Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Revisiting the Plasmodium falciparum RIFIN family: from comparative genomics to 3D-model prediction

<p>Abstract</p> <p>Background</p> <p>Subtelomeric <it>RIFIN </it>genes constitute the most abundant multigene family in <it>Plasmodium falciparum</it>. <it>RIFIN </it>products are targets for the human immune response and contribute to the antigenic variability of the parasite. They are transmembrane proteins grouped into two sub-families (RIF_A and RIF_B). Although recent data show that RIF_A and RIF_B have different sub-cellular localisations and possibly different functions, the same structural organisation has been proposed for members of the two sub-families. Despite recent advances, our knowledge of the regulation of <it>RIFIN </it>gene expression is still poor and the biological role of the protein products remain obscure.</p> <p>Results</p> <p>Comparative studies on <it>RIFINs </it>in three clones of <it>P. falciparum </it>(3D7, HB3 and Dd2) by Multidimensional scaling (MDS) showed that gene sequences evolve differently in the 5'upstream, coding, and 3'downstream regions, and suggested a possible role of highly conserved 3' downstream sequences. Despite the expected polymorphism, we found that the overall structure of <it>RIFIN </it>repertoires is conserved among clones suggesting a balance between genetic drift and homogenisation mechanisms which guarantees emergence of novel variants but preserves the functionality of genes. Protein sequences from a <it>bona fide </it>set of 3D7 RIFINs were submitted to predictors of secondary structure elements. In contrast with the previously proposed structural organisation, no signal peptide and only one transmembrane helix were predicted for the majority of RIF_As. Finally, we developed a strategy to obtain a reliable 3D-model for RIF_As. We generated 265 possible structures from 53 non-redundant sequences, from which clustering and quality assessments selected two models as the most representative for putative RIFIN protein structures.</p> <p>Conclusion</p> <p>First, comparative analyses of <it>RIFIN </it>repertoires in different clones of <it>P. falciparum </it>provide insights on evolutionary mechanisms shaping the multigene family. Secondly, we found that members of the two sub-families RIF_As and RIF_Bs have different structural organization in accordance with recent experimental results. Finally, representative models for RIF_As have an "Armadillo-like" fold which is known to promote protein-protein interactions in diverse contexts.</p

On the semiclassical treatment of Hawking radiation

In the context of the semiclassical treatment of Hawking radiation we prove the universality of the reduced canonical momentum for the system of a massive shell self gravitating in a spherical gravitational field within the Painlev\'e family of gauges. We show that one can construct modes which are regular on the horizon both by considering as hamiltonian the exterior boundary term and by using as hamiltonian the interior boundary term. The late time expansion is given in both approaches and their time Fourier expansion computed to reproduce the self reaction correction to the Hawking spectrum.Comment: 18 pages, LaTeX, Corrected typo

Factors affecting soil invertebrate biodiversity in agroecosystems of the Po Plain area (Italy)

Soil is a fundamental component of the biosphere, whose properties and quality are affected by human activities, such as agriculture. Soil health is fundamental for different ecosystem services and soil biota has a crucial role in maintaining it. Elucidating how different crops and agricultural practices affect soil invertebrates communities is of relevance. In the present study, a DNA metabarcoding approach was adopted to evaluate the effects of different biotic and abiotic factors, including agricultural practices, on the composition and diversity of soil invertebrate communities of different agro-ecosystems (Po Plain-Italy). At this aim, the DNA markers and the more effective primers in retrieving soil metazoan communities were established. Bulk soil samples from different agro-ecosystems (i.e., cornfield, alfalfa, paddy fields, vineyard, stable meadow, woodland) were collected and, processed for obtaining 18S rRNA and coi sequences (raw reads analyzed using QIIME2 and R). Soil physical and chemical parameters were measured for each soil sample (e.g., pH, carbon-nitrogen ratio, texture, porosity) and metadata on farms management were retrieved. The most efficient primer pairs in recovering soil metazoans were M620F/M1260R for 18S rRNA, and mlCOIintF/jgHCO2198R for coi gene. Soil communities resulted dominated by Nematoda, Arthropoda, Annelida, Rotifera and Tardigrada. The most diverse invertebrate communities have been found in the soil of stable meadows and woodlands, while cornfields showed the lowest level of diversity. The diversity of soil invertebrate communities (Hill numbers) was positively correlated with the level of porosity and carbon-nitrogen ratio, while it was negatively correlated with the phosphate abundance. This pattern probably reflects the negative effect of excessive fertilization with phosphates on soil fauna, while the abundance of organic matter and microhabitats were found to enhance the presence of more complex communities. Other soil properties were correlated only with specific taxa (e.g., pH was negatively correlated with the diversity of Annelida and Rotifera)

Magnetostriction-driven muon localization in an antiferromagnetic oxide

Magnetostriction results from the coupling between magnetic and elastic degrees of freedom. Though it is associated with a relatively small energy, we show that it plays an important role in determining the site of an implanted muon, so that the energetically favorable site can switch on crossing a magnetic phase transition. This surprising effect is demonstrated in the cubic rocksalt antiferromagnet MnO which undergoes a magnetostriction-driven rhombohedral distortion at the Néel temperature T_{N}=118  K. Above T_{N}, the muon becomes delocalized around a network of equivalent sites, but below T_{N} the distortion lifts the degeneracy between these equivalent sites. Our first-principles simulations based on Hubbard-corrected density-functional theory and molecular dynamics are consistent with the experimental data and help to resolve a long-standing puzzle regarding muon data on MnO, as well as having wider applicability to other magnetic oxides

