Surgery for Pediatric Ureteropelvic Junction Obstruction-Comparison of Outcomes in Relation to Surgical Technique and Operating Discipline in Germany.

INTRODUCTION: Surgery for ureteropelvic junction obstruction (UPJO) is performed by both pediatric surgeons (PS) and urologists (URO). The aim of this study was to analyze treatment modalities for UPJO and results in relation to the surgical technique and the operating discipline in Germany. MATERIALS AND METHODS: Data of patients aged 0 to 18 years were extracted from a major public health insurance (covering ∼5.7 million clients) during 2009 to 2016 and were analyzed for sociodemographic variables, surgical technique, and treating discipline. Logistic regression analysis was performed for the risk of a complication within the first postoperative year. RESULTS: A total of 229 children (31.0% female) were included. Laparoscopic pyeloplasty (LP) was performed in 58 (25.3%) patients (8.6 ± 6.4 years), and open pyeloplasty (OP) was applied in 171 (74.7%; 4.6 ± 5.9 years). LP was the dominant technique in females (p < 0.02); males preferentially underwent OP (p < 0.02). Length of hospital stay was 4.3 days (p = 0.0005) shorter in LP compared with that in OP, especially in children ≤ 2 years (6.7 days, p = 0.007). PS operated on 162 children (70.7%), and URO performed surgery on 67 patients (29.3%). The mean age of children operated by PS (3.5 ± 4.7 years) was significantly younger compared with that operated by URO (10.8 ± 6.5 years, p < 0.0001). Complication rates were independent of surgical technique or treating specialty. CONCLUSION: In Germany, UPJO was treated by LP in 25.3% of patients, which was associated with a shorter length of stay, especially in children ≤ 2 years. Complication rates were independent of the operating specialty and surgical technique. Therefore, LP should be further promoted for the treatment of UPJO in small children.

The developing temporal bone: computed tomography measurements and assessment of suture closure from birth to 18 years of age.

PURPOSE: To describe the normal CT appearance of the developing temporal bone in children from birth to 18 years of age. METHODS: Two hundred and six temporal bone CTs of children from 0.14 to 18.95 years were retrospectively selected and reviewed. Temporal bones were measured in a standardized slice orientation using the length of the basal turn of the cochlea, the length and width of the petrous bone, the coronal extent, trailing edge and anterior-posterior dimension of the temporal bone and the angle between petrous bone's length and the midsagittal line in the axial plane showing the basal turn of the cochlea in its greatest extent. Two sutures, two synchondroses and three fissures of the temporal bone were evaluated and graded. RESULTS: Chosen measurements and calculations demonstrate an increase of values from 0 to 18 years with the greatest increase occurring during the first 2 years of life. The angle between the basal turn of the cochlea and the midsagittal line shows a large variability. Logarithmic trend lines illustrate larger measurements of males as compared to females. The ratio of the basal turn of the cochlea and the length of the petrous bone is about 1:4.1 (f/m) during the first year of life and about 1:6.1 (f)/1:6.8 (m) from 17 years onwards. Results of suture closure are described using box-and-whisker plots. CONCLUSIONS: The developing temporal bone grows the most during the first 2 years of life. Knowledge of changing proportions and suture closure is essential for evaluation of temporal bone CT of children.

Electronic approaches to restoration of sight.

Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.

Holographic display system for restoration of sight to the blind.

OBJECTIVE: We present a holographic near-the-eye display system enabling optical approaches for sight restoration to the blind, such as photovoltaic retinal prosthesis, optogenetic and other photoactivation techniques. We compare it with conventional liquid crystal displays (LCD) or digital light processing (DLP)-based displays in terms of image quality, field of view, optical efficiency and safety. APPROACH: We detail the optical configuration of the holographic display system and its characterization using a phase-only spatial light modulator. MAIN RESULTS: We describe approaches to controlling the zero diffraction order and speckle related issues in holographic display systems and assess the image quality of such systems. We show that holographic techniques offer significant advantages in terms of peak irradiance and power efficiency, and enable designs that are inherently safer than LCD or DLP-based systems. We demonstrate the performance of our holographic display system in the assessment of cortical response to alternating gratings projected onto the retinas of rats. SIGNIFICANCE: We address the issues associated with the design of high brightness, near-the-eye display systems and propose solutions to the efficiency and safety challenges with an optical design which could be miniaturized and mounted onto goggles.

Photovoltaic retinal prosthesis: implant fabrication and performance.

The objective of this work is to develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 µm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 µm wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280, 140 and 70 µm) with active electrodes of 80, 40 and 20 µm diameter were fabricated. The turn-on voltages of the one-diode, two-series-connected diode and three-series-connected diode structures are approximately 0.6, 1.2 and 1.8 V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ∼0.36 A W(-1), at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution.

Acinetobacter, Aeromonas and Trichococcus populations dominate the microbial community within urban sewer infrastructure.

We evaluated the population structure and temporal dynamics of the dominant community members within sewage influent from two wastewater treatment plants (WWTPs) in Milwaukee, WI. We generated > 1.1 M bacterial pyrotag sequences from the V6 hypervariable region of 16S rRNA genes from 38 influent samples and two samples taken upstream in the sanitary sewer system. Only a small fraction of pyrotags from influent samples (∼ 15%) matched sequences from human faecal samples. The faecal components of the sewage samples included enriched pyrotag populations from Lactococcus and Enterobacteriaceae relative to their fractional representation in human faecal samples. In contrast to the large number of distinct pyrotags that represent faecal bacteria such as Lachnospiraceae and Bacteroides, only one or two unique V6 sequences represented Acinetobacter, Aeromonas and Trichococcus, which collectively account for nearly 35% of the total sewage community. Two dominant Acinetobacter V6 pyrotags (designated Acineto tag 1 and Acineto tag 2) fluctuated inversely with a seasonal pattern over a 3-year period, suggesting two distinct Acinetobacter populations respond differently to ecological forcings in the system. A single nucleotide change in the V6 pyrotags accounted for the difference in these populations and corresponded to two phylogenetically distinct clades based on full-length sequences. Analysis of wavelet functions, derived from a mathematical model of temporal fluctuations, demonstrated that other abundant sewer associated populations including Trichococcus and Aeromonas had temporal patterns similar to either Acineto tag 1 or Acineto tag 2. Populations with related temporal fluctuations were found to significantly correlate with the same WWTP variables (5-day BOD, flow, ammonia, total phosphorous and suspended solids). These findings illustrate that small differences in V6 sequences can represent phylogenetically and ecologically distinct taxa. This work provides insight into microbial community composition and dynamics within the defined environment of urban sewer infrastructure.

Immunological stimuli change expression of genes and neutrophil function in fathead minnow Pimephales promelas Rafinesque.

Fathead minnows Pimephales promelas were exposed to lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] to observe immunological responses during simulated bacterial and viral challenge at the level of gene expression and granulocyte function. Complementary DNA libraries were created from LPS- and poly(I:C)-treated fish and c. 5000 expressed sequence tags (ESTs) were sequenced. The ESTs were subjected to BLASTx analysis and 1500 genes were annotated, grouped by function and 20 immune genes were selected for expression studies by real-time PCR. Lipopolysaccharide treatment significantly downregulated expression of interferon regulatory factor 2 binding protein 1 (nine-fold), Chemokine (C-X-C motif) ligand 12a (three-fold) and TNF-related apoptosis-inducing ligand, TRAIL (two-fold). In poly(I:C)-treated fish, a significant upregulation was observed for IFN-inducible and antiviral proteins belonging to the family of Mx proteins (73-fold) and chemokine CCL-C5a (28-fold). Blood neutrophil count was significantly increased in poly(I:C)-treated fish at 24 and 48 h post-injection. Neutrophil extracellular trap release and respiratory burst of kidney granulocytes were suppressed in poly(I:C)-treated fish, while degranulation of primary granules was not affected significantly by the treatment. The changes in gene expression and neutrophil function in P. promelas exposed to LPS and poly(I:C) support the use of this species as an alternative model for studies of pathogen effects on the innate immune system of fishes.

Persistent petrosquamosal sinus: high incidence in cases of complete aplasia of the semicircular canals.

PURPOSE: To determine the frequency and to describe the morphologic characteristics and associated skull base anomalies of the petrosquamosal sinus (PSS) in cochlear implant candidates with complete aplasia of the semicircular canals (SCCs). MATERIALS AND METHODS: Ethics committee approval was obtained. Index cases were retrospectively selected from an electronic database in which all inner ear malformations observed in patients presenting to a tertiary referral center between 1995 and 2010 were collected. Computed tomography (CT) data were reviewed by neuroradiologists. Clinical consequences of the neuroradiologic findings were analyzed. The Pearson χ(2) test and the Mann-Whitney U test were used to determine significant differences between the number of PSSs observed in cases of complete aplasia of the SCCs and the number observed in cases of other types of inner ear malformations. RESULTS: Inner ear malformations were analyzed in 241 patients. Thirty-one patients (13%) with bilateral SCC aplasia were identified. Among 31 patients, a uni- or bilateral PSS was observed in 25 (81%). In the ears with SCC aplasia, a PSS was observed in 40 (65%) of 62. The three cases in which these PSS occupy the largest area correlate with bilateral absence of the jugular foramen. In seven of eight ears with a PSS, the PSS inhibited surgical exposure or resulted in accidental opening of the PSS during surgery. In all other patients with inner ear malformations, a PSS was observed in 39 (9%) of 412 ears only. CONCLUSION: The PSS presents a risk for cochlear implant surgery that can be detected by the neuroradiologist in advance. Venous CT angiography is advisable in certain cases. The previous assumption that a persistent PSS is encountered more frequently in cases of skull base deformity can be affirmed in the special situation of complete aplasia of the SCCs.

Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs.

Many agents are being considered for treatment of Parkinson disease (PD). Given the large number of agents and the limited resources to evaluate new agents, it is essential to reduce the likelihood of advancing ineffective agents into large, long-term Phase III trials. Futility design methodology addresses this goal. The authors describe how a single-arm Phase II futility study uses a short-term outcome to compare a treatment group response to a predetermined hypothesized or historically based control response. The authors present advantages and limitations of futility designs along with examples derived from the data archive of a large Phase III efficacy study of treatments to delay PD progression, the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. Using the same control progression rate and treatment effect assumptions used to power the original DATATOP trial, the authors calculated the number of subjects needed to conduct two 12-month futility studies. DATATOP was designed to enroll 800 patients. Using data on 124 consecutive subjects randomized into each of the DATATOP treatment groups, the authors identified tocopherol as futile and deprenyl as worthy of further study. Using Phase II information, DATATOP could have been simplified from a 2 x 2 factorial design to a comparison of deprenyl vs placebo. While not testing efficacy, futility designs provide a strategy for discarding treatments unlikely to be effective in Phase III. A limitation is the dependence on historical data or hypothesized outcomes for untreated controls. Futility studies may decrease the time to identify treatments unworthy of further pursuit and reduce subjects' exposure to futile treatments.

The cyanobacterial origin of potent anticancer agents originally isolated from sea hares.

It is increasingly evident that the true biological origin of many metabolites originally isolated from certain marine macroorganisms is cyanobacterial. For example, several dolastatins, potent cytotoxic compounds originally derived from the sea hare Dolabella auricularia, have now been isolated from marine cyanobacteria of the genera Lyngbya and Symploca. This review discusses the isolation of dolastatins and close structural analogues from cyanobacteria. Biosynthetic signatures of metabolites isolated from sea hares, but which are most probably cyanobacterial in origin, are also presented. Finally, some more complex ecology involving movement of cyanobacterial metabolites through the marine food web is presented.

Furodysin lactone and pyrodysinoic acid, new sesquiterpenes from a Philippines Dysidea species.

Chemical investigation of a Dysidea sponge, collected at Siquijor, Philippines, has afforded two new sesquiterpenoid metabolites, which we have termed furodysin lactone (1) and pyrodysinoic acid (2). The known 3,6,11-trihydroxy-9,11-secoergostane-7,24(28)-dien-9-one (3) was also encountered. Structure elucidation of the isolated metabolites involved high-field 2-D NMR spectroscopy including (1)H-(1)H COSY, HSQC, and HMBC.

Dysideaprolines A-F and barbaleucamides A-B, novel polychlorinated compounds from a Dysidea species.

Chemical investigation of a marine sponge, Dysidea sp., collected at Bararin Island, Philippines, has afforded the novel metabolites 1-6, proline-derived analogues of dysidenin (7). We have termed compounds 1-6 dysideaprolines A-F, respectively. Also isolated were compounds 8 and 9, structural analogues of barbamide (10), a metabolite originally isolated from the cyanobacterium Lyngbya majuscula. We have termed these novel compounds barbaleucamides A (8) and B (9). It is most probable that the compounds presented here are actually derived from a symbiotic cyanobacterium found in close association with the Dysidea sp. Structure elucidation of the isolated metabolites involved high-field 2D NMR spectroscopy including (1)H-(1)H COSY, HSQC, and HMBC.

Continuous production of (R)-phenylacetylcarbinol in an enzyme-membrane reactor using a potent mutant of pyruvate decarboxylase from Zymomonas mobilis.

The optimization of a continuous enzymatic reaction yielding (R)-phenylacetylcarbinol (PAC), an intermediate of the L-ephedrine synthesis, is presented. We compare the suitability of three pyruvate decarboxylases (PDC), PDC from Saccharomyces cerevisiae, PDC from Zymomonas mobilis, and a potent mutant of the latter, PDCW392M, with respect to their application in the biotransformation using acetaldehyde and benzaldehyde as substrates. Among these, the mutant enzyme was the most active and most stable one. The reaction conditions of the carboligation reaction were investigated by determining initial rate velocities with varying substrate concentrations of both aldehydes. From the resulting data a kinetic model was inferred which fits the experimental data with sufficient reliability to deduce the optimal concentrations of both substrates for the enzymatic process. The results demonstrate that the carboligation is most efficiently performed using a continuous reaction system and feeding both aldehydes in equimolar concentration. Initial studies using a continuously operated enzyme-membrane reactor gave (R)-PAC with a space-time yield of 81 g L(-1). d(-1) using a substrate concentration of 50 mM of both aldehydes. The yield was easily increased by cascadation of enzyme-membrane reactors. The new strategy allows the synthesis of (R)-PAC from cheap substrates in an aqueous reaction system. It thereby overcomes the limitation of by-product formation that severely limits the current fermentative process.

Chemical defenses of the sacoglossan mollusk Elysia rufescens and its host Alga bryopsis sp.

Sacoglossans are a group of opisthobranch mollusks that have been the source of numerous secondary metabolites; however, there are few examples where a defensive ecological role for these compounds has been demonstrated experimentally. We investigated the deterrent properties of the sacoglossan Elysia rufescens and its food alga Bryopsis sp. against natural fish predators. Bryopsis sp. produces kahalalide F, a major depsipeptide that is accumulated by the sacoglossan and that shows in vitro cytotoxicity against several cancer cell lines. Our data show that both Bryopsis sp. and Elysia rufescens are chemically protected against fish predators, as indicated by the deterrent properties of their extracts at naturally occurring concentrations. Following bioassay-guided fractionation, we observed that the antipredatory compounds of Bryopsis sp. were present in the butanol and chloroform fractions, both containing the depsipeptide kahalalide F. Antipredatory compounds of Elysia rufescens were exclusively present in the dichloromethane fraction. Further bioassay-guided fractionation led to the isolation of kahalalide F as the only compound responsible for the deterrent properties of the sacoglossan. Our data show that kahalalide F protects both Brvopsis sp. and Elysia rufescens from fish predation. This is the first report of a diet-derived depsipeptide used as a chemical defense in a sacoglossan.

Ugibohlin: a new dibromo-seco-isophakellin from Axinella carteri.

Chemical investigation of a marine sponge, Axinella carteri, collected on a reed slope of Talakanen Island, Phillipines, has afforded the new metabolite ugibohlin (1), along with its known cyclic derivative dibromoisophakellin (2). Structure elucidation of the isolated metabolites involved high-field 2D NMR spectroscopy including (1)H-(1)H COSY, HSQC, and HMBC. Revised chemical shift assignments are provided for 2.

'Upenamide: An unprecedented macrocyclic alkaloid from the Indonesian sponge Echinochalina sp.

'Upenamide (1) represents a new class of macrocyclic marine alkaloid possessing both spirooxaquinolizidinone and hemiaminal ring systems. It was isolated from the Indonesian sponge Echinochalina sp. The gross structure of 1 was elucidated by spectroscopic methods and accurate mass measurements. A suggestion is made as to its biogenetic origin.

Role of intestinal surfactant-like particles as a potential reservoir of uropathogenic Escherichia coli.

The binding of uropathogenic Escherichia coli is mediated at the tips of pili by the PapG adhesin, which recognizes the Galalpha(1-4)Gal disaccharide on the uroepithelial surface. These receptors have been identified unequivocally in the human and murine urinary tracts but not in intestinal epithelium, yet uropathogenic E. coli strains are commonly found in normal colonic microflora. The gastrointestinal tract from duodenum to rectum elaborates a phospholipid-rich membrane particle with surfactant-like properties. In these studies, we report that purified murine particles contain a receptor recognized by the class I PapG adhesin because: (1) PapD-PapG complexes and class I pili bound to surfactant-like particles in a solid-phase assay, whereas binding was not detected in microvillous membranes derived from the same tissues, (2) purified PapD-PapG complex bound to a glycolipid receptor detectable in lipid extracts from the particles, and (3) soluble Galalpha(1-4)Gal inhibited the adhesin by 72% from binding to surfactant-like particles. The Galalpha(1-4)Gal receptor present in the intestinal surfactant-like particle which overlies the intestinal mucosa could provide one means to establish an intestinal habitat for uropathogenic E. coli.

A new depsipeptide from the sacoglossan mollusk Elysia ornata and the green alga Bryopsis species.

A new cyclic depsipeptide, kahalalide O (1), was isolated from the sacoglossan Elysia ornata and its algal diet Bryopsis sp. The structure was elucidated primarily by NMR and MS spectral methods, and the stereochemistry of the amino acid residues was determined by chiral HPLC and Marfey analyses. Unlike the related metabolite kahalalide F, which is in development as a potential anticancer agent, kahalalide O (1) was inactive in arresting the growth of P-388, A549, HT29, and MEL28 cancer cell lines in vitro.

Binding of pili from uropathogenic Escherichia coli to membranes secreted by human colonocytes and enterocytes.

PapG adhesins mediate the binding of uropathogenic Escherichia coli. Although receptors for these adhesins have not been demonstrated in intestinal epithelia, the colonic microflora includes strains of uropathogenic E. coli. We now report that surfactant-like particles secreted by the human intestine contain receptors for PapG adhesins and may provide an intestinal habitat for uropathogenic bacteria.