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Background: In the current COVID-19 pandemic caused by the SARS-Coronavirus-2 (SARS-CoV-2) it is important to understand if breast milk may be a vehicle of infection. The possible transmission of the virus via breastfeeding is still largely unexplored. Methods: This is a prospective collaborative observational study where samples of human milk from 12 breastfeeding mothers positive for SARS-Coronavirus 2 were collected. Search for the viral RNA in breast milk samples was performed by real-time PCR methodology. All the newborns underwent a clinical follow up for the first month of life or until the finding of two sequential negative swabs. Findings: In eleven cases the search for SARS-CoV-2 RNA in milk samples resulted negative and in one case it was positive. Eleven of the twelve newborns were exclusively breastfed in the first month of life and closely monitored. Clinical outcome was uneventful. Four newborns tested positive for SARS-CoV-2 and were all detected in the first 48 hours of life, after the onset of maternal symptoms. Also the clinical course of these 4 infants, including the one who received mother’s milk positive for SARS-CoV-2, was uneventful, and all of them became SARS-CoV-2 negative within 6 weeks of life. Interpretations: Our study supports the view that SARS-CoV-2 positive mothers do not expose their newborns to additional risk of infection by breastfeeding. This is an important message that should be given to mothers and healthcare providers in this moment of uncertainty due to the COVID-19 pandemic. Clearly, the recommended hygiene measures for direct breastfeeding, as well as for milk expression when a mother and her infant need to be separated, must be carefully followed. Funding: This Study was supported by University of Turin (grant RILO2019 to EB and DL). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the local Ethical Committee (protocol number 0039684), and informed consent to participate in the study was obtained from each mother.

Summary We report the case of a 31-week gestational age neonate with Candida albicans sepsis and a hepatic abscess. Diagnosis relied on clinical and radiological signs of sepsis, liver function impairment and culture isolation of Candida spp. from sterile sites. Liver ultrasound documented the presence of a multiloculated abscess. Treatment with micafungin (3 mg/kg/day) resulted in normalization of liver function and inflammatory laboratory values and improvement of clinical condition. After 30 days of treatment, the liver abscess resolved and at the 8-month follow up the infant is doing well. Prompt diagnosis and antifungal treatment avoided surgical drainage and liver surgery in this high-risk neonate.

Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission.We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them.Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation.Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Summary Near infrared spectroscopy (NIRS) monitoring is a new challenge for clinicians who deal with early detection of dangerous hypoperfusion in the brain, as well as in splanchnic and renal districts in critically ill preterm infants. Previous studies performed on infants and children with congenital heart disease, demonstrated the efficacy of this non-invasive method in managing hypoperfusive states pre, post and during cardiac surgery. Its use has improved post surgery outcome. NIRS monitoring has been used also to assess therapeutic intervention utility. Early identification of silent hypoperfusion has made NIRS use in preterm infants very interesting for neonatologists, especially where other techniques have failed. In this work, literature on this topic has been carefully examined, particularly the “two site NIRS” use in preterm infants, to evaluate how regional splanchnic oxygen saturation changes, both in physiological events, such as enteral feeding and in hemodynamic disorders, that occur in patients with significant patent ductus and in hypoperfusive states that lead to necrotizing enterocolitis.

Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis.

Two proteins were isolated, in a stable form, from bovine brain by ion exchange chromatography, gel filtration and ultracentrifugation on glycerol gradient. They were identified as 20S and 26S proteasomes on the basis of molecular mass, migration velocity on non-denaturing gels, immunoreactivity, multipeptidase activity and the 26S proteasome also for dependence on ATP for the degradation of short peptides and ubiquitinylated proteins. However, the 26S proteasome has some properties not yet described for its counterpart of other tissues and from brain of this and other species. In particular, the ATP concentration required by the 26S proteasome to reach maximal peptidase activity was approximately 40-fold lower than the one required for maximal proteolytic activity on polyubiquitinylated substrates. Moreover, plots of substrate concentration vs. velocity gave a saturation curve for the 26S proteasome only, which, for the trypsin-like and post-glutamyl peptide hydrolase activities fitted the Michaelis–Menten equation, whereas for the chymotrypsin-like activity indicated multibinding site kinetics with positive cooperativity (n=2.32±0.38). As concerns the 20S proteasome, its electrophoretic pattern on native gel revealed a single protein band, a feature, to our knowledge, not yet described for the brain particle of any species.

1. 1. The incubation of human fresh circulating lymphocytes with insulin leads to modifications in the behaviour of the pyruvate dehydrogenase complex (PDH) when the contact medium is supplemented with 50 μM Ca 2+ and Mg 2+ 2. 2. To investigate the mechanism involved in the PDH responsiveness to insulin in circulating lymphocytes and the role of Ca 2+ and Mg 2+ in this process, the PDH activity was assayed in lymphocytes combined with insulin and/or a number of substances whose mechanism of action is partially known. 3. 3. Of these some have been seen to mimick insulin effects on PDH, whereas other were tested for the first time in this study.

1. 1. The results of this study indicates that the binding of insulin to brain plasma membranes activates a membrane protease which, by a trypsin like mechanism, produces a soluble factor that modulates the PDH behaviour when added to brain mitochondria. 2. 2. The supernatant from brain plasma membranes incubated with 0.5 mg/ml trypsin added to mitochondria increases PDH activity levels and cancels PDH inhibition by NaF, as has already been seen when the plasma membranes are incubated with 25 μ U/ml insulin. No such effects are obtained when the incubation is run out with 0.5 mg/ml chymotrypsin. 3. 3. The supernatants from insulin or trypsin treated plasma membranes retain their activating properties on mitochondrial PDH also after dansylation; from these preparations a dansylated active on PDH material was separated by monodimensional chromatography on HPTLC silica Gel plates, using chloroform/1-butanol (93:7 v/v) as a solvent. 4. 4. Insulin incubation of plasma membranes pretreated with protease inhibitors (leupeptin, phenylmethylsulfonylfluoride) or with exogenous trypsin, but not chymotrypsin substrates (esters of arginine and tyrosine) yields an inactive supernatant on PDH. 5. 5. Insulin treated plasma membrane supernatants lose all stimulating properties on PDH after incubation for 1 hr with 2 mg/ml trypsin or chymotrypsin.