Emergence and Spread of SARS-CoV-2 Lineages B.1.1.7 and P.1 in Italy

Italy’s second wave of SARS-CoV-2 has hit hard, with more than three million cases and over 100,000 deaths, representing an almost ten-fold increase in the numbers reported by August 2020. Herein, we present an analysis of 6515 SARS-CoV-2 sequences sampled in Italy between 29 January 2020 and 1 March 2021 and show how different lineages emerged multiple times independently despite lockdown restrictions. Virus lineage B.1.177 became the dominant variant in November 2020, when cases peaked at 40,000 a day, but since January 2021 this is being replaced by the B.1.1.7 ‘variant of concern’. In addition, we report a sudden increase in another documented variant of concern—lineage P.1—from December 2020 onwards, most likely caused by a single introduction into Italy. We again highlight how international importations drive the emergence of new lineages and that genome sequencing should remain a top priority for ongoing surveillance in Italy.     

Correlation between wing bone microstructure and different flight styles: The case of the griffon vulture (gyps fulvus) and greater flamingo (phoenicopterus roseus)

Flying is the main means of locomotion for most avian species, and it requires a series of adaptations of the skeleton and of feather distribution on the wing. Flight type is directly associated with the mechanical constraints during flight, which condition both the morphology and microscopic structure of the bones. Three primary flight styles are adopted by avian species: flapping, gliding, and soaring, with different loads among the main wing bones. The purpose of this study was to evaluate the cross-sectional microstructure of the most important skeletal wing bones, humerus, radius, ulna, and carpometacarpus, in griffon vultures (Gyps fulvus) and greater flamingos (Phoenicopterus roseus). These two species show a flapping and soaring flight style, respectively. Densitometry, morphology, and laminarity index were assessed from the main bones of the wing of 10 griffon vultures and 10 flamingos. Regarding bone mineral content, griffon vultures generally displayed a higher mineral density than flamingos. Regarding the morphology of the crucial wing bones involved in flight, while a very slightly longer humerus was observed in the radius and ulna of flamingos, the ulna in griffons was clearly longer than other bones. The laminarity index was significantly higher in griffons. The results of the present study highlight how the mechanics of different types of flight may affect the biomechanical properties of the wing bones most engaged during flight.     

One-year recombinant growth hormone therapy does not improve hemoglobin state and morphology of erythrocytes in growth hormone deficient children

An increase in growth rates of children suffering from growth hormone deficiency (GHD) subjected to recombinant growth hormone treatment (rGHT) was shown to be accompanied by acceleration of metabolic processes that may stimulate oxygen consumption in various organs and tissues. Therefore, oxygen-transporting properties of RBC should undergo considerable changes during the rGHT. The aim of this study was to examine the effects of rGHT on erythrocyte shape and hemoglobin state in GHD children. The level of oxyhemoglobin (Oxy-Hb) in RBC was analyzed by Raman spectroscopy. The RBC count, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and other parameters were calculated. The blood of eleven treatment-naive prepubertal children with GHD (aged 3–9, median 5.7 years) was examined and compared with control group (aged 5–7; median 6.0 years) at three time points: 0, 3 and 12 months of rGHT. Before rGHT, the MI in GHD children was higher (median 0.48 vs 0.14 p = 0.0018) and the RBC count was lower (median 4.20 vs 4.96 10¹² cells/L p = 0.0022) than in control group. After the treatment, cell count in GHD patients did not differ significantly from the control group, but Oxy-Hb level became higher (median 0.64 vs 0.41 p = 0.0075). During rGHT, MCV decreased (median 80.3 vs 83.2 μm³ p = 0.0231). Morphological and functional characteristics of erythrocytes in GHD children were shown to differ significantly from the healthy control group. A twelve-month rGHT partially improved some of the studied parameters but Oxy-Hb level and echinocyte count remained high.     

(In)accuracy of blood pressure measurement in 14 Italian hospitals

OBJECTIVES:: The diagnosis and control of hypertension depend on accurate measurement of blood pressure (BP). The literature on the accuracy of BP recording by health professionals is, however, limited, and no study directly interviewed patients in the hospital setting. This multicenter cross-sectional study aimed at evaluating the compliance to current recommendations on BP measurement by health professionals directly from patients and to investigate potential predictors of higher quality in BP recording. METHODS:: A trained nurse interviewed a random sample of adult patients hospitalized for an ordinary admission (except in the emergency room) lasting more than one night, without mental disorder, who had their BP routinely measured by the hospital personnel less than 3?h before. The questionnaire contained 15 items on the main procedures that are common to current guidelines. RESULTS:: Fourteen public hospitals from seven regions of Italy participated, and 1334 questionnaires were collected. Nine of the recommended practices were followed in the majority (>70%) of BP recordings, whereas some others were infrequent or rare: in 98.6, 82.2 and 81.1% of the participants, respectively, the arm circumference was never recorded, BP was measured only once, and BP was never recorded in both arms. Overall, 10 or more recommended procedures were followed during 33.4% recordings. At multivariate analysis, physicians were less likely than nurses to provide a more accurate BP measurement. CONCLUSIONS:: The operator's compliance to some recommendations in BP measurement is unacceptably low. This survey provides detailed indications for medical directors on the procedures and settings to prioritize in educational programs, which are definitely needed.     

Enterovirus 71 pathogenicity in monkeys and cotton rats

Enterovirus 71 (EV71) is a neurovirulent non-polio enterovirus that can cause severe central nervous system (CNS) infection in infants. Vervet monkeys infected intracerebrally or intramuscularly with EV71 isolates from the Bulgarian outbreak of 1975 developed clinical manifestations and pathological signs of encephalomyelitis and spinal poliomyelitis that were similar to EV71 neuroinfection in children. In addition, vervet monkeys with encephalomyelitis had severe alterations in the choroid plexus. EV71 neuroinfection could also be reproduced in young (3- to 4-week old) cotton rats with clinical and pathological signs comparable with those observed in vervet monkeys.     

A Case of Compound Mutations in the MYBPC3 Gene Associated with Biventricular Hypertrophy and Neonatal Death

Hypertrophic cardiomyopathy (HCM) is a familial, genetically determined, primary cardiomyopathy caused by mutations in genes coding for proteins of the sarcomere, or, less frequently, genes involved in storage diseases. In pediatric settings, pure HCM has an estimated incidence of 4.7 per million children. The disease is often sub-clinical and goes unrecognized mainly because most patients with HCM have only mild symptoms, if any. However, sudden cardiac death, the most dramatic clinical occurrence and the primary concern for patients and physicians alike, may be the first manifestation of the disease. We describe a case of compound heterozygosity in the MYBPC3 gene (p.Glu258Lys and IVS25-1G>A) associated with biventricular hypertrophy, atrial enlargement and subsequent neonatal death 33 days postpartum. Other studies have reported compound and/or double heterozygosis in the same or different sarcomeric genes during childhood and adulthood, and neonatal presentations have also been described. Our observations show that the combination of a missense (p.Glu258Lys) and a splice-site mutation (IVS25-1G>A) profoundly affects the clinical course. In families in which parental mutations are known, preimplantation (where ethically and legally feasible) or prenatal genetic screening should be adopted because: (1) neonatal HCM in genetic heterozygosity is potentially lethal and (2) heart disease is the most common developmental malformation and the leading cause of neonatal mortality and morbidity.     

Studies of novel variants associated with Hb F in Sardinians and Tanzanians in sickle cell disease patients from Cameroon

High level of Hb F has been shown to improve survival in sickle cell disease. Among 453 Cameroonians with sickle cell disease, we have investigated 18 selected single-nucleotide polymorphisms (SNPs) in novel and suggestive loci associated with Hb F level identified through a genomewide association study in sickle cell disease patients in Tanzania, and whole-genome sequencing of a population from Sardinia. Seven of 10 variants reported in Sardinians were either monomorphic or very rare in the Cameroonians. No associations were observed with any SNPs and Hb F levels in Cameroonians affected by sickle cell disease. The present study illustrates the complexity of replicating Hb F-promoting variants association results across populations.     

Parent perspectives on childhood vaccination: How to deal with vaccine hesitancy and refusal?

Background

The aims of the study are to evaluate attitudes about childhood vaccines and vaccine refusal or delay among parents and to assess the role played by the variables mapped as potential determinants to suggest strategies that could improve childhood vaccination rates.

Mutational landscape of patients with acute promyelocytic leukemia at diagnosis and relapse

Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.