Lower-Body Resistance Training Reduces Interleukin-1ß and Transforming Growth Factor-ß1 Levels and Fatigue and Increases Physical Performance in Breast Cancer Survivors.

ABSTRACT: Martins, FM, Santagnello, SB, de Oliveira Junior, GN, de Sousa, JdFR, Michelin, MA, Nomelini, RS, Murta, EFC, and Orsatti, FL. Lower-body resistance training reduces interleukin-1ß and transforming growth factor-ß1 levels and fatigue and increases physical performance in breast cancer survivors. J Strength Cond Res 37(2): 439-451, 2023-This article ascertains whether resistance training (RT) improves inflammatory markers, fatigue (sensations and fatigability), and physical performance in breast cancer survivors (BCS) and investigates whether the changes in the inflammatory markers, fatigue, and physical performance are associated with each other. Volunteers were randomly divided into 2 groups: control group (n = 11) and RT group (n = 11). Resistance training (3 sets of 8-12 repetitions with 80% 1 repetition maximum (1RM) on 4 exercises-leg extension, leg curl, 45° leg press, and calf raise) was performed 3 times a week for 12 weeks. Self-reported fatigue (SRF), fatigability (critical torque [CT] and W prime [W']), muscle strength, and circulating inflammatory markers were assessed using the Brief Fatigue Inventory, iDXA, 1RM test, protocol of 60 maximal voluntary isometric contractions, and enzyme-linked immunosorbent assay, respectively. Resistance training reduced interleukin (IL)-1ß, transforming growth factor (TGF)-ß1, and SRF score and increased muscle strength, 6-minute walk test (6MWT), CT, and W'. In the RT group, the changes in SRF were positively associated with the changes in IL-1ß. The changes in muscle strength were associated with the changes in CT and W', and the changes in the 6MWT were associated with the changes in CT, W', muscle strength, and SRF. Resistance training improved fatigue and physical performance and reduced IL-1ß, and TGF-ß1 in BCS. Although improvement in fatigability seems to be dependent on the increase in muscle strength, improvement in the sensation of fatigue seems to be dependent on the reduction in IL-1ß after RT. Increase in physical performance seems to be dependent on improvement in muscle strength and fatigue.

CIN Extension at Colposcopy: Relation to Treatment and Blood Parameters.

OBJECTIVE: To determine the colposcopic lesion size that predicts the presence of residual lesion in patients with cervical intraepithelial neoplasia (CIN) 2/3, to aid gynaecologists in selecting conservative management. METHODS: Data from 51 patients with low- and high-grade squamous intraepithelial lesions were evaluated. Colposcopic images were captured and lesion areas were calculated. Polymerase chain reaction (PCR) for human papillomavirus was performed. Laboratory parameters were evaluated. Receiver operating characteristic (ROC) curves were used to obtain cut-off values for lesion area. The performance of PCR in the detection of high-grade CIN was assessed. A flowchart was created to compare the costs of related procedures in the Brazilian health system. RESULTS: For CIN 2/3 treated with excisional surgery, the best cut-off value for lesion area below which no residual lesion was present was 21 019 pixels2 (58.87 mm2). The cut-off value that predicted compromised surgical margins was 155 577.65 pixels2 (435.75 mm2). Among all patients with CIN, lesion area correlated inversely with neutrophil/lymphocyte ratio (NLR; r = -0.446, P = 0.001), platelet/lymphocyte ratio (PLR; r = -0.438, P = 0.001), and absolute number of leukocytes (r = -0.351, P = 0.011). Conservative clinical management with semi-annual clinical follow-up was found to reduce direct costs to the Brazilian Health System by R $909.82 (US $169.42). CONCLUSION: CIN reflects systemic alteration, leading to altered NLRs, PLRs, and absolute numbers of leukocytes. Patients with high-grade CIN and colposcopic lesion areas <21 019 pixels2 could benefit from conservative management, which would result in cost savings for the Brazilian health system.

Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and -noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3, and MGMT genes.

