First Report of Alphacoronavirus Circulating in Cavernicolous Bats from Portugal

The emergence of novel coronaviruses (CoVs) has emphasized the need to understand their diversity and distribution in animal populations. Bats have been identified as crucial reservoirs for CoVs, and they are found in various bat species worldwide. In this study, we investigated the presence of CoVs of four cavernicolous bats in six locations in the centre and south of Portugal. We collected faeces, anal, and buccal swab samples, as well as air samples from the locations using a Coriolis air sampler. Our results indicate that CoVs were more readily detected in faecal samples compared to anal and buccal swab samples. No CoVs were detected in the air samples. Phylogenetic analysis showed that the detected viruses belong to the Alphacoronavirus genus. This study represents the first report of Alphacoronaviruses circulating in bats in Portugal and highlights the importance of continuous surveillance for novel CoVs in bat populations globally. Ongoing surveillance for CoVs in bat populations is essential as they are a vital source of these viruses. It is crucial to understand the ecological relationships between animals, humans, and the environment to prevent and control the emergence and transmission of infectious diseases. Further ecological studies are needed to investigate the factors contributing to the emergence and transmission of zoonotic viruses.Mahima Hemnani thanks Fundacao para a Ciencia e a Tecnologia (FCT) for the financial support of her PhD work under the Maria de Souza scholarship contract number 2021.09380.BD. This work was also funded by FCT, under the projects UIDB/04750/2020, LA/P/0064/2020, UIDP/00772/2020 and LA/P/0059/2020

Detection of vanA-containing Enterococcus species in faecal microbiota of gilthead seabream (Sparus aurata)

Vancomycin-resistant Enterococcus faecalis, E. faecium and E. durans isolates with the genotype vanA were detected in 7 of 118 faecal samples (5.9%) of natural gilthead seabream recovered off the coast of Portugal, and one vancomycinresistant isolate/sample was further characterized. The genes erm(B), tet(L), tet(M), aac(6')-aph(2"), aph(3')-IIIa and/ or ant(6)-Ia were identified in most of the 7 vancomycin-resistant enterococci. Sequence types ST273, ST313 and ST76 were detected in three E. faecium isolates and ST6 in two E. faecalis isolates. VanA-containing enterococci are suggested to be disseminated in fish in marine ecosystems close to areas of human activity

Effects of pidotimod and bifidobacteria mixture on clinical symptoms and urinary metabolomic profile of children with recurrent respiratory infections: a randomized placebo-controlled trial

Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators as pidotimod or probiotics, but there is limited evidence of their efficacy on clinical features or on urine metabolic profile

Zimmer Natural Nail and ELOS nails in pertrochanteric fractures.

BACKGROUND: Pertrochanteric fractures of the femur in the elderly are very common. As the average age of the population increases, the incidence of such fractures also raises, resulting in high healthcare costs. The type of surgical devices employed for their surgical management influences these costs. METHODS: A comparative clinical study was conducted on patients operated by one single surgeon between December 2018 and November 2020 in a high-volume regional referral centre. All patients who received a Zimmer Natural Nail (ZNN) or ELOS devices were included. RESULTS: In 119 (66.48%) of the 179 fractures, a ZNN nail was used. Post-operatively, the TAD (tip-to-apex distance) was measured at an average value of 17.05 (4.42-41.85) mm and the CalTAD (calcar-referenced TAD) at an average of 20.76 (10.82-43.63) mm. The mean hospitalization time was 10.19 (4-22) days. In the other 60 trochanteric fractures, an ELOS nail was used. Post-operative imaging indicated a TAD of 19.65 (5.08-31.4) mm and a CalTAD of 22.86 mm (12.66-33.77). The average time of the operation was 45.82 (20-110) min. The average period of hospitalization was 10.45 (5-24) days. CONCLUSION: Both devices give similar results in terms of short-term post-operative outcome and hospitalization. The price difference between the devices does not translate in different short-term results on the operated patients

Health-care organization for the management and surveillance of SARS-CoV-2 infection in children during pandemic in Campania region, Italy

Background: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. Methods: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. Result: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2–9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5–19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. Conclusion: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes

Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance

B-cell chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided

SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL

Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, pae-diatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telen-cephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants (CNVs) of the ARX locus found in patients presenting wide-ranging phenotypic variations including ID, speech delay, hypotonia and psychiatric abnormalities. We also report on a further novel Xp21.3 duplication detected in a male patient with moderate ID and carrying a fully duplicated copy of the ARX locus and the ultraconserved enhancers. As consequences of this rearrangement, the patient-derived lymphoblastoid cell line shows abnormal activity of the ARX-KDM5C-SYN1 regulatory axis. Moreover, the three-dimensional (3D) structure of the Arx locus, both in mouse embryonic stem cells and cortical neurons, provides new insight for the functional consequences of ARX duplications. Finally, by comparing the clinical features of the 16 CNVs affecting the ARX locus, we conclude that—depending on the involvement of tissue-specific enhancers—the ARX duplications are ID-associated risk CNVs with variable expressivity and penetrance

Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia

In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules