New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study

Background: A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. Methods: Two cohorts of preterm neonates born at < 32weeks of gestational age, consecutively observed during 2years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. Results: We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2cohorts were similar. Moderate hypothermia (body temperature ≤ 35.9° C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. Conclusions: If realized according to the proposed architectural standards, renovation of DR and NICU may represent an opportunity to reduce morbidity in preterm neonates

Morbidity associated with patent ductus arteriosus in preterm newborns: a retrospective case-control study

Introduction: Association between persistency of a patent ductus arteriosus (PDA) and morbidity in preterm newborns is still controversial. We aimed to investigate the relation between PDA and morbidity in a large retrospective study. Methods: A case-control study including neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU), with gestational age (GA) &lt; 32 weeks or body birth weight (BW) &lt; 1500 g, over a 5-year period. Newborns were divided into Cases and Controls, according with the presence or absence of a hemodynamically significant PDA (hs-PDA). Results: We enrolled 85 Cases and 193 Controls. Subjects with hs-PDA had significantly (p &lt; 0.001) lower GA (26.7 w, 95%CI 27.1–28.0 vs. 30.1 w, 95%CI 29.7–30.4), BW (1024 g, 95% CI 952–1097 vs. 1310 g 95%CI 1263–1358) and an increased morbidity (60.0% vs. 18.7%). In a sub-group of extremely preterm newborns (GA ≤ 28 weeks and BW ≤ 1000 g), the rate of bronchopulmonary dysplasia (BPD) was significantly increased in Cases (31.7%) compared with Controls (5.9%, p = 0.033). Multivariate analysis showed that morbidity significantly depended on hs-PDA, GA and BW, and that, in extremely preterms, the hs-PDA represented an independent risk factor for BPD. Conclusions: Occurrence of the main morbidities of prematurity depended by hs-PDA, in association with GA, BW, and use of prenatal steroids. In extremely premature babies, hs-PDA is a risk factor for BPD, one of the most important morbidity of prematurity, independently by other confounding variables

Nutritional intake influences zinc levels in preterm newborns: an observational study

(1) Background: Zinc is a key element for protein synthesis in preterm newborns. Early aggressive nutrition, promoting protein synthesis, may increase zinc consumption; (2) Methods: We performed a prospective observational study, to assess the relationship between early macronutrients intake and serum zinc levels, in preterm newborns with Gestational Age (GA) of 24-35 weeks, consecutively observed in Neonatal Intensive Care Unit (NICU). (3) Results: We enrolled 130 newborns (GA 31.5 ± 2.8). A significant negative correlation between serum zinc level at 28 days of life and energy (r -0.587, p &lt; 0.001) and protein intake (r -0.556, p &lt; 0.001) in the first week of life was observed. Linear regression analysis showed that zinc levels depended on energy (β -0.650; p &lt; 0.001) and protein (β -0.669; p &lt; 0.001) intake given through parenteral nutrition (PN) in the first week of life; (4) Conclusions: zinc status of preterm neonates was influenced by early protein and energy intake. An additional zinc supplementation should be considered when high protein and energy intake are received by preterm newborns in the first week of life

Fecal High-Mobility Group Box 1 as a Marker of Early Stage of Necrotizing Enterocolitis in Preterm Neonates

Introduction: An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC.Materials and Methods: A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital “Umberto I” in Rome, from July 2015 to December 2016. Stool samples obtained from cases (preterm newborns with NEC) and controls (newborns without NEC) were collected at the enrolment (T0) and within 7–14 days after the first sample collection (T1). HMGB1, extracted and measured with western blot, was reported as densitometry units (DUS).Results: HMGB1 levels in 30 cases (n = 28—Bell stage 1, n = 2 Bell stage 2) were higher [T0: 21,462 DUS (95% CI, 16,370–26,553 DUS)—T1: 17,533 DUS (95% CI, 13,052–22,014 DUS)] than in 30 preterm controls [T0: 9,446 DUS (95% CI, 6,147–12,746 DUS)—T1: 9,261 DUS (95% CI, 5,126–13,396 DUS), p &lt; 0.001). Preterm newborns showed significant higher levels of HMGB1 (15,690 DUS (95% CI, 11,929–19,451 DUS)] in comparison with 30 full-term neonates with birth weight &gt;2,500 g [6,599 DUS (95% CI, 3,141–10,058 DUS), p = 0.003]. Multivariate analysis showed that the risk of NEC was significantly (p = 0.012) related to the HMGB1 fecal levels at T0.Conclusions: We suggest fecal HMGB1 as a reliable marker of early NEC in preterm neonates. This study supports further investigation on the role of fecal HMGB1 assessment in managing preterm newborns at risk of NEC. Further studies are advocated to evaluate diagnostic accuracy of this marker in more severe forms of the disease

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson’s disease

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration

Iron capture through CD71 drives perinatal and tumor-associated Treg expansion

: Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth

Measurement of the very rare K+→π+ννˉK^+ \to \pi^+ \nu \bar\nu decay

The decay K+→π+νν¯ , with a very precisely predicted branching ratio of less than 10−10 , is among the best processes to reveal indirect effects of new physics. The NA62 experiment at CERN SPS is designed to study the K+→π+νν¯ decay and to measure its branching ratio using a decay-in-flight technique. NA62 took data in 2016, 2017 and 2018, reaching the sensitivity of the Standard Model for the K+→π+νν¯ decay by the analysis of the 2016 and 2017 data, and providing the most precise measurement of the branching ratio to date by the analysis of the 2018 data. This measurement is also used to set limits on BR(K+→π+X ), where X is a scalar or pseudo-scalar particle. The final result of the BR(K+→π+νν¯ ) measurement and its interpretation in terms of the K+→π+X decay from the analysis of the full 2016-2018 data set is presented, and future plans and prospects are reviewed

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes