Simulation of low-energy impacts on the human hand for prediction of peak reaction forces and bone fracture.

Hands of workers in extractive and heavy-duty industries are susceptible to suffering injuries of varying severity. Improved safety procedures and new technologies for production and maintenance tasks have contributed to reducing the severity of injuries. However, manual tasks with high-risk factors can still lead to hand injuries. Hand bone fractures and dislocations can be caused by relatively small objects impacting a region of the hand at velocities in the range of 1.3 to 1.6 m per second. This impact can produce significant functional, physical, and psychological consequences in those affected and result in high costs derived from medical care. This study presents the results of a finite element simulation study conducted to reproduce impacts with energies in the range of 7 to 10 Joules of an object on the dorsal region of the hand. Simulation results are compared to previous experimental results obtained from controlled impact tests performed using cadaveric hand specimens. The vertical peak reaction force (PRF) as a function of the impact position was used as a primary outcome for comparisons. Simulation results for all impact positions were within the standard deviation measured experimentally, with differences in the PRF values in the range of -5.3% to 4.9%. Bone stress analyses at the position of impacts showed the locations where the maximum principal stress exceeded the bone strength, as well as the variability in the correspondence between the stress distribution predicted by the FE models and the fracture rate distribution observed experimentally.

Experimental evaluation of impact-resistant gloves using surrogate hands.

Injuries to the hand and fingers with varying degrees of severity are widespread in industries such as mining and oil and gas production. This study presents the results of tests carried out to measure the impact performance for commonly used impact-resistant gloves (metacarpal gloves). Sets of surrogate hands made out of a 3D-printed skeletal structure and soft tissues represented by synthetic gel were manufactured and subjected to controlled impact tests. The calibration and validation of the surrogates were based on impact response data reported previously for cadaveric specimens. Calibrated surrogate hand specimens were tested to assess the impact protection of typical metacarpal gloves. Each type of metacarpal glove provided different levels of protection measured by the decrease in the peak impact reaction force and the fractures detected after the impacts. Results indicated that surrogate specimens suffered fractures in 77% and 33% of the impacts for unprotected and protected hands, respectively.

Mechanical Characterization of Synthetic Gels for Creation of Surrogate Hands Subjected to Low-Velocity Impacts.

The development of human body simulators that can be used as surrogates for testing protective devices and measures requires selecting synthetic materials with mechanical properties closely representative of the human tissues under consideration. For impact tests, gelatinous materials are often used to represent the soft tissues as a whole without distinguishing layers such as skin, fat, or muscles. This research focuses on the mechanical characterization of medical-grade synthetic gels that can be implemented to represent the soft tissues of the hand. Six grades of commercially available gels are selected for quasi-static hardness and firmness tests as well as for controlled low-velocity impact tests, which are not routinely conducted by gel manufacturers and require additional considerations such as energy level and specimen sizes relevant to the specific application. Specimens subject to impacts represent the hand thicknesses at the fingers, knuckles, and mid-metacarpal regions. Two impact test configurations are considered: one with the gel specimens including a solid insert representing a bone and one without this insert. The impact behavior of the candidate gels is evaluated by the coefficient of restitution, the energy loss percentage, and the peak reaction force at the time of impact. The resulting values are compared with similar indicators reported for experiments with cadaveric hands. Relatively softer gels, characterized by Shore OOO hardness in the range of 32.6 ± 0.9 to 34.4 ± 2.0, closely matched the impact behavior of cadaveric specimens. These results show that softer gels would be the most suitable gels to represent soft tissues in the creation of surrogate hands that can be used for extensive impact testing, thus, minimizing the need for cadaveric specimens.

Effects of wearing of metacarpal gloves on hand dexterity, function, and perceived comfort: A pilot study.

Metacarpal gloves are commonly used in heavy-duty industries such as mining and are typically thicker and bulkier than manufacturing or assembly industrial gloves. This pilot study investigates the impact of wearing metacarpal gloves on hand dexterity, functional capabilities, and perceived comfort. Four types of commercially available metacarpal gloves were selected for evaluation in a randomized controlled trial. Evaluations included turning and placing tests, also grip, pinch, and screwdriver tests, and rating of the perceived level of effort. Dexterity test results showed that metacarpal gloves significantly reduced the ability to perform motor tasks requiring coordination compared to bare hands. Hand functions such as gripping, pinching, and forearm rotations were not significantly affected. However, the perceived level of effort needed to complete those hand functions increased as the metacarpal glove's bulkiness increased. High levels of mechanical protection typically offered by metacarpal gloves can inversely affect hand dexterity and hand exertion.

Experimental evaluation of protected and unprotected hands under impact loading.

Hand injuries are a significant problem in many industries with relatively high incidence rates and injury severity. Many workers are required to wear impact protective gloves to protect their hands from impact-related hazards. This research presents the results of an experimental quantification of metacarpal gloves performance subjected to controlled impacts. Thirteen cadaveric hands were used to conduct a set of controlled impact tests on protected and unprotected hands. The controlled impacts targeted the proximal interphalangeal (PIP) joints, the metacarpophalangeal (MCP) joints, and the middle section of the metacarpal bones. Two types of metacarpal gloves commonly used in mining and oil and gas operations were selected for the tests. These gloves include different material and protection configurations on the dorsal side of the hand. The performance of selected gloves was quantified using the maximum reaction force to the impact and number of bone fractures. A total of 191 impacts produced 108 fractures, from which 71% corresponded to the unprotected hands and 40% to the protected hands. Depending on the impact position and type of glove used, the effect of protection ranged from no change up to a 23% reduction in peak reaction force.

Genomic and expression profiling reveal molecular heterogeneity of disseminated tumor cells in bone marrow of early breast cancer.

Detection of disseminated tumor cells (DTCs) in bone marrow is an established negative prognostic factor. We isolated small pools of (~20) EPCAM-positive DTCs from early breast cancer patients for genomic profiling. Genome-wide copy number profiles of DTC pools (n = 45) appeared less aberrant than the corresponding primary tumors (PT, n = 16). PIK3CA mutations were detected in 26% of DTC pools (n = 53), none of them were shared with matched PTs. Expression profiling of DTC pools (n = 30) confirmed the upregulation of EPCAM expression and certain oncogenes (e.g., MYC and CCNE1), as well as the absence of hematopoietic features. Two expression subtypes were observed: (1) luminal with dual epithelial-mesenchymal properties (high ESR1 and VIM/CAV1 expression), and (2) basal-like with proliferative/stem cell-like phenotype (low ESR1 and high MKI67/ALDH1A1 expression). We observed high discordance between ESR1 (40%) and ERRB2 (43%) expression in DTC pools vs. the clinical ER and HER2 status of the corresponding primary tumors, suggesting plasticity of biomarker status during dissemination to the bone marrow. Comparison of expression profiles of DTC pools with available data from circulating tumor cells (CTCs) of metastatic breast cancer patients revealed gene expression signatures in DTCs that were unique from those of CTCs. For example, ALDH1A1, CAV1, and VIM were upregulated in DTC pools relative to CTCs. Taken together, analysis of pooled DTCs revealed molecular heterogeneity, possible genetic divergence from corresponding primary tumor, and two distinct subpopulations. Validation in larger cohorts is needed to confirm the presence of these molecular subtypes and to evaluate their biological and clinical significance.

Expanded Genomic Profiling of Circulating Tumor Cells in Metastatic Breast Cancer Patients to Assess Biomarker Status and Biology Over Time (CALGB 40502 and CALGB 40503, Alliance).

Purpose: We profiled circulating tumor cells (CTCs) to study the biology of blood-borne metastasis and to monitor biomarker status in metastatic breast cancer (MBC).Methods: CTCs were isolated from 105 patients with MBC using EPCAM-based immunomagnetic enrichment and fluorescence-activated cells sorting (IE/FACS), 28 of whom had serial CTC analysis (74 samples, 2-5 time points). CTCs were subjected to microfluidic-based multiplex QPCR array of 64 cancer-related genes (n = 151) and genome-wide copy-number analysis by array comparative genomic hybridization (aCGH; n = 49).Results: Combined transcriptional and genomic profiling showed that CTCs were 26% ESR1-ERBB2-, 48% ESR1+ERBB2-, and 27% ERBB2+ Serial testing showed that ERBB2 status was more stable over time compared with ESR1 and proliferation (MKI67) status. While cell-to-cell heterogeneity was observed at the single-cell level, with increasingly stable expression in larger pools, patient-specific CTC expression "fingerprints" were also observed. CTC copy-number profiles clustered into three groups based on the extent of genomic aberrations and the presence of large chromosomal imbalances. Comparative analysis showed discordance in ESR1/ER (27%) and ERBB2/HER2 (23%) status between CTCs and matched primary tumors. CTCs in 65% of the patients were considered to have low proliferation potential. Patients who harbored CTCs with high proliferation (MKI67) status had significantly reduced progression-free survival (P = 0.0011) and overall survival (P = 0.0095) compared with patients with low proliferative CTCs.Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time. Clin Cancer Res; 24(6); 1486-99. ©2018 AACR.

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.

Selective atrial vagal denervation guided by spectral mapping to treat advanced atrioventricular block.

AIMS: Asymptomatic nocturnal long ventricular pauses are usually detected accidentally and it has been suggested that they may lead to sudden death. Identification of predisposing factors could prevent cardiovascular events. METHODS AND RESULTS: We report the case of a patient with frequent asymptomatic nocturnal ventricular pauses of 3-11 s, characteristic of a vagally mediated atrioventricular (AV) block. Echocardiography, treadmill test, thyroid function test levels, and polysomnogram were normal. In an attempt to reduce the risk, it was decided that an atrial vagal denervation induced by radiofrequency (RF) ablation (cardioneuroablation) could be useful. Spectral mapping was used to localize endocardial vagal innervation in the right and left aspects of the inter-atrial septum, responsible for the sinus node and AV node modulation, and RF pulses were applied in those sites only. After finishing the procedure, significant changes were observed in the heart rate (66-90 b.p.m.), atrial-His interval (115-74 ms), Wenckebach cycle length (820-570 ms), and sinus node recovery time (1100-760 ms). Follow-up Holter recording demonstrated that the number of ventricular pauses had reduced from 438 to 0. Heart rate and time domain characteristics were compatible with vagal denervation. CONCLUSION: Ablation of the endocardial vagal innervation sites seems to be safe and efficient in reducing the frequency and the length of the ventricular pauses. It was possible by identifying certain spectral components of the atrial electrogram, resulting in a conservative approach.

Reconstrucción mamaria post-mastectomía: contribución de cirujanos plásticos argentinos / Post- mastectomy breast reconstruction: contribution of argentine plastic surgeons

Se describen los inicios -a finales del siglo XIX- de las técnicas de reconstrucción mamaria post-mastectomía. Se enumeran las técnicas más importantes que las continuaron y quiénes las crearon en el mundo. Se destacan los aportes de dos cirujanos plásticos argentinos, Julián Fernández (1965) y Enrique Gandolfo (1982), que utilizaron tejidos autólogos del abdomen, colgajos dermograso con abordaje vertical y musculo-cutáneo con abordaje horizontal, respectivamente.

Early (late nineteenth century) techniques post-mastectomy breast reconstructions are described. Techniques that continued and its creators in the world are listed. The contributions of two plastic surgeons from Argentina, Julian Fernandez (1965) and Enrique Gandolfo (1982), who used autologous tissue from the abdomen, dermofat flaps vertically approach and musculocutaneous flaps with horizontal approach, respectively stand.

Selenoprotein and antioxidant genes and the risk of high-grade prostate cancer and prostate cancer recurrence.

BACKGROUND: Observational studies suggest an inverse association between selenium and risk of prostate cancer. However, randomized controlled trials of selenium supplementation have reported conflicting results. Thus, we examined plasma selenium and selenium-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with non-metastatic disease. METHODS: We measured plasma selenium and genotyped 73 single nucleotide polymorphisms in TXNRD1, TXNRD2, GPX1, GPX3, GPX4, SEP15, SEPP1, SELENBP1, OGG1, and CAT among 568 men with non-metastatic prostate cancer who underwent radical prostatectomy. We examined associations between plasma selenium, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥8 or 7 with primary score ≥4; n = 111) using logistic regression, and risk of prostate cancer recurrence (61 events; 3.8 y median follow-up) using Cox proportional hazards regression. RESULTS: Plasma selenium was not associated with risk of high-grade prostate cancer or prostate cancer recurrence. Less common alleles of rs11913319 in TXNRD2 and rs125701 in OGG1 were associated with an increased risk of high-grade prostate cancer. We observed associations between the risk of prostate cancer recurrence and multiple SNPs in TXNRD1, TXNRD2, GPX3, and SEP15. These associations were no longer statistically significant after adjustment for multiple comparisons. CONCLUSIONS: Among men with non-metastatic prostate cancer, there is suggestive evidence that genetic variation in selenoproteins and related antioxidant enzymes may be associated with risk of high-grade disease at diagnosis and prostate cancer recurrence.

Accessory atrioventricular pathways refractory to catheter ablation: role of percutaneous epicardial approach.

