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Identifying therapeutics to delay, and potentially reverse, age-related cognitive decline is critical in light of the increased incidence of dementia-related disorders forecasted in the growing older population1. Here we show that platelet factors transfer the benefits of young blood to the ageing brain. Systemic exposure of aged male mice to a fraction of blood plasma from young mice containing platelets decreased neuroinflammation in the hippocampus at the transcriptional and cellular level and ameliorated hippocampal-dependent cognitive impairments. Circulating levels of the platelet-derived chemokine platelet factor 4 (PF4) (also known as CXCL4) were elevated in blood plasma preparations of young mice and humans relative to older individuals. Systemic administration of exogenous PF4 attenuated age-related hippocampal neuroinflammation, elicited synaptic-plasticity-related molecular changes and improved cognition in aged mice. We implicate decreased levels of circulating pro-ageing immune factors and restoration of the ageing peripheral immune system in the beneficial effects of systemic PF4 on the aged brain. Mechanistically, we identified CXCR3 as a chemokine receptor that, in part, mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain. Together, our data identify platelet-derived factors as potential therapeutic targets to abate inflammation and rescue cognition in old age.
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Envelhecimento , Cognição , Disfunção Cognitiva , Doenças Neuroinflamatórias , Nootrópicos , Fator Plaquetário 4 , Animais , Masculino , Camundongos , Envelhecimento/sangue , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Doenças Neuroinflamatórias/sangue , Doenças Neuroinflamatórias/complicações , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/prevenção & controle , Fator Plaquetário 4/sangue , Fator Plaquetário 4/metabolismo , Fator Plaquetário 4/farmacologia , Fator Plaquetário 4/uso terapêutico , Nootrópicos/sangue , Nootrópicos/metabolismo , Nootrópicos/farmacologia , Nootrópicos/uso terapêutico , Plasma/química , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Transcrição Gênica/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacosRESUMO
The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.
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Aedes/microbiologia , Aedes/fisiologia , Controle de Mosquitos/métodos , Mosquitos Vetores/microbiologia , Mosquitos Vetores/fisiologia , Wolbachia/patogenicidade , Aedes/crescimento & desenvolvimento , Animais , China , Copulação , Estudos de Viabilidade , Feminino , Humanos , Mordeduras e Picadas de Insetos/prevenção & controle , Larva/crescimento & desenvolvimento , Larva/microbiologia , Larva/fisiologia , Masculino , Mosquitos Vetores/crescimento & desenvolvimento , Controle de Qualidade , ReproduçãoRESUMO
AIM: To determine personal and organisational factors associated with work performance and illness outcomes during presenteeism in a cohort of nurses. BACKGROUND: Presenteeism is prevalent in nursing populations. It is known to be associated with impaired health and performance loss. Knowledge about the factors associated with presenteeism may help foster better health and performance in this group. METHODS: A survey (N = 270) was conducted in a population of nurses working with older adults. Hierarchical multiple regression was used to explore factors associated with performance loss and illness outcomes during presenteeism. RESULTS: Work performance and illness outcomes were often reported as poor during presenteeism. Less negative illness perceptions and work engagement were associated with better work performance and illness outcomes. Older age and manager support were also associated with better work performance. Non-organisational causes of illness were associated with better illness outcomes. CONCLUSION: Performance levels and illness outcomes during presenteeism are associated with a combination of illness-related, individual, attitudinal and organisational factors. IMPLICATIONS FOR NURSING MANAGEMENT: Fostering engagement, support, good relationships and a hazard-free environment may improve performance and health during presenteeism.
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Enfermeiras e Enfermeiros , Desempenho Profissional , Idoso , Estudos Transversais , Humanos , Presenteísmo , Inquéritos e QuestionáriosRESUMO
Despite the worldwide popularity of running as a sport for children, relatively little is known about its impact on injury and illness. Available studies have focused on adolescent athletes, but these findings may not be applicable to preadolescent and pubescent athletes. To date, there are no evidence or consensus-based guidelines identifying risk factors for injury and illness in youth runners, and current recommendations regarding suitable running distances for youth runners at different ages are opinion based. The International Committee Consensus Work Group convened to evaluate the current science, identify knowledge gaps, categorise risk factors for injury/illness and provide recommendations regarding training, nutrition and participation for youth runners.
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Corrida/lesões , Corrida/fisiologia , Adolescente , Fatores Etários , Índice de Massa Corporal , Tamanho Corporal , Osso e Ossos/fisiologia , Criança , Morte Súbita Cardíaca/etiologia , Pé/fisiologia , Humanos , Força Muscular , Necessidades Nutricionais , Condicionamento Físico Humano/efeitos adversos , Condicionamento Físico Humano/métodos , Fatores de Risco , Fatores Sexuais , Sapatos , Estresse MecânicoRESUMO
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain management. However, animal studies have demonstrated negative effects of NSAIDs on bone and tendon healing after commonly performed procedures such as rotator cuff repair. The purpose of this study was to evaluate the effects of postoperative NSAID use on opioid use, pain control, and shoulder outcomes after arthroscopic rotator cuff repair. METHODS: A randomized, double-blind, placebo-controlled trial of postoperative NSAID use was performed in patients undergoing primary arthroscopic rotator cuff surgery at a single institution. Patients were randomized to receive ibuprofen or placebo for 2 weeks postoperatively, in addition to opioid medication. They were instructed to keep a daily pain diary for the first week after surgery, which was returned at their first postoperative visit for analysis. Visual analog scale (VAS) pain scores, shoulder range of motion, and 12-item Short Form Survey, Disabilities of the Arm, Shoulder and Hand, and American Shoulder and Elbow Surgeons (ASES) scores were collected. Assessment of rotator cuff healing was performed using ultrasound at 1 year postoperatively. RESULTS: A total of 50 patients in the placebo group and 51 patients in the ibuprofen group were included for analysis. There were no differences in age, race, sex, history of preoperative NSAID or opioid use, or operative findings between groups. The amount of mean total morphine milligram equivalents (MMEs) used in the first postoperative week was lower in the ibuprofen group than in the placebo group (168 MMEs vs. 211 MMEs, P = .04). Early VAS scores on postoperative days 3, 4, 5, and 6 were lower in the ibuprofen group, but there was no difference in mean VAS scores between groups by 6 weeks after surgery. At 6 months, mean forward flexion and the mean ASES score were higher in the ibuprofen group than in the placebo group: 162° vs. 153° (P = .03) and 86 vs. 78 (P = .02), respectively. There were no differences in shoulder motion or 12-item Short Form Survey, Disabilities of the Arm, Shoulder and Hand, or ASES scores at 1 year. At 1 year after surgery, 7 patients in the ibuprofen group had evidence of tendon retear diagnosed on ultrasound (5 partial and 2 full thickness) compared with 13 patients in the placebo group (5 partial and 8 full thickness), but this difference was not statistically significant (P = .20). CONCLUSION: Postoperative ibuprofen use reduces opioid requirements and decreases patient pain levels in the first week after arthroscopic rotator cuff repair. In addition, ibuprofen use after rotator cuff repair does not lead to an increased risk of tendon retear.
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Lesões do Manguito Rotador , Manguito Rotador , Anti-Inflamatórios , Anti-Inflamatórios não Esteroides/efeitos adversos , Artroscopia , Humanos , Amplitude de Movimento Articular , Lesões do Manguito Rotador/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Musculoskeletal ultrasound imaging is increasingly being used for static and dynamic imaging of tendons, muscles, ligaments, and bones. New, hand-held, pocket-sized ultrasounds are more portable and affordable. The purpose of this study was to evaluate the feasibility of pocket-sized ultrasound to diagnose shoulder pathology. DESIGN: Prospective cohort study. SETTING: Tertiary Care Hospital. METHODS: Ten consecutive patients (mean age 54; range 42-68 years) referred for a shoulder ultrasound for evaluation of shoulder pain were recruited. A diagnostic ultrasound was performed first with a pocket-sized ultrasound machine (VScan; General Electric, Northville, MI) and cine images saved for later review. Next, standard diagnostic ultrasound by a radiology technician specialized in musculoskeletal ultrasound was performed using (LOGIQ; General Electric, Northville, MI) ultrasound. The radiology report from the standard diagnostic ultrasound was used as the gold standard for diagnoses. Two independent evaluators, a musculoskeletal-trained radiologist and a sports-medicine-trained physician with over 8 years of experience with musculoskeletal ultrasound, reviewed the images from the pocket-sized ultrasound. RESULTS: Nine of the studies were diagnosed with a pathologic entity during the standard diagnostic ultrasound and 1 was found to be normal. Diagnoses ranged from biceps tendinopathy, calcific tendonitis, and partial-articular-sided rotator cuff tear. Evaluator 1 correctly identified 7/10 diagnoses and evaluator 2 correctly identified 8/10 diagnoses. The evaluators also rated their confidence in diagnosis as 4.2/5 and the image quality as 3.7/4 from the pocket-sized ultrasound. DISCUSSION: The findings from this study demonstrate that pocket-sized, hand-held ultrasound machines may be used to identify shoulder pathology.
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Testes Imediatos , Lesões do Ombro/diagnóstico por imagem , Ombro/diagnóstico por imagem , Ultrassonografia/instrumentação , Adulto , Idoso , Artralgia/etiologia , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Ligamentos Articulares/diagnóstico por imagem , Ligamentos Articulares/lesões , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/lesões , Osteoartrite/diagnóstico por imagem , Estudos Prospectivos , Tendinopatia/diagnóstico por imagemRESUMO
The study objective was to examine the effects of three days of sleep restriction on maximal jump performance and joint coordination. Eleven elite cyclists obtained a one-week baseline of habitual sleep then restricted sleep to 4 h/night (SR) for three nights assessed through self-report and actigraphy. Pre and post-intervention measures were a box drop maximal vertical jump with 3D motion capture to assess physical performance and biomechanical changes, and Psychomotor Vigilance Task (PVT) assessed changes in response time. Associations between biomechanical, physical, and cognitive performance measures were assessed. Participants restricted reported sleep from 7.4 ± 0.5 h/night at baseline to 4.0 ± 0.2 h/night and actigraphy indicated 6.7 ± 0.7 to 3.7 ± 0.2 h/night. Following SR, jump height decreased (0.44 ± 0.09 vs. 0.42 ± 0.10 m, p = 0.02, g = 0.21). Hip sagittal/knee frontal (Δ15.5°, p = 0.04, g = 0.40) and hip frontal/knee frontal (Δ11.0°, p < 0.01, g = 0.44) plane coordination variability increased after SR. Hip sagittal/knee frontal plane coordination variability after SR was associated with increasingly slower PVT response time (r = 0.63, p = 0.03). These findings suggest SR for three days decreased maximal jump performance. SR increased joint coordination variability and was associated with greater impairment in response time. SR leads to deviations from preferred movement patterns, which may have implications for decrements in athlete performance and increased injury risk.
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Desempenho Atlético/fisiologia , Desempenho Psicomotor , Tempo de Reação , Sono , Actigrafia , Adulto , Atletas , Estudos Cross-Over , Humanos , MasculinoRESUMO
Running is a popular sport for children in the United States. However, review of available literature on health effects and safety recommendations for youth running has not been previously conducted. Unique factors for injury include periods of growth during puberty and potential for growth plate injury. Youth runners may benefit from activities that incorporate high-impact loading and multidirectional movement for optimal bone maturation, exercises to strengthen tendons and muscles, and strategies aimed at improving running biomechanics to reduce risk of injury. In addition, addressing lifestyle factors, including nutrition and sleep is essential for a runner's general health. Similar to other sports, sports specialization should not be encouraged in youth runners. Reducing running-related injury in growing children and assessing readiness for running should be based on a combination of physical, emotional, psychological, social, and cognitive factors. Youth runners require individualized training and competition to safely participate in the sport.
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Traumatismos em Atletas/prevenção & controle , Condicionamento Físico Humano/métodos , Corrida/lesões , Corrida/fisiologia , Adolescente , Fenômenos Biomecânicos , Osso e Ossos , Sistema Cardiovascular , Criança , Cognição , Emoções , Feminino , Humanos , Masculino , Força Muscular , Sistema Respiratório , Fatores de Risco , Fatores Sexuais , EsportesRESUMO
Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted.
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Artérias/fisiologia , Frequência Cardíaca/fisiologia , Resistência à Insulina/fisiologia , Caracteres Sexuais , Rigidez Vascular/fisiologia , Adulto , Glicemia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Jejum/sangue , Feminino , Hemoglobinas Glicadas/análise , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Pré-Menopausa/fisiologia , Fatores de RiscoRESUMO
Bacteria associated with the parthenogenetic troglobiont sand fly Deanemyia maruaga were characterized by sequencing cloned 16S rDNA PCR products. Eleven novel partial 16S rDNA sequences, with varying degrees of similarity to Actinobacteria, were identified. None of the sequences identified had homology to those known from parthenogenesis-inducing bacteria.
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The COVID-19 pandemic resulted in a sudden switch to remote working that many organisations and workers were unprepared for. The study investigates the perceived impact of remote working on workers' health and influencing factors. The topic has received limited attention within published studies. A cross-sectional online survey was distributed to IT and communication remote workers in Malta (N=459). Closed-ended questions were analysed quantitatively in order to identify perceived changes in health. Open-ended questions were analysed qualitatively to determine the perceived reasons for such changes. More workers reported that their health had deteriorated than improved during the first 12 months of the pandemic. Greater proportions of remote work were associated with improved levels of health. Several factors were perceived to have influenced levels of health, including: health behaviours, such as physical activity, nutrition, and sleep; the development of disease, particularly mental health issues; work related factors, such as social support, work demands, and the blurring of work-life boundaries; and personal factors, including family life and leisure. The study concludes that remote working can be beneficial for health when workers engage in the correct health-promoting behaviours and are provided with the necessary support, both during their working and private life.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Malta , Nível de Saúde , ComunicaçãoRESUMO
Purpose: To use T1ρ and T2 magnetic resonance imaging to evaluate the effect of leukocyte-poor platelet-rich plasma (LP-PRP) injections on knee cartilage health and to correlate structural changes with patient-reported outcome measurements. Methods: Ten patients with symptomatic unilateral mild-to-moderate knee osteoarthritis (Kellgren-Lawrence Grade 1-2) underwent T1ρ and T2 magnetic resonance imaging of both the symptomatic and contralateral knee before injection and 6 months after injection with LP-PRP. Patient-reported outcome questionnaires (Knee Osteoarthritis Outcome Score and International Knee Documentation Committee) that evaluate the domains of pain, symptoms, activities of daily living, sports function, and quality of life were completed at baseline, 3 months, 6 months, and 12 months after injection. T1ρ and T2 relaxation times, which are correlated with the proteoglycan and collagen concentration of cartilage, were measured in compartments with and without chondral lesions. Results: Ten patients were prospectively enrolled (9 female, 1 male) with a mean age of 52.9 years (range, 42-68) years and mean body mass index of 23.2 ± 1.9. Significant increases in Knee Osteoarthritis Outcome Score for all subscales and International Knee Documentation Committee scores were observed 3 months after injection and the improvements were sustained at 12 months. T1ρ and T2 values of compartments with chondral lesions were observed to significantly decrease by 6.0% (P = .036) and 7.1% (P = .017) 6 months after LP-PRP injection, respectively. No significant associations between T1ρ and T2 relaxation times and improvement in patient-reported outcomes were observed. Conclusions: Patients undergoing LP-PRP injections for the treatment of mild-to-moderate knee osteoarthritis had increased proteoglycan and collagen deposition in the cartilage of affected compartments by 6 months after injection. Patient-reported outcomes scores improved 3 months after injection and were sustained through 1 year after injection, but these improvements were not associated with the changes in proteoglycan and collagen deposition in knee cartilage. Level of Evidence: Level II, prospective cohort study.
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BACKGROUND: Nutrition and physical activity are associated with prostate cancer recurrence and mortality. Few randomized controlled trials (RCT) have examined the effects of long-term exercise and diet changes on prostate cancer clinical, biological, and patient-reported outcomes. METHODS: Prostate 8-II is a 4-arm RCT among 200 men with prostate cancer who chose radical prostatectomy (RP) as their primary treatment. Men are enrolled prior to RP and randomized to exercise-only, diet-only, exercise + diet, or usual care (50/arm). Participants begin their assigned intervention 0-5 weeks prior to RP and continue for 24-months following surgery. The 3 active intervention arms receive access to a web-portal and text messages, coaching calls, and other intervention resources (e.g., heart rate sensor and resistance bands and/or recipe booklet). Weekly exercise goals for the exercise intervention groups are 150 min moderate or 75 min vigorous aerobic exercise, 2 strength sessions, and 2 flexibility sessions. Diet intervention groups work with a dietitian to customize their goals (e.g., increase cruciferous vegetables, cooked tomatoes, healthy fats, fish; limit processed meats, whole milk). The primary endpoint is biochemical recurrence. Secondary endpoints include change in tumor biomarkers from biopsy to RP as well as patient-reported outcomes (e.g., quality-of-life), blood and urine biomarkers, and anthropometry at 0, 6, 12, and 24 months. CONCLUSION: This 4-arm RCT will examine the impact of change in exercise and diet (alone or in combination) on prostate cancer recurrence, biology, and quality-of-life.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Recidiva Local de Neoplasia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Dieta , Exercício Físico , Prostatectomia/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Active surveillance (AS) is standard care for most men with low-risk prostate cancer (PC); yet, many men on AS eventually undergo curative therapy. Interventions to lower the risk of cancer progression and fear of recurrence among men on AS for PC are needed. OBJECTIVE: To determine the effect of aerobic exercise on cardiorespiratory fitness, body size, and quality of life (QOL) among men on AS for PC. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 1:1 randomized controlled trial among 51 men with low-risk PC who elected AS. Participants were enrolled at the University of California, San Francisco. INTERVENTION: The 16-wk intervention included a home-based walking program with a nonlinear exercise prescription tailored to baseline fitness level, heart rate monitor, and weekly phone call with an exercise physiologist. Controls received printed materials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cardiorespiratory fitness was measured using VO2peak; secondary outcomes included change in body size, anxiety, and QOL. Analyses were based on intention to treat. RESULTS AND LIMITATIONS: Between 2016 and 2021, we randomized 51 men to intervention (n = 26) or control (n = 25). Follow-up was 88% (45/51), 85% (22/26) in the intervention and 92% (23/25) in the control group. At 16 wk, the intervention group had a higher mean VO2peak than the control group (31.9 ± 4.7 vs 27.2 ± 4.8 ml/kg/min; group × time effect p value: <0.001). Additionally, the intervention group reported less fear of PC recurrence and urinary obstruction/irritation, while controls reported more of these two QOL measures, from 0 to 16 wk (p = 0.04 and 0.03, respectively). Two participants discontinued the intervention, including one due to knee pain related to the study. CONCLUSIONS: A home-based walking program improved VO2peak and reduced urinary obstruction/irritation and fear of recurrence among men on AS for PC. PATIENT SUMMARY: Moderate to vigorous aerobic exercise improves fitness and quality of life among men on active surveillance for prostate cancer.
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BACKGROUND: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood. METHODS: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks. RESULTS: A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76%) with a median age of 71 years (range: 51-84) and 10.5 years (range: 0.9-26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea. CONCLUSIONS: The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted.
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Neoplasias de Próstata Resistentes à Castração , Treinamento Resistido , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Projetos Piloto , FadigaRESUMO
Neutrophils rely predominantly on glycolytic metabolism for their biological functions, including reactive oxygen species (ROS) production. Although pyruvate kinase M2 (PKM2) is a glycolytic enzyme known to be involved in metabolic reprogramming and gene transcription in many immune cell types, its role in neutrophils remains poorly understood. Here, we report that PKM2 regulates ROS production and microbial killing by neutrophils. Zymosan-activated neutrophils showed increased cytoplasmic expression of PKM2. Pharmacological inhibition or genetic deficiency of PKM2 in neutrophils reduced ROS production and Staphylococcus aureus killing in vitro. In addition, this also resulted in phosphoenolpyruvate (PEP) accumulation and decreased dihydroxyacetone phosphate (DHAP) production, which is required for de novo synthesis of diacylglycerol (DAG) from glycolysis. In vivo, PKM2 deficiency in myeloid cells impaired the control of infection with Staphylococcus aureus. Our results fill the gap in the current knowledge of the importance of lower glycolysis for ROS production in neutrophils, highlighting the role of PKM2 in regulating the DHAP and DAG synthesis to promote ROS production in neutrophils.
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Neutrófilos , Piruvato Quinase , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neutrófilos/metabolismo , Fosforilação , GlicóliseRESUMO
In 2011, the Nobel Prize in Physiology or Medicine was awarded to three immunologists: Bruce A. Beutler, Jules A. Hoffmann, and Ralph M. Steinman. While Steinman was honored for his work on dendritic cells and adaptive immunity, Beutler and Hoffman received the prize for their contributions to discoveries in innate immunity. In 1996, Hoffmann found the toll gene to be crucial for mounting antimicrobial responses in fruit flies, first implicating this developmental gene in immune signaling. Two years later, Beutler built on this observation by describing a Toll-like gene, tlr4, as the receptor for the bacterial product LPS, representing a crucial step in innate immune activation and protection from bacterial infections in mammals. These publications spearheaded research in innate immune sensing and sparked a huge interest regarding innate defense mechanisms in the following years and decades. Today, Beutler and Hoffmann's research has not only resulted in the discovery of the role of multiple TLRs in innate immunity but also in a much broader understanding of the molecular components of the innate immune system. In this review, we aim to collect the discoveries leading up to the publications of Beutler and Hoffmann, taking a close look at how early advances in both developmental biology and immunology converged into the research awarded with the Nobel Prize. We will also discuss how these discoveries influenced future research and highlight the importance they hold today.
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Lipopolissacarídeos , Receptor 4 Toll-Like , Animais , Imunidade Inata , Mamíferos , Prêmio Nobel , Transdução de SinaisRESUMO
To contribute to knowledge of the epidemiology of American cutaneous leishmaniasis (ACL) among indigenous people living in sylvatic regions, we studied the sand fly fauna collected in areas of disease transmission in the Brazilian Amazon. Here we report two datasets comprising occurrence data for sand flies from the Suruwaha Indigenous Land in the state of Amazonas collected in 2012-2013, and the Wajãpi Indigenous Land in the state of Amapá collected in 2013-2014. Sand flies were collected using unbaited CDC-like light traps at various sites within each study area and were identified to either genus or species-level by taxonomists with expertise in Amazonian fauna. A total of 4,646 records are reported: 1,428 from the Suruwaha and 3,218 from the Wajãpi. These records will contribute to a better understanding of ACL transmission dynamics, as well as the distribution of insect vectors, in these areas.
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PURPOSE: To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. MATERIAL AND METHODS: Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. RESULTS: No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. CONCLUSION: T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise.