Effects of aerobic exercise on molecular aspects of asthma: involvement of SOCS-JAK-STAT.

BACKGROUND: Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation. METHODS: C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52. RESULTS: AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL- 10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001). CONCLUSIONS: AT reduces asthma phenotype involving SOCSJAK- STAT signaling.

Pain and distress outcomes in infants and children: a systematic review.

The aim of the present study was to systematically review the recent literature about pain and distress outcomes in children and critically analyze the methodological quality of the reports. The systematic review was based on the PRISMA statement and performed by selecting articles that are indexed in scientific databases. The methodological quality of reports was examined using STROBE statement, for observational studies, and CONSORT statement, for randomized controlled trials. The PedIMMPACT consensus was used to evaluate the psychometric quality of pain instruments. We analyzed 23 empirical studies, including 14 randomized controlled trials, seven cross-sectional studies, and two studies with cohort designs. Fourteen studies included preschool- and schoolchildren, and nine studies included infants. Regarding studies with infants, pain responses were evaluated by heart rate, crying and behavioral observation scales, and distress was evaluated only by salivary cortisol. Four-handed care and sensorial saturation interventions were used to evaluate efficacy to reduce pain and distress responses. Concerning studies with children, both pain and distress responses were evaluated by self- and hetero-reports, behavioral observation and/or physiological measures. Distraction was effective for reducing pain and distress during burn dressing changes and needle procedures, and healing touch intervention reduced distress and pain in chronic patients. All of the studies scored at least 60% in the methodological quality assessment. The pain outcomes included measures of validity that were classified as well-established by the PedIMMPACT. This systematic review gathers scientific evidence of distress-associated pain in children. Pain and distress were measured as distinct constructs, and their associations were poorly analyzed.

Audiovisual distraction for pain relief in paediatric inpatients: A crossover study.

BACKGROUND: Pain is a stressful experience that can have a negative impact on child development. The aim of this crossover study was to examine the efficacy of audiovisual distraction for acute pain relief in paediatric inpatients. METHOD: The sample comprised 40 inpatients (6-11 years) who underwent painful puncture procedures. The participants were randomized into two groups, and all children received the intervention and served as their own controls. Stress and pain-catastrophizing assessments were initially performed using the Child Stress Scale and Pain Catastrophizing Scale for Children, with the aim of controlling these variables. The pain assessment was performed using a Visual Analog Scale and the Faces Pain Scale-Revised after the painful procedures. Group 1 received audiovisual distraction before and during the puncture procedure, which was performed again without intervention on another day. The procedure was reversed in Group 2. Audiovisual distraction used animated short films. A 2 × 2 × 2 analysis of variance for 2 × 2 crossover study was performed, with a 5% level of statistical significance. RESULTS: The two groups had similar baseline measures of stress and pain catastrophizing. A significant difference was found between periods with and without distraction in both groups, in which scores on both pain scales were lower during distraction compared with no intervention. The sequence of exposure to the distraction intervention in both groups and first versus second painful procedure during which the distraction was performed also significantly influenced the efficacy of the distraction intervention. CONCLUSION: Audiovisual distraction effectively reduced the intensity of pain perception in paediatric inpatients. SIGNIFICANCE: The crossover study design provides a better understanding of the power effects of distraction for acute pain management. Audiovisual distraction was a powerful and effective non-pharmacological intervention for pain relief in paediatric inpatients. The effects were detected in subsequent acute painful procedures.

Pain and distress outcomes in infants and children: a systematic review

The aim of the present study was to systematically review the recent literature about pain and distress outcomes in children and critically analyze the methodological quality of the reports. The systematic review was based on the PRISMA statement and performed by selecting articles that are indexed in scientific databases. The methodological quality of reports was examined using STROBE statement, for observational studies, and CONSORT statement, for randomized controlled trials. The PedIMMPACT consensus was used to evaluate the psychometric quality of pain instruments. We analyzed 23 empirical studies, including 14 randomized controlled trials, seven cross-sectional studies, and two studies with cohort designs. Fourteen studies included preschool- and schoolchildren, and nine studies included infants. Regarding studies with infants, pain responses were evaluated by heart rate, crying and behavioral observation scales, and distress was evaluated only by salivary cortisol. Four-handed care and sensorial saturation interventions were used to evaluate efficacy to reduce pain and distress responses. Concerning studies with children, both pain and distress responses were evaluated by self- and hetero-reports, behavioral observation and/or physiological measures. Distraction was effective for reducing pain and distress during burn dressing changes and needle procedures, and healing touch intervention reduced distress and pain in chronic patients. All of the studies scored at least 60% in the methodological quality assessment. The pain outcomes included measures of validity that were classified as well-established by the PedIMMPACT. This systematic review gathers scientific evidence of distress-associated pain in children. Pain and distress were measured as distinct constructs, and their associations were poorly analyzed.

Who runs the fastest? Anthropometric and physiological correlates of 20 m sprint performance in male soccer players.

