Effects of high-definition transcranial direct current stimulation combined with inspiratory muscle training for treating respiratory sequelae of long COVID: A case series.

INTRODUCTION: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High-definition transcranial direct current stimulation (HD-tDCS) has been tested in patients with COVID-19; however, previous studies did not investigate the HD-tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID. CASE PRESENTATION: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD-tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention. IMPLICATIONS ON PHYSIOTHERAPY PRACTICE: HD-tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID.

Effects of a cardiopulmonary rehabilitation protocol on functional capacity, dyspnea, fatigue, and body composition in individuals with post-COVID-19 syndrome: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Reduced functional capacity, dyspnea, fatigue, and changes in body composition are common in patients with post-COVID-19 syndrome (PCS), and cardiopulmonary rehabilitation may improve these parameters. Thus, the present study verified the effects of cardiopulmonary rehabilitation (respiratory, aerobic, and resistance muscle training) on submaximal exercise tolerance, dyspnea, fatigue, and body composition. METHODS: This controlled and randomized clinical trial applied a six-week outpatient intervention protocol in individuals over 18 years old (n = 33) with a diagnosis of COVID-19 confirmed by polymerase chain reaction. These individuals were allocated to cardiopulmonary rehabilitation (n = 17) or control groups (i.e., educational lectures; n = 16). The cardiopulmonary rehabilitation group performed respiratory, aerobic, and resistance muscle training. Submaximal exercise tolerance, dyspnea, fatigue, and body composition were assessed before and after the protocol. RESULTS: After 6 weeks, the cardiopulmonary rehabilitation group increased the tolerance to submaximal exercise, with a difference of 100.46 m (95% confidence interval [CI]: 7.40-193 m) in the distance walked on the six-minute walk test, reduced dyspnea (-1.45, 95% CI: -1.98--0.92) in the modified Medical Research Council, and increased 0.63 kg (95% CI: 0.09-1.18 kg) of muscle mass in the upper limbs compared with the control group. CONCLUSION: The six-week cardiopulmonary rehabilitation protocol improved functional capacity, reduced dyspnea, and increased muscle mass in the upper limbs in individuals with PCS. Thus, these results supported the protocol use in this population and encourage further studies to assess its effectiveness in a large sample.

Bioactive compounds of honey from different regions of Brazil: the effect of simulated gastrointestinal digestion on antioxidant and antimicrobial properties.

Monofloral and multifloral honey produced in different regions may have different bioactive compounds and antioxidant capacities, resulting in changes in the antimicrobial activity of honey. However, many of these compounds degrade due to the extreme digestion conditions, which may inhibit the antimicrobial activity. Given this context, this study aimed to describe the bioactive compounds of honey produced in Brazil and verify if honey samples from different botanical and geographical origins differ in bioactive compounds, and if honey maintains its antimicrobial activity after digestion simulation. Multivariate analysis was used to identify characteristics that differentiated the honey samples according to the botanical and geographical origin criteria. The amount of the bioactive compounds varied significantly: the total phenolic compound content varied from 20.49 to 101.44 mg GAE per 100 g, flavonoids varied from 1.41 to 13.52 mg QE per 100 g, phenolic acids varied from 13.61 to 56.41 mg CAE per 100 g, and carotenoids varied from 0.66 to 4.27 mg ß-carotene per g. Multifloral honey (H22) produced in the dry season of northeastern Brazil presented the highest bioactive compound concentration except for the carotenoid content. HPLC-MS analysis showed the presence of six hydroxybenzoic acids, four hydroxycinnamic acids, eight flavonols, three flavanones, two flavones and two isoflavonoids; Pterodon pubescens monofloral honey (H14) from midwestern Brazil stood out in terms of the carotenoid content. All analyzed honey samples exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli bacteria before digestive process simulation, and bacteria were inhibited during in vitro digestion; this activity decreased during the simulation of the oral phase, remained in the gastric phase, and disappeared in the intestinal phase.

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence.

Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women's blood.

