Bone quality in beta-thalassemia intermedia: relationships with bone quantity and endocrine and hematologic variables.

We report the first evaluation of bone quality in 70 thalassemia intermedia (TI) patients (37 males, 33 females, age 41 ± 12 years). Thirty-three patients (47%) had been transfused, 34 (49%) had been splenectomized, 39 (56%) were on iron chelation therapy, and 11 (16%) were on hydroxyurea. Mean hemoglobin was 9.2 ± 1.5 g/dl, median ferritin 537 ng/dl (range 14-4893), and mean liver iron concentration 7.6 ± 6.4 mg Fe/g dw. Fifteen patients (21%) had endocrinopathies, and 29 (41%) had vitamin D deficiency. Bone quantity (bone mineral density, BMD) and bone quality (trabecular bone score, TBS) were evaluated by densitometry. In 53/70 patients (76%), osteopathy was found (osteoporosis in 26/53, osteopenia in 27/53). BMD values were higher in the never-transfused patients and in the not-chelated group. A highly significant correlation was found between splenectomy and BMD at all the sites, with lower values in the splenectomized patients. TBS values were significantly lower in TI patients than in 65 non-thalassemic controls (1.22 vs 1.36, p < 0.01), mainly in those splenectomized and in the transfused and chelated groups (p < 0.01). TBS did not correlate with liver iron concentration values. Our data disclose the major role of non-invasive bone quality evaluation in TI patients, especially those with the worst health state, to obtain a comprehensive assessment of fracture risk. Splenectomy seems to play a major part in bone complications.

Impact of noise in holography with extended references in the low signal regime.

Signal-to-noise ratio is a key factor in lensless imaging, particularly for low diffraction signal experiments in the single shot regime. We present our recent study of the noise impact on holography with extended references. Experimental data have been measured in single shot acquisition using an intense coherent soft X-ray high harmonic source. The impact of hardware and software noise under various detection conditions is discussed. A final comparison between single shot and multi-shot regimes is given.

Treating chronic lymphocytic leukemia with obinutuzumab: safety and efficacy considerations.

INTRODUCTION: Obinutuzumab is a novel glycoengineered type II anti-CD20 monoclonal antibody (MoAb) with a higher affinity for CD20 epitope. It was approved by the United States Food and Drug Administration (FDA) in November 2013 for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL). AREAS COVERED: This article evaluates the safety of obinutuzumab in CLL patients, also addressing pharmacokinetics/pharmacodynamics (PK/PD), clinical use and efficacy. Moreover, a comparison with other anti-CD20 MoAb is performed. The principal available studies on obinutuzumab are reviewed, focusing on CLL. A PubMed literature search (August 2002 to September 2015) was conducted using the terms obinutuzumab, GA101, anti-CD20 antibody, and CLL. EXPERT OPINION: Obinutuzumab, a third-generation anti-CD20 MoAb, is a safe and effective treatment for elderly patients who are un-fit for fludarabine-based regimen. Its use, proven in the CLL11 study and the results of many ongoing trials evaluating other obinutuzumab-based regimen can lead obinutuzumab to be a candidate to replace rituximab as the first-line treatment option.

Adaptation at Specific Loci. III. Field Behavior and Survivorship Differences among Colias Pgi Genotypes Are Predictable from IN VITRO Biochemistry.

Previous work on the phosphoglucose isomerase (PGI) polymorphism of Colias butterflies led to predictions concerning aspects of differential survivorship and fecundity among the polymorphic genotypes in the wild. Explicit assumptions underlying these predictions were that functional differences among genotypes at the in vitro biochemical level reflected roughly corresponding differences in vivo, and that the interaction of such differences with the thermal dependence of flight capacity was correctly understood. All those predictions tested were confirmed. We now report experimental designs for testing three more of these predictions. They concern both differential survivorship and the flight activity component of differential fecundity. We find, as predicted: (1) certain heterozygotes, kinetically most effective at low temperature, begin flight earlier in the day than do other genotypes (six replicates); (2) among the three most common genotypes, the order of kinetic effectiveness, i.e., 3/4 > 3/3 >> 4/4, is reflected in asymmetric order of heterotic advantage, 3/4 > 3/3 >> 4/4, in time of flight initiation, breadth of flight time and/or overall flight density through the day (six replicates); (3) under high temperature stress, the usual survivorship advantage of kinetically favored genotypes is reversed, and the three most thermally stable genotypes show better survivorship.--These results strengthen further the case for direct natural selection on this locus. Implications for population sampling practices, for studies of the adaptive organization of metabolism, and for studies of the interaction of genetic variation with patterns of environmental variability are discussed.

Beta-thalassaemia intermedia: evaluation of endocrine and bone complications.

OBJECTIVE: Data about endocrine and bone disease in nontransfusion-dependent thalassaemia (NTDT) is scanty. The aim of our study was to evaluate these complications in ß-TI adult patients. METHODS: We studied retrospectively 70 ß-TI patients with mean followup of 20 years. Data recorded included age, gender, haemoglobin and ferritin levels, biochemical and endocrine tests, liver iron concentration (LIC) from T2*, transfusion regimen, iron chelation, hydroxyurea, splenectomy, and bone mineralization by dual X-ray absorptiometry. RESULTS: Thirty-seven (53%) males and 33 (47%) females were studied, with mean age 41 ± 12 years, mean haemoglobin 9.2 ± 1.5 g/dL, median ferritin 537 (range 14-4893), and mean LIC 7.6 ± 6.4 mg Fe/g dw. Thirty-three patients (47%) had been transfused, occasionally (24/33; 73%) or regularly (9/33; 27%); 37/70 (53%) had never been transfused; 34/70 patients had been splenectomized (49%); 39 (56%) were on chelation therapy; and 11 (16%) were on hydroxyurea. Endocrinopathies were found in 15 patients (21%): 10 hypothyroidism, 3 hypogonadism, 2 impaired glucose tolerance (IGT), and one diabetes. Bone disease was observed in 53/70 (76%) patients, osteoporosis in 26/53 (49%), and osteopenia in 27/53 (51%). DISCUSSION AND CONCLUSIONS: Bone disease was found in most patients in our study, while endocrinopathies were highly uncommon, especially hypogonadism. We speculate that low iron burden may protect against endocrinopathy development.