Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division.

Tumor-specific CD8+ T cells (TST) in patients with cancer are dysfunctional and unable to halt cancer progression. TST dysfunction, also known as exhaustion, is thought to be driven by chronic T cell antigen receptor (TCR) stimulation over days to weeks. However, we know little about the interplay between CD8+ T cell function, cell division and epigenetic remodeling within hours of activation. Here, we assessed early CD8+ T cell differentiation, cell division, chromatin accessibility and transcription in tumor-bearing mice and acutely infected mice. Surprisingly, despite robust activation and proliferation, TST had near complete effector function impairment even before undergoing cell division and had acquired hallmark chromatin accessibility features previously associated with later dysfunction/exhaustion. Moreover, continued tumor/antigen exposure drove progressive epigenetic remodeling, 'imprinting' the dysfunctional state. Our study reveals the rapid divergence of T cell fate choice before cell division in the context of tumors versus infection.

The perception of healthcare professionals, through their own personal experiences, of the use of music therapy in hospitalised children and adolescents.

BACKGROUND: Music therapy is an emerging and useful methodology for improving patient environments within healthcare fields. However, although it has been shown that music therapy interventions with hospitalised children and adolescents have been used for decades with positive effects, there are currently very few studies that specifically describe the perspectives of healthcare professionals regarding the value of music therapy when applied in these patients. OBJECTIVES: To describe the insights of healthcare professionals regarding music therapy, both on a personal level and in terms of its usefulness in the care of hospitalised children and adolescents. DESIGN: This was a qualitative descriptive-exploratory study with focus groups. PARTICIPANTS: Eighteen healthcare professionals. METHODS: In January 2023, two focus groups, containing nine healthcare professionals each, were created to collect data regarding their experiences concerning the effect of music therapy on hospitalised children and adolescents. Before recording their opinions, all these professionals participated in an interactive music therapy session. The thematic analysis in this work was performed using MAXQDA® software. RESULTS: Two main categories emerged: (a) the effects of music therapy on healthcare professionals, and (b) the benefits of music therapy to patients (children and adolescents). CONCLUSIONS: Music therapy was valued positively by healthcare professionals who described the benefits its use has for hospitalised children and adolescents. They also expressed positive viewpoints regarding the use of music therapy to improve their own self-knowledge and self-care. IMPLICATIONS TO PRACTICE: Healthcare professionals may utilise music therapists to improve patient outcomes and reduce the negative effects of hospitalisation.

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Assessment of depression, anxiety and stress levels in the Ecuadorian general population during social isolation due to the COVID-19 outbreak: a cross-sectional study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic with serious consequences that have led to the implementation of unprecedented social isolation measures. At the early stages of the pandemic, Ecuador was one of the most affected countries in Latin America. The objective of this study was to assess the levels of depression, anxiety and stress in the Ecuadorian general population during the social isolation period due to COVID-19. METHODS: A web-based survey consisting of 31 short-answer and multiple-choice questions was administered to the general population from April 22-May 3, 2020. Mental health status was assessed through the Depression, Anxiety and Stress Scale-21 Items (DASS-21) questionnaire. Ordinal logistic analyses were used to identify potential risk factors associated with the severity of mental health issues. RESULTS: A total of 626 individuals were included. Most of them were females (60.5%), and their mean age was 29.6 ± 11.7 years. Approximately 17.7% of the respondents had moderate to very severe levels of depression, 30.7% had similar levels of anxiety, and 14.2% experienced stress. Female sex, younger age, student status, and having a relative diagnosed with COVID-19 were associated with significantly higher levels of depression, anxiety and stress. Ordinal regression models showed that being a student was a risk factor for having more severe levels of depression (OR = 3.67; 95% CI = 2.56-5.26, p: 0.0001), anxiety (OR= 1.86; 95% CI= 1.35-2.55, p: 0.0001), and stress (OR = 2.17; 95% CI= 1.47-3.19, p: 0.0001). Having a relative with COVID-19 was also found to be a risk factor only for depression (OR= 1.70; 95% CI= 1.03-2.80, p: 0.036) and anxiety (OR = 2.17; 95% CI= 1.35-3.47, p: 0.001). Additionally, male sex,  older age, and having more children were found to be protective factors for the three conditions. CONCLUSIONS: Our findings suggest that social isolation due to the COVID-19 outbreak has impacted the mental health of the general population in Ecuador. We identified potential risk and protective factors that could serve as a foundation from which to develop psychological strategies to safeguard the mental health of our population during the current pandemic.

