RESUMO
The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle-tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.
Assuntos
Junção Miotendínea , Tendões , Masculino , Humanos , Tendões/fisiologia , Núcleo Celular/metabolismo , Músculo Esquelético/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Forminas/metabolismoRESUMO
Prematurity has physical consequences, such as lower birth weight, decreased muscle mass and increased risk of adult-onset metabolic disease. Insulin-like growth factor 1 (IGF-1) has therapeutic potential to improve the growth and quality of muscle and tendon in premature births, and thus attenuate some of these sequalae. We investigated the effect of IGF-1 on extensor carpi radialis muscle and biceps brachii tendon of preterm piglets. The preterm group consisted of 19-day-old preterm (10 days early) piglets, treated with either IGF-1 or vehicle. Term controls consisted of groups of 9-day-old piglets (D9) and 19-day-old piglets (D19). Muscle samples were analysed by immunofluorescence to determine the cross-sectional area (CSA) of muscle fibres, fibre type composition, satellite cell content and central nuclei-containing fibres in the muscle. Tendon samples were analysed for CSA, collagen content and maturation, and vascularization. Gene expression of the tendon was measured by RT-qPCR. Across all endpoints, we found no significant effect of IGF-1 treatment on preterm piglets. Preterm piglets had smaller muscle fibre CSA compared to D9 and D19 control group. Satellite cell content was similar across all groups. For tendon, we found an effect of age on tendon CSA, and mRNA levels of COL1A1, tenomodulin and scleraxis. Immunoreactivity for elastin and CD31, and several markers of tendon maturation, were increased in D9 compared to the preterm piglets. Collagen content was similar across groups. IGF-1 treatment of preterm-born piglets does not influence the growth and maturation of skeletal muscle and tendon.
Assuntos
Animais Recém-Nascidos , Fator de Crescimento Insulin-Like I , Músculo Esquelético , Tendões , Animais , Fator de Crescimento Insulin-Like I/metabolismo , Suínos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Tendões/efeitos dos fármacos , Tendões/metabolismo , Nascimento Prematuro , Feminino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Peptídeos Semelhantes à InsulinaRESUMO
BACKGROUND: Prolonging effects of adjuncts to local anaesthetics in peripheral nerve blocks have been demonstrated in randomised clinical trials. The chosen primary outcome and anticipated effect size have major impact on the clinical relevance of results in these trials. This scoping review aims to provide an overview of frequently used outcomes and anticipated effect sizes in randomised trials on peripheral nerve block adjuncts. METHODS: For our scoping review, we searched MEDLINE, Embase and CENTRAL for trials assessing effects of adjuncts for peripheral nerve blocks published in 10 major anaesthesia journals. We included randomised clinical trials assessing adjuncts for single-shot ultrasound-guided peripheral nerve blocks, regardless of the type of interventional adjunct and control group, local anaesthetic used and anatomical localization. Our primary outcome was the choice of primary outcomes and corresponding anticipated effect size used for sample size estimation. Secondary outcomes were assessor of primary outcomes, the reporting of sample size calculations and statistically significant and non-significant results related to the anticipated effect sizes. RESULTS: Of 11,854 screened trials, we included 59. The most frequent primary outcome was duration of analgesia (35/59 trials, 59%) with absolute and relative median (interquartile range) anticipated effect sizes for adjunct versus placebo/no adjunct: 240 min (180-318) and 30% (25-40) and for adjunct versus active comparator: 210 min (180-308) and 17% (15-28). Adequate sample size calculations were reported in 78% of trials. Statistically significant results were reported for primary outcomes in 45/59 trials (76%), of which 22% did not reach the anticipated effect size. CONCLUSION: The reported outcomes and associated anticipated effect sizes can be used in future trials on adjuncts for peripheral nerve blocks to increase methodological homogeneity.