BACKGROUND: Epicardial mapping and ablation of accessory pathways through a subxiphoid approach can be an alternative when endocardial or epicardial transvenous mapping has failed. METHODS AND RESULTS: We reviewed acute and long-term follow-up of 21 patients (14 males) referred for percutaneous epicardial accessory pathway ablation. There was a median of 2 previous failed procedures. All patients were highly symptomatic, 8 had atrial fibrillation (3 with cardiac arrest) and 13 had frequent symptomatic episodes of atrioventricular reentrant tachycardia. Six patients (28.5%) had a successful epicardial ablation. Five patients (23.8%) underwent a successful repeated endocardial mapping, and ablation after epicardial mapping yielded no early activation site. Epicardial mapping was helpful in guiding endocardial ablation in 2 patients (9.5%), showing that the earliest activation was simultaneous at the epicardium and endocardium. Four patients (19%) underwent successful open-chest surgery after failing epicardial/endocardial ablation. Two patients (9.5%) remained controlled under antiarrhythmic drugs after unsuccessful endocardial/epicardial ablation. Two patients had a coronary sinus diverticulum and one a right atrium to right ventricle diverticulum. Three patients acquired postablation coronary sinus stenosis. There was no major complication related to pericardial access. CONCLUSIONS: Percutaneous epicardial approach is an alternative when conventional endocardial or transvenous epicardial ablation fails in the elimination of the accessory pathway. A new attempt by endocardial approach was successful in a significant number of patients. Open-chest surgery may be required in symptomatic cases refractory to endocardial-epicardial approach.

Late Outcome of a Randomized Study on Oral Magnesium for Premature Complexes / Evolução Tardia de Estudo Randomizado com Uso de Magnésio Via Oral em Extrassístoles Sintomáticas

Background: Ventricular and supraventricular premature complexes (PC) are frequent and usually symptomatic. According to a previous study, magnesium pidolate (MgP) administration to symptomatic patients can improve the PC density and symptoms. Objective: To assess the late follow-up of that clinical intervention in patients treated with MgP or placebo. Methods: In the first phase of the study, 90 symptomatic and consecutive patients with PC were randomized (double-blind) to receive either MgP or placebo for 30 days. Monthly follow-up visits were conducted for 15 months to assess symptoms and control electrolytes. 24-hour Holter was performed twice, regardless of symptoms, or whenever symptoms were present. In the second phase of the study, relapsing patients, who had received MgP or placebo (crossing-over) in the first phase, were treated with MgP according to the same protocol. Results: Of the 45 patients initially treated with MgP, 17 (37.8%) relapsed during the 15-month follow-up, and the relapse time varied. Relapsing patients treated again had a statistically significant reduction in the PC density of 138.25/hour (p < 0.001). The crossing-over patients reduced it by 247/hour (p < 0.001). Patients who did not relapse, had a low PC frequency (3 PC/hour). Retreated patients had a 76.5% improvement in symptom, and crossing-over patients, 71.4%. Conclusion: Some patients on MgP had relapse of symptoms and PC, indicating that MgP is neither a definitive nor a curative treatment for late follow-up. However, improvement in the PC frequency and symptoms was observed in the second phase of treatment, similar to the response in the first phase of treatment. .

Fundamento: Extrassístoles (ES) ventriculares e supraventriculares são frequentes e muitas vezes sintomáticas. Segundo estudo prévio, a administração de pidolato de magnésio (PMg) a pacientes sintomáticos pode resultar na melhora da densidade das ES e dos sintomas relacionados. Objetivo: Avaliar os resultados dessa intervenção clínica inicial no seguimento tardio de pacientes recebendo PMg ou placebo. Métodos: Noventa pacientes com ES, sintomáticos e consecutivos foram randomizados (duplo-cego) para receber PMg ou placebo por 30 dias. Visitas mensais de seguimento (15 meses) foram realizadas para avaliar a sintomatologia e controlar eletrólitos. O Holter de 24 horas foi realizado sempre que sintomáticos, ou duas vezes, independentemente dos sintomas. Na segunda fase do estudo, os pacientes cujos sintomas recidivassem, seja do grupo PMg ou placebo (crossing over), receberam PMg seguindo-se o mesmo protocolo. Resultados: Dos 45 pacientes que receberam inicialmente o PMg, 17 (37,8%) apresentaram recidiva dos sintomas em tempo variável nos 15 meses. Os pacientes com recidiva e tratados uma segunda vez apresentaram redução estatisticamente significante na densidade de ES de 138,25/hora (p < 0,001). Os pacientes de crossing reduziram em 247/hora (p < 0,001). Nos pacientes que não apresentaram recidiva, a frequência de ES foi baixa (3 ES/hora). A melhora dos sintomas foi de 76,5% nos retratados e de 71,4% nos de crossing. Conclusão: Houve recorrência de sintomas e das ES em alguns pacientes que usaram PMg, deixando claro não ser essa uma forma de tratamento definitivo ou curativo no seguimento tardio. Contudo, houve também melhora na frequência de ES e de sintomas em uma segunda etapa de tratamento, semelhante à resposta na primeira etapa. .

Baroreflex sensitivity and its association with arrhythmic events in Chagas disease.

BACKGROUND: Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence. OBJECTIVE: To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias. METHOD: Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram). RESULTS: GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028). CONCLUSION: The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

Displasia arritmogênica do ventrículo direito: relato de caso e revisão dos critérios diagnósticos e atuais das indicações de cardiodesfibrilador implantável / Arrhythmogenic right ventricular dysplasia: case report and review of diagnostic criteria and current indications for implantable cardioverter defibrillator(ICD)

A displasia arritmogênica do ventrículo direito é uma forma de cardiomiopatia geneticamentedeterminada, que afeta primariamente o ventrículo direito. Caracteriza-se pela substituição dos miócitos portecido fibrogorduroso. É considerada uma doença cardíaca potencialmente letal e tem sido associada a arritmias,insuficiência cardíaca e morte súbita. Relata-se o caso clínico de um paciente jovem, em que a síncope foi aprimeira manifestação da doença.

Arrhythmogenic right ventricular dysplasia is a genetically determined form of cardiomyopathy thatprimarily affects the right ventricle. It is characterized by a gradual replacement of the myocytes by adipose andfibrous tissue. It is considered a potentially lethal heart disease and has been associated with arrhythmias, heartfailure, and sudden death. In this paper, we report a clinical case of a young man that presented syncope as firstmanifestation of the disease.

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease / A Sensibilidade do Barorreflexo e sua Associação com Eventos Arrítmicos na Doença de Chagas

Background: Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence. Objective: To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias. Method: Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram). Results: GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028). Conclusion: The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias. .

Fundamento: Morte súbita é a principal causa de morte na doença de Chagas (DC), mesmo em pacientes com fração de ejeção (FE) preservada, sugerindo que fatores desestabilizadores do substrato arritmogênico (modulação autonômica) contribuam para a sua ocorrência. Objetivo: Determinar a sensibilidade do barorreflexo (SBR) em pacientes com DC na forma indeterminada (GI), arritmogênica com TVNS (GII) e com TVS (GIII) a fim de avaliar sua associação com a ocorrência e complexidade da arritmia. Método: Quarenta e dois pacientes chagásicos foram submetidos à monitorização do ECG e PA contínua e não invasiva (TASK force monitor). Foi determinada a SBR (método da fenilefrina), a variabilidade da frequência cardíaca (VFC) ao Holter 24 h. e FE (ecocardiograma). Resultados: O GIII apresentou menor SBR (6,09 ms/mmHg) quando comparado aos GII (11,84) e GI (15,23). A diferença foi significativa entre os GI e GIII (p = 0,01). Correlacionando SBR com densidade de extrassístoles ventriculares (EV), observou-se que a baixa densidade de EV (< 10/h.) associou-se com SBR preservada. Nos pacientes com alta densidade de EV (> 10/h.), somente 59% tinham SBR preservada (p = 0,003). Os pacientes com SBR deprimida apresentavam maior densidade de EV (p = 0,01), independente da FE. A SBR foi a única variável relacionada à ocorrência de TVS (p = 0,028). Conclusão: A SBR está preservada na forma indeterminada da DC. O comprometimento da SBR é progressivo e acompanha a evolução da doença, sendo mais intenso nos pacientes com arritmias ventriculares mais complexas. O grau de disfunção autonômica não se correlacionou com a FE, mas sim com a densidade e complexidade da arritmia ventricular. .

Physical activity and prostate gene expression in men with low-risk prostate cancer.

PURPOSE: Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown. METHODS: We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance. Differential gene expression, gene set, and pathway analyses were conducted comparing dichotomous groups defined by type, intensity, and amount of physical activity reported. RESULTS: Cell cycling and DNA repair pathways were up-regulated in men who participated in ≥ 3 h/week vigorous activity compared with men who did not. In addition, canonical pathways involved in cell signaling and metabolism, the cellular effects of sildenafil (Viagra), and the Nrf2-mediated oxidative stress response were modulated in men who reported ≥ 3 h/week of vigorous activity. Differential expression analysis at the individual gene level revealed modest differences between men who performed vigorous activity for ≥ 3 h/week and those who did not. There were no differences in prostate gene expression in comparisons with exercise groupings that did not consider both duration and intensity of activity. CONCLUSIONS: Prostate gene expression and pathway analyses revealed sets of transcripts that may be modulated in normal prostate tissue by participating in ≥ 3 h/week of vigorous activity after diagnosis of low-risk prostate cancer. These findings suggest potential biological mechanisms by which vigorous activity may reduce risk of prostate cancer progression and warrant further study and validation.