Patients with Spondylodiscitis following Chemoradiotherapy for Head and Neck Cancer in a Portuguese Cancer Hospital: A Case Report.

Introduction: Head and neck cancer is an umbrella term for tumor manifestations across the head and neck regions, including the oral cavity, pharynx (including the naso, oro, and hypopharynx), larynx, and sinuses. Treatment options for head and neck cancer include surgery, radiation therapy, chemotherapy, and immunotherapy, with specific treatment plans depending upon individual tumor location and staging, together with overall patient health status. Furthermore, definitive chemoradiotherapy (CRT) has emerged as a highly effective therapeutic option for locoregional advanced head and neck squamous cell cancer. However, such therapy has also been linked to the development of spondylodiscitis. Spondylodiscitis consists of an infection starting at the vertebral endplates and spreading into the intervertebral discs, typically manifesting in adults. Case Presentation and Conclusion: This case report describes our clinical team's experience in managing three separate cases of spondylodiscitis following CRT for head and neck tumors that presented at our clinic for diagnosis and treatment in order to identify predisposing factors that underlie the link between CRT and spondylodiscitis.

Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis. / Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real.

BACKGROUND: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. OBJECTIVES: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. METHODS: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. RESULTS: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. CONCLUSIONS: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

FUNDAMENTO: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. OBJETIVOS: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. MÉTODOS: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. RESULTADOS: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. CONCLUSÕES: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement.

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68-77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82-1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3-6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Assessment of myocardial strain patterns in patients with left bundle branch block using cardiac magnetic resonance.

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.

Atingimento das Metas de Colesterol LDL em Pacientes com Histórico de Infarto Agudo do Miocárdio: Estudo Transversal do Mundo Real / Attainment of LDL-Cholesterol Goals in Patients with Previous Myocardial Infarction: A Real-World Cross-Sectional Analysis

Resumo Fundamento: As diretrizes da Sociedade Europeia de Cardiologia recomendam um nível de colesterol LDL (LDL-C) < 55 mg/dL para pacientes com doença cardiovascular estabelecida. Embora a fórmula de Friedewald ainda seja amplamente utilizada para estimar o LDL-C, a fórmula mais recente de Martin-Hopkins mostrou maior precisão. Objetivos: Nosso objetivo foi avaliar: A) a proporção de pacientes que atingiram a meta de LDL-C e as terapias utilizadas em um centro terciário; B) o impacto da utilização do método de Martin-Hopkins em vez do método de Friedewald na proporção de pacientes controlados. Métodos: Estudo transversal monocêntrico, incluindo pacientes consecutivos pós-infarto do miocárdio, acompanhados por 20 cardiologistas, em um hospital terciário. Os dados foram coletados retrospectivamente de consultas clínicas realizadas após abril de 2022. Para cada paciente, os níveis de LDL-C e o atingimento das metas foram estimados a partir de um perfil lipídico ambulatorial, utilizando as fórmulas de Friedewald e Martin-Hopkins. Um valor-p bicaudal < 0,05 foi considerado estatisticamente significativo para todos os testes. Resultados: Foram incluídos 400 pacientes (com 67 ± 13 anos, 77% do sexo masculino). Utilizando a fórmula de Friedewald, a mediana de LDL-C sob terapia foi de 64 (50-81) mg/dL, e 31% tinham LDL-C dentro da meta. Estatinas de alta intensidade foram usadas em 64% dos pacientes, 37% estavam em uso de ezetimiba e 0,5% estavam em uso de inibidores de PCSK9. A terapia combinada de estatina de alta intensidade + ezetimiba foi utilizada em 102 pacientes (26%). A aplicação do método de Martin-Hopkins reclassificaria um total de 31 pacientes (7,8%). Entre aqueles considerados controlados pela fórmula de Friedewald, 27 (21,6%) teriam LDL-C estimado por Martin-Hopkins acima da meta. Conclusões: Menos de um terço dos pacientes pós-infarto do miocárdio apresentaram LDL-C dentro da meta. A aplicação da fórmula de Martin-Hopkins reclassificaria um quinto dos pacientes presumivelmente controlados no grupo de pacientes não controlados.

