Atomistic simulations reveal impacts of missense mutations on the structure and function of SynGAP1.

De novo mutations in the synaptic GTPase activating protein (SynGAP) are associated with neurological disorders like intellectual disability, epilepsy, and autism. SynGAP is also implicated in Alzheimer's disease and cancer. Although pathogenic variants are highly penetrant in neurodevelopmental conditions, a substantial number of them are caused by missense mutations that are difficult to diagnose. Hence, in silico mutagenesis was performed for probing the missense effects within the N-terminal region of SynGAP structure. Through extensive molecular dynamics simulations, encompassing three 150-ns replicates for 211 variants, the impact of missense mutations on the protein fold was assessed. The effect of the mutations on the folding stability was also quantitatively assessed using free energy calculations. The mutations were categorized as potentially pathogenic or benign based on their structural impacts. Finally, the study introduces wild-type-SynGAP in complex with RasGTPase at the inner membrane, while considering the potential effects of mutations on these key interactions. This study provides structural perspective to the clinical assessment of SynGAP missense variants and lays the foundation for future structure-based drug discovery.

Retrospective cohort study shows that the risks for retinopathy of prematurity included birth age and weight, medical conditions and treatment.

AIM: This study described the characteristics and risk factors of neonates who developed retinopathy of prematurity (ROP) and severe treatable ROP in two Egyptian neonatal intensive care units (NICUs). METHODS: This retrospective cohort study comprised 108 preterm neonates who were screened for ROP after being admitted to the two NICUs run by Cairo University Hospital from June 2014 to May 2015. Patients were examined using digital fundus photography and indirect ophthalmoscopy was performed if ROP was detected. RESULTS: Retinopathy of prematurity occurred in 75 patients. Late-onset sepsis, ventilation and hypercapnia were independently associated with ROP. Patients who developed severe treatable ROP had a younger gestational age (GA) than patients who did not develop ROP or developed mild or moderate ROP (29 weeks, range 27-33 weeks versus 32 weeks, range 28-36 weeks, p = 0.002) and a lower birthweight (1200 g, range 980-1590 g versus 1460 g, range 770-2475 g, p = 0.029). The risk factors associated with severe treatable ROP included the duration of admission, the duration of incubator oxygen, late-onset sepsis, intraventricular haemorrhage, total parenteral nutrition and the duration of caffeine citrate therapy. CONCLUSION: This study showed that the risks for ROP were wide-ranging and included GA and weight, medical conditions and treatment.

Morbidity and outcome of severe respiratory syncytial virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) is the main cause of severe acute respiratory infection (SARI) in infants and young children. This study aimed to identify risk factors for intensive care unit (ICU) admission, prolonged length of stay (PLOS), and mortality in patients hospitalized with SARI caused by RSV. METHODS: This prospective cohort study included children hospitalized with SARI (according to the World Health Organization definition) and whose laboratory results proved RSV infection during the period from February 2010 to May 2011. RESULTS: Out of 240 enrolled patients, 24 patients (10%) were admitted to the ICU, 57 patients (24.3%) had a PLOS of >9 days and 12 patients (5%) died. The presence of cyanosis (P = 0.000; OR, 351.7) and lung consolidation (P = 0.006, OR, 9.3) were independent risk factors associated with ICU admission. The need for ICU admission (P = 0.000; OR, 6.1) and lung consolidation (P = 0.008, OR, 2.46) were independent risk factors associated with PLOS. The presence of an underlying congenital heart disease (P = 0.03, OR, 18.3), thrombocytopenia (P = 0.04, OR, 32.86) and mechanical ventilation (P = 0.000; OR, 449.4) were the only independent risk factors associated with mortality in our study. CONCLUSIONS: Early recognition of risk factors for complicated RSV disease on admission prompts early interventions and early ICU admissions for these children.

Significance of Polymers with "Allyl" Functionality in Biomedicine: An Emerging Class of Functional Polymers.

In recent years, polymer-based advanced drug delivery and tissue engineering have grown and expanded steadily. At present, most of the polymeric research has focused on improving existing polymers or developing new biomaterials with tunable properties. Polymers with free functional groups offer the diverse characteristics needed for optimal tissue regeneration and controlled drug delivery. Allyl-terminated polymers, characterized by the presence of a double bond, are a unique class of polymers. These polymers allow the insertion of a broad diversity of architectures and functionalities via different chemical reactions. In this review article, we shed light on various synthesis methodologies utilized for generating allyl-terminated polymers, macromonomers, and polymer precursors, as well as their post-synthesis modifications. In addition, the biomedical applications of these polymers reported in the literature, such as targeted and controlled drug delivery, improvement i aqueous solubility and stability of drugs, tissue engineering, and antimicrobial coatings, are summarized.

Synthesis of an Azide- and Tetrazine-Functionalized [60]Fullerene and Its Controlled Decoration with Biomolecules.

Bingel cyclopropanation between Buckminster fullerene and a heteroarmed malonate was utilized to produce a hexakis-functionalized C60 core, with azide and tetrazine units. This orthogonally bifunctional C60 scaffold can be selectively one-pot functionalized by two pericyclic click reactions, that is, inverse electron-demand Diels-Alder and azide-alkyne cycloaddition, which with appropriate ligands (monosaccharides, a peptide and oligonucleotides tested) allows one to control the assembly of heteroantennary bioconjugates.

Functional block copolymer micelles based on poly (jasmine lactone) for improving the loading efficiency of weakly basic drugs.

Functionalization of polymers is an attractive approach to introduce specific molecular forces that can enhance drug-polymer interaction to achieve higher drug loading when used as drug delivery systems. The novel amphiphilic block copolymer of methoxy poly(ethylene glycol) and poly(jasmine lactone) i.e., mPEG-b-PJL, derived from renewable jasmine lactone provides free allyl groups on the backbone thus, allowing flexible and facile post-synthesis functionalization. In this study, mPEG-b-PJL and its carboxyl functionalized polymer mPEG-b-PJL-COOH were utilised to explore the effect of ionic interactions on the drug-polymer behaviour. Various drugs with different pK a values were employed to prepare drug-loaded polymeric micelles (PMs) of mPEG-b-PJL, mPEG-b-PJL-COOH and Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) via a nanoprecipitation method. Electrostatic interactions between the COOH pendant on mPEG-b-PJL-COOH and the basic drugs were shown to influence the entrapment efficiency. Additionally, molecular dynamics (MD) simulations were employed to understand the polymer-drug interactions at the molecular level and how polymer functionalization influenced these interactions. The release kinetics of the anti-cancer drug sunitinib from mPEG-b-PJL and mPEG-b-PJL-COOH was assessed, and it demonstrated a sustainable drug release pattern, which depended on both pH and temperature. Furthermore, the cytotoxicity of sunitinib-loaded micelles on cancer cells was evaluated. The drug-loaded micelles exhibited dose-dependent toxicity. Also, haemolysis capacity of these polymers was investigated. In summary, polymer functionalization seems a promising approach to overcome challenges that hinder the application of polymer-based drug delivery systems such as low drug loading degree.

On the Effect of Lattice Topology on Mechanical Properties of SLS Additively Manufactured Sheet-, Ligament-, and Strut-Based Polymeric Metamaterials.

Cellular lattices with architectural intricacy or metamaterials have gained a substantial amount of attention in the past decade due to the recent advances in additive manufacturing methods. The lattice topology controls its physical and mechanical properties; therefore, the main challenge is selecting the appropriate lattice topology for a desired function and application. In this work, we comprehensively study the topology-property relationship of three classes of polymer metamaterials based on triply periodic minimal surfaces (TPMS) of sheet/shell and ligament types, and other types of well-known strut-based lattices. The study uses a holistic approach of designing, additive manufacturing, microstructural characterization, and compressive uniaxial mechanical testing of these polymer lattices that are 3D-printed using the laser powder bed fusion technique known as selective laser sintering (SLS). In total, 55 lattices with different topologies and relative densities were 3D-printed and tested. Printing quality was assessed using scanning electron microscopy and micro-computed tomography. The extracted mechanical properties of elastic modulus, yield strength, plateau strength, and energy absorption are thoroughly compared between the different lattice architectures. The results show that all the investigated ligament-based TPMS polymer lattices exhibit bending-dominated elastic and plastic behavior, indicating that they are suitable candidates for energy absorbing applications. The sheet-based TPMS polymer lattices, similarly to the well-known Octet-Truss lattice, exhibited an elastic stretching-dominated mode of deformation and proved to have exceptional stiffness as compared to all other topologies, especially at low relative densities. However, the sheet-based TPMS polymer lattices exhibited a bending-dominated plastic behavior which is mainly driven by manufacturing defects. Overall, however, sheet-based TPMS polymer lattices exhibited the best mechanical properties, followed by strut-based lattices and finally by ligament-based TPMS lattices. Finally, it is depicted that at high relative densities, the mechanical properties of lattices of various architectures tend to converge, which implies that the topological effect is more significant at low relative densities. Generally, this study provides important insights about the selection of polymer mechanical metamaterials for various applications, and shows the superiority of TPMS-based polymer metamaterials as compared to several other classes of polymer mechanical metamaterials.

