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Listeriosis is currently the fifth most common foodborne disease in Europe. Most cases are sporadic; however, outbreaks have also been reported. Compared to other foodborne infections, listeriosis has a modest incidence but can cause life-threatening complications, especially in elderly or immunocompromised people and pregnant women. In the latter case, the pathology can be the cause of premature birth or spontaneous abortion, especially if the fetus is affected during the first months of gestation. The causative agent of listeriosis, Listeria monocytogenes , is characterized by the innate ability to survive in the environment and in food, even in adverse conditions and for long periods. Ready-to-eat food represents the category most at risk for contracting listeriosis. This study presents the result of an investigation carried out on a case of maternal-fetal transmission of listeriosis which occurred in 2020 in central Italy and which was linked, with a retrospective approach, to other cases residing in the same city of the pregnant woman. Thanks to the use of next-generation sequencing methodologies, it was possible to identify an outbreak of infection, linked to the consumption of ready-to-eat sliced products sold in a supermarket in the investigated city.

Background: S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns., Methods: We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns., Results: S100B and LT showed a pattern of concentration characterized by higher levels (P < 0.01, for all) at 33-36 weeks gestation (GA) followed by a progressive decrease (P < 0.01, for all) from 37 onwards with a dip at term. Both S100B and LT were gender-dependent with significantly (P < 0.01, for all) higher levels in females in preterm and term groups. S100B (R = 0.68; P < 0.001) and LT (R = 0.40; P = 0.005) correlated with GA at sampling. A positive significant correlation (R = 0.87; P < 0.001) between S100B and LT was found., Conclusions: The present data showing a correlation between S100B and LT supports the notion of a LT trophic role in the CNS. Further investigations in high-risk infants are needed to elucidate LT involvement in the pathophysiological cascade of events leading to CNS development and damage., (© 2022. The Author(s).)

Lutein is a dietary carotenoid preferentially accumulated in the eye and the brain in early life and throughout the life span. Lutein accumulation in areas of high metabolism and oxidative stress such as the eye and the brain suggest a unique role of this ingredient during the development and maturation of these organs of common embryological origin. Lutein is naturally provided to the developing baby via the cord blood, breast milk and then infant diet. The presence of this carotenoid depends on fruit and vegetable intakes and its bioavailability is higher in breastmilk. This paper aims to review the anatomical development of the eye and the brain, explore the presence and selective deposition of lutein in these organs during pregnancy and infancy and, based on its functional characteristics, present the latest available research on the beneficial role of lutein in the pediatric population. The potential effects of lutein in ameliorating conditions associated with increase oxidative stress such as in prematurity will be also addressed. Since consumption of lutein rich foods falls short of government guidelines and in most region of the world infant formulas lack this bioactive, dietary recommendations for pregnant and breastfeeding women and their child can help to bridge the gap.

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy., (© 2021 Wiley Periodicals LLC.)

CHARGE syndrome is a rare genetic multiple-malformation disorder characterized by wide phenotypic variability. It is often caused by heterozygous variants in CHD7 and, more rarely, SEMA3E. Although craniofacial alterations are frequent in this condition, to date craniosynostosis is not considered part of the clinical spectrum. Here, we report bi-coronal craniosynostosis in a newborn affected by CHARGE syndrome caused by the de novo heterozygous c.6157C>T, p.(Arg2053*) CHD7 variant. We found two additional subjects in the literature with different craniosynostoses and distinct CHD7 alterations. The inclusion of CHD7-related CHARGE syndrome in the group of rare causes of syndromic craniosynostoses is proposed., (© 2021 Wiley Periodicals LLC.)