RESUMO
BACKGROUND: Managing postoperative pain while minimizing opioid-related adverse drug events (ORADEs) remains a significant challenge. The OPIâ¢AID Zone Tool is proposed as a novel clinical decision support tool that - both graphically and in a scoring-system - represents the relationship between pain management and the occurrence of ORADEs, aiming to enhance patient outcomes in postoperative care. The OPIâ¢AID Zone Tool places pain score on the x-axis and an ORADE score on the y-axis, and stratifies patients into five zones to reflect the composite impact of pain severity and ORADEs on the quality of postoperative patient care. The study will have two key aims: (1) to explore whether the OPIâ¢AID Zone Tool can function as a composite outcome measure for postoperative pain and ORADEs, and (2) to evaluate the use of the OPIâ¢AID Zone Tool in visual presentations and for evaluation of patients' postoperative pain management quality. METHODS: This prospective observational cohort study will include 200 adults undergoing various surgical procedures in general anesthesia with a subsequent stay in the post-anesthesia care unit (PACU) at Bispebjerg Hospital, Denmark. Substudy 1 primary outcome: To assess whether a zone score in the OPIâ¢AID Zone Tool is associated with patient-perceived health (EQ VAS), quality of recovery (QoR-PACU), and time to discharge readiness in PACU, and if the zone score has a stronger association than pain and ORADE score in themselves. Substudy 2 primary outcome: To assess how the use of intraoperative non-opioid analgesics impact where patients are placed in the OPIâ¢AID Zone Tool's XY scatterplot right after surgery. To assess if patients who receive more comprehensive non-opioid analgesic basic regimens, generally fall into lower zones. CONCLUSION: The OPIâ¢AID Zone Tool could potentially be a valuable clinical decision-making tool for optimizing postoperative care by simultaneously addressing pain management and the risk of ORADEs. By computing a composite measure of these two critical outcomes, the tool could guide more nuanced and patient-centered analgesic regimens, potentially improving patient satisfaction and operational efficiency in postoperative settings. The tool's applicability will be explored in this observational pilot and followed up in a planned series of studies (opiaid.dk).
Assuntos
Analgésicos Opioides , Manejo da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Manejo da Dor/métodos , Medição da Dor/métodos , Estudos de Coortes , AdultoRESUMO
BACKGROUND: Morphine-sparing effects are often used to evaluate non-opioid analgesic interventions. The exact effect that would warrant the implementation of these interventions in clinical practice (a minimally important difference) remains unclear. We aimed to determine this with anchor-based methods. METHODS: This was a post hoc analysis of three studies investigating pain management after hip or knee arthroplasty (PANSAID [NCT02571361], DEX-2-TKA [NCT03506789] and Pain Map [NCT02340052]). The overall population was median aged 70, median ASA 2, 54% female. We examined the correlation between 0 and 24 h postoperative iv morphine equivalent consumption and the severity of nausea, vomiting, sedation and dizziness. The anchor was different severity degrees of these opioid-related adverse events. The primary outcome was the difference in morphine consumption between patients experiencing no versus only mild events. Secondary outcomes included the difference in morphine consumption between patients with mild versus moderate and moderate versus severe events. We used Hodges-Lehmann median differences, exact Wilcoxon-Mann-Whitney tests and quantile regression. RESULTS: The difference in iv morphine consumption was 6 mg (95% confidence interval: 4-8) between patients with no versus only mild events, 5 mg (2-8) between patients with mild versus moderate events and 0 mg (-4 to 4) between patients with moderate versus severe events. CONCLUSIONS: In populations comparable to this post-hoc analysis (orthopaedic surgery, median age 70 and ASA 2), we suggest a minimally important difference of 5 mg for 0-24 h postoperative iv morphine consumption.
Assuntos
Artroplastia do Joelho , Morfina , Humanos , Feminino , Idoso , Masculino , Morfina/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Tontura/induzido quimicamente , Dor Pós-Operatória/etiologia , Analgésicos Opioides/efeitos adversos , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Método Duplo-CegoRESUMO
BACKGROUND: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPIâ¢AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. METHODS: Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). CONCLUSION: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPIâ¢AID) that will be validated and tested clinically against standard of care.
RESUMO
INTRODUCTION: While the use of camping stoves in poorly ventilated areas is discouraged, the need to address dehydration challenges in harsh arctic conditions has led to their unconventional use inside snow caves for snow melting, subjecting occupants to unknown carbon monoxide (CO) levels. This study, located at sea level in northeastern Greenland, aimed to assess CO levels and dynamics during short cooking sessions in newly constructed emergency snow caves. METHODS: In 5 snow caves, constructed according to the same design principles by 4 different individuals, a single MSR Whisperlite multifuel burner, primed with ethanol and burning white gas, was used to melt snow. CO concentrations were monitored every minute until all the snow in a 5-L pot was converted to water and CO levels returned to below 10 ppm. RESULTS: A total of 16 experiments conducted showed that the priming phase generated the highest CO peaks, with a maximum of 120 ppm. Time-weighted averages ranged from 14 ppm to 67 ppm, with trial durations of 15 to 21 min. A single trial with a dirty burner resulted in up to a 10-fold increase in CO levels. CONCLUSIONS: While single, short cooking sessions of less than 10 min burn time in newly constructed snow caves may be tolerated under specific conditions, the study highlighted substantial variation between caves and the importance of using clean burners, emphasizing the need for further research to gain a comprehensive understanding of CO exposure dynamics in snow caves.
Assuntos
Monóxido de Carbono , Culinária , Neve , Humanos , Monóxido de Carbono/análise , Culinária/métodos , Groenlândia , Poluição do Ar em Ambientes Fechados/análiseRESUMO
BACKGROUND: The leading principle in peri-operative pain management is multimodal analgesia, which reduces opioid requirements and associated adverse effects. Pragmatic pain trials should optimally test interventions in addition to multimodal non-opioid analgesics and interventions to ensure clinical relevance and baseline levels of opioid consumption that reflect clinical settings. We aimed to investigate opioid consumption and use of non-opioid analgesics administered adjunct to interventions in post-operative pain trials after total hip and knee arthroplasty. METHODS: A systematic literature search was conducted 7 January 2020 in The Cochrane Library's CENTRAL, PubMed, and EMBASE. Trials investigating analgesic interventions for post-operative pain in adults undergoing total hip or knee arthroplasty were included. The primary outcome was the aggregated median 0-24 h post-operative opioid consumption. Further, we assessed the use of paracetamol, non-steroidal anti-inflammatory drugs, gabapentinoids, high-dose glucocorticoids, local infiltration analgesia and nerve blocks administered as co-interventions equally to all participants. We assessed trends over time for all outcomes. RESULTS: Of 14,200 records, 570 trials were included. Median 0-24 h opioid consumption was 21 and 22 mg iv morphine equivalents in hip and knee arthroplasty trials, respectively. Meta-regression showed no overall linear correlation between opioid consumption and publication year. The use of multimodal non-opioid analgesia increased over time, though only 48% of trials published from 2010 to 2020 administered two or more non-opioid analgesics. Applying more non-opioid analgesics was associated with lower opioid consumption in intervention groups. CONCLUSION: Post-operative 0-24 h morphine consumption was median 21-22 mg. The demonstrated differences in non-opioid multimodal analgesic regimens between research and clinical settings, can potentially diminish the demonstrated opioid-sparing effects of trial interventions when such are implemented in a clinical context.
