Most caregivers (92%) and providers (81% [30/37]) were "very satisfied." Parent-reported system navigation improved from enrollment to follow-up (+8.2 [95% confidence interval 2.9, 13.6], P = .003; scale 0-100). Spanish-speaking parents reported decreased skills-related barriers (-18.4 [95% confidence interval -1.8, -34.9], P = .03; scale 0-100). CONCLUSIONS: The Family Bridge Program was feasible, acceptable, and may have potential for overcoming barriers for hospitalized children at risk for disparities.

Psychosocial characteristics and cognitive function in community-dwelling adults over 50 years old from the Mexican Health and Aging Study (MHAS)

Aging is an inevitable process that can be associated with cognitive impairment. Evidence about the simultaneous evaluation of psychosocial variables that could be associated with cognitive function is crucial. We aimed to determine the association between psychosocial characteristics and cognition in adults over 50 years in Mexico. The fifth round of the Mexican Health and Aging Study (MHAS) (2018) provides the basis for this paper. The study is part of a longitudinal analysis, for which wave pasting 2012, 2015, and 2018 were performed. The final sample comprised 6,709 individuals. Ten psychosocial variables were measured through scales or specific questions. Cognition was assessed with the Cross-Cultural Cognitive Examination (CCCE). Confounders included sociodemographics, multimorbidity, and functionality. The analysis was performed by adjusting the regression model. Of the total sample, 2,761 (41.1%) were men; 3,948 (58.8%) were women. The mean age was 68.2 years (SD = 8.1). Cognition is significantly affected in people with higher age (ß=-1.30, Cl 95% -1.54, -.1.06 p= 0.000), less schooling (ß=.559, CI 95% .498, .621 p<0.001), depressive symptoms (ß=-.066, CI 95% -.115, -.018 p=0.007), those who do not perform any volunteer service (ß=-.057, CI 95% -.102, -.102 p=0.013), or do not participate in decision making (ß=-.242, CI 95% -.295, -.189 p<0.001), low internal locus of control (ß=-.012., CI 95% -.023, -.001 p=0.023), and poor economic perception (ß=-.070., CI 95% -.115, -.024 p=0.002). When analyzing the cognitive function of older people, it is vital to consider the possible related psychosocial variables.

El envejecimiento es un proceso inevitable que puede asociarse al deterioro cognitivo. La evidencia sobre la evaluación simultánea de variables psicosociales que pudieran estar asociadas con la función cognitiva es crucial. Nuestro objetivo fue determinar la asociación entre las características psicosociales y la cognición en adultos mayores de 50 años en México. La quinta ronda del Estudio Mexicano de Salud y Envejecimiento (ENASEM) (2018) proporciona la base para este trabajo. El estudio forma parte de un análisis longitudinal, para el que se recabaron datos en 2012, 2015 y 2018. La muestra final estuvo compuesta por 6,709 individuos. Se midieron diez variables psicosociales a través de escalas o preguntas específicas. La cognición se evaluó con el Cross-Cultural Cognitive Examination (CCCE). Entre los factores de confusión se incluyeron los sociodemográficos, la multimorbilidad y la funcionalidad. El análisis se realizó ajustando un modelo de regresión. De la muestra total, 2.761 (41,1%) eran hombres; 3.948 (58,8%) eran mujeres. La edad media era de 68,2 años (DE = 8,1). La cognición se ve significativamente afectada en las personas con mayor edad (ß=-1,30, Cl 95% -1,54, -.1.06 p<0.001), menor escolaridad (ß=-.559, IC 95% .498, .621 p<0.001), síntomas depresivos (ß=-.066, IC 95% -.115, -.018 p=0.007), quienes no realizan ningún servicio voluntario (ß=-.057, IC 95% -.102, -.102 p=0. 013), o no participan en la toma de decisiones (ß=-.242, CI 95% -.295, -.189 p<0.001), presentan bajo locus de control interno (ß=-.012., CI 95% -.023, -.001 p=0.023), y pobre percepción económica (ß=-.070., CI 95% -.115, -.024 p=0.002). Al analizar la función cognitiva de las personas mayores, es vital considerar las posibles variables psicosociales relacionadas.