Respiratory Muscle Strength and Quality of Life in Patients With Heart Failure and Their Main Correlated Factors: A Cross-sectional Study.

BACKGROUND: Heart failure may cause peripheral and respiratory muscle alterations, dyspnea, fatigue, and exercise intolerance, worsening the quality of life of patients. OBJECTIVES: The aims of this study were to analyze respiratory muscle strength and quality of life of patients with heart failure and correlate them with clinical variables and functional classification. METHODS: This cross-sectional study involved patients with heart failure. A manovacuometer assessed maximum inspiratory and expiratory pressures, and quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire. Functional classification was categorized according to the New York Heart Association (NYHA) class in I, II, III, or IV. RESULTS: We included 60 patients (66.7% male) with a mean age of 62.0 years and mean left ventricular ejection fraction of 42.0%. Maximum inspiratory pressure and maximum expiratory pressure were close to normal (>70% of predicted) in most patients; however, a subgroup composed mostly of patients with dilated heart failure and NYHA class III (n = 21) presented low maximum inspiratory pressure values (59.2%; 95% confidence interval, 55.7%-62.8%). The mean total score of the Minnesota Living with Heart Failure Questionnaire was 44.4 points, being negatively correlated with left ventricular ejection fraction (r = -0.29, P = .02). Patients with NYHA class III and disease duration longer than 120 months presented higher total (P < .01) and physical dimension scores. CONCLUSIONS: Most patients had respiratory muscle strength close to normal; however, those with dilated heart failure and NYHA class III presented low maximum inspiratory pressure values. Quality of life was moderately compromised, mainly because of long disease duration, NYHA class III, and low left ventricular ejection fraction.

Effects of Doxycycline Treatment on Hematological Parameters, Viscosity, and Cytokines in Canine Monocytic Ehrlichiosis.

This study aimed to analyze the hematological parameters, blood viscosity, and cytokines of dogs infected by Ehrlichia canis untreated and treated with doxycycline. Initially, 47 dogs were examined, and 36 were suspected to have canine monocytic ehrlichiosis, which was confirmed through molecular polymerase chain reaction tests. This study consisted of 25 dogs, with 11 being healthy and 14 testing positive for E. canis. The dogs were divided into experimental groups based on their test results, including a control group of healthy dogs (N = 11), a group of infected dogs without treatment (N = 7), and a group of infected dogs treated with doxycycline (N = 7) at a 10 mg/kg dose every 12 h for 28 days. Blood samples were taken to determine hematological parameters, viscosity, and cytokine levels. It was observed that, regardless of doxycycline treatment, there was a reduction in total leukocytes and lymphocytes in infected dogs with Ehrlichia canis. The eosinophils and platelets decreased in dogs with Ehrlichia canis infections without treatment. Monocytes, eosinophils, and platelets increased when the dogs were treated with doxycycline. Regardless of treatment, infected dogs' blood viscosity was lower than uninfected dogs. Infected dogs showed lower TNF-α and increased IL-1ß. There was a correlation between the blood viscosity with the cytokines IL-10 and IL-12 in the infected dogs. The eosinophil count correlated with TNF-α in the group of infected and untreated dogs. In conclusion, treating dogs with monocytic ehrlichiosis using doxycycline can increase platelet and eosinophil levels but may also increase IL-1ß and monocyte levels, exacerbating inflammation. Therefore, evaluating viscosity and cytokine levels is important when treating dogs with this condition.

Polarization of Melatonin-Modulated Colostrum Macrophages in the Presence of Breast Tumor Cell Lines.