PURPOSE: Aberrant DNA methylation is present in virtually all types of human cancer. There is no clear evidence that methylation status can predict bad prognosis in patients with CIN recurrence in HIV infected. This study evaluates the relationship between aberrant methylation of CpG islands of CDH1, TIMP3 and MGMT genes and CIN recurrence in HIV-infected and -noninfected women. METHODS: This is a nested case-control study involving 33 cases with CIN recurrence and 114 controls without recurrence, HIV infected and noninfected, treated with LEEP, between 1999 and 2004. Recurrence diagnosis was established after biopsy. Genes methylation profile was assessed by MSP-PCR technique in formalin-fixed, paraffin-embedded cone specimens. Statistical analysis was performed to compare categorical variables, using χ2 test with Yates correction and Fisher's exact test. Multivariate analysis was carried out using logistic regression. RESULTS: CIN recurrence was more frequent in women with glandular involvement (OR 11.6; 95% CI 2.93-45.89) and compromised surgical margins (OR 2.5; 95% CI 0.87-7.27) in the cervical cone and in HIV-infected women (OR 2.47; 95% CI 0.87-7.05). One methylated allele of CDH1, TIMP3 and MGMT genes was present in 87.9% women with CIN recurrence. Promoter hypermethylation of TIMP3 and MGMT was detected in women with CIN recurrence and without CIN recurrence independent of HIV infection with significant difference between groups (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.

Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats.

OBJECTIVE: We studied the effect of resistance exercise (RE) on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF). MATERIAL AND METHODS: Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams) were randomly allocated into five groups: control group (CT-Sham; n = 6); group with rheumatoid arthritis (RA; n = 6); group with rheumatoid arthritis subjected to RE (RAEX; n = 6); ovariectomy group with rheumatoid arthritis (RAOV; n = 6); and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6). After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. RESULTS: The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA) of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV), but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. CONCLUSIONS: LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1). However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

Helper T lymphocyte response in the peripheral blood of patients with intraepithelial neoplasia submitted to immunotherapy with pegylated interferon-α.

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-ß is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

Fracture in Irradiated Rat Femur: A Description of an Experimental Model and Evaluation of its Effectiveness.

Objective We aim to describe an experimental model for studying femoral fractures in rats after exposure to ionizing radiation, demonstrating a way to apply a substance for analysis, the method for patterning fracture and irradiation, and how to evaluate its effectiveness based on radiographic studies. Methods We used 24 rats divided into 2 groups of 12 animals each. The STUDY group was exposed to ionizing radiation and treated with saline solution, and the CONTROL group was not exposed to radiation and was treated with saline solution. All animals were subjected to standardized fracture of the right femur that was fixed with intramedullary wire. The efficiency of the bone union was assessed by radiographic exam. Results Fracture healing was more efficient in bones not exposed to ionizing radiation ( p = 0.012). All fractures met the criteria of being simple, diaphyseal, transverse or short oblique. Conclusion The experimental model presented is an efficient alternative for the study of fractures in irradiated bones in rats.

Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus.

INTRODUCTION: To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. METHODS: 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. RESULTS: Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). CONCLUSIONS: ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.

Factors associated with recurrence of cervical intraepithelial neoplasia after conization in HIV-infected and noninfected women.

PURPOSE: To identify risk factors associated with recurrence of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedures in women with and without human immunodeficiency virus (HIV). METHODS: A total of 33 patients with recurrent CIN and 105 without recurrence were contrasted using a nested case-control design. The patients were enrolled between 1999 and 2004. Recurrence diagnosis was established after conization, and tissues were fixed in formalin and embedded in paraffin. Polymerase chain reaction was used to detect the human papillomavirus genome (HPV DNA) types 6, 11, 16, 18, 31, 33, and 35. Statistical analysis was performed using χ² test with Yates correction and the Fisher's exact test for comparison of categorical variables. Multivariate analysis was carried out using logistic regression models. RESULTS: Human immunodeficiency virus infection (p = 0.001), glandular involvement (p = 0.000), and compromised margins (p = 0.02) were significantly associated with CIN recurrence. HPV DNA was positive in 57.6% of patients with CIN recurrence. High-risk HPV subtypes were detected in most cases but were not associated with recurrence (p = 0.27). In multivariate analysis, HIV infection and glandular involvement were independently associated with CIN recurrence. CONCLUSIONS: Human immunodeficiency virus infection and glandular involvement are associated with CIN recurrence.

Prophylactic Dendritic Cell Vaccination in Experimental Breast Cancer Controls Immunity and Hepatic Metastases.

BACKGROUND/AIM: Liver metastases are among the principal mortality causes in cancer patients. Dendritic cell immunotherapies have shown promising results in some tumors by mediating immunological mechanisms that could be involved in liver metastases during primary tumor growth. The present study aimed to evaluate the impact of prophylactic dendritic cell vaccination on the liver of mice with 4T1 mouse breast carcinoma. MATERIALS AND METHODS: Adult female Balb/c mice were submitted or not to vaccination with dendritic cells before the induction of 4T1 tumor lineage. Liver tissues from mice were analyzed by flow cytometry (markers CD3, CD4, CD8, CD25, IL-10, IL-12, IL-17, TNF-α, IFN-γ, T-bet, GATA3, RORγt, and FoxP3) and hematoxylin-eosin. The dendritic cell vaccine was differentiated and matured ex vivo from the bone marrow. RESULTS: Prophylactic vaccination reduced areas of liver metastases (p=0.0049), induced an increase in the percentage of total T and cytotoxic T lymphocytes (p<0.0001), as well as FoxP3+ (p<0.0001). It also increased the levels of cytokines IL-10 and IL-17 in helper T lymphocytes (p<0.0001). CONCLUSION: The prophylactic dendritic cell vaccine changed the cell phenotype in the immune response of liver, and it was able to reduce metastases. Cytotoxic T cells and regulatory T lymphocytes were more present, likewise, the production of IL-10 and IL-7 simultaneously, demonstrating that the vaccine can induce a state of control of pro-inflammatory responses, which can provide a less favorable environment for metastatic tumor growth.

Immunological Characteristics between αß TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice.

OBJECTIVE: To evaluate the antitumoral role of γδ TDC cells and αß TDC cells in an experimental model of breast cancer. METHODS: Thirty female Balb/c mice were divided into 2 groups: control group (n = 15) and induced-4T1 group (n = 15), in which the mice received 2 × 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αß TDC (TCRαß+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17). RESULTS: A total of 26.53% of γδ TDC - control group (p < 0.0001) - the proportion of αß TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p < 0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αß TDC, but it decreased under conditions of tumor-related immune system response (p < 0.0001). CONCLUSION: Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

OBJETIVO: Esclarecer o possível papel antitumoral das células TDC γδ e TDC αß em um modelo experimental de câncer de mama. MéTODOS: Trinta baços de camundongos Balb/c analisados por citometria de fluxo, separados entre grupo controle (n = 15) e o grupo tumoral induzido por 4T1 (n = 15). RESULTADOS: Presença de 26,53% de TDC γδ nos camundongos do grupo controle (p < 0,0001), proporção de TDC αß menor em células esplênicas do que TDC γδ; no entanto, estes dois tipos de células são reduzidos em condições tumorais (p < 0,0001), e a proporção de citocinas IFN-γ, TNF-α, IL-12 e IL-17 produzidas pelas célula TDC γδ foi maior do que as produzidas pelas células TDC αß, mas foram diminuídas sob condições de resposta ao sistema imunológico relacionada ao tumor (p < 0,0001). CONCLUSãO: Camundongos saudáveis induzidos ao tumor de mama 4T1 apresentaram TDC com repertório TCR γδ. Estas células expressam moléculas citotóxicas de linfócitos T, produzindo citocinas proinflamatórias anti-tumor.

Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures.

INTRODUCTION: Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. OBJECTIVE: To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. METHODS: Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. RESULTS: Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. CONCLUSION: We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.

Pathways of IFN-alpha Activation in Patients with Cervical Intraepithelial Neoplasia (CIN).

OBJECTIVE: The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5'OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. RESULTS: Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. CONCLUSION: Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.

OBJETIVO: O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) MéTODOS: Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2'-5'-oligoadenilato sintetase (2'5'OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. RESULTADOS: Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. CONCLUSãO: Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.

