Healthy preterm newborns: Altered innate immunity and impaired monocyte function.

Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

Maternal singing sustains preterm hospitalized newborns' autonomic nervous system maturation: an RCT.

BACKGROUND: Premature birth is known to affect the newborn's autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants' autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters. METHODS: In this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking. RESULTS: The intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037). CONCLUSIONS: The preterm infant's vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition. IMPACT: Maternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU. No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation. Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant's development and it can be easily implemented in the care of preterm infants. TRIAL REGISTRATION: NCT04759573, retrospectively registered, 17 February 2021.

Cranial ultrasound in preterm infants ≤ 32 weeks gestation-novel insights from the use of very high-frequency (18-5 MHz) transducers: a case series.

The quality of cranial ultrasound has improved over time, with advancing technology leading to higher resolution, faster image processing, digital display, and back-up. However, some brain lesions may remain difficult to characterize: since higher frequencies result in greater spatial resolution, the use of additional transducers may overcome some of these limitations. The very high-frequency transducers (18-5 MHz) are currently employed for small parts and lung ultrasound. Here we report the first case series comparing the very high-frequency probes (18-5 MHz) with standard micro-convex probes (8-5 MHz) for cranial ultrasound in preterm infants. In this case series, we compared cranial ultrasound images obtained with a micro-convex transducer (8-5 MHz) and those obtained with a very high-frequency (18-5 MHz) linear array transducer in 13 preterm infants ≤ 32 weeks gestation (9 with cerebral abnormalities and 4 with normal findings). Ultrasound examinations using the very high-frequency linear transducer and the standard medium-frequency micro-convex transducer were performed simultaneously. We also compared ultrasound findings with brain MRI images obtained at term corrected age. Ultrasound images obtained with the very high-frequency (18-5 MHz) transducer showed high quality and accuracy. Notably, despite their higher frequency and expected limited penetration capacity, brain size is small enough in preterm infants, so that brain structures are close to the transducer, allowing for complete evaluation.    Conclusion: We propose the routine use of very high-frequency linear probes as a complementary scanning modality for cranial ultrasound in preterm infants ≤ 32 weeks gestation. What is Known: • Brain lesions in preterm infants may remain insufficiently defined through conventional cranial ultrasound scan. • Higher frequency probes  offer better spatial resolution but have a narrower filed of exploration and limited penetration capacity. What is New: • Very high-frequency probes were compared with standard medium-frequency probes for cranial ultrasound in infants  ≤ 32 weeks' gestation. • Thanks to the smaller skull size of preterm infants, the new very high-frequency transducers allowed a complete and accurate evaluation.

Exposure to Prolonged Rupture of Membranes at Term Increases the Risk for Ventilatory Support in Uninfected Neonates.

OBJECTIVE: The effects of prolonged rupture of membranes (ROMs) on perinatal outcomes are still unclear, and it remains controversial for the management of those labors. This study aims to evaluate how the exposure of pregnant women to a prolonged ROM (≥ 24 hours) affects maternal and neonatal outcomes. STUDY DESIGN: This retrospective cohort study included singleton pregnant women at term delivering between January 2019 and March 2020 in a tertiary hospital. All relevant sociodemographic, pregnancy, and perinatal variables (maternal age, prepregnancy body mass index, labor, and delivery outcomes) were collected anonymously. Data were compared between the "ROM < 24 hours" and "ROM ≥ 24 hours" study groups. RESULTS: A total of 2,689 dyads were included in the study and divided according to their ROM-delivery time: ROM <24 hours (2,369 women, 88.1%), and ROM ≥ 24 hours (320 women, 11.9%). Maternal baseline characteristics were comparable except for the rate of nulliparous women, which was significantly higher among patients with ROM ≥ 24 hours. No significant differences were found regarding infectious neonatal outcomes. However, mechanical ventilation and continuous positive airway pressure were more common among neonates born after ROM ≥ 24 hours. The greater likelihood of neonatal respiratory distress was also confirmed among infants born to Group-B Streptococcus-negative women with ROM ≥ 24 hours (15 out of 267 neonates, 5.6% vs. 52 out of 1,529 with ROM < 24 hours, 3.4%, p = 0.04). CONCLUSION: According to the actual expectant policy, prolonged ROM is associated with an increased risk of respiratory support in noninfected neonates. Further investigations are required to explain such an association. KEY POINTS: · The management of women with prolonged rupture of membranes is controversial.. · The exposure of pregnant women to a prolonged rupture of membranes affects neonatal outcomes.. · Prolonged rupture of membranes is associated with an increased risk of respiratory support, in group-B Streptococcus-negative neonates..

Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG.

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.

Pharmacists' awareness of COVID-19 and perceptions of their roles, barriers, and roles of policymakers: Exploring the Middle East and North Africa (MENA).

BACKGROUND: The coronavirus disease (COVID-19) was declared in January 2020 as a public health emergency of international concern. The Middle East and North Africa (MENA) suffered from several pandemics previously. Pharmacists have vital roles to play to prevent the spread of this virus. OBJECTIVES: To assess the COVID-19 awareness amongst pharmacists from Arabic-speaking countries located in the MENA region, and to assess their perspectives of their role, barriers, and roles of the educational institutions/pharmaceutical associations. METHODS: An online survey was conducted to run a descriptive cross-sectional study in Jordan from 12th to 22nd April 2020. The questionnaire was validated (face validity) and put on Facebook and directed for pharmacists only (clarified in the introduction of the questionnaire). Assessment of pharmacists' awareness (20 questions) about pandemics and COVID-19, their perceived roles and barriers, and roles of the educational institutions (eg, universities) and pharmaceutical associations (eg, Pharmacists Syndicate) was performed. Data were analysed using Statistical Package for the Social Science (SPSS). RESULTS: Study participants (n = 2589) had a mean age of 29.3 (8.2) years and 1329 (51.5%) were females. Most of the participants were from Egypt (n = 819, 40.8%), followed by Jordan, Algeria, and Syria. Regarding the sources of information about coronavirus management, 60.8% of participants got their information from social media. Fear of contracting the coronavirus while performing their duties was reported by the majority of pharmacists as the main barrier to delivering their roles (82.3%). The majority of pharmacists identified positive roles for the pharmaceutical institutions (74.8%) and pharmaceutical associations (63.6%). CONCLUSION: Pharmacists from the MENA countries believe they got enough education previously about pandemics, and the majority follow the latest coronavirus updates from social media. Fear was reported as the major barrier that requires resolution by the policymakers. Certain gaps in the awareness about COVID-19 were identified.

Overwhelming sepsis in a neonate affected by Zellweger syndrome due to a compound heterozygosis in PEX 6 gene: a case report.

BACKGROUND: Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period. CASE PRESENTATION: A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test. CONCLUSIONS: ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.

Serial clinical observation for management of newborns at risk of early-onset sepsis.

PURPOSE OF REVIEW: Current management approaches for asymptomatic neonates at risk of early onset sepsis remain controversial. Strategies based entirely on clinical observation (SCO, serial clinical observation) have gained consensus. RECENT FINDINGS: We briefly compare different strategies for managing asymptomatic newborns suggested in four high-income countries. Then this review details the existing differences in carrying out the SCO in the United Kingdom, the USA, and Italy; the experiences from the studies performed using the SCO; and open questions regarding this strategy. Advantages and limitations of SCO are also discussed. There is a need to assess which symptoms at birth are more predictive of early onset sepsis and therefore require immediate interventions versus those symptoms that can be monitored and re-evaluated. SUMMARY: SCO strategy may require changes in the processes of newborn care at birthing centers. Nonetheless, SCO is safe and is associated with fewer laboratory evaluations and unnecessary antibiotics. Thoughtful and thorough practices related to the care of all newborns will benefit any birthing centre. VIDEO ABSTRACT: http://links.lww.com/MOP/A40.

Endocrine-Disrupting Chemicals and Their Effects during Female Puberty: A Review of Current Evidence.

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.

Analysis of Commercial Hand Sanitisers amid CoViD-19: Are We Getting the Products that We Need?

The CoViD-19 pandemic has caused a sudden spike in demand and production of hand sanitisers. Concerns are rising regarding the quality of such products, as the safeguard of consumers is a priority worldwide. We analyse here the ethanolic content of seven off-the-shelf hand sanitiser gels (two biocides and five cosmetics) from the Italian market, using gas chromatography. The WHO recommends that products containing ethanol should have 60-95% (v/v) alcohol. Four of the tested hand gels have ethanolic contents within the recommended range, while three products (all cosmetics) contain < 60% (v/v), i.e. 52.1% (w/w), ethanol. The product with the lowest alcoholic content has 37.1% w/w ethanol. Toxic methanol is not found in any of the hand sanitisers. We show, in addition, that products with the highest ethanolic content have generally greater antibacterial activity. In conclusion, all tested products are complying with the EU regulations, as the three "substandard" products are classified as cosmetics, whose purpose is cleaning and not disinfecting. Nevertheless, if such hand cleaners were inappropriately used as hand disinfectants, they might be ineffective. Thus, consumer safety relays on awareness and ability to distinguish between biocidal and cosmetics hand gels. The obtained results might sensitise the scientific community, health agencies and ultimately consumers towards the risks of using hand sanitisers of substandard alcoholic concentration. If the wrong product is chosen by consumers, public health can be compromised by the inappropriate use of "low-dosed" cosmetic gels as disinfectants, particularly during the period of the CoViD-19 pandemic.

Worse global intellectual and worse neuropsychological functioning in preterm-born children at preschool age: a meta-analysis.

AIM: Preterm births (<32 weeks of gestational age) are associated with cognitive problems that are difficult to diagnose in infancy but potentially detectable at preschool age. This review aimed to evaluate the extent to which total intelligence quotient (IQ) and neuropsychological functions at ages three to five years differ between children born at <32 weeks gestational age or < 1500 g birth weight and children born at term. The secondary aim was to determine whether cognitive performance differs between extremely preterm (EPT)/extremely low birth weight (ELBW) children and very preterm (VPT) or very low birth weight (VLBW) children. METHODS: PubMed and PsycINFO databases were searched for cohort studies comparing IQ and neuropsychological functions in term-born and preterm-born children born after 1994. RESULTS: At ages three to five years, preterm-born children, compared with term-born ones, had worse IQ mean score (d = -0.77 [95% confidence interval -0.88 to -0.66]), attention, memory, visuomotor integration skill and executive functions. No differences were found between VPT/VLBW and EPT/ELBW children. CONCLUSION: Preterm-born children showed poorer IQ and neuropsychological functions compared with term-born subjects already at preschool age. The extent of differences is similar to that detected at a later age.

Evaluation of the Disintegration Action of Soy Polysaccharide by Image Analysis.

Here we investigated the disintegration action of the natural superdisintegrant soy polysaccharide (SP) and benchmarked it against sodium starch glycolate (SSG) and crospovidone (XPVP). Kinetics and mechanism of disintegration of various tablet formulations were monitored using a USB microscope connected to a computer, followed by image analysis. SP acts mainly by a swelling mechanism and it is most effective at concentrations of 4-8%. Its disintegration action is comparable with that of SSG and XPVP, in most cases. However, SP underperforms compared with these superdisintegrants, in extremely hard tablets containing a hydrophobic component. Moreover, it is more negatively affected by the concentration of magnesium stearate than SSG and XPVP. The disintegration action of SP is not affected by pH and ionic strength of the medium, but it is compromised by the presence of ethanol. This indicates that the concomitant administration of alcoholic beverages might hamper the disintegration of SP-containing tablets. Overall, SP is a promising tablet disintegrant for pharmaceutical and nutraceutical products.

Group B streptococcus late-onset disease,contaminated breast milk and mothers persistently GBS negative: report of 3cases.

BACKGROUND: Human milk is fundamental for its nutritional properties and to protect newborns, but it is not sterile and can sometime transmit bacteria. Few anecdotal cases suggest that breast milk could be a possible source of group B Streptococcus (GBS) late onset disease, although the pathogenesis is not entirely understood. CASE PRESENTATION: We report 3 cases of GBS late onset disease in full-term newborns. Fresh breast milk cultures yielded GBS, but mothers of neonates had no signs of mastitis and remained persistently GBS negative at rectovaginal site. CONCLUSIONS: Breast milk containing group B Streptococcus can be a risk factor for late onset disease. The persistent negative maternal GBS status supports the assumption that newborns, colonised in the throat, could be the initial source of GBS, while the mammary gland could act as a GBS replication site. It is unclear whether a low bacterial load may represent only contamination rather than true milk infection.

Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

Influence of Testing Parameters on In Vitro Tramadol Release from Poloxamer Thermogels using the Immersion Cell Method.

The immersion cell is an in vitro performance test of drug release from semisolids. Several studies made use of immersion cells to investigate drug release from thermosensitive Poloxamer-based gels; however, specifications on the parameter setting are not yet available. Therefore, the aim of this study was to evaluate the influence of testing parameters on tramadol (a model drug) release, release rate, and dissolution efficiency (DE) from Poloxamer gels, using immersion cells. The thermosensitive gelling formulation showed batch-to-batch uniformity of gelling behavior, drug content, and drug release. The use of a membrane in the immersion cell resulted in slower drug release as compared to the absence of a membrane. Moreover, the faster the paddle rotation, the faster the drug release was. Membrane thickness showed a strong and significant linear relationship with corresponding DE values (Pearson's correlation coefficient, r = -0.9470; p = 0.004). Factors that did not influence drug release include paddle position, i.e., distance between paddle and membrane, as well as membrane mean pore size. This study sets forth the importance of carefully controlling the following parameters including presence/absence of membrane, paddle rotation speed, and membrane thickness during the setup of release experiments from gels using immersion cells.

Hypothermia reduces seizure burden and improves neurological outcome in severe hypoxic-ischemic encephalopathy: an observational study.

AIM: To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic-ischemic encephalopathy (HIE). METHOD: We compared polygraphic electroencephalography monitoring and outcome data in 39 cooled and 33 non-cooled term newborn infants, born between January 2005 and March 2013, and hospitalized because of signs of asphyxia and moderate to severe HIE. RESULTS: Cooled newborn infants had fewer seizures (14/39 vs 20/33 p=0.036) and status epilepticus (7/39 vs 13/33, p=0.043), a lower mean duration of seizures (18mins vs 133mins, p=0.026), fewer administered antiepileptic drugs (median 0 vs 1, p=0.045), and more commonly a good outcome at 24 months (normal/mild motor impairment in 32/39 vs 16/33, p=0.003). Seizure burden (accumulated duration of seizures over a defined period) in cooled patients with both moderate (0.0 vs 0.1; p=0.045) and severe HIE (0.3 vs 4.9; p=0.018) was lower than in non-cooled patients. Compared with non-cooled patients, a good outcome was more common in cooled newborn infants with severe HIE (p=0.003). INTERPRETATION: Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.

Identifying skull fractures after head trauma in infants with ultrasonography: is that possible?

Management of pediatric head trauma requires a delicate balance between accuracy and safety, with a dual emphasis on prompt diagnosis while minimizing radiation exposure. Ultrasonography (US) shows promise in this regard. A case study involving a 10-month-old infant with acute right parietal swelling revealed the utility of US in detecting a corresponding hypoechoic lesion, along with an underlying suspected fracture line of the vault and subdural hematoma. Subsequent CT confirmed the fracture, while MRI confirmed the subdural hematoma. At one-month follow-up, MRI demonstrated hematoma reabsorption, while US revealed a bone callus in its advanced phase. Although US is not yet standard practice for pediatric head trauma, its ability to detect fractures in infants suggests its potential role: when a fracture is evident on US, it may serve as an indication to perform neuroimaging. Potentially, adoption of US could contribute to mitigation of children's exposure to ionizing radiation.