Human colostrum and milk contain diverse cells and soluble components that have the potential to act against tumors. In breast cancer, macrophages play a significant role in immune infiltration and contribute to the progression and spread of tumors. However, studies suggest that these cells can be reprogrammed to act as an antitumor immune response. This study aimed to evaluate the levels of melatonin and its receptors, MT1 (melatonin receptor 1) and MT2 (melatonin receptor 2), in colostrum and assess the differentiation and polarization of the colostrum macrophages modulated by melatonin in the presence of breast tumor cells. Colostrum samples were collected from 116 mothers and tested for their melatonin and receptor levels. The colostrum cells were treated with or without melatonin and then cultured for 24 h in the presence or absence of breast tumor cells. The results showed that melatonin treatment increased the expression of MT1 and MT2 in the colostrum cells. Furthermore, melatonin treatment increased the percentage of M1 macrophages and decreased the percentage of M2 macrophages. When the colostrum macrophages were cocultured with breast tumor cells, melatonin reduced the percentage of both macrophage phenotypes and the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8). These data suggest that melatonin can regulate the inflammatory process via M1 macrophages in the tumor microenvironment and, simultaneously, the progression of M2 macrophages that favor tumorigenesis.

An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation.

The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds.

New ruthenium(II) complexes with cyclic thio- and semicarbazone: evaluation of cytotoxicity and effects on cell migration and apoptosis of lung cancer cells.

We describe the synthesis, physicochemical characterization, and in vitro antitumor assays of four novel analogous ruthenium(II) complexes with general formula cis-[RuII(N-L)(P-P)2]PF6, where P-P = bis(diphenylphosphine)methane (dppm, in complexes 1 and 2) or bis(diphenylphosphine)ethane (dppe, in complexes 3 and 4) and N-L = 5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (Btsc, in complexes 1 and 3) or 5,6-diphenyltriazine-3-one (Bsc, in complexes 2 and 4). The data were consistent with cis arrangement of the biphosphine ligands. For the Btsc and Bsc ligands, the data pointed to monoanionic bidentate coordination to ruthenium(II) through N,S and N,O, respectively. Single-crystal X-ray diffraction showed that complex 1 crystallized in the monoclinic system, space group P21/c. Determination of the cytotoxicity profiles of complexes 1-4 gave SI values ranging from 1.19 to 3.50 against the human lung adenocarcinoma cell line A549 and the non-tumor lung cell line MRC-5. Although the molecular docking studies suggested that the interaction between DNA and complex 4 was energetically favorable, the experimental results showed that they interacted weakly. Overall, our results demonstrated that these novel ruthenium(II) complexes have interesting in vitro antitumor potential and this study may contribute to further studies in medicinal inorganic chemistry.

Melatonin and Cytokines Modulate Daily Instrumental Activities of Elderly People with SARS-CoV-2 Infection.

The Comprehensive Geriatric Assessment analyzes the health and quality of life of the elderly. Basic and instrumental daily activities may be compromised due to neuroimmunoendocrine changes, and studies suggest that possible immunological changes occur during infections in the elderly. Thus, this study aimed to analyze cytokine and melatonin levels in serum and correlate the Comprehensive Geriatric Assessment in elderly patients with SARS-CoV-2 infection. The sample consisted of 73 elderly individuals, 43 of whom were without infection and 30 of whom had positive diagnoses of COVID-19. Blood samples were collected to quantify cytokines by flow cytometry and melatonin by ELISA. In addition, structured and validated questionnaires were applied to assess basic (Katz) and instrumental (Lawton and Brody) activities. There was an increase in IL-6, IL-17, and melatonin in the group of elderly individuals with infection. In addition, a positive correlation was observed between melatonin and IL-6 and IL-17 in elderly patients with SARS-CoV-2 infection. Furthermore, there was a reduction in the score of the Lawton and Brody Scale in the infected elderly. These data suggest that the melatonin hormone and inflammatory cytokines are altered in the serum of the elderly with SARS-CoV-2 infection. In addition, there is a degree of dependence, mainly regarding the performance of daily instrumental activities, in the elderly. The considerable impact on the elderly person's ability to perform everyday tasks necessary for independent living is an extremely important result, and changes in cytokines and melatonin probably are associated with alterations in these daily activities of the elderly.

Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus.

