Effects of Non-Invasive Ventilation with different modalities in patients undergoing heart surgery: Protocol for a randomized controlled clinical trial.

INTRODUCTION: The thoracic surgical procedure leads to a reduction in respiratory muscle strength. To restore it, certain strategies must be employed. Physiotherapy utilizes resources and techniques such as deep breathing stimulation, cough stimulation, use of incentive spirometers, mobilization, and ambulation. However, at times these resources and techniques may prove insufficient, and additional measures, such as Non-Invasive Ventilation (NIV), are employed Pieczkoski (2017). Non-Invasive Positive Pressure Ventilation (NPPV) has been utilized to expedite pulmonary function recovery as well as to prevent and treat postoperative pulmonary complications Nasrala 2018. NIV diminishes the risk of ventilator-associated complications due to its non-invasive nature. Consequently, NIV has been adopted to avert post-extubation complications in postoperative patients Liu 2020. The objective of this study is to conduct a randomized clinical trial and assess the efficacy of NIV in comparison to conventional physiotherapy in terms of pulmonary function among patients undergoing cardiac surgery at a selected hospital in Campina Grande, Paraíba, Brazil. METHODS AND ANALYSES: This randomized, controlled, double-blind (patient and analyst) clinical trial will be conducted at Hospital João XXIII in Campina Grande, Paraíba, Brazil. Patients do not know which group they are allocated to. Those in the group that use CPAP or BIPAP will not be able to distinguish one from the other. The data analyst at the end of the collections will also be blinded. Only the health professional who will be applying the protocol cannot be blinded. The sample size, determined via sample calculation, yielded a total of 21 patients per group (63 patients). The patients will be allocated into 3 groups (CPAP group - CPAP + standard physiotherapy, BiPAP group - BiPAP + standard physiotherapy, and Control group - standard physiotherapy) in a 1:1:1 allocation ratio. The control group will receive the usual physiotherapeutic treatment as per the kinesiotherapy protocol. The treatment will be administered twice daily, starting in the ICU and progressing to the ward. In the CPAP group, nasal CPAP at 10cmH2O will be administered for 1 hour, twice daily, using an approved device. In the BiPAP group, nasal BiPAP with an IPAP of 13cmH2O and EPAP of 8cmH2O will be administered for 1 hour, twice daily, using an approved device. The NIV sessions will be conducted over the course of 5 days of hospitalization, both in the ICU and the ward. Assessments will be conducted at two time points: on day 1 preoperatively and on day 5 postoperatively. The following measures will be evaluated: pulmonary function, length of hospital stay, presence of postoperative pulmonary complications, score of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) in its Portuguese version, functional capacity, the Global Perception of Change Scale, and the Functional Independence Measure (MIF). The normality of variables will be assessed using the Shapiro-Wilk test. IBM SPSS Statistics Base 25.0, using the Shapiro-Wilk test for normality and paired Student's t-test for pre-post intervention comparison. They will use linear mixed effects models for longitudinal analysis and GLMMs to compare NIV effects over time between groups. They will employ ITT for missing data, INAR models for time dependence, fixed effects models for endogeneity, and Cohen's d for effect sizes. Parametric model assumptions will be checked, and various models will be considered for data characteristics. PRIMARY OUTCOMES: Pulmonary function, Length of hospital stay. SECOND OUTCOMES: Score of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) in Portuguese version, Funcional capacity, The global perception of change scale, The functional independence measure (MIF), pO2 (partial pressure of oxygen), pCO2 (partial pressure of carbon dioxide), HCO3 (bicarbonate), Arterial Oxygen Saturation (SaO2), Base Excess (BE), Presence of lung complications. OTHER PRE-SPECIFIED OUTCOMES: Duration of cardiopulmonary bypass, type of surgery, personal history, preoperative ejection fraction, previous respiratory complications, body mass index (BMI), gender and age. TRIAL REGISTRATION: Trial register number NCT05966337.

Aberrant TIMP-1 production in tumor-associated fibroblasts drives the selective benefits of nintedanib in lung adenocarcinoma.

The fibrotic tumor microenvironment is a pivotal therapeutic target. Nintedanib, a clinically approved multikinase antifibrotic inhibitor, is effective against lung adenocarcinoma (ADC) but not squamous cell carcinoma (SCC). Previous studies have implicated the secretome of tumor-associated fibroblasts (TAFs) in the selective effects of nintedanib in ADC, but the driving factor(s) remained unidentified. Here we examined the role of tissue inhibitor of metalloproteinase-1 (TIMP-1), a tumor-promoting cytokine overproduced in ADC-TAFs. To this aim, we combined genetic approaches with in vitro and in vivo preclinical models based on patient-derived TAFs. Nintedanib reduced TIMP-1 production more efficiently in ADC-TAFs than SCC-TAFs through a SMAD3-dependent mechanism. Cell culture experiments indicated that silencing TIMP1 in ADC-TAFs abolished the therapeutic effects of nintedanib on cancer cell growth and invasion, which were otherwise enhanced by the TAF secretome. Consistently, co-injecting ADC cells with TIMP1-knockdown ADC-TAFs into immunocompromised mice elicited a less effective reduction of tumor growth and invasion under nintedanib treatment compared to tumors bearing unmodified fibroblasts. Our results unveil a key mechanism underlying the selective mode of action of nintedanib in ADC based on the excessive production of TIMP-1 in ADC-TAFs. We further pinpoint reduced SMAD3 expression and consequent limited TIMP-1 production in SCC-TAFs as key for the resistance of SCC to nintedanib. These observations strongly support the emerging role of TIMP-1 as a critical regulator of therapy response in solid tumors.

Orbicularis muscle graft for treating deep glabellar rhytids / Enxerto de músculo orbicular para tratamento de rítide glabelar profunda

ABSTRACT Purpose To evaluate the efficacy of grafting a preseptal strip of orbicularis muscle to treat deep static glabellar wrinkles. Methods This was a prospective, interventional, case series study that included patients aged between 21 and 80, who underwent upper and lower blepharoplasty, and who presented varying degrees of deep static glabellar rhytids. After marking the glabellar rhytid, a subcision was made with 40 x 12mm needle along the entire length of the glabellar wrinkle. The orbicularis muscle graft was set into the recipient pocket already created in the glabella. The patients answered a self-assessment form about the results using the subject Global Aesthetic Improvement Scale after 6 months. Results Seventeen glabellar rhytid fillings were performed. As for the subjective evaluation of the result of the specific glabella filling procedure, the patients were distributed as follows: 12 rhytids (70.6%; 12 out of 17) were self-assessed as much better; 4 rhytids (23.6%; 3 out of 17) were self-assessed as better, and 1 rhytid (5.8%; 1 of 17) was self-assessed as unchanged. Conclusion This technique has excellent results, is easy to perform, has low morbidity and presents a high degree of satisfaction when patients evaluated themselves.

RESUMO Objetivo Avaliar a eficácia do enxerto de uma tira pré-septal do músculo orbicular no tratamento de rugas glabelares estáticas profundas. Métodos Trata-se de estudo prospectivo, intervencionista, do tipo série de casos, que incluiu pacientes com idade entre 21 e 80 anos, submetidos à blefaroplastia superior ou superior e inferior e que apresentavam graus variados de rítides glabelares estáticas profundas. Após marcação da rítide glabelar, foi feita subcisão com agulha 40x12mm em toda a extensão da ruga glabelar, criando uma porta de entrada para o enxerto e formando um leito receptor na hipoderme. O enxerto do músculo orbicular foi inserido no leito glabelar. Os pacientes foram acompanhados considerando pós-operatório mínimo de 6 meses. Eles responderam a um formulário de autoavaliação sobre os resultados por meio da Escala Global Aesthetic Improvement Scale. Resultados Foram realizados 17 enxertos de rítides glabelares (três pacientes submetidos ao procedimento bilateral). Quanto à avaliação subjetiva do resultado do procedimento, os pacientes foram distribuídos da seguinte forma: 12 rítides (70,6%; 12 de 17) autoavaliaram-se como muito melhores; 4 rítides (23,6%; 3 de 17) foram autoavaliadas como melhores e 1 rítide (5,8%; 1 de 17) foi autoavaliada como inalterada. Conclusão A presente técnica apresenta excelentes resultados, é de fácil execução, apresenta baixa morbidade e alto grau de satisfação na autoavaliação.

Comparação das respostas neuromusculares e bioquímicas entre pacientes com DPOC e indivíduos saudáveis / Comparison of neuromuscular and biochemical responses between patients with COPD and healthy subjects

Objetivo: Comparar as respostas neuromusculares e bioquímicas do dano e fadiga muscular do quadríceps femoral entre indivíduos com doença pulmonar obstrutiva crônica (DPOC) e saudáveis. Métodos: Estudo observacional, transversal e comparativo. A amostra foi composta por 18 indivíduos alocados em dois grupos distintos: Grupo DPOC (GD) e grupo saudáveis (GS), os quais foram avaliados por meio da espirometria, do desempenho neuromuscular do quadríceps, dos marcadores bioquímicos do dano e fadiga muscular, da fatigabilidade e da dor muscular. Resultados: Observou-se diferença estatisticamente significante na potência média entre o GD e GS (99,9 ± 21,0 vs 145,1 ± 51,5, respectivamente; p= 0,02) e uma tendência das médias de pico de torque (85,7 ± 24,4 vs 104,4 ± 31,0; p= 0,45) e trabalho total (1.305,5 ± 329,9 vs 1.671,5 ± 444,5; p= 0,06) serem menores no GD que no GS, respectivamente. A concentração da LDH imediatamente após o teste isocinético foi significantemente maior no GD que no GS (402,3 ± 33,6 vs 289,4 ± 33,6, respectivamente; p= 0,03). Conclusões: O presente estudo mostrou que pacientes com DPOC tem redução da capacidade de gerar força em um determinado período de tempo quando comparado a indivíduos saudáveis. A dosagem plasmática dos marcadores bioquímicos não permitiu confirmar que os pacientes com DPOC tem maior nível de dano muscular quando realizam exercício que os controles saudáveis.

Objective: To compare neuromuscular and biochemical responses of femoral quadriceps muscle damage and fatigue between chronic obstructive pulmonary disease (COPD) and healthy subjects. Methods: Observational, transversal and comparative study. The sample consisted of 18 subjects assigned to two distinct groups: COPD group (CG) and healthy group (HG), who were assessed by spirometry, quadriceps neuromuscular performance, biochemical markers of muscle damage and fatigue, fatigability and muscle pain. Results: Statistically significant difference was observed in mean power between CG and HG (99.9 ± 21.0 vs. 145.1 ± 51.5, respectively; p= 0.02) and a tendency of mean peak torque (85.7 ± 24.4 vs 104.4 ± 31.0, p= 0.45) and total work (1,305.5 ± 329.9 vs 1.671.5 ± 444.5; p= 0.06) were smaller in the CG than HG, respectively. The LDH concentration immediately after the isokinetic test was significantly higher in the CG than HG (402.3 ± 33.6 vs 289.4 ± 33.6, respectively; p= 0.03). Conclusions: The present study showed that patients with COPD have a reduced ability to generate force over a given period of time when compared to healthy subjects. The plasma levels of biochemical markers did not confirm that patients with COPD have a higher level of muscle damage when exercising than healthy controls.

Development of a New Questionnaire to Assess Parental Perceived Barriers When Promoting Healthy Eating Habits in Young Children: First Findings.