Mature locomotion involves modular spinal drives generating a set of fundamental patterns of motoneuron activation, each timed at a specific phase of locomotor cycles and associated with a stable muscle synergy. How locomotor modules develop and to what extent they depend on prior experience or intrinsic programs remains unclear. To address these issues, we herein leverage the presence at birth of two types of locomotor-like movements, spontaneous kicking and weight-bearing stepping. The former is expressed thousands of times in utero and postnatally, whereas the latter is elicited de novo by placing the newborn on the ground for the first time. We found that the neuromuscular modules of stepping and kicking differ substantially. Neonates kicked with an adult-like number of temporal activation patterns, which lacked a stable association with systematic muscle synergies across movements. However, on the ground neonates stepped with fewer temporal patterns but all structured in stable synergies. Since kicking and ground-stepping coexist at birth, switching between the two behaviors may depend on a dynamic reconfiguration of the underlying neural circuits as a function of sensory feedback from surface contact. We tracked the development of ground-stepping in 4- to 48-mo-old infants and found that, after the age of 6 mo, the number of temporal patterns increased progressively, reaching adult-like conformation only after independent walking was established. We surmise that mature locomotor modules may derive by combining the multiple patterns of repeated kicking, on the one hand, with synergies resulting from fractionation of those revealed by sporadic weight-bearing stepping, on the other hand., Competing Interests: The authors declare no competing interest.

Background: The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016-2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis., Methods: Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29-36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016-2017, versus 2 seasons before (2014-2015 and 2015-2016) and one season after (2017-2018) the AIFA limitation., Results: During the 2016-2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016-2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk., Conclusions: The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29-36 wGA) infants aged < 6 months at the beginning of the RSV season.

Objectives: To investigate the modulation of genes whose expression level is indicative of stress and toxicity following exposure to three anaesthesia techniques, general anaesthesia (GA), regional anaesthesia (RA), or integrated anaesthesia (IA)., Methods: Patients scheduled for hip arthroplasty receiving GA, RA and IA were enrolled at Rizzoli Orthopaedic Institute of Bologna, Italy and the expression of genes involved in toxicology were evaluated in peripheral blood mononuclear cells (PBMCs) collected before (T0), immediately after surgery (T1), and on the third day (T2) after surgery in association with biochemical parameters., Results: All three anaesthesia methods proved safe and reliable in terms of pain relief and patient recovery. Gene ontology analysis revealed that GA and mainly IA were associated with deregulation of DNA repair system and stress-responsive genes, which was observed even after 3-days from anaesthesia. Conversely, RA was not associated with substantial changes in gene expression., Conclusions: Based on the gene expression analysis, RA technique showed the smallest toxicological effect in hip arthroplasty., Trial Registration: ClinicalTrials.gov number NCT03585647., Competing Interests: The authors have declared that no competing interests exist.

Objective: This report discusses the neurological involvement in respiratory syncytial virus (RSV) infection in neonates., Study Design: We present a case report of a 2-month-old infant affected by a bronchiolitis RSV-positive, with syndrome of inappropriate antidiuretic hormone secretion (SIADH) correlated seizure and encephalopathy., Results: RSV infection can be associated as a serious disease in newborns involving the central nervous system (CNS) and causing seizures or acute encephalopathy. RSV may be also responsible for SIADH and seizures associated with hyponatremia. The RSV related encephalopathy could be caused by different mechanisms, such as direct viral invasion of the CNS or by indirect mechanism mediated by inflammatory cytokines. In addition, it can be favored by severe hyponatremia and SIADH that can cause cerebral edema. Some studies highlight that this virus-related encephalopathy lead to sudden infant death syndrome., Conclusion: In presence of neurological involvement during RSV-infection must be taken in consideration to performing instrumental test to detect cerebral edema. In addiction could be useful to dose inflammatory cytokines, and to consider the immune-modulatory therapy., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate surfactant effectiveness for the treatment of respiratory distress syndrome (RDS) in late preterm infants., Methods: We performed a retrospective cohort study of infants born between 34 +0 and 36 +6  weeks of gestation admitted for respiratory failure in seven perinatal centers from January 2010 to December 2014. We evaluated changes of FiO 2 , PaO 2 and a/APO 2 in surfactant-treated patients, and the need and duration of MV, the duration of noninvasive respiratory support, stay in NICU and in hospital in surfactant-treated and untreated late preterm infants with RDS alone., Results: We studied 562 infants with RDS, 252 (45%) were treated with surfactant and 310 (55%) were not. FiO 2 , PaO 2 and a/APO 2 significantly improved after surfactant treatment. The adjusted odds ratio for the need of MV and the adjusted differences of duration of noninvasive respiratory support, and of NICU and hospital stay were not different in the surfactant and non-surfactant groups., Conclusions: Surfactant therapy was followed by a quick and persisting significant improvement of respiratory function in late preterm infants with RDS. Surfactant did not improve short-term outcomes in our population probably because other factors such as the gestational age, occurrence of complications and poor feeding play a relevant role.

Background: Lutein (LT) is a naturally occurring xanthophyll carotenoid most predominant in the central nervous system (CNS), but its neurotrophic role is still debated. We therefore investigated whether cord blood concentrations correlated with a well-established neurobiomarker, namely activin A., Methods: We conducted a prospective study on the distribution of LT and activin A in arterial cord blood of healthy preterm (n=50) and term (n=82) newborns according to weeks of gestational age (wGA) and gender., Results: LT and activin A showed a pattern of concentration characterized by higher levels (P<0.01, for all) at 33-36 wGA followed by a progressive decrease (P<0.01, for all) from 37 onwards with a dip at term. Both LT and activin A were gender-dependent with significantly (P<0.01, for all) higher levels in all recruited females and after sub-grouping for preterm and term births. LT (R=0.33; P<0.001) correlated with wGA at sampling. There were significant positive correlations between lutein and activin A in male (R=0.93; P<0.001) and female (R=0.89; P<0.001) groups., Conclusions: The present data showing a correlation between LT and activin A support the notion of a neurotrophic role gender-dependent for LT and open the way to further investigations correlating LT with well-established biochemical markers of CNS development/damage., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Aim: Despite advances in perinatal management, there is a flat trend in incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. The main feature of BPD development in preterm infants is an imbalance between increased exposure to free radicals and inadequate antioxidant defences. We investigated the associations between BPD and lipid hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar lavage fluid (BALF)., Methods: In this prospective study, BALF samples were collected from 44 preterm infants with RDS and oxidative stress markers were measured in 11 with BPD and 33 controls without BPD., Results: LOOH levels were significantly higher (p < 0.01) in the BPD group (median 16.35; 25th-75th centile 13.75-17.05 nmol/mL) than in the no BPD group (median 13.18; 25th-75th centile 12.92-13.63 nmol/mL). Conversely, GSH levels were significantly lower in the BPD group (p < 0.01) (median 11.52; 25th-75th centile 6.95-13.85 μmol/mg) than the no BPD group (median: 18.69; 25th-75th centile: 13.89-23.64 μmol/mg). Multiple regression analysis showed significant correlations between BPD and mechanical ventilation time (p < 0.01) and LOOH levels (p < 0.05)., Conclusion: Early LOOH level increases in preterm infants developing BPD suggest that lung biochemical monitoring of sick infants might be possible and BPD could be predicted early by evaluating biomarkers., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Adrenomedullin (AM) is a potent angiogenic, antioxidant and anti-inflammatory peptide protecting the developing lung from injury due to bronchopulmonary dysplasia (BPD) of the preterm infant. At this stage, no data on the potential effects of chorioamnionitis (CA) occurrence and glucocorticoids (GC) administration on AM in developing lungs are still lacking., Objective: to investigate, in a sheep-based model, the positive/side-effects of combined exposure to CA and GC on AM concentrations measured in bronchoalveolar lavage fluid (BALF)., Methods: Time-mated ewes were randomly admitted to one of six treatment groups receiving injection: saline (controls); lipopolysaccharide (L) in intra-amniotic fluid treated alone at 7 or 14 d before delivery or associated with betamethasone (B) intramuscularly; B treated alone (7d) or associated with L (14d). Lambs were surgically delivered at 120 days gestation and euthanized. BALF was used for AM measurement in the studied groups., Results: AM BALF levels significantly ( p  < 0.05, for all) changed both to B and L exposure in a time-dependent manner. The latter was characterized by AM levels at short term superimposable to controls, whilst significantly ( p  > 0.05) decreased at long-term. The former showed increased AM at short and decreased at long-term ( p  < 0.05, for all), respectively., Conclusions: the present results showing AM BALF changes in a sheep-based model support the AM role in the hemodynamic patterns due to CA and BPD occurrence and open the way to further studies investigating the role of vasoactive agents as trustable markers of lung development/damage.

Congenital leukemia is a very rare severe condition and leukemia cutis may represent the presenting sign of this malignancy, sometimes preceding hematological findings of weeks. Typical clinical features include multiple red to purple papules, macules and nodules due to direct infiltration of the skin by malignant cells. We illustrate these cutaneous findings in a patient with congenital leukemia and tetralogy of Fallot.

Background: Late preterm (LP) are at higher risk than term infants to develop infections due to their more immature immune system. Little data about the risks and incidence of infection and sepsis in LP are present in literature., Aims: To evaluate treated infection rates and risk factors for infection in moderate and late preterm infants (gestational age = 32-36 weeks)., Study Design: We retrospectively studied a population of 771 moderate and late preterm infants consecutively admitted to our unit from June 2008 to November 2013., Results: Treated infections were 128, with an incidence of 16.6%; the 90% (n = 115) occurred during the first 72 hours of life. Blood cultures were positive in 22% of cases, umbilical venous catheter cultures were positive in 26% of cases; Coagulase-negative staphylococci were the most frequently isolated pathogens. Patients of the sepsis group had a C-reactive protein (CRP) mean value of 28.27 mg/L and a procalcitonin mean value of 25.3 μg/L. Risk factors for infections were umbilical venous catheter (UVC) insertion (χ(2) = 15.9; p ≤ 0.05), prophylaxis with antenatal corticosteroids (χ(2) = 16.7; p ≤ 0.05) and birth by cesarean section, with observed values very similar to the expected values (χ(2) = 15.9; p = 0.1). Respiratory symptoms were found in 47 of the 60 patients in the sepsis group (78.3%)., Conclusions: Late and moderate preterm infants have an increased significant risk of infection compared to term infants. Infections, given the high frequency of negative cultures in neonates, should be often suspected and treated on the basis of clinical features and inflammatory markers, trying always to avoid a possible overtreatment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Contaminant biodegradation in unsaturated soils may reduce the risks of vapor intrusion. However, the reported rates show large variability and are often derived from slurry experiments that are not representative of unsaturated conditions. Here, different laboratory setups are used to derive the biodegradation capacity of an unsaturated soil layer through which gaseous toluene migrates from the water table upwards. Experiments in static unsaturated soil microcosms at 6-30 % water-filled porosity (WFP) and unsaturated soil columns at 9, 14, and 27 % WFP were compared with liquid batches containing the same culture of Alicycliphilus denitrificans. The biodegradation rates for the liquid batches were orders of magnitude lower than for the other setups. Hence, liquid batches do not necessarily reflect optimal conditions for bacteria; either oxygen or toluene mass transfer at the cell scale or the absence of soil-water-air interfaces seemed to be limiting bacterial activity. For the column setup, the rates were limited by mass supply. The microcosm results could be described by apparent first-order biodegradation constants that increased with WFP or through a numerical model that included biodegradation as a first-order process taking place in the liquid phase only. The model liquid phase first-order rates varied between 6.25 and 20 h(-1) and were not related to the water content. Substrate availability was the primary factor limiting bioactivity, with evidence for physiological stress at the lowest water-filled porosity. The presented approach is useful to derive liquid phase biodegradation rates from experimental data and to include biodegradation in vapor intrusion models.

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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Lutein is an antioxidant carotenoid exerting a key role in eye health, but no reference curve in the perinatal period is available., Design and Methods: We conducted a prospective study on the distribution of lutein and its metabolite 3'-oxolutein in arterial cord blood of preterm (n=40) and term (n=76) newborns according to gestational age, sex and delivery modalities., Results: Lutein and 3'-oxolutein concentrations peaked at the beginning of third trimester (P<0.01, for both) being higher in the preterm than in term group. From 36 weeks onwards, lutein and 3'-oxolutein levels progressively decreased reaching the lowest levels at term between 41 and 42 weeks (P<0.01, for both). Lutein and 3'-oxolutein significantly (P<0.01, for all) correlated with each other (R=0.33) and with gestational age at sampling (R=0.31 and R=0.38 for lutein and 3-oxolutein, respectively) (P<0.001, for all). Indeed, lutein and 3'-oxolutein concentrations were significantly higher (P<0.05, for all) in female than in male and significantly lower (P<0.01, for both) in newborns delivered by caesarean section when compared to vaginal delivery., Conclusions: Since macula densa and retina are sites of lutein accumulation, the present findings open-up a new cue on the potential role of lutein in the prevention of the retinopathy of prematurity., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

A one-dimensional numerical model was developed and used to identify the key processes controlling vapor intrusion risks by means of a sensitivity analysis. The model simulates the fate of a dissolved volatile organic compound present below the ventilated crawl space of a house. In contrast to the vast majority of previous studies, this model accounts for vertical variation of soil water saturation and includes aerobic biodegradation. The attenuation factor (ratio between concentration in the crawl space and source concentration) and the characteristic time to approach maximum concentrations were calculated and compared for a variety of scenarios. These concepts allow an understanding of controlling mechanisms and aid in the identification of critical parameters to be collected for field situations. The relative distance of the source to the nearest gas-filled pores of the unsaturated zone is the most critical parameter because diffusive contaminant transport is significantly slower in water-filled pores than in gas-filled pores. Therefore, attenuation factors decrease and characteristic times increase with increasing relative distance of the contaminant dissolved source to the nearest gas diffusion front. Aerobic biodegradation may decrease the attenuation factor by up to three orders of magnitude. Moreover, the occurrence of water table oscillations is of importance. Dynamic processes leading to a retreating water table increase the attenuation factor by two orders of magnitude because of the enhanced gas phase diffusion., (Copyright © 2012 SETAC.)

Background: Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia., Aims: To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia., Study Design: prospective, observational, multicenter., Subjects: 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy., Methods: All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin >17 mg/dL or need for phototherapy., Results: Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age., Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Unlabelled: Preterm newborns may be discharged when clinical conditions are stable and maturity of physiological functions has been gained, but no precise indications on weight and GA to be reached before discharge are available. In our NICU we have observed in the last five years 234 newborns < 32 weeks of GA; we have decided to transfer from incubators at the mean weight of 1737 g, regardless of their GA and birth weight and to discharge at a mean weight of 1966 g, the lowest mean weight in comparison to the other twelve NICUs of the Lazio region. We have analyzed if the major diseases affecting those newborns (RDS, mechanical ventilation, PDA, IVH/PVL, PHH, NEC, ROP, sepsis ) have influenced weight at discharge in 13 NICUs of Lazio region., Conclusions: in our NICU the discharge of ELBW/VLBW preterm newborns < 32 weeks GA and/or < 1500 g can be feasible at a mean weight close to 1900 g. An early transfer from incubator at a mean weight of 1737 g promotes an early discharge from hospital. Major diseases affecting those newborn haven't influenced weight at discharge.

Growth hormone deficiency (GHD) related to standard dose chemotherapy has rarely been described. We report on a case of localized ganglioneuroblastoma treated by carboplatin/etoposide for 2 courses and surgery, which developed a serious GHD after 56 months. At present, the child is growing on by GH replacement therapy. We discuss about the hypothesis that GHD may be related to chemotherapy and we report a review of previous published cases.

Many reactions in cells proceed via the sequestration of two DNA molecules in a synaptic complex. SfiI is a member of a growing family of restriction enzymes that can bind and cleave two DNA sites simultaneously. We present here the structures of tetrameric SfiI in complex with cognate DNA. The structures reveal two different binding states of SfiI: one with both DNA-binding sites fully occupied and the other with fully and partially occupied sites. These two states provide details on how SfiI recognizes and cleaves its target DNA sites, and gives insight into sequential binding events. The SfiI recognition sequence (GGCCNNNN[downward arrow]NGGCC) is a subset of the recognition sequence of BglI (GCCNNNN[downward arrow]NGGC), and both enzymes cleave their target DNAs to leave 3-base 3' overhangs. We show that even though SfiI is a tetramer and BglI is a dimer, and there is little sequence similarity between the two enzymes, their modes of DNA recognition are unusually similar.

Background: Neonatal onset hypopituitarism is a life-threatening, potentially treatable endocrine disease. A possible cause is congenital absence of the anterior pituitary gland, a condition very rarely reported in the literature., Methods: A series of 5 cases of children with pituitary aplasia referred to the Centre of Paediatric Endocrinology 'Rina Balducci', Tor Vergata University, Rome, is presented., Results: Major clinical features in our patients were respiratory distress on the first day of life, in spite of uneventful pregnancy, labour and delivery, metabolic acidosis, non-cholestatic jaundice, hypotonia, severe hypoglycaemia, hypogenitalism, and midline defects. Diagnosis was established by endocrine tests during hypoglycaemia and hypothalamic-pituitary MRI scan. Symptoms disappeared soon after replacement therapy was started., Conclusion: We stress the importance of performing baseline endocrine tests as soon as possible during hypoglycaemia and MRI of the brain aimed at visualizing the hypothalamic-pituitary area in neonates with hypogenitalism and severe unexplained hypoglycaemia, so that the irreversible neurological and developmental consequences of panhypopituitarism can be prevented by adequate replacement therapy., (Copyright 2004 S. Karger AG, Basel)

The genes coding for the EcoHK31I and EaeI restriction-modification (R-M) systems from Escherichia coli strain HK31 and Enterobacter aerogenes, respectively, have been cloned and sequenced. Both ENases recognize and cleave Y/GGCCR leaving 4 nucleotide 5'-protruding ends, while the MTases modify the internal cytosine. The systems were isolated on a 2.3kb AseI fragment for EcoHK31I, and a 4.6 kb HindIII fragment for EaeI. The R and M genes of both systems converge and overlap by 14 nucleotides. Previously, we found that M.EcoHK31I consisted of two subunits, (alpha and beta), with the beta subunit being translated from an alternative open reading frame within the gene encoding the alpha subunit. Sequence comparison between the EcoHK31I and EaeI systems reveals striking similarity. The eaeIM gene also encodes alpha and beta polypeptides of 309 and 176 amino acids which share 96% and 97% identity, respectively, with those of ecoHK31IM. ecoHK31IR and eaeIR encode proteins of 318 and 315 aa, respectively, which share 92% identity but are otherwise unique in the GenBank database. The EaeI and the EcoHK31I R-M systems were found to be flanked by genes coding for integrases. It is possible that these integrases have facilitated the transfer of this system among different bacterial species.

An unusual case of Primary Carcinoma of the vagina was recently observed. The patient was treated surgically in 1981 for squamous cervical carcinoma in situ (CIN 3); eight years later the same patient was treated for squamous carcinoma of the vagina that involved the upper, median and lower tract. She was treated with radical colpectomy and VBP chemotherapy for three courses. The pathology, natural history and treatment are discussed.

Acute appendicitis is the most common diagnosis made (in the Western world) in patients with an "acute abdomen." Although the mortality rate has been vastly reduced, the diagnostic inaccuracy rate of 15% to 20% has remained unchanged in the past 100 years. In this article, the authors report the ultrasonographic findings in 80 patients examined using a small linear-array transducer, which enables direct visualization of the inflamed appendix. During 22 months, 80 patients (28 males and 52 females; age range, 3 to 81 years; mean, 32.3 years) with equivocal clinical signs and symptoms of acute appendicitis were examined sonographically. Of the 29 patients whose appendicitis was verified at surgery, ultrasonography was positive in 26, with an overall sensitivity of 90%. Of the 51 patients who did not have appendicitis, ultrasonography was negative in all, with a specificity of 100%. The authors concur with reports in the literature that ultrasonography is helpful in diagnosing appendicitis.

Chronic portal-systemic encephalopathy (CPSE) following portal-systemic shunts may be incapacitating and non-responsive to intensive medical management. Between 1960 and 1980, 12 patients with cirrhosis who were institutionalized with CPSE underwent colonic exclusion. Cirrhosis was due to alcohol in ten patients and to cryptogenic liver disease in two. Nine patients had previously undergone end-to-side portacaval shunts and two patients had had mesocaval shunts. One patient had a spontaneous shunt between splenic and renal veins. Ten patients underwent colectomy and ileosigmoidostomy; one had colectomy, ileostomy, and mucous fistula; and one had colonic bypass and ileosigmoidostomy. Four patients died postoperatively. Survivors were clinically improved and able to leave a closed institutional environment. Colectomy may be considered in disabling cases of CPSE unresponsive to medical therapy; it is a final effort at functional rehabilitation. Although mortality is high, improvement in functional status can be expected among survivors of the operation.