O envelhecimento é um processo inevitável que pode estar associado a défices cognitivos. A evidência sobre a avaliação simultânea de variáveis psicossociais que podem estar associadas à função cognitiva é crucial. O nosso objetivo foi determinar a associação entre as características psicossociais e a cognição em adultos com mais de 50 anos no México. A quinta rodada do Estudo Mexicano de Saúde e Envelhecimento (MHAS) (2018) fornece a base para este artigo. O estudo faz parte de uma análise longitudinal, para a qual foram realizadas colagens de ondas 2012, 2015 e 2018. A amostra final foi composta por 6.709 indivíduos. Dez variáveis psicossociais foram medidas por meio de escalas ou perguntas específicas. A cognição foi avaliada com o Cross-Cultural Cognitive Examination (CCCE). Os factores de confusão incluíram dados sociodemográficos, multimorbilidade e funcionalidade. A análise foi efectuada através do ajuste do modelo de regressão. Da amostra total, 2.761 (41,1%) eram homens; 3.948 (58,8%) eram mulheres. A idade média foi de 68,2 anos (DP = 8,1). A cognição é significativamente afetada nas pessoas com mais idade (ß=-1,30, Cl 95% -1,54, -.1.06 p= 0.000), menor escolaridade (ß=.559, IC 95% .498, .621 p<0.001), sintomas depressivos (ß=-.066, IC 95% -.115, -.018 p=0.007), aqueles que não realizam nenhum serviço voluntário (ß=-.057, IC 95% -.102, -.102 p=0. 013), ou não participam na tomada de decisões (ß=-.242, IC 95% -.295, -.189 p<0.001), baixo locus de controlo interno (ß=-.012., IC 95% -.023, -.001 p=0.023), e fraca perceção económica (ß=-.070., IC 95% -.115, -.024 p=0.002). Ao analisar a função cognitiva dos idosos, é vital considerar as possíveis variáveis psicossociais relacionadas.

Comparison between Injury Severity Score (ISS) and New Injury Severity Score (NISS) in predicting mortality of thoracic trauma in a tertiary hospital / Comparação entre o Injury Severity Score (ISS) e o New Injury Severity Score (NISS) na predição da mortalidade de traumas torácicos atendidos em um hospital terciário

ABSTRACT Introduction: measuring the severity of traumatic injuries is crucial for predicting clinical outcomes. Whereas the Injury Severity Score (ISS) has limitations in assigning scores to injuries at the same site, the New Injury Severity Score (NISS) corrects for this problem by taking into account the three most severe injuries regardless of the region of the body. This study seeks to comprehend the clinical and epidemiological profile of trauma patients while comparing the effectiveness of scales for predicting mortality. Methods: a descriptive, observational and retrospective study using records of patients who underwent thoracotomy at the Hospital das Clínicas of the Federal University of Triângulo Mineiro between 2000 and 2019. Demographic data, mechanisms of injury, affected organs, length of stay and mortality were analyzed. Injury severity was assessed using the ISS and NISS, and statistical analyses were conducted using MedCalc and SigmaPlot. Results: 101 patients were assessed, on average 29.6 years old, 86.13% of whom were men. The average duration of hospitalization was 10.9 days and the mortality rate was 28.7%. The ROC curve analysis revealed a sensitivity of 68.97%, specificity of 80.56% and area under the curve of 0.837 for the ISS, and 58.62%, 94.44% and 0.855 for the NISS, respectively. The Youden index was 0.49 for the ISS and 0.53 for the NISS. Conclusion: the study demonstrated comparable efficacy of NISS and ISS in predicting mortality. These findings hold significance in the hospital setting. Professionals must be familiar with these scales to utilize them competently for each patient.

RESUMO Introdução: a medição da gravidade das lesões traumáticas é essencial para prever os desfechos clínicos. Enquanto o Injury Severity Score (ISS) tem limitações ao atribuir pontuações às lesões no mesmo local, o New Injury Severity Score (NISS) corrige esse problema ao considerar as três lesões mais graves independentemente da região corporal. Este estudo visa entender o perfil clínico-epidemiológico dos pacientes traumatizados, comparando a eficácia das escalas para prever mortalidade. Métodos: estudo descritivo, observacional e retrospectivo utilizando registros de pacientes submetidos à toracotomia no Hospital das Clínicas da Universidade Federal do Triângulo Mineiro entre 2000 e 2019. Dados demográficos, mecanismos de lesão, órgãos afetados, tempo de internação e mortalidade foram analisados. A gravidade das lesões foi avaliada usando o ISS e NISS, e as análises estatísticas foram conduzidas no MedCalc e SigmaPlot. Resultados: Foram avaliados 101 pacientes, em média com 29,6 anos, sendo 86,13% homens. A média da internação foi de 10,9 dias e a taxa de mortalidade foi de 28,7%. A análise da curva ROC revelou uma sensibilidade de 68,97%, especificidade de 80,56% e área sob a curva de 0,837 para o ISS, e 58,62%, 94,44% e 0,855 para o NISS, respectivamente. O índice de Youden indicou 0,49 para o ISS e 0,53 para o NISS. Conclusão: o estudo demonstrou semelhante eficácia entre o NISS e o ISS na previsão de mortalidade. Esses resultados geram implicações importantes na aplicação dessas escalas no ambiente hospitalar. É essencial que os profissionais conheçam tais escalas para aplica-las adequadamente no contexto de cada paciente.

Association Between Symptoms of Chronic Psychological Distress and Myocardial Ischemia Induced by Mental Stress in Patients With Coronary Artery Disease.

Background Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease and is associated with a greater risk of future cardiovascular events. The association between chronic symptoms of psychological distress and mental stress-induced ischemia is not clear. Methods and Results We used a composite score of psychological distress derived from symptoms of depression, posttraumatic stress disorder, anxiety, anger, and perceived general stress. Participants underwent myocardial perfusion imaging with both mental (public speaking task) and conventional (exercise or pharmacological) stress testing. Overall, 142 (15.9%) patients experienced mental stress-induced myocardial ischemia. After adjusting for demographic factors, medical history, and medication use, patients in the highest tertile of psychological distress score had 35% higher odds of having mental stress-induced ischemia compared to those in the lowest tertile (odds ratio [OR], 1.35 [95% CI, 1.06-2.22]). Stratified analyses showed that the association between psychological distress score and mental stress-induced myocardial ischemia was significantly associated only within the subgroup of patients with a prior myocardial infraction, with patients with a prior myocardial infarction in the highest tertile having a 93% higher odds of developing myocardial ischemia with mental stress (95% CI, 1.07-3.60). There was no significant association between psychological distress and conventional stress-induced ischemia (OR, 1.19 [95% CI, 0.87-1.63]). Conclusions Among patients with a history of myocardial infarction, a higher level of psychosocial distress is associated with mental stress-induced myocardial ischemia but not with ischemia induced by a conventional stress test.

Performance of the ACC/AHA Pooled Cohort Cardiovascular Risk Equations in Clinical Practice.

BACKGROUND: The performance of the American College of Cardiology/American Heart Association pooled cohort equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) in real-world clinical practice has not been evaluated extensively. OBJECTIVES: The goal of this study was to test the performance of PCE to predict ASCVD risk in the community, and determine if including individuals with values outside the PCE range (ie, age, blood pressure, cholesterol) or statin therapy initiation over follow-up would significantly affect PCE predictive capabilities. METHODS: The PCE was validated in a community-based cohort of consecutive patients who sought primary care in Olmsted County, Minnesota, between 1997 and 2000, followed-up through 2016. Inclusion criteria were similar to those of PCE derivation. Patient information was ascertained by using the record linkage system of the Rochester Epidemiology Project. ASCVD events (nonfatal and fatal myocardial infarction and ischemic stroke) were validated in duplicate. Calculated and observed ASCVD risk and c-statistics were compared across predefined groups. RESULTS: This study included 30,042 adults, with a mean age of 48.5 ± 12.2 years; 46% were male. Median follow-up was 16.5 years, truncated at 10 years for this analysis. Mean ASCVD risk was 5.6% ± 8.73%. There were 1,555 ASCVD events (5.2%). The PCE revealed good performance overall (c-statistic 0.78) and in sex and race subgroups; it was highest among non-White female subjects (c-statistic 0.81) and lowest in White male subjects (c-statistic 0.77). Out-of-range values and initiation of statin medication did not affect model performance. CONCLUSIONS: The PCE performed well in a community cohort representing real-world clinical practice. Values outside PCE ranges and initiation of statin medication did not affect performance. These results have implications for the applicability of current strategies for the prevention of ASCVD.

Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.

The severity of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and it is not yet clearly understood which patients will progress to liver fibrosis or cirrhosis. SPARC (Secreted Protein Acidic and Rich in Cysteine) has been involved in NAFLD pathogenesis in mice and humans. The aim of this study was to investigate the role of SPARC in inflammasome activation, and to evaluate the relationship between the hepatic expression of inflammasome genes and the biochemical and histological characteristics of NAFLD in obese patients. In vitro studies were conducted in a macrophage cell line and primary hepatocyte cultures to assess the effect of SPARC on inflammasome. A NAFLD model was established in SPARC knockout (SPARC-/-) and SPARC+/+ mice to explore inflammasome activation. A hepatic RNAseq database from NAFLD patients was analyzed to identify genes associated with SPARC expression. The results were validated in a prospective cohort of 59 morbidly obese patients with NAFLD undergoing bariatric surgery. Our results reveal that SPARC alone or in combination with saturated fatty acids promoted IL-1ß expression in cell cultures. SPARC-/- mice had reduced hepatic inflammasome activation during the progression of NAFLD. NAFLD patients showed increased expression of SPARC, NLRP3, CASP1, and IL-1ß. Gene ontology analysis revealed that genes positively correlated with SPARC are linked to inflammasome-related pathways during the progression of the disease, enabling the differentiation of patients between steatosis and steatohepatitis. In conclusion, SPARC may play a role in hepatic inflammasome activation in NAFLD.