RESUMO
Patients with therapy-refractory or high-risk relapsed classical Hodgkin lymphoma are typically treated with the high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) to consolidate the response to salvage therapy. The combination of brentuximab vedotin with gemcitabine has recently been shown to be an effective and safe salvage regimen. While the majority of patients with complete responses to this regimen ultimately underwent HDC/ASCT consolidation, four subjects, reported herein, achieved durable complete remissions lasting more than 4 years after the study treatment but without ASCT consolidation. Further investigation of treatment strategies incorporating targeted agents may allow omission of HDC/ASCT for select patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Imunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Criança , Desoxicitidina/análogos & derivados , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Transplante de Células-Tronco , Transplante Autólogo , GencitabinaRESUMO
The novel coronavirus may impact exercise habits of those with intellectual disabilities. Due to the mandated discontinuation of face-to-face research, investigators must adapt projects to protect all involved while collecting objective physical activity metrics. This brief report outlines a modification process of research methods to adhere to social distancing mandates present during COVID-19. Actions taken included electronic consent and assent forms, an electronic survey, and mailing an accelerometer with included instructions. The amended research methods were implemented without risk for virus transmission or undue burden on the research team, participant, or caregiver. Recruitment was likely impacted by the coronavirus-mediated quarantine, plausibly resulting in bias. Objective physical activity data collection can be sufficiently modified to protect those with intellectual disabilities and investigators. Future research designs may require greater participant incentives and the creation of in-home participation.
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COVID-19 , Deficiência Intelectual , Exercício Físico , Humanos , Distanciamento Físico , Inquéritos e QuestionáriosRESUMO
ß-alanine supplementation increases muscle carnosine content and improves anaerobic exercise performance by enhancing intracellular buffering capacity. ß-alanine ingestion in its traditional rapid-release formulation (RR) is associated with the symptoms of paresthesia. A sustained-release formulation (SR) of ß-alanine has been shown to circumvent paresthesia and extend the period of supply to muscle for carnosine synthesis. The purpose of this investigation was to compare 28 days of SR and RR formulations of ß-alanine (6 g day-1) on changes in carnosine content of the vastus lateralis and muscle fatigue. Thirty-nine recreationally active men and women were assigned to one of the three groups: SR, RR, or placebo (PLA). Participants supplementing with SR and RR formulations increased muscle carnosine content by 50.1% (3.87 mmol kg-1ww) and 37.9% (2.62 mmol kg-1ww), respectively. The change in muscle carnosine content in participants consuming SR was significantly different (p = 0.010) from those consuming PLA, but no significant difference was noted between RR and PLA (p = 0.077). Although participants ingesting SR experienced a 16.4% greater increase in muscle carnosine than RR, fatigue during maximal voluntary isometric contractions was significantly attenuated in both SR and RR compared to PLA (p = 0.002 and 0.024, respectively). Symptoms of paresthesia were significantly more frequent in RR compared to SR, the latter of which did not differ from PLA. Results of this study demonstrated that only participants consuming the SR formulation experienced a significant increase in muscle carnosine. Differences in the muscle carnosine response between these formulations may have practical significance for athletic populations in which small changes may have important implications on performance.
Assuntos
Carnosina/biossíntese , Preparações de Ação Retardada/administração & dosagem , Suplementos Nutricionais , Músculo Esquelético/efeitos dos fármacos , Parestesia/prevenção & controle , beta-Alanina/administração & dosagem , Adulto , Carnosina/agonistas , Método Duplo-Cego , Esquema de Medicação , Exercício Físico , Feminino , Humanos , Contração Isométrica/efeitos dos fármacos , Masculino , Fadiga Muscular/efeitos dos fármacos , Fadiga Muscular/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Parestesia/metabolismo , Parestesia/fisiopatologiaRESUMO
PURPOSE: To examine the reliability and the maturity-related differences of fatigue thresholds (FTs) among youth males. METHODS: Twenty-nine youth males (11-17 y) completed 2 ramp exercise tests on a cycle ergometer. Systemic FTs were calculated from gas exchange and ventilation variables. Localized FTs were calculated from electromyography and near-infrared spectroscopy of the vastus lateralis. All FTs were determined using the maximal distance method and expressed relative to maximal oxygen consumption. All participants were grouped according to the number of years from peak height velocity into PRE- (< -1.5 y), PERI- (-1.5 to +1.5 y) and POST- (> +1.5 y) peak height velocity. Reliability was assessed with intraclass correlation coefficients, and differences between groups were assessed with analysis of variance and Cohen's d coefficients. RESULTS: Analysis of variance revealed significant group differences with PRE having significantly greater systemic pulmonary FTs than POST, while localized muscular FTs were significantly greater in PRE when compared with PERI and POST. All FTs exhibited excellent reliability (intraclass correlation coefficient > .75) in all maturity groups. CONCLUSION: Maturity status appears to influence the onset of FTs among youth male athletes, with FTs occurring later in younger athletes. Furthermore, all FTs were reliable measures regardless of maturity.
Assuntos
Desempenho Atlético/fisiologia , Exercício Físico/fisiologia , Fadiga Muscular/fisiologia , Músculo Esquelético/fisiologia , Adolescente , Atletas/estatística & dados numéricos , Criança , Eletromiografia/métodos , Ergometria/métodos , Humanos , Pulmão/fisiologia , Masculino , Consumo de Oxigênio/fisiologia , Reprodutibilidade dos Testes , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
BACKGROUND: Advance care planning (ACP) conversations help individuals exercise autonomy and make informed decisions about their care. There are many ACP resources available to support the process of advance care planning, yet available resources not universally accepted and under-utilized in clinical practice. OBJECTIVE: This study aims to systematically evaluate commonly available general ACP patient educational resources using a comprehensive approach to assess elements ranging from resource inclusion to health literacy. DESIGN: Systematic evaluation of general ACP educational resources METHODS: ACP educational resources were systematically identified and evaluated for: Patient Education Materials Assessment Tool (PEMAT) score, Flesch-Kincaid reading ease and grade level, cost, languages available, and categories of content including Advance directive/Healthcare proxy, Physician Order for Life-Sustaining Treatment (POLST), Living will, values, preferences, and goals. RESULTS: Educational resources (nâ¯=â¯20) were identified. These resources were classified as information resources, workbooks, interactive websites, or and activities/conversation guides. The average PEMAT understandability score was 86 (range 58-100) and the average actionability was 90 (range 40-100). Two resources met Flesch-Kincaid reading ease and grade level. Eight were available in English only, nine in two languages, and three in more than two languages. Three explicitly discussed completion of POLST forms. The majority of the resources adequately addressed the content of advanced directives and health care proxy, values, goals, and preferences for future care. The level of time commitment required to use each resource also varied considerably. CONCLUSION: We present a comprehensive evaluation of resources to support ACP. Using the Transtheoretical Model, we provide a guide for the use of these educational resources based on patient readiness. This review allows clinicians to identify aspects of each resource that may be helpful in preparing older adults for future healthcare decsions. Our analysis has identified the need to continue to refine these educational resources so that they can reach a broad population with varying needs. Advance care planning (ACP) conversations help individuals exercise autonomy and make informed decisions about their care. There are many ACP educational resources available to support the process of advance care planning, yet available resources are not universally accepted and under-utilized in clinical practice. We present a comprehensive evaluation of 20 educational resources to support ACP. Educational resources were identified and evaluated for: Patient Education Materials Assessment Tool (PEMAT) score, Flesch-Kincaid reading ease and grade level, cost, languages available, and categories of content. Using the Transtheoretical Model, we provide a guide for the use of these educational resources based on patient readiness. This review allows clinicians to identify aspects of each resource that may be helpful in preparing older adults for future healthcare decisions. Our analysis has identified the need to continue to refine these educational resources so that they can reach a broad population with varying needs.
