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1.
bioRxiv ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38106053

RESUMO

Diverse neuron classes in hippocampal CA1 have been identified through the heterogeneity of their cellular/molecular composition. How these classes relate to hippocampal function and the network dynamics that support cognition in primates remains unclear. Here we report inhibitory functional cell groups in CA1 of freely-moving macaques whose diverse response profiles to network states and each other suggest distinct and specific roles in the functional microcircuit of CA1. In addition, pyramidal cells that were segregated into superficial and deep layers differed in firing rate, burstiness, and sharp-wave ripple-associated firing. They also showed strata-specific spike-timing interactions with inhibitory cell groups, suggestive of segregated neural populations. Furthermore, ensemble recordings revealed that cell assemblies were preferentially organized according to these strata. These results suggest sublayer-specific circuit organization in hippocampal CA1 of the freely-moving macaques that may underlie its role in cognition.

2.
Brain Stimul ; 17(1): 35-38, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38128826

RESUMO

BACKGROUND: Essential tremor (ET) can be debilitating. Treatments for ET include beta-blockers and surgical interventions. Low-intensity focused ultrasound (LIFU) may offer an office-based non-invasive alternative. OBJECTIVE: This pilot open label clinical trial explores safety, feasibility, and potential efficacy of LIFU in treatment of ET. METHODS: We report outcomes from the first 10 participants in this IRB-approved trial of LIFU for treatment of ET. The ventral intermediate nucleus of the thalamus (Vim) was targeted using structural and functional MRI. Participants underwent eight 10-min sessions of LIFU targeting the contralateral (Vim) to the most affected hand. Safety was closely monitored; Global Rating of Change (GRC) and The Essential Tremor Rating Scale (TETRAS) scores were collected. RESULTS: No adverse effects were reported. Eight participants reported a GRC ≥2. TETRAS performance subscale demonstrated clinically significant improvement in all participants. CONCLUSION: Preliminary findings support LIFU's safety and feasibility. The potential efficacy encourages additional sham-controlled studies.


Assuntos
Tremor Essencial , Tremor , Humanos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/terapia , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem , Resultado do Tratamento , Projetos Piloto
3.
Scand J Trauma Resusc Emerg Med ; 31(1): 100, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093335

RESUMO

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Idoso , Estudos Prospectivos , Estudos de Viabilidade , Austrália , Parada Cardíaca Extra-Hospitalar/terapia , Hospitais , Reperfusão , Estudos Retrospectivos
4.
bioRxiv ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38168449

RESUMO

Flexible learning is a hallmark of primate cognition, which arises through interactions with changing environments. Studies of the neural basis for this flexibility are typically limited by laboratory settings that use minimal environmental cues and restrict interactions with the environment, including active sensing and exploration. To address this, we constructed a 3-D enclosure containing touchscreens on its walls, for studying cognition in freely moving macaques. To test flexible learning, two monkeys completed trials consisting of a regular sequence of object selections across four touchscreens. On each screen, the monkeys had to select by touching the sole correct object item ('target') among a set of four items, irrespective of their positions on the screen. Each item was the target on exactly one screen of the sequence, making correct performance conditioned on the spatiotemporal sequence rule across screens. Both monkeys successfully learned multiple 4-item sets (N=14 and 22 sets), totaling over 50 and 80 unique, conditional item-context memoranda, with no indication of capacity limits. The enclosure allowed freedom of movements leading up to and following the touchscreen interactions. To determine whether movement economy changed with learning, we reconstructed 3D position and movement dynamics using markerless tracking software and gyroscopic inertial measurements. Whereas general body positions remained consistent across repeated sequences, fine head movements varied as monkeys learned, within and across sequence sets, demonstrating learning set or "learning to learn". These results demonstrate monkeys' rapid, capacious, and flexible learning within an integrated, multisensory 3-D space. Furthermore, this approach enables the measurement of continuous behavior while ensuring precise experimental control and behavioral repetition of sequences over time. Overall, this approach harmonizes the design features that are needed for electrophysiological studies with tasks that showcase fully situated, flexible cognition.