Abstract Background: The European Society of Cardiology guidelines recommend an LDL-cholesterol (LDL-C) < 55 mg/dL for patients with established cardiovascular disease. While the Friedewald equation to estimate LDL-C is still widely used, the newer Martin-Hopkins equation has shown greater accuracy. Objectives: We aimed to assess: A) the proportion of patients reaching LDL-C goal and the therapies used in a tertiary center; B) the impact of using the Martin-Hopkins method instead of Friedewald's on the proportion of controlled patients. Methods: A single-center cross-sectional study including consecutive post-myocardial infarction patients followed by 20 cardiologists in a tertiary hospital. Data was collected retrospectively from clinical appointments that took place after April 2022. For each patient, the LDL-C levels and attainment of goals were estimated from an ambulatory lipid profile using both Friedewald and Martin-Hopkins equations. A two-tailed p-value of < 0.05 was considered statistically significant for all tests. Results: Overall, 400 patients were included (aged 67 ± 13 years, 77% male). Using Friedewald's equation, the median LDL-C under therapy was 64 (50-81) mg/dL, and 31% had LDL-C within goals. High-intensity statins were used in 64% of patients, 37% were on ezetimibe, and 0.5% were under PCSK9 inhibitors. Combination therapy of high-intensity statin + ezetimibe was used in 102 patients (26%). Applying the Martin-Hopkins method would reclassify a total of 31 patients (7.8%). Among those deemed controlled by Friedewald's equation, 27 (21.6%) would have a Martin-Hopkins' LDL-C above goals. Conclusions: Less than one-third of post-myocardial infarction patients had LDL-C within the goal. Applying the Martin-Hopkins equation would reclassify one-fifth of presumably controlled patients into the non-controlled group.

Assessment of the quality of life and mental health of healthcare students during the COVID-19 pandemic.

OBJECTIVE: to evaluate the quality of life (QOL) and the presence of symptoms related to depression, anxiety, and stress among students in the healthcare field, in comparison to the period before the COVID-19 pandemic. METHODS: A comparative cross-sectional research was conducted at a Brazilian public university. QOL was assessed using the WHOQOL-bref scale, while symptoms of depression, anxiety, and stress were evaluated using the DASS-21 scale. Descriptive and inferential analyses were employed to compare the two time periods. RESULTS: A total of 355 students participated in this study. During the pandemic, there were significant increases in severe depression symptoms (15.1% versus 24.8%), moderate anxiety (18.3% versus 29.4%), and moderate stress (40.9% versus 53.8%) observed among the participants. Additionally, a significant reduction in QOL was noted, particularly in the domain of social relationships (65.2 versus 59.6, p-value 0.029). CONCLUSION: The study highlights a deterioration in both the quality of life and the mental health of healthcare students during the COVID-19 pandemic.

Síntomas de depresión, ansiedad y estrés en estudiantes del área de la salud e impacto en la calidad de vida / Symptoms of depression, anxiety and stress in health students and impact on quality of life / Sintomas de depressão, ansiedade e estresse em estudantes da saúde e impacto na qualidade de vida

Objetivo: evaluar la asociación entre la calidad de vida y la presencia de síntomas de depresión, ansiedad y estrés en estudiantes universitarios del área de la salud. Método: estudio transversal que incluyó a 321 estudiantes de carreras del área de la salud. La calidad de vida se midió mediante la escala de la Organización Mundial de la Salud, versión abreviada, en los dominios físico, psicológico, relaciones sociales y ambiente, y los síntomas se evaluaron por la escala de depresión, ansiedad y estrés. Se realizó un análisis multivariante por medio de regresión lineal robusta para evaluar la asociación entre la calidad de vida y los síntomas presentados. Resultados: se observó una asociación negativa entre la calidad de vida y los síntomas de depresión en todos los dominios, mientras que los síntomas de ansiedad tuvieron una asociación negativa en el dominio ambiente, y los síntomas de estrés tuvieron una asociación negativa en el dominio psicológico. La gravedad de los síntomas se asoció desfavorablemente con la calidad de vida, es decir, cuanto mayor la gravedad de los síntomas, menores las puntuaciones medias en todos los dominios. Conclusión: los síntomas de depresión, ansiedad y estrés fueron prevalentes e impactaron negativamente en la calidad de vida de los estudiantes, especialmente en presencia de síntomas depresivos. Las puntuaciones disminuidas se asociaron significativamente con la gravedad de los síntomas.

Objective: to evaluate the association between quality of life and presence of symptoms of depression, anxiety, and stress in college students in the health area. Method: cross-sectional study that included 321 students from undergraduate courses in the health area. Quality of life was measured using the World Health Organization scale, abbreviated version, in the physical, psychological, social relations and environment domains, and symptoms were assessed by the depression, anxiety and stress scale. Multivariate analysis was performed using robust linear regression to evaluate the association between quality of life and symptoms. Results: a negative association was observed between the quality of life and depression symptoms in all domains, while anxiety symptoms showed a negative association in the environment domain, and stress symptoms had a negative association in the psychological domain. Symptom severity was unfavorably associated with quality of life, that is, the greater the symptom severity, the lower the mean scores in all domains. Conclusion: symptoms of depression, anxiety, and stress were prevalent and had a negative impact on students' quality of life, especially in the presence of depressive symptoms. The decrease in scores was significantly associated with the severity of symptoms.

Objetivo: avaliar a associação entre qualidade de vida e presença de sintomas de depressão, ansiedade e estresse em estudantes universitários da área da saúde. Método: estudo transversal que incluiu 321 estudantes de cursos de graduação da área da saúde. A qualidade de vida foi mensurada por meio da escala da Organização Mundial da Saúde, versão abreviada, nos domínios físico, psicológico, relações sociais e meio ambiente, e os sintomas avaliados pela escala de depressão, ansiedade e estresse. Foi realizada análise multivariada utilizando regressão linear robusta para avaliar a associação entre qualidade de vida e sintomas apresentados. Resultados: observou- se associação negativa entre qualidade de vida e sintomas de depressão em todos os domínios, enquanto os sintomas de ansiedade apresentaram associação negativa no domínio meio ambiente, e os sintomas de estresse tiveram associação negativa no domínio psicológico. A gravidade dos sintomas associou-se de forma desfavorável com a qualidade de vida, ou seja, quanto maior a gravidade dos sintomas, menor a média dos escores em todos os domínios. Conclusão: sintomas de depressão, ansiedade e estresse mostraram-se prevalentes e com impacto negativo na qualidade de vida dos estudantes, principalmente na presença de sintomas depressivos. A diminuição dos escores foi significativamente associada à gravidade dos sintomas.

Longitudinal genomic analyses of automatically-recorded vaginal temperature in lactating sows under heat stress conditions based on random regression models.