Assuntos
Planejamento Antecipado de Cuidados , Diretivas Antecipadas , Letramento em Saúde , Educação de Pacientes como Assunto , Tomada de Decisões , Recursos em Saúde , HumanosRESUMO
Attenuating TNFα/TNFr1 signaling in monocytes has been proposed as a means of mitigating inflammation. The purpose of this study was to examine the effects of a milk protein supplement on TNFα and monocyte TNFr1 expression. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) ingested supplement (SUPP) or placebo (PL) immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL), immediately (IP), 30-min (30P), 1-h (1H), 2-h (2H), and 5-h (5H) post-exercise to assess plasma concentrations of myoglobin; tumor necrosis factor-alpha (TNFα); and expression of tumor necrosis factor receptor 1 (TNFr1) on classical, intermediate, and non-classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Plasma TNFα concentrations were "likely attenuated" (91.6% likelihood effect) from BL to 30P in the SUPP group compared with PL (d = 0.87; mean effect: 2.3 ± 2.4 pg mL-1). TNFr1 expressions on classical (75.9% likelihood effect) and intermediate (93.0% likelihood effect) monocytes were "likely attenuated" from BL to 2H in the SUPP group compared with PL (d = 0.67; mean effect: 510 ± 670 RFU, and d = 1.05; mean effect: 2500 ± 2300 RFU, respectively). TNFr1 expression on non-classical monocytes was "likely attenuated" (77.6% likelihood effect) from BL to 1H in the SUPP group compared with PL (d = 0.69; mean effect: 330 ± 430 RFU). Ingestion of a milk protein supplement immediately post-exercise appears to attenuate both plasma TNFα concentrations and TNFr1 expression on monocyte subpopulations in resistance-trained men.
Assuntos
Suplementos Nutricionais , Proteínas do Leite/administração & dosagem , Monócitos/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Treinamento Resistido , Fator de Necrose Tumoral alfa/sangue , Adulto , Células Cultivadas , Estudos Cross-Over , Ingestão de Alimentos , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Masculino , Monócitos/citologia , Adulto JovemRESUMO
OBJECTIVE: ß-alanine (BA) is a nonproteogenic amino acid that combines with histidine to form carnosine. The amount taken orally in individual doses, however, is limited due to symptoms of paresthesia that are associated with higher doses. The use of a sustained-release formulation has been reported to reduce the symptoms of paresthesia, suggesting that a greater daily dose may be possible. The purpose of the present study was to determine whether increasing the daily dose of BA can result in a similar increase in muscle carnosine in a reduced time. METHODS: Eighteen men and twelve women were randomized into either a placebo (PLC), 6-g BA (6G), or 12-g BA (12G) groups. PLC and 6G were supplemented for 4 weeks, while 12G was supplemented for 2 weeks. A resting blood draw and muscle biopsy were obtained prior to (PRE) and following (POST) supplementation. Plasma and muscle metabolites were measured by high-performance liquid chromatography. The loss in peak torque (ΔPT) was calculated from maximal isometric contractions before and after 250 isokinetic kicks at 180°·sec-1 PRE and POST. RESULTS: Both 12G (p = 0.026) and 6G (p = 0.004) increased muscle carnosine compared to PLC. Plasma histidine was decreased from PRE to POST in 12G compared to PLC (p = 0.002) and 6G (p = 0.001), but no group x time interaction (p = 0.662) was observed for muscle histidine. No differences were observed for any hematological measure (e.g., complete blood counts) or in symptoms of paresthesia among the groups. Although no interaction was noted in ΔPT, a trend (p = 0.073) was observed. CONCLUSION: Results of this investigation indicate that a BA supplementation protocol of 12 g/d-1, using a sustained-release formulation, can accelerate the increase in carnosine content in skeletal muscle while attenuating paresthesia.