Social cognitive models suggest a crucial role played by perceived barriers in promoting healthy behaviors, including healthy eating. We aimed to develop a new questionnaire to assess parental perceived barriers to healthy feeding in young children and perform the instrument's preliminary psychometric evaluation. The initial pool of items was developed based on reviews and qualitative studies. First, we conducted an online, descriptive, cross-sectional study with 278 parents of 2-6-year-old children to examine its factorial structure and internal consistency. Then, a second study with 168 parents from a similar population assessed convergent/discriminant and known-groups validity. The exploratory factorial analysis confirmed the scale's theoretical structure. Five scales were found: Child-Related Barriers, Parent-Related Barriers-Vegetables and Fruit, Parent-Related Barriers-Added Sugars, Social Context-Related Barriers, and Cost-Related Barriers. All scales presented adequate reliability. We found weak to moderate, negative, and significant correlations between child- and parent-related barriers regarding vegetables and fruits, feeding practices to promote children's eating self-regulation, and food parenting self-efficacy. Additionally, parents who perceived their children as easy and well-regulated reported significantly fewer child-related barriers than parents with poorly self-regulated and inhibited children. The results support the instrument's preliminary psychometric adequacy regarding its validity and reliability and corroborate earlier empirical studies about the main parental barriers when promoting young children's healthy eating habits.

Associação entre insegurança e consumo alimentar em universitários brasileiros durante a pandemia de COVID-19 / Association between food insecurity and consumption in Brazilian university students during the COVID-19 pandemic

Introdução. A COVID-19 impactou a garantia de uma alimentação adequada e saudável, inclusive entre universitários, que parecem constituir um grupo suscetível à Insegurança Alimentar (IA). Objetivo. Verificar a associação entre IA e marcadores de consumo alimentar em universitários durante a pandemia de COVID-19. Materiais e métodos. Estudo transversal com 5407 estudantes de instituições de ensino superior de todas as regiões do Brasil. Os dados foram coletados entre agosto/2020 e fevereiro/2021. O consumo alimentar foi avaliado por marcadores de alimentação saudável utilizados num inquérito nacional de saúde (VIGITEL). Os níveis de IA foram classificados pela Escala Brasileira de Insegurança Alimentar em Segurança Alimentar (SA) e IA leve, moderada e grave. A associação entre IA e marcadores de consumo foi avaliada por meio de regressão logística, considerando frequência semanal de consumo < 3 dias e ≥ 3 dias. Resultados. 37% dos universitários estavam em algum grau de IA. Verificou-se maior chance de baixa frequência de consumo de feijão (OR 1,81), verduras e legumes (OR 4,76), frutas (OR 3,99), lácteos (OR 3,98) e carnes (OR 3,41), e maiores chances de maior consumo de frango (OR 1,14) e ovos (OR 2,04) entre aqueles em IA (p<0,05). Em sua maioria, os valores foram mais expressivos quanto maior o grau de IA. Conclusões. Maiores níveis de IA mostraram-se associados a uma menor chance de consumo alimentar saudável por universitários. Instituições de ensino superior podem executar papéis importantes no combate e assistência à IA nessa população(AU)

Introduction. COVID-19 has impacted access to an adequate and healthy diet, including university students, who seem to constitute a group susceptible to Food Insecurity (FI). Objective. To verify the association between FI and food consumption markers in university students during the COVID-19 pandemic. Materials and Methods. We conducted a cross- sectional study with 5407 students from higher education institutions from all regions of Brazil. Data were collected between August/2020 and February/2021. We evaluated food consumption using the healthy eating markers from a Brazilian national health survey (VIGITEL). We classified the FI levels according to the Brazilian Food Insecurity Scale into Food Security (FS) and mild, moderate, and severe FI. We evaluated the association between FI and consumption markers using logistic regression, considering the weekly frequency of consumption of < 3 days and ≥ 3 days. Results. 37% of the university students had in some degree of FI. We found a greater chance of lower frequency of consumption of beans (OR 1.81), vegetables (OR 4.76), fruits (OR 3.99), dairy products (OR 3.98), and meat (OR 3. 41), and greater chances of increased consumption of chicken (OR 1.14) and eggs (OR 2.04) among those in FI (p<0.05). Overall, the values were more expressive the higher the degree of FI. Conclusions. Higher FI levels were associated with a lower chance of healthy food consumption in university students. Higher education institutions can play a relevant role in addressing and administering the FI in this population(AU)

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer.

Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1-5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity.

Changes in Functional Outcomes After an Inpatient Rehabilitation Program for Solid-Organ Transplant Recipients.

Introduction: Outpatient exercise training has been shown to be beneficial for solid organ transplant recipients. Little is known about the effects of inpatient rehabilitation programs for recipients with a more complicated postoperative course. Research Question: This study was designed to (1) describe the changes in functional outcomes after an inpatient rehabilitation program, and (2) determine whether the changes in lower body strength and quadriceps strength are associated with changes in functional exercise capacity. Design: This was a single-arm prospective longitudinal study. The recipients participated in an inpatient rehabilitation program twice a day, 7 days a week for 3 to 4 weeks. Outcome Measures Included: 2-Minute Walking Test, Timed Up and Go, Berg Balance Scale, 30-Second Sit to Stand, biceps and quadriceps strength, Functional Independence Measure, SF-36, and Canadian Occupational Performance Measure. Results: Twenty-eight patients (54% female, mean age = 55 [11]) completed the study. Participants were mostly liver (42%) and lung recipients (35%). There were statistically significant improvements in all outcomes after the intervention. There was no relationship between changes in functional exercise capacity and quadriceps strength or lower body strength. Conclusion: An inpatient rehabilitation program may improve several functional outcomes and health-related quality of life in transplant recipients with a complicated postoperative course.

Efficacy of home-based inspiratory muscle training in patients post-covid-19: Protocol for a randomized clinical trial.

INTRODUCTION: Current evidence suggests the emergence of a novel syndrome (long COVID syndrome) due to sequels and persistent COVID-19 symptoms. Respiratory muscle training improves respiratory muscle strength, exercise capacity, diaphragm thickness, and dyspnea, especially in patients with decreased respiratory muscle strength. This study aims to evaluate the effectiveness of a protocol for home-based inspiratory muscle training to improve respiratory muscle strength, dyspnea, and quality of life of patients post-COVID-19. METHODS AND ANALYSES: This randomized, controlled, double-blind clinical trial will be conducted at the Instituto de Medicina Tropical of Universidade Federal do Rio Grande do Norte (Brazil). Sample size will be determined using maximal inspiratory pressure after a pilot study with five patients per group (total of 10 patients). Patients included in the study will be evaluated in three moments: pre-training (initial), post-training (three weeks), and retention (24 weeks). The sample will be randomized in two groups: active (IMT using 30% of IMT and load increase of 10% of initial IMT every week. Patients will perform 30 repetitions, twice a day (morning and afternoon), for seven consecutive days, and six weeks) and SHAM (IMT without load). The following measurements will be assessed: anthropometry, respiratory muscle strength, pulmonary volume and capacity, dyspnea, perception of effort and lower limb fatigue, handgrip strength, functional capacity, anxiety, depression, and functional status. After initial evaluation, all patients will receive a POWERbreathe® (POWERbreathe®, HaB Ltd, Southam, UK) device to perform the training. Normality will be verified using Shapiro-Wilk or Kolmogorov-Smirnov, according to the number of patients included. Variables presenting nonparametric distribution will be compared using Wilcoxon (intragroup analysis) and Mann-Whitney test (intergroup analysis), whereas repeated measures two-way ANOVA will be performed in case of parametric distribution. Dunn's post hoc test will be used to identify significant differences in the two-way ANOVA test. PRIMARY OUTCOMES: Respiratory muscle strength, dyspnea, and quality of life of post-COVID-19 patients. SECOND OUTCOMES: Pulmonary function, dyspnea, exercise tolerance, handgrip strength, anxiety, depression, and functional status. TRIAL REGISTRATION: Trial register number NCT05077241.

In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells.