BACKGROUND: Automatic and continuous recording of vaginal temperature (TV) using wearable sensors causes minimal disruptions to animal behavior and can generate data that enable the evaluation of temporal body temperature variation under heat stress (HS) conditions. However, the genetic basis of TV in lactating sows from a longitudinal perspective is still unknown. The objectives of this study were to define statistical models and estimate genetic parameters for TV in lactating sows using random regression models, and identify genomic regions and candidate genes associated with HS indicators derived from automatically-recorded TV. RESULTS: Heritability estimates for TV ranged from 0.14 to 0.20 over time (throughout the day and measurement period) and from 0.09 to 0.18 along environmental gradients (EG, - 3.5 to 2.2, which correspond to dew point values from 14.87 to 28.19 ËšC). Repeatability estimates of TV over time and along EG ranged from 0.57 to 0.66 and from 0.54 to 0.77, respectively. TV measured from 12h00 to 16h00 had moderately high estimates of heritability (0.20) and repeatability (0.64), indicating that this period might be the most suitable for recording TV for genetic selection purposes. Significant genotype-by-environment interactions (GxE) were observed and the moderately high estimates of genetic correlations between pairs of extreme EG indicate potential re-ranking of selection candidates across EG. Two important genomic regions on chromosomes 10 (59.370-59.998 Mb) and16 (21.548-21.966 Mb) were identified. These regions harbor the genes CDC123, CAMK1d, SEC61A2, and NUDT5 that are associated with immunity, protein transport, and energy metabolism. Across the four time-periods, respectively 12, 13, 16, and 10 associated genomic regions across 14 chromosomes were identified for TV. For the three EG classes, respectively 18, 15, and 14 associated genomic windows were identified for TV, respectively. Each time-period and EG class had uniquely enriched genes with identified specific biological functions, including regulation of the nervous system, metabolism and hormone production. CONCLUSIONS: TV is a heritable trait with substantial additive genetic variation and represents a promising indicator trait to select pigs for improved heat tolerance. Moderate GxE for TV exist, indicating potential re-ranking of selection candidates across EG. TV is a highly polygenic trait regulated by a complex interplay of physiological, cellular and behavioral mechanisms.

Genomic predictions and GWAS for heat tolerance in pigs based on reaction norm models with performance records and data from public weather stations considering alternative temperature thresholds.

Genetic improvement of livestock productivity has resulted in greater production of metabolic heat and potentially greater susceptibility to heat stress. Various studies have demonstrated that there is genetic variability for heat tolerance and genetic selection for more heat tolerant individuals is possible. The rate of genetic progress tends to be greater when genomic information is incorporated into the analyses as more accurate breeding values can be obtained for young individuals. Therefore, this study aimed (1) to evaluate the predictive ability of genomic breeding values for heat tolerance based on routinely recorded traits, and (2) to investigate the genetic background of heat tolerance based on single-step genome-wide association studies for economically important traits related to body composition, growth and reproduction in Large White pigs. Pedigree information was available for 265,943 animals and genotypes for 8686 animals. The studied traits included ultrasound backfat thickness (BFT), ultrasound muscle depth (MDP), piglet weaning weight (WW), off-test weight (OTW), interval between farrowing (IBF), total number of piglets born (TNB), number of piglets born alive (NBA), number of piglets born dead (NBD), number of piglets weaned (WN) and weaning-to-estrus interval (IWE). The number of phenotypic records ranged from 6059 (WN) to 172,984 (TNB). Single-step genomic reaction norm predictions were used to calculate the genomic estimated breeding values for each individual. Predictions of breeding values for the validation population individuals were compared between datasets containing phenotypic records measured in the whole range of temperatures (WR) and datasets containing only phenotypic records measured when the weather station temperature was above 10°C (10C) or 15°C (15C), to evaluate the usefulness of these datasets that may better reflect the within-barn temperature. The use of homogeneous or heterogeneous residual variance was found to be trait-dependent, where homogeneous variance presented the best fit for MDP, BFT, OTW, TNB, NBA, WN and IBF, while the other traits (WW and IWE) had better fit with heterogeneous variance. The average prediction accuracy, dispersion and bias values considering all traits for WR were 0.36 ± 0.05, -0.07 ± 0.13 and 0.76 ± 0.10, respectively; for 10C were 0.39 ± 0.02, -0.05 ± 0.07 and 0.81 ± 0.05, respectively; and for 15C were 0.32 ± 0.05, -0.05 ± 0.11 and 0.84 ± 0.10, respectively. Based on the studied traits, using phenotypic records collected when the outside temperature (from public weather stations) was above 10°C provided better predictions for most of the traits. Forty-three and 62 candidate genomic regions were associated with the intercept (overall performance level) and slope term (specific biological mechanisms related to environmental sensitivity), respectively. Our results contribute to improve genomic predictions using existing datasets and better understand the genetic background of heat tolerance in pigs. Furthermore, the genomic regions and candidate genes identified will contribute to future genomic studies and breeding applications.