Influence of an Exergaming Training Program on Reducing the Expression of IL-10 and TGF-ß in Cancer Patients.

Objective: To evaluate the effect of exergaming in the plasma levels of adipokines (interleukin [IL]-1ß, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]), Th1 (IL-2, IL-12, and interferon gamma [IFN-γ]), Th2 (IL-4 and IL-33), Th17 (IL-17 and IL-23), and regulatory T (Treg) (IL-10 and transforming growth factor-beta [TGF-ß]) in cancer patients undergoing treatment. Materials and Methods: We conducted a quasi-experimental control clinical trial using exergaming in all groups through the Xbox 360 Kinect™. The game used in this study was called Your Shape Fitness Evolved 2012. The volunteer participants played the game two to three times per week, for a total of 20 sessions. Forty-five volunteer participants were divided into 3 groups: cancer patients undergoing chemotherapy and/or radiotherapy treatment (chemotherapy and/or radiotherapy group CRG; n = 15); cancer patients who finished chemotherapy and/or radiotherapy treatment (cancer accompaniment group CAG; n = 15); and the control group (volunteers without a cancer diagnosis CG; n = 15). In the pre- and post-training period, all volunteers submitted to blood collection procedures using the enzyme-linked immunosorbent assay (ELISA). This test was used to obtain the levels of adipokines expression (IL-1ß, IL-6, IL-8, and TNF-α) and the cytokine profiles Th1 (IL-2, IL-12, and IFN-γ), Th2 (IL-4 and IL-33), Th17 (IL-17 and IL-23), and Treg (IL-10 and TGF-ß). Results: After exergaming, the CRG showed significant reductions in proinflammatory cytokines (IL-6: P < 0.05; IL-10: P = 0.038; TGF-ß: P = 0.049) and for CAG (IL-10: P = 0.034), as well as a reduction in the expression of cytokines related to the action of T lymphocytes. Conclusion: Exergaming promoted changes in the expression of cytokine profiles IL-6, IL-10, and TGF-ß, which correlated with the action profiles of CD4+ T lymphocytes.

Progress in the use of immunotherapy to treat uterine cervical cancer.

Cervical intraepithelial neoplasia has a high incidence in many of the world's populations, and it has been hypothesized to be a precursor of uterine cervical cancer. Cervical intraepithelial neoplasia also shares similar pathological traits with human papillomavirus infections. Various surgical treatments have been proposed over the years for the treatment of cervical intraepithelial neoplasia, including conization, hysterectomy and, more recently, a loop electrosurgical excisional procedure. However, a higher recurrence rate of the disease has been observed after these procedures. Therefore, immunotherapy has been proposed as a potential treatment to be used in conjunction with surgery, or independently, as treatment for cervical intraepithelial neoplasia. Currently, immunotherapy includes the application of recombinant viral proteins, vaccines, or antibody- and dendritic cell-based therapies. In this review, we summarize the development and testing of these immunotherapy approaches, particularly in regard to their application for the treatment of cervical intraepithelial neoplasia.

High-intensity body weight training is comparable to combined training in changes in muscle mass, physical performance, inflammatory markers and metabolic health in postmenopausal women at high risk for type 2 diabetes mellitus: A randomized controlled clinical trial.

OBJECTIVE: This study compared the effects of 12 weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2). METHODS: In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (n = 8) and COMT (n = 8). The HIBWT group performed a training protocol (length time ~28 min) consisting of ten sets of 60 s of high intensity exercise interspersed by a recovery period of 60 s of low intensity exercise. The COMT group performed a training protocol (length time ~60 min) consisting of a 30 min walk of moderate intensity following by five resistance exercises. All training sessions were performed in the university gym facility three days a week (no consecutive days) for 12 weeks. All outcomes (body composition, muscle function, and IR and inflammatory markers) were assessed at the baseline and at the end of the study. RESULTS: Both groups increased (P < 0.05) muscle mass index (MMI), 6MWT, and interleukin 1 receptor antagonist and decreased fasting glucose, glycated hemoglobin, Insulin, HOMA-IR, and monocyte chemoattractant protein-1 (trend, P = 0.056). HIBWT effects were indistinguishable (P > 0.05) from the effects of COMT. There was a significant (P < 0.05) interaction of time by the group in muscle strength, indicating that only the COMT increased the muscle strength. CONCLUSIONS: This study suggests that changes in HOMA, IL-1ra, 6MWT, and MMI with HITBW are similar when compared to COMT in PW at high risk of TDM2. TRIAL REGISTRATION: The patients were part of a 12-week training study (ClinicalTrials.gov Identifier: NCT03200639).

