Covid-19 Social Distancing, Lifestyle and Health Outcomes Among Persons Living with HIV (PLWH): A Web-based Survey.

We investigated changes in lifestyle, depressive symptoms, self-perception of health, and body weight changes of persons living with HIV (PLWH) during the COVID-19 social distancing (SD). In a Web-based cross-sectional survey, participants (n = 406) were questioned about lifestyle and health status before and during SD. Most responders were men, 50 + years old, high education level; 49.8% had their income reduced during SD. About 9% were diagnosed with COVID-19, of whom 13.5% required hospitalization. During SD: - most participants did not change their food intake, although 25% replaced healthy foods with unhealthy ones; -more than half mentioned poor sleep quality; -about 50% increased their sedentary behavior. Depressive symptoms (reported by 70.9%) were associated with sedentary behavior, poor sleep quality, and reduced income. About one-third had a negative perception of their health status, which was inversely associated with practicing physical exercises and positively associated with sedentarism and poor sleep quality. More than half increased their body weight, which was associated with a lower intake of vegetables. The older age reduced the odds of the three outcomes. Carefully monitoring PLWH regarding SD will enable early interventions toward health.

RESUMEN: En este trabajo investigamos los cambios en el estilo de vida, síntomas depresivos, autopercepción de salud y cambios en el peso corporal de las personas que viven con el VIH (PVCV) durante el distanciamiento social (DS) de COVID-19. En una encuesta transversal en línea, se preguntó a los participantes (n = 406) sobre el estilo de vida y el estado de salud antes y durante el DS. La mayoría de los encuestados eran hombres, mayores de 50 años, con alto nivel educativo. El 49,8% tuvo una disminución en sus ingresos durante el DS. El 9,1% fue diagnosticados con COVID-19, de los cuales 13,5% requirió hospitalización. Durante el DS: - la mayoría de los participantes no cambió su ingesta de alimentos, aunque el 25% reemplazó los alimentos saludables por los no saludables; más de la mitad mencionó mala calidad del sueño; cerca del 50% aumentó su comportamiento sedentario. Los síntomas depresivos (referidos por el 70,9%), fueron incrementados por el sedentarismo, la mala calidad del sueño y reducción de la renta. Cerca de un tercio tenía una percepción negativa de su estado de salud, que se redujo con la práctica de ejercicio físico y aumentó con el sedentarismo y la mala calidad del sueño. Más de la mitad aumentó su peso corporal, lo que se asoció con una menor ingesta de vegetales. Una edad más avanzada redujo las probabilidades de los tres desenlaces. El monitoreo cuidadoso de las PVCV con respecto al DS permitirá intervenciones tempranas para la salud.

Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy.

A possible precision-medicine approach to treating obstructive sleep apnoea (OSA) involves targeting ventilatory instability (elevated loop gain) using supplemental inspired oxygen in selected patients. Here we test whether elevated loop gain and three key endophenotypic traits (collapsibility, compensation and arousability), quantified using clinical polysomnography, can predict the effect of supplemental oxygen on OSA severity.36 patients (apnoea-hypopnoea index (AHI) >20 events·h-1) completed two overnight polysomnographic studies (single-blinded randomised-controlled crossover) on supplemental oxygen (40% inspired) versus sham (air). OSA traits were quantified from the air-night polysomnography. Responders were defined by a ≥50% reduction in AHI (supine non-rapid eye movement). Secondary outcomes included blood pressure and self-reported sleep quality.Nine of 36 patients (25%) responded to supplemental oxygen (ΔAHI=72±5%). Elevated loop gain was not a significant univariate predictor of responder/non-responder status (primary analysis). In post hoc analysis, a logistic regression model based on elevated loop gain and other traits (better collapsibility and compensation; cross-validated) had 83% accuracy (89% before cross-validation); predicted responders exhibited an improvement in OSA severity (ΔAHI 59±6% versus 12±7% in predicted non-responders, p=0.0001) plus lowered morning blood pressure and "better" self-reported sleep.Patients whose OSA responds to supplemental oxygen can be identified by measuring their endophenotypic traits using diagnostic polysomnography.

Predicting epiglottic collapse in patients with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is characterised by pharyngeal obstruction occurring at different sites. Endoscopic studies reveal that epiglottic collapse renders patients at higher risk of failed oral appliance therapy or accentuated collapse on continuous positive airway pressure. Diagnosing epiglottic collapse currently requires invasive studies (imaging and endoscopy). As an alternative, we propose that epiglottic collapse can be detected from the distinct airflow patterns it produces during sleep.23 OSA patients underwent natural sleep endoscopy. 1232 breaths were scored as epiglottic/nonepiglottic collapse. Several flow characteristics were determined from the flow signal (recorded simultaneously with endoscopy) and used to build a predictive model to distinguish epiglottic from nonepiglottic collapse. Additionally, 10 OSA patients were studied to validate the pneumotachograph flow features using nasal pressure signals.Epiglottic collapse was characterised by a rapid fall(s) in the inspiratory flow, more variable inspiratory and expiratory flow and reduced tidal volume. The cross-validated accuracy was 84%. Predictive features obtained from pneumotachograph flow and nasal pressure were strongly correlated.This study demonstrates that epiglottic collapse can be identified from the airflow signal measured during a sleep study. This method may enable clinicians to use clinically collected data to characterise underlying physiology and improve treatment decisions.

Evaluating the influence of ultra-processed food intake on associations between dietary indices with systemic inflammation in adulthood and old ages.

BACKGROUND & AIMS: Low-grade systemic inflammation (LGSI) is critical to developing many chronic diseases. In turn, it has been shown that the diet can modulate favorably or unfavorably the inflammatory status. Thus, evaluating the diet from appropriate approaches is fundamental; to do so, there are different proposals for dietary indexes. We aimed to: (i) investigate the association between three well-known dietary indexes and LGSI biomarkers; (ii) test these associations individually or in combination with an indicator of ultra-processed foods (UFPs) intake. (iii) as an additional aim, hypothesizing that all the indexes should be capable of identifying the inflammatory potential of diet, we tested the hypothesis that these indexes agree and correlate with each other. METHODS: Cross-sectional population-based data of adults and older persons (n = 583). Dietary data were obtained through two non-consecutive 24-h dietary recalls (24HDR) and calculated for Dietary Inflammatory Index (DII), Mediterranean-Style Dietary Pattern Score (MSDPS); Brazilian Healthy Eating Index - Revised (BHEI-R) and energy ingested from UPFs (UPFs ratio). An LGSI score was created from some plasma inflammatory biomarkers [C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and adiponectin]. Logistic and linear regression models tested the associations between dietary indexes and LGSI score. RESULTS: The MSDPS and DII were significantly associated with our inflammatory score, but the BHEI-R did not. Including UPFs in regression models did not increase the strength of these associations. CONCLUSIONS: From the three scores, the dietary inflammatory index and the Mediterranean-style dietary pattern score (MSDPS) were the ones that showed significant association with the inflammatory biomarker. The combination of the indexes with a ratio of UPF intake did not increase the significance of our analyses. The best agreement between the indexes was found between MSDPS and UPFs ratio; the only pair of indexes considered concordant and correlated was the BHEI-R and DII.

Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence.

The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers (n=53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN, SFRP2, and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR, we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1, PGR, VCAN, and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-ß. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer.

Quantifying the Arousal Threshold Using Polysomnography in Obstructive Sleep Apnea.

Study Objectives: Precision medicine for obstructive sleep apnea (OSA) requires noninvasive estimates of each patient's pathophysiological "traits." Here, we provide the first automated technique to quantify the respiratory arousal threshold-defined as the level of ventilatory drive triggering arousal from sleep-using diagnostic polysomnographic signals in patients with OSA. Methods: Ventilatory drive preceding clinically scored arousals was estimated from polysomnographic studies by fitting a respiratory control model (Terrill et al.) to the pattern of ventilation during spontaneous respiratory events. Conceptually, the magnitude of the airflow signal immediately after arousal onset reveals information on the underlying ventilatory drive that triggered the arousal. Polysomnographic arousal threshold measures were compared with gold standard values taken from esophageal pressure and intraoesophageal diaphragm electromyography recorded simultaneously (N = 29). Comparisons were also made to arousal threshold measures using continuous positive airway pressure (CPAP) dial-downs (N = 28). The validity of using (linearized) nasal pressure rather than pneumotachograph ventilation was also assessed (N = 11). Results: Polysomnographic arousal threshold values were correlated with those measured using esophageal pressure and diaphragm EMG (R = 0.79, p < .0001; R = 0.73, p = .0001), as well as CPAP manipulation (R = 0.73, p < .0001). Arousal threshold estimates were similar using nasal pressure and pneumotachograph ventilation (R = 0.96, p < .0001). Conclusions: The arousal threshold in patients with OSA can be estimated using polysomnographic signals and may enable more personalized therapeutic interventions for patients with a low arousal threshold.

Stable Breathing in Patients With Obstructive Sleep Apnea Is Associated With Increased Effort but Not Lowered Metabolic Rate.

Study objectives: In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines. Methods: Twelve OSA patients (apnea-hypopnea index >15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure). Results: Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 ± 20 vs. 213 ± 18 mL/min), despite elevated respiratory effort during stable breathing (26 ± 2 versus 23 ± 2 cmH2O, p = .03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p = .04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO2 by 14% in both cases (p = .02, .03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort. Conclusions: OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events.

Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults.

