Risk factors for endocrine complications in transfusion-dependent thalassemia patients on chelation therapy with deferasirox: a risk assessment study from a multicentre nation-wide cohort

Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3-13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1-1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1-1.4, P

An approach for predicting the stability of vertical cuts in cohesionless soils above the water table

Temporary vertical excavations in cohesionless (granular soils) pose a problem for conventional ‘two-phase’ soil mechanics theory since non-zero collapse height is not predicted using the classical ‘dry/saturated’ shear strength criterion, given that cohesionless soils above the water table are assumed to be dry. An extension of the classical shear strength equation to account for the effect of matric suction on the effective stress in partially saturated soil is presented here that is incorporated into the bound theorems of plasticity. A simple validation experiment is reported to test the concept following which, a case study is presented that explores the extent to which matric suction and its impact on shear strength can explain the large safe vertical cut height that is often observed in cohesionless pozzolan deposits in the field. Lastly, the impact of rainfall events and subsequent ponded infiltration is investigated using a very simple analytical technique based on the classical Terzaghi consolidation solution. The research presented here gives practitioners with no particular expertise in the mechanics of unsaturated soil, techniques to assess the stability of geostructures involving unsaturated cohesionless soils that are based on simple calculation techniques taught in undergraduate courses

Evaluation of Masticatory Muscle Function Using Digital versus Traditional Techniques for Mockup Fabrication: A Controlled Prospective Study

Background: the aim of this longitudinal prospective study was to analyze the effect of digital and traditional mockup on masticatory muscle activity in patients with teeth wear, rehabilitated with an increase of occlusal vertical dimension. Subjects and Methods: a sample of 22 adult patients who were about to receive a prosthetic rehabilitation was divided into a study group (3M; 9F; mean age 42 ± 0.8 years), treated using the digital mockup; and a control group (2M; 8F; mean age 37 ± 0.5 years), treated using the conventional technique (traditional) mockup. Electromyographic activity of anterior temporalis and masseter muscles were evaluated before the beginning of the treatment (T0), at mockup insertion (T1), after treatment (T2) and each lapse of time lasted 2–5 months. Results: the comparison between the two groups at different time gaps revealed that at ∆1 (T1–T0) only the impact index (IMP) showed significant difference and no other significant variation was observed between the two groups at ∆2 (T2–T1) and ∆3 (T2–T0). It concludes that traditional and digital methods generally have nonsignificant differences. Conclusions: both methods seem to be effective in prosthetic rehabilitation and give comparable effects on masticatory muscles

Super-Resolution Imaging of Bacteria in a Microfluidics Device

<div><p>Bacteria have evolved complex, highly-coordinated, multi-component cellular engines to achieve high degrees of efficiency, accuracy, adaptability, and redundancy. Super-resolution fluorescence microscopy methods are ideally suited to investigate the internal composition, architecture, and dynamics of molecular machines and large cellular complexes. These techniques require the long-term stability of samples, high signal-to-noise-ratios, low chromatic aberrations and surface flatness, conditions difficult to meet with traditional immobilization methods. We present a method in which cells are functionalized to a microfluidics device and fluorophores are injected and imaged sequentially. This method has several advantages, as it permits the long-term immobilization of cells and proper correction of drift, avoids chromatic aberrations caused by the use of different filter sets, and allows for the flat immobilization of cells on the surface. In addition, we show that different surface chemistries can be used to image bacteria at different time-scales, and we introduce an automated cell detection and image analysis procedure that can be used to obtain cell-to-cell, single-molecule localization and dynamic heterogeneity as well as average properties at the super-resolution level.</p></div

An attempt to induce transient immunosuppression pre-erythrocytapheresis in a girl with sickle cell disease, a history of severe delayed hemolytic transfusion reactions and need for hip prosthesis

We report on a case of delayed hemolytic transfusion reaction (DHTR) occurred 7 days after an erythrocytapheresis or eritroexchange procedure (EEX) treated with rituximab and glucocorticoids in a 15-years old patient with sickle cell disease. EEX was performed despite a previous diagnosis of alloimmunization, in order to reduce hemoglobin S rate before a major surgery for avascular necrosis of the femoral head. A first dose of rituximab was administered before EEX. However, rituximab couldn’t prevent DHTR that occurred with acute hemolysis, hemoglobinuria and hyper-bilirubinemia. A further dose of rituximab and three boli of methylprednisolone were given after the onset of the reaction. It is likely that the combined use of rituximab and steroids managed to gradually improve both patient’s general conditions and hemoglobin levels. Nor early or late side effects were registered in a 33-months follow-up period. This report suggests the potential effectiveness and safety of rituximab in combination with steroids in managing and mitigating the symptoms of delayed post-transfusional hemolytic reactions in alloimmunized patients affected by sickle cell disease with absolute need for erythrocytapheresis

A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up

Electroluminescent devices based on nanosilicon multilayer structures

In this contribution we give an overview of our development of size-controlled multilayered ensembles of silicon nanocrystals (Si-NCs) for efficient light emitting devices (LEDs). The ensembles of Si-NCs embedded in silicon dioxide are grown by chemical vapour deposition methods and by using standard microelectronic processes. The formation of nanocrystals is monitored by several analytical techniques. Novel LED architectures of nanocrystal ensembles which improve electrical injection and light emission are described. Charge tunnelling in nanosilicon superlattices, light emission efficiency under direct and alternating current injection, and device stability are discussed

smSRM of bacteria in agarose pads.

<p><b> A. smSRM imaging of bacteria in agarose pads.</b> (i) A double-side adhesive o-ring was placed on a coverslip and melted agarose was added to create an adhering surface for the bacteria. (ii) Bacterial cells, previously stained with the membrane dye FM4-64 mixed with fiducial marks, were deposited on agarose and the pad was sealed with a clean coverslip. The sample was finally fixed on an Attofluor cell (Invitrogen) to avoid bacterial motion during microscopy. (iii–iv) Sequential imaging of bacterial membrane and SpoIIIE (iii) Epi-fluorescence image of the cell membrane was collected by exiting at 532 nm. (iv) smSRM images were collected by using continuous excitation with a 532 nm laser and by applying regular pulses of photo-activation with a 405 nm laser. <b>B–C. Lateral drift during smSRM acquisition in agarose pads.</b> Lateral drift over the full acquisition period was assessed by plotting the trajectories of fluorescent beads in <i>x</i> (B) and <i>y</i> (C) coordinates over time. Each colored trajectory corresponds to a single fluorescent bead. <b>D–E. Alignment correction in smSRM experiments in agarose pads.</b> Distortion arising from chromatic aberrations was quantified from the distance between the same fluorescent beads observed in two different emission channels (D) and corrected by using a linear transformation procedure (E) (see Materials and Methods). Each dot represents a different bead and the abcissa represents the <i>x</i> coordinate of each bead. Error bars represent the precision of localization before (D) and after (E) drift and alignment correction. <b>F–G. Bleed-through of the membrane staining agent FM4-64 during smSRM imaging in agarose pads. (i)</b> Image of a cell in the SpoIIIE-PA (SpoIIIE-eosFP) (F) and FM4-64 (G) channels. (ii) Line scans of the fluorescence signal across a <i>B. subtilis</i> cell (white dotted line in panels F-i and G-i) in the two observation channels (green and red lines, respectively). For comparison, the line scan of the fluorescence intensity emitted by a single SpoIIIE-PA protein was overlapped in F-ii (black dotted line). As expected, the signal-to-noise ratio and contrast in the red channel are adequate (SNR = 40/contrast = 2.3, panel G-ii). However, even at low dye concentrations the fluorescence signal from FM4-64 bleeds into the SpoIIIE-PA channel (SNR = 8/contrast = 1.3, panel F-ii), compromising single-molecule detection, lowering the localization precision, and often leading to false positive localizations. For comparison, in the single-molecule trace shown in F-ii the signal to noise ratio is 30, and the contrast is 3. <b>H. SpoIIIE localization observed by smSRM in agarose pads.</b> Pointillist representation of SpoIIIE-PA localization in <i>B. subtilis</i> at different cell stages. Each green dot represents a single fluorescent event detected in a single frame during the smSRM acquisition. False positive localizations can be observed scattered homogeneously over the cell membrane.</p