Increased natural killer activity does not prevent progression of experimental kala-azar

Kala-azar is the visceral form of leishmaniasis and it is caused by intracellular parasites from the complex Leishmania donovani. Golden hamster (Mesocricetus auratus) infected with Leishmania donovani develop a disease very similar to human Kala-azar. There is conspicuous hipergammaglobulinaemia and their T cells do not respond to stimulation with parasite antigens. We used this experimental model to evaluate the natural killer (NK) activity during the initial phase of the disease. Outbred hamsters infected by intravenous route with 5.106 amastigotes of L. donovani 1S showed a concurrent increase in the spleen weight and in the spleen cell number. Using the single cell assay we detected a significant increase in the percentage of NK effector cells on the 4th day of infection. Imprints from spleen and liver showed at days 14 and 28 a significant increase in the parasite burden. These results show that the increased NK activity in the beginning of the infection was not able to restrain the progression of the disease in this experimental model.

MicroRNA Signature Obtained From the Comparison of Aggressive With Indolent Non-Hodgkin Lymphomas: Potential Prognostic Value in Mantle-Cell Lymphoma

Purpose Mantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis.MethodsWe assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL.ResultsFourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores.ConclusionEleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL. (C) 2013 by American Society of Clinical Oncology

Daily photosynthesis, water relations, and ion concentrations of uuonymus irrigated with treated wastewater

Euonymus japonica Thunb. (euonymus) plants were submitted for 9 months to two irrigation treatments using water from different sources: a control (C) water with electrical conductivity (EC) less than 1.2 dS.m(-1) and reclaimed wastewater (RW) with EC approximate to 4 dS.m(-1). At the end of the experiment, no differences in the total dry weight were observed between treatments, whereas the leaf dry mass increased (to the detriment of the root part in RW plants). Throughout the day, the stem water potential (Psi(stem)) of the RW plants was lower than in C, whereas stomatal conductance (g(S)) was slightly reduced in RW from 0800 HR to 1200 HR, but no significant variation in photosynthesis (P-n) or energy conversion efficiency (F'(v)/F'(m)) in photosystem II was detected through the effect of salinity. Gas exchange and fluorescence showed a tendency to increase after midday in plants treated with RW. The photosynthetic behavior and fluorescence of RW plants may have been related to the nitrogen and chlorophyll content of the leaves, confirming the resistance of the photosynthetic mechanism to salinity in this species in these conditions. The toxic effects produced by high concentrations of boron (B), sodium (Na+) and chloride (Cl-) were offset by the effect of other ions like magnesium (Mg2+), potassium (K+), and phosphorus (P) in plants irrigated with RW, thus improving their physiological status without decreasing their ornamental value.

Pulsing With Low Concentration Gibberellin Plus Benzyladenine or Commercial Floral Preservatives Affect Postharvest Longevity, Quality, and Leaf Chlorosis of Cut Lilies and Gladioli

Effects of pulsing with different concentrations of gibberellin plus benzyladenine (GA(4+7) + BA), a proprietary mixture of GA(4+7) plus BA in a commercial floral preservative (GA(4+7) + BA + preservative), or a propriety mixture of sugar plus acidifier developed for bulbous flowers (floral bulb preservative) were studied on postharvest performance and quality of cut lily (Lilium hybrids) and gladiolus ( Gladiolus hybrids) flowers. Pulsing of cut stems of lily with GA(4+7) + BA at 5 or 2 mL.L-1 GA(4+7) + BA + preservative for 20 hours at 3 +/- 1 degrees C extended the vase life and controlled leaf chlorosis of 'Cobra'oriental lily and 'Cappuccino'and Pot Corn'asiatic lily. Cut 'Orange Art'asiatic lily performed best when pulsed with GA(4+7) + BA at 10 mg.L-1. For cut gladiolus, pulsing with GA(4+7) + BA at 10 mg.L-1 extended the vase life of 'Alice', 'Mammoth', and 'Passion', while 'Scarlet'had the longest vase life when pulsed with 5 mg.L-1 GA(4+7) + BA. GA(4+7) + BA + preservative also extended the vase life and controlled leaf chlorosis, but the floral bulb preservative had no effect on vase life extension or preventing leaf chlorosis of lilies. Gladiolus cultivars had no or minor leaf chlorosis during vase period. Overall, overnight pulsing with GA(4+7) + BA + or GA(4+7) + BA + preservative extended the vase life and prevented leaf chlorosis

In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups

OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AM I). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), >= 50 and <60 (n = 477),>= 60 and <70 (n = 545), >= 70 and <80 (n = 495), and years (n = 209). Hyperglycemia was defined as initial glucose >= 115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001.), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity

OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

FALCAI MJ, LOUZADA MJQ, DE PAULA FJA, OKUBO R, VOLPON JB. A modified technique of rat tail suspension for longer periods of observation. Aviat Space Environ Med 2012; 83:1176-80. Background: Rat tail suspension is an accepted method to create experimental osteopenia. However, suspension periods longer than 3 wk may cause tail skin sloughing or rat slippage. The hypothesis was that a traction system with skeletal anchorage through one tail vertebra would prolong the suspension time without significant complications. Methods: There were 80 young adult female Wistar rats that were submitted to one of the following interventions: skeletal tail suspension (N = 20), skin tail suspension (N = 20), no intervention (N = 20), and a baseline control (N = 20). All animals were followed up either for 3 (N = 10) or 6 (N = 10) wk. Animals were assessed for clinical signs of stress and tolerance to suspension. The femur evaluation was in terms of mineral density content, mechanical resistance, and histomorphometry. Results/Discussion: All animals reached the 3-wk end point. However, for the 6-wk period, seven animals suspended by the skin traction method were discarded (70%) because of signs of stress and skin sloughing. In contrast, there was one loss in the skeletal suspension group (10%). All suspended animals developed similar osteopenia at 3 wk characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass. At 6 wk, all suspended animals had similar osteopenic parameters, but they were not statistically different from those of the rats in the 3-wk groups. Therefore, suspension longer than 3 wk did not increase the bone deterioration in the femur.

Translation and Cross-cultural Adaptation of the Lower Extremity Functional Scale Into a Brazilian Portuguese Version and Validation on Patients With Knee Injuries

STUDY DESIGN: Clinical measurement. OBJECTIVE: To translate and culturally adapt the Lower Extremity Functional Scale (LEFS) into a Brazilian Portuguese version, and to test the construct and content validity and reliability of this version in patients with knee injuries. BACKGROUND: There is no Brazilian Portuguese version of an instrument to assess the function of the lower extremity after orthopaedic injury. METHODS: The translation of the original English version of the LEFS into a Brazilian Portuguese version was accomplished using standard guidelines and tested in 31 patients with knee injuries. Subsequently, 87 patients with a variety of knee disorders completed the Brazilian Portuguese LEES, the Medical Outcomes Study 36-Item Short-Form Health Survey, the Western Ontario and McMaster Universities Osteoarthritis Index, and the International Knee Documentation Committee Subjective Knee Evaluation Form and a visual analog scale for pain. All patients were retested within 2 days to determine reliability of these measures. Validation was assessed by determining the level of association between the Brazilian Portuguese LEFS and the other outcome measures. Reliability was documented by calculating internal consistency, test-retest reliability, and standard error of measurement. RESULTS: The Brazilian Portuguese LEES had a high level of association with the physical component of the Medical Outcomes Study 36-Item Short-Form Health Survey (r = 0.82), the Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.87), the International Knee Documentation Committee Subjective Knee Evaluation Form (r = 0.82), and the pain visual analog scale (r = -0.60) (all, P<.05). The Brazilian Portuguese LEES had a low level of association with the mental component of the Medical Outcomes Study 36-Item Short-Form Health Survey (r = 0.38, P<.05). The internal consistency (Cronbach alpha = .952) and test-retest reliability (intraclass correlation coefficient = 0.957) of the Brazilian Portuguese version of the LEES were high. The standard error of measurement was low (3.6) and the agreement was considered high, demonstrated by the small differences between test and retest and the narrow limit of agreement, as observed in Bland-Altman and survival-agreement plots. CONCLUSION: The translation of the LEFS into a Brazilian Portuguese version was successful in preserving the semantic and measurement properties of the original version and was shown to be valid and reliable in a Brazilian population with knee injuries. J Ort hop Sports Phys Ther 2012;42(11):932-939, Epub 9 October 2012. doi:10.2519/jospt.2012.4101

Muscle Atrophy and Functional Deficits of Knee Extensors and Flexors in People With Chronic Stroke

Background. Further clarification is needed with regard to the degree of atrophy in individual muscle groups and its possible relationship to joint torque deficit poststroke. Objective. The purpose of this study was to investigate quadriceps and hamstring muscle volume and strength deficits of the knee extensors and flexors in people with chronic hemiparesis compared with a control group. Design. This was a cross-sectional study. Methods. Thirteen individuals with hemiparesis due to chronic stroke (hemiparetic group) and 13 individuals who were healthy (control group) participated in this study. Motor function, quadriceps and hamstring muscle volume, and maximal concentric and eccentric contractions of the knee extensors and flexors were assessed. Results. Only the quadriceps muscle of the paretic limb showed reduced muscle volume (24%) compared with the contralateral (nonparetic) limb. There were no differences in muscle volume between the hemiparetic and control groups. The peak torque of the paretic-limb knee extensors and flexors was reduced in both contraction modes and velocities compared with the nonparetic limb (36%-67%) and with the control group (49%-75%). The nonparetic limb also showed decreased extensor and flexor peak torque compared with the control group (17%-23%). Power showed similar deficits in strength (12%-78%). There were significant correlations between motor function and strength deficits (.54-.67). Limitations. Magnetic resonance imaging coil length did not allow measurement of the proximal region of the thigh. Conclusions. There were different responses between quadriceps and hamstring muscle volumes in the paretic limb that had quadriceps muscle atrophy only. However, both paretic and nonparetic limbs showed knee extensor and flexor torque and power reduction.