Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

Diabetic Ketoacidosis Complicated With Previously Unknown Gitelman Syndrome in a Tunisian Child

Gitelman syndrome (GS) is an auto- somal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. In the great majority of cases, GS is caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive NaCl co- transporter (NCCT), which is specifically expressed in the apical membrane of cells along the distal convoluted tubul

Mesozoic mammaliaforms illuminate the origins of pelage coloration

Pelage coloration, which serves numerous functions, is crucial to the evolution of behavior, physiology, and habitat preferences of mammals. However, little is known about the coloration of Mesozoic mammaliaforms that coevolved with dinosaurs. In this study, we used a dataset of melanosome (melanin-containing organelle) morphology and quantitatively measured hair colors from 116 extant mammals to reliably reconstruct the coloration of six Mesozoic mammaliaforms, including a previously undescribed euharamiyidan. Unlike the highly diverse melanosomes discovered in feathered dinosaurs, hairs in six mammaliaforms of different lineages and diverse ecomorphotypes showed uniform melanosome geometry, corresponding to dark-brown coloration consistent with crypsis and nocturnality. Our results suggest that the melanosome variation and color expansion seen in extant mammals may have occurred during their rapid radiation and diversification after the Cretaceous-Paleogene extinction

Millimetric observations with a high-altitude 2.6-m ground based telescope

High atmospheric performances are necessary to ensure efficient sub/millimetre cosmological observations from ground. Low atmospheric components fluctuations along the line of sight are a must for best detector applications. Such site constraints are attained only at in specific places around the world: highaltitude observatories or, equivalently, polar regions. We are currently involved in cosmological observations with the MITO project from an Alpine ground station which satisfies such requirements: the Testa Grigia mountain at 3500 m a.s.l., AO—Italy. The Chacaltaya laboratory at 5200 m a.s.l. could also be an appropriate mm-site. One of the goals of MITO is the multifrequency observation of nearby rich clusters of galaxies for measuring the Sunyaev-Zel’dovich effect. Combined S-Z and X-ray measurements yield the Hubble constant and other cosmological information. A dedicated instrument has been designed to minimize spurious contaminations on the signals. The telescope is a 2.6 m Cassegrain with a wobbling subreflector and a 4-band single pixel photometer installed at the focal plane. The bolometric detectors are cooled down to 300 mK by a double stage He3-He4 fridge

Millimetric observations with a high-altitude 2.6-m ground based telescope

High atmospheric performances are necessary to ensure efficient sub/millimetre cosmological observations from ground. Low atmospheric components fluctuations along the line of sight are a must for best detector applications. Such site constraints are attained only at in specific places around the world: highaltitude observatories or, equivalently, polar regions. We are currently involved in cosmological observations with the MITO project from an Alpine ground station which satisfies such requirements: the Testa Grigia mountain at 3500 m a.s.l., AO—Italy. The Chacaltaya laboratory at 5200 m a.s.l. could also be an appropriate mm-site. One of the goals of MITO is the multifrequency observation of nearby rich clusters of galaxies for measuring the Sunyaev-Zel’dovich effect. Combined S-Z and X-ray measurements yield the Hubble constant and other cosmological information. A dedicated instrument has been designed to minimize spurious contaminations on the signals. The telescope is a 2.6 m Cassegrain with a wobbling subreflector and a 4-band single pixel photometer installed at the focal plane. The bolometric detectors are cooled down to 300 mK by a double stage He3-He4 fridge

Melanin concentration gradients in modern and fossil feathers.

In birds and feathered non-avian dinosaurs, within-feather pigmentation patterns range from discrete spots and stripes to more subtle patterns, but the latter remain largely unstudied. A ∼55 million year old fossil contour feather with a dark distal tip grading into a lighter base was recovered from the Fur Formation in Denmark. SEM and synchrotron-based trace metal mapping confirmed that this gradient was caused by differential concentration of melanin. To assess the potential ecological and phylogenetic prevalence of this pattern, we evaluated 321 modern samples from 18 orders within Aves. We observed that the pattern was found most frequently in distantly related groups that share aquatic ecologies (e.g. waterfowl Anseriformes, penguins Sphenisciformes), suggesting a potential adaptive function with ancient origins

Half a century of caddisfly casings (Trichoptera) with microplastic from natural history collections

Plant science

The diagnosis and management of chronic constipation in Italy: results from a survey conducted among italian gastroenterologists

Background: Chronic constipation (CC) is one of the most common disorders of gut-brain interaction (DGBI). The management of CC requires specific skills due to its complex and multifactorial pathophysiology and its multistep treatment. The aims of this study were to evaluate the availability and the use of diagnostic tools for CC in Italy and the therapeutic management of CC by Italian gastroenterologists (GEs). Methods: A survey was conducted during the 28th meeting of the Italian Federation of Digestive Disease Societies (FISMAD; Rome, Italy, 11-14 May 2022). The survey explored the presence of a clinic dedicated to DGBIs, the availability and the use of specific diagnostic tools, the routine use of digital rectal examination (DRE), and the therapeutic approach to CC by Italian GEs. Results: The survey was taken by 236 GEs. The most significant results were that 42% of respondents had a clinic dedicated to DGBI in their institute; DRE was regularly performed by 56.8% of GEs when evaluating a CC patient; young GEs (≤40 years) performed DRE less frequently than older ones (p &lt; 0.001); anorectal manometry was available to 44.3% of GEs; balloon expulsion test (BET) was available to 19.1% of GEs; GEs with a clinic dedicated to DGBI had more frequent access to anorectal physiology testing (p &lt; 0.001); diet and lifestyle advice were the most frequently prescribed treatments; and fiber and macrogol were the second and third most prescribed treatments, respectively. Conclusions: The survey provides an interesting picture of CC management by Italian GEs. The results are in line with previous data collected about 10 years ago among Italian GEs ("CHRO.CO.DI.T.E study"); DRE is still rarely performed by Italian GEs (particularly by young GEs). The availability of anorectal physiology testing is still limited, and BET, which could be easily performed in everyday clinical settings, is rarely performed. Lifestyle suggestions, macrogol and fiber are the preferred treatment, as recommended by all guidelines. These results will be useful to identify as yet unmet educational needs and critical issues to improve CC management

Long-Term Outcome of Fanconi Anemia Patients From the Italian Registry on Behalf of the Marrow Failure Study Group of the AIEOP (Italian Association for Pediatric Haematology-Oncology)

We analyzed 193 Fanconi anemia patients from the Italian Registry, focusing on hematological outcome, cancer risk, and mortality, both in transplanted (n = 130, 67.4% of the cohort) and non-transplanted (n = 63, 36.6% of the cohort) patients. After a median follow-up of 7 years, almost all patients developed cytopenia that was more frequent in patients receiving hematopoietic stem cell transplantation (HSCT). The cumulative overall survival from birth was 91.0% at age 10 years, 71.6% at age 20, and 47.4% at age 30 years; the median survival age was 29.1 years. When stratifying patients by indication for transplantation (moderate vs. severe cytopenia vs. persistent poor prognosis cytogenetic alterations/acute myeloid leukemia), we found a 5-year cumulative mortality higher, though not significantly (p = 0.281) in the last group. Cancers were the second most common cause of death in the whole cohort after infections. Head and neck squamous cell carcinoma was the most frequent cancer, followed by hematologic neoplasms. The cumulative incidence of solid/hematological malignancy remarkably increased after 20 years of age and was 51.7% at age 40 years. The risk of malignancies was greater in subjects who received HSCT (sub-distribution azard ratio 2.9, 95% CI: 1.1–7.5, p = 0.024). We also identified a small group of patients with stable or even improved cytopenia over time without transplant, thus confirming that bone marrow failure is not automatic in all patients and heightening the importance of tight monitoring to surveil on the worsening of hematopoietic function and cancer occurrence. Overall, this study provides important findings that may help to make robust clinical decisions