Decreased T cell apoptosis and T cell recovery during highly active antiretroviral therapy (HAART)

T cell apoptosis represents a common mechanism of T cell depletion in HIV-1-infected individuals reflecting maturational and functional T cell abnormalities either directly or indirectly induced by the virus. In the present study, the effects of highly active antiretroviral therapy (HAART) on the spontaneous apoptosis of distinct T cell subsets were investigated during a 6-month follow-up in a cohort of HIV-1-infected individuals with CD4(+) cell counts between 100 and 500 cells/microliter and plasma HIV-1 RNA levels >/=10, 000 copies/ml. We determined that the rapid and sustained increase of both naive (CD45RA(+)CD62L(+)) and memory (CD45R0(+) and CD45RA(+)/CD62L(-)) CD4(+) and, to as lesser extent, CD8(+) T cells in peripheral blood was associated with a significant decrease of apoptotic CD4(+) and CD8(+) as well as CD3(+)CD4(-)CD8(-) T cells. Among CD4(+) lymphocytes, at enrollment, the highest frequency of apoptotic cells was observed within the memory compartment, as defined by CD45R0 expression. During HAART, however, the frequency of CD4(+)CD45R0(+) apoptotic T cells progressively decreased in association with a significant downregulation of surface activation markers that indicated decreased levels of systemic immune stimulation. These results indicate that effective viral suppression can contribute to progressive normalization of maturational and functional T cell abnormalities responsible for the high levels of T cell apoptosis in HIV-1-infected individuals. This, in turn, may contribute to a reduced rate of T cell loss and immune reconstitution during HAART.     

Whole‐genome amplification for the detection of molecular targets and minimal residual disease monitoring in acute lymphoblastic leukaemia

Accurate genomic characterization requires sufficient amounts of optimal quality DNA. An approach for increasing the DNA amount is the whole‐genome amplification (WGA) method. We applied WGA to the molecular quantification and minimal residual disease (MRD) evaluation of acute lymphoblastic leukaemia (ALL), aiming to compare the results obtained from genomic DNA and amplified DNA with WGA, and to evaluate the applicability and the reliability of WGA‐DNA. Twenty paired samples from adult ALL patients were sequenced to identify the functional germline V‐D‐J segment at diagnosis; real‐time quantitative polymerase chain reaction (RQ‐PCR) quantitative analysis was performed both at diagnosis and follow‐up. Genomic DNA and WGA‐DNA screening identified equivalent 87 rearrangements. At diagnosis, the quantitative evaluation of genomic DNA samples showed 1 logarithm difference to WGA‐DNA samples; these levels are comparable, being within the degree of acceptability and confidence. In the follow‐up samples, RQ‐PCR analysis on genomic DNA and WGA showed concordant MRD results in 16/18 samples, while 2/18 were MRD‐positive outside the quantitative range by RQ‐PCR (i.e. <5 × 10^?5) on genomic DNA and MRD‐negative on WGA‐DNA. WGA‐DNA enables: (i) the design of accurate targets for MRD evaluation in ALL patients, (ii) accurate disease quantification at diagnosis, (iii) MRD quantification comparable to genomic DNA.     

Regression of cardiac hypertrophy: morphometric and biochemical studies in rat heart after swimming training

There is currently little information about the morphological changes of the myocardium accompanying the reversal of cardiac hypertrophy. In this study the hypothesis was tested that myocardial alterations induced by exercise will regress within a short interval after the end of training. Rat hearts were examined using morphometric and biochemical methods at the end of a 9-week period of endurance training and also 7, 10 and 14 days after its termination. At the end of the training period the heart weight had increased by 65% but the weight ratio of the right and left ventricular wall remained unchanged. A decline in the DNA content by 27% as well as a decrease in the volume density of the interstitial space by 14% and in the number of interstitial cell nuclei by 32% against controls, are explained by a 30% increase in the width of myofibres. The capillary density was reduced by 22% but the volume density of capillaries remained nearly constant as a result of widening of the capillary diameter by 27%. The surface density of capillaries was diminished by 10%. Ultrastructurally an increase in the ratio of mitochondrial to myofibrillar volume density was observed in the myocytes of hypertrophied hearts as compared to controls (0.54 and 0.63, respectively). Fourteen days after termination of training, 80% of the increment in heart weight had regressed. At this time the width of the myofibres and the volume density of the interstitial space had nearly normalized, while the capillary to fibre ratio had significantly increased. The ratio of mitochondrial and myofibrillar volume density became nearly normal, and a confluence of intermyofibrillar mitochondria resulted in significantly longer organelles. The increased DNA content 10 days after the training, as compared to controls, is attributable to the genesis of non-myocardial cells during the hypertrophic growth and their persistence during regression. The study has shown that cardiac hypertrophy induced by physical training nearly completely regresses within 14 days after termination of conditioning. The increased capillary to fibre ratio indicates neoformation of transversely oriented capillary branches in hypertrophy which particularly becomes apparent in two-dimensional estimation in the regression period. In comparison with myofibres, regression of capillaries seems to be delayed. The decline of heart weight and a significantly diminished RNA content during the regression of hypertrophy suggest that reduced synthesis is responsible for the decrease in heart weight.     

Volar PEEK plate for distal radius fracture: analysis of adverse events

European Journal of Orthopaedic Surgery & Traumatology - The aim of the present retrospective study was to evaluate complications following carbon-fiber-reinforced polyetheretherketon...     

Impact of family empowerment model on satisfaction and children’s length of stay in hospital

Objective

The purpose of the study was to identify the impact of family empowerment model intervention on family satisfaction and children’s length of stay in the hospital due to pneumonia.

Changes in long-term glycemic control and performance indicators in a cohort of type 2 diabetic patients cared for by general practitioners: findings from the "Modena Diabetes Project"

BACKGROUND AND AIM: General practitioners (GPs) are being increasingly asked to play a key role in the shared care of people with diabetes mellitus, but data concerning the effects of this in Italy are still scarce. We therefore evaluated the 4-year follow-up changes in outcomes and performance indicators in type 2 diabetic patients cared for by GPs in the framework of the "Modena Diabetes Project". METHODS AND RESULTS: Seventy-four percent of the local GPs participating in the project (387 out of 521) sent 5260 paired baseline and follow-up datasheets. The baseline characteristics of the type 2 diabetic patients (49.6% male) were a mean age of 67.3+/-11.2 years, a mean disease duration of 10.9+/-7.4 years, a mean BMI of 28.7+/-4.8 kg/m2, and a mean HbA1c level 7.56+/-1.52%. After four years follow-up, the individual before/after match-paired outcomes revealed an improvement in glycemic control: HbA1c levels significantly decreased to 7.39+/-1.31%, and the percentage of patients with HbA1c level of <6.5% significantly increased from 15.7% to 22.1%. There was also a significant decrease in body weight (from 78.3+/-14.8 to 77.6+/-14.6 kg) and BMI (from 28.8+/-4.8 to 28.5+/-4.9 kg/m2). The time trends of glycemic control significantly improved during the 4-year follow up, but those of the body weight and BMI values did not. Furthermore, the percentages of performance indicators matching the expected rate of recurrence per each year of follow-up significantly improved during the study period. CONCLUSIONS: Long-term glycemic control and the performance indicators relating to the type 2 diabetic patients participating in our shared care programme progressively improved.