Subcritical Water Extraction for Valorisation of Almond Skin from Almond Industrial Processing.

Almond skin (AS) is an agro-industrial residue from almond processing that has a high potential for valorisation. In this study, subcritical water extraction (SWE) was applied at two temperatures (160 and 180 °C) to obtain phenolic-rich extracts (water-soluble fraction) and cellulose fibres (insoluble fraction) from AS. The extraction conditions affected the composition and properties of both valorised fractions. The dry extracts obtained at 180 °C were richer in phenolics (161 vs. 101 mg GAE. g-1 defatted almond skin (DAS)), with greater antioxidant potential (1.063 vs. 1.490 mg DAS.mg-1 DPPH) and showed greater antibacterial effect (lower MIC values) against L. innocua (34 vs. 90 mg·mL-1) and E. coli (48 vs. 90 mg·mL-1) than those obtained at 160 °C, despite the lower total solid yield (21 vs. 29%) obtained in the SWE process. The purification of cellulose from the SWE residues, using hydrogen peroxide (H2O2), revealed that AS is not a good source of cellulose material since the bleached fractions showed low yields (20-21%) and low cellulose purity (40-50%), even after four bleaching cycles (1 h) at pH 12 and 8% H2O2. Nevertheless, the application of a green, scalable, and toxic solvent-free SWE process was highly useful for obtaining AS bioactive extracts for different food, cosmetic, or pharmaceutical applications.

Genetic parameters for automatically-measured vaginal temperature, respiration efficiency, and other thermotolerance indicators measured on lactating sows under heat stress conditions.

BACKGROUND: Genetic selection based on direct indicators of heat stress could capture additional mechanisms that are involved in heat stress response and enable more accurate selection for more heat-tolerant individuals. Therefore, the main objectives of this study were to estimate genetic parameters for various heat stress indicators in a commercial population of Landrace × Large White lactating sows measured under heat stress conditions. The main indicators evaluated were: skin surface temperatures (SST), automatically-recorded vaginal temperature (TV), respiration rate (RR), panting score (PS), body condition score (BCS), hair density (HD), body size (BS), ear size, and respiration efficiency (Reff). RESULTS: Traits based on TV presented moderate heritability estimates, ranging from 0.15 ± 0.02 to 0.29 ± 0.05. Low heritability estimates were found for SST traits (from 0.04 ± 0.01 to 0.06 ± 0.01), RR (0.06 ± 0.01), PS (0.05 0.01), and Reff (0.03 ± 0.01). Moderate to high heritability values were estimated for BCS (0.29 ± 0.04 for caliper measurements and 0.25 ± 0.04 for visual assessments), HD (0.25 ± 0.05), BS (0.33 ± 0.05), ear area (EA; 0.40 ± 0.09), and ear length (EL; 0.32 ± 0.07). High genetic correlations were estimated among SST traits (> 0.78) and among TV traits (> 0.75). Similarly, high genetic correlations were also estimated for RR with PS (0.87 ± 0.02), with BCS measures (0.92 ± 0.04), and with ear measures (0.95 ± 0.03). Low to moderate positive genetic correlations were estimated between SST and TV (from 0.25 ± 0.04 to 0.76 ± 0.07). Low genetic correlations were estimated between TV and BCS (from - 0.01 ± 0.08 to 0.06 ± 0.07). Respiration efficiency was estimated to be positively and moderately correlated with RR (0.36 ± 0.04), PS (0.56 ± 0.03), and BCS (0.56 ± 0.05 for caliper measurements and 0.50 ± 0.05 for the visual assessments). All other trait combinations were lowly genetically correlated. CONCLUSIONS: A comprehensive landscape of heritabilities and genetic correlations for various thermotolerance indicators in lactating sows were estimated. All traits evaluated are under genetic control and heritable, with different magnitudes, indicating that genetic progress is possible for all of them. The genetic correlation estimates provide evidence for the complex relationships between these traits and confirm the importance of a sub-index of thermotolerance traits to improve heat tolerance in pigs.

External validation of the unifying concept for the quantitative assessment of functional mitral regurgitation.

PURPOSE: A novel conceptual framework was introduced to enhance the quantitative assessment of functional mitral regurgitation (FMR) and improve risk stratification. However, the data was derived from a single-center cohort and lack external validation. We aimed to validate the proposed algorithm using a different patient population. METHODS: Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) were retrospectively identified at a single-center. The cohort was stratified in low, intermediate and high-risk according to the proposed framework, on the basis of effective regurgitant orifice area (EROA) and regurgitant volume (RegVol). Patients within the intermediate-risk group were subsequently reclassified into either the low-risk category (Regurgitant Fraction, RegFrac < 50%) or the high-risk category (RegFrac ≥ 50%) based on their regurgitant fraction. The primary endpoint was all-cause mortality. RESULTS: A total of 572 patients were included. During a median follow-up of 3.8 years there were 254 deaths (44%). On multivariable analysis, the proposed thresholds for FMR severity remained independently associated with all-cause mortality (adjusted hazard ratio: 1.488; 95% confidence interval [CI]: 1.110-2.013; p-value = 0.010). This algorithm demonstrated superior discriminative ability (C-statistic: 0.664) compared to contemporary guidelines (C-statistic: 0.522; p-value for comparison < 0.001). Additionally, it resulted in a significant improvement in the net reclassification index (0.162; p-value < 0.001). CONCLUSIONS: Within our cohort, the application of the proposed concept demonstrated a significant association with a higher risk of all-cause mortality. Moreover, this conceptual framework showcased the potential to improve the accuracy of risk prediction beyond current guidelines.

Influence of Age on the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Obstructive Coronary Disease in Symptomatic Patients.

Concerns have been raised about the added diagnostic value of coronary artery calcium score (CACS) of 0 for reducing the likelihood of obstructive coronary artery disease (CAD) in younger patients. Our study aimed to assess the influence of age on the value of CAC = 0 in symptomatic patients who underwent coronary computed tomography angiography (CCTA). We conducted a 2-center retrospective study assessing symptomatic patients with suspected CAD who underwent CACS and CCTA. Pretest probability was calculated according to the Juarez-Orozco method and obstructive CAD was defined as ≥50% luminal stenosis. The diagnostic likelihood ratios and negative predictive values were used to assess the diagnostic value of a CACS of 0 to rule out obstructive CAD. A total of 2,043 patients (mean age 60 ± 11 years, 60% women, 48.5% CACS of 0) were analyzed. The pretest probability of obstructive CAD increased with age, whereas the proportion of patients with a CACS of 0 decreased with age. The added diagnostic value of a CACS of 0 was lower in younger patients (negative likelihood ratios ranging from 0.36 for <50 years to 0.10 for ≥70 years). However, the prevalence of obstructive CAD in patients with a CACS of 0 was low in all age groups. In a cohort of symptomatic patients who underwent CCTA for suspected CAD, the added diagnostic value of a CACS of 0 decreases significantly at younger ages. However, it is offset by their lower pretest probabilities, yielding high negative predictive values independently of age.

Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats.

OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17ß-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17ß-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17ß-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1ß, IL-10 and tumour necrosis factor-α were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17ß-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17ß-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1ß increased after I/R and 17ß-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1ß and IL-10 in lung explants, reduced by 17ß-oestradiol. CONCLUSIONS: Our results showed that 17ß-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17ß-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.

Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19).

BACKGROUND: Evidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson's disease (PD) and dementia up to 6 and 12 months after infection, respectively. Longer follow-ups with comparison groups are needed to clarify the potentially increased risk of neurodegenerative diseases in COVID-19 survivors, namely those infected before mass vaccination. METHODS: A prospective study started in July 2022 with four cohorts of 150 individuals each, defined according to SARS-CoV-2 infection and hospitalisation status between March 2020 and February 2021: cohort 1-hospitalised due to SARS-CoV-2 infection; cohort 2-hospitalised, COVID-19-free; cohort 3-infected, not hospitalised; cohort 4-not infected, not hospitalised. Cohort 2 will be matched to cohort 1 according to age, sex, level of hospitalisation care and length of stay; cohort 4 will be age-matched and sex-matched to cohort 3. Baseline, 1-year and 2-year follow-up evaluations will include: cognitive performance assessed with the Montreal Cognitive Assessment (MoCA) and neuropsychological tests; the assessment of prodromal markers of PD with Rapid Eye Movement Sleep Behaviour Disorder single-question Screen and self-reported olfactory and gustative alterations; screening of PD with the 9-item PD screening questionnaire; gait evaluation with Timed Up&Go test. Suspected cases of cognitive impairment and PD will undergo a clinical evaluation by a neurologist. Frequency measures of neurological complications, prodromal markers and diagnoses of dementia and PD, will be presented. The occurrence of cognitive decline-the difference between baseline and 1-year MoCA scores 1.5 SD below the mean of the distribution of the variation-will be compared between cohorts 1 and 2, and cohorts 3 and 4 with OR estimated using multivariate logistic regression. ETHICS AND DISSEMINATION: This study received ethics approval from the Ethics Committees of the health units Unidade Local de Saúde de Matosinhos and Centro Hospitalar de Entre Douro e Vouga, and informed consent is signed for participating. Results will be disseminated among the scientific community and the public.

Single Modality vs. Multimodality: What Works Best for Lung Cancer Screening?

In a clinical context, physicians usually take into account information from more than one data modality when making decisions regarding cancer diagnosis and treatment planning. Artificial intelligence-based methods should mimic the clinical method and take into consideration different sources of data that allow a more comprehensive analysis of the patient and, as a consequence, a more accurate diagnosis. Lung cancer evaluation, in particular, can benefit from this approach since this pathology presents high mortality rates due to its late diagnosis. However, many related works make use of a single data source, namely imaging data. Therefore, this work aims to study the prediction of lung cancer when using more than one data modality. The National Lung Screening Trial dataset that contains data from different sources, specifically, computed tomography (CT) scans and clinical data, was used for the study, the development and comparison of single-modality and multimodality models, that may explore the predictive capability of these two types of data to their full potential. A ResNet18 network was trained to classify 3D CT nodule regions of interest (ROI), whereas a random forest algorithm was used to classify the clinical data, with the former achieving an area under the ROC curve (AUC) of 0.7897 and the latter 0.5241. Regarding the multimodality approaches, three strategies, based on intermediate and late fusion, were implemented to combine the information from the 3D CT nodule ROIs and the clinical data. From those, the best model-a fully connected layer that receives as input a combination of clinical data and deep imaging features, given by a ResNet18 inference model-presented an AUC of 0.8021. Lung cancer is a complex disease, characterized by a multitude of biological and physiological phenomena and influenced by multiple factors. It is thus imperative that the models are capable of responding to that need. The results obtained showed that the combination of different types may have the potential to produce more comprehensive analyses of the disease by the models.

Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease resulting from a deficiency of the enzyme phenylalanine hydroxylase (PAH). Hyperphenylalaninemias (HPA) due to PAH deficiency are accompanied by a wide variety of clinical, biochemical, and molecular features. To identify and characterize pathogenic variants in the PAH gene and establish a correlation between genotype and biochemical phenotype in patients with PKU from state of Pará in the North Region of Brazil. METHODS: All 13 exons of the PAH gene from 32 patients (21 PKU and 11 non-PKU HPA) were amplified by PCR and submitted to DNA sequencing (Sanger). Biochemical data were obtained from the patients' medical records. RESULTS: Molecular analysis identified 17 pathogenic variants and 3 nonpathogenic variants. The most frequent pathogenic variants were IVS10-11G>A (7.9%), p. Arg261Gln (7.9%), p. Val388Met (6.3%) and p. Ile65Thr (4.7%). Was observed correlations and inconsistencies between genotype and biochemical phenotype. CONCLUSION: In PKU patients from state of Pará, North Region of Brazil, a heterogeneous mutation spectrum was revealed, in which the most frequent mutations are variants commonly observed in other Brazilian studies and in the region of the Iberian Peninsula.