Assuntos
Analgésicos não Narcóticos , Artroplastia de Quadril , Artroplastia do Joelho , Adulto , Humanos , Manejo da Dor , Analgésicos Opioides , Analgésicos não Narcóticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Analgésicos/uso terapêutico , Dor Pós-Operatória/etiologia , Morfina/uso terapêutico , Estudos EpidemiológicosRESUMO
BACKGROUND: The patient-relevant minimal important difference for opioid consumption remains undetermined, despite its frequent use as primary outcome in trials on postoperative pain management. A minimal important difference is necessary to evaluate whether significant trial results are clinically relevant. Further, it can be used as effect size to ensure that trials are powered to find clinically relevant effects. By exploring the dose-response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects. METHODS: This is a post-hoc analysis of aggregated data from two clinical trials (PANSAID NCT02571361 and DEX2TKA NCT03506789) and one observational cohort study (Pain Map NCT02340052) on pain management after total hip and knee arthroplasty. The primary outcome is the Hodges-Lehmann median difference in opioid consumption between patients with no opioid-related adverse effects and patients experiencing the mildest degree of one or more opioid-related adverse effects (i.e., mild nausea, sedation and/or dizziness or vomiting). Secondary outcomes include the Hodges-Lehmann median difference in opioid consumption that corresponds to one point on a cumulated opioid-related adverse event 0-10 scale. Further, we will explore the proportion of patients that experience opioid-related adverse effects for consecutive opioid dose intervals of 2 mg iv morphine equivalents. Quantile regression will be used to assess any significant interactions with patient baseline characteristics. CONCLUSIONS: This study will hopefully bring us one step closer to determining relevant opioid reductions and thereby improve our understanding of intervention effects and planning of future trials.
Assuntos
Analgésicos Opioides , Dor Pós-Operatória , Humanos , Analgésicos Opioides/efeitos adversos , Estudos de Coortes , Morfina/uso terapêutico , Manejo da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/induzido quimicamenteRESUMO
BACKGROUND: We review the efficacy and safety of dexmedetomidine and clonidine as perineural or systemic adjuvants for brachial plexus blocks (BPB). METHODS: We included randomised controlled trials on upper limb surgery with BPBs in adults, comparing dexmedetomidine with clonidine or either drug with placebo. The primary outcome was duration of analgesia. Secondary outcomes included adverse and serious adverse events. The review was conducted using Cochrane standards, trial sequential analyses (TSA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 101 trials with 6248 patients. Overall, duration of analgesia was prolonged with both clonidine (176 min [TSA adj. 95% CI: 118, 205, p < .00001; 33 trials]) and dexmedetomidine (292 min [TSA adj. 95% CI: 245 329, p < .00001; 53 trials]), but was longer for dexmedetomidine than clonidine (205 min [TSA adj. 95% CI: 157, 254, p < .00001; 19 trials]). Compared with placebo, dexmedetomidine was associated with bradycardia (RR 4.2 [95% CI 2.2, 8.3]), and both clonidine (RR 4.5 [95% CI 1.1, 18.3]) and dexmedetomidine (RR 3.9 [95% CI 2.0, 7.5]) were associated with hypotension. Serious adverse events were mostly related to block technique. GRADE-rated quality of evidence was low or very low. CONCLUSION: Alpha2-receptor agonists used as adjuvants for BPBs lead to a prolonged duration of analgesia, with dexmedetomidine as the most efficient. Alpha2-receptor agonists were associated with increased risk of cardiovascular adverse events. The quality of evidence was low to very low.
