Absence of ATM leads to altered NK cell function in mice.

Ataxia-telangiectasia (A-T) is a rare disorder caused by genetic defects of A-T mutated (ATM) kinase, a key regulator of stress response, and characterized by neurodegeneration, immunodeficiency, and high incidence of cancer. Here we investigated NK cells in a mouse model of A-T (Atm-/-) showing that they are strongly impaired at killing tumor cells due to a block of early signaling events. On the other hand, in Atm-/- littermates with thymic lymphoma NK cell cytotoxicity is enhanced as compared with ATM-proficient mice, possibly via tumor-produced TNF-α. Results also suggest that expansion of exhausted NKG2D+ NK cells in Atm-/- mice is driven by low-level expression of stress-inducible NKG2D ligands, whereas development of thymoma expressing the high-affinity MULT1 ligand is associated with NKG2D down-regulation on NK cells. These results expand our understanding of immunodeficiency in A-T and encourage exploring NK cell biology in A-T patients in the attempt to identify cancer predictive biomarkers and novel therapeutic targets.

Use of Plant Extracts in Polymeric Scaffolds in the Regeneration of Mandibular Injuries.

Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C, n = 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ, n = 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER, n = 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction.

Therapeutic potential of psychedelics: History, advancements, and unexplored frontiers.

Psychedelics (serotonergic hallucinogens) are psychoactive substances that can alter perception and mood, and affect cognitive functions. These substances activate 5-HT2A receptors and may exert therapeutic effects. Some of the disorders for which psychedelic-assisted therapy have been studied include depression, addiction, anxiety and post-traumatic stress disorder. Despite the increasing number of studies reporting clinical effectiveness, with fewer negative symptoms and, additionally, minimal side effects, questions remain to be explored in the field of psychedelic medicine. Although progress has been achieved, there is still little understanding of the relationship among human brain and the modulation induced by these drugs. The present article aimed to describe, review and highlight the most promising findings in the literature regarding the (putative) therapeutic effects of psychedelics.

Percutaneous closure of patent ductus arteriosus versus surgical treatment in low-birth-weight preterms: a systematic review and meta-analysis.

INTRODUCTION: The optimal management of a patent ductus arteriosus in a population of preterm infants is controversial. Traditionally, when the patent ductus arteriosus does not close either with conservative treatment or in response to pharmacological therapy, the only option is surgical closure. However, transcatheter occlusion might provide a therapeutic alternative. METHODS: We searched PubMed, Embase, and Cochrane databases for non-randomised and randomised controlled trials that compared transcatheter percutaneous closure of patent ductus arteriosus with surgical ligation in low-birth-weight preterm infants (<2,500 g). A random-effects model was used for outcomes with high heterogeneity. RESULTS: We included twelve studies comprising 4,668 low-birth-weight preterm infants, of whom 966 (20.7%) were in the transcatheter percutaneous closure group, and 3,702 (79.3%) patients were included in the surgical group. All-cause mortality (OR 0.28; 95% confidence interval 0.18-0.423; p < 0.00001; I2 = 0%) and haemodynamic instability (OR 0.10; 95% confidence interval 0.05-0.21; p < 0.001; I2 = 14%) were significantly lower in the transcatheter percutaneous closure group. There was no significant difference between transcatheter and surgical patent ductus arteriosus closure for the outcomes of bronchopulmonary dysplasia (0.93; 95% confidence interval 0.46-1.87; p = 0.83; I2 = 0%) and major complications (OR 0.76; 95% confidence interval 0.34-1.69; p = 0.51; I2 = 43%). CONCLUSION: These findings suggest that transcatheter patent ductus arteriosus closure in preterm infants under 2,500 g is a safe and effective alternative to surgical treatment. There was a substantial reduction in all-cause mortality and haemodynamic instability with transcatheter intervention compared to surgical closure.

Effect of radiopacifier and liquid in the physicochemical and biological properties of calcium silicate clinker Angelus: A laboratory investigation.

