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Microbial adhesion reduction as well as platelet compatibility improvement have been suggested as the key requirements for developing blood-contacting synthetic biomaterials. Surface grafting of hydrophilic polyethylene glycol chains or alkyl chains with zwitterionic terminal ends has been proposed for reducing microbial or platelet adhesion. Nonetheless, none has been reported to incorporate both polyethylene glycol and zwitterionic terminal functionality on the same surface-grafted alkyl chain. In this investigation, a novel surface modification scheme was reported for grafting zwitterionic alkyl chains with or without polyethylene glycol as the spacer. It was noted the bacterial adhesion reduction capability on the zwitterionic modified surface was dependent upon the use of polyethylene glycol spacer or not and the strain of microbe tested. Besides, the zwitterionic modified ones all showed greater antimicrobial adhesion capability than the surface modified with polyethylene glycol alone. On the other hand, significantly reduced platelet adhesion and activation were found, but with no statistical differences noted among the polyethylene glycol-modified surface and zwitterionic ones, with or without polyethylene glycol spacer. These suggested that the use of polyethylene glycol spacer on the zwitterionic terminated surface could further enhance the antimicrobial adhesion against gram-negative bacterial while still keeping its platelet compatibility.

Reducing microbial infections associated with biomedical devices or articles/furniture noted in a hospital or outpatient clinic remains a great challenge to researchers. Due to its stability and low toxicity, the N-halamine compound has been proposed as a potential antimicrobial agent. It can be incorporated into or blended with the FDA-approved biomaterials. Surface grafting or coating of N-halamine was also reported. Nevertheless, the hydrophobic nature associated with its chemical configuration may affect the microbial interactions with the chlorinated N-halamine-containing substrate. In this study, a polymerizable N-halamine compound was synthesized and grafted onto a polyurethane surface via a surface-initiated atom transfer radical polymerization (SI-ATRP) scheme. Further, using the sequential SI-ATRP reaction method, different hydrophilic monomers, namely poly (ethylene glycol) methacrylate (PEGMA), hydroxyethyl methacrylate (HEMA), and [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), were also grafted onto the polyurethane (PU) substrate before the N-halamine grafting reaction to change the surface properties of the N-halamine-modified substrate. It was noted that the chains containing the hydrophilic monomer and the polymerizable N-halamine compound were successfully grafted onto the PU substrate. The degree of chlorination was improved with the introduction of a hydrophilic monomer, except the HEMA. All of these hydrophilic monomer-containing N-halamine-modified PU substrates demonstrated a more than 2 log CFU reduction after microbial incubation. In contrast, the surface modified with N-halamine only exhibited significantly less antimicrobial efficacy instead. This is likely due to the synergistic effects caused by the reduced chlorine content, as well as the reduced surface interactions with the microbes.

This work describes the synthesis of novel antimicrobial agents consisting of N-halamine and dual quaternary ammonium with different alkyl chain lengths and their antimicrobial applications for PET nonwovens. The antimicrobial agents were grafted onto PET nonwovens via esterification with a crosslinker, 1,2,3,4-butanetetracarboxylic acid (BTCA). The cyclic amide structure in the antimicrobial agents could be easily converted to N-halamine after immersion in a diluted chlorine bleach solution. Variations in surface chemical composition of the modified PET nonwovens were examined by XPS. Antimicrobial activities of the nonwovens/fabrics were tested against S. aureus (Gram-positive) and E. coli (Gram-negative) strains. Systematic investigation showed the antibacterial activities were dependent upon the alkyl chain length. The synergism of N-halamine and dual quaternary ammonium could lead to significant antimicrobial activity with inactivation of up to 90% of S. aureus and E. coli after 10 minute contact. This work suggested that the novel composite biocides with N-halamine and dual quaternary ammonium groups and the associated surface modification methods could be of use for further developing antimicrobial nonwoven applications.

Styrenic thermoplastic elastomers (TPEs) consist of styrenic blocks. They are connected with other soft segments by a covalent linkage and are widely used in human life. However, in biomedical applications, TPEs need to be chemically hydrogenated in advance to enhance their properties such as strong UV/ozone resistance and thermal-oxidative stability. In this study, films composed of sulfonated hydrogenated TPEs were evaluated. Hydrogenated tert-butyl styrene&ndash, styrene&ndash, isoprene block copolymers were synthesized and selectively sulfonated to different degrees by reaction with acetyl sulfate. By controlling the ratio of the hydrogenated tert-butyl styrene&ndash, isoprene block copolymer and acetyl sulfate, sulfonated films were optimized to demonstrate sufficient mechanical integrity in water as well as good biocompatibility. The thermal plastic sulfonated films were found to be free of cytotoxicity and platelet-compatible and could be potential candidates in biomedical film applications such as wound dressings.

