Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Free carrier enhanced depletion in ZnO nanorods decorated with bimetallic AuPt nanoclusters.

The decoration of semiconductor nanostructures with small metallic clusters usually leads to an improvement of their properties in sensing or catalysis. Bimetallic cluster decoration typically is claimed to be even more effective. Here, we report a detailed investigation of the effects of Au, Pt or AuPt nanocluster decoration of ZnO nanorods on charge transport, photoluminescence and UV sensitivity. ZnO nanorods were synthesized by chemical bath deposition while decoration with small nanoclusters (2-3 nm in size) was achieved by a laser-ablation based cluster beam deposition technology. The structural properties were investigated by scanning electron microscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy and Rutherford backscattering spectrometry, and the optoelectronic properties by current-voltage and photoluminescence measurements. The extent of band bending at the cluster-ZnO interface was quantitatively modeled through numerical simulations. The decoration of ZnO nanorods with monometallic Au or Pt nanoclusters causes a significant depletion of free electrons below the surface, leading to a reduction of UV photoluminescence, an increase of ZnO nanorod dark resistance (up to 200 times) and, as a consequence, an improved sensitivity (up to 6 times) to UV light. These effects are strongly enhanced (up to 450 and 10 times, respectively) when ZnO nanorods are decorated with bimetallic AuPt nanoclusters that substantially augment the depletion of free carriers likely due to a more efficient absorption of the gas molecules on the surface of the bimetallic AuPt nanoclusters than on that of their monometallic counterparts. The depletion of free carriers in cluster decorated ZnO nanorods is quantitatively investigated and modelled, allowing the application of these composite materials in UV sensing and light induced catalysis.

Failure to thrive: the importance of measuring the electrolytes.

Diabetes insipidus (DI) is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (centraldiabetesinsipidus, CDI) or renalinsensitivity to AVP (nephrogenicdiabetesinsipidus, NDI). We report a case of a child with congenital NDI.

Congenital renal anomalies imaging: a valuable tool for pediatricians.

The purpose of this article is to review the main congenital anomalies of kidneys and urinary tract that can be diagnosed prenatally and postnatally by imaging technique. The incidence of congenital anomalies of the kidney and urinary tract during the past decade has been estimated to be 0.4 to 4.0 cases per 1000 births. Congenital kidney disease can evolve in chronic disease in childhood and in adulthood. A diagnostic imaging of the various congenital renal and urological conditions allows pediatricians to make a correct diagnosis and treatment. Because of the concerns about long-term effects of ionizing radiation, the most commonly and first used imaging modality for evaluation of the urinary system is ultrasound.

Pediatric urolithiasis.

Urolithiasis is a well-known condition that can affect any part of the urinary tract. With a rate of 3-5% the incidence of upper urinary tract for long has been higher in adults (1-3), but recently it has increased among children reaching 3,3% . Indeed, more than 1% of all urinary stones are seen in patients aged less than 18 years (4). Pediatric urolithiasis is endemic in Turkey and Far East and it is probably due to malnutrition and racial factors (5). The spontaneous stone passage is more likely in children than in adults, indeed ureteral calculi spontaneously pass into 41-63% of children (1). Rate of stone passage depends on size and stone location in the urinary system. Stones sized less than 5 mm have a passage rate ranging from 40% to 98%, whilst stones > 5 mm have between 55% and 50% (6). In the last decade, the use of alpha blockers has proven well efficacious in helping spontaneous passage of distal ureteric stones in adults (7-9). The latest EAU guidelines support their use in adults while remain vague about their use in children because of unclear safety and efficacy (4). In search of evidence supporting or not the use of medical expulsive therapy in children we reviewed the literature dealing with the management of urolithiasis in pediatric patients. The primary aim of the present study was to evaluate the efficacy of medical expulsive therapy (MET), defined as stone expulsion rate, with a-blockers compared to a control group. The secondary aim was to assess the safety, defined as side effects rate, of MET compared to a control group.

Alport's syndrome.

Alport's syndrome (AS, OMIM 301050) is a hereditary disorder characterized by progressive renal failure, hearing impairment and ocular changes. It is clinically and genetically heterogeneous and in its natural history, renal disease progresses from microscopic haematuria to proteinuria, and finally to progressive renal insufficiency. AS is caused by an inherited defect in a type IV collagen, a structural material, expressed in many tissues that is essential for the normal function of different parts of the body. In most of cases, about the 85%, Alport's syndrome is X-linked and is originated by mutations in the COL4A5 gene. In the remaining cases, it may be inherited in either an autosomal recessive, or rarely in an autosomal dominant manner. Mostly, the condition is caused by mutations in the COL4A3 or COL4A4 genes. Coexisting mutations in COL4A3, COL4A4, COL4A5 or COL4A6 were found to cause an Alport's syndrome phenotype with digenic inheritance. Diagnosis of the condition is based on family history, clinical signs, and specific procedures such as a kidney biopsy. The diagnosis can be confirmed by genetic testing. Treatment may include use of a hearing aid, hemodialysis, and peritoneal dialysis to treat those with end-stage renal failure, and, as the last step, kidney transplantation. Firstly described by Arthur C. Alport's, in 1927, over the years it has become a pathology of high scientific interest. At the moment, thanks to advances in diagnostic techniques, it is possible to make an early diagnosis avoiding irreversible damages and life -threatening complications.

Monosymptomatic enuresis: the therapeutic weapons.

Nocturnal enuresis (NE) was defined by the World Health Organization (ICD-10) and the American Psychiatric Association (DSM-5) as bed-wetting in children aged >5 years. In cases of mental retardation, the developmental age may be equivalent to 5 years. In this review, we focus on the current knowledge about the etiology of enuresis and the most recent therapeutical options. Both non-pharmacological and pharmacological therapies are included, although the relative effectiveness of each remains uncertain. To date, motivational, alarm and drug therapies are the mainstay of treatment. Alarm therapy remains the first-line treatment modality for NE, while desmopressin is the most commonly used medical treatment.

Renal involvement in paediatric Fabry disease.

Anderson-Fabry Disease (AFD) is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficient or absent activity of the lysosomal enzyme, α-galactosidase A, resulting in the progressive multisystem lysosomal accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Among the wide spectrum of clinical signs and symptoms and the life-threatening complications of Fabry disease, renal failure causes significant morbidity and mortality. Various evidence shows that the accumulation of Gb3 in different renal cells is present since the first years of life, many years and usually decades before manifest symptoms and signs of renal involvement. Early renal damage can be demonstrated by clinical signs as microalbuminuria and proteinuria, developing as early as in the second decade of life. A decline in GFR is uncommon at paediatric ages but may be seen as early as adolescence. Renal biopsy is rarely used in paediatric patients with Fabry disease although evidence shows that it may be considered a valid tool for the diagnosis of early and potentially reversible nephropathy, as well as for the evaluation of the effectiveness of enzyme replacement therapy (ERT). Although there is consensus in considering the early initiation of ERT as the only tool able to prevent the progression of nephropathy, the issue on the correct timing for the onset of ERT in pediatric age remains open in the management of this chronic and progressive disease.

Conservative management in congenital severe bilateral hydronephrosis related to uretero-pelvic junction obstruction.

We report our experience in conservative management of patients with prenatal and neonatal diagnosis of severe bilateral ureteropelvic junction obstruction (UPJO), focusing on the actual predictors of renal function impairment or spontaneous resolution. Between 1996 and 2006, 20 patients with bilateral severe hydronephrosis related to UPJO were included in the study. Indications for surgery were an increased hydronephrosis, decreased renal function, onset of symptoms. Conservatively treated patients were followed up for 3 months to 10 years with renal ultrasound, DTPA diuretic, urine culture. At first renal scan, 22 out of 40 renal units had a poor, 10 an intermediary and 8 a good drainage. Pyeloplasty was required in 10 of the 40 kidneys, while 30 out of 40 kidneys were followed conservatively. At the end of follow up, sieric normalized creatinine and estimated glomerular filtration rate were normal in all patients. Our data showed that bilateral severe hydronephrosis related to UPJO can be safely managed in a similar manner of a unilateral case. A poor drainage could be considered a negative predictive factor in the feasibility of a conservative management.

Ureterocystoplasty (bladder augmentation) in a 16 year-old boy with Goldenhar syndrome.

The use of the dilated ureter for bladder augmentation is universally accepted for its lower rate of complications compared to the use of gastrointestinal segments. We report the case of a 16 yearold boy affected by Goldenhar syndrome who presented with neurogenic bladder with small-capacity, 5° grade vescico-ureteral reflux (VUR) with megaureter and bilateral hydronephrosis. Bladder augmentation using the distal dilated ureter, transuretero-ureterostomy left to right and Mitrofanoff's appendicovescicostomy were performed. Six months after surgery voiding cystourethrogram (VCUG) revealed a compliant bladder with a functional capacity of 400 ml. Ureterocystoplasty is a safe and effective method of augmenting small capacity urinary bladder. We suggest using the ureter, when available, instead of using gastrointestinal segments.

Cardiac dysfunction in children with essential obesity: preliminary data.

Obesity in children has been recognized as a major underlying factor of the pathogenesis of several diseases and a reduced life expectancy. This study aims to verify if clinical parameters, such as waist circumference and/or body mass index and biohumoral and inflammatory parameters can help predict cardiac structural and functional alterations, through an echocardiogram test in obese children and adolescents. Children were prospectively enrolled at the AUOC outpatients' department of Emergency Paediatrics, University Hospital, Messina, from June to December 2017. Clinical, metabolic parameters and an inflammation marker (HMGB1) were evaluated and a transthoracic echocardiogram was carried out. Twenty-two obese subjects were prospectively enrolled.HMGB1 values were 12.6 ± 2ng/ml, significantly higher compared to a previously studied healthy control group. A significant positive correlation was found both between total cholesterol levels and HMGB1 values (r=0.846, p=0.000) and between LDL cholesterol and HMBG1 values (r=0.663, p=0.001). No correlation was found between clinical, biohumoral and echocardiograph parameters. In obese children cardiac parameters obtained from echocardiogram tests may be in the normal range. However, other parameters may be altered in the early phase, showing that infantile obesity can compromise myocardial functions, even in the absence of comorbidities. Furthermore, the evaluation of concentrations of HMBG1 could explain how an initial inflammation can trigger the condition of meta-inflammation.

Hemodialysis in children: how, when and why.

End-stage renal diseases requiring chronic dialysis are rare in childhood and adolescence, but they are associated with high mortality and impaired quality of life (1, 2). The most common disease that causes chronic kidney disease (CKD) is primary glomerular disease (GD), followed by congenital abnormalities of the kidney and urinary tract, cystic, hereditary or congenital disorders and, more rarely, secondary GD. However, patients with secondary GD, urologic disorders, and metabolic diseases have greater mortality risk than patients with primary GD (3). Here, we focused on the different options of treatment available, and specifically we compared peritoneal dialysis and hemodialysis, showing pros and cons between them.

Laparoscopic transposition of lower pole crossing vessels in children with extrinsic pelvi-ureteric junction obstruction: a worthy alternative to dismembered pyeloplasty.

Pelviureteric junction obstruction (PUJO) due to intrinsic or extrinsic causes is a common problem in childhood. Extrinsic compression by a lower pole-crossing blood vessel can present symptomatically in older children. In these cases, laparoscopies Vascular Hitch can represent a valid alternative to pyeloplasty dismembered. We analyzed the data of 4 children affected by extrinsic PUJO treated at our institution with the laparoscopic Vascular Hitch procedure modified by Chapman. Surgical indications included presence of clinical symptoms, worsening of intermittent hydronephrosis, signs of obstruction on the MAG-3 scan, clear or suspected images of polar crossing vessels on CT scan or Uro-MRI. All procedures were completed laparoscopically. No complications occurred. Mean follow-up was 13 months with resolution of symptoms and PUJ obstruction and significant improvement of hydronephrosis in all cases. When blood vessels crossing lower pole represent the pure mechanical cause of UPJ obstruction the laparoscopic Vascular Hitch procedure represents an excellent alternative to dismembered pyeloplasty. It is less technically demanding then pyeloplasty and is associated with a lower complication rate. The main challenge is to intraoperatively ascertain the absence of associated intrinsic stenosis.

Laparoscopic nephrectomy in children with Wilms tumor. Considerations after 10 years of experience.

Despite laparoscopy in children is considered safe and is routinely used for several procedures, even in neonates and in pediatric oncology, its role in the treatment of pediatric renal tumors is still controversial. This study analyzes the results of laparoscopic nephrectomy for Wilms Tumor (WT) in pediatric age compared with open nephrectomy after 10 years of experience in a single centre. From 1993 in our center of reference for pediatric oncology, 30 patients with WT have been treated. We performed 21 open nephrectomy and in the last 10 years 9 laparoscopic nephrectomy. In all patients treated laparoscopically, the same technique made by the same equip was used. Compared with patients treated by open surgery, we did not find a significant difference in terms of outcome and survival. In the open surgery group, two patients had lung relapse while in the other group there was one local relapse. These three children obtained and maintained a second complete remission with chemotherapy. Open surgery complications were a tumor rupture in two cases, and an episode of pancreatitis 10 days after surgery. In the laparoscopic group, there were two conversions to open surgery not considered as complications but a surgical choice for cystic areas present in the tumor. As far as complications and oncologic outcomes are concerned, both techniques showed similar results. In experienced hands, laparoscopy proves to be an attractive alternative to open surgery for pediatric renal tumors.

L10-FeNi films on Au-Cu-Ni buffer-layer: a high-throughput combinatorial study.

The fct L10-FeNi alloy is a promising candidate for the development of high performance critical-elements-free magnetic materials. Among the different materials, the Au-Cu-Ni alloy has resulted very promising; however, a detailed investigation of the effect of the buffer-layer composition on the formation of the hard FeNi phase is still missing. To accelerate the search of the best Au-Cu-Ni composition, a combinatorial approach based on High-Throughput (HT) experimental methods has been exploited in this paper. HT magnetic characterization methods revealed the presence of a hard magnetic phase with an out-of-plane easy-axis, whose coercivity increases from 0.49 kOe up to 1.30 kOe as the Au content of the Cu-Au-Ni buffer-layer decreases. Similarly, the out-of-plane magneto-crystalline anisotropy energy density increases from 0.12 to 0.35 MJ/m3. This anisotropy is attributed to the partial formation of the L10 FeNi phase induced by the buffer-layer. In the range of compositions we investigated, the buffer-layer structure does not change significantly and the modulation of the magnetic properties with the Au content in the combinatorial layer is mainly related to the different nature and extent of interlayer diffusion processes, which have a great impact on the formation and order degree of the L10 FeNi phase.

Safety and efficacy assessment of a GLP-1 mimetic: insulin glargine combination for treatment of feline diabetes mellitus.

A commonly used therapeutic strategy for type 2 diabetes mellitus (DM) in humans involves the use of synthetic incretin hormone-based therapies including exenatide, a glucagon-like pepetide-1 hormone agonist. Glucagon-like pepetide-1 agonists can be used alone or as an ancillary therapy with other agents, including insulin and oral antihyperglycemics. Little is known about the role of these therapies for DM in cats. Therefore, the primary objective of this study was to evaluate the safety and efficacy of short-acting exenatide combined with insulin, as compared to placebo and insulin for the treatment of DM in cats. Treatment with exenatide was well tolerated; only 2 cats developed side effects requiring dose reduction. Two cats (25%) went into diabetic remission while receiving exenatide and insulin, whereas remission was not reported during placebo treatment. The average change in the daily exogenous insulin dose was significant (ß = -0.56 U/kg, 95% confidence interval, -0.96 to -0.15, P = 0.007), and the dose of insulin administered was lower during exenatide treatment. The average weight loss experienced on exenatide was significantly higher than on placebo (ß = 0.65 kg, 95% confidence interval, 0.09-1.21, P = 0.02). There was no significant difference in any of the hormone concentrations evaluated for cats on exenatide vs placebo treatments. Overall, the treatment of diabetic cats with insulin and a fixed dose of exenatide was found to be safe. The weight loss and decreased exogenous insulin requirement experienced with exenatide treatment could be a significant benefit for overweight diabetic cats and warrants further evaluation.

A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid.

Polyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative-strand RNA virus. Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encapsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex. One polyamide molecule, UMSL1011, was found to inhibit infection of VSV. To confirm that the polyamide targeted the nucleocapsid, a nucleocapsid-like particle (NLP) was incubated with UMSL1011. The encapsidated RNA in the polyamide-treated NLP was protected from thermo-release and digestion by RNase A. UMSL1011 also inhibits viral RNA synthesis in the intracellular activity assay for the viral RNA-dependent RNA polymerase. The crystal structure revealed that UMSL1011 binds the structured RNA in the nucleocapsid. The conclusion of our studies is that the RNA in the nucleocapsid is a viable antiviral target of polyamides. Since the RNA structure in the nucleocapsid is similar in all negative-strand RNA viruses, polyamides may be optimized to target the specific RNA genome of a negative-strand RNA virus, such as respiratory syncytial virus and Ebola virus.IMPORTANCE Negative-strand RNA viruses (NSVs) include several life-threatening pathogens, such as rabies virus, respiratory syncytial virus, and Ebola virus. There are no effective antiviral drugs against these viruses. Polyamides offer an exceptional opportunity because they may be optimized to target each NSV. Our studies on vesicular stomatitis virus, an NSV, demonstrated that a polyamide molecule could specifically target the viral RNA in the nucleocapsid and inhibit viral growth. The target specificity of the polyamide molecule was proved by its inhibition of thermo-release and RNA nuclease digestion of the RNA bound in a model nucleocapsid, and a crystal structure of the polyamide inside the nucleocapsid. This encouraging observation provided the proof-of-concept rationale for designing polyamides as antiviral drugs against NSVs.

ß-Alanine and N-terminal cationic substituents affect polyamide-DNA binding.

Minor-groove binding hairpin polyamides (PAs) bind specific DNA sequences. Synthetic modifications can improve PA-DNA binding affinity and include flexible modules, such as ß-alanine (ß) motifs to replace pyrroles (Py), and increasing compound charge using N-terminal cationic substituents. To better understand the variations in kinetics and affinities caused by these modifications on PA-DNA interactions, a comprehensive set of PAs with different numbers and positions of ß and different types of N-cationic groups was systematically designed and synthesized to bind their cognate sequence, the λB motif. The λB motif is also a strong binding promoter site of the major groove targeting transcription factor PU.1. The PA binding affinities and kinetics were evaluated using a spectrum of powerful biophysical methods: thermal melting, biosensor surface plasmon resonance and circular dichroism. The results show that ß inserts affect PA-DNA interactions in a number and position dependent manner. Specifically, a ß replacement between two imidazole heterocycles (ImßIm) generally strengthens binding. In addition, N-terminal cationic groups can accelerate the association between PA and DNA, but the bulky size of TMG can cause steric hindrance and unfavourable repulsive electrostatic interactions in some PAs. The future design of stronger binding PA requires careful combination of ßs and cationic substituents.

Improved Antiviral Activity of a Polyamide Against High-Risk Human Papillomavirus Via N-Terminal Guanidinium Substitution.

We report the synthesis of two novel pyrrole-imidazole polyamides with N-terminal guanidinium or tetramethylguanidinium groups and evaluate their antiviral activity against three cancer-causing human papillomavirus strains. Introduction of guanidinium improves antiviral activity when compared to an unsubstituted analog, especially in IC90 values. These substitutions change DNA-binding preferences, while binding affinity remains unchanged.

Precursory changes in seismic velocity for the spectrum of earthquake failure modes.

Temporal changes in seismic velocity during the earthquake cycle have the potential to illuminate physical processes associated with fault weakening and connections between the range of fault slip behaviors including slow earthquakes, tremor and low frequency earthquakes1. Laboratory and theoretical studies predict changes in seismic velocity prior to earthquake failure2, however tectonic faults fail in a spectrum of modes and little is known about precursors for those modes3. Here we show that precursory changes of wave speed occur in laboratory faults for the complete spectrum of failure modes observed for tectonic faults. We systematically altered the stiffness of the loading system to reproduce the transition from slow to fast stick-slip and monitored ultrasonic wave speed during frictional sliding. We find systematic variations of elastic properties during the seismic cycle for both slow and fast earthquakes indicating similar physical mechanisms during rupture nucleation. Our data show that accelerated fault creep causes reduction of seismic velocity and elastic moduli during the preparatory phase preceding failure, which suggests that real time monitoring of active faults may be a means to detect earthquake precursors.