The aim of the present study was to examine the relationship of 20 m sprint performance with anthropometrical and physiological parameters in male soccer players. A hundred and 81 soccer players from the region of Athens (age 23.4 ± 5.0 yrs, body mass 73.4 ± 7.7 kg, height 180.0 ± 5.9 cm, body fat (BF) 14.4 ± 3.6%), classified into quartiles according to 20 m sprint time (group A, 2.84-3.03 s; group B, 3.04-3.09 s; group C, 3.10-3.18 s; group D, 3.19-3.61 s), participated. Soccer players in group A were younger and had better performance in vertical jumps and in the Wingate anaerobic test (WAnT, p < 0.05). Sprint time correlated to age (r = 0.27), body mass (r = 0.23), body height (r = 0.20), BF (r = 0.23), vertical jumps (-0.58 ≤ r ≤ -0.50) and the WAnT (-0.45 ≤ r ≤ -0.30, p < 0.05). In summary, the magnitude of correlations of sprint time with measures of lower limbs muscle strength and power (WAnT and jumps) was larger than with anthropometric measures (body mass and BF).

Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

Trace samples of human blood in mosquitoes as a forensic investigation tool.

Investigations of any type of crime invariably starts at the crime scene by collecting evidence. Thus, the purpose of this research was to collect and analyze an entomological trace from an environment that is similar to those of indoor crime scenes. Hematophagous mosquitoes were collected from two residential units; saliva of volunteers that were residents in the units was also collected for genetic analysis as reference samples. We examined the allele frequencies of 15 short tandem repeat loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) and amelogenin. A total of 26 female hematophagous mosquitoes were identified as Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus; we were able to obtain 11 forensically valid genetic profiles, with a minimum of 0.028203 ng/µL of human DNA. Thus, the results of this study showed that it was possible to correlate human genetic information from mosquitoes with the volunteer reference samples, which validates the use of this information as forensic evidence. Furthermore, we observed mixed genetic profiles from one mosquito. Therefore, it is clearly important to collect these insects indoors where crimes were committed, because it may be possible to find intact genetic profiles of suspects in the blood found in the digestive tract of hematophagous mosquitoes for later comparison to identify an offender and/or exclude suspects.

Evaluation of miltefosine for the treatment of dogs naturally infected with L. infantum (=L. chagasi) in Brazil.

Dogs naturally infected with Leishmania Infantum (=L. chagasi) were treated with miltefosine using different therapeutic regimens. The animals were evaluated for clinical evolution, biochemical parameters, parasite load (by real-time PCR), cytokine levels and humoral response. After treatment and during the following 24 months, there was progressive clinical improvement and complete recovery in 50% (7/14) of the treated animals. There was a decrease in the smear positivity of the bone marrow after treatment, and there was also a gradual and constant decrease in positive cultures at the end of the follow-up period. However, the PCR detection of parasite DNA remained positive. In general, all animals presented a significant increase in parasite load 6 months after treatment. The IFN-γ levels in all the groups tended to increase during follow-up period, regardless of the miltefosine dose administered. The IL-4 and IL-10 levels of the animals tended to decrease during follow-up, except after 300 days when only IL-10 increased. The serum antibodies identified antigens that ranged from 116 kDa to less than 29 kDa in the Western blot assay. Furthermore, 300 days after treatment, qualitative and quantitative differences in the antigen profiles were observed. Antigens of 97 and 46 kDa were the most intensely recognized. Higher levels of antigen-specific Leishmania IgG were detected before and 300 days after treatment in all groups. Taking together, the improvement in the clinical symptoms was not followed by parasitological clearance, suggesting that treatment with miltefosine is not recommended, especially in endemic areas like Brazil, where children are the major victims and dogs are involved in the maintenance of the parasite cycle.

In vitro micronuclei tests to evaluate the genotoxicity of surface water under the influence of tanneries.

Leather manufacturing has a high potential for environmental pollution due to hides and chemicals that are not completely absorbed during the tanning process. This study aims to investigate the mutagenic potential of surface water samples from Cadeia and Feitoria rivers (RS, Brazil) in areas influenced by tanneries and leather footwear industry. Micronucleus assays using V79 cells and human lymphocytes were used. Cells were exposed to surface water collected bimonthly from three sites for a year, totaling six samples. Significant MN induction in human lymphocytes was shown by 83% of samples from sites FEI001 and CAD001 located downstream from the industrial area, followed by FEI004 (33%), upstream. Only a single sample from site FEI004 showed a positive response for MN in V79 cells. Thirteen discordant and five concordant responses were found between the two in vitro tests. Mutagenic agents were found at the sites where chemical quality was worst, corroborating studies on chronic toxicity, oxidative stress and mutagenicity performed in this area. The assay using human lymphocytes was more sensitive than V79 cells to detect the contaminants from this area, showing that it is an excellent biomarker of environmental genotoxicity.

Aerobic exercise is safe and effective in systemic sclerosis.