Stability and change in public health studies in Colombia and Mexico: an exploratory approach based on co-word analysis.

OBJECTIVE: To determine the level of stability or change in topic areas published by public health journals in Latin America and the Caribbean, using keywords and co-word analysis, in order to support evidence-based research planning. METHODS: Keywords were extracted from papers indexed in Scopus® that were published by the Revista de Salud Pública (RSP; Colombia), the Salud Pública de México (SPM; Mexico), and the Revista Peruana de Medicina Experimental y Salud Pública (RPMESP; Peru) for three periods: 2005 - 2007, 2008 - 2010, and 2011 - 2013. Co-word analysis was used to examine keywords extracted. Textual information was analyzed using centrality measures (inbetweenness and closeness). The hypothesis of stability/change of thematic coverage was tested using the Spearman's rho correlation coefficient. VOSviewer was used to visualize the co-word maps. RESULTS: A moderate level of change in thematic coverage was observed in 2005 - 2010, as evidenced by the correlation coefficients for two of the 3-year periods, 2005 - 2007 and 2008 - 2010: 0.545 for RSP and 0.593 for SPM. However, in 2008 - 2013, more keywords remained constant from one period to the next, given the size of the correlation coefficients for the last 3-year periods: 2008 - 2010 and 2011 - 2013: 0.727 for RSP and 0.605 for SPM. CONCLUSION: The research hypothesis was partially accepted given that just two consecutive 3-year periods showed a statistically-significant degree of stability in thematic coverage in public health studies. In that sense, this study provides compelling evidence of the effectiveness of using a combined approach for examining the dynamics of thematic coverage: centrality measures for identifying the main keywords and visual inspection for detecting the structure of textual information.

The impact of research on health education/health literacy on policymaking in Latin America and the Caribbean Region.

Background: In this study, we addressed the gap between health research and policymaking in Latin America and the Caribbean (LAC), focusing on health education/health literacy. Despite growing research, translating findings into effective policies needs to be improved. We explored the factors that make research on health education and health literacy to be referenced and mentioned in policy documents in LAC (and in Peru). We proposed a model based on the hypothesis that the relationship between research and policymaking depends on the research strength of scientific evidence, timing, and social media activity. Methods: A mixed-methods approach was employed, combining quantitative and qualitative data analysis. Quantitative data sources included multidisciplinary databases, altmetric data, and citations of policy documents. For data analysis, we obtained descriptive statistics to identify patterns and then verified the association between variables using χ2. The negative binomial regression was used to test the empirical model introduced above. Quantitative analysis was complemented by analysis of responses to a set of open questions from a sample of Peruvian health policymakers. Results: We found that timing, strength of evidence, and social media activity were significant predictors of research cited in policy documents. Policy documents tended to rely more on qualitative evidence. A positive correlation between timing and cites in policy documents highlighted the importance of timely dissemination, whereas social media activity, while having an impact, had a relatively minor effect. Peruvian policymakers' responses emphasized the role of political context, the relevance of results, and policymakers' commitment to incorporating research into policies. Conclusion: Strength of evidence, social media engagement, and publication timing are key predictors of citations for health education/literacy research in LAC policy documents. However, qualitative findings highlight challenges, including some distrust in research findings, together with limited access to relevant research. The findings offer opportunities to enhance evidence-informed health education/health literacy policy decisions. Implications: To increase the influence on health policymakers, researchers should prioritize the timely dissemination of solid evidence, considering both traditional and digital platforms. Policymakers should focus on the quality and relevance of evidence when formulating policies.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

BACKGROUND: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiated in mice with early sporadic lesions as compared with late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, impact TST function and liver cancer progression. METHODS: Mice with a germline floxed allele of the SV40 large T antigen (TAG) undergo spontaneous recombination and activation of the TAG oncogene, leading to rare early cancerous TAG-expressing lesions that inevitably progress to established liver cancer. We assessed the immunophenotype (CD44, PD1, TCF1, and TOX expression) and function (TNFα and IFNγ cytokine production) of tumor/TAG-specific CD8 T cells in mice with early and late liver lesions by flow cytometry. We vaccinated mice, either alone or in combination with ICB, to test whether these immunotherapeutic interventions could stop liver cancer progression and improve survival. RESULTS: In mice with early lesions, a subset of TST were PD1+ TCF1+ TOX- and could produce IFNγ while TST present in mice with late liver cancers were PD1+ TCF1lo/- TOX+ and unable to make effector cytokines. Strikingly, vaccination with attenuated TAG epitope-expressing Listeria monocytogenes (LMTAG) blocked liver cancer development and led to a population of TST that were PD1-heterogeneous, TCF1+ TOX- and polyfunctional cytokine producers. Vaccine-elicited TCF1+TST could self-renew and differentiate, establishing them as progenitor TST. In contrast, ICB administration did not slow cancer progression or improve LMTAG vaccine efficacy. CONCLUSION: Vaccination, but not ICB, generated a population of functional progenitor TST and halted cancer progression in a clinically relevant model of sporadic liver cancer. In patients with early cancers or at high risk of cancer recurrence, immunization may be the most effective strategy.

Management of embolic splenic abscess secondary to aortic valve endocarditis - case report and review of literature.

BACKGROUND: Splenic abscess is a serious complication associated with infective endocarditis. There is still contradicting evidence regarding the optimal treatment pathway including timing of valve intervention and the approach for managing splenic foci. CASE PRESENTATION: We present a case of a hybrid staged approach in which we successfully performed a laparoscopic splenectomy following percutaneous abscess drainage and a delayed aortic valve replacement. CONCLUSIONS: A multidisciplinary teamwork is fundamental in providing optimal care for patients with distant complications associated with infective endocarditis. Our hybrid approach seems safe and feasible.

Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control.

Background: Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however only a subset of patients with certain types of cancer achieves durable remissions. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically-relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiate in mice with early sporadic lesions as compared to late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, reprogram TST and impact liver cancer progression. Methods: Mice with a germline floxed allele of the SV40 large T antigen (TAG) undergo spontaneous recombination and activation of the TAG oncogene, leading to rare early pre-cancerous lesions that inevitably progress to established liver cancer. We assessed the immunophenotype and function of TAG-specific CD8 T cells in mice with early and late liver lesions. We vaccinated mice, either alone or in combination with ICB, to test whether these immunotherapeutic interventions could stop liver cancer progression. Results: In mice with early lesions, a subset of TST were PD1 + TCF1 + TOX - and could produce IFNγ, while TST present in mice with late liver cancers were PD1 + TCF1 lo/- TOX + and unable to make effector cytokines. Strikingly, vaccination with attenuated TAG epitope-expressing Listeria monocytogenes (LM TAG ) blocked liver cancer development and led to a population of TST that were TCF1 + TOX - TST and polyfunctional cytokine producers. In contrast, ICB administration did not slow cancer progression or improve LM TAG vaccine efficacy. Conclusion: Vaccination, but not ICB, generated a population of progenitor TST and halted cancer progression in a clinically relevant model of sporadic liver cancer. In patients with early cancers or at high-risk of cancer recurrence, immunization may be the most effective strategy. What is already known on this topic: Immunotherapy, including immune checkpoint blockade and cancer vaccines, fails to induce long-term remissions in most patients with cancer. What this study adds: Hosts with early lesions but not hosts with advanced cancer retain a progenitor TCF1+ TST population. This population can be reprogrammed and therapeutically exploited by vaccination, but not ICB, to block tumor progression. How this study might affect research practice or policy: For people at high-risk of cancer progression, vaccination administered when a responsive progenitor TST population is present may be the optimal immunotherapy to induce long-lasting progression-free survival.

Detection of thermotolerant coliforms and SARS-CoV-2 RNA in sewage and recreational waters in the Ecuadorian coast: A call for improving water quality regulation.

Wastewater surveillance represents an alternative approach to regulating contamination and the early detection of infectious agents and outbreaks of diseases of public health importance. This study evaluated domestic wastewater effects on recreational waters in estuarine and seawater bodies in Guayas and Santa Elena provinces in Ecuador, South America. Fecal indicator bacteria (thermotolerant coliforms) served as key indicators for evaluation. Physical, chemical, and microbiological quality markers following the Ecuadorian environmental quality standard and the discharge of effluents to the water resource were analyzed. Samples were collected from 44 coastal sites and 2 oxidation lagoons during the dry and rainy seasons of 2020 and 2021, respectively. SARS-CoV-2 RNA was detected in samples with higher E. coli concentrations using reverse transcription quantitative PCR to detect the genes N and ORF1ab. All samples analyzed for SARS-CoV-2 showed Ct ˂ 40 for at least one gene. Four samples showed at least 20 genome copies of gene N per reaction. These were at an artisanal fishing port, an estuarine area (Palmar), a recreational bay, and an oxidation lagoon. A moderate correlation was found between SARS-CoV-2 RNA, thermotolerant coliform and E. coli (p-value ≤ 0.0037), and a strong and positive correlation between thermotolerant coliform and E. coli. (p-value ≤ 0.00001), highlighting the utility of these established parameters as a proxy of the virus. Significant differences were found in the concentrations of thermotolerant coliforms between seasons (p-value = 0.016) and sites (p-value = 0.005). The highest levels of coliforms were found in the dry season (63000 MPN/100 mL) in Anconcito and during the rainy season (14000 MPN/100 mL) at Esterillo in Playas County. It is recommended that the decentralized autonomous governments of the surveyed provinces in Ecuador implement urgent corrective actions and establish medium-term mechanisms to minimize a potential contamination route. Additional parameters must be included in the monitoring, such as Enterococcus and intestinal parasites, due to their public health implications. In the oxidation lagoons, maintenance actions must be carried out, including the dissolution of sediments, an increase in water retention times, and in situ treatment of the sludge, to improve the system's performance.

Psychopathology in a sample of candidate patients for bariatric surgery.

BACKGROUND: The prevalence of morbid obesity and the popularity of bariatric surgery have grown in recent years. Many surgical protocols require that the candidates undergo a pre-operative psychological evaluation. We describe the psychopathological characteristics of both clinical syndromes (Axis I of the DSM-IV), as well as personality disorders (Axis II of the DSM-IV), in a sample of morbidly obese patients accepted as bariatric surgery candidates and who participate in a specific surgery preparatory programme, and we analyze its relationship with personality clusters. METHODS: The Millon Clinical Multiaxial Inventory-III (MCMI-III) scores from 50 patients attending for bariatric surgery were cluster analyzed in hopes of identifying clinical subgroups corresponding to typical personality profiles. RESULTS: With regard to personality disorders, the highest prevalence was found in the histrionic disorder, followed by obsessive- compulsive disorder. Cluster analysis revealed three personality profiles, which were validated by examining demographics, morphological variables, scores on anxiety and depression psychometric scales, and MCMI-III clinical scales scores. Groups were different in virtually all the MCMI-III clinical scores, as well as in depression and trait anxiety, with Cluster 3 presenting the worst scores. CONCLUSIONS: These findings suggest that morbidly obese patients are heterogeneous in their psychological profiles, highlighting Cluster C disorders.

Health Literacy Concepts, Themes, and Research Trends Globally and in Latin America and the Caribbean: A Bibliometric Review.