5.
ESMO Open ; 7(4): 100530, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35921760

RESUMO

BACKGROUND: Activation of leukemia inhibitory factor (LIF) is linked to an immunosuppressive tumor microenvironment (TME), with a strong association between LIF expression and tumor-associated macrophages (TAMs). MSC-1 (AZD0171) is a humanized monoclonal antibody that binds with high affinity to LIF, promoting antitumor inflammation through TAM modulation and cancer stem cell inhibition, slowing tumor growth. In this phase I, first-in-human, open-label, dose-escalation study, MSC-1 monotherapy was assessed in patients with advanced, unresectable solid tumors. MATERIALS AND METHODS: Using accelerated-titration dose escalation followed by a 3 + 3 design, MSC-1 doses of 75-1500 mg were administered intravenously every 3 weeks (Q3W) until progression or unmanageable toxicity. Additional patients were enrolled in selected cohorts to further evaluate safety, pharmacokinetics (PK), and pharmacodynamics after escalation to the next dose had been approved. The primary objective was characterizing safety and determining the recommended phase II dose (RP2D). Evaluating antitumor activity and progression-free survival (PFS) by RECIST v1.1, PK and immunogenicity were secondary objectives. Exploratory objectives included pharmacodynamic effects on circulating LIF and TME immune markers. RESULTS: Forty-one patients received treatment. MSC-1 monotherapy was safe and well tolerated at all doses, with no dose-limiting toxicities. The maximum tolerated dose was not reached and the RP2D was determined to be 1500 mg Q3W. Almost half of the patients had treatment-related adverse events (TRAEs), with no apparent trends across doses; no patients withdrew due to TRAEs. There were no objective responses; 23.7% had stable disease for ≥2 consecutive tumor assessments. Median PFS was 5.9 weeks; 23.7% had PFS >16 weeks. On-treatment changes in circulating LIF and TME signal transducers and activators of transcription 3 signaling, M1:M2 macrophage populations, and CD8+ T-cell infiltration were consistent with the hypothesized mechanism of action. CONCLUSIONS: MSC-1 was very well tolerated across doses, with prolonged PFS in some patients. Biomarker and preclinical data suggest potential synergy with checkpoint inhibitors.


Assuntos
Antineoplásicos , Neoplasias , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Humanos , Dose Máxima Tolerável , Microambiente Tumoral
7.
Math Biosci Eng ; 19(12): 11903-11934, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-36653980

RESUMO

A model with both casual and long-term partnerships is considered with respect to the impact of a pre-exposure prophylaxis (PrEP) on the spread of HIV. We consider the effect of the effectiveness of PrEP, the rate that susceptible individuals choose to take PrEP, and compliance with the daily dose of the pre-exposure prophylaxis. The rate of infection in long-term partnerships is computed using a linearized expected value as a means for including the nonlocal effects of long-term partnerships while maintaining computational feasibility. The reproduction numbers for models with casual partnerships, long-term partnerships, and a combination of both are analytically computed and global stability of both disease-free and endemic equilibria is shown. Sensitivity and PRCC analysis results suggest that increasing the compliance among the current PrEP users is a more effective strategy in the fight against the HIV epidemic than increased coverage with poor compliance. Furthermore, an analysis of the reproduction number shows that models with either casual or monogamous long-term partnerships can reach the desired $ R_0 < 1 $ threshold for high enough levels of compliance and uptake, however, a model with both casual and monogamous long-term partnerships will require additional interventions. Methods highlighted in this manuscript are applicable to other incurable diseases or diseases with imperfect vaccines effected by long-term partnerships.


Assuntos
Fármacos Anti-HIV , Epidemias , Infecções por HIV , Profilaxia Pré-Exposição , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Profilaxia Pré-Exposição/métodos , Reprodução , Epidemias/prevenção & controle , Fármacos Anti-HIV/uso terapêutico
8.
Phys Rev Lett ; 127(16): 162501, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723594

RESUMO

We report an improved measurement of the free neutron lifetime τ_{n} using the UCNτ apparatus at the Los Alamos Neutron Science Center. We count a total of approximately 38×10^{6} surviving ultracold neutrons (UCNs) after storing in UCNτ's magnetogravitational trap over two data acquisition campaigns in 2017 and 2018. We extract τ_{n} from three blinded, independent analyses by both pairing long and short storage time runs to find a set of replicate τ_{n} measurements and by performing a global likelihood fit to all data while self-consistently incorporating the ß-decay lifetime. Both techniques achieve consistent results and find a value τ_{n}=877.75±0.28_{stat}+0.22/-0.16_{syst} s. With this sensitivity, neutron lifetime experiments now directly address the impact of recent refinements in our understanding of the standard model for neutron decay.

9.
Dis Esophagus ; 34(12)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34155508

RESUMO

Geographic differences in eosinophilic esophagitis (EoE) prevalence suggest the possibility that environmental exposures contribute to EoE pathogenesis. We aimed to examine the association between environmental quality and risk of EoE, using the Environmental Quality Index (EQI), which provides quantification of environmental quality in five domains: air, land, water, built, and sociodemographic for all counties in the United States. To do this, we performed a case-control study in a large pathology database. EoE cases were defined by ≥15 eosinophils per high-power field with other pathologic diagnoses excluded; controls did not have EoE. The pathology data were geocoded and linked with the EQI by county of residence. Logistic regression was used to estimate odds ratio (OR and 95% confidence interval [CI]) of EoE with overall EQI and for each domain, after adjusting for sex, age, and proportion minority race or ethnicity at the county level (higher EQI score indicates worse environmental quality). Of 29,802 EoE cases and 593,329 controls analyzed, odds of EoE were highest in the worst quintile of EQI (OR 1.25; 95% CI: 1.04-1.50), which was largely explained by poor scores in the water domain (OR: 1.33; 1.17-1.50). Conversely, odds of EoE were reduced with higher scores in the air domain (OR: 0.87, 0.74-1.03) and land domain (OR 0.87; 0.76-0.99). Poor EQI, mostly reflected by poor water quality, was associated with increased odds of EoE, while poor air and land quality were inversely associated with EoE. Additional work to identify specific water pollutants that may have an etiologic role in EoE may be warranted.


Assuntos
Esofagite Eosinofílica , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/etiologia , Humanos , Razão de Chances , Prevalência , Estados Unidos/epidemiologia
10.
Contemp Clin Trials Commun ; 22: 100788, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34056143

RESUMO

OBJECTIVES: The COVID-19 pandemic has been a significant stressor worldwide and reports of psychological distress, depression, sedentary lifestyles, and overall decreased wellbeing are increasing. Yoga practices have been found to improve mental and physical health. The purpose of this randomized controlled trial is to compare Isha yoga practitioners to controls on perceived stress, resilience, wellbeing, and protection and recovery from COVID-19. Trial Design. In this prospective randomized control trial, the effects of yoga practices are being compared between seasoned yoga practitioners with two controls who are age (±3 years), gender matched, and living in the same neighborhood. METHODS: Participants will be asked to complete a series of web-based surveys at baseline, six weeks, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess stress, mood states, resilience, and overall wellbeing. Questionnaires, weekly activity diaries, and medical history, will be collected using REDCap. RESULTS: We hypothesize that routine yoga practice during the COVID-19 pandemic will reduce stress, enhance well-being, and provide protective effects against COVID-19. CONCLUSION: With the growing concern about the physical and mental impacts of COVID-19 and increased interest in alternative practices such as yogic practices, this study will contribute to the growing body of evidence about the safety and efficacy of yoga for emotional, mental, and physical health conditions.

11.
Clin Microbiol Infect ; 27(2): 283.e1-283.e7, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32505584

RESUMO

OBJECTIVES: Little is known about maturation of the airway microbiota during early childhood and the consequences of early-life antibiotic exposure. METHODS: In a population-based birth cohort of 902 healthy Finnish children, we applied deep neural network models to investigate the relationship between the nasal microbiota (measured by 16S rRNA gene sequencing at up to three time points) and child age during the first 24 months. We also performed stratified analyses according to antibiotic exposure during the age period 0-2 months. RESULTS: The dense deep neural network analysis successfully modelled the relationship between 232 bacterial genera and child age with a mean absolute error of 4.3 (95%CI 4.0-4.7) months. Similarly, the recurrent neural network analysis also successfully modelled the relationship between 215 genera and child age with a mean absolute error of 0.45 (95%CI 0.42-0.47) months. Among the genera, Staphylococcus spp. and members of the Corynebacteriaceae decreased with age, while Dolosigranulum and Moraxella increased with age in the first 2 years of life (all false discovery rate (FDR) = 0.001). In children without early-life antibiotic exposure, Dolosigranulum increased with age (FDR = 0.001). By contrast, in those with early-life antibiotic exposure, Haemophilus increased with age (FDR = 0.002). CONCLUSIONS: In this prospective birth cohort of healthy children, we demonstrated the development of the nasal microbiota, with shifts in specific genera constituting maturation, in the first 2 years of life. Antibiotic exposures during early infancy were related to different age-discriminatory bacteria.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/classificação , Nariz/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Fatores Etários , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Pré-Escolar , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Finlândia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Microbiota/efeitos dos fármacos , Redes Neurais de Computação , Nariz/efeitos dos fármacos , Filogenia , Estudos Prospectivos
12.
J Small Anim Pract ; 61(8): 504-511, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32692404

RESUMO

OBJECTIVE: To describe the clinical features and outcome of functional thyroid tumours in dogs. MATERIALS AND METHODS: Retrospective multi-institutional study of 70 dogs diagnosed with thyroid mass and concurrent hyperthyroidism. Clinical data regarding presentation, treatment, outcome and functional thyroid status were retrieved. RESULTS: Overall median survival of dogs with functional thyroid tumours was 35.1 months and 1- and 3-year survival rates were 83 and 49%, respectively. Median survival time was 72.6 months for dogs treated with surgical excision and 15.7 months for dogs that did not receive surgery. Of the 50 dogs treated by surgery and for which thyroid status was known following treatment, 64% developed hypothyroidism after surgery. Histopathologically confirmed metastasis was identified in 3% of dogs. CLINICAL SIGNIFICANCE: Dogs with functional thyroid tumours may survive a long time after surgical excision, although post-operative hypothyroidism is common.


Assuntos
Doenças do Cão , Hipotireoidismo/veterinária , Neoplasias da Glândula Tireoide/veterinária , Animais , Cães , Estudos Retrospectivos , Resultado do Tratamento
13.
Neurosci Lett ; 714: 134612, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698025

RESUMO

The effects of 4NO2PDPMe and 4APDPMe, which are thalidomide (Tha) analogs that act as selective phosphodiesterase (PDE-4) inhibitors, on estrous behavior (lordosis and proceptive behaviors) and on uterine contraction were studied in ovariectomized (OVX) estrogen-primed Sprague Dawley (SD) and in intact non-pregnant Wistar rats, respectively. We found that intracerebroventricular (ICV) infusion of either 4NO2PDPMe or 4APDPMe (20 to 80 µg) stimulated intense lordosis and proceptive behavior in response to mounts from a sexually active male, within the first 4 h after infusion, and persisting for up to 24 h. Inhibitors of the progesterone receptor (RU486, administered subcutaneously), the estrogen receptor (tamoxifen, ICV), the adenylate cyclase (AC)/ cyclic AMP (cAMP)/protein kinase A (PKA) pathway (administered ICV), and the mitogen activated protein kinase (MAPK) pathway (administered ICV) significantly decreased lordosis and proceptive behavior induced by Tha analogs. Uterine contractility studies showed that Tha analogs inhibited both the K+- and the Ca2+-induced tonic contractions in rat uterus. Tha analogs were equally effective, but 4APDPMe was more potent than 4NO2PDPMe. These results strongly suggest the central role of cAMP in both processes, sexual behavior, and uterine relaxation, and suggest that Tha analogs may also act as Ca2+-channel blockers.


Assuntos
AMP Cíclico/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Ftalimidas/farmacologia , Propionatos/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Talidomida/análogos & derivados , Contração Uterina/efeitos dos fármacos , Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Cálcio , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Didesoxiadenosina/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios/farmacologia , Estro , Feminino , Técnicas In Vitro , Infusões Intraventriculares , Injeções Subcutâneas , Lordose , Luteolíticos/farmacologia , Mifepristona/farmacologia , Ovariectomia , Potássio , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptores de Progesterona , Tamoxifeno/farmacologia , Talidomida/farmacologia , Contração Uterina/metabolismo , Útero/efeitos dos fármacos
15.
Ann Oncol ; 29(2): 386-391, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29267861

RESUMO

Background: Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer. Patients and methods: We identified 105 303 men age 66 years or older who were diagnosed with stages I-III prostate cancer from 1992 through 2006 using the Surveillance, Epidemiology, and End Results-Medicare linked database, excluding patients with a history of RA. χ2 test was used to compare 5-year Kaplan-Meier rates of RA diagnoses. Competing risk Cox regression using inverse probability of treatment weighting was utilized to examine the association between pharmacologic ADT and diagnosis of RA. Results: The 43% of patients (N = 44 785) who received ADT experienced a higher 5-year rate of RA diagnoses compared with men who did not (5.4% versus 4.4%, P < 0.001). Receipt of any ADT was associated with a 23% increased risk of being diagnosed with RA (hazard ratio 1.23, 95% confidence interval 1.09-1.40, P = 0.001). The risk of being diagnosed with RA increased with a longer duration of ADT, from 19% with 1-6 months and 29% with 7-12 months to 33% with ≥13 months (Ptrend < 0.001). Conclusions: Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with RA in this large cohort of elderly men with prostate cancer. The risk was higher with a longer duration of ADT. Linking ADT to an increased risk of being diagnosed with an autoimmune condition adds to mounting evidence of the adverse effects of ADT that should prompt physicians to thoughtfully weigh its risks and benefits.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Artrite Reumatoide/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Programa de SEER
16.
Science ; 359(6371): 97-103, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29097493

RESUMO

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunoterapia , Melanoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/terapia , Animais , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/genética , Humanos , Melanoma/imunologia , Metagenoma , Camundongos , Neoplasias Cutâneas/imunologia
17.
Gait Posture ; 57: 305-309, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28728130

RESUMO

It has long been proposed that the gait alterations associated with barefoot running are mediated by alterations in sensory feedback, yet there has been no data to support this claim. Thus, the purpose of this study was to examine the role of superficial plantar cutaneous feedback in barefoot and shod running. METHODS: 10 healthy active subjects (6 male, 4 female); mass: 65.2+9.7kg; age: 27+7.1years participated in this study. 10 over-ground running trials were completed in each of the following conditions: barefoot (BF), shod (SHOD), anesthetized barefoot (ANEST BF) and anesthetized shod (ANEST SHOD). For the anesthetized conditions 0.1-0.3mL of 1% lidocaine was injected into the dermal layer of the plantar foot below the metatarsal heads, lateral column and heel. 3-dimensional motion analysis and ground reaction force (GRF) data were captured as subjects ran over a 20m runway with a force plate at 12m. Kinematic and kinetic differences were analyzed via two-way repeated measure ANOVAs. RESULTS: The differences in gait between the BF and SHOD conditions were consistent with previous research, with subjects exhibiting a significant decrease in stride length and changing from rearfoot strike when SHOD to fore/midfoot strike when BF. Additionally, BF running was associated with decreased impact peak magnitudes and peak vertical GRFs. Despite anesthetizing the plantar surface, there was no difference between the BF and ANEST BF conditions in terms of stride length, foot strike or GRFs. CONCLUSION: Superficial cutaneous sensory receptors are not primarily responsible for the gait changes associated with barefoot running.


Assuntos
Adaptação Fisiológica , Pé/fisiologia , Marcha/fisiologia , Corrida/fisiologia , Sapatos , Tato/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Cinética , Masculino , Adulto Jovem
18.
Prostate Cancer Prostatic Dis ; 20(4): 389-394, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28462945

RESUMO

BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Terapia de Salvação
19.
Ann Oncol ; 28(5): 1098-1104, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453693

RESUMO

Background: In 2012, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, despite evidence that Black men are at a higher risk of prostate cancer-specific mortality (PCSM). We evaluated whether Black men of potentially screening-eligible age (55-69 years) are at a disproportionally high risk of poor outcomes. Patients and methods: The SEER database was used to study 390 259 men diagnosed with prostate cancer in the United States between 2004 and 2011. Multivariable logistic regression modeled the association between Black race and stage of presentation, while Fine-Gray competing risks regression modeled the association between Black race and PCSM, both as a function of screening eligibility (age 55-69 years versus not). Results: Black men were more likely to present with metastatic disease (adjusted odds ratio [AOR] 1.65; 1.58-1.72; P < 0.001) and were at a higher risk of PCSM (adjusted hazard ratio [AHR] 1.36; 1.27-1.46; P < 0.001) compared to non-Black men. There were significant interactions between race and PSA-screening eligibility such that Black patients experienced more disproportionate rates of metastatic disease (AOR 1.76; 1.65-1.87 versus 1.55; 1.47-1.65; Pinteraction < 0.001) and PCSM (AHR 1.53; 1.37-1.70 versus 1.25; 1.14-1.37; Pinteraction = 0.01) in the potentially PSA-screening eligible group than in the group not eligible for screening. Conclusions: Racial disparities in prostate cancer outcome among Black men are significantly worse in PSA-screening eligible populations. These results raise the possibility that Black men could be disproportionately impacted by recommendations to end PSA screening in the United States and suggest that Black race should be included in the updated USPSTF PSA screening guidelines.


Assuntos
Neoplasias da Próstata/diagnóstico , Negro ou Afro-Americano , Idoso , Detecção Precoce de Câncer , Disparidades em Assistência à Saúde , Humanos , Calicreínas/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Fatores de Risco , Programa de SEER , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
Prostate Cancer Prostatic Dis ; 20(3): 300-304, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28349981

RESUMO

BACKGROUND: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. We wanted to evaluate how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referral practice (SRP) compared to a traditional urologic practice. METHODS: A total of 17 982 men aged 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. A total of 13 SRPs in the state of Texas were evaluated. We used multilevel logistic regression models that evaluated the odds of receiving a specific type of treatment. RESULTS: Men diagnosed in SRPs were more likely to receive upfront treatment (vs watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs 89%; adjusted odds ratio (AOR) 1.61, 95% confidence interval (CI) 1.30-2.00; P<0.001) and were more likely to be treated with external beam radiation (47.4% vs 34.1%; AOR 1.59, 95% CI 1.37-1.84; P<0.001). This persisted for both favorable and unfavorable risk cancer. Median annual prostate cancer care cost was $2460 (95% CI $1663-$3368) higher for men diagnosed by SRPs. Limitations include data limited to men aged 65 years or older and geographic concentration of SRPs in Texas may not depict nationwide patterns. CONCLUSIONS: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia/instrumentação , Idoso , Idoso de 80 Anos ou mais , Custos de Cuidados de Saúde , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Radioterapia/economia , Resultado do Tratamento , Urologistas
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