Therapeutic oligonucleotides are powerful tools for the inhibition of potential targets involved in cancer. We describe the effect of two Polypurine Reverse Hoogsteen (PPRH) hairpins directed against the ERBB2 gene, which is overexpressed in positive HER-2 breast tumors. The inhibition of their target was analyzed by cell viability and at the mRNA and protein levels. The combination of these specific PPRHs with trastuzumab was also explored in breast cancer cell lines, both in vitro and in vivo. PPRHs designed against two intronic sequences of the ERBB2 gene decreased the viability of SKBR-3 and MDA-MB-453 breast cancer cells. The decrease in cell viability was associated with a reduction in ERBB2 mRNA and protein levels. In combination with trastuzumab, PPRHs showed a synergic effect in vitro and reduced tumor growth in vivo. These results represent the preclinical proof of concept of PPRHs as a therapeutic tool for breast cancer.

Acute effects of NIV on peripheral muscle function and aerobic performance in patients with chronic obstructive pulmonary disease: a pilot study.

BACKGROUND: Non-invasive ventilation (NIV) reduces respiratory load and demands on peripheral muscles. METHODS: This study aims to evaluate the acute effects of bi-level NIV on peripheral muscle function during isokinetic exercise and aerobic performance in chronic obstructive pulmonary disease (COPD) patients. This is a pilot crossover study performed with a non-probabilistic sample of 14 moderate to very severe COPD patients. Procedures carried out in two days. Dyspnea, quality of life, lung function, respiratory muscle strength, functional capacity (6-min walk test-6MWT), and isokinetic assessment of the quadriceps were assessed. Blood samples (lactate, lactate dehydrogenase, and creatine kinase concentration) were also collected. Right after, NIV was performed for 30 min (bi-level or placebo, according to randomization) followed by new blood sample collection, 6MWT, and isokinetic dynamometer tests. Before and after evaluations, the subjective perception of dyspnea and fatigue in the lower limbs was quantified. After a wash-out period of seven days, participants returned, and all assessments were performed again. RESULTS: NIV showed improvements in perceived exertion and dyspnea after isokinetic exercise (p < 0.02 and p < 0.05, respectively). CONCLUSIONS: NIV improves the perception of dyspnea and fatigue during the isokinetic exercise.

Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment.

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.

Food Insecurity and Associated Factors in Brazilian Undergraduates during the COVID-19 Pandemic.

Undergraduates may face challenges to assure food security, related to economic and mental distress, especially during the COVID-19 pandemic. This study aimed to assess food insecurity and its associated factors in undergraduates during the COVID-19 pandemic. An online cross-sectional study was conducted from August 2020 to February 2021 with 4775 undergraduates from all Brazilian regions. The questionnaire contained socio-economic variables, the validated Brazilian food insecurity scale, and the ESQUADA scale to assess diet quality. The median age of the students was 22.0 years, and 48.0% reported income decreasing with the pandemic. Food insecurity was present in 38.6% of the students, 4.5% with severe food insecurity and 7.7% moderate. Logistic regressions showed students with brown and black skin color/race presented the highest OR for food insecurity; both income and weight increase or reduction during the pandemic was also associated with a higher OR for food insecurity, and better diet quality was associated with decreased OR for food insecurity. Our study showed a considerable presence of food insecurity in undergraduates. Policy for this population must be directed to the most vulnerable: those with brown and black skin color/race, who changed income during the pandemic, and those presented with difficulties maintaining weight and with poor diet quality.

Phenolic Lipids Derived from Cashew Nut Shell Liquid to Treat Metabolic Diseases.

Metabolic diseases are increasing at staggering rates globally. The peroxisome proliferator-activated receptors (PPARα/γ/δ) are fatty acid sensors that help mitigate imbalances between energy uptake and utilization. Herein, we report compounds derived from phenolic lipids present in cashew nut shell liquid (CNSL), an abundant waste byproduct, in an effort to create effective, accessible, and sustainable drugs. Derivatives of anacardic acid and cardanol were tested for PPAR activity in HEK293 cell co-transfection assays, primary hepatocytes, and 3T3-L1 adipocytes. In vivo studies using PPAR-expressing zebrafish embryos identified CNSL derivatives with varying tissue-specific activities. LDT409 (23) is an analogue of cardanol with partial agonist activity for PPARα and PPARγ. Pharmacokinetic profiling showed that 23 is orally bioavailable with a half-life of 4 h in mice. CNSL derivatives represent a sustainable source of selective PPAR modulators with balanced intermediate affinities (EC50 ∼ 100 nM to 10 µM) that provide distinct and favorable gene activation profiles for the treatment of diabetes and obesity.