RATIONALE: The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages. OBJECTIVES: We tested the hypothesis that administration of a single dose of 4-AP 10 mg extended release would increase genioglossus activity (electromyography of the genioglossus muscle [EMGGG]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility. METHODS: We performed a randomized controlled crossover proof-of-concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the physiology laboratory. RESULTS: EMGGG during wakefulness and NREM sleep and upper airway collapsibility measured during NREM sleep were unchanged between placebo and 4-AP nights. Tonic but not phasic EMGGG during REM sleep was higher on the 4-AP night when measured as a percentage of maximal voluntary activation (median [interquartile range] 0.3 [0.5] on placebo vs. 0.8 [1.9] %max on 4 AP; P = 0.04), but not when measured in µV or as a percentage of wakefulness value. CONCLUSIONS: A single dose of 4-AP 10 mg extended release showed only a small increase in tonic EMGGG during REM sleep in this group of healthy subjects. We speculate that a higher dose of 4-AP may further increase EMGGG. However, given the potentially severe, dose-related adverse effects of this drug, including seizures, the administration of 4-AP does not appear to be an effective strategy to increase genioglossus activity during sleep in humans. Clinical Trial registered with clinicaltrials.gov (NCT02656160).

Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma.

BACKGROUND: Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+) and recurrent head and neck squamous cell carcinoma (HNSCC) may increase our understanding of the complex biology of this disease. METHODS: Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative) or tumor recurrence (recurrent or non-recurrent tumor) after treatment (surgery with neck dissection followed by radiotherapy). Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. RESULTS: The most frequent alterations were the repression of modules in negative lymph node (N0) and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. CONCLUSIONS: The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway, specially apoptosis and interactions between tumor cells and the stroma.

Comparação entre o estado nutricional de mulheres idosas e mulheres jovens: relação com a leptina e o IGF-I / Comparison of nutritional status between young and elderly women: relation with leptin and IGF-I

Objetivos: comparar, entre mulheres idosas e mulheres jovens, o estado nutricional a partir de variáveis antropométricas, dietéticas e bioquímicas, buscando relação com as concentrações plasmáticas de leptina e IGF-I. Métodos: 18 mulheres voluntariamente recrutadas foram distribuídas em dois grupos: I= idosas (mais de 60 anos, n=10) e J= jovens (entre 20-30anos, n=8). Foram avaliados: índice de massa corporal (IMC), circunferência de cintura (CC) e composição corporal (massa gorda e massa livre de gordura) por bioimpedância elétrica; três diários alimentares calculados quantitativamente em energia, macronutrientes e colesterol; concentrações plasmáticas de glicose, lipídeos, albumina, leptina e IGF-I. Resultados: O grupo I apresentou maiores valores de IMC, CC, percentual de gordura corporal e concentração plasmática de leptina e lipoproteínas de baixa densidade. O grupo J apresentou maiores valores para as concentrações plasmáticas de IGF-I e para o percentual de massa magra. A leptina correlacionou-se positiva e significativamente com a massa gorda e com a CC na análise do grupo todo. Após o ajuste da leptina pela massa gorda, não foram observadas diferenças entre os grupos. Após o ajuste do IGF-I pela massa livre de gordura, o grupo J apresentou maiores valores. As concentrações plasmáticas de albumina e de glicose apresentaram-se dentro da normalidade e sem diferenças entre os grupos. Conclusões: as concentrações de leptina são mais elevadas em mulheres idosas, proporcionalmente ao aumento da massa gorda, em especial a gordura visceral. Foi possível identificar relação entre leptina, eixo somatotrófico, e metabolismo hepático de lipoproteínas. O balanço energético foi negativo para ambos os grupos, porém não foram identificados desvios no estado nutricional, o que pode indicar subnotificação de relatos alimentares e supernotificação de atividade física.

Aim: to compare nutritional status between old and young women, from anthropometric, dietetic and biochemical variables, looking for relation with leptin and IGF-Iconcentration. Methods: 18 voluntary women were distributed in two groups: -more than 60 yearsold (n=10), named “old” (O); - between 20-30 years (n=8), named “young” (Y). They were evaluated:body mass index (BMI), waist circumference (WC) and body composition by bioelectric impedance (fat mass and fat free mass); diet evaluation by three food diary calculated by energy, macronutrients and cholesterol; plasmatic concentration of lipids, glucose, albumin, leptin and IGF-I. Results: “O”group presented higher values from BMI, WC, percent body fat, leptin levels and low density lipoproteins. “Y” group presented higher values from IGF-I and percent lean body mass. Leptin correlated positive and significantly with fat mass and WC, when analyzed for all individuals. After adjustment of leptin for body fat, there were not significant differences between groups. After adjustment of IGF-I by body lean mass, “Y” presented higher values. Conclusions: leptin levels are higher in old women, proportional to an increase in body fat, specifically visceral fat. It was possible to identify a relation among leptin, somatotrophic axis and liver lipoprotein metabolism. Energetic balance was negative for all the subjects without any deviation in nutritional status; its hould be due to underreporting of food ingestion and overreporting of physical activity.