Gestational diabetes mellitus is an important public health problem and has been associated with the development of pregnancy-specific urinary incontinence. The interaction is related to hyperglycemia, and inflammatory and hormonal patterns, which favor functional alterations in different organs and systems. Several genes associated with human diseases have been identified and partially characterized. Most of these genes are known to cause monogenic diseases. However, about 3 % of diseases do not fit the monogenic theory due to the complex interactions between multiple genes and environmental factors, as in chronic metabolic diseases such as diabetes. The nutritional, immunological, and hormonal patterns associated with changes in maternal metabolism may influence and contribute to greater susceptibility to urinary tract disorders. However, early systematic reviews have not yielded consistent findings for these associations. This literature review summarizes important new findings from integrating nutrigenomics, hormones, and cytokines in women with Gestational diabetes mellitus and pregnancy-specific urinary incontinence. Changes in maternal metabolism due to hyperglycemia can generate an inflammatory environment with increased inflammatory cytokines. This environment modulated by inflammation can alter tryptophan uptake through food and thus influence the production of serotonin and melatonin. As these hormones seem to have protective effects against smooth muscle dysfunction and to restore the impaired contractility of the detrusor muscle, it is assumed that these changes may favor the onset of urinary incontinence specific to pregnancy.

Leptin, Adiponectin, and Melatonin Modulate Colostrum Lymphocytes in Mothers with Obesity.

Pregnancy complicated by obesity is associated with adverse triggered gestational and neonatal outcomes, with reductions in the subtypes of CD4+ T-lymphocytes representing the modulators of inflammation. It needs to be better established how maternal nutritional statuses impact the neuroendocrine-immune system's action and affect the immunological mechanisms of the maternal-infant relationship via breastfeeding. This study examined the effects of maternal obesity on human colostrum lymphocytes and the intracellular mechanisms of lymphocyte modulation in the presence of leptin, adiponectin, and melatonin via cell proliferation; the release of intracellular calcium; and apoptosis induction. This cross-sectional study analyzed colostrum samples from 52 puerperal splits and divided them into overweight and eutrophic groups. Colostrum lymphocytes underwent immunophenotyping and cell proliferation by flow cytometry and intracellular calcium release and apoptosis assays by immunofluorescence in the presence or absence of hormones. Significant differences were considered when p < 0.05 by the chi-square or t-test. Maternal obesity reduced the population of T-lymphocytes and TCD4+ in human colostrum and proliferative activities (p < 0.05). These hormones restore lymphocyte proliferation to a level similar to the eutrophic group (p < 0.05). Leptin, adiponectin, melatonin hormones, and biological actions consolidated in the scientific literature also represent maternal and infant protection mechanisms via colostrum and the modulation of human colostrum lymphocytes.

Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC).

BACKGROUND: and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue. METHODS: Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact Scale (MFIS). Pain level, anxiety severity and quality of life were secondary outcomes assessed, respectively, through the McGill Questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and WHOQOL. RESULTS: Active HD-tDCS resulted in significantly greater reduction in fatigue compared to sham HD-tDCS (mean group MFIS reduction of 22.11 points vs 10.34 points). Distinct effects of HD-tDCS were observed in fatigue domains with greater effect on cognitive (mean group difference 8.29 points; effect size 1.1; 95% CI 3.56-13.01; P < .0001) and psychosocial domains (mean group difference 2.37 points; effect size 1.2; 95% CI 1.34-3.40; P < .0001), with no significant difference between the groups in the physical subscale (mean group difference 0.71 points; effect size 0.1; 95% CI 4.47-5.90; P = .09). Compared to sham, the active HD-tDCS group also had a significant reduction in anxiety (mean group difference 4.88; effect size 0.9; 95% CI 1.93-7.84; P < .0001) and improvement in quality of life (mean group difference 14.80; effect size 0.7; 95% CI 7.87-21.73; P < .0001). There was no significant difference in pain (mean group difference -0.74; no effect size; 95% CI 3.66-5.14; P = .09). CONCLUSION: An intervention with M1 targeted HD-tDCS paired with a rehabilitation program was effective in reducing fatigue and anxiety, while improving quality of life in people with PASC.