Machine learning-based approaches for cancer prediction using microbiome data.

Emerging evidence of the relationship between the microbiome composition and the development of numerous diseases, including cancer, has led to an increasing interest in the study of the human microbiome. Technological breakthroughs regarding DNA sequencing methods propelled microbiome studies with a large number of samples, which called for the necessity of more sophisticated data-analytical tools to analyze this complex relationship. The aim of this work was to develop a machine learning-based approach to distinguish the type of cancer based on the analysis of the tissue-specific microbial information, assessing the human microbiome as valuable predictive information for cancer identification. For this purpose, Random Forest algorithms were trained for the classification of five types of cancer-head and neck, esophageal, stomach, colon, and rectum cancers-with samples provided by The Cancer Microbiome Atlas database. One versus all and multi-class classification studies were conducted to evaluate the discriminative capability of the microbial data across increasing levels of cancer site specificity, with results showing a progressive rise in difficulty for accurate sample classification. Random Forest models achieved promising performances when predicting head and neck, stomach, and colon cancer cases, with the latter returning accuracy scores above 90% across the different studies conducted. However, there was also an increased difficulty when discriminating esophageal and rectum cancers, failing to differentiate with adequate results rectum from colon cancer cases, and esophageal from head and neck and stomach cancers. These results point to the fact that anatomically adjacent cancers can be more complex to identify due to microbial similarities. Despite the limitations, microbiome data analysis using machine learning may advance novel strategies to improve cancer detection and prevention, and decrease disease burden.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

BACKGROUND: Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. METHODS: A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. RESULTS: A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. CONCLUSION: Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Implications of three different testing strategies in the diagnostic approach to patients with stable chest pain and low pretest probability of obstructive coronary artery disease.

INTRODUCTION: The clinical implications of a widespread adoption of guideline recommendations for patients with stable chest pain and low pretest probability (PTP) of obstructive coronary artery disease (CAD) remain unclear. We aimed to assess the results of three different testing strategies in this subgroup of patients: A) defer testing; B) perform coronary artery calcium score (CACS), withholding further testing if CACS â€‹= â€‹0 and proceeding to coronary computed tomography angiography (CCTA) if CACS>0; C) perform CCTA in all. METHODS: Two-center cross-sectional study assessing 1328 symptomatic patients undergoing CACS and CCTA for suspected CAD. PTP was calculated based on age, sex and symptom typicality. Obstructive CAD was defined as any luminal stenosis ≥50% on CCTA. RESULTS: The prevalence of obstructive CAD was 8.6% (n â€‹= â€‹114). In the 786 patients (56.8%) with CACS â€‹= â€‹0, 8.5% (n â€‹= â€‹67) had some degree of CAD [1.9% (n â€‹= â€‹15) obstructive, and 6.6% (n â€‹= â€‹52) nonobstructive]. Among those with CACS>0 (n â€‹= â€‹542), 18.3% (n â€‹= â€‹99) had obstructive CAD. The number of patients needed to scan (NNS) to identify one patient with obstructive CAD was 13 for strategy B vs. A, and 91 for strategy C vs. B. CONCLUSIONS: Using CACS as gatekeeper would decrease CCTA use by more than 50%, at the cost of missing obstructive CAD in one in 100 patients. These findings may help inform decisions on testing, which will ultimately depend on the willingness to accept some diagnostic uncertainty.