Although considerable efforts have been made to vary the alkyl chain length in the quaternary ammonium compounds (QACs) for optimizing the antibacterial activity, only few researchers have systematically investigated the combinatory effects of alkyl chain length and another acryl monomers with the different chemical configuration on the antibacterial activity of the modified substrate. In this study, by surface grafting of various copolymeric brushes, different modified cotton substrates were prepared by surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization reaction for exploring the effects of alkyl chain length of QACs and the fluorine content on antibacterial and anti-microbial adhesion characteristics. The quaternized monomers used were prepared by quaternization of 2-(dimethylamino) ethyl methacrylate (DMAEMA) with 1-bromooctane (DMAEMA + 8), and 1-bromopropane (DMAEMA + 3). The fluoro-containing monomer was 2,2,2-Trifluoroethyl methacrylate (TFEMA). Ethyl methacrylate (EMA) was also used for comparison. Results have shown that the optimal antibacterial and anti-microbial adhesion characteristics were noted on the substrates grafted with DMAEMA + 8 and TFEMA. This can be attributed to the enhanced degree of surface quaternization due to the hydrophobic interactions between the grafted TFEMA and DMAEMA + 8 chains, leading to an increase in antibacterial efficacy of modified cotton substrates.

Hydrogenated styrenic block copolymers (HSBCs) have been used in medical tubing for many years due to their high clarity, flexibility, kink resistance, and toughness. However, when it comes to blood storage applications, HSBC compounds&rsquo, market has been limited because of their high hydrophobicity, which may trigger platelet adhesion when contacting with blood. HSBC needs to be physically or chemically modified in advance to make it blood compatible, however, HSBC has strong UV/ozone resistance, thermooxidative stability, and excellent processing capability, which increases the difficulty of the chemical modification process as unsaturated dienes has been converted to saturated stable midblocks. Moreover, medical HSBC-containing compounds primarily make up with the non-polar, hydrophobic nature and benign characteristics of other common ingredients (U.S. Pharmacopeia (USP) grades of mineral oil and polypropylene), which complicates the realization of using HSBC-containing compounds in blood-contacting applications, and this explains why few studies had disclosed chemical modification for biocompatibility improvement on HSBC-containing compounds. Sulfonation has been reported as an effective way to improve the material&rsquo, s blood/platelet compatibility. In this study, hydrogenated tert-butyl styrene (tBS)-styrene-isoprene block copolymers were synthesized and its blends with polypropylene and USP grades of mineral oil were selectively sulfonated by reaction with acetyl sulfate. By controlling the ratio of the hydrogenated tBS-styrene-isoprene block copolymer in the blend, sulfonated films were optimized to demonstrate sufficient physical integrity in water as well as thermal stability, hydrophilicity, and platelet compatibility.

The adipose stem cell is a potential candidate for the autologous chondrocytes repairing approach because of the abundance of fat in the animal body and its versatile differentiation capability. In this study, rat adipose stem cells (rASCs) were seeded into anti-oxidative N-acetylcysteine (NAC) grafted polyurethane (PU) scaffold and then combined with short dynamic compressive stimulation (24 h) to induce rASCs chondrogenesis differentiation in vitro. The inner pore surface of the PU scaffold was first modified via alginate and type I collagen to promote rASCs adherence. The modified layers crosslinked by genipin showed outstanding stability after ultrasonic treatment, indicating the modified layers were stable and can keep the cells adhesion well during dynamic compressive stimulation. After inner pore surface modification and 10 mM NAC grafting, the PU scaffold-A-C-G (graft 10 mM NAC) has shown the best proliferation efficiency with homogeneous cell distribution after 72hr static culture. After short term dynamic compressive stimulation, significant gene expression in chondrogenic markers, Sox-9, and Aggrecan, were noted in both PU scaffold-A-C-G and PU scaffold-A-C-G (graft 10 mM NAC). Considering the cell proliferation efficiency and gene expression, the anti-oxidative NAC grafted PU scaffold combined with short term dynamic compressive stimulation could be useful for cell culturing in stem cell therapy.

Titanium (Ti) and its alloys possess mechanical properties that are desirable in many biomedical applications compared to other metals. Furthermore, the native metal oxide layer that prevents further oxidation is also known to be biocompatible. However, clinical findings have shown that titanium and its alloys are prone to adverse bioreactions such as platelet adhesion and activation which could lead to thrombogenic complications. It has been found that surfaces modified with fluorocarbons could reduce the degree of both platelet adhesion and activation. Nevertheless, direct fluorocarbon deposition onto titanium substrates would require significant technical efforts. Instead, this research utilized a facile coating process with novel copolymers containing 2,2,2-trifluoroethyl methacrylate (TFEMA) and vinylphosphonic acid (VPA) to modify the titanium surface, giving the surface lower surface energy and higher hydrophobicity, significantly reducing the thrombus formation while exhibiting good cytocompatibility. The anchorage group, phosphonic acid provided by VPA, can be covalently bound to the oxide surface of titanium metal. Via free radical polymerization, VPA and TFEMA formed copolymers with different hydrophobicity were then used to modify titanium substrates, on which a series of surface characterization, in vitro platelet adhesion tests, and cytotoxicity assays were performed. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis of the copolymers and the modification of Ti substrates. The platelet adhesion tests showed significantly reduced amount of adherent platelets on certain copolymer-modified Ti substrates with low degrees of activation. The in vitro cytotoxicity assays further highlighted that the modifications conducted on Ti does not induce cytotoxicity.

Creating a surface with anti- or reduced fouling characteristics can lead to a reduction in nonspecific protein adsorption as well as the bacterial adhesion and platelet adhesion/activation that occur as follows. A zwitterionic polymer that consists of both cationic and anionic functionalities have been reported as an effective material to achieve these goals, likely resulted from the strongly-adsorbed hydration layer after being immersed in the physiological environment. In this investigation, a novel beta-thiopropionate-based zwitterionic monomer, 2-ammonio-3-((3-(2-hydroxy-3-(methacryloyloxy)propoxy)-3-oxopropyl)thio)-3-methylbutanoate (DPAMA), was synthesized through a facial process. And then the hydrophobic polypropylene was surface modified with this novel zwitterionic polymer through the surface-initiated atom transfer radical polymerization technique. Surface characterization analyses have been employed to investigate the modified surface properties in each reaction stage.

This work describes the synthesis of novel antimicrobial agents consisting of

Cell culturing with physical stimulation has been in research focus lately because the human body and tissue are continuously receiving different mechanical stress in daily activities. Nevertheless, the study of the synergetic effect on cellular adhesion and proliferation by the dynamic stretching culture system on different surface grafted hydrophilic layers was rare. This study hypothesized the MG-63 cellular adhesion and proliferation will be affected by the surface chemistry under dynamic culturing. The PDMS cell culturing substrate was surface grafted with five common biocompatible materials, namely alginate, type I collagen, fibronectin, poly- l -lysine, and laminin. Results have indicated that neither surface charge nor surface hydrophilicity can be correlated well with the MG-63 cell adhesion and proliferation in the static or dynamic culture. The type I collagen grafted PDMS substrate in combination with appropriate physical stimulation showed excellent proliferation and expression of osteoblast associated proteins in MG-63, likely due to the adaption of the surface grafted layer to the extracellular environment. Moreover, the surface grafted type I collagen layer remained stable after ultrasonic cleaning. Henceforth, the combination of dynamic culture system and proper modification layer could be useful in selecting proper biomaterials for clinical uses as well as for future tissue/cell cultivation applications.

The adipose-derived stem cell has been used in various regenerative medicine research due to its multiple differentiation capabilities. Developing a stable and quick approach for the differentiation of stem cells is a critical issue in tissue regenerative field. In this investigation, rat adipose-derived stem cells (rADSCs) were seeded onto the type I collagen/transforming growth factor β1 (TGF-β1) immobilized polydimethylsiloxane (PDMS) substrate and then combined with short term dynamic stretching stimulation (intermittent or continuous stretching for 6 h) to induce the rADSCs chondrogenesis differentiation using the induction medium without growth factors added in vitro. Via regulating the extracellular chemical- and mechano-receptors of the cultured rADSCs, the chondrogenic differentiation was examined. After 72 h of static culture, proteoglycan secretion was noted on the surfaces modified by collagen with or without TGF-β1. After different stretching stimulations, significant proteoglycan secretion was noted on the surface modified by both collagen and collagen/TGF-β1, especially after the intermittent stretching culturing. Nonetheless, genetic expression of the chondrogenic markers: SOX-9, Col2a1, and aggrecan, instead, were dependent upon the surface grafted layer and the stretching mode utilized. These findings suggested that the surface chemical characteristics and external mechanical stimulation could synergistically affect the efficacy of chondrogenic differentiation of rADSCs.

This study proposed novel methods for Staphylococcus epidermidis biofilm and 16S rRNA of infection-related bacteria detection. S. epidermidis biofilm was attached onto self assembled monolayers (SAMs) coated Au substrate of an extended-gate field-effect-transistor (EGFET) sensor with immobilized extracellular matrix protein, fibronectin. Biofilm mostly composed of positively charged polysaccharide intercellular adhesin (PIA) significantly contributed threshold voltage (VTH) shift from −6.67 to −94 mV for biofilm yielded by 3.8 × 106 to 3.8 × 108 CFU/ml S. epidermidis and obtained limit of detection (LOD) of 9 × 105 CFU/ml S. epidermidis. SAMs-Au surface functionalization and its properties after fibronectin immobilization showed an optimal surface roughness from atomic force microscope (AFM) view. The presence of biofilm on the surface was validated by (scanning electron microscope) SEM screening after 1 h incubation at 37 °C. Cellular response to antibiotic treatment against biofilm achieved as contaminated dialysate was treated with and without Vancomycin. The hybridization of a highly conserved gene, 16S rRNA of S. epidermidis and Staphylococcus aureus, the most leading pathogenic bacteria in peritoneal dialysis patients, was also successfully recorded. Findings suggested that Au-EGFET is a promising sensing biochip for detection of bacterial biofilm and determination of species involved in the infection.

A 2-month-old Taiwanese term baby boy was referred to us for feeding intolerance and failure to thrive. He weighed 2700 g at birth but only gained 600 g in 2 months (

BACKGROUND: Deferasirox (DFRA) is a new approved oral iron chelator. Its advantages are that it is convenient and better tolerated and adhered to due to “once-daily” oral dosage. However, its use in the field is limited and it is yet to be subjected to postmarketing surveillance. CASE REPORT: A 18.75-year-old male with β-thalassemia major received oral DFRA therapy due to transfusional iron overload for 27 months. He had received iron chelation therapy with deferoxamine injection together with oral deferiprone. However, his compliance was poor (very high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25 months of DFRA therapy, the serum ferritin level declined from 4097 to 1343 ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome, hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator. After we discontinued DFRA, he recovered fully without hepatic dysfunction, thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia. CONCLUSIONS: Our case illustrates the potential risks of DFRA-induced renal toxicity, hepatic dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and hematopoietic function is mandatory for patients undergoing treatment with DFRA. Further investigation of the potential risk and adverse effects of long-term DFRA use is necessary.

Background: Despite recent advances in molecular epidemiology and pathogenecity analyses of extraintestinal Escherichia coli infections, detailed analyses identifying virulence factors of E. coli isolates from pediatric urosepsis patients have not been reported. This study was conducted to explore and differentiate bacterial virulence factors associated with urosepsis and 2 other severe parenchymal infections, acute pyelonephritis (APN) and acute lobar nephronia (ALN), in pediatric patients. Methods: Patients included in this study were those who fulfilled the diagnostic criteria of urosepsis, APN, and ALN, without underlying disease or structural anomalies, excluding those with vesicoureteral reflux. Patients with cystitis were included as controls. E. coli isolates from urine (cystitis, APN, and ALN) or blood (urosepsis) specimens were analyzed using polymerase chain reaction (PCR) for 25 virulence genes. Results: A total of 147 children (24 cystitis, 45 APN, 48 ALN, and 30 urosepsis) were enrolled in the study. Distinct syndrome-specific differences in the distribution for certain virulence genes, but conservation across syndromes for others, were found. In addition, urosepsis isolates presented higher aggregate virulence factor scores (P < 0.0001) compared with cystitis, APN, and ALN isolates. By contrast, cystitis isolates showed significantly lower aggregate virulence factor scores than all 3 invasive urinary bacterial infections; APN (P < 0.01), ALN (P < 0.01), and urosepsis (P < 0.0001). Conclusions: Our findings suggested that urosepsis isolates carry more virulence factors and are likely more urovirulent compared with cystitis, APN, and ALN isolates.

Acute lobar nephronia (ALN) is a complicated acute renal infection that is part of the progression of the inflammatory process of acute pyelonephritis that can progress to renal abscess if left untreated. We examined the place of ALN in the spectrum of upper urinary tract infections.: The medical records of all patients diagnosed with ALN by computed tomography (CT) were reviewed retrospectively in terms of their demographic characteristics, clinical presentations, and laboratory findings. The patterns of the ALN lesions were checked on all contrast-enhanced CT films and the volume of the CT lesions (the extent of renal involvement) was estimated in every patient. Then, the correlation between the clinical presentation and CT lesions was examined.: Two distinct CT patterns of ALN lesions were observed in 127 patients: 94 simple ALN and 33 complicated ALN. Simple ALN appeared as striated or wedge-shaped, poorly defined regions of homogeneously decreased nephrographic density, whereas the lesions of complicated ALN showed heterogeneously decreased nephrographic density after contrast enhancement. The volume fraction of the CT lesions correlated well with the duration of fever before (P = 0.006) and after (P0.001) treatment in patients with simple ALN, while only the correlation between the fever duration after treatment and the volume fraction of the CT lesions (P0.001) was significant in patients with complicated ALN. Patients with complicated ALN were generally older (P = 0.004) and febrile longer after starting antibiotic treatment (P0.001). All treatment failures were in the complicated ALN group.: Children with ALN comprise 2 groups with different clinical presentations and treatment responses: simple ALN and complicated ALN. We suggest that simple ALN be regarded as a continuation of acute pyelonephritis and require 2 weeks of antibiotic treatment, while complicated ALN is a distinct more severe form requiring a 3-week or longer therapy regimen as the treatment of choice.

SUMMARY: Aims: To assess postnatal kidney volume development and to compare the intrauterine and extrauterine kidney growth curves of premature infants. Methods: One hundred neonates were enrolled in this study, and all infants had their kidney volumes measured by renal ultrasound examination. Group GA consisted of 44 neonates who were evaluated within 48 h after birth, and their gestational ages were used in the analysis. Group CA included 56 premature infants born before 34 weeks of gestation and was evaluated 14–96 days after birth, and their conceptional ages were used in the analysis. Left kidney volume, body weight, body height and age were used in the correlation analysis. Results: There was a better kidney growth rate for Group GA infants than for Group CA infants (P = 0.001). Kidney volumes in Group CA infants were thus apparently larger than those of the Group GA infants before 31 weeks of age, but they were smaller after 31 weeks of age. Group GA infants had a significantly faster growth in body weight (P = 0.001) and body height (P

Background: Acute lobar nephronia (ALN) is a severe renal parenchymal inflammatory disease that has been diagnosed with increasing frequency as a result of newer noninvasive diagnostic modalities. Escherichia coli is the most common bacterial pathogen isolated from the urine samples of ALN patients. This prospective study was conducted to elucidate and distinguish the bacterial virulence factors associated with ALN and acute pyelonephritis (APN) in pediatric patients. Methods: Patients included in the present study were those suspected of an upper urinary tract infection who underwent ultrasonographic, computed tomographic and technetium 99m-dimercapto-succinic acid scintigraphic evaluation to distinguish between ALN and APN. The E. coli isolates from the urine samples of patients were screened with polymerase chain reaction analysis for various urovirulence genes. Pulsed-field gel electrophoresis was used to analyze the genetic association of the isolates. Results: A total of 88 patients were enrolled. Forty-six patients were diagnosed with ALN and 42 with APN. Demographic characteristics and clinical results were similar except for longer fever duration before admission, longer fever continuation following antibiotic treatment and higher C-reactive protein values noted in the ALN group. Diverse genotypes were found among the E. coli isolates in both groups. Among the pathogenetic determinants examined, multivariate logistic regression analysis indicated that a papG II allele was the only significant urovirulence factor associated with ALN (P < 0.005; odds ratio, 17.16). This association was independent of the presence of VUR. Conclusions: While no specific genetic lineage was identified among the E. coli isolates studied, a papG II gene was found to be strongly associated with the cause of ALN among pediatric patients.

Luteimonas huabeiensis HB-2 is a novel and newly isolated strain, which shows a superior property of oil displacement. Here, we present a 4.3-Mb assembly of its genome. The key genes for phospholipid and fatty acid metabolism were annotated, which are crucial for crude oil emulsification and recovery.

Renal abscess is a rare disease in childhood and early diagnosis is essential to minimize the renal damages. Experiences gained from this 10-year study on patients with CT-proved diagnosis include the varied clinical presentations and use of sonographic-marked nephromegaly and focal mass as indications for further CT diagnosis.

Chi-Hui Cheng1, 3, Yong-Kwei Tsau4 and Tzou-Yien Lin2, 3 1Division of Pediatric Nephrology and 2Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, Taoyuan, 3College of Medicine, Chang Gung University, Taoyuan, 4Division of Pediatric Nephrology, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

We determined whether nephromegaly on ultrasound can be used to identify patients with urinary tract infection at increased risk for renal scarring, and we investigated the effect of vesicoureteral reflux on renal scarring.We enrolled hospitalized patients with a first febrile urinary tract infection. All patients underwent renal ultrasound and most patients underwent voiding cystourethrography. Renal scarring was assessed using (99m)technetium dimercapto-succinic acid renal scintigraphy at least 6 months after treatment. Children with recurrent urinary tract infections before scintigraphy were excluded from the study.A total of 545 children (80 with and 465 without nephromegaly) were enrolled. Infection was more severe in patients with than without nephromegaly. The incidence of renal scarring was significantly higher in patients with nephromegaly (90% vs 32%, p0.001), in kidneys with nephromegaly (80.5% vs 18.7%, p0.001) and in kidneys with vesicoureteral reflux (41.5% vs 22.2%, p0.001). Kidneys with nephromegaly had a greater incidence of reflux. The finding of nephromegaly is associated with a greatly increased likelihood of renal scarring in patients with vesicoureteral reflux.Our results indicate that ultrasound diagnosis of nephromegaly at onset is associated with a high incidence of renal scarring, and identification of nephromegaly at onset and vesicoureteral reflux are significant risk factors for renal scarring in children with a first febrile urinary tract infection. Nephromegaly is associated with an increased frequency of vesicoureteral reflux and increased likelihood of renal scarring in patients with reflux.

Deferasirox (DFRA) is a new approved oral iron chelator. Its advantages are that it is convenient and better tolerated and adhered to due to "once-daily" oral dosage. However, its use in the field is limited and it is yet to be subjected to postmarketing surveillance.A 18.75-year-old male with β-thalassemia major received oral DFRA therapy due to transfusional iron overload for 27 months. He had received iron chelation therapy with deferoxamine injection together with oral deferiprone. However, his compliance was poor (very high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25 months of DFRA therapy, the serum ferritin level declined from 4097 to 1343 ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome, hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator. After we discontinued DFRA, he recovered fully without hepatic dysfunction, thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia.Our case illustrates the potential risks of DFRA-induced renal toxicity, hepatic dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and hematopoietic function is mandatory for patients undergoing treatment with DFRA. Further investigation of the potential risk and adverse effects of long-term DFRA use is necessary.

Background: Patient susceptibility to bacterial urinary tract infections, which is determined by complex pathogen-host interactions, varies between individuals due to genetic variation. The neutrophil-dependent innate immune system is an important part of keeping the urinary tract sterile. This study was performed to explore single nucleotide polymorphisms (SNPs) in genes associated with neutrophil-dependent immunity in pediatric patients with severe parenchymal infections. Methods: The subjects included patients who fulfilled the diagnostic criteria of acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying disease or structural anomalies (excluding vesicoureteral reflux). Genotyping of the genes encoding toll-like receptor 4 (TLR-4), interleukin-8 (IL-8), and IL-8 receptors CXCR1 and CXCR2 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis. Results: A total of 17 SNPs, including missense SNPs and those located in promoter regions, were initially selected for genotyping. Only 4 SNPs with a heterozygosity rate >0.01 were evaluated further. The observed genotype frequencies satisfied Hardy-Weinberg equilibrium. Statistical analysis revealed that only IL-8 (rs4073, −251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases. Following the elimination of vesicoureteral reflux, which is a significant risk factor for severe parenchymal infection, a single SNP in IL-8 (rs4073) was found to be associated with clinically severe ALN. Conclusions: The AA genotype and A allele of the IL-8 SNP is related to patient susceptibility to parenchymal infection and is correlated with the severity of infection in pediatric APN and ALN patients, probably due to the upregulation of IL-8 expression.

Background The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. To evaluate the effect of the vaccination, we conducted an active, prospective, large-scale, long-term, and multicenter study to assess the prevalence of nasopharyngeal Streptococcus pneumoniae carriage in Taiwanese children. Methods This study was performed at three tertiary teaching hospitals in northern, central, and southern Taiwan. Questionnaires provided demographic, family/household, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and serotypes. In addition, influenza virus and Staphylococcus aureus were recovered from nasopharyngeal and nasal swabs, respectively. Results Between July 2005 and July 2008, 857 pneumococcal strains were recovered from a total of 6057 children aged >2 months to 5 years (carriage rate, 14.1%). Carriage rates differed geographically and varied with subject age. In a multivariate analysis, having at least one sibling, attendance at day-care centers, a history of otitis media, and history of upper respiratory tract infection in the previous 2 weeks were each associated with a higher risk of pneumococcal colonization of the nasopharynx. Staphylococcus aureus nasal colonization was inversely associated with nasopharyngeal carriage of pneumococcus ( p = 0.000; odds ratio [OR]: 0.48; 95% CI: 0.39–0.58). Daycare attendance was the only risk factor for carriage of penicillin non-susceptible S. pneumoniae (OR: 2.37; 95% CI: 1.22–4.88). Although vaccination rates rose from 2005 to 2008, no concomitant decrease in S. pneumoniae carriage occurred. The rate of penicillin resistance among S. pneumoniae isolates was 92.8% (using the meningitis criteria). The prevalence of cefotaxime resistance (21.6%) was higher than that of penicillin (6.9%; non-meningitis criteria). Slightly more than half (57.4%) of the isolates belonged to strains covered by the heptavalent pneumococcal conjugate vaccine when both vaccine and vaccine-related serotypes were included. Conclusions Although vaccination rates rose from 2005 to 2008, no concomitant decrease occurred in S. pneumoniae carriage. Interaction between S. aureus and S. pneumoniae may influence vaccination efficacy. These findings provide baseline data to further compare pneumococcal carriage rates and antibiotic resistance patterns in Taiwanese children as vaccination rates continue to increase.

Escherichia coli is the most common pathogen associated with acute lobar nephronia (ALN), a clinically more severe parenchymal inflammatory disease that requires a longer duration of antibiotic treatment than acute pyelonephritis (APN). This study was conducted to unravel the virulence differences between clinical isolates of E. coli from pediatric ALN and APN patients. A total of 88 urinary isolates of E. coli were investigated. They were identified from radiologically diagnosed ALN and APN patients and had previously been molecularly characterized for important urovirulence genes. Madin-Darby canine kidney (MDCK) epithelial cells were used as an in vitro model. Multivariate logistic regression analyses indicated that ALN isolates were more likely to show adhesion (p0.05; odds ratio [OR], 3.81; 95% confidence interval [CI], 1.23-11.80) and cytotoxicity (p0.001; OR, 10.42; 95% CI, 3.03-35.89). However, no difference in the penetration ability was noted. Henceforth, the ability to adhere to and produce cytotoxicity against uroepithelial cells appears a prerequisite factor for E. coli to cause more severe bacterial kidney infection, such as ALN.

OBJECTIVE. The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux.METHODS. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded.RESULTS. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum β-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups.CONCLUSIONS. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum β-lactamase-producing bacteria or multidrug-resistant uropathogens other than E coli for breakthrough urinary tract infections; therefore, these antibiotics are not appropriate for prophylactic use in patients with vesicoureteral reflux. Co-trimoxazole remains the preferred prophylactic agent for vesicoureteral reflux.

To measure the kidney size in children with Kawasaki disease (KD) and to delineate the condition of nephromegaly, 20 children with KD were enrolled in our study. Kidney sizes were measured during acute stage in these patients. Twenty healthy children and 15 febrile children served as healthy controls and fever controls, respectively. To delineate the possible mechanism, we also evaluated kidney volume (KV) in 13 other patients with KD during the acute phase and after the recovery phase as well as 26 healthy children. Plasma hepatocyte growth factor (HGF) and transforming growth factor-beta1 (TGF-beta1) levels were determined for all children. Kidney lengths and KV in patients with KD during the acute phase were significantly larger than those of healthy children. There was no kidney enlargement in healthy controls and after the recovery phase. The ratio of patient plasma HGF/TGF-beta1 during the acute phase and after the recovery phase correlated positively with the degree of nephromegaly in all patients. These results confirm the presence of large kidneys in children with KD. Our data also suggest that an elevated HGF/TGF-beta1 ratio may be responsible for the transient nephromegaly in these children.

Background Inflammasome innate immune response activation has been demonstrated in various inflammatory diseases and microbial infections. However, to our knowledge, no study has examined the inflammasome-dependent pathways in patients with urinary tract infection. Defective or variant genes associated with innate immunity are believed to alter the host’s susceptibility to microbial infection. This study investigated genetic polymorphisms in genes encoding inflammasomes and the subsequent released cytokines in pediatric patients with severe renal parenchymal infections. Methodology This study included patients diagnosed with acute pyelonephritis (APN) and acute lobar nephronia (ALN) who had no underlying disease or structural anomalies other than vesicoureteral reflux (VUR). Single nucleotide polymorphism (SNP) genotyping was performed in the genes associated with inflammasome formation and activation (NLRP3, CARD8) and subsequent IL–1β cytokine generation (IL–1β). Principal Findings A total of 40 SNPs were selected for initial genotyping. Analysis of samples from 48 patients each and 96 controls revealed that only nine SNPs (five SNPs in NLRP3; three SNPs in CARD8; one SNP in IL–1β) had heterozygosity rates >0.01. Hardy–Weinberg equilibrium was satisfied for the observed genotype frequencies of these SNPs. Analysis excluding patients with VUR, a well-known risk factor for severe UTIs, revealed a lower frequency of the CC genotype in NLRP3 (rs4612666) in patients with APN and ALN than in controls. Correction for multiple-SNP testing showed that the non-VUR subgroup of the APN+ALN combined patient groups remained significantly different from the control group (P < 0.0055). Conclusions This study is the first to suggest that the inflammasome-dependent innate immunity pathway is associated with the pathogenesis of pediatric severe renal parenchymal infections. Further investigation is warranted to clarify its pathogenic mechanism.

OBJECTIVE. Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen.METHODS. Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures.RESULTs. A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>105 colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course.CONCLUSION. A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.

We previously showed a positive correlation between nephromegaly and plasma hepatocyte growth factor (HGF)/transforming growth factor beta1 (TGF-beta1) ratio in children with biliary atresia. The purpose of this study is to examine the possible reversibility of nephromegaly in patients with biliary atresia.We evaluated kidney volume in 13 patients with biliary atresia before and after liver transplantation, 6 patients with hepatoblastoma, and 26 healthy children. Plasma HGF and TGF-beta1 levels were determined for all children.We noted significant nephromegaly in children with biliary atresia before liver transplantation compared with healthy children and children after liver transplantation (P0.001 and P = 0.006 for intercepts, P = 0.064 and P = 0.753 for slopes by analysis of covariance, respectively). The highest plasma HGF levels and HGF/TGF-beta1 ratios and the lowest TGF-beta1 concentrations were found in children with biliary atresia before liver transplantation (P0.001). No statistically significant nephromegaly was observed in children with biliary atresia after liver transplantation or those with hepatoblastoma despite the presence of a mildly increased plasma HGF level and HGF/TGF-beta1 ratio. Plasma HGF/TGF-beta1 ratio correlated positively with degree of nephromegaly in all patients (r = 0.717; P0.001).Our data suggest that liver transplantation reverses the nephromegaly present in children with biliary atresia and that plasma HGF/TGF-beta1 ratio may be associated with the development of nephromegaly in patients with biliary atresia.

The aims of this study were to determine whether renal pelvis dilation on ultrasound was reliable in predicting vesicoureteral reflux (VUR) and to assess the relationship of other clinical information of VUR in children with urinary tract infection (UTI).We retrospectively reviewed clinical data, renal echo, and voiding cystourethrogram (VCUG) results in hospitalized children with their first episode of UTI, aged from 1 month to 5 years, during a 1-year period.There were 114 children with 228 kidneys eligible for the study. Unilateral pelvis size greater than 8 mm had 2.4 (p = 0.049, 95% CI: 1.0-5.9) and 3.7 (p = 0.025, 95% CI: 1.2-11.3) times greater risk for VUR and severe reflux, respectively. The sensitivity in detecting severe reflux was 27.8%, and the specificity was 90.5%. The positive and negative predictive values in suggesting severe VUR were 20.0% and 93.6%, respectively. The sum of bilateral pelvis sizes greater than 16 mm had higher risk for VUR and severe reflux (4.1 and 4.6 times) and similar specificity and negative predictive value for severe reflux. Age, gender, C-reactive protein, leukocytosis, pyuria and acute pyelonephritis did not show significant relationships to the reflux.Unilateral pelvis size greater than 8 mm or the sum of the bilateral pelvis sizes greater than 16 mm was associated with VUR, especially severe VUR. The possibility of severe reflux was lower than 10% when the reverse criteria were applied. However, the dilation of the renal pelvis did not predict all VUR precisely. We concluded that VCUG should still be performed in hospitalized children with UTI.