Assuntos
Bloqueio do Plexo Braquial , Plexo Braquial , Dexmedetomidina , Agonistas de Receptores Adrenérgicos alfa 2 , Adulto , Clonidina , HumanosRESUMO
BACKGROUND: New-onset atrial fibrillation (NOAF) is common in hospitalised patients with critical illness and associated with worse outcomes. Several interventions are available in the management of NOAF, but the overall effectiveness and safety of these interventions compared with placebo or no treatment are unknown. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials (RCT) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses, the Cochrane Collaboration, and Grading of Recommendations Assessment, Development and Evaluation statements. We searched RCTs assessing any pharmacological and non-pharmacological treatment compared with placebo or no treatment in critically ill hospitalised patients with NOAF. The primary outcomes were all-cause mortality, adverse events, and health-related quality of life. RESULTS: We included 16 trials (n = 1891) evaluating seven interventions. All trials were adjudicated 'some concerns' or 'high risk' of bias. The evidence is very uncertain for mortality (RR 0.53, 95% CI 0.03-8.30), adverse events (RR 1.28, 95% CI 0.85-1.92), and treatment efficacy i.e. rhythm control (RR 1.54, 95% CI 1.20-1.97; TSA-adjusted CI 0.56-4.53) between pharmacological treatment and placebo/no treatment (very low certainty evidence). There were no data for health-related quality of life or most of our secondary outcomes. CONCLUSIONS: The existing data are insufficient to firmly conclude on effects of any intervention against NOAF on any outcome in hospitalised patients with critical illness. Randomised trials of the most frequently used interventions against NOAF are warranted in these patients.
Assuntos
Fibrilação Atrial , Estado Terminal , Fibrilação Atrial/tratamento farmacológico , Viés , Estado Terminal/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Between 9% and 20% of patients experience moderate to severe persistent postoperative pain after total hip or knee arthroplasty. Severe immediate postoperative pain limits rehabilitation and is associated with the development of persistent postoperative pain. Therefore, perioperative analgesic and physiotherapeutic interventions are of interest to reduce persistent pain. In two systematic reviews with identical methodology, we aim to investigate the effects of (a) perioperative analgesic interventions and (b) physiotherapeutic interventions in reducing persistent pain after total hip and knee arthroplasty. METHODS: We will include randomised and cluster-randomised controlled trials on perioperative analgesic and physiotherapeutic interventions for patients undergoing elective total hip or knee arthroplasty for osteoarthritis. After contact with the authors, trials without pain data 3-24 months postoperatively will be excluded. Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists will be searched for eligible trials. Two authors will independently screen, extract data and assess the risk of bias. The primary outcome is pain scores 3-24 months postoperatively. Meta-analyses will be performed for interventions with two or more trials. We will conduct trial sequential analyses and assign Grading of Recommendations, Assessment, Development and Evaluation (GRADE) ratings. CONCLUSION: No previous review on reduction of persistent postoperative pain has included non-pharmacological or invasive analgesic techniques. These two reviews with identical methodology will summarise the evidence of analgesic and physiotherapeutic perioperative interventions to prevent persistent pain. PROSPERO REGISTRATION: CRD42021284175.
Assuntos
Artroplastia do Joelho , Dor Pós-Operatória , Analgésicos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como AssuntoRESUMO
Blunted muscle hypertrophy and impaired regeneration with aging have been partly attributed to satellite cell (SC) dysfunction. However, true muscle regeneration has not yet been studied in elderly individuals. To investigate this, muscle injury was induced by 200 electrically stimulated (ES) eccentric contractions of the vastus lateralis (VL) of one leg in seven young (20-31 years) and 19 elderly men (60-73 years). This was followed by 13 weeks of resistance training (RT) for both legs to investigate the capacity for hypertrophy. Muscle biopsies were collected Pre- and Post-RT, and 9 days after ES, for immunohistochemistry and RT-PCR. Hypertrophy was assessed by MRI, DEXA, and immunohistochemistry. Overall, surprisingly comparable responses were observed between the young and elderly. Nine days after ES, Pax7+ SC number had doubled (P < .05), alongside necrosis and substantial changes in expression of genes related to matrix, myogenesis, and innervation (P < .05). Post-RT, VL cross-sectional area had increased in both legs (~15%, P < .05) and SCs/type II fiber had increased ~2-4 times more with ES+RT vs RT alone (P < .001). Together these novel findings demonstrate "youthful" regeneration and hypertrophy responses in human elderly muscle. Furthermore, boosting SC availability in healthy elderly men does not enhance the subsequent muscle hypertrophy response to RT.