Design of nanoconstructs that exhibit enhanced hemostatic efficiency and bioabsorbability.

Hemorrhage is a prime cause of death in civilian and military traumatic injuries, whereby a significant proportion of death and complications occur prior to paramedic arrival and hospital resuscitation. Hence, it is crucial to develop hemostatic materials that are able to be applied by simple processes and allow control over bleeding by inducing rapid hemostasis, non-invasively, until subjects receive necessary medical care. This tutorial review discusses recent advances in synthesis and fabrication of degradable hemostatic nanomaterials and nanocomposites. Control of assembly and fine-tuning of composition of absorbable (i.e., degradable) hemostatic supramolecular structures and nanoconstructs have afforded the development of smart devices and scaffolds capable of efficiently controlling bleeding while degrading over time, thereby reducing surgical operation times and hospitalization duration. The nanoconstructs that are highlighted have demonstrated hemostatic efficiency pre-clinically in animal models, while also sharing characteristics of degradability, bioabsorbability and presence of nano-assemblies within their compositions.

Development of an Immunochromatographic Strip Using Conjugated Gold Nanoparticles for the Rapid Detection of Klebsiella pneumoniae Causing Neonatal Sepsis.

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and the spread of multi-drug-resistant bacteria. In this work, we deployed bioinformatics and proteomics analyses to determine a promising target that could be used for the identification of a major neonatal sepsis causative agent, Klebsiella pneumoniae. A 19 amino acid peptide from a hypothetical outer membrane was found to be very specific to the species, well conserved among its strains, surface exposed, and expressed in conditions simulating infection. Antibodies against the selected peptide were conjugated to gold nanoparticles and incorporated into an immunochromatographic strip. The developed strip was able to detect as low as 105 CFU/mL of K. pneumoniae. Regarding specificity, it showed negative results with both Escherichia coli and Enterobacter cloacae. More importantly, in a pilot study using neonatal sepsis cases blood specimens, the developed strip selectively gave positive results within 20 min with those infected with K. pneumoniae without prior sample processing. However, it gave negative results in cases infected with other bacterial species.

Clinical Characteristics of Preterm Neonates with Aggressive Posterior Retinopathy of Prematurity.

PURPOSE: We aimed to identify the risk factors that may predispose preterm neonates to develop aggressive posterior retinopathy of prematurity (APROP). METHODS: This retrospective case control study included 16 infants with APROP in zone 1 or posterior zone 2. Thirty-four gestational age and birth weight-matched controls with stage 2 or less ROP were included. We reviewed medical records on infant birth and postnatal characteristics. RESULTS: Patients who developed APROP had a significantly longer duration of caffeine therapy, were significantly more likely to be small for gestational age (SGA), and were more likely to have a positive blood culture than patients who developed less severe ROP. Patients with APROP who required retreatment had received inotropes for a longer duration of time, had received more plasma transfusions, were more likely to have IVH, and had a greater decrease in the serum hemoglobin during hospitalization. CONCLUSION: Being SGA, receiving caffeine for a longer duration, and having culture-proven sepsis were associated with APROP. IVH, a low serum hemoglobin, the need for more plasma transfusions, and a longer duration of inotropes were associated with APROP which required retreatment.

A Novel Surface-Exposed Polypeptide Is Successfully Employed as a Target for Developing a Prototype One-Step Immunochromatographic Strip for Specific and Sensitive Direct Detection of Staphylococcus aureus Causing Neonatal Sepsis.

Neonatal sepsis is a life-threatening condition and Staphylococcus aureus is one of its major causes. However, to date, no rapid and sensitive diagnostic tool has been developed for its direct detection. Bioinformatics analyses identified a surface-exposed 112-amino acid polypeptide of the cell wall protein NWMN_1649, a surface protein involved in cell aggregation and biofilm formation, as being a species-specific and highly conserved moiety. The polypeptide was cloned, purified, and used to immunize mice to raise specific immunoglobulins. The purified antibodies were conjugated to gold nano-particles and used to assemble an immunochromatographic strip (ICS). The developed prototype ICS detected as low as 5 µg purified polypeptide and 102 CFU/mL S. aureus within 15 min. The strip showed superior ability to directly detect S. aureus in neonatal sepsis blood specimens without prior sample processing. Moreover, it showed no cross-reaction in specimens infected with two other major causes of neonatal sepsis; coagulase-negative staphylococci and Klebsiella pneumoniae. The selected NWMN_1649-derived polypeptide demonstrates success as a promising biomolecule upon which a prototype ICS has been developed. This ICS provides a rapid, direct, sensitive, and specific option for the detection of S. aureus causing neonatal sepsis. Such a tool is urgently needed especially in resources-limited countries.

Association of TLR polymorphisms with bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a leading cause of morbidity and mortality during infancy. Evidence suggests that the Toll-like receptor (TLR) signaling pathway plays an integral role in lung inflammation and injury. This study aimed to detect single nucleotide polymorphisms (SNPs) in TLR pathway genes [TLR5 and Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP)] among preterm neonates and to determine their association with the development and severity of bronchopulmonary dysplasia.

Anti-oxidant profiles and markers of oxidative stress in preterm neonates.

BACKGROUND: Preterm birth is associated with an increased oxidant burden which places these infants at a higher risk of injury. AIMS: This prospective study aimed to assess levels of antioxidants and a marker of oxidative stress in preterm neonates. OBJECTIVES: (i) To compare levels of anti-oxidants [vitamin A, vitamin E, catalase, total anti-oxidant status (TAS)] as well as malondialdehyde level (MDA) (a marker of lipid peroxidation) between preterm and full-term neonates; (ii) to determine changes in the values of measured vitamins at birth and at discharge among preterm neonates; and (iii) to compare levels of anti-oxidants with MDA levels in relation to complications of prematurity and outcome. METHODS: The study was undertaken in 100 preterm neonates and 100 full-term neonates as a control group. MDA was estimated by a thiobarbituric acid-reactive technique; TAS was determined using a Randox assay kit; catalase activity was measured spectrophotometrically and vitamin A and E levels were estimated by high performance liquid chromatography. RESULTS: The plasma levels of vitamin A, vitamin E, TAS and catalase were significantly lower in the preterm than in the full-term group (P < 0.01), and the plasma level of MDA was significantly higher in preterm than full-term neonates (P < 0.01). Vitamin A and E levels in preterm neonates were significantly higher at discharge than at birth (P < 0.01). Vitamin A, vitamin E and catalase levels at birth were significantly lower in patients who developed necrotizing enterocolitis or bronchopulmonary dysplasia than in those who did not. CONCLUSION: Preterm neonates are exposed to increased oxidant stress at birth and are susceptible to anti-oxidant deficiencies. A higher dose of enteral vitamin A supplementation in preterm neonates might reduce morbidity and improve outcome. Further studies are warranted to evaluate the appropriate dose of oral vitamin E supplementation for preterm neonates.

Polymorphisms of Vascular Endothelial Growth Factor and Retinopathy of Prematurity.

PURPOSE: Retinopathy of prematurity (ROP) is a major problem among preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of factors such as vascular endothelial growth factor (VEGF). The authors investigated the association of ROP with VEGF genetic polymorphisms and clinical (maternal, perinatal, neonatal) risk factors among preterm infants admitted to the neonatal intensive care unit. METHODS: The frequencies of VEGF 634 C/G and VEGF 936 C/T polymorphisms were determined in DNA from 102 preterm infants by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: The frequency of the VEGF 634 CG genotype was significantly higher, whereas the frequency of the VEGF 634 CC genotype was significantly lower among neonates with ROP. The frequencies of the VEGF 634 GG, VEGF 936 CC, and VEGF 936 CT genotypes were similar in both groups. The distribution of VEGF 634 G allele was significantly different between the two groups. By logistic regression analysis, low birth weight, presence of maternal disease, respiratory distress syndrome, hypotension, and VEGF 634 CG genotype remained significant risk factors for the development of ROP. CONCLUSIONS: The results support the hypothesis that the carrier state of VEGF 634 C/G polymorphism has an impact on the risk of ROP in infants. A broader study may suggest that this marker could be used as an indicator in the screening for ROP.

Comparison of digital imaging screening and indirect ophthalmoscopy for retinopathy of prematurity.

The aims of this study were to determine the incidence and severity of retinopathy of prematurity (ROP) using digital imaging screening, confirm findings by indirect opthalmoscopy, and document risk factors of ROP in the neonatal intensive care unit (NICU) of a large tertiary hospital in a developing country. This prospective cohort study included infants with gestational age (GA) ≤ 32 wk, birth weight (BW) ≤ 1,500 g, or older and heavier neonates who were critically ill. Two hundred twenty two eyes (111 infants) were screened with digital imaging (Ret-Cam) and indirect ophthalmoscopy until retinal vascularization was complete or the disease regressed. Perinatal risk factors for ROP were analyzed. The overall incidence of ROP was 18.9 %. The incidence of ROP requiring treatment was 5.4 % (12/222) of the total eyes screened. Lower GA and blood transfusion were independent risk factors associated with ROP by multivariate analysis (p = 0.001, OR = 0.562, 95 % CI = 0.395-0.802, and p = 0.027, OR = 6.11, 95 % CI = 1.22-30.44, respectively). Digital imaging facilitated timely screening and detection of ROP, and enabled transfer of images, allowing early intervention for patients who required treatment.

Profile of cystic fibrosis in a single referral center in Egypt.

It was generally believed that Cystic fibrosis (CF) is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children's Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L) were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR) gene. Thirty-six patients (36%) had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%), failure to thrive in 27 (75%), steatorrhea in 24 (66.7%), and hepatobiliary involvement in 5 (13.9%). Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8%) patients, 8 (25%) were homozygous, 14 (43.8%) were heterozygous, and 10 (31.3%) tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

Risk factors of prolonged hospital stay in children with viral severe acute respiratory infections.

INTRODUCTION: Severe acute lower respiratory infections (SARIs) are one of the major causes of morbidity and mortality in young children, especially in developing countries. The present study focused on detection of risk factors for prolonged hospital stays among children with viral SARIs. METHODOLOGY: A sentinel surveillance study was conducted at Cairo University Hospital (CUH) between February 2010 and May 2011. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all children admitted with SARIs. Viruses were identified using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Out of 1,046 children, 380 (36%) were positive for one or more viruses; these included respiratory syncytial virus (RSV) (22.9%), adenovirus (6.2%), parainfluenza viruses (PIVs1-3) (5.1%), human metapneumovirus (HMPV) (4.5%), influenza A (1.4%), and influenza B (0.6%). Viral etiology was mainly detected in children under one year of age (88.9%). Prolonged length of stay was independently associated with the presence of cyanosis and underlying chronic illness (OR 7.4, CI: 1.8-30.32 [p = 0.005], OR 2.5, CI: 1.36-4.64 [p = 0.004], respectively). Virus type did not affect the length of hospital stay (p > 0.05). Oxygen therapy was required in 91% of the patients. A total of 43 patients (11.6%) required intensive care admission. Twenty-one patients (5.5%) died, and 15 of them (71.4%) had an underlying chronic illness. CONCLUSIONS: The study demonstrated the important burden of respiratory viruses as a cause of SARI in hospitalized children in a tertiary Egyptian hospital. Cyanosis and underlying chronic illness were significantly associated with prolonged length of stay.

Frequency of Helicobacter pylori infection among Egyptian children presenting with gastrointestinal manifestations.

BACKGROUND AND AIMS: Recurrent abdominal pain (RAP) and other gastrointestinal (GI) symptoms are common complaints among children. The role of Helicobacter pylori in the causation of these complaints remains controversial. The aim of this study was to determine the frequency of H. pylori infection among children presenting with GI manifestations and to determine the most common clinical presentation of the infection in Egyptian children. PATIENTS AND METHODS: This prospective cross-sectional study included 150 consecutive patients aged 5-15 years who presented to the outpatient clinic of Cairo University's Specialized Pediatric Hospital with GI complaints. Screening for H. pylori infection was performed using a 13C-urea breath test (13C-UBT), and in patients whose 13C-UBT was positive, diagnosis was confirmed by visualizing the bacterium in biopsy specimens obtained by GI endoscopy. RESULTS: RAP was the most frequent GI complaint of the study population (82%), followed by anorexia (6.7%), vomiting (6.7%), and chronic diarrhea (4.7%). Seventy percent of these patients were positive for the 13C-UBT. Ninety-one of the patients who complained of RAP had a positive 13C-UBT, whereas the remaining 32 patients who had RAP had a negative 13C-UBT, a difference that was statistically significant (P=0.023). However, no statistically significant differences were found between the 13C-UBT result among patients with anorexia, vomiting, or diarrhea (P=0.153, 1.00, and 0.447, respectively). CONCLUSION AND RECOMMENDATIONS: Screening for H. pylori infection should be performed for school-aged children who have GI complaints, especially for those who complain of RAP.

Amino acid and acylcarnitine profiles in premature neonates: a pilot study.

OBJECTIVE: To investigate the longitudinal changes in amino acid (AA) and acylcarnitine (AC) profiles of preterm neonates over the first 2 wk of life, and to detect any significant deviation from full term values that requires change of cut-off values used for detection of metabolic disorders in preterm neonates. METHODS: This observational analytical longitudinal study was conducted on 131 premature neonates (gestational age ranged from 27 to 36 wk) and 143 healthy full-term neonates. Dried blood spots were taken on the 5th and 14th postnatal day from the premature neonates and on day 5 from full term neonates for neonatal screening. Samples were analyzed for AA and AC using tandem mass spectrometer. RESULTS: Most AA significantly decreased on day 14 compared to day 5 among preterm neonates (p < 0.05). The combined values of total carnitine (TC), total acylcarnitine (tAC) and short-chain acylcarnitines on day 5 among preterm neonates were statistically significantly higher compared to the day 14 sample (p 0.0001), whereas no statistically significant difference was found regarding the values of medium-, long-chain acylcarnitines, tAC/FC, and FC/TC (p > 0.05). The levels of AA of preterm neonates were statistically significantly higher than that of the controls (p < 0.05). The values of TC, tAC, short-, medium- and long-chain acylcarnitines, were significantly higher than those of the controls (p < 0.05). The reference ranges for preterm neonates were determined using the 1st and 99.9th percentiles. CONCLUSIONS: AA and AC showed an age-related distribution of their concentrations. This underlines the importance of using appropriate reference values when working with a prematurely born population.

Empirical antibiotic treatment and the risk of necrotizing enterocolitis and death in very low birth weight neonates.

BACKGROUND AND OBJECTIVES: Antibiotics are one of the most overused drugs in the neonatal unit. Our objective was to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis (NEC) and/or death in very low birth weight (VLBW) neonates with sterile initial postnatal culture results. DESIGN AND SETTING: A retrospective cohort analysis of VLBW neonates admitted to a tertiary center during the period from 1 January 2008 to 31 december 2009. PATIENTS AND METHODS: The study included VLBW neonates who had been inborn and admitted to the neonatal intensive care unit within the first 24 hours after birth. We used descriptive statistics to characterize the study population, and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent NEC and/or death. RESULTS: Of 328 VLBW neonates admitted to our center, 207 (63%) survived >5 days and received initial empirical antibiotic treatment for ≥5 days. The median duration of initial empirical antibiotic therapy was 7 days (range 5-10 days). those neonates were more likely to be of younger gestational age, lower birth weight, and to have lower Apgar scores (P<.001, .001 and .017, respectively). each empirical treatment day was associated with increased odds of death (or 1.45, CI 1.24-1.69), NEC (or 1.32, CI 1.05-1.65), and the composite measure of NEC or death (or 2.13, CI 1.55-2.93). CONCLUSION: The use of prolonged initial empirical antibiotic therapy in VLBW neonates with initial sterile culture results may be associated with an increased risk of NEC or death and should be used with caution.