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1.
R Soc Open Sci ; 11(6): 240601, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39253402

RESUMO

Genetic differentiation between populations inhabiting ecologically different habitats might appear because of limited dispersal and gene flow, which may lead to patterns of phenotypic divergence and local adaptation. In this study, we use dispersal, genotypic (24 microsatellite loci) and phenotypic (body size and clutch size) data to analyse patterns of genetic structuring and phenotypic divergence in a blue tit (Cyanistes caeruleus) population inhabiting a continuous and heterogeneous woodland along a valley. The two slopes of the valley differ in their forest formations and environmental conditions. Findings showed that most blue tits reproduced within their natal slope. Accordingly, microsatellite analyses revealed that populations of blue tits established in the two slopes show subtle genetic differentiation. The two genetic populations diverged in clutch size, exceeding the level of differentiation expected based on genetic drift, hence suggesting divergent selection (or other processes promoting divergence) on this life-history trait. Our findings reveal that restricted dispersal and spatial heterogeneity may lead to genetic differentiation among bird populations at a surprisingly small scale. In this respect, it is worth highlighting that such differentiation occurs for an organism with high dispersal capacity and within a continuous woodland. Moreover, we show that small-scale ecological differences, together with limited gene flow, can result in selection favouring different phenotypes even within the same continuum population.

2.
Interv Pain Med ; 3(1): 100379, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39239498

RESUMO

Objectives: To evaluate the effectiveness of cervical transforaminal epidural steroid injection (CTFESI) for the treatment of unilateral cervical radicular pain. Design: Single-group prospective cohort study. Methods: Outcomes included ≥50% reductions in Numeric Rating Scale (NRS) for arm pain, ≥30% Neck Disability Index (NDI-5) improvement, health-related quality of life (EQ-5D), global improvement (PGIC), personal goal achievement (COMBI), Chronic Pain Sleep Index (CPSI), and healthcare utilization at one, three, six, and 12 months. Data analysis included descriptive statistics with the calculations of 95% confidence intervals (CIs), contingency table analysis, and multilevel logistic regression (LR) analysis, including a worst-case (WC) sensitivity analysis in which missing data were treated as treatment failure. Participants who were treated surgically were considered failures in the categorical analyses. Results: 33 consecutively enrolled participants (63.6% females, 51.2 ± 12.2 years of age, BMI 28.3 ± 4.5 kg/m2) were analyzed. Success rates for ≥50% reduction in NRS for arm pain at one, three, six and 12 months were 57.6% (95% CI 40.8-72.8%), 71.9% (95% CI 54.6-84.4%), 64.5% (95% CI 46.9-78.9%), and 64.5% (95% CI 46.9-78.9%). Success rates for ≥30% improvement in NDI-5 were 60.6% (95% CI 43.7-75.3%), 68.8% (95% CI 51.4-82.0%), 61.3% (95% CI 43.8-76.3%), and 71.0% (95% CI 53.4-83.9%). In WC analysis, success rates for ≥50% arm NRS and NDI-5 were 0-4.3% lower between 1 and 12 months. PGIC scores were at least "much improved" or "very much improved," in 48.4-65.6% of participants between 1 and 12 months. 6.1%, 6.1%, and 3.0% had one, two, or three repeat injections, respectively. 18.2% of participants underwent surgery by 12 months. Participants showed significant improvements in arm NRS and NDI-5 after treatment (p < 0.05), multilevel logistic regression models showed no significant decline in improvements across the follow-up time points (p > 0.05). Conclusion: Statistically significant and clinically meaningful improvements in pain and disability were observed after CTFESI for up to 12 months in individuals with unilateral cervical radicular pain.

3.
JAMA ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259563

RESUMO

Importance: Numerous studies show that early palliative care improves quality of life and other key outcomes in patients with advanced cancer and their caregivers, although most lack access to this evidence-based model of care. Objective: To evaluate whether delivering early palliative care via secure video vs in-person visits has an equivalent effect on quality of life in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: Randomized, multisite, comparative effectiveness trial from June 14, 2018, to May 4, 2023, at 22 US cancer centers among 1250 patients within 12 weeks of diagnosis of advanced NSCLC and 548 caregivers. Intervention: Participants were randomized to meet with a specialty-trained palliative care clinician every 4 weeks either via video visit or in person in the outpatient clinic from the time of enrollment and throughout the course of disease. The video visit group had an initial in-person visit to establish rapport, followed by subsequent virtual visits. Main Outcomes and Measures: Equivalence of the effect of video visit vs in-person early palliative care on quality of life at week 24 per the Functional Assessment of Cancer Therapy-Lung questionnaire (equivalence margin of ±4 points; score range: 0-136, with higher scores indicating better quality of life). Participants completed study questionnaires at enrollment and at weeks 12, 24, 36, and 48. Results: By 24 weeks, participants (mean age, 65.5 years; 54.0% women; 82.7% White) had a mean of 4.7 (video) and 4.9 (in-person) early palliative care encounters. Patient-reported quality-of-life scores were equivalent between groups (video mean, 99.7 vs in-person mean, 97.7; difference, 2.0 [90% CI, 0.1-3.9]; P = .04 for equivalence). Rate of caregiver participation in visits was lower for video vs in-person early palliative care (36.6% vs 49.7%; P < .001). Study groups did not differ in caregiver quality of life, patient coping, or patient and caregiver satisfaction with care, mood symptoms, or prognostic perceptions. Conclusions and Relevance: The delivery of early palliative care virtually vs in person demonstrated equivalent effects on quality of life in patients with advanced NSCLC, underscoring the considerable potential for improving access to this evidence-based care model through telehealth delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03375489.

4.
PLoS Negl Trop Dis ; 18(9): e0012482, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39255310

RESUMO

BACKGROUND: Climate change and urbanization will alter the global distribution of disease vectors, changing the disease burden in yet unpredictable ways. Aedes aegypti is a mosquito responsible for transmitting dengue, Zika, chikungunya, and yellow fever viruses that breeds in containers associated with urban environments. We sought to understand how ambient temperature and larval densities in the immature aquatic phases determine adult life history traits and dengue virus loads post-infection. We predicted that larval crowding and high temperatures would both lead to smaller mosquitoes that might struggle to invest in an immune response and, hence, would exhibit high viral loads. METHODS: We first examined larval densities from urban and rural areas via a meta-analysis. We then used these data to inform a laboratory-based 2x2 design examining the interacting effects of temperature (21 vs. 26°C) and density (0.2 vs. 0.4 larvae/mL) on adult life history and dengue virus loads. RESULTS: We found that urban areas had an ~8-fold increase in larval densities compared to more rural sites. In the lab, we found that crowding had more impact on mosquito traits than temperature. Crowding led to slower development, smaller mosquitoes, less survival, lower fecundity, and higher viral loads, as predicted. The higher temperature led to faster development, reduced fecundity, and lower viral loads. The virus-reducing effect of higher temperature rearing was, however, overwhelmed by the impact of larval crowding when both factors were present. CONCLUSIONS: These data reveal complex interactions between the environmental effects experienced by immature mosquitoes and adult traits. They especially highlight the importance of crowding with respect to adult viral loads. Together, these data suggest that urban environments might enhance dengue virus loads and, therefore, possibly transmission, a concerning result given the increasing rates of urbanization globally.


Assuntos
Aedes , Vírus da Dengue , Dengue , Larva , Mosquitos Vetores , Carga Viral , Aedes/virologia , Aedes/fisiologia , Animais , Vírus da Dengue/fisiologia , Larva/virologia , Dengue/transmissão , Dengue/virologia , Mosquitos Vetores/virologia , Mosquitos Vetores/fisiologia , Mosquitos Vetores/crescimento & desenvolvimento , Temperatura , Feminino , Aglomeração , Humanos
5.
Psychiatry Res Commun ; 4(1)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39301562

RESUMO

People may be more likely to exercise if they have self-efficacy for exercise (SEE). We conducted an exploratory analysis of SEE using data from a clinical trial designed to increase physical activity (N = 340). We evaluated correlates of baseline SEE and the relationship between baseline SEE and physical activity. Low SEE at baseline was correlated with lower well-being, physical activity, and higher depression at baseline. Participants with high (vs. low) baseline SEE had higher physical activity (but no differential change in activity) over time. These data highlight the potential role of SEE in psychological health and physical activity.

6.
Sci Data ; 11(1): 1031, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333537

RESUMO

We present the Manually Annotated GONG Filaments in H-alpha Observations (MAGFiLO v1.0) dataset. This dataset contains 10,244 annotated filaments from 1,593 observations captured by the Global Oscillation Network Group (GONG), spanning the years 2011 through 2022. Each annotation details one filament's segmentation, minimum bounding box, spine, and magnetic field chirality. With a total of over one thousand person-hours of annotation, and a double-blind review process, we ensured high-quality ground-truth data. Our inter-annotator agreement reaches a Kappa score of 0.66. We also verified that the hemispheric preference of filaments as annotated in MAGFiLO aligns with the findings from similar datasets of much smaller sample sizes. MAGFiLO is the first dataset of its size, enabling advanced deep learning models to identify filaments and their features with unprecedented precision. It also provides a testbed for solar physicists interested in large-scale analysis of filaments. In this report, we document the details of the annotation and the post-processing phases that were applied.

7.
Nat Chem Biol ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103633

RESUMO

Clinical resistance to rat sarcoma virus (Ras)-G12C inhibitors is a challenge. A subpopulation of cancer cells has been shown to undergo genomic and transcriptional alterations to facilitate drug resistance but the immediate adaptive effects on Ras signaling in response to these drugs at the single-cell level is not well understood. Here, we used Ras biosensors to profile the activity and signaling environment of endogenous Ras at the single-cell level. We found that a subpopulation of KRas-G12C cells treated with Ras-G12C-guanosine-diphosphate inhibitors underwent adaptive signaling and metabolic changes driven by wild-type Ras at the Golgi and mutant KRas at the mitochondria, respectively. Our Ras biosensors identified major vault protein as a mediator of Ras activation through its scaffolding of Ras signaling pathway components and metabolite channels. Overall, methods including ours that facilitate direct analysis on the single-cell level can report the adaptations that subpopulations of cells adopt in response to cancer therapies, thus providing insight into drug resistance.

8.
J Clin Oncol ; : JCO2400048, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088766

RESUMO

PURPOSE: In patients with lung cancer, dyspnea is one of the most prevalent and disabling symptoms, for which effective treatments are lacking. We examined the efficacy of a nurse-led brief behavioral intervention to improve dyspnea in patients with advanced lung cancer. METHODS: Patients with advanced lung cancer reporting at least moderate breathlessness (n = 247) were enrolled in a randomized trial of a nurse-led two-session intervention (focused on breathing techniques, postural positions, and fan therapy) versus usual care. At baseline and weeks 8 (primary end point), 16, and 24, participants completed measures of dyspnea (Modified Medical Research Council Dyspnea Scale [mMRCDS]; Cancer Dyspnoea Scale [CDS]), quality of life (Functional Assessment of Cancer Therapy-Lung [FACT-L]), psychological symptoms (Hospital Anxiety and Depression Scale), and activity level (Godin-Shephard Leisure Time Physical Activity Questionnaire). To examine intervention effects, we conducted analysis of covariance and longitudinal mixed effects models. RESULTS: The sample (Agemean = 66.15 years; 55.9% female) primarily included patients with advanced non-small cell lung cancer (85.4%). Compared with usual care, the intervention improved the primary outcome of patient-reported dyspnea on the mMRCDS (difference = -0.33 [95% CI, -0.61 to -0.05]) but not the CDS total score at 8 weeks. Intervention patients also reported less dyspnea on the CDS sense of discomfort subscale (difference = -0.59 [95% CI, -1.16 to -0.01]) and better functional well-being per the FACT-L (difference = 1.39 [95% CI, 0.18 to 2.59]) versus the control group. Study groups did not differ in overall quality of life, psychological symptoms, or activity level at 8 weeks or longitudinally over 24 weeks. CONCLUSION: For patients with advanced lung cancer, a scalable behavioral intervention alleviated the intractable symptom of dyspnea. Further research is needed on ways to enhance intervention effects over the long-term and across additional outcomes.

9.
Endocr Pract ; 30(10): 963-969, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39025300

RESUMO

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m2 (CKD stage 4), eGFR<15 mL/min/1.73 m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Masculino , Feminino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Idoso , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Estudos de Coortes , Insuficiência Renal , Idoso de 80 Anos ou mais , Diálise Renal
10.
J Sport Rehabil ; 33(7): 570-581, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39069291

RESUMO

CONTEXT: Horizontal hops can provide insight into how athletes can tolerate high-intensity single-leg stretch loads and are commonly used in athlete monitoring and injury management. Variables like flight, contact, and total time provide valuable diagnostic information to sports science professionals. However, gold-standard assessment tools (eg, 3-dimensional motion capture, force plates) require monetary and technological resources. Therefore, we used a tablet and free software to determine the between-rater, within-rater, and test-retest variability of the temporal events of multiple horizontal hop tests. DESIGN: Reliability study. METHODS: Nine healthy males (20.8 [1.3] y, 71.4 [9.8] kg, 171.7 [4.5] cm) across various university sports teams and clubs volunteered and performed several triple (3-Hop) and quintuple (5-Hop) horizontal hops over 3 testing sessions. Six raters detected temporal events from video to determine between-rater variability, while a single rater quantified within-session and test-retest variability. The temporal variables of flight time, ground contact time for each individual hop, and the total time of each hoping series were determined. The consistency of measures was interpreted using the coefficient of variation and interclass correlation coefficients (ICC). RESULTS: Good to excellent between-rater consistency was observed for all hops (ICC = .85-1.00). Absolute (coefficient of variation ≤ 2.0%) and relative consistency (ICC = .98-1.00) was excellent. Test-retest variability showed acceptable levels of absolute consistency (coefficient of variation ≤ 8.7%) and good to excellent consistency in 10/16 variables (ICC = .81-.93), especially those later in the hopping cycle. CONCLUSIONS: A tablet and free digitizing software are reliable in detecting temporal events during multiple horizontal hops, which could have exciting implications for power diagnostics and return-to-play decisions. Therefore, rehabilitation and performance professionals can confidently utilize the highly accessible equipment from this study to track multiple hop performances.


Assuntos
Gravação em Vídeo , Humanos , Masculino , Adulto Jovem , Reprodutibilidade dos Testes , Teste de Esforço/métodos , Teste de Esforço/normas , Desempenho Atlético/fisiologia , Fenômenos Biomecânicos
11.
Kidney Int ; 106(4): 723-735, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38969296

RESUMO

Glomerular filtration rate (GFR) decline is used as surrogate endpoint for kidney failure. Interventions that reduce chronic kidney disease (CKD) progression often exert acute GFR reductions which differ from their long-term benefits and complicate the estimation of long-term benefit. Here, we assessed the utility of two alternative trial designs (wash-out design and active run-in randomized withdrawal design) that attempt to exclude the impact of acute effects. Post-hoc analyses of two clinical trials that characterized the effect of an intervention with acute reductions in GFR were conducted. The two trials included a wash-out period (EMPA-REG Outcome testing empagliflozin vs placebo) or an active run-in period with a randomized withdrawal (SONAR testing atrasentan vs placebo). We compared the drug effect on GFR decline calculated from the first on-treatment visit to the end of treatment (chronic slope in a standard randomized trial design) with GFR change calculated from randomization to end of wash out, or GFR change from treatment-specific baseline GFR values (GFR at start-of-run-in for placebo and end-of-run-in for atrasentan) until end-of-treatment. The effect of empagliflozin versus placebo on chronic GFR slope was 1.72 (95% confidence interval 1.49-1.94) mL/min/1.73 m2/year, similar to total GFR decline from baseline to the end of wash-out period using a linear mixed model 1.64 (1.44-1.85) mL/min/1.73 m2/year). The effect of atrasentan versus placebo on chronic GFR slope was 0.72 (0.32-1.11) mL/min/1.73 m2/year, similar to total slope from a single slope model when estimated from treatment specific baseline GFR values 0.77 (0.39-1.14) mL/min/1.73 m2/year). Statistical power of the two designs outperformed the standard randomized design. Thus, wash-out and active-run-in randomized-withdrawal trial designs are appropriate models to compute treatment effects on GFR decline.


Assuntos
Atrasentana , Compostos Benzidrílicos , Taxa de Filtração Glomerular , Glucosídeos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/diagnóstico , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Masculino , Feminino , Atrasentana/uso terapêutico , Atrasentana/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Pessoa de Meia-Idade , Projetos de Pesquisa , Idoso , Progressão da Doença , Resultado do Tratamento , Rim/fisiopatologia , Rim/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Antagonistas do Receptor de Endotelina A/uso terapêutico
12.
Eur J Appl Physiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953975

RESUMO

PURPOSE: Eccentric quasi-isometric (EQI) resistance training is emerging as a promising option in sports medicine and rehabilitation. Despite prior research on EQI contractions in quadriceps and biceps brachii, their use in hamstring injury contexts is underexplored. Therefore, our study examines and contrasts the biomechanics and fatigue effects of EQI training on knee extensors and flexors. METHODS: Following familiarization, 16 healthy, active participants (9 men, 7 women; 23.5 ± 2.6 years, 72.1 ± 12.8 kg, 173.4 ± 10.7 cm) performed, in random order, four EQI contractions for knee extensions and flexions, respectively. EQI contractions were isotonically loaded to 70% of concentric (60°·s-1) maximal voluntary contraction. Rest between repetitions was set at three minutes, while four minutes separated each muscle group. Peak torque, mean torque, and optimal angle were evaluated pre- and post-bouts. Inter-repetition contraction time and angular velocity were also assessed. RESULTS: Average torque was 160.9 ± 44.2 and 71.5 ± 23.2 Nm for the extensors and flexors. Peak and mean torque significantly decreased for both extensors (p < 0.001, d = 0.70-0.71) and flexors (p ≤ 0.022, d = 0.36) after EQI contractions, respectively. However, the optimal angle increased for extensors (p < 0.001, d = 1.00) but not flexors (p = 0.811, d = 0.06). During EQI contractions, knee flexors exhibited greater intra-repetition velocity than extensors (p = 0.002; η2 = 0.50). Decreases in inter-repetition time and range of motion were more consistent for the extensors. CONCLUSIONS: Distinct responses exist when comparing EQI contractions of the knee extensors and flexors, particularly their effect on peak torque angles. These findings suggest knee flexors may require lower relative intensities to align more closely with extensor EQI contractions.

13.
Anal Chem ; 96(29): 11751-11759, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-38980117

RESUMO

Neutralizing antibodies (nAbs) produced from infection or vaccination play an important role in acquired immunity. Determining virus-specific nAb titers is a useful tool for measuring aquired immunity in an individual. The standard methods to do so rely on titrating serum samples against live virus and monitoring viral infection in cultured cells which requires high biosafety level containment. The surrogate virus neutralization test (sVNT) reduces the biohazards and it is suitable for designing rapid test device in a lateral flow assay (LFA) format. Here, we introduce the fabrication and development of a unique paper-based LFA device for determining the level of SARS-CoV-2 nAb in a sample with a semiquantitative direct colorimetric readout. A LFA-based gradient assay design was used to facilitate the sVNT, where the spike glycoprotein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) stand in as proxies for viruses and cells, respectively. The gradient assay employed multiple test dots of ACE2 spotted in increasing concentration along the sample flow path and gold nanoparticle-conjugated RBD for readout. In this way, the number of developed spots is inversely proportional to the concentration of nAbs present in the sample. The assay was tested with both standard solutions of nAb as well as human serum samples. We have demonstrated that the device can effectively provide semiquantitative test results of nAbs by direct instrument-free colorimetric detection.


Assuntos
Anticorpos Neutralizantes , COVID-19 , Testes de Neutralização , Papel , SARS-CoV-2 , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Humanos , Testes de Neutralização/métodos , COVID-19/diagnóstico , COVID-19/virologia , COVID-19/imunologia , COVID-19/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Colorimetria/métodos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
14.
JAMA ; 332(6): 471-481, 2024 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-38824442

RESUMO

Importance: Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. Objective: To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Design, Setting, and Participants: Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Intervention: Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Main Outcomes and Measures: Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. Results: The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). Conclusions and Relevance: A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03337399.


Assuntos
Neoplasias Pulmonares , Cuidados Paliativos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Cuidados Paliativos/métodos , Assistência Centrada no Paciente , Qualidade de Vida , Assistência Terminal/métodos , Estadiamento de Neoplasias
15.
Artigo em Inglês | MEDLINE | ID: mdl-38885096

RESUMO

Peripheral nerve stimulation (PNS) is an effective means to elicit sensation for rehabilitation of people with loss of a limb or limb function. While most current PNS paradigms deliver current through single electrode contacts to elicit each tactile percept, multi-contact extraneural electrodes offer the opportunity to deliver PNS with groups of contacts individually or simultaneously. Multi-contact PNS strategies could be advantageous in developing biomimetic PNS paradigms to recreate the natural neural activity during touch, because they may be able to selectively recruit multiple distinct neural populations. We used computational models and optimization approaches to develop a novel biomimetic PNS paradigm that uses interleaved multi-contact (IMC) PNS to approximate the critical neural coding properties underlying touch. The IMC paradigm combines field shaping, in which two contacts are active simultaneously, with pulse-by-pulse contact and parameter variations throughout the touch stimulus. We show in simulation that IMC PNS results in better neural code mimicry than single contact PNS created with the same optimization techniques, and that field steering via two-contact IMC PNS results in better neural code mimicry than one-contact IMC PNS. We also show that IMC PNS results in better neural code mimicry than existing PNS paradigms, including prior biomimetic PNS. Future clinical studies will determine if the IMC paradigm can improve the naturalness and usefulness of sensory feedback for those with neurological disorders.


Assuntos
Simulação por Computador , Nervos Periféricos , Tato , Humanos , Tato/fisiologia , Nervos Periféricos/fisiologia , Modelos Neurológicos , Biomimética , Algoritmos , Eletrodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Percepção do Tato/fisiologia
16.
Phys Med Rehabil Clin N Am ; 35(3): 637-650, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945656

RESUMO

Achieving effective community reintegration is important to maximize recovery in patients with traumatic brain injury, simultaneously limiting caregiver burden and improving satisfaction with quality of life. Certain medical complications that are common after brain injury may impact community reintegration, and should be addressed by the physician in a systematic approach. Additionally certain social and environmental factors such as mobility or return to work or school may arise, and should be addressed proactively by the physician. Inpatient/residential or outpatient programs with case management and a multi-disciplinary team can facilitate community reentry for patients, and should be considered when available.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/reabilitação , Lesões Encefálicas Traumáticas/psicologia , Integração Comunitária , Qualidade de Vida
17.
J Neural Eng ; 21(3)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38861967

RESUMO

Objective. We intend to chronically restore somatosensation and provide high-fidelity myoelectric control for those with limb loss via a novel, distributed, high-channel-count, implanted system.Approach.We have developed the implanted Somatosensory Electrical Neurostimulation and Sensing (iSens®) system to support peripheral nerve stimulation through up to 64, 96, or 128 electrode contacts with myoelectric recording from 16, 8, or 0 bipolar sites, respectively. The rechargeable central device has Bluetooth® wireless telemetry to communicate to external devices and wired connections for up to four implanted satellite stimulation or recording devices. We characterized the stimulation, recording, battery runtime, and wireless performance and completed safety testing to support its use in human trials.Results.The stimulator operates as expected across a range of parameters and can schedule multiple asynchronous, interleaved pulse trains subject to total charge delivery limits. Recorded signals in saline show negligible stimulus artifact when 10 cm from a 1 mA stimulating source. The wireless telemetry range exceeds 1 m (direction and orientation dependent) in a saline torso phantom. The bandwidth supports 100 Hz bidirectional update rates of stimulation commands and data features or streaming select full bandwidth myoelectric signals. Preliminary first-in-human data validates the bench testing result.Significance.We developed, tested, and clinically implemented an advanced, modular, fully implanted peripheral stimulation and sensing system for somatosensory restoration and myoelectric control. The modularity in electrode type and number, including distributed sensing and stimulation, supports a wide variety of applications; iSens® is a flexible platform to bring peripheral neuromodulation applications to clinical reality. ClinicalTrials.gov ID NCT04430218.


Assuntos
Eletromiografia , Humanos , Eletromiografia/métodos , Eletrodos Implantados , Tecnologia sem Fio/instrumentação , Telemetria/instrumentação , Telemetria/métodos , Desenho de Equipamento/métodos , Músculo Esquelético/fisiologia , Músculo Esquelético/inervação
18.
J Am Chem Soc ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836636

RESUMO

The rate of frontal ring-opening metathesis polymerization (FROMP) using the Grubbs generation II catalyst is impacted by both the concentration and choice of monomers and inhibitors, usually organophosphorus derivatives. Herein we report a data-science-driven workflow to evaluate how these factors impact both the rate of FROMP and how long the formulation of the mixture is stable (pot life). Using this workflow, we built a classification model using a single-node decision tree to determine how a simple phosphine structural descriptor (Vbur-near) can bin long versus short pot life. Additionally, we applied a nonlinear kernel ridge regression model to predict how the inhibitor and selection/concentration of comonomers impact the FROMP rate. The analysis provides selection criteria for material network structures that span from highly cross-linked thermosets to non-cross-linked thermoplastics as well as degradable and nondegradable materials.

19.
J Am Acad Orthop Surg ; 32(18): 849-855, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38718257

RESUMO

INTRODUCTION: The prevalence of sacroiliac joint (SIJ) pathology generating lower back pain is increasing, often requiring SI joint fusion in refractory cases. Similarly, total hip arthroplasty (THA) is an increasing procedure in the older growing population. Prior SIJ fusion in patients undergoing THA has increased hip dislocation. This study aims to determine the prevalence of preexisting THA in SIJ fusion patients at our institution. METHODS: After institutional review board approval, we completed a retrospective review of consecutive SIJ fusion cases performed by fellowship-trained orthopaedic spine surgeons between October 2019 and June 2022. The senior surgeon reviewed pelvis radiographs to determine whether a THA was present. Patient demographics, surgical history, SIJ fusion date, and laterality information from study participants' medical records were collected and analyzed. RESULTS: We screened 157 consecutive cases and excluded 45 not meeting the inclusion criteria. One hundred twelve radiographs were reviewed, with seven additional patients excluded. The final analysis consisted of 105 patients (33M:72F). The mean age was 50.4 ± 13.8 years, and the mean body mass index was 29.1 ± 6.1 kg/m 2 . SIJ fusion laterality included 51 right (48.6%), 44 left (41.9%), and 10 bilateral (9.5%). One patient (0.95%) had a preexisting right THA, and two patients (1.9%) underwent ipsilateral THA after SIJ fusion. CONCLUSIONS: This study demonstrated a low prevalence (0.95%) of preexisting THA in SIJ fusion patients at our institution, similar to the THA prevalence of the total US population. Additional research is needed to determine the outcomes of patients with preexisting THA undergoing SIJ fusion.


Assuntos
Artroplastia de Quadril , Articulação Sacroilíaca , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevalência , Adulto , Fusão Vertebral , Idoso
20.
J Sport Health Sci ; 13(6): 820-840, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38754733

RESUMO

BACKGROUND: Assessment and quantification of skeletal muscle within the aging population is vital for diagnosis, treatment, and injury/disease prevention. The clinical availability of assessing muscle quality through diagnostic ultrasound presents an opportunity to be utilized as a screening tool for function-limiting diseases. However, relationships between muscle echogenicity and clinical functional assessments require authoritative analysis. Thus, we aimed to (a) synthesize the literature to assess the relationships between skeletal muscle echogenicity and physical function in older adults (≥60 years), (b) perform pooled analyses of relationships between skeletal muscle echogenicity and physical function, and (c) perform sub-analyses to determine between-muscle relationships. METHODS: CINAHL, Embase, MEDLINE, PubMed, and Web of Science databases were systematically searched to identify articles relating skeletal muscle echogenicity to physical function in older adults. Risk-of-bias assessments were conducted along with funnel plot examination. Meta-analyses with and without sub-analyses for individual muscles were performed utilizing Fisher's Z transformation for the most common measures of physical function. Fisher's Z was back-transformed to Pearson's r for interpretation. RESULTS: Fifty-one articles (n = 5095, female = ∼2759, male = ∼2301, 72.5 ± 5.8 years, mean ± SD (1 study did not provide sex descriptors)) were extracted for review, with previously unpublished data obtained from the authors of 13 studies. The rectus femoris (n = 34) and isometric knee extension strength (n = 22) were the most accessed muscle and physical qualities, respectively. The relationship between quadriceps echogenicity and knee extensor strength was moderate (n = 2924, r = -0.36 (95% confidence interval: -0.38 to -0.32), p < 0.001), with all other meta-analyses (grip strength, walking speed, sit-to-stand, timed up-and-go) resulting in slightly weaker correlations (r:  -0.34 to -0.23, all p < 0.001). Sub-analyses determined minimal differences in predictive ability between muscle groups, although combining muscles (e.g., rectus femoris + vastus lateralis) often resulted in stronger correlations with maximal strength. CONCLUSION: While correlations are modest, the affordable, portable, and noninvasive ultrasonic assessment of muscle quality is a consistent predictor of physical function in older adults. Minimal between-muscle differences suggest that echogenicity estimates of muscle quality are systemic. Therefore, practitioners may be able to scan a single muscle to estimate full-body skeletal muscle quality/composition, while researchers should consider combining multiple muscles to strengthen the model.


Assuntos
Força Muscular , Músculo Esquelético , Ultrassonografia , Humanos , Idoso , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Força Muscular/fisiologia , Envelhecimento/fisiologia , Pessoa de Meia-Idade
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