Whole-body low-dose CT recognizes two distinct patterns of lytic lesions in multiple myeloma patients with different disease metabolism at PET/MRI

We evaluated differences in density and 18F-FDG PET/MRI features of lytic bone lesions (LBLs) identified by whole-body low-dose CT (WB-LDCT) in patients affected by newly diagnosed multiple myeloma (MM). In 18 MM patients, 135 unequivocal LBLs identified by WB-LDCT were characterized for inner density (negative or positive Hounsfield unit (HU)), where negative density (HU\u2009<\u20090) characterizes normal yellow marrow whereas positive HU correlates with tissue-like infiltrative pattern. The same LBLs were analyzed by 18F-FDG PET/DWI-MRI, registering DWI signal with ADC and SUV max values. According to HU, 35 lesions had a negative density (-\u200956.94\u2009\ub1\u200931.87 HU) while 100 lesions presented positive density (44.87\u2009\ub1\u200923.89 HU). In seven patients, only positive HU LBLs were demonstrated whereas in eight patients, both positive and negative HU LBLs were detected. Intriguingly, in three patients (16%), only negative HU LBLs were shown. At 18F-FDG PET/DWI-MRI analysis, negative HU LBLs presented low ADC values (360.69\u2009\ub1\u2009154.38\u2009 7\u200910-6 mm2/s) and low SUV max values (1.69\u2009\ub1\u20090.56), consistent with fatty marrow, whereas positive HU LBLs showed an infiltrative pattern, characterized by higher ADC (mean 868.46\u2009\ub1\u2009207.67\u2009 7\u200910-6 mm2/s) and SUV max (mean 5.04\u2009\ub1\u20091.94) values. Surprisingly, histology of negative HU LBLs documented infiltration by neoplastic plasma cells scattered among adipocytes. In conclusion, two different patterns of LBLs were detected by WB-LDCT in MM patients. Both types of lesions were indicative for active disease, although only positive HU LBL were captured by 18F-FDG PET/DWI-MRI imaging, indicating that WB-LDCT adds specific information

Retroperitoneal extension of massive ulcerated testicular seminoma through the inguinal canal: A case report.

Introduction: Testicular cancers represent about 5% of all urological malignancies and 1-1.5% of all male neoplasms. Most of the testicular cancers are localized (68%) at diagnosis. Bulky masses in the scrotum are rare. We present a rare case of bulky testicular cancer with retroperitoneal spread through the inguinal canal. Case report: A 44-year-old man came to the emergency department referring weakness and the presence of a scrotal mass. At physical examination, a voluminous mass was found, with necrotic phenomena within the scrotum. Abdomen was tense and sore. Abdominal CT scan revealed a bulky testicular mass spreading to the retroperitoneal space through the inguinal canal with node enlargement. Patient underwent orchiectomy with excision of infiltrated scrotum skin. Histologic diagnosis confirmed a typical form seminoma. The patient was then treated with a cisplatin-based chemotherapy, with a partial response. The patient recently relapsed and he is being treated with a new line of chemotherapy and subsequent surgery with or without radiotherapy. Conclusions: We described a rare presentation of testicular cancer. This case highlights the importance of a multidisciplinary approach to rare testis tumour presentation and early diagnosis for testicular cancers

The Non-Invasive Diagnosis of Chronic Coronary Syndrome: A Focus on Stress Computed Tomography Perfusion and Stress Cardiac Magnetic Resonance

Coronary artery disease is still a major cause of death and morbidity worldwide. In the setting of chronic coronary disease, demonstration of inducible ischemia is mandatory to address treatment. Consequently, scientific and technological efforts were made in response to the request for non-invasive diagnostic tools with better sensitivity and specificity. To date, clinicians have at their disposal a wide range of stress-imaging techniques. Among others, stress cardiac magnetic resonance (S-CMR) and computed tomography perfusion (CTP) techniques both demonstrated their diagnostic efficacy and prognostic value in clinical trials when compared to other non-invasive ischemia-assessing techniques and invasive fractional flow reserve measurement techniques. Standardized protocols for both S-CMR and CTP usually imply the administration of vasodilator agents to induce hyperemia and contrast agents to depict perfusion defects. However, both methods have their own limitations, meaning that optimizing their performance still requires a patient-tailored approach. This review focuses on the characteristics, drawbacks, and future perspectives of these two techniques

Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Undergoing Orthopedic and Hand Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication in any type of surgery and can occur up to one year after the procedure in the case of implant placement. In the field of orthopedic and hand surgery, the rate of SSIs is a relevant issue, considering the need for the placement of synthesis devices and the type of some interventions (e.g., exposed fractures). This work aims to provide guidance on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing orthopedic and hand surgery in order to standardize the management of patients and to reduce, on the one hand, the risk of SSI and, on the other, the development of antimicrobial resistance. The following scenarios were considered: (1) bloodless fracture reduction; (2) reduction of unexposed fracture and grade I and II exposed fracture; (3) reduction of grade III exposed fracture or traumatic amputation; (4) cruel fracture reduction with percutaneous synthesis; (5) non-traumatic amputation; (6) emergency intact skin trauma surgery and elective surgery without synthetic media placement; (7) elective orthopedic surgery with prosthetic and/or synthetic media placement and spinal surgery; (8) clean elective hand surgery with and without bone involvement, without use of synthetic means; (9) surgery of the hand on an elective basis with bone involvement and/or with use of synthetic means. This manuscript has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding the behavior to be adopted in the peri-operative setting in neonatal and pediatric orthopedic and hand surgery. The specific scenarios developed are aimed at guiding the healthcare professional in practice to ensure the better and standardized management of neonatal and pediatric patients, together with an easy consultation