Fracture in Irradiated Rat Femur: A Description of an Experimental Model and Evaluation of its Effectiveness / Fratura em fêmur irradiado de rato: Descrição de um modelo experimental e avaliação de sua eficácia

Abstract Objective We aim to describe an experimental model for studying femoral fractures in rats after exposure to ionizing radiation, demonstrating a way to apply a substance for analysis, the method for patterning fracture and irradiation, and how to evaluate its effectiveness based on radiographic studies. Methods We used 24 rats divided into 2 groups of 12 animals each. The STUDY group was exposed to ionizing radiation and treated with saline solution, and the CONTROL group was not exposed to radiation and was treated with saline solution. All animals were subjected to standardized fracture of the right femur that was fixed with intramedullary wire. The efficiency of the bone union was assessed by radiographic exam. Results Fracture healing was more efficient in bones not exposed to ionizing radiation (p = 0.012). All fractures met the criteria of being simple, diaphyseal, transverse or short oblique. Conclusion The experimental model presented is an efficient alternative for the study of fractures in irradiated bones in rats.

Resumo Objetivo Nosso objetivo é descrever um modelo experimental para estudo de fraturas de fêmur em ratos após exposição a radiação ionizante, demonstrando uma forma de aplicação de uma substância para análise, o método de padronização de fratura e irradiação e a forma de avaliação de sua eficácia com base em estudos radiográficos. Métodos Utilizamos 24 ratos divididos em dois grupos de 12 animais cada. O grupo ESTUDO foi exposto à radiação ionizante e tratado com soro fisiológico, enquanto o grupo CONTROLE não foi exposto à radiação e foi tratado com soro fisiológico. Todos os animais foram submetidos à fratura padronizada do fêmur direito e sua fixação com fio intramedular. A eficácia da consolidação óssea foi determinada por exame radiográfico. Resultados A cicatrização de fraturas foi mais eficiente em ossos não expostos à radiação ionizante (p = 0,012). Todas as fraturas atenderam aos critérios de serem simples, diafisárias, transversas ou oblíquas curtas. Conclusão O modelo experimental apresentado é uma boa alternativa para o estudo de fraturas em ossos irradiados em ratos.

Utilization of human papillomavirus testing for cervical cancer prevention in a university hospital.

This study aimed to evaluate the performance and cost of using polymerase chain reaction (PCR) and hybrid capture in the detection of cervical intraepithelial neoplasia (CIN) in patients with cytological abnormalities (ASCUS/low-grade squamous intraepithelial lesion--LSIL), and the feasibility of implementing these methods in Brazil's Unified National Health System (SUS). Colposcopy gave a negative predictive value of 92.86% and efficiency of 87.8% for diagnosing CIN. The sensitivity of PCR and hybrid capture for detecting CIN was 83.33% and 66.67%, respectively, and the negative predictive value for diagnosing CIN2/CIN3 was 100% and 94.74%, respectively. The annual cost for 80 patients was lower when all patients with ASCUS/LSIL were referred for colposcopy than when HPV testing was performed and those with positive results were referred for colposcopy. Therefore, at present, it is financially unfeasible for the National Health System to implement HPV testing to screen patients with cytological abnormalities (ASCUS/LSIL). However, considering that large-scale use might make such methods cheaper, PCR should be the chosen method, since it is less expensive, more sensitive, and has a high negative predictive value.

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions.

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-ß) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c+ pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR+ pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR+ pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c+ pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the process of differentiation of DCs. Furthermore, activated lymphocytes may induce a better maturation of monocyte-derived DCs, and the presence of mononuclear cells appears to contribute to the DC differentiation process.

