Sleep duration and quality during the COVID-19 pandemic and the association with physical activity and screen time among Brazilian college students.

BACKGROUND: As a result of social isolation during the COVID-19 pandemic, changes in sleep patterns have been observed in many countries, as well as changes in physical activity and screen time. The objective was to investigate sleep duration and quality during the COVID-19 pandemic and its association with physical activity and screen time. METHODS: Cross-sectional study with students from a University in Rio de Janeiro who answered an online questionnaire between August 2020 and March 2021. Physical activity was assessed using IPAQ-SF. Sleep was investigated based on questions about duration and sleep quality change, and screen time through self-reported questions. Multinomial logistic regression was performed to assess the association between physical activity and screen time with sleep duration and quality. Secondary analyses investigated the influence of the isolation time on this association. The confounding factors used were diagnosis of COVID-19, time of isolation, anxiety, depression, skin color, and gender. RESULTS: A total of 771 college students with a mean age of 24.5 years (±8.6) answered the questionnaire. About 75% reported more than 8 h of screen time per day and 49.8% were physically inactive. Regarding sleep, 54.9% had worsening sleep, while 40.6% had inadequate sleep duration during the pandemic. Physical activity was associated with improved sleep quality (Odds ratio (OR) 1.72; confidence interval (95% CI) 1.05-2.97). Also, physically active students who spent more than 14 weeks in social isolation demonstrated improved sleep quality (OR 1.99; 95% CI 1.02-3.78) compared to physically inactive individuals. No association was observed for sleep duration. No association was observed between screen time and sleep quality, or sleep duration. CONCLUSION: During the COVID-19 pandemic, there was considerable worsening of sleep quality, and physical activity was positively associated with improved sleep quality.

A multicomponent family intervention, combined with salt reduction for children with obesity: a factorial randomized study protocol.

BACKGROUND: Clinical trials to treat childhood obesity show modest results, weight regain and high dropout rates. Children with obesity often live in families with habits that contribute to unhealthy weight gain. This study will test whether a family intervention with a Brazilian-adapted Planetary Healthy Diet (PHD) and reduced portion sizes, along with increased physical activity and reduced sedentary behavior, can reduce excessive weight gain. The protocol promotes the intake of in natura products and water and reduces ultra-processed foods, sugar, and sodium. It encourages family lifestyle changes and physical activities, with randomized allocation to experimental and control groups. The responsible family member will be evaluated during follow-up. The control group will receive a print of the Brazilian dietary guideline. METHODS: A factorial crossover design will also allocate families to receive reduced sodium salt plus anti-inflammatory herbs and a placebo salt. Both the control and intervention groups will be randomly assigned to the sequence of both salts. The approach aims to reduce body weight expectations and evaluate salt's impact on blood pressure. It includes a 1-month intervention, 1-month washout, and 1-month intervention with monthly clinic visits and teleservice by health professionals. The primary outcomes will be the variation in the Body Mass Index (BMI) of the children. BMI and the variation in the blood pressure of the pair (child/mother or father) as well as waist circumference (WC) and waist-to-height ratio (WHtR) will also be measured. DISCUSSION: The project will test the effectiveness of the use of the recommendations of the PHD, physical activity and a salt-reduced sodium. The results of the present study will allow the refinement of interventions aimed at the treatment of childhood obesity and may help develop guidelines for the treatment of obesity in Brazilian children. TRIAL REGISTRATION: The study is registered in the Brazilian Registry of Clinical Trials (RBR-10 mm62vs). Registered 10 February 2023.

Mudança na quantidade e qualidade do sono durante o período da pandemia de Covid-19 e a associação com atividade física e comportamento sedentário / Change in the quantity and quality of sleep during the period of the Covid-19 pandemic and association with physical activity and sedentary behavior

O ano de 2020 foi marcado pela pandemia de Covid-19, com países de todo mundo adotando alguma forma de isolamento social, inclusive o Brasil. O maior tempo em casa decorrente das restrições impostas pela pandemia tem sido associado a mudanças no padrão de atividade física e comportamentos sedentários, bem como no padrão de sono. O presente estudo investigou possíveis mudanças na qualidade e duração do sono, durante a pandemia de Covid-19, e a associação com atividade física e comportamento sedentário. Trata-se de um estudo transversal, a partir de uma amostra de 771 estudantes adultos universitários, que ingressaram no ano de 2019 na Universidade do Estado do Rio de Janeiro (UERJ). A coleta de dados foi realizada via web, entre agosto de 2020 e março de 2021, a partir de um questionário enviado por e-mail para todos os alunos. Matricularam-se, no ano de 2019, 4115 alunos. Desses 3973 possuíam e-mail ativo, 1 recusou assinar o termo de consentimento e 771 responderam ao questionário. Para minimizar os efeitos da alta taxa de não resposta (80,6%) realizou-se uma ponderação segundo sexo e curso. Nas análises, foram utilizadas prevalências expandidas, intervalo de confiança de 95% e estimadores de associação por regressão logística que utilizou o procedimento survey do software SAS. Regressão logística multinominal comparou piora à categoria melhora do sono/não alteração. A prevalência ponderada de inatividade física, definida como o não alcance de 150 minutos semanais de atividade física, foi de 51,7% nas mulheres e 41,4% nos homens. Já para o tempo sedentário, apenas 24,8% da amostra demonstrou passar menos de 8 horas por dia nesses comportamentos. Mais de 50% da população declararam piora na qualidade do sono, bem como sintomas de ansiedade e depressão. Somente 16,2% dos estudantes referiram melhora do sono. Houve um aumento de prevalência de estudantes com duração excessiva de sono (10,5%), que não se associou ao padrão de atividade física. Quanto à qualidade do sono, comparados aos estudantes inativos, os ativos não apresentar proteção significativa para piora do sono (OR: 0,9; 95% IC: 0,65 ­ 1,35), nem quando estratificado por ansiedade, depressão ou tempo de isolamento. Os sedentários também não apresentaram associação significativas com a qualidade do sono. Conclui-se que a pandemia afetou negativamente a saúde de jovens universitários, piorando o sono e apresentando mais tempo sedentário. A piora do sono não foi atenuada pela pratica de atividade física.

The year 2020 was marked by the Covid-19 pandemic, with countries around the world adopting some form of social isolation, including Brazil. More time at home resulting from the restrictions imposed by the pandemic has been associated with changes in the pattern of physical activity and sedentary behaviors, as well as in the sleep pattern. The present study investigated possible changes in sleep quality and duration during the Covid-19 pandemic and the association with physical activity and sedentary behavior. This is a cross-sectional study, based on a sample of 771 adult university students, who joined the University of the State of Rio de Janeiro (UERJ) in 2019. Data collection was carried out via the web, between August 2020 and March 2021, using a questionnaire sent by email to all students. In 2019, 4115 students enrolled. Of these 3973 had active e-mail, 1 refused to sign the consent form and 771 responded to the questionnaire. To minimize the effects of the high non-response rate (80.6%) a weighting was performed according to sex and course. In the analyses, expanded prevalences, a 95% confidence interval and association estimators were used by logistic regression using the SAS software survey procedure. Multinomial logistic regression compared worsening to the improved sleep/no change category. The weighted prevalence of physical inactivity, defined as not achieving 150 minutes of physical activity per week, was 51.7% in women and 41.4% in men. As for the sedentary time, only 24.8% of the sample showed to spend less than 8 hours a day in these behaviors. More than 50% of the population reported worsening sleep quality, as well as symptoms of anxiety and depression. Only 16.2% of students reported improved sleep. There was an increase in the prevalence of students with excessive sleep duration (10.5%), which was not associated with the pattern of physical activity. As for sleep quality, compared to inactive students, active students did not present significant protection for sleep worsening (OR: 0.9; 95% CI: 0.65 ­ 1.35), not even when stratified by anxiety, depression or time of isolation. Sedentary individuals also showed no significant association with sleep quality. It is concluded that the pandemic negatively affected the health of university students, worsening sleep and presenting more sedentary time. The worsening of sleep was not attenuated by the practice of physical activity.

Putative link between Polo-like kinases (PLKs) and Toll-like receptor (TLR) signaling in transformed and primary human immune cells.

Toll-like receptors (TLRs) are important sentinels of bacterial and viral infection and thus fulfil a critical sensory role in innate immunity. Polo-like kinases (PLKs), a five membered family of Ser/Thr protein kinases, have long been studied for their role in mitosis and thus represent attractive therapeutic targets in cancer therapy. Recently, PLKs were implicated in TLR signaling in mice but the role of PLKs in TLR signaling in untransformed primary immune cells has not been addressed, even though PLK inhibitors are in clinical trials. We here identified several phospho-serine and phospho-threonine residues in the known TLR pathway kinases, Interleukin-1 receptor-associated kinase (IRAK) 2 and IRAK4. These sites lie in canonical polo-box motifs (PBM), sequence motifs known to direct recruitment of PLKs to client proteins. Interestingly, PLK1 was phosphorylated and PLK 2 and 3 mRNA induced upon TLR stimulation in primary immune cells, respectively. In whole blood, PLK inhibition disparately affected TLR mediated cytokine responses in a donor- and inhibitor-dependent fashion. Collectively, PLKs may thus potentially interface with TLR signaling in humans. We propose that temporary PLK inhibitor-mediated blockade of TLR-signaling in certain patients receiving such inhibitors during cancer treatment may cause adverse effects such as an increased risk of infections due to a then compromised ability of the TLR recognition system to sense and initiate cytokine responses to invading microbes.

Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase.

BACKGROUND: The Nod-like receptor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive. OBJECTIVE: We sought to identify novel regulators of the NLRP3 inflammasome in human cells with a view to exploring interference with inflammasome activity at the level of such regulators. METHODS: After proteome-wide phosphoproteomics, the identified novel regulator BTK was studied in human and murine cells by using pharmacologic and genetic BTK ablation. RESULTS: Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration-approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1ß processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB). BTK affected apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and caspase-1 cleavage and interacted with NLRP3 and ASC. S aureus infection control in vivo and IL-1ß release from cells of patients with Muckle-Wells syndrome were impaired by ibrutinib. Notably, IL-1ß processing and release from immune cells isolated from patients with cancer receiving ibrutinib therapy were reduced. CONCLUSION: Our data suggest that XLA might result in part from genetic inflammasome deficiency and that NLRP3 inflammasome-linked inflammation could potentially be targeted pharmacologically through BTK.

CD11b expression on polymorphonuclear leukocytes from patients with ankylosing spondylitis in a lipopolysaccharide-stimulated whole blood ex vivo model.

AIM: Ankylosing spondylitis (AS) is a chronic inflammatory disease that compromises the axial skeleton, causing pain and disability. The involved mechanisms are not completely understood, but evidence suggests a role of the gut microbiota in eliciting innate immune responses. We conducted an experimental study to determine if AS patients exhibit an enhanced inflammatory response to microbial compounds. METHOD: We incubated whole peripheral blood of AS patients and healthy controls with phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) for 48 h with saturating levels of labeled antibodies (CD66b, CD11b and human leukocyte antigen type DR [HLA-DR]) for flow cytometry. CD11b and HLA-DR expression levels were assessed in polymorphonuclear leukocytes (PMN) (CD66b high - HLA-DR low). We also measured basal CD11b and HLA-DR levels on circulating PMN (without incubation). RESULTS: We found that CD11b and HLA-DR levels were similarly elevated in response to LPS on PMNs from healthy controls (HC) and AS patients. Basal levels of CD11b and HLA-DR on circulating PMN from AS patients and HC were similar. However, significantly lower levels of CD11b and HLA-DR were observed in PMNs from AS patients than HC in response to incubation with PBS for 48 h. CONCLUSION: We concluded that the response of AS innate immune cells to LPS is similar to that observed in immune cells from HCs, and suggested that the lower PMN activation of AS patients after 48 h saline incubation is mainly due to anti-inflammatory medication.

Isoniazid-induced control of Mycobacterium tuberculosis by primary human cells requires interleukin-1 receptor and tumor necrosis factor.

Proinflammatory cytokines are critical mediators that control Mycobacterium tuberculosis (Mtb) growth during active tuberculosis (ATB). To further inhibit bacterial proliferation in diseased individuals, drug inhibitors of cell wall synthesis such as isoniazid (INH) are employed. However, whether INH presents an indirect effect on bacterial growth by regulating host cytokines during ATB is not well known. To examine this hypothesis, we used an in vitro human granuloma system generated with primary leukocytes from healthy donors adapted to model ATB. Intense Mtb proliferation in cell cultures was associated with monocyte/macrophage activation and secretion of IL-1ß and TNF. Treatment with INH significantly reduced Mtb survival, but altered neither T-cell-mediated Mtb killing, nor production of IL-1ß and TNF. However, blockade of both IL-1R1 and TNF signaling rescued INH-induced killing, suggesting synergistic roles of these cytokines in mediating control of Mtb proliferation. Additionally, mycobacterial killing by INH was highly dependent upon drug activation by the pathogen catalase-peroxidase KatG and involved a host PI3K-dependent pathway. Finally, experiments using coinfected (KatG-mutated and H37Rv strains) cells suggested that active INH does not directly enhance host-mediated killing of Mtb. Our results thus indicate that Mtb-stimulated host IL-1 and TNF have potential roles in TB chemotherapy.

Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus.

MicroRNAs are important posttranscriptional regulators of gene expression, which have been shown to fine-tune innate immune responses downstream of pattern recognition receptor (PRR) signaling. This study identifies miR-650 as a novel PRR-responsive microRNA that is downregulated upon stimulation of primary human monocyte-derived dendritic cells (MDDCs) with a variety of different microbe-associated molecular patterns. A comprehensive target search combining in silico analysis, transcriptional profiling, and reporter assays reveals that miR-650 regulates several well-known interferon-stimulated genes, including IFIT2 and MXA. In particular, downregulation of miR-650 in influenza A infected MDDCs enhances the expression of MxA and may therefore contribute to the establishment of an antiviral state. Together these findings reveal a novel link between miR-650 and the innate immune response in human MDDCs.

Activation of lymphoma-associated MyD88 mutations via allostery-induced TIR-domain oligomerization.

Myeloid differentiation 88 (MyD88) is the key signaling adapter of Toll-like and interleukin-1 receptors. Recurrent lymphoma-associated mutations, particularly Leu265Pro (L265P), within the MyD88 Toll/interleukin-1 receptor (TIR) domain sustain lymphoma cell survival due to constitutive nuclear factor κB signaling. We found that mutated TIR domains displayed an intrinsic propensity for augmented oligomerization and spontaneous formation of cytosolic Myddosome aggregates in lymphoma cell lines, mimicking the effect of dimerized TIR domains. Blocking of MyD88 oligomerization induced apoptosis. The L265P TIR domain can recruit the endogenous wild-type MyD88 for oligomer formation and hyperactivity. Molecular dynamics simulations and analysis of additional mutations suggest that constitutive activity is caused by allosteric oligomerization.