Analysis of respiratory muscle strength and its relationship with functional capacity between different field tests in patients with heart failure.

OBJECTIVE: To analyze respiratory muscle strength of patients with heart failure (HF) and correlate with functional capacity. METHODS: This cross-sectional study involved patients with compensated HF of both sexes, aged above 18 years. Respiratory muscle strength was assessed by measuring maximum inspiratory (MIP) and expiratory pressures (MEP) using a manovacuometer. Patients were randomized into two groups to assess functional capacity: six-minute walk test (6MWT) and incremental shuttle walk test (ISWT). RESULTS: Forty-eight patients were evaluated (23 from 6MWT and 25 from ISWT group). Most were male (67.8%), with mean age of 62.3 years and left ventricular ejection fraction of 40.8%. Mean predicted values of MIP [81.2% (74.7-87.8%)] and MEP [95.6% (88.2-103.0%)] did not indicate respiratory muscle weakness. The higher the New York Heart Association (NYHA) functional class, the lower the MIP (p = .011) and MEP (p = .016) values. Physically active patients presented higher respiratory muscle strength than those sedentary (MIP: 104.5 vs. 71.9 cmH2O, p < .001; MEP: 120.0 vs. 91.1 cmH2O, p = .004). Functional capacity was impaired [6MWT: 416.0 m (372.8-459.3 m); ISWT: 304 m (263.4-344.9 m)], and distance covered in the ISWT was shorter than 6MWT group (p < .001). Distance covered in the ISWT group presented a moderate positive correlation with MIP (r = 0.45; p = .022) and MEP (r = 0.41; p = .041). CONCLUSION: Most patients with HF presented respiratory muscle strength close to predicted values; however, sedentary patients and those with high NYHA functional class, showed reduced MIP and MEP. Functional capacity was reduced, and MIP and MEP correlated with distance covered in the ISWT.

Resistin Modulates the Functional Activity of Colostral Macrophages from Mothers with Obesity and Diabetes.

BACKGROUND: Obesity and diabetes are major public health problems. Resistin is an adipokine that links the two diseases. There are few reports regarding colostrum cells and resistin from mothers with obesity and diabetes. Thus, this study aimed to determine the functional activity of macrophages present in the breast milk and colostrum of diabetic mothers with obesity and the effects of resistin on these cells. METHODS: The women were divided according to BMI and glycemic status into normal weight non-diabetic, obese non-diabetic, normal weight type 2 diabetic, or obese type 2 diabetic groups. ELISA determined the resistin in colostrum. The cell subsets and apoptosis were determined by flow cytometry and the functional activity of cells by fluorescence microscopy. RESULTS: The resistin levels were higher in the colostrum from diabetic mothers with obesity. The frequencies of CD14+ cells and cells expressing CD95+, independent of resistin treatment, were higher in the colostrum from diabetic mothers with obesity. The frequency of cells expressing CD14+CD95+ was higher in cells not treated with resistin in the colostrum from diabetic mothers with obesity. Apoptosis, irrespective of the presence of resistin, increased, whereas microbicidal activity decreased in cells from diabetic mothers with obesity. CONCLUSION: The data suggest that hyperglycemia associated with low-grade inflammation caused by obesity affects the percentage of cells expressing CD14+CD95+, death by apoptosis, and microbicidal indices; meanwhile, resistin restored the microbicidal activity of colostrum cells.

Zinc(II) complexes bearing N,N,S ligands: Synthesis, crystal structure, spectroscopic analysis, molecular docking and biological investigations about its antifungal activity.