Assuntos
Envelhecimento , Hipertrofia/fisiopatologia , Desenvolvimento Muscular , Músculo Esquelético/citologia , Regeneração , Células Satélites de Músculo Esquelético/citologia , Adulto , Idoso , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Músculo Quadríceps/citologia , Músculo Quadríceps/fisiologia , Treinamento Resistido , Células Satélites de Músculo Esquelético/fisiologia , Adulto JovemRESUMO
BACKGROUND: Sample size determination is essential for reliable hypothesis testing in clinical trials and should rely on adequate sample size calculations with alpha, beta, variance, and an effect size being the minimal clinically important difference (MCID). This facilitates interpretation of the clinical relevance of statistically significant results. No gold standard for MCIDs exists in postoperative pain research. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for English language articles on randomised trials investigating analgesic interventions after total hip or knee arthroplasty. Primary outcomes were the reported MCIDs for pain score and cumulated rescue opioid consumption. Secondary outcomes included reported sample size calculations and propensity to report statistical significance without reaching MCID. Trend analyses were conducted using statistical process control. RESULTS: We included 570 trials. Median MCID for 0-24 h opioid consumption was 10 mg i.v. morphine equivalents for absolute reductions (interquartile range [IQR]: 6.8-14.5) and relative 40% (IQR: 30-50%). Median MCIDs for pain scores were absolute 15 mm at rest (IQR: 10-20) and 18 mm during movement (IQR: 10-20) on a 0-100 mm VAS and relative 30% (IQR: 20-30%). No trends were demonstrated for MCIDs. Adequate sample size calculations were reported in 34% of trials. In 46% of trials with statistically significant primary outcomes, the differences did not reach the predetermined MCID. CONCLUSIONS: We provide clinician-perceived MCID estimates for rescue opioid consumption and pain scores that can be used for sample size calculations until reliable evidence-based patient-rated MCIDs emerge. Nearly half of the trials with significant findings did not reach the predetermined MCID.
Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Humanos , Diferença Mínima Clinicamente Importante , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation. METHODS: Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65-94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn ), and neural cell adhesion molecule (NCAM). RESULTS: Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65-94 years) was negatively associated with AchRγ mRNA. DISCUSSION: Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.
Assuntos
Envelhecimento/genética , Fibras Musculares Esqueléticas/metabolismo , Cadeias Pesadas de Miosina/genética , Moléculas de Adesão de Célula Nervosa/genética , Músculo Quadríceps/inervação , Receptores Colinérgicos/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Humanos , Masculino , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Músculo Quadríceps/metabolismo , RNA Mensageiro/metabolismo , Receptores Nicotínicos/genéticaRESUMO
INTRODUCTION: The relationship between fiber size and myonuclear content is poorly understood. METHODS: Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed. RESULTS: When comparing fibers of similar size, no effect of training or age was found for myonuclear domain. There was a linear relationship between fiber area and myonuclei per fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and domain (r = 0.97-0.99; P < 0.0001), with a markedly smaller domain in fibers <3,000 µm(2). A higher proportion of type II fibers <3,000 µm(2) was observed in the old subjects. CONCLUSIONS: These findings suggest that age-related reductions in myonuclear domain size could be explained by the greater proportion of small fibers. The data also highlight the usefulness of determining fiber-size-based clusters for gaining mechanistic insight into the relationship between skeletal muscle fiber size and myonuclear content.