Predicting Functional Capacity From Measures of Muscle Mass in Postmenopausal Women.

BACKGROUND: Menopause increases body fat and decreases muscle mass and strength, which contribute to sarcopenia. The amount of appendicular muscle mass has been frequently used to diagnose sarcopenia. Different measures of appendicular muscle mass have been proposed. However, no studies have compared the most salient measure (appendicular muscle mass corrected by body fat) of the appendicular muscle mass to physical function in postmenopausal women. OBJECTIVE: To examine the association of 3 different measurements of appendicular muscle mass (absolute, corrected by stature, and corrected by body fat) with physical function in postmenopausal women. DESIGN: Cross-sectional descriptive study. SETTING: Outpatient geriatric and gynecological clinic. PARTICIPANTS: Forty-eight postmenopausal women with a mean age (standard deviation [SD]) of 62.1 ± 8.2 years, with mean (SD) length of menopause of 15.7 ± 9.8 years and mean (SD) body fat of 43.6% ± 9.8%. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Appendicular muscle mass measure was measured with dual-energy x-ray absorptiometry. Physical function was measured by a functional capacity questionnaire, a short physical performance battery, and a 6 minute-walk test. Muscle quality (leg extensor strength to lower-body mineral-free lean mass ratio) and sum of z scores (sum of each physical function tests z score) were performed to provide a global index of physical function. RESULTS: The regression analysis showed that appendicular muscle mass corrected by body fat was the strongest predictor of physical function. Each increase in the standard deviation of appendicular muscle mass corrected by body fat was associated with a mean sum of z score increase of 59% (standard deviation), whereas each increase in absolute appendicular muscle mass and appendicular muscle mass corrected by stature were associated with a mean sum of z scores decrease of 23% and 36%, respectively. Muscle quality was associated with appendicular muscle mass corrected by body fat. CONCLUSION: These findings indicate that appendicular muscle mass corrected by body fat is a better predictor of physical function than the other measures of appendicular muscle mass in postmenopausal women. LEVEL OF EVIDENCE: I.

Atypical squamous cells of undetermined significance: analysis of microbiology, cytological criteria and clinical conduct.

AIMS: To differentiate between two types of atypical squamous cells of undetermined significance (ASCUS): probably neoplastic (PN) or probably reactive (PR), and, in accordance with the recommendations on screening protocols of the Emilia-Romagna Region (PSRER), Italy, to define the best management to follow and the prognosis. Furthermore, the associations between ASCUS and infectious agents and human papillomavirus (HPV) were evaluated. METHODS: Fifty-eight ASCUS smears were reviewed and sorted; if a diagnosis of ASCUS was confirmed, the smear was classified as PR or PN, and the PSRER group was identified. Then, colposcopy was performed with checks for infectious agents (culture evaluation with cytological or clinical criteria) and HPV (hybrid capture). RESULTS: The ASCUS frequency was 3.96%. Of the 58 cases, 33 (56.9%) were diagnosed as ASCUS on review, of which 15 cases were PN and 18 were PR, while 23 (39.7%) smears were normal and 2 (3.4%) showed cervical intraepithelial neoplasia (CIN). There was a higher frequency of bacterial vaginosis (BV) and HPV in ASCUS PR patients compared with normal cytology, and a higher frequency of CIN in ASCUS PN patients compared with normal controls (P < 0.05). By grouping ASCUS 1 and 3, we observed a higher frequency of CIN and of high-grade colposcopy findings compared with ASCUS 2 and 4 (P < 0.05). From the 23 cases not found to be ASCUS, 18 (87.5%) had normal cytology and colposcopy results on the first follow-up. CONCLUSIONS: Classification of ASCUS as either PN or PR helps in clinical conduct and prognosis, because a higher frequency of CIN is found in ASCUS PN. ASCUS subdivisions, based on PSRER and colposcopy, may facilitate the clinical conduct because ASCUS 1 and 3 with high-grade colposcopic findings proved to be related to the presence of CIN. We propose that initial ASCUS cytology be reviewed, and if it is confirmed, colposcopy should be performed. For those cases found to be normal on review of the cytology results, it is suggested that a cytological check-up be carried out every 6 months.