Primary neural leprosy: clinical, neurophysiological and pathological presentation and progression.

Disability in leprosy is a direct consequence of damage to the peripheral nervous system which is usually worse in patients with no skin manifestations, an underdiagnosed subtype of leprosy known as primary neural leprosy. We evaluated clinical, neurophysiological and laboratory findings of 164 patients with definite and probable primary neural leprosy diagnoses. To better understand the disease progression and to improve primary neural leprosy clinical recognition we compared the characteristics of patients with short (≤12 months) and long (>12 months) disease duration. Positive and negative symptoms mediated by small-fibres were frequent at presentation (∼95%), and symptoms tend to manifest first in the upper limbs (∼68%). There is a consistent phenotypic variability between the aforementioned groups. Deep sensory modalities were spared in patients evaluated within the first 12 months of the disease, and were only affected in patients with longer disease duration (∼12%). Deep tendon reflexes abnormalities were most frequent in patients with longer disease duration (P < 0.001), as well as motor deficits (P = 0.002). Damage to large fibres (sensory and motor) is a latter event in primary neural leprosy. Grade-2 disability and nerve thickening was also more frequent in cases with long disease duration (P < 0.001). Primary neural leprosy progresses over time and there is a marked difference in clinical phenotype between patients with short and long disease duration. Patients assessed within the first 12 months of symptom onset had a non-length-dependent predominant small-fibre sensory neuropathy, whilst patients with chronic disease presented an asymmetrical all diameter sensory-motor neuropathy and patchily decreased/absent deep tendon reflexes.

Breakfast skipping and cardiometabolic risk factors in adolescents: Systematic review.

OBJECTIVE: To systematically review the results of the association between breakfast skipping and cardiometabolic risk factors in adolescents. METHODS: The articles were searched in May 2020 from PubMed, Virtual Health Library, Scopus, Web of Science and Scientific Electronic Library Online (SciELO). The review included observational studies conducted with adolescents (10-19 years old), which estimated the association of breakfast skipping with at least one outcome (markers of body adiposity, blood pressure, serum lipid and glucose levels). Regarding the risk of bias, the articles were evaluated using the Research Triangle Institute (RTI) Item Bank on bias risk and accuracy of observational studies. The quality of the evidence was assessed by the Grade rating. RESULTS: A total of 43 articles involving 192,262 participants met the inclusion criteria and were considered in this review. The prevalence of breakfast skipping ranged from 0.7% to 94% and 60.5% of studies were classified with low risk of bias. The significant association between breakfast skipping and cardiometabolic risk factors was found in twenty-nine cross-sectional articles (n = 106,031) and four longitudinal articles (n = 5,162) for excess adiposity, in three articles (n = 8,511) for high total cholesterol levels, low-density lipoprotein and triglycerides, and in three studies (n = 6,303) for high blood pressure levels. However, there was no significant association between breakfast skipping and glycemic profile. According to the Grade rating, all the associations had low quality of evidence. CONCLUSION: The results of this review suggest that breakfast skipping is associated with cardiometabolic risk factors in adolescents aged 10 to 19 years. However, considering the low quality of the evidence, the present results should be interpreted carefully. In addition, our findings highlight the importance of standardizing the definition of breakfast skipping and that more prospective studies are needed to determine how skipping breakfast can affect cardiometabolic risk factors in the long time.

Poor sleep quality, excessive daytime sleepiness and association with mental health in college students.

AIM: To estimate the prevalence of poor sleep quality and excessive daytime sleepiness (EDS) among college students and to analyse their association with aspects of mental health. SUBJECTS AND METHODS: A cross-sectional study carried out with 1113 college students, enrolled in full-time courses at a public university in the Mid-West region of Brazil. Data were collected through a self-administered questionnaire with questions about demographics, socioeconomics, mental health, sleep quality, and EDS. Measurements of weight and height were taken to assess weight status using the body mass index. Multivariate logistic regression models were used to estimate the associations between perceived stress (classified as light, moderate, and high) and presence of depressive symptoms with poor sleep quality and presence of EDS. RESULTS: High prevalence of poor sleep quality (65.5%) and EDS (55%) was observed. In the adjusted models, poor sleep quality was significantly associated with moderate and high perceived stress and presence of depressive symptoms. For EDS, there was also a significant association with moderate and high perceived stress and presence of depressive symptoms. CONCLUSIONS: High prevalence of poor sleep quality and EDS was found among college students. Perceived stress and presence of depressive symptoms were significantly associated with both evaluated outcomes.

Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis.

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs' role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

Associação entre composição domiciliar e consumo alimentar em adolescentes: uma revisão sistemática / Association between household composition and dietary consumption in adolescents: a systematic review

Objetivo: Revisar sistematicamente a associação entre composição domiciliar e consumo alimentar em adolescentes. Métodos: Trata-se de revisão sistemática da literatura. A busca dos artigos foi realizada nas bases de dados MEDLINE via PubMed, Scientific Electronic Library Online (SciELO), Web of Science, Biblioteca Virtual em Saúde, Embase e Scopus. Os artigos foram avaliados por meio do Research Triangle Institute (RTI) Item Bank sobre risco de viés e acurácia de estudos observacionais. Foram avaliados estudos observacionais com adolescentes (10-19 anos de idade). Resultados: Dos 2.324 artigos encontrados, 11 atenderam aos critérios de inclusão, 9 de delineamento transversal e 2 longitudinais. Quanto à avaliação do consumo alimentar, foram avaliadas as frequências de: jantar em família, consumo de café da manhã, consumo de refeições, omissão do café da manhã, consumo de grupos alimentares, número de refeições realizadas durante o dia, assim como densidade energética de grupos alimentares e o Índice de Alimentação Saudável. Observou-se que adolescentes que moravam com ambos os pais apresentaram maior frequência de consumo do café da manhã e maior consumo de vegetais. Preferências alimentares mais positivas e saudáveis foram mais frequentes entre adolescentes que residiam em famílias nucleares. Por outro lado, consumo irregular de café da manhã e consumo de marcadores de alimentação não saudável foram mais frequentes entre adolescentes residentes em domicílios monoparentais, com família reconstituída e famílias extensas. Conclusão: Adolescentes que moravam com ambos os pais apresentaram melhor consumo alimentar. Ressalta-se a necessidade de considerar a composição domiciliar ao planejar programas de promoção da alimentação saudável entre adolescentes. (AU)

Objective: To review systematically the association between household composition and eating habits of adolescents. Methods: Systematic literature review. The search of articles was conducted on the databases MEDLINE via PubMed, Scientific Electronic Library Online (SciELO), Web of Science, Virtual Health Library, Embase and Scopus. The articles were assessed through the Research Triangle Institute (RTI) Item Bank for risk of bias and accuracy of observational studies. Observational studies with adolescents (aged 10-19 years) were carried out. Results: Of 2,324 articles found, 11 met the eligibility criteria, nine being cross-sectional and two longitudinal studies. With respect to dietary habits, we assessed the following frequencies: family dinner, breakfast, meals consumption, breakfast skipping, food groups eaten, number of meals eaten per day, as well as energy density of food groups and the Healthy Diet Demetra Index. It was found that adolescents who lived with both parents had a higher frequency of having breakfast and eating more vegetables. The most positive and healthy food preferences were more frequent for adolescents who lived in nuclear families. On the other hand, irregular breakfast consumption and consumption of unhealthy food markers were more frequent among adolescents living in single-parent households, in reconstituted and extended families. Conclusion: Adolescents living with both parents have better eating patterns. The need to consider the household composition when planning healthy eating promotion programs for adolescents is highlighted. (AU)