(1) Background: Health literacy (HL) debates have increased significantly in the last two decades. HL concepts/themes and models have achieved substantial development in the US and Europe. Although there have been some efforts to develop HL in Latin America and the Caribbean (LAC), these seem to be few and scattered. This paper reviews and discusses developments of HL concepts and themes globally and in LAC over the last two decades. (2) Purpose: This study aimed to identify the prevalent health literacy concepts/themes deployed globally and in LAC as reported in academic journals from 2005 to 2022. We looked into which fields of knowledge have been informing HL research over the last decades. (3) Methods: We conducted a structured search on the Web of Science (WoS), Scopus, PubMed, and SciELO databases to extract the textual data for bibliometric analysis. We analyzed the textual data with VOSviewer and Biblioshiny to better understand health literacy themes and strands currently being researched in the LAC region. We conducted the searches in two periods: the first in May 2023 and the second in October 2023. (4) Results: The bibliometric study highlighted five WoS categories informing most HL global studies: (i) public environmental occupational health; (ii) environmental sciences; (iii) health policy services; (iv) health care science services; and (v) communication. The two predominant categories in LAC are public environmental occupation health and health policy services. Journals hosting HL publications come from these WoS categories. Themes in HL publications can be organized into four thematic clusters: (i) analytical (research designs, analytic techniques, and criteria for examining HL data); (ii) psychometric (measurement properties of data collection tools); (iii) pragmatic (practical issues related to implementing HL programs); and (iv) well-being (effectiveness of HL programs on mental health and illness treatment). (5) Conclusions: There is expanding interest in health literacy among scholars. The number of publications has increased substantially, particularly over the last five years. These are dominated by the Global North. The metrics show that LAC and Africa are trailing in publications. There is an emerging focus on adult literacy, functional/low health literacy, and their effect on improving capabilities, comprehension, and communication regarding health-related topics.

Differences in the Quality of Life of Patients Recently Diagnosed with Crohn's Disease and Ulcerative Colitis.

Inflammatory bowel diseases (IBD) are chronic diseases, encompassing Crohn's disease (CD) and ulcerative colitis (UC). An IBD diagnosis has an impact on the quality of life of patients; this impact can be different according to the type of disease. OBJECTIVE: This study aimed to analyze the differences in the impact on quality of life in the early stages after diagnosis in patients with CD and UC. PATIENTS AND METHODS: This was an observational, multi-center, and cross-sectional study, with the participation of 156 patients recently diagnosed with IBD (<6 months) from 4 hospitals from the Health Council of the Valencian Community. The patients were assessed through the use of the Inflammatory Bowel Disease Questionnaire (IBDQ-32), which measures the quality of life when living with IBD. RESULTS: The sample was composed of 80 patients with CD (51.0%) and 76 patients with a UC diagnosis. The mean age was 42.3 ± 16.2. The CD patients were more affected (42.5%) in their general quality of life than the UC patients (17.1%) (p = 0.001). In the dimensions of the IBDQ-32, the patients with CD showed significant differences in the systemic, emotional, and social spheres. The bowel dimension scores were similar in both groups. CONCLUSIONS: The patients who were recently diagnosed with CD were more affected regarding their quality of life as compared to those who were diagnosed with UC. Psychological care must be considered to mitigate the impact of an IBD diagnosis.

Psychometric Validity of the Minnesota Tobacco Withdrawal Scale in Smokers Attempting to Quit: Longitudinal Invariance across Smokers and Abstainers.

Tobacco withdrawal symptoms vary during smoking cessation increasing relapse risk; therefore, a longitudinal invariant measure seems necessary to validly assess withdrawal changes. This study aimed to examine the psychometric properties of the 7-item Minnesota Tobacco Withdrawal Scale (MTWS) during cessation, and to analyze longitudinal invariance across smokers and abstainers. We conducted a longitudinal study with 309 Spanish smokers (56.2 ± 9.9 years; 52.4% women). We assessed withdrawal at three occasions: pre-treatment (T1), week-12 (T2), and week-24 (T3). Reliability, validity, and invariance analyses were performed. MTWS reliability remained adequate over time (ωT1 = 0.78; ωT2 = 0.68; ωT3 = 0.80) in both smokers and abstainers, with satisfactory temporal stability (ICC = 0.73). MTWS correlations with anxiety, depression, and nicotine dependence (rs > 0.3) supported convergent and concurrent validity. MTWS showed no correlation with craving at T2 (rs < 0.24), suggesting discriminant validity. Unifactorial structure proved partial scalar invariance across time (χ2 = 246.009; CFI = 0.91; IFI = 0.91; SRMR = 0.09), yet longitudinal invariance between abstainers and smokers was not supported. Across groups, partial scalar invariance was only achieved at T2. Noninvariance at T3 was mainly due to item irritability (dMACS = 0.93). The MTWS is reliable and valid measure to assess withdrawal changes during cessation. Long-term MTWS comparisons between smokers and abstainers should be taken with caution since different withdrawal patterns may exist.

Biological, demographic, and health factors associated with HPV infection in Ecuadorian women.

Objectives: The study aims to identify the correlation between human papillomavirus (HPV) infection and sociodemographic and sexual reproductive health factors in Ecuadorian women from March to August 2019. Methods: 120 women were randomly selected from two gynecological clinics to complete a questionnaire and provide a biospecimen. PCR-Hybridization was used to genotype 37 HPV serotypes in samples obtained by endo-cervical brushing for liquid-based cytology. Sociodemographic and sexual health data were collected through a validated questionnaire during a medical consultation. Mathematical modeling of HPV infection was done using bivariate logistic regression. Results: 65.0% of the women sampled had an HPV infection; 74.3% of these women had co-infections with other HPV genotypes. Out of the women who were HPV positive, 75.6% were diagnosed with high-risk genotypes from HPV strains 18, 35, 52, and 66. Parity, immunosuppression, and use of oral contraception/intrauterine devices (IUDs) were identified as associated variables. The explanatory model had a sensitivity of 89.5% and a specificity of 73.8%. Conclusion: The predominant strains of HPV among Ecuadorian women are diverse. The risk of HPV infection is a complex phenomenon where biological and psychosocial variables are integrated into a model. In populations with limited access to health services, low socioeconomic status, and negative sociocultural beliefs about sexually transmitted infections (STIs), surveys can be used as a pre-screening step for HPV infections. The diagnostic value of the model should be tested in multicenter studies that include women from all over the country.

Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.

T cells recognize several types of antigens in tumors, including aberrantly expressed, nonmutated proteins, which are therefore shared with normal tissue and referred to as self/shared-antigens (SSA), and mutated proteins or oncogenic viral proteins, which are referred to as tumor-specific antigens (TSA). Immunotherapies such as immune checkpoint blockade (ICB) can activate T-cell responses against TSA, leading to tumor control, and also against SSA, causing immune-related adverse events (irAE). To improve anti-TSA immunity while limiting anti-SSA autoreactivity, we need to understand how tumor-specific CD8+ T cells (TST) and SSA-specific CD8+ T (SST) cells differentiate in response to cognate antigens during tumorigenesis. Therefore, we developed a genetic cancer mouse model in which we can track TST and SST differentiation longitudinally as liver cancers develop. We found that both TST and SST lost effector function over time, but while TST persisted long term and had a dysfunctional/exhausted phenotype (including expression of PD1, CD39, and TOX), SST exited cell cycle prematurely and disappeared from liver lesions. However, SST persisted in spleens in a dysfunctional TCF1+PD-1- state: unable to produce effector cytokines or proliferate in response to ICB targeting PD-1 or PD-L1. Thus, our studies identify a dysfunctional T-cell state occupied by T cells reactive to SSA: a TCF1+PD-1- state lacking in effector function, demonstrating that the type/specificity of tumor antigen may determine tumor-reactive T-cell differentiation.

Attitudes toward depression among Ecuadorian physicians using the Spanish-validated version of the Revised Depression Attitude Questionnaire (R-DAQ).

PURPOSE: Depression is inadequately recognized and managed, and physicians' attitudes toward this condition and its treatment may play a part in this. This study aimed to assess Ecuadorian physicians' attitudes toward depression. METHODS: This was a cross-sectional study conducted using the validated Revised Depression Attitude Questionnaire (R-DAQ). The questionnaire was delivered to Ecuadorian physicians, and the response rate was 88.8%. RESULTS: 76.4% of participants had never received previous training in depression, and 52.1% of them indicated neutral or limited professional confidence when dealing with depressed patients. More than two-thirds of the participants reported an optimistic attitude toward the generalist perspective of depression. CONCLUSION: Overall, physicians in Ecuador's healthcare settings were optimistic and held positive attitudes toward patients with depression. However, a lack of confidence in the management of depression and a need for ongoing training were found, especially among medical professionals who are not in daily contact with patients with depression.

Coregulated approach to feeding preterm infants with lung disease: effects during feeding.

BACKGROUND: Very preterm (VP) infants are at risk for poor oral feeding endurance, early cessation of eating, poor fluid management with aspiration risk, behavioral distress, and unstable heart rate (HR) and oxygenation during feeding. OBJECTIVE: The study aims to determine the preliminary effectiveness of a coregulated approach (CoReg) to oral feeding for VP infants at risk for lung disease. METHODS: A randomized, within-subject, cross-over design was used with 20 VP infants requiring oxygen at the start of oral feeding. Infants were bottle-fed by the Usual Care approach and by the CoReg approach on two consecutive days for an average of four feedings each. Intervention components included coregulation of suck, swallow, and breathe rhythms using enhanced auditory assessment, infant-guided feeding onsets, and infant positioning in a semielevated, side-lying position. Infant physiology metrics (HR and SaO2) were collected continuously before and during the feeding. Behavioral and auditory indicators of regulation were coded continuously from videotape during the feeding. RESULTS: Up to 75 feedings were analyzed (40 Usual Care and 35 CoReg) using repeated measures modeling. CoReg feedings were characterized by more frequent preparation of the infant for the feeding, were more commonly initiated in response to infant readiness cues, had more rest periods and breath regulation events, and had fewer sucking stimulation events. CoReg feedings had less SaO2 variability, decline, and time spent in a desaturated state; less HR fluctuation and decline; less behavioral disorganization; better fluid management; and less observed effort to breathe. DISCUSSION: Support is provided for an approach to feeding vulnerable infants. Enhanced auditory assessment of infant feeding rhythms increases the responsiveness of the feeder and improves infant behavioral and physiological responses.

The relevance of music therapy in paediatric and adolescent cancer patients: a scoping review.

BACKGROUND: Music therapy is an emerging and useful methodology to improve the quality of life of children and adolescents with cancer. OBJECTIVES: The objective of this scoping review was to examine the available literature and offer an analysis of the relevance of music therapy in paediatric oncology. We considered the effects of music therapy on children and adolescents with cancer as well as the perception of this population, their families, music therapists, and health professionals regarding the music therapy sessions conducted. Finally, we analysed the characteristics of the distinct types of music therapy interventions reported in the literature. METHODS: In this review, we applied the methodology proposed by Arksey and O'Malley. After performing a comprehensive academic literature database search, 522 articles were identified of which, 27 met the inclusion criteria. RESULTS: The results shed light on the use of music therapy as a means to facilitate self-esteem, to improve the physical, emotional, and cognitive aspects related to disease and, to a lesser extent, alleviate their physiological symptoms. Both children and adolescents with cancer were represented in the academic literature. The most prevalent findings described in these studies were the benefits of music therapy in terms of improved psychological well-being and social relationships in this population. CONCLUSIONS: Music therapy interventions are generally well received, not only by children and adolescents with cancer, but also by their families, music therapists, and health professionals. Nevertheless, several gaps were identified in some of the studies we considered, including a lack of specificity regarding the results obtained or music therapy intervention methods used.

Planetary Health and Health Education in Brazil: Towards Better Trained Future Health Professionals.

Brazil is Latin America's largest country and has a strong economy, but it is also characterised by many inequalities. These are very conspicuous in the health sector, particularly in health education, which is expected to modernise according to the planetary health (PH) perspective. This paper describes the health education scenario in Brazil and undertakes an analysis of the postgraduate health programmes and policies in place, identifying the extent to which these support the cause of PH. To achieve this goal, this paper deploys a bibliometric analysis to gain a better understanding of the research streams related to higher education and PH. In addition, it presents and discusses selected case studies in the field and cross-checks documents from the Brazilian Ministry of Education against five domains of PH in education. The results indicate that despite some progress to date and the fact that some programmes are in place, there is a perceived need for policies and efforts from education organisations towards connecting PH principles in the education of current and future health professionals.