Assuntos
Carnosina/metabolismo , Suplementos Nutricionais , Músculo Esquelético/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Esportiva , beta-Alanina/administração & dosagem , Adulto , Dieta , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Relação Dose-Resposta a Droga , Exercício Físico , Feminino , Histidina/sangue , Humanos , Masculino , Músculo Esquelético/metabolismo , Avaliação Nutricional , Parestesia/tratamento farmacológico , Cooperação do Paciente , Inquéritos e Questionários , Adulto Jovem , beta-Alanina/sangueRESUMO
PURPOSE: To examine the mitogen-activated protein kinase (MAPK) family of signaling proteins following typical high volume (HV) and high intensity (HI) lower body resistance exercise protocols in resistance-trained men. METHODS: Ten resistance-trained men (24.7 ± 3.4 year; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) performed each resistance exercise protocol in a random, counterbalanced order. The HV protocol utilized a load of 70 % 1-RM for sets of 10-12 repetitions with a 1-min rest period length between sets and exercises. The HI protocol utilized a load of 90 % 1-RM for sets of 3-5 repetitions with a 3-min rest period length between sets and exercises. Both protocols included six sets of barbell back squats and four sets of bilateral leg press, bilateral hamstring curls, bilateral leg extensions, and seated calf raises. Fine needle muscle biopsies of the vastus lateralis were completed at baseline (BL) and 1-h post exercise (1H). RESULTS: No significant differences over time were noted for phosphorylation of MEK1, ERK1/2, p38, MSK1, ATF2, p53, or c-Jun (p > 0.05). No significance between trial interactions was noted for phosphorylation of MAPK signaling proteins, including MEK1, ERK1/2, p38, JNK, MSK1, ATF2, STAT1, p53, c-Jun, or HSP27 (p > 0.05). However, significant time effects were observed for phosphorylation of JNK (p < 0.01), HSP27 (p < 0.01), and STAT1 (p = 0.03). Phosphorylation of JNK, HSP27, and STAT1 was significantly elevated from BL at 1H for both HV and HI. CONCLUSIONS: HV and HI lower body resistance exercise protocols appear to elicit similar MAPK activation in resistance-trained men.
Assuntos
Treinamento Intervalado de Alta Intensidade/métodos , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Músculo Esquelético/fisiologia , Condicionamento Físico Humano/fisiologia , Treinamento Resistido/métodos , Exercício Físico/fisiologia , Humanos , Perna (Membro)/fisiologia , Masculino , Condicionamento Físico Humano/métodos , Esforço Físico/fisiologia , Aptidão Física/fisiologia , Adulto JovemRESUMO
PURPOSE: The NF-κB signaling pathway regulates multiple cellular processes following exercise stress. This study aims to examine the effects of an acute lower-body resistance exercise protocol and subsequent recovery on intramuscular NF-κB signaling. METHODS: Twenty-eight untrained males were assigned to either a control (CON; n = 11) or exercise group (EX; n = 17) and completed a lower-body resistance exercise protocol consisting of the back squat, leg press, and leg extension exercises. Skeletal muscle microbiopsies were obtained from the vastus lateralis pre-exercise (PRE), 1-hour (1H), 5-hours (5H), and 48-hours (48H) post-resistance exercise. Multiplex signaling assay kits (EMD Millipore, Billerica, MA, USA) were used to quantify the total protein (TNFR1, c-Myc) or phosphorylation status of proteins belonging to the NF-κB signaling pathway (IKKa/b, IkBα, NF-κB) using multiplex protein assay. Repeated measures ANOVA analysis was used to determine the effects of the exercise bout on intramuscular signaling at each time point. Additionally, change scores were analyzed by magnitude based inferences to determine a mechanistic interpretation. RESULTS: Repeated measures ANOVA indicated a trend for a two-way interaction between the EX and CON Group (p = 0.064) for c-Myc post resistance exercise. Magnitude based inference analysis suggest a "Very Likely" increase in total c-Myc from PRE-5H and a "Likely" increase in IkBα phosphorylation from PRE-5H post-resistance exercise. CONCLUSION: Results indicated that c-Myc transcription factor is elevated following acute intense resistance exercise in untrained males. Future studies should examine the role that post-resistance exercise NF-κß signaling plays in c-Myc induction, ribosome biogenesis and skeletal muscle regeneration.
Assuntos
Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , NF-kappa B/metabolismo , Condicionamento Físico Humano/métodos , Treinamento Resistido/métodos , Humanos , Masculino , Comportamento Sedentário , Transdução de Sinais/fisiologia , Estresse Fisiológico/fisiologia , Adulto JovemRESUMO
Boone, CH, Hoffman, JR, Gonzalez, AM, Jajtner, AR, Townsend, JR, Baker, KM, Fukuda, DH, and Stout, JR. Changes in plasma aldosterone and electrolytes following high-volume and high-intensity resistance exercise protocols in trained men. J Strength Cond Res 30(7): 1917-1923, 2016-Program variables such as training intensity, volume, and rest interval length are known to elicit distinct hormonal, metabolic, and physical responses. However, little is known regarding resistance exercise (RE) program design and the fluid regulatory response. This investigation aimed to compare the plasma aldosterone (ALD), electrolyte, plasma volume (PV), and osmolality (Posm) responses following high-volume (HV; 4-6 × 10-12 reps, 70% 1 repetition maximum [1RM], 60-s rest) and high-intensity (HI; 6 × 3-5 reps, 90% 1RM, 180-second rest) RE protocols. Ten experienced, resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) performed each protocol in a random, counterbalanced order. Blood samples were obtained at baseline (BL), immediately (IP), 30 minutes (30P), and 1 hour (1H) postexercise. Significant trial × time interactions (p < 0.01) were observed in Posm, sodium (Na), and potassium (K), whereas a trend (p = 0.06) was observed for ALD. The PV shift from BL-30P was greater than BL-IP and BL-1H (p ≤ 0.05), but no significant between-trial differences were noted. Comparisons between RE protocols revealed significantly greater (p ≤ 0.05) elevations during HV vs. HI in Posm at IP, 30P, and 1H; and Na at IP and 30P. During HV, significant reductions (p ≤ 0.05) were noted in K at IP compared with HI. Area under the curve analysis indicates a trend (p = 0.07) toward a higher ALD response following HV compared with HI. Results of this study indicate that high-volume, moderate-intensity resistance exercise seems to augment the fluid regulatory response to a greater extent than low-volume, high-intensity training.
Assuntos
Aldosterona/sangue , Eletrólitos/sangue , Treinamento Resistido/métodos , Adulto , Humanos , Masculino , Concentração Osmolar , Volume Plasmático , Distribuição Aleatória , Descanso/fisiologia , Adulto JovemRESUMO
This study examined the influence of recovery time on fatigue indices, performance (total work [TW], peak power [PP], and mean power [MP]), and oxygen consumption during repeated sprint ability (RSA) on a cycle ergometer. Eight recreationally-trained men performed 3 RSA protocols consisting of 10 × 6 s sprints with 12 s, 18 s, and 24 s rest intervals between each sprint. Fatigue indices were determined as percent decrement (%Dec) and rate of decline using either a log transform method or standard slope approach for TW, PP, and MP during respective RSA protocols. The maximal VO2 value in response to given sprint intervals and the minimal VO2 value in response to given rest periods (VO2 work and VO2 rest, respectively) were recorded. A repeated measures analysis of variance was used to analyze all variables. Average VO2 work was not different among rest interval trials. Average VO2 rest with 12 s rest was greater than 18 s and 24 s (2.16 ± 0.17 L · min(-1), 1.91 ± 0.18 L · min(-1), 1.72 ± 0.15 L · min(-1), respectively), while 18 s was greater than 24 s. Average TW and MP were greater with 24 s rest than 12 s (4,604.44 ± 915.98 J vs. 4,305.46 ± 727.17 J, respectively), with no differences between RSA protocols for PP. No differences in %Dec were observed. Both methods of calculating rates of decline per sprint for PP and TW were greater during 12 s than 18 s or 24 s. Since changes were only noted between the 12 s and 24 s protocols, a 6 s differential in rest intervals may not be enough to elicit alterations in TW, PP, MP, or %Dec in RSA performance. Rate of decline may be a more sensitive measure of fatigue than %Dec.
Assuntos
Teste de Esforço/métodos , Fadiga/prevenção & controle , Descanso/psicologia , Corrida/fisiologia , Adulto , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Recuperação de Função Fisiológica/fisiologia , Adulto JovemAssuntos
Planejamento Antecipado de Cuidados/organização & administração , Atitude do Pessoal de Saúde , Enfermagem de Cuidados Críticos/organização & administração , Recursos Humanos de Enfermagem Hospitalar/psicologia , Satisfação do Paciente , Assistência Terminal/organização & administração , Assistência Terminal/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Chimeric Antigen Receptor (CAR) T-cell treatment is associated with several unique toxicities, and the short-term symptom trajectory in the immediately after therapy is well-documented. However, little is known about patients' long-term symptom experience. The study aimed to elicit the symptom experience of adult patients in remission after CAR T-cell therapy for B cell lymphoma. DATA SOURCES: A qualitative descriptive design with thematic analysis was utilized. Recruitment occurred at a tertiary academic medical center using the following inclusion criteria: adult recipient of CAR T-cell therapy for B-cell lymphoma between 3 and 12 months prior to enrollment, and currently in remission. Semi-structured interviews were conducted, transcripts were inductively coded, and team members met weekly to ensure rigor. The final sample included 10 patients: Seven received tisagenlecleucel and three received lisocabtagene marleucel and were a median of 169 days post-infusion and 65 years of age. CONCLUSIONS: Participants continued to report symptoms, including fatigue, neuropathy, low endurance, insomnia, memory problems, and pain. Most symptoms improved over time. Some symptoms interfered with social activities, work, driving, and physical activity, though participants reported that most symptoms existed prior to CAR T-cell therapy, and overall, found CAR T-cell therapy acceptable. IMPLICATIONS FOR NURSING PRACTICE: Patients in remission after CAR T-cell therapy often continue to experience symptoms. Nurses should continue to assess this growing patient population and determine if patients require additional symptom management or support. Further research is needed to understand long-term symptom trajectory and associations with prior lines of therapy and CAR T-cell therapy.
Assuntos
Imunoterapia Adotiva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Idoso , Adulto , Linfoma de Células B/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos de Linfócitos T/uso terapêutico , Pesquisa QualitativaRESUMO
Gape-limited predators (e.g., snakes, many fish) are not generally expected to pose a predation threat to prey that are too large for them to swallow. However, the extent to which snakes predate on prey that exceed their gape limitation remains largely unknown. We conducted the first study to investigate the influence of both prey and predator sizes on the frequency of ingestion success by snakes in a natural system. We combined survival monitoring of an avian prey species (Aplonis opaca) via radio-telemetry with a survey of the size distribution of their major predator (Boiga irregularis) on Guam. This allowed us to assess (1) the frequency of unsuccessful ingestion by the predator, (2) whether the size of the prey predicts ingestion success, (3) whether the size of the predator predicts ingestion success, and (4) the relationship between prey and predator sizes in successful ingestion attempts. We found that nearly half (47.95%) of ingestion attempts by snakes on fledgling birds were unsuccessful, and no instances where unsuccessful ingestion caused the mortality of the snake. Attempts to consume smaller fledglings were as likely to be unsuccessful as attempts to swallow larger fledglings. However, snakes that successfully ingested fledglings were among the largest snakes in the population, and larger than average conspecifics attracted to endothermic prey. The smallest snakes that successfully ingested fledglings attained remarkably high relative prey mass values for their species, consuming prey weighing up to 79.9% of their own mass. Our study indicates that B. irregularis routinely predate prey that are too large for them to successfully ingest, which causes mortality to the prey but poses little risk to the predator. The potential reward for snakes in consuming oversized prey may outweigh the inherent risks, while instances of predation that do not result in consumption may have considerable impacts on prey populations.
RESUMO
Background: Psilocybin-assisted therapies (PAT) are reemerging as a treatment for complex distress often prompting mystical experiences, enhanced meaning, and spiritual wellbeing. We sought to investigate how measures of spirituality are employed in experimental studies of PAT conducted with seriously ill adults. Methods: We included experimental studies of psilocybin conducted with seriously ill adults, which employed measures that contained spirituality and mysticism concepts within their domains or subdomains. Included studies were peer-reviewed and published in English language (up to December 2021). Results: Seven articles met our inclusion criteria. A total of 12 unique instruments were identified. The most frequently used instruments were the Mystical Experience Questionnaire (MEQ30), the Functional Assessment of Chronic Illness Therapy-Spirituality (FACIT-Sp-12), and the Demoralization Scale (DS-I/II) (used in four studies each), followed by the Persisting Effects Questionnaire (PEQ) (used in three studies). Overall, studies did not consistently define and contextualize spirituality domains and subdomains studied. Conclusions: Despite well-recognized significance of spirituality in PAT, there was considerable heterogeneity in number and types of spirituality measures employed across studies. There also seemed a lack of attention to defining and operationalizing spirituality and its domains and subdomains. This is notable as spirituality and overlapping concepts (eg mystical experiences) contributes substantially to this body of research and patients' therapeutic outcomes. Towards developing more rigorous science of spirituality in PAT research, there is a critical need to evaluate and refine measures of spirituality to enhance their utility and replicability, limit participant burden, and better contextualize spirituality-related findings and outcomes.
Assuntos
Alucinógenos , Psilocibina , Adulto , Humanos , Psilocibina/uso terapêutico , Alucinógenos/uso terapêutico , Espiritualidade , Misticismo , Inquéritos e QuestionáriosRESUMO
It is critical to characterize the natural history of albuminuria in patients with sickle cell anemia (SCA); however, these data are currently lacking and affecting evidence-based guidelines. We performed a natural history study of the development of pediatric albuminuria. We identified participants with hemoglobin SS/SB0 thalassemia ≥5 years with albumin to creatinine ratio (ACR) measurements performed at a steady-state clinic visit. Participants were characterized as either persistent, intermittent, or never albuminuria. We determined the prevalence of persistent albuminuria, use of ACR ≥100 mg/g as a predictor, and variation in ACR measurements. We mirrored this study to determine the variation in albuminuria measurements in the SCA murine model. Among 355 participants with HbSS/SB0 thalassemia with 1728 ACR measurements, we identified 17% with persistent and 13% with intermittent albuminuria. Thirteen percent of participants with persistent albuminuria developed an abnormal ACR before 10 years of age. A single ACR measurement ≥100 mg/g was associated with 55.5 times (95% confidence interval, 12.3-527) higher odds of having persistent albuminuria. Among participants with ACR ≥100 mg/g, we identified significant variability in the results of repeated measurements. The median ACR at the initial and next measurements were 175.8 mg/g (interquartile range [IQR], 135-242) and 117.3 mg/g (IQR, 64-292). The human variability in ACR was mirrored by â¼20% variability in albuminuria in murine model. This evidence suggests adopting standards for repeating ACR measurements, consider screening for ACR before 10 years of age, and using an ACR >100 mg/g as a risk factor for progression. Pediatric and murine renoprotective clinical trials need to consider the high variability in repeated ACR measurements.
Assuntos
Anemia Falciforme , Talassemia , Humanos , Criança , Animais , Camundongos , Albuminúria/etiologia , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Modelos Animais de Doenças , Taxa de Filtração Glomerular , Creatinina , Anemia Falciforme/epidemiologia , Hemoglobina FalciformeRESUMO
BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare, chronic, and life-threatening childhood autoimmune disease. Currently, there are recommended, reliable and validated measurement tools for assessment of skin disease activity in JDM including the Disease Activity Score (skinDAS), Cutaneous Assessment Tool (CAT), and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). The Physician's global assessment skin visual analog scale (Skin VAS) is also widely used for skin activity in JDM. For the purpose of comparative international studies, we wanted to compare these tools to the Physician's skin VAS (as a standard) to identify which performs better. OBJECTIVES: We sought to compare the correlations of these scoring tools, and separately assess the responsiveness each tool demonstrates following patient treatment, in order to see if one tool may be preferred. This was determined by assessing how well these tools correlate with each other, and the Physician's skin VAS over time, as well as the responsiveness of each tool after patient treatment. METHODS: Skin scores were recorded at a baseline (first visit after June 1st, 2018) and all follow-up office visits at the Juvenile Dermatomyositis Clinic. Following baseline visits, patients were followed up as clinically indicated. A subset of newly diagnosed patients (inception cohort) was identified. Correlations were assessed at the baseline visit and over time for the whole cohort. The correlations over time were derived using Generalized Estimating Equations (GEEs). Standardized response means with 95% confidence intervals were calculated to test score responsiveness for the nested inception cohort. RESULTS: The skinDAS, CAT and CDASI all correlated highly with each other and with the Physician's skin VAS. The three scoring tools accurately reflected Physician's skin VAS scores over time. In addition, all tools showed moderate to high responsiveness following treatment. CONCLUSION: All studied skin score tools performed well in our study and appear to be useful. Since no tool far outperforms the others, arbitrary consensus will be needed to select a single standard measurement tool for the purposes of efficiency and global comparability.
Assuntos
Doenças Autoimunes , Dermatomiosite , Humanos , Dermatomiosite/diagnóstico , Pele , Consenso , Medição da DorRESUMO
Methotrexate (MTX) is widely employed for children with cancer, but is also associated with persistent cognitive deficits among survivors. The present study investigated the mechanisms behind long-term cognitive dysfunction after juvenile animals are treated with MTX. Male and female Long-Evans rats were treated with a combination of 6 systemic doses (0.5 mg/kg/dose intraperitoneally) and 4 intrathecal doses (1 mg/kg) beginning at post-natal age 3 weeks, a schedule designed to mimic repeated exposure given to children with leukemia. Behavioral testing was conducted at 60-61 weeks of age, followed by analysis of brain histolopathology. This MTX regimen had no acute toxicity and no effect on growth. The spatial memory and visual memory deficits observed at 13 and 17 weeks of age persisted 1 year after MTX exposure in both females and males. Significantly decreased cell proliferation and increased hippocampal microglial activation were observed in MTX-treated females when compared to the controls, with a similar trend in the male groups. In addition, MTX treatment significantly increased the number of TUNEL positive cells in the periventricular area. Our study demonstrates that a clinically relevant regimen of systemic and intrathecal MTX induces persistent deficits in cognition, lasting approximately 1 year after the last injection. The mechanisms behind MTX-induced deficits are likely multifactorial, including suppression of neurogenesis, microglial activation, and increased brain cell apoptosis. Our study suggests female and male animals differ in susceptibility to MTX-induced neurotoxicity and provides insights for developing therapeutic approaches to prevent treatment related cognitive impairment among children with ALL.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/fisiopatologia , Metotrexato/farmacologia , Síndromes Neurotóxicas/fisiopatologia , Fatores Etários , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Sobreviventes de Câncer , Modelos Animais de Doenças , Feminino , Masculino , Metotrexato/administração & dosagem , Microglia/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Ratos , Ratos Long-Evans , Fatores Sexuais , Fatores de TempoRESUMO
A major advancement in the use of radio telemetry has been the development of automated radio tracking systems (ARTS), which allow animal movements to be tracked continuously. A new ARTS approach is the use of a network of simple radio receivers (nodes) that collect radio signal strength (RSS) values from animal-borne radio transmitters. However, the use of RSS-based localization methods in wildlife tracking research is new, and analytical approaches critical for determining high-quality location data have lagged behind technological developments. We present an analytical approach to optimize RSS-based localization estimates for a node network designed to track fine-scale animal movements in a localized area. Specifically, we test the application of analytical filters (signal strength, distance among nodes) to data from real and simulated node networks that differ in the density and configuration of nodes. We evaluate how different filters and network configurations (density and regularity of node spacing) may influence the accuracy of RSS-based localization estimates. Overall, the use of signal strength and distance-based filters resulted in a 3- to 9-fold increase in median accuracy of location estimates over unfiltered estimates, with the most stringent filters providing location estimates with a median accuracy ranging from 28 to 73 m depending on the configuration and spacing of the node network. We found that distance filters performed significantly better than RSS filters for networks with evenly spaced nodes, but the advantage diminished when nodes were less uniformly spaced within a network. Our results not only provide analytical approaches to greatly increase the accuracy of RSS-based localization estimates, as well as the computer code to do so, but also provide guidance on how to best configure node networks to maximize the accuracy and capabilities of such systems for wildlife tracking studies.