Several studies have established that systemic sclerosis patients have a reduced exercise capacity when compared to healthy individuals. It is relevant to evaluate whether aerobic exercise in systemic sclerosis patients is a safe and effective intervention to improve aerobic capacity. Seven patients without pulmonary impairment and seven healthy controls were enrolled in an 8-week program consisting of moderate intensity aerobic exercise. Patients and controls had a significant improvement in peak oxygen consumption (19.72+/-3.51 vs. 22.27+/-2.53 and 22.94+/-4.70 vs. 24.55+/-3.00, respectively, p=0.006), but difference between groups was not statistically significant (p=0.149). This finding was reinforced by the fact that at the end of the study both groups were able to perform a significantly higher exercise intensity when compared to baseline, as measured by peak blood lactate (1.43+/-0.51 vs. 1.84+/-0.33 and 1.11+/-0.45 vs. 1.59+/-0.25, respectively, p=0.01). Patients improved the peak exercise oxygen saturation comparing to the baseline (84.14+/-9.86 vs. 90.29+/-5.09, p=0.048). Rodnan score was similar before and after the intervention (15.84+/-7.84 vs.12.71+/-4.31, p=0.0855). Digital ulcers and Raynaud's phenomenon remained stable. Our data support the notion that improving aerobic capacity is a feasible goal in systemic sclerosis management. The long term benefit of this intervention needs to be determined in large prospective studies.

Reduced exercise capacity in systemic sclerosis patients without pulmonary involvement.

OBJECTIVE: To evaluate the exercise capacity of women with systemic sclerosis (SSc) without pulmonary involvement using a cardiopulmonary stress test. METHODS: Thirteen consecutive female SSc patients [mean age 40.8+/-14 years, mean body mass index (BMI) 25.5+/-3.7 kg/m2] without pulmonary and cardiac involvement and 13 healthy sedentary female controls (mean age 41.6+/-9.1 years, mean BMI 23.7+/-3.8 kg/m2) matched by age and BMI underwent a maximum cardiopulmonary stress test (Bruce protocol). The following parameters were analysed: peak oxygen uptake (VO2peak), anaerobic threshold (AT), respiratory compensation point (RCP) and metabolic equivalent (MET) of the VO2peak. Comparisons between groups were analysed using the Student t-test. RESULTS: Forced vital capacity (FVC; 92.2+/-14.2% predicted) and carbon monoxide diffusion lung capacity (DL CO; 85.8+/-5.8% predicted) were within the normal range in SSc patients. VO2peak of SSc patients was significantly reduced in comparison to the control group (19.8+/-4.6 vs. 23.7+/-4.5 mL/kg/min, p = 0.04). SSc patients also had a significant reduction in MET at peak exercise (5.6+/-1.3 vs. 6.7+/-1.3 MET, p = 0.04) and a significant shorter time interval between AT and RCP compared to the control group (112.6+/-95.6 vs. 164.0+/-65.3 s, p = 0.03). CONCLUSION: SSc patients without pulmonary impairment have reduced exercise capacity. Abnormal vascular response to exercise may account for this finding, as the vascular system is one of the major target organs in this pathological condition.

Giant diverticula of the colon: a clinical assessment.

Giant colonic diverticulum is a rare complication of diverticular disease. In the English literature, only 81 cases have been described. Twelve patients had complications caused by the giant diverticulum. Seventy patients were treated operatively, and three died. Elective resection of the diverticulum and the adjacent colon with primary anastomosis is the ideal treatment. The significant number of complications caused by the giant diverticulum and the low morbidity and mortality rate associated with surgical treatment reinforce the importance of accurate diagnosis and elective treatment of this disorder.

Ischemic intervals during warm blood cardioplegia in the canine heart evaluated by phosphorus 31-magnetic resonance spectroscopy.

OBJECTIVE: Warm blood cardioplegia requires interruption by ischemic intervals to aid visualization. We evaluated the safety of repeated interruption of warm blood cardioplegia by normothermic ischemic periods of varying durations. METHODS: In three groups of isolated cross-perfused canine hearts, left ventricular function was measured before and for 2 hours of recovery after arrest, which comprised four 15-minute periods of cardioplegia alternating with three ischemic intervals of 15, 20, or 30 minutes (I15, I20, and I30). Metabolism was continuously measured by phosphorus 31-magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate level fell progressively as ischemia was prolonged; after recovery, adenosine triphosphate was 99% +/- 6%, 90% +/- 1% (p = 0.0004 vs control), and 68% +/- 3% (p = 0.0002) of control levels in I15, I20, and I30, respectively. Intracellular acidosis with ischemia was most marked in I30. After recovery, left ventricular maximal systolic elastance at constant heart rate and coronary perfusion pressure was maintained in I15 but fell to 85% +/- 3% in I20, (p = 0.003) and to 65% +/- 6% (p = 0.003) of control values in I30, while relaxation (tau) was prolonged only in I30 (p = 0.007). CONCLUSIONS: Hearts recover fully after three 15-minutes periods of ischemia during warm blood cardioplegia, but deterioration, significant with 20-minute periods, is profound when the ischemic periods are lengthened to 30 minutes. This suggests that in the clinical setting warm cardioplegia can be safely interrupted for short intervals, but longer interruptions require caution.