In the present work, the synthesis, characterization, antifungal activity, molecular docking study and in silico approach of five thiosemicarbazone derivatives and their corresponding zinc(II) complexes are described. The compounds were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic measurements, molar conductivity measurements, emission spectra, high-resolution mass spectrometry and X ray study. The antifungal activity of the free ligands and synthesized compounds was preliminarily evaluated against Candida albicans (ATCC 90028), Candida tropicalis (ATCC 13803) and Candida glabrata (ATCC 2001), by the minimum inhibitory concentration (MIC) assay. Two complexes, 4 (MIC = 3.18 to 6.37 µM) and 5 (MIC = 25.95 µM for all) showed promising results, being highly active against all strains evaluated. The X-ray analyses shown that the complex 2 crystallizes in the centrosymmetric space group P21/c of the monoclinic system and the coordination sphere around zinc(II) atom is better described as slightly distorted octahedral. The Hirshfeld surface (HS) analysis showed that non-classical H···H and C···H/H···C contacts contribute with 65.9% while the S···H and N···H (21%) and Cl···H and O···H interactions (12%) complete the HS area. The molecular docking results, performed against CYP51 enzyme (sterol 14α-demethylase) of C. albicans and C. glabrata shows that the complexes 4 (ΔG = -10.75 and - 12.90 kcal/ mol) and 5 (ΔG = -11.12 and - 14.53 kcal/ mol) showed the highest binding free energies of all compounds. The ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) in silico parameters evaluated showed promising results for all compounds.

Effects of Modified Melatonin Release on Human Colostrum Neutrophils to Induce Death in the MCF-7 Cell Line.

Cancer is one of the diseases with the highest mortality rate today, with breast cancer being the second most common type among the Brazilian population. Due to its etiological complexity and inefficiency of treatments, studies have focused on new forms of treatment. Among these forms of treatment, hormonal therapy seems to be an excellent auxiliary mechanism in tumoricidal activity, and melatonin has great potential as a modulator of the immune system. Thus, the present study is aimed at evaluating the effect of the hormone melatonin on the coculture of colostrum polymorphonuclear cells and MCF-7 cancer cells and evaluates the effect of this hormone using a modified transport system. A feasibility analysis was performed by fluorescence microscopy at three cell incubation times, 2 hours, 24 hours, and 72 hours. The measurement of cytokines in the cell supernatant occurred in 24 hours, and the apoptosis assay was performed in 72 hours using flow cytometry. The results showed higher levels of cell viability in groups treated with melatonin and less viability in groups containing a coculture of polymorphonuclear cells and MCF-7 after 72 hours of incubation. Furthermore, the apoptosis and necrosis rates were higher in coculture polymorphonuclear and MCF-7 cells, especially in groups containing microemulsion as a modified release agent. These data suggest that melatonin, especially if associated with a modified release system, has immunomodulatory effects on human colostrum polymorphonuclear cells. These cells can play a crucial role in the resolution of the tumor through their mediation and inflammatory action.

Efficacy of a rehabilitation protocol on pulmonary and respiratory muscle function and ultrasound evaluation of diaphragm and quadriceps femoris in patients with post-COVID-19 syndrome: a series of cases.

This study assessed the efficacy of a pulmonary rehabilitation (PR) on pulmonary and respiratory muscle function and thickness of quadriceps femoris and diaphragm of patients with post-COVID-19 syndrome. This series of cases followed nine patients who performed PR twice a week for six weeks. Patients received the following PR program: lung expansion therapy; respiratory muscle training; upper limb strength exercises; aerobic exercises on a treadmill. After the program, we observed increased peak expiratory flow (26.03%), forced vital capacity (FVC) (7.14%), forced expiratory volume in the first second (FEV1) (9.55%), and ratio between FEV1/FVC (6.19%). All parameters of respiratory muscle strength and endurance were improved. Diaphragmatic thickening fraction and thickness of quadriceps femoris also improved, whereas echo intensity of quadriceps reduced. Thus, RP protocol improved pulmonary function, respiratory muscle strength and endurance, and thickness of diaphragm and quadriceps femoris, and reduced echo intensity of quadriceps in patients with post-COVID-19 syndrome.

Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial.

BACKGROUND AND PURPOSE: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19. METHODS: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated. RESULTS: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups. CONCLUSIONS: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia.