Human Milk's Hidden Gift: Implications of the Milk Microbiome for Preterm Infants' Health

Breastfeeding is considered the gold standard for infants' nutrition, as mother's own milk (MOM) provides nutritional and bioactive factors functional to optimal development. Early life microbiome is one of the main contributors to short and long-term infant health status, with the gut microbiota (GM) being the most studied ecosystem. Some human milk (HM) bioactive factors, such as HM prebiotic carbohydrates that select for beneficial bacteria, and the specific human milk microbiota (HMM) are emerging as early mediators in the relationship between the development of GM in early life and clinical outcomes. The beneficial role of HM becomes even more crucial for preterm infants, who are exposed to significant risks of severe infection in early life as well as to adverse short and long-term outcomes. When MOM is unavailable or insufficient, donor human milk (DHM) constitutes the optimal nutritional choice. However, little is known about the specific effect of DHM on preterm GM and its potential functional implication on HMM. The purpose of this narrative review is to summarize recent findings on HMM origin and composition and discuss the role of HMM on infant health and development, with a specific focus on preterm infants

Integrating gestures and words to communicate in full-term and low-risk preterm late talkers

Young children use gestures to practice communicative functions that foster their receptive and expressive linguistic skills. Studies investigating the use of gestures by late talkers are limited. This study aimed to investigate the use of gestures and gesture–word combinations and their associations with word comprehension and word and sentence production in late talkers. A further purpose was to examine whether a set of individual and environmental factors accounted for interindividual differences in late talkers’ gesture and gesture–word production. Sixty-one late talkers, including 35 full-term and 26 low-risk preterm children, participated in the study. Parents filled out the Italian short forms of the MacArthur–Bates Communicative Development Inventories (MB–CDI), “Gesture and Words” and “Words and Sentences” when their children were 30-months-old, and they were then invited to participate in a book-sharing session with their child. Children’s gestures and words produced during the book-sharing session were transcribed and coded into CHAT of CHILDES and analyzed with CLAN. Types of spontaneous gestures (pointing and representational gestures) and gesture–word combinations (complementary, equivalent, and supplementary) were coded. Measures of word tokens and MLU were also computed. Correlational analyses documented that children’s use of gesture–word combinations, particularly complementary and supplementary forms, in the book-sharing session was positively associated with linguistic skills both observed during the session (word tokens and MLU) and reported by parents (word comprehension, word production, and sentence production at the MB–CDI). Concerning individual factors, male gender was negatively associated with gesture and gesture–word use, as well as with MB–CDI action/gesture production. In contrast, having a low-risk preterm condition and being later-born were positively associated with the use of gestures and pointing gestures, and having a family history of language and/or learning disorders was positively associated with the use of representational gestures. Furthermore, a low-risk preterm status and a higher cognitive score were positively associated with gesture–word combinations, particularly complementary and supplementary types. With regard to environmental factors, older parental age was negatively associated with late talkers’ use of gestures and pointing gestures. Interindividual differences in late talkers’ gesture and gesture–word production were thus related to several intertwined individual and environmental factors. Among late talkers, use of gestures and gesture–word combinations represents a point of strength promoting receptive and expressive language acquisition

Night Sleep and Parental Bedtime Practices in Low-Risk Preterm and Full-Term Late Talkers

Night sleep and parental bedtime practices have rarely been investigated in late talkers. This study aimed to explore: night sleep, parental bedtime practices, and their associations in late talkers as well as individual, socio-demographic, and socio-relational factors affecting them. Parents of 47 30-month-old late talkers, born low-risk preterm (n = 24) or full-term (n = 23), with an expressive vocabulary size <= 10th percentile measured by the MacArthur-Bates Communicative Development Inventory Words and Sentences, and normal cognitive abilities measured by the Bayley Scales, completed the Infant Sleep Questionnaire, the Parental Interactive Bedtime Behaviour Scale, and the Parenting Stress Index Short Form. Results showed slight settling difficulties, night wakings, and frequent co-sleeping in late talkers. Encouraging autonomy practices were frequently used by parents, rather than active physical comforting ones. Recurrent settling difficulties were reported by parents who often applied encouraging autonomy practices, whereas greater night waking problems and frequent co-sleeping were reported by parents who often left their child crying. Low-risk preterm birth and mother's parenting stress predicted total sleep difficulties and night wakings; first-born, high maternal education level and mother's parenting stress predicted settling difficulties; mother's parenting stress was the only predictor for co-sleeping and leaving to cry. These findings have relevant implications for improving late talkers' night sleep and their parents' bedtime practices

Small RNA teg49 Is Derived from a sarA Transcript and Regulates Virulence Genes Independent of SarA in Staphylococcus aureus

Expression of virulence factors in Staphylococcus aureus is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The sarA locus consists of three overlapping transcripts generated from three distinct promoters, all containing the sarA open reading frame (ORF). The 5= untranslated regions (UTRs) of these transcripts contain three separate regions 711, 409, and 146 nucleotides (nt) upstream of the sarA translation start, the functions of which remain unknown. Re- cent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely produced from the sarA P3 and sarA P1 transcripts of the sarA locus, respectively. In this report, we utilized a variety of sarA promoter mutants and cshA and rnc mutants to ascertain the contributions of these factors to the generation of teg49. We also defined the transcriptional regulon of teg49, including virulence genes not regulated by SarA. Phenotypically, teg49 did not impact biofilm formation or affect overall SarA expres- sion significantly. Comparative analyses of RNA-Seq data between the wild-type, teg49 mutant, and sarA mutant strains indicated that 133 genes are significantly upregulated while 97 are downregulated in a teg49 deletion mutant in a sarA- independent manner. An abscess model of skin infection indicated that the teg49 mutant exhibited a reduced bacterial load compared to the wild-type S. aureus. Overall, these results suggest that teg49 sRNA has a regulatory role in target gene regulation independent of SarA. The exact mechanism of this regulation is yet to be dissected

Impact of patent ductus arteriosus on non-invasive assessments of lung fluids in very preterm infants during the transitional period

This prospective observational study aimed to evaluate whether lung fluids, assessed by lung ultrasonography and transthoracic electrical bioimpedance (TEB), may be influenced by the presence of a haemodynamically significant patent ductus arteriosus (hsPDA) in very preterm infants during the transitional period. Infants < 32 weeks of gestational age (GA) admitted to the neonatal intensive care units of IRCCS AOU Bologna and Niguarda Metropolitan Hospital of Milan (Italy) underwent a daily assessment of a lung ultrasound score (LUS) and of a TEB-derived index of thoracic fluid contents (TFC) during the first 72 h after birth. Echocardiographic scans were simultaneously performed to evaluate the concomitant ductal status (hsPDA vs. restrictive or closed duct). The correlation between LUS, TFC, and the ductal status was tested using generalized estimating equations. Forty-six infants (median GA: 29 [interquartile range, IQR: 27-31] weeks; median birth weight: 1099 [IQR: 880-1406] g) were included. At each daily evaluation, the presence of a hsPDA was associated with significantly higher LUS and TFC compared with a restrictive or closed ductus (p < 0.01 for all comparisons). These results were confirmed significant even after adjustment for GA and for the ongoing modality of respiratory support.Conclusion: Even during the first 72 h of life, the presence of a hsPDA determines a significant increase in pulmonary fluids which can be non-invasively detected and monitored over time using lung ultrasonography and TEB

The front end electronics for the drift chamber readout in MEG experiment upgrade

Front-end electronics plays an essential role in drift chambers for time resolution and, therefore, spatial resolution. The use of cluster timing techniques, by measuring the arriving times of all the individual ionization clusters after the first one, may enable to reach resolutions even below 100 μm in the measurement of the impact parameter. A high performance front-end electronics, characterized by low distortion, low noise and a wide bandwidth has been developed with the purpose to implement cluster timing techniques in the new drift chamber for the upgrade of the MEG experiment at Paul Sherrer Institut (CH)

Diagnostic challenges of an incidental finding: case report of definitely-congenital glioblastoma multiforme in a very preterm infant

Background: Congenital brain tumors are extremely rare in the neonatal population, and often associated with a poor prognosis. The diagnostic suspicion is often aroused at antenatal scans or postnatally, if clinical signs and symptoms of increased intracranial pressure become evident. We present a case of definitely congenital glioblastoma multiforme incidentally diagnosed in a preterm infant, aiming to raise clinical awareness on this condition and to highlight the challenges of the related diagnostic work-up. Case presentation: This female infant was born at 31 weeks’ gestation after an uneventful pregnancy. No abnormalities were detected at antenatal ultrasound scans and genetic tests. Head circumference at birth was on the 25th centile. A routine brain ultrasound scan performed on day 1 revealed a large, inhomogeneous lesion in the right cerebral hemisphere, with contralateral midline shift, which was confirmed by brain magnetic resonance imaging (MRI). Eye fundus and routine blood exams, including platelets count, coagulation screening and C-reactive protein, were normal. Given the high risk of complications, surgical biopsy of the lesion was temporarily hold and a daily sonographic follow-up was undertaken. Although head circumference growth was steady on the 25th centile, progressive changes of the lesion were detected by cranial ultrasound. The repeat MRI scans showed a significant enlargement of the mass, with contralateral midline shift and signs of intralesional and intraventricular bleeding. In view of this worsening, surgical resection was performed. The histological examination of the lesion biopsy documented a GFAP+ highly cellular neoplasm, with no mutation on SMARCB1 gene. At the molecular analysis, mutations on IDH and H3F3A genes were absent, whereas MGMT promoter was unmethylated. The diagnosis was grade IV glioblastoma IDH wild-type. Conclusions: Congenital glioblastoma multiforme is an extremely rare but highly aggressive neoplasm. Since intralesional biopsy is not often feasible in affected neonates, knowledge of the associated clinical and neuroradiological features is particularly important, as they can also add useful information on the neoplasm behavior. Specimens from open surgical resection allow to perform a definite histological analysis and an extended molecular characterization, with relevant prognostic implications

Defined \u3b1-synuclein prion-like molecular assemblies spreading in cell culture

BACKGROUND: \u3b1-Synuclein (\u3b1-syn) plays a central role in the pathogenesis of synucleinopathies, a group of neurodegenerative disorders that includes Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Several findings from cell culture and mouse experiments suggest intercellular \u3b1-syn transfer. RESULTS: Through a methodology used to obtain synthetic mammalian prions, we tested whether recombinant human \u3b1-syn amyloids can promote prion-like accumulation in neuronal cell lines in vitro. A single exposure to amyloid fibrils of human \u3b1-syn was sufficient to induce aggregation of endogenous \u3b1-syn in human neuroblastoma SH-SY5Y cells. Remarkably, endogenous wild-type \u3b1-syn was sufficient for the formation of these aggregates, and overexpression of the protein was not required. CONCLUSIONS: Our results provide compelling evidence that endogenous \u3b1-syn can accumulate in cell culture after a single exposure to exogenous \u3b1-syn short amyloid fibrils. Importantly, using \u3b1-syn short amyloid fibrils as seed, endogenous \u3b1-syn aggregates and accumulates over several passages in cell culture, providing an excellent tool for potential therapeutic screening of pathogenic \u3b1-syn aggregates

Portuguese cacholeira blood sausage: A first taste of its microbiota and volatile organic compounds

Among typical Portuguese sausages, the cacholeira blood sausage undoubtedly represents one of the most popular preparations. To the authors’ knowledge, a lack of information on both the microbiota and the volatile organic compounds (VOCs) of this blood-containing sausage emerges from the available scientific literature. This study represents the first characterization of physico-chemical, microbiological and volatile traits of Portuguese cacholeira blood sausage. To this end, ready-to-eat cacholeira blood sausages were collected from two production batches manufactured in summer (batch 1) and autumn (batch 2). Viable counts showed active microbial communities mainly composed by lactic acid bacteria, coagulase negative cocci, enterococci and eumycetes. The metataxonomic approach showed a simple bacterial composition, which was dominated by Lactobacillus sakei in both the analyzed batches (1 and 2) considered. Carnobacterium, Enterococcus, Kluyvera, Lactococcus and Serratia were found as minor genera. The mycobiota varied according to the production season. Batch 1 was dominated by Starmerella apicola, Debaryomyces hansenii and Candida tropicalis, whereas batch 2 was dominated by D. hansenii. Moreover, Aspergillus spp., Kurtzmaniella zeylanoides, Saccharomyces cerevisiae, Kurtzmaniella santamariae, Brettanomyces bruxellensis and Pichia kluyveri were detected in both the batches as minority species. Seventy-two volatile compounds were identified, including esters, phenols, terpenoids, acids, alcohols, ketones, aldehydes, lactones, furans, sulphur and nitrogen compounds. Significant differences were seen in the amount of some compounds, as a feasible consequence of differences in the raw materials, artisan production and seasonality

A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings. Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, <12 h; quasi-optimal, between 12–24 h; acceptable, between 24–48 h; suboptimal, >48 h). Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases. Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios