Enteroviral Infections in the First Three Months of Life

Enteroviruses (EVs) are an important source of infection in the paediatric age, with most cases concerning the neonatal age and early infancy. Molecular epidemiology is crucial to understand the circulation of main serotypes in a specific area and period due to their extreme epidemiological variability. The diagnosis of EVs infection currently relies on the detection of EVs RNA in biological samples (usually cerebrospinal fluid and plasma, but also throat swabs and feces) through a poly-merase chain reaction assay. Although EVs infections usually have a benign course, they sometimes become life threatening, especially when symptoms develop in the first few days of life. Mortality is primarily associated with myocarditis, acute hepatitis, and multi-organ failure. Neurodevelopmental sequelae have been reported following severe infections with central nervous system involvement. Unfortunately, at present, the treatment of EVs infections is mainly supportive. The use of specific antiviral agents in severe neonatal infections has been reported in single cases or studies includ-ing few neonates. Therefore, further studies are needed to confirm the efficacy of these drugs in clinical practice

Can Fraction of Inspired Oxygen Predict Extubation Failure in Preterm Infants?

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre-and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates

Activity of N-Acetylcysteine Alone and in Combination with Colistin against Pseudomonas aeruginosa Biofilms and Transcriptomic Response to N-Acetylcysteine Exposure

Chronic colonization by Pseudomonas aeruginosa is critical in cystic fibrosis (CF) and other chronic lung diseases, contributing to disease progression. Biofilm growth and a propensity to evolve multidrug resistance phenotypes drastically limit the available therapeutic options. In this perspective, there has been growing interest in evaluating combination therapies, especially for drugs that can be administered by nebulization, which allows high drug concentrations to be reached at the site of infections while limiting systemic toxicity. Here, we investigated the potential antibiofilm activity of N-acetylcysteine (NAC) alone and in combination with colistin against a panel of P. aeruginosa strains (most of which are from CF patients) and the transcriptomic response of a P. aeruginosa CF strain to NAC exposure. NAC alone (8,000 mg/L) showed a limited and strain-dependent antibiofilm activity. Nonetheless, a relevant antibiofilm synergism of NAC-colistin combinations (NAC at 8,000 mg/L plus colistin at 2 to 32 mg/L) was observed with all strains. Synergism was also confirmed with the artificial sputum medium model. RNA sequencing of NAC-exposed planktonic cultures revealed that NAC (8,000 mg/L) mainly induced (i) a Zn21 starvation response (known to induce attenuation of P. aeruginosa virulence), (ii) downregulation of genes of the denitrification apparatus, and (iii) downregulation of flagellar biosynthesis pathway. NAC-mediated inhibition of P. aeruginosa denitrification pathway and flagellum-mediated motility were confirmed experimentally. These findings suggested that NAC-colistin combinations might contribute to the management of biofilm-associated P. aeruginosa lung infections. NAC might also have a role in reducing P. aeruginosa virulence, which could be relevant in the very early stages of lung colonization. © 2022 Valzano et al

Progressive osseous heteroplasia: A case report with an unexpected trigger

Progressive osseous heteroplasia (POH) is a rare genetic disorder characterised by progressive heterotopic ossification (HO) within the skin and subcutaneous tissues. The condition is caused by heterozygous inactivating mutations of the GNAS gene and usually presents in infancy. We describe the case of a white male ex-preterm who was first referred because of subcutaneous calcium deposits along the right arm after extravasation of parenteral nutrition. As these lesions progressed, a skin biopsy was undertaken which revealed intramembranous ossification. Genetic testing revealed a constitutional, de novo, heterozygous, nonsense variant in the GNAS gene that has not previously been described, but which is consistent with patient's clinical diagnosis of POH. No endocrine abnormalities or other signs congruent with overlapping conditions were detected. To the best of our knowledge, this is the first case describing an inflammatory trigger in POH. Trials with intravenous bisphosphonate and glucocorticoid as well as with topical sodium thiosulphate were attempted without clinical improvement. Excision of the calcifications and physiotherapy seem to have provided a partial improvement on mobility of the elbow. This case widens the spectrum of phenotypes seen in GNAS mutation disorders and suggests that alternative anti-inflammatory treatments may be effective. Mutations in GNAS should be considered in cases of significant progressive calcium deposition after extravasation injury

In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 \ub5g/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes

Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca2+ Homeostasis

Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca2+ imaging and Ca2+ selective microelectrodes we found that changes in e-c coupling, SR Ca2+content and resting [Ca2+] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca2+ regulation than Jct/CASQ association

Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy

SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired

Awareness of health risks related to body art practices among youth in Naples, Italy: a descriptive convenience sample study

<p>Abstract</p> <p>Background</p> <p>Body art practices have emerged as common activities among youth, yet few studies have investigated awareness in different age groups of possible health complications associated with piercing and tattooing.</p> <p>Methods</p> <p>We investigated perceptions of and knowledge about health risks. To highlight differences among age groups, we gathered data from students at high schools and universities in the province of Naples.</p> <p>Results</p> <p>Of 9,322 adolescents, 31.3% were pierced and 11.3% were tattooed. Of 3,610 undergraduates, 33% were pierced and 24.5% were tattooed (p < 0.05). A higher number of females were pierced in both samples, but there were no gender differences among tattooed students. Among high school students, 79.4% knew about infectious risks and 46% about non-infectious risks; the respective numbers among university students were 87.2% and 59.1%. Only 3.5% of students in high school and 15% of university undergraduates acknowledged the risk of viral disease transmission; 2% and 3% knew about allergic risks. Among adolescents and young adults, 6.9% and 15.3%, respectively, provided signed informed consent; the former were less knowledgeable about health risks (24.7% vs. 57.1%) (p < 0.05). Seventy-three percent of the high school students and 33.5% of the university students had body art done at unauthorized facilities. Approximately 7% of both samples reported complications from their purchased body art.</p> <p>Conclusions</p> <p>Results indicate a need for adequate information on health risks associated with body art among students in Naples, mainly among high school students. Therefore, adolescents should be targeted for public health education programs.</p

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

<p>Abstract</p> <p>Background</p> <p>The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.</p> <p>Methods</p> <p>A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.</p> <p>Results</p> <p>Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.</p> <p>Conclusion</p> <p>Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.</p