Assuntos
Envelhecimento , Núcleo Celular/fisiologia , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/fisiologia , Adulto , Idoso , Análise de Variância , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: We examined whether diastolic left ventricular function in young and senior lifelong endurance runners was significantly different from that in sedentary age-matched controls, and whether lifelong endurance running appears to modify the age-related decline in diastolic left ventricular function. DESIGN: The study comprised 17 senior athletes (age: 59-75 years, running distance: 30-70 km/week), 10 young athletes (age: 20-36 years, matched for running distance), and 11 senior and 12 young weight-matched sedentary controls. Peak early (E) and late (A) mitral inflow and early (e') and late (a') diastolic and systolic (s') annular longitudinal tissue Doppler velocities were measured by echocardiography during four stages (rest, supine bike exercise at 30% and 60% of maximal workload, and recovery). RESULTS: The athletes had marked cardiac remodeling, while overall differences in mitral inflow and annular tissue Doppler velocities during rest and exercise were more associated with age than with training status. The senior participants had lower E/A at rest, overall lower E, e' and s', and greater E/e' compared to the young participants (all values of P < 0.05). The athletes had greater E/A (P = 0.004), but tissue Doppler velocities were not different from those of the controls. CONCLUSIONS: Lifelong endurance running was not found to be associated with major attenuation of the age-related decline in diastolic function at rest or during exercise.
Assuntos
Envelhecimento , Valva Mitral/fisiologia , Resistência Física , Corrida , Função Ventricular Esquerda , Adulto , Fatores Etários , Idoso , Ciclismo , Estudos de Casos e Controles , Estudos Transversais , Diástole , Ecocardiografia Doppler , Teste de Esforço , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Adulto JovemRESUMO
In this study, we developed a novel badminton-specific speed test (BST). The test was designed to mimic match play. The test starts in the center of the court and consists of 5 maximal actions to sensors located in each of the 4 corners of the court. The 20 actions are performed in randomized order as dictated by computer screen shots displayed 1 second after completion of the previous action. We assessed day-to-day variation in elite players, and specificity of the test was evaluated by comparing 30-m sprint performance and time to complete the BST in 20 elite players, 21 skilled players, and 20 age-matched physical active subjects (non-badminton players). Sprint performance was similar across groups, whereas the elite players were significantly (p ≤ 0.05) faster in the BST (total test time: 32.3 ± 1.1 seconds; average: 1.6 seconds per action) than the skilled (34.1 ± 2.0 seconds) and non-badminton players (35.7 ± 1.7 seconds). Day-to-day coefficient of variation (CV) of the BST was 0.7% for the elite players, whereas CV for repeated tests on the same day was 1.7% for elite, 2.6% for skilled, and 2.5% for non-badminton players. On this basis, we suggest that the BST may be valuable for evaluation of short-term maximal movement speed in badminton players. Thus, the BST seems to be sport specific, as it may discriminate between groups (elite, less trained players, and non-badminton players) with similar sprinting performance, and the low test-retest variation may allow for using the BST to evaluate longitudinal changes, for example, training effects or seasonal variations.
Assuntos
Desempenho Atlético/fisiologia , Teste de Esforço/métodos , Movimento/fisiologia , Esportes com Raquete/fisiologia , Adolescente , Adulto , Desempenho Atlético/classificação , Humanos , Masculino , Reprodutibilidade dos Testes , Corrida/fisiologia , Adulto JovemRESUMO
STUDY OBJECTIVE: Initial out-of-hospital analgesia is sometimes hampered by difficulties in achieving intravenous access or lack of skills in administering intravenous opioids. We study the safety profile and apparent analgesic effect of intranasal fentanyl in the out-of-hospital setting. METHODS: In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses of either 50 or 100 µg, and the ambulance crew recorded adverse effects and numeric rating scale (0 to 10) pain scores before and after treatment. RESULTS: Our 903 evaluable patients received a mean cumulative fentanyl dose of 114 µg (range 50 to 300 µg). There were no serious adverse effects and no use of naloxone. Thirty-six patients (4%) experienced mild adverse effects: mild hypotension, nausea, vomiting, vertigo, abdominal pain, rash, or decrease of Glasgow Coma Scale score to 14. The median reduction in pain score was 3 (interquartile range 2 to 5) after fentanyl administration. CONCLUSION: The out-of-hospital administration of intranasal fentanyl in doses of 50 to 100 µg is safe and appears effective.