The aim of this study was to evaluate the effect of radiopacifier calcium tungstate and manipulation with distilled water (DW) or liquid with additives (LA) on calcium silicate clinker Angelus (CL) properties, compared with MTA (Angelus, Brazil) and MTA Repair HP (MTAHP, Angelus, Brazil). The physicochemical properties, cellular viability and bioactivity were evaluated. ANOVA/Tukey and Bonferroni tests were performed (α = 0.05). There was no difference in material setting time (p > 0.05). MTA and MTAHP were similar (p > 0.05) and had greater radiopacity than CL + DW and CL + LA (p < 0.05). All experimental materials showed mass increase, alkalinisation capacity, besides biocompatibility and bioactivity at 3 and 7 days. The different liquids had no influence in the biological properties and bioactivity of the calcium silicate clinker Angelus. Calcium tungstate provided radiopacity, without changing the setting time, maintaining the mass increase and alkalinisation ability of the calcium silicate materials.

Strength and endurance training in cytokine and body composition of people with hiv/aids / Entrenamiento de fuerza y resistencia en citoquinas y composición corporal de personas con vih/sida / Treinamento de força e resistência em citocinas e composição corporal de pessoas com hiv/aids

ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial.

RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado.

RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado.

Electrical stimulation of the auricular branch of the vagus nerve potentiates analgesia induced by physical exercise in mice with peripheral inflammation.

Objective: This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) associated with physical exercise, i.e., swimming, in mice with peripheral inflammation. Methods: The pain model was induced by intraplantar (i.pl.) injection of Freund's complete adjuvant (CFA). Sixty-four male Swiss mice (35-40 g) received an i.pl. of CFA and underwent behavioral tests, i.e., mechanical hyperalgesia, edema, and paw temperature tests. Additionally, cytokine levels, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay. Mice were treated with swimming exercise for 30 min alone or associated with different time protocols (10, 20, or 30 min) of stimulation in the left ear with random frequency during four consecutive days. Results: pVNS for 20 min prolonged the antihyperalgesic effect for up to 2 h, 24 h after CFA injection. pVNS for 30 min prolonged the antihyperalgesic effect for up to 7 h, 96 h after CFA injection. However, it did not alter the edema or temperature at both analyzed times (24 and 96 h). Furthermore, the combination of pVNS plus swimming exercise, but not swimming exercise alone, reduced IL-6 levels in the paw and spinal cord, as well as IL-10 levels in the spinal cord. Conclusion: pVNS potentiates the analgesic effect induced by swimming, which may be, at least in part, mediated by the modulation of inflammatory cytokines in the periphery (paw) and central nervous system (spinal cord). Therefore, the combination of these therapies may serve as an important adjunctive treatment for persistent inflammatory pain.

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice.

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

In Vivo Evaluation of Collagen and Chitosan Scaffold, Associated or Not with Stem Cells, in Bone Repair.

Natural polymers are increasingly being used in tissue engineering due to their ability to mimic the extracellular matrix and to act as a scaffold for cell growth, as well as their possible combination with other osteogenic factors, such as mesenchymal stem cells (MSCs) derived from dental pulp, in an attempt to enhance bone regeneration during the healing of a bone defect. Therefore, the aim of this study was to analyze the repair of mandibular defects filled with a new collagen/chitosan scaffold, seeded or not with MSCs derived from dental pulp. Twenty-eight rats were submitted to surgery for creation of a defect in the right mandibular ramus and divided into the following groups: G1 (control group; mandibular defect with clot); G2 (defect filled with dental pulp mesenchymal stem cells-DPSCs); G3 (defect filled with collagen/chitosan scaffold); and G4 (collagen/chitosan scaffold seeded with DPSCs). The analysis of the scaffold microstructure showed a homogenous material with an adequate percentage of porosity. Macroscopic and radiological examination of the defect area after 6 weeks post-surgery revealed the absence of complete repair, as well as absence of signs of infection, which could indicate rejection of the implants. Histomorphometric analysis of the mandibular defect area showed that bone formation occurred in a centripetal fashion, starting from the borders and progressing towards the center of the defect in all groups. Lower bone formation was observed in G1 when compared to the other groups and G2 exhibited greater osteoregenerative capacity, followed by G4 and G3. In conclusion, the scaffold used showed osteoconductivity, no foreign body reaction, malleability and ease of manipulation, but did not obtain promising results for association with DPSCs.

Electrical Stimulation of the Auricular Branch Vagus Nerve Using Random and Alternating Frequencies Triggers a Rapid Onset and Pronounced Antihyperalgesia via Peripheral Annexin A1-Formyl Peptide Receptor 2/ALX Pathway in a Mouse Model of Persistent Inflammatory Pain.

This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) by comparing the effects of alternating and random frequencies in an animal model of persistent inflammatory hyperalgesia. The model was induced by Freund's complete adjuvant (CFA) intraplantar (i.pl.) injection. Mice were treated with different protocols of time (10, 20, or 30 min), ear laterality (right, left or both), and frequency (alternating or random). Mechanical hyperalgesia was evaluated, and some groups received i.pl. WRW4 (FPR2/ALX antagonist) to determine the involvement. Edema, paw surface temperature, and spontaneous locomotor activity were evaluated. Interleukin-1ß, IL-6, IL-10, and IL4 levels were verified by enzyme-linked immunosorbent assay. AnxA1, FPR2/ALX, neutrophil, M1 and M2 phenotype macrophage, and apoptotic cells markers were identified using western blotting. The antihyperalgesic effect pVNS with alternating and random frequency effect is depending on the type of frequency, time, and ear treated. The pVNS random frequency in the left ear for 10 min had a longer lasting antihyperalgesic effect, superior to classical stimulation using alternating frequency and the FPR2/ALX receptor was involved in this effect. There was a reduction in the levels of pro-inflammatory cytokines and an increase in the immunocontent of AnxA1 and CD86 in mice paw. pVNS with a random frequency in the left ear for 10 min showed to be optimal for inducing an antihyperalgesic effect. Thus, the random frequency was more effective than the alternating frequency. Therefore, pVNS may be an important adjunctive treatment for persistent inflammatory pain.

Predicting surgical operative time in primary total knee arthroplasty utilizing machine learning models.

BACKGROUND: Prolonged surgical operative time is associated with postoperative adverse outcomes following total knee arthroplasty (TKA). Increasing operating room efficiency necessitates the accurate prediction of surgical operative time for each patient. One potential way to increase the accuracy of predictions is to use advanced predictive analytics, such as machine learning. The aim of this study is to use machine learning to develop an accurate predictive model for surgical operative time for patients undergoing primary total knee arthroplasty. METHODS: A retrospective chart review of electronic medical records was conducted to identify patients who underwent primary total knee arthroplasty at a tertiary referral center. Three machine learning algorithms were developed to predict surgical operative time and were assessed by discrimination, calibration and decision curve analysis. Specifically, we used: (1) Artificial Neural Networks (ANNs), (2) Random Forest (RF), and (3) K-Nearest Neighbor (KNN). RESULTS: We analyzed the surgical operative time for 10,021 consecutive patients who underwent primary total knee arthroplasty. The neural network model achieved the best performance across discrimination (AUC = 0.82), calibration and decision curve analysis for predicting surgical operative time. Based on this algorithm, younger age (< 45 years), tranexamic acid non-usage, and a high BMI (> 40 kg/m2) were the strongest predictors associated with surgical operative time. CONCLUSIONS: This study shows excellent performance of machine learning models for predicting surgical operative time in primary total knee arthroplasty. The accurate estimation of surgical duration is important in enhancing OR efficiency and identifying patients at risk for prolonged surgical operative time. LEVEL OF EVIDENCE: Level III, case control retrospective analysis.

Hirschsprung Disease and Intestinal Neuronal Dysplasia Type B: Is There a Difference in the Clinical Presentation of These Two Diseases?

BACKGROUND: Although the signs and symptoms that comprise the clinical presentation of Hirschsprung disease (HD) and intestinal neuronal dysplasia type B (IND-B) are well established, no studies have specifically compared the clinical characteristics presented by patients with these diseases. We compared the clinical pictures of patients with HD and IND-B at the time of histopathological diagnosis. METHODS: This was a single-center, retrospective, analytical, and comparative study. We included 119 patients aged 0-15 years diagnosed with HD or IND-B. Information from the medical records of these patients was retrieved to obtain demographic and clinical information at the time of diagnosis. The data were compared statistically according to the characteristics of the variables. RESULTS: Sixty-nine patients (58.0%) were diagnosed with HD, and 50 (42.0%) had IND-B. The HD group had significantly more individuals with symptom onset in the neonatal period (p = 0.001), delayed meconium clearance (p < 0.001), failure to thrive (p = 0.02), and acute complications, such as enterocolitis (p = 0.049) or acute abdominal obstruction (p = 0.031), more commonly requiring emergency surgery (p < 0.001). Patients with IND-B were diagnosed at a significantly older age (p = 0.002). They more commonly had chronic constipation as their main symptom (p = 0.004), with local complications, such as evacuation bleeding (p = 0.007). CONCLUSION: There were significant differences between the clinical pictures of patients with HD and IND-B. Knowledge of each disease's most common signs and symptoms can help direct diagnostic susception and initial management.

Genome Sequence of CaiB, a DR Cluster Actinobacteriophage That Infects Gordonia rubripertincta.

CaiB is a DR cluster actinobacteriophage that was isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540 as the host. The genome is 61,620 bp, has a GC content of 68.6%, and contains 85 predicted protein coding genes. CaiB has several putative operons and has repeated intergenic regions that may be involved in gene regulation.

Neonatal hypoxia-ischemia induces dysregulated feeding patterns and ethanol consumption that are alleviated by methylphenidate administration in rats.

Impulsivity, as observed in patients diagnosed with Attention-deficit/hyperactivity disorder (ADHD), can induce dysregulated behaviors such as binge eating and drug addiction. We previously demonstrated that neonatal hypoxia-ischemia (HI) resulted in ADHD-like behaviors in rats and that methylphenidate (MPH) administration (the first therapeutic option for ADHD) reversed these deficits. Here, we aimed at investigating addictive-like behaviors, such as the reward-based feeding behavior (using the BioDAQ monitor) and ethanol consumption (using the IA2BC procedure) in adult animals subjected to neonatal HI and treated with or without MPH. Male Wistar rats were divided into four groups (n = 10-12/group): control saline (CTS), CTMPH, HI saline (HIS) and HIMPH. The HI procedure was conducted at postnatal day (PND) 7 and behavioral analyses between PND 60-90, in which MPH (2.5 mg/kg, i.p.) was administered 30 min prior to each behavioral evaluation (6 sessions in BioDAQ and 12 sessions in the IA2BC protocol). HI animals had a dysregulated feeding intake shortly after eating a small piece of the palatable diet, and MPH reversed this dysregulated pattern. However, when the palatable diet was freely available, MPH stimulated a higher intake of this diet in the first exposure day, and this effect was potentialized in HIMPH rats. Increased ethanol intake was observed in HI rats, and MPH administration alleviated this behavior; contrarily, MPH treatment in control rats induced an increase in ethanol consumption. The present findings give additional support to the relationship between neonatal HI and ADHD but the differential response to MPH in control or HI animals highlights the importance of avoiding indiscriminate use of MPH by healthy individuals.

Preventive treatment with fish oil facilitates the antidepressant-like effect of antidepressant drugs in type-1 diabetes mellitus rats: Implication of serotonergic system.

Treating depression associated with type-1 diabetesmellitus(T1DM) is a major clinical challenge. Fish oil (FO), composed mostly of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been pointed out as quite promising for the treatment of depression given its neuroprotective property. Although DHA and EPA exert several physiological actions, DHA is known to play a critical role in postnatal brain development. This study aimed to investigate the effect of preventive treatment with FO (with more DHA in the composition) alone or associated with antidepressant drugs on depression-like behaviors and brain monoamines levels of juvenile induced-T1DM rats. Thus, prepubescent rats were submitted to a prolonged treatment with vehicle (VEH) or FO (50% of DHA and 20% EPA) starting 4 weeks before the induction of experimental T1DM (on day 28) by streptozotocin. When combined, the treatment with vehicle, fluoxetine (FLX, a selective serotonin reuptake inhibitor) or imipramine (IMI, a tricyclic antidepressant) started at week 6 (day 42) and lasted for 2 weeks (until day 56). The behavioral tests were conducted on days 55 and 56, followed by hippocampal and prefrontal cortex dissection for neurochemical analyses. Our results showed that induced-T1DM rats pretreated with FO showed a significant increase of EPA and DHA in plasma, indicative of an increase in the systemic availability of these acids. As previously observed, induced-T1DM rats presented increased immobility and decreased swimming and climbing frequencies in the modified forced swimming test, indicative of depressive-like behavior. Only the combined treatment - FO plus antidepressants (FLX or IMI - both in the highest dose) - was able to induce a significant improvement of depressive-like behaviors. Here, it is noteworthy that swimming behavior has been associated with an increase in serotonergic neurotransmission. Interestingly, our data showed that the combined treatment (FO + antidepressants - including the ineffective dose of FLX) was able to increase the swimming of animals more significantly compared to animals not pretreated with FO. In addition, confirming these assumptions, the decreased 5-HT levels in the hippocampus from induced-T1DM rats were increased after treatment with FLX (highest dose) or IMI (both doses), being this increase more pronounced in animal pretreated with FO. Intriguingly, in these animals pretreated with FO, the ineffective dose of FLX in association with FO was able to increase the levels of 5-HT. The decreased hippocampal levels of noradrenaline were increased only after IMI treatment, not being influenced by FO pretreatment. In conclusion, ours results pointed out that the choice of the DHA/EPA ratio may be an important factor to be considered for the FO antidepressant-like effectper se,but the FO treatment in this composition associated with the antidepressant drugs - especially that ones that increase preferentially the availability of 5-HT -, may represent a better alternative of treatment to individuals with T1DM-associated depression.

Low Psychological Well-being in Men Who Have Sex with Men (MSM) During the Shelter-in-Place Orders to Prevent the COVID-19 Spread: Results from a Nationwide Study.

INTRODUCTION: Little is known about how sheltering in place to contain the spread of COVID-19 over extended periods affects individuals' psychological well-being. This study's objective was to analyze the factors associated with MSM's (men who have sex with men) low psychological well-being in the COVID-19 pandemic context. METHOD: This cross-sectional study was conducted online across Brazil (26 states and federal district) in April and May 2020. The participants were recruited using snowball sampling and Facebook posts. Data were collected using social media and MSM dating apps. We estimated the prevalence, crude prevalence ratio (PR), and the respective confidence intervals (CI95%). RESULTS: The prevalence of low psychological well-being found in the sample was 7.9%. Associated factors were belonging to the youngest group (PR 2.76; CI95% 1.90-4.01), having polyamorous relationships (PR 2.78; CI95% 1.51-5.11), not complying with social isolation measures (PR 6.27; CI95% 4.42-8.87), not using the social media to find partners (PR 1.63; CI95% 1.06-2.53), having multiple sexual partners (PR 1.80; CI95% 1.04-3.11), having reduced the number of partners (PR 2.67; CI95% 1.44-4.95), and group sex (PR 1.82; CI95% 1.23-2.69). CONCLUSION: The well-being of MSM living in Brazil was negatively affected during the social distancing measures intended to control the spread of COVID-19. The variables that contributed the most to this outcome include social isolation, relationships established with partners, and sexual behavior. POLICY IMPLICATIONS: Planning and implementing public policies and actions to promote psychological well-being are needed to improve MSM's resilience by adopting safe strategies and behavior.

Molecular docking study and antireabsorptive activity of a semi-synthetic coumarin derivative from Platymiscium floribundum in the ligature-induced periodontitis in rats: the involvement of heme oxygenase-1.

OBJETIVE: This study aimed to evaluate the anti-resorptive activity of a semi-synthetic coumarin derivative from Platymiscium floribundum, named 6,7-dimethoxy-3-nitrocoumarin. MATERIAL AND METHODS: Molecular docking studies were performed to test the binding performance of the derivative against targets associated with alveolar bone loss (TNF-α, IL-1ß, and catalase) and a target considered an antioxidant defense (HO-1) during periodontitis. Periodontitis was induced by placing a nylon ligature around the second molars. The rats received for 11 days 6,7-dimethoxy-3-nitrocoumarin (0.01, 0.1, or 1 mg/kg) or vehicle. We investigated by RT-qPCR analysis (TNF-α, IL-1ß, and HO-1 mRNA expression levels) and by colorimetric assay (catalase activity) the mechanism of action mediated by 6,7-dimethoxy-3-nitrocoumarin. The in vivo toxicity of 6,7-dimethoxy-3-nitrocoumarin was evaluated. RESULTS: 6,7-Dimethoxy-3-nitrocoumarin (0.1 or 1 mg/kg) reduced alveolar bone loss (1.05 ± 0.24), when compared to vehicle-treated group (3.05 ± 0.30). The interactions of 6,7-dimethoxy-3-nitrocoumarin and the four targets (TNF-α, IL-1ß, catalase, and HO-1) showed firm bonds above 6.0 kcal/mol. 6,7-dimethoxy-3-nitrocoumarin (1 mg/kg) lowered mRNA expression levels of TNF-α (2.33 ± 0.56) and IL-1ß (19.87 ± 2.9), while it increased both the mRNA expression levels of HO-1 (43.40 ± 1.05) and the catalase activity (46.42 ± 4.59), when compared to vehicle-treated group (46.29 ± 8.43; 37.83 ± 4.38; 1.58 ± 0.11; 8.93 ± 1.86, respectively). The animals did not show any signs of toxicity. CONCLUSION: 6,7-Dimethoxy-3-nitrocoumarin decreased inflammatory bone loss in the ligature-induced periodontitis in rats, and the activation of the HO-1 pathway may contribute, at least partially, to its protective effects by reducing TNF-α and IL-1ß mRNA levels and increasing catalase activity. CLINICAL RELEVANCE: 6,7-Dimethoxy-3-nitrocumarin could be used as an adjunct to subgingival instrumentation during active and supportive periodontal treatment.

Exercise may improve balance on parkinson patients / El ejercicio puede mejorar el equilibrio en los pacientes de parkinson

ABSTRACT: Parkinson's disease can harm the functional capacity of a person, which may lead to a worse motor coordination and balance, increasing the risk of falls, and consequently to morbidities or even death. So, complimentary therapies to the drug therapy as exercise programs the aim to increase coordination and balance may avoid the possible falls that may occur and to increase the life quality for people with this illness. Thus, the present study is aimed to verify the efficiency of a four-week exercise program formed by balance and motor coordination on people living with Parkinson using Berg scale to evaluate it. Twelve individuals (64.18 ± 9.54 years; 73.83 ± 14.97 kg; 168.25 ± 8.24 cm) were submitted to two sessions each week consisted of exercises divided in three series of 90 seconds, in a total of eight sessions. The Berg scores increase significatively (p = 0.033) from 43.58 ± 6.53 to 46 ± 5.22. Since scores less than 45 mean a high probability of falls, it is possible to say that the applied program was effective in increase the balance for these individuals, consequently, leading to a better functional capacity and a possible better life quality.

RESUMEN: La enfermedad de Parkinson deteriora la capacidad funcional del paciente al afectar su coordinación motora y el equilibrio, lo que puede provocar caídas y, en consecuencia, morbilidades asociadas o incluso la muerte. De esta manera, las terapias auxiliares de la terapia farmacológica, como los programas de ejercicio físico que buscan mejorar la coordinación y el equilibrio, pueden ayudar a evitar el riesgo de caídas y, por lo tanto, mejorar la calidad de vida de las personas afectadas por esta enfermedad. Por tanto, el presente estudio tiene como objetivo verificar la efectividad de un programa de ejercicios de cuatro semanas que incluye ejercicios de equilibrio y coordinación motora para mejorar el equilibrio de las personas con Parkinson, utilizando la escala de Berg. Doce personas (64,18 ± 9,54 años; 73,83 ± 14,97 kg; 168,25 ± 8,24 cm) se sometieron a dos sesiones semanales de ejercicios divididos en tres series de 90 segundos para cada ejercicio, para un total de ocho sesiones. La puntuación de los individuos en la escala de Berg aumentó significativamente (p = 0,033) de 43,58 ± 6,53 a 46 ± 5,22. Sabiendo que los puntajes inferiores a 45 significan una probabilidad considerable de caídas, es posible afirmar que el programa de ejercicio aplicado fue efectivo para mejorar el equilibrio de los individuos y, en consecuencia, puede conducir a una mejora en la capacidad funcional del individuo y una posible mejora en la calidad de vida.

Trunk muscle function and anterior and posterior limits of stability in community-dwelling older adults.

BACKGROUND: Understanding of the influence of trunk muscles on the older adult's limit of stability (LOS) is important for clinical practice. OBJECTIVE: To compare the anterior and posterior LOS and the flexor and extensor trunk muscle function; verify the association of trunk muscles and LOS, and the association of LOS and the previous falls of community-dwelling older adults. METHODS: Sample characterization data, trunk muscle function (peak torque - PT and torque steadiness - TS), LOS and previous falls (6 months) were collected from 79 older people. Comparisons were made between the variables of the anterior/posterior LOS (Reaction time, Movement velocity, Maximum excursion, Directional control), between trunk extensors/flexors muscle function and between TS at 10% and at 50%. Associations were made between the anterior/posterior LOS and the number of previous falls and between LOS and trunk muscle function. RESULTS: The posterior LOS was worse than the anterior LOS, except for the reaction time. The flexor muscles obtained a lower PT, but better performance in TS. The TS at 10% of the trunk extensor was associated with the posterior directional control (p = 0.032). There was no association between trunk muscle function and the anterior LOS, or between previous falls and LOS. CONCLUSIONS: The older adults presented worse performance in the posterior LOS and worse TS in the trunk extensor muscles, although the trunk extensor muscles presented a higher PT. Although no association between LOS and previous falls, the better the TS at 10% of the trunk extensors, better posterior directional control.

Bifidobacterium Strains Present Distinct Effects on the Control of Alveolar Bone Loss in a Periodontitis Experimental Model.

Periodontitis is an inflammatory disease induced by a dysbiotic oral microbiome. Probiotics of the genus Bifidobacterium may restore the symbiotic microbiome and modulate the immune response, leading to periodontitis control. We evaluated the effect of two strains of Bifidobacterium able to inhibit Porphyromonas gingivalis interaction with host cells and biofilm formation, but with distinct immunomodulatory properties, in a mice periodontitis model. Experimental periodontitis (P+) was induced in C57Bl/6 mice by a microbial consortium of human oral organisms. B. bifidum 1622A [B+ (1622)] and B. breve 1101A [B+ (1101)] were orally inoculated for 45 days. Alveolar bone loss and inflammatory response in gingival tissues were determined. The microbial consortium induced alveolar bone loss in positive control (P + B-), as demonstrated by microtomography analysis, although P. gingivalis was undetected in oral biofilms at the end of the experimental period. TNF-α and IL-10 serum levels, and Treg and Th17 populations in gingiva of SHAM and P + B- groups did not differ. B. bifidum 1622A, but not B. breve 1101A, controlled bone destruction in P+ mice. B. breve 1101A upregulated transcription of Il-1ß, Tnf-α, Tlr2, Tlr4, and Nlrp3 in P-B+(1101), which was attenuated by the microbial consortium [P + B+(1101)]. All treatments downregulated transcription of Il-17, although treatment with B. breve 1101A did not yield such low levels of transcripts as seen for the other groups. B. breve 1101A increased Th17 population in gingival tissues [P-B+ (1101) and P + B+ (1101)] compared to SHAM and P + B-. Administration of both bifidobacteria resulted in serum IL-10 decreased levels. Our data indicated that the beneficial effect of Bifidobacterium is not a common trait of this genus, since B. breve 1101A induced an inflammatory profile in gingival tissues and did not prevent alveolar bone loss. However, the properties of B. bifidum 1622A suggest its potential to control periodontitis.