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Girls with cloacal malformation are at risk of bladder dysfunction, with nearly 90% exhibiting some degree of dysfunction. Surgical dissection, particularly with total urogenital mobilization (TUM), has been hypothesized as a cause of worsening bladder function despite this population commonly having associated vertebral and spinal cord abnormalities that may also explain bladder dysfunction. More recently there has been great effort to select the appropriate surgical technique for cloacal repair in each patient in order to minimize dissection and potential damage to the bladder. We aimed to evaluate the effect of surgical cloacal repair on bladder function based on pre and post-surgery urodynamics (UDS) testing. A prospectively collected database of patients with anorectal malformation at a single center was queried for girls with cloacal malformations who had undergone surgical repair from 2015 to 2022. It is our current protocol to perform UDS before and after cloacal repair. Only patients who completed both pre and post-surgery UDS were included. UDS were evaluated and classified using the UMPIRE protocol. A total of 48 patients were included in the cohort. The majority of patients (79.2%) had stable or improved UDS post-op leaving 10 patients (20.8%) who had worsening UDS. Long common channel (≥3 cm) was the only factor significantly associated with worsening UDS. (p = 0.03) Nearly 30% (n = 8) of those undergoing UGS had worse post-op UDS compared to 9.5% (n = 2) with TUM. All patients who worsened UDS initially had safe UDS that changed to intermediate, except for one who worsened to hostile in the setting of significant social challenges and non-compliance. Only common channel length was predictive of worsening UDS, while the type of surgical approach and spine status were not. While the overall risk of worsening UDS after TUM is only 9.5%, patients with normal spines undergoing TUM had the lowest risk, seen in only one in 15 patients (6.6%). Common channel length was the most significant predictor of worsening UDS, while spine status and surgical technique (TUM vs UGS) did not significantly impact this finding. By following this established surgical protocol based on common channel and urethral lengths, is rare for the surgical cloacal repair to result in worsening post-op UDS, particularly in those undergoing TUM for short common channel and normal spine. [ABSTRACT FROM AUTHOR]

To perform a single institution review of spinal instead of general anesthesia for pediatric patients undergoing surgical procedures. Spinal success rate, intraoperative complications, and postoperative outcomes including unplanned hospital admission and emergency department visits within seven days are reported. Retrospective chart review of pediatric patients who underwent spinal anesthesia for surgical procedures from 2016 until 2022. Data collected included patient demographics, procedure and anesthetic characteristics, intraoperative complications, unplanned admissions, and emergency department returns. The study cohort included 1221 patients. Ninety-two percent of the patients tolerated their surgical procedure without requiring conversion to general anesthesia, and 78% of patients that had spinals placed successfully did not receive any sedation following lumbar puncture. The most common intraoperative event was systolic blood pressure below 60 mm Hg (14%), but no cases required administration of vasoactive agents, and no serious intraoperative adverse events were observed. Post-Anesthesia Care Unit Phase I was bypassed in 72% of cases with a median postoperative length of stay of 84 min. Forty-six patients returned to the emergency department following hospital discharge, but no returns were due to anesthetic concerns. Spinal anesthesia is a viable and versatile option for a diversity of pediatric surgical procedures. We noted a low incidence of intraoperative and postoperative complications. There remain numerous potential advantages of spinal anesthesia over general anesthesia in young pediatric patients particularly in the ambulatory setting. IV. Retrospective cohort treatment study. [ABSTRACT FROM AUTHOR]

Methionine sulfoxide reductases (MSRs) are key enzymes in the cellular oxidative defense system. Reactive oxygen species oxidize methionine residues to methionine sulfoxide, and the methionine sulfoxide reductases catalyze their reduction back to methionine. We previously identified the cholesterol transport protein STARD3 as an in vivo binding partner of MSRA (methionine sulfoxide reductase A), an enzyme that reduces methionine-S-sulfoxide back to methionine. We hypothesized that STARD3 would also bind the cytotoxic cholesterol hydroperoxides and that its two methionine residues, Met307 and Met427, could be oxidized, thus detoxifying cholesterol hydroperoxide. We now show that in addition to binding MSRA, STARD3 binds all three MSRB (methionine sulfoxide reductase B), enzymes that reduce methionine-R-sulfoxide back to methionine. Using pure 5, 6, and 7 positional isomers of cholesterol hydroperoxide, we found that both Met307 and Met427 on STARD3 are oxidized by 6α-hydroperoxy-3βhydroxycholest-4-ene (cholesterol-6α-hydroperoxide) and 7αhydroperoxy-3β-hydroxycholest-5-ene (cholesterol-7α-hydroperoxide). MSRs reduce the methionine sulfoxide back to methionine, restoring the ability of STARD3 to bind cholesterol. Thus, the cyclic oxidation and reduction of methionine residues in STARD3 provides a catalytically efficient mechanism to detoxify cholesterol hydroperoxide during cholesterol transport, protecting membrane contact sites and the entire cell against the toxicity of cholesterol hydroperoxide. [ABSTRACT FROM AUTHOR]

Genetic cardiomyopathies involving intrinsic abnormalities of the heart, are frequently driven by gain-of-function mutations, producing toxic proteins or mRNAs that contribute to the disease pathogenesis. Treatment typically includes standard of care therapy for heart failure and arrhythmias rather than targeting the underlying genetic cause. Antibody-Oligonucleotide Conjugates (AOCs) offer a novel method to deliver small interfering RNA (siRNA) therapeutics directly to cardiac cells, holding a significant promise for precision medicine in cardiology, particularly for patients affected by gain-of-function mutations.. AOCs can be designed for precision cardiology therapies by reducing the expression of the targeted gene.. To evaluate the delivery and efficacy of AOCs to reduce the expression of targeted mRNA in heart.. We developed AOCs towards mice or non-human primates (NHPs) utilizing anti-TfR1 monoclonal antibodies conjugated to siRNA against the DMPK mRNA via a stable chemical linker. To evaluate the novel AOC platform to deliver siRNA and silence genes in the heart, mice were administered systemic intravenous AOC at 3 mg/kg (siRNA dose), and tissues were evaluated for siRNA concentration and Dmpk mRNA reduction on day 28. To evaluate the translation and tolerability of the AOC in larger species, NHPs were administered systemic intravenous AOC (2, 6 or 45 mg/kg siRNA dose) and tissues were evaluated for siRNA concentration and DMPK mRNA reduction.. A single dose of AOC at 3 mg/kg in mice resulted in approximately 75% reduction of Dmpk mRNA in both the heart and gastrocnemius muscle by day 28. However, no mRNA reduction was observed in the liver, despite similar siRNA concentrations in the liver and gastrocnemius tissues, with cardiac siRNA delivery being about 10 times greater. In NHPs, a single dose of AOC at 6 mg/kg led to significant DMPK mRNA reduction across various striated muscle tissues, including the heart, with no significant reduction observed in non-muscle tissues. A dose-response effect was also observed in cardiac DMPK mRNA reduction in NHPs following 9 months of chronic treatment (2 or 45 mg/kg). Additionally, AOC mediated reduction of DMPK mRNA in NHPs for 9 months was not associated with any adverse effects.. Our data suggests that AOC technology can efficiently deliver siRNA to the heart, significantly reducing the expression of targeted genes. This approach holds great promise as a therapeutic option for a subset of cardiomyopathies due to toxic gain-of-function mutations, particularly those with limited or nonexistent treatment options. [ABSTRACT FROM AUTHOR]

Patients with anorectal malformations (ARM) commonly have associated urologic anomalies. Few large studies exist to accurately characterize the incidence or associations between severity of malformation and urologic diagnosis. The purpose of our study was to determine the incidence of urologic diagnoses in a large cohort of children with ARM and evaluate for any correlation between severity of ARM and the incidence and number of associated urologic diagnoses. A retrospective review was performed of patients with ARM treated at our pediatric colorectal center. All patients underwent protocolized urologic screening. ARM subtypes were ordered with increasing severity as follows in males: perineal, bulbar, prostatic and bladder neck fistulae. Females were similarly categorized as perineal, vestibular and vaginal fistulae followed by cloaca with <3 cm common channel and cloaca with >3 cm common channel. The following urologic diagnoses were assessed to determine whether a correlation existed with the severity of the ARM subtype: hydronephrosis, vesicoureteral reflux (VUR), solitary kidney, renal ascent anomalies (ectopic or pelvic), renal fusion anomalies (horseshoe or cross fused kidney), duplex kidney, hypospadias and undescended testicle. ARM subtypes were defined by distal rectal anatomy. A total of 712 patients were included in our study with a mean age of 4 years and of whom 45% were male. The overall rate of urologic anomalies was greater in males than females (65% vs 56% p < 0.026). In both sexes, the rate of urologic anomalies increased with increasing severity of ARM subtype (p <0.00010) finding that males with bladder neck fistula and females with cloacal malformations, particularly with long common channels, being the highest incidence. In males and females, the rate of hydronephrosis increased as the complexity of ARM increased and this correlated significantly (p < 0.0001 vs p < 0.0003 respectively). Similarly, the incidence of VUR also increased as complexity of ARM increased in both males and females (p = 0.01 and p <0.0001 respectively). The remaining urologic diagnoses were not significantly correlated with severity of ARM. Urologic anomalies occur at a high rate in children with ARM and appear to increase in frequency with increasing complexity of ARM subtype. These findings stress the importance of proper ARM screening and proactive collaboration with a clinician with expertise in pediatric urology early in the management of such children to improve early recognition of urologic diagnoses. Level III. [ABSTRACT FROM AUTHOR]

• A comprehensive review of MPPT techniques. • Review of high gain resonant soft-switching dc-dc converters. • Review of high gain current-fed dc-dc converters. • Review of multilevel inverters for high solar power generation. Power generated by PV panels is highly vulnerable to uncertain weather conditions, and impedance connected to its terminals. Therefore, to maximize the energy productivity from panels by controlling output impedance, a power electronic converter capable of adopting maximum power point tracking (MPPT) technique is required. This paper includes a comprehensive review of basic and advanced MPPT techniques proposed to address the variations in temperature, irradiance, partial shading conditions. Power processing equipment such as dc/dc converters and inverters are mandatory in extracting power from PV panels and utilizing either for standalone systems or grid integration. Grid integration is a major focus where access to utility line ranging from domestic micro-inverters (<300 W) to solar generation (>MW). A centralized inverter topology interfaces a MW power rating PV farm consisting several parallel strings of series connected PV panels to the grid. This review article contributes on presenting an overview of the state-of-the-art power electronics systems for integration of PV panels to the grid. Various interfacing power electronic architectures covering micro-inverter, central inverter up to modular inverter approach operating at low switching frequency and high switching frequency with resonant and pulse-width modulated (PWM) soft-switching or hard-switching are reported. Various voltage-fed and current-fed multi-level inverters for such architectures are studied and discussed. [ABSTRACT FROM AUTHOR]

This paper focuses on identifying crash risk factors associated with injury severity of teen drivers. Crash data obtained from the Highway Safety and Information System (HSIS) for the entire state of North Carolina, for years 2011 to 2013, was used for analysis and modeling. Among all the crashes during the study period, a total of 62,990 crashes involving teen drivers (15 to 19 years) were analyzed. A partial proportionality odds model was developed to identify factors contributing to injury severity of teen drivers. The results obtained indicate that teen drivers driving sports utility vehicles and pickup trucks are more likely to be severely injured when compared to teen drivers driving passenger cars. Teen drivers are more likely to be severely injured on weekdays, particularly during peak hours. The chances of teen drivers getting involved in severe injury crashes on Tuesdays and Fridays is higher when compared to Sundays. Age, gender, road configuration, terrain, adverse weather condition, and access control are observed to have a significant effect on teen driver's injury severity. • Teen drivers driving sports utility vehicles and pickup trucks are more likely to be severely injured compared to passenger cars. • Teen drivers are more likely to be severely injured on weekdays, particularly during peak hours. • The chances of teen drivers getting involved in severe injury crashes on Tuesdays and Fridays is higher compared to Sundays. • Age, gender, road configuration, terrain, adverse weather condition, and access control are observed to have a significant effect on teen driver's injury severity. [ABSTRACT FROM AUTHOR]

Highlights • Road, weather, and geometric characteristics have a similar effect on crash injury severity of at-fault and not at-fault drivers. • Driver age, gender, and physical condition influence crash injury severity of not at-fault drivers. • Vehicle type, and, the number and type of traffic rule violations influence crash injury severity of not at-fault drivers. • Motorcyclists and drivers 70 years or older are observed to be the most vulnerable road users. Abstract This paper examines and compares the effect of selected variables on driver injury severity of, both, at-fault and not at-fault drivers. Data from the Highway Safety Information System (HSIS) for the state of North Carolina was used for analysis and modeling. A partial proportional odds model was developed to examine the effect of each variable on injury severity of at-fault driver and not at-fault driver, and, to examine how each variable affects these two drivers’ injury severity differently. Road characteristics, weather condition, and geometric characteristics were observed to have a similar effect on injury severity in a crash to at-fault and not at-fault drivers. Age of the driver, physical condition, gender, vehicle type, and, the number and type of traffic rule violations were observed to play a significant role in the injury severity of not at-fault drivers when compared to at-fault drivers in the crash. Moreover, motorcyclists and drivers 70 years or older are observed to be the most vulnerable road users. [ABSTRACT FROM AUTHOR]

Abstract Background and aim The sacral ratio (SR) is a well-established tool to quantify sacral development in patients with anorectal malformations (ARM) and can be used as a predictor of fecal continence. We hypothesized that a lower SR correlated with the presence of urologic and renal malformations. Methods We retrospectively reviewed the medical records of patients with ARM treated at our center from 2014 to 2016. We measured the lateral SR as a marker for sacral development and assessed the spine for the presence of tethered cord (TC). Urological and renal anomalies, including single kidney, hydronephrosis, hypospadias, vesicoureteral reflux (VUR), ectopic ureter, and penoscrotal transposition were assessed. Analysis of variance (ANOVA), t-tests, and multivariable linear regression were used to test for differences in SR with consideration of associated urologic malformations and tethered cord. Results 283 patients with ARM were included for analysis (156 females). The median age was 39 months (10–90). Among these, 178 (55.6%) had 1 or more urologic malformations, and 81 (25.3%) had a TC. Hydronephrosis, high-grade VUR (3–5), solitary kidney, and tethered cord were significantly associated with lower SR (p < 0.01). In multivariable regression models, the presence of urologic abnormalities remained significantly associated with lower a SR despite the presence or absence of TC (p < 0.001). Conclusion SR is a potentially useful indicator of certain urologic anomalies including hydronephrosis, high grade VUR, and solitary kidney in patients with ARM. This association is independent of the presence of TC. A sacral ratio as a part of the VACTERL screening can help the surgeon identify which patients need closer urologic follow up. Level of evidence IV [ABSTRACT FROM AUTHOR]

Summary Cicatrix formation, which can form after neonatal circumcision to entrap the glans penis, presents a therapeutic challenge. Previous studies in the literature have described either using a topical steroid cream or stretching of the scar tissue with an instrument but not a combination of both modalities. In our experience, monotherapy has resulted in significant recurrence and/or need for further treatment. We present our successful experience that combines cicatrix stretching with a hemostat using local anesthesia in the office followed by several weeks of topical steroids with a minority of patients needing any additional therapy. [ABSTRACT FROM AUTHOR]

The objective of this research is to identify factors associated with crashes due to overcorrection or oversteering of vehicles. Crash data was collected from 2011 to 2013 for the State of North Carolina in the United States. Logistic regression modeling was used to analyze crash data because of the dichotomous nature of the dependent variable (overcorrection or oversteering). The crash involvement due to overcorrection or oversteering of a vehicle decreased as the age of the driver increased. Drivers are 2.22 times more likely to overcorrect or oversteer when ill, 3.44 times more likely to overcorrect or oversteer when under fatigue, and 1.61 times more likely to overcorrect or oversteer when fallen asleep compared to normal physical conditions. Overall, driver characteristics and speed limit tend to play a major role in overcorrection or oversteering of vehicles. Programs to reduce impaired driving might help in the reduction of overcorrection or oversteering related crash fatalities or injuries. Additionally, training and driver education programs focusing on identified factors associated with crashes due to overcorrection or oversteering of vehicles will benefit drivers on how to respond during emergency or panic situations. [ABSTRACT FROM AUTHOR]

Lewis X (Le X ) is a branched trisaccharide Galβ1→4(Fucα1→3)GlcNAc that is expressed on many cell surface glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of glycopeptides bearing Le X remains a major limitation for structure-function studies of the Le X determinant. Here we report a total synthesis of a Le X pentasaccharide 1 using a regioselective 1-benzenesulfinyl piperidine/triflic anhydride promoted [3 + 2] glycosylation. The presence of an Fmoc-threonine amino acid facilitates incorporation of the pentasaccharide in solid phase peptide synthesis, providing a route to diverse O -linked Le X glycopeptides. The described approach is broadly applicable to the synthesis of a variety of complex glycopeptides containing O -linked Le X or sialyl Lewis X (sLe X ). [ABSTRACT FROM AUTHOR]

Summary Background Spinal anesthesia (SA) is an effective technique that has been used in children for years. With growing concern with regard to the risks of general anesthesia (GA), we developed a SA program to provide an alternative option. We present our initial experience with this program. Objective To implement a SA program at a large tertiary care pediatric center and assess the safety and efficacy of the technique as an alternative to GA for urologic surgery. Study design/methods We prospectively collected data on all children undergoing SA at our institution. We recorded demographics, procedure, time required for placement of the SA, length of surgery, success of lumbar puncture, success of attaining adequate surgical anesthesia, need for supplemental systemic sedation, conversion to GA, and perioperative complications. Results SA was attempted in 105 consecutive children (104 boys, 1 girl) with a mean age of 7.4 ± 4.3 months (range 19 days–24 months) and mean weight of 8.3 ± 1.7 kg (range 3.5–13.7). Placement of the SA was successful in 93/105 children (89%). Inability to achieve lumbar puncture (cerebrospinal fluid was not obtained) meant that SA was abandoned in seven (7%) patients and GA was administered. In five patients in whom SA was successful and surgery was begun, 5/93 (5%) required conversion to GA: two because of evisceration of intestine through large hernia defects related to coughing and abdominal irritation, two because of lack of motor blockade despite an adequate sensory block, and one because of an inability to place an intravenous catheter in the lower extremities (required per SA protocol). If necessary, an intravenous catheter can be placed in the upper extremity, but this must be weighed against the fact that the block has already been placed and is of limited duration. Overall, SA was successful (SA was placed and surgery was completed without conversion to GA) in 88/105 children (84%). No additional sedation and no systemic anesthetic agents were required in 75/88 children (85%). The average time required to place the SA was 3.8 ± 2.7 min (range 1–12). The average time for the surgical procedure was 38.3 ± 23.1 min (range 10–122). No patient required conversion to GA because of recession of block. There were no surgical complications. Discussion/conclusions SA is a safe and efficacious technique for routine pediatric urological procedures. SA should be considered for cases such as neonatal torsion or patients with significant cardiac or pulmonary comorbidities when the risks of GA are often weighed against the risks of non-intervention. [ABSTRACT FROM AUTHOR]

Benign vaginal masses are relatively uncommon in adults, with an estimated incidence of 1.6% in an adult urogynecologic surgical population, and the incidence in adolescents is unknown. The most common midline anterior vaginal wall mass is a urethral diverticulum, but the differential diagnosis of anterolateral wall masses is broad and includes cysts of embryonic origin (Mullerian cysts, Gartner's duct cysts), Skene's duct cysts, epithelial inclusion cysts, endometriosis, leiomyoma, fibroma, and lipoma. We present a case of anterior vaginal wall mass due to a previously unreported etiology. Our patient is a 17 year-old nonbinary person with a history of chronic pelvic pain. Surgical history includes cystoscopy with bilateral injection of Deflux in 2018 for vesicoureteral reflux (VUR). They presented for LNG-IUD insertion under sedation and examination revealed a firm, smooth 1 cm nodule palpable in the midline anterior vaginal wall which was unable to be visualized on speculum exam. The remainder of the pelvic exam was typical and pelvic ultrasound showed a typical uterine shape without evidence of pelvic mass. Given its location in the anterior vagina, initial suspicion was for urethral diverticulum, thus the patient was referred to urology for consultation. The patient has a history of chronic dysuria and perineal pain, but no typical urinary symptoms of urethral diverticulum. Urology performed cystoscopy and examination under anesthesia in coordination with gynecology, which revealed mound-like prominences of both ureteral orifices consistent with prior bilateral Deflux injection. Digital manipulation of the vaginal mass during cystoscopy correlated with movement of the mounds of Deflux material. Benign vaginal masses are rare and poorly understood, especially in the adolescent population. A vaginal mass due to injection of Deflux material has not been previously reported. Injection of Deflux, a bulking agent composed of dextranomer microspheres suspended in hyaluronic acid, is an endoscopic method of correcting VUR. Compared to ureteral reimplantation, Deflux injection is safer and has few reported serious complications. Calcification of Deflux material can occur as early as 3 years following injection and may mimic a ureteral stone on imaging; there have otherwise been no reported long-term sequelae of calcification. The incidence of a palpable vaginal mass in patients with a history of Deflux injection may increase as this technique becomes more common and should be included in the differential diagnosis of vaginal mass in patients with a history of VUR. Supporting Figures or Tables https://www.abstractscorecard.com/uploads/Tasks/upload/19245/RGXGDRUQ-1376941-1-ANY.pdf https://www.abstractscorecard.com/uploads/Tasks/upload/19245/RGXGDRUQ-1376941-2-ANY.pdf [ABSTRACT FROM AUTHOR]

Introduction A significant number of internationally adopted children have congenital birth defects. As a specialist center for colorectal diagnoses, we evaluate such children with an anorectal malformation (ARM) and have found that a significant number need a reoperation. Knowledge of the common complications following ARM surgery has led us to develop treatment algorithms for patients with unknown past medical and surgical history, a situation typically encountered in the adopted population. Methods The results of investigations, indications, and rate of reoperation were assessed for adopted children with an ARM evaluated between 2014 and 2016. Results 56 patients (28 males) were identified. 76.8% required reoperative surgery. Mislocation of the anus outside the sphincter complex was seen in 50% of males and 39.3% of females. Anal stricture, rectal prolapse, retained vaginal septum, and a strictured vaginal introitus were also common. Conclusion The reoperative surgery rate in the internationally adopted child with an ARM is high. Complete, systematic evaluation of these children is required to identify complications following initial repair. Development of mechanisms to improve the primary surgical care these children receive is needed. [ABSTRACT FROM AUTHOR]

The introduction of pneumococcal conjugate vaccines has led to the emergence of non-vaccine serotypes, which contributed to invasive pneumococcal disease in Canada and worldwide. A significant increase in the prevalence of non-13-valent pneumococcal conjugate vaccine (PCV-13)-included serotypes 22F, 15A, and 8 was observed from 2009 to 2013 in Ontario (all p values < 0.01). In this study, whole genome sequencing was conducted on the 25 isolates of serotype 22F, seven of 15A and 10 of 8 to investigate the population structure and antibiotic resistance. All seven serotype 15A isolates were found to be multidrug resistant. From whole genome analysis, we observed recombination events among serotypes 22F, 15A and 8 populations. Serotype 22F (ST433) has emerged into two sub-populations, with 28% (7/25) exhibiting recombination events, and five also acquiring macrolide resistance as a result of recombination. This study enhances the knowledge on the molecular evolution of emerging non-PCV-13 vaccine serotype 22F, including acquisition of resistance genes through recombination events. It underpins the importance of whole genome sequencing in studying Streptococcus pneumoniae population structures and dynamics, and its utility in molecular surveillance. [ABSTRACT FROM AUTHOR]

Obtaining retrograde access into a ureter that has been previously reimplanted in a cross-trigonal fashion can be a challenging procedure. We describe a percutaneous vesicoscopic approach to obtain access into a reimplanted ureter to perform ureteroscopy and laser lithotripsy. [ABSTRACT FROM AUTHOR]

This paper reports on the design, fabrication, characterisation and deployment of a multi-measurand optical fibre sensor (MMS) that is capable of simultaneously monitoring strain, temperature, refractive index and cross-linking chemistry. The sensor design is based on the extrinsic fibre Fabry–Perot interferometer. A feature of this sensor system is that a conventional multi-channel fibre-coupled near-infrared spectrometer is used to monitor the four independent parameters. The issues relating to the measurement resolution of the individual sensors and the associated interrogation equipment are discussed. The MMS was embedded in between the fourth and fifth plies of an eight-ply E-glass plain-weave fabric. A commercially available thermosetting epoxy/amine resin system was used to impregnate the fabric layers manually. The laminated preform was vacuum-bagged and cured in an autoclave. The following parameters were monitored: the depletion rates of the epoxy and amine functional groups in the resin system; the temperature in close proximity to the “chemical sensor”; the evolution of strain; and the refractive index of the resin system. The effect of post-processing on the output from the embedded optical fibre sensors is also considered. [ABSTRACT FROM AUTHOR]

Abstract: Roxithromycin, erythromycin, ciprofloxacin and sulfamethoxazole are frequently detected antibiotics in environmental waters. Direct and indirect photolysis of these problematic antibiotics were investigated in pure and natural waters (fresh and salt water) under irradiation of different light sources. Fundamental photolysis parameters such as molar absorption coefficient, quantum yield and first order rate constants are reported and discussed. The antibiotics are degraded fastest under ultraviolet 254nm, followed by 350nm and simulated solar radiation. The composition of the matrix (pH, dissolved organic content, chloride ion concentration) played a significant role in the observed photodegradation. Under simulated solar radiation, ciprofloxacin and sulfamethoxazole degrade relatively quickly with half-lives of 0.5 and 1.5h, respectively. However, roxithromycin and erythromycin, macrolides are persistent (half-life: 2.4–10days) under solar simulation. The transformation products (15) of the targeted antibiotics produced under irradiation experiments were identified using high resolution mass spectrometry and degradation pathways were proposed. [Copyright &y& Elsevier]

Antiangiogenic therapy is a promising new treatment modality for cancer, but it generally produces only transient tumor regression. We have previously devised a tumor-targeted nanosystem, in which a pentapeptide, CGKRK, delivers a proapoptotic peptide into the mitochondria of tumor blood vessel endothelial cells and tumor cells. The treatment was highly effective in glioblastoma mouse models completely refractory to other antiangiogenic treatments. Here, we identify p32/gC1qR/HABP, a mitochondrial protein that is also expressed at the cell surface of activated (angiogenic) endothelial cells and tumor cells, as a receptor for the CGKRK peptide. The results demonstrate the ability of p32 to cause internalization of a payload bound to p32 into the cytoplasm. We also show that nardilysin, a protease capable of cleaving CGKRK, plays a role in the internalization of a p32-bound payload. As p32 is overexpressed and surface displayed in breast cancers, we studied the efficacy of the nanosystem in this cancer. We show highly significant treatment results in an orthotopic model of breast cancer. The specificity of cell surface p32 for tumor-associated cells, its ability to carry payloads to mitochondria, and the efficacy of the system in important types of cancer make the nanosystem a promising candidate for further development.Molecular Therapy (2013); 21 12, 2195-2204. doi:10.1038/mt.2013.191 [ABSTRACT FROM AUTHOR]

Abstract: Vaginal tumors in children are uncommon. This report describes the rare case of an atypical smooth muscle tumor arising from the vagina in a pediatric patient managed with tumor resection, vaginal reconstruction, and continent urinary diversion. We also discuss a review of the literature and a brief report detailing our experience with pediatric vaginal tumors. [Copyright &y& Elsevier]

Abstract: An immuno-informatics study was conducted to determine possible pre-existing T cellular immunity to the recently emerged swine-origin triple reassortant H3N2 variant (S-OtrH3N2v-2011) which acquired the matrix gene of influenza A (H1N1)pdm09. Given the genetic origin of S-OtrH3N2v-2011, our study focused on the hemagglutinin (HA) and matrix1 (M1) proteins to identify common and conserved T cell epitopes. We compared HA CD4+ T cell epitopes of S-OtrH3N2v-2011 with seasonal H3N2 (1968–2011)-HA proteins. M1 CD4+ and CD8+ T cell epitopes of S-OtrH3N2v-2011 were compared with the M1 proteins of seasonal H1N1 (1977–2009) and A (H1N1)pdm09 (2009–2011) subtypes. The results revealed a high conservancy of epitopes localized particularly on HA2 and the entire M1 protein. The overall cross reactivity of predicted CD4+ T cell epitopes with previously experimentally defined (Immuno Epitope Database) CD4+ T epitopes of HA and M1 proteins was ∼51%. CD8+ T cell cross-reactivity of ∼74% was documented for M1 protein. Analysis suggests possible pre-existing CD4+ T cell immunity to S-OtrH3N2v-2011 in the human population. [Copyright &y& Elsevier]

Abstract: Experimental observations of signature changes of bulk soil electrical conductivity (EC) due to CO2 leakage were carried out at a field site at Bozeman, Montana, to investigate the change of soil geophysical properties in response to possible leakage of geologically sequestered CO2. The dynamic evolution of bulk soil EC was measured during an engineered surface leakage of CO2 through in situ continuous monitoring of bulk soil EC, soil moisture, soil temperature, rainfall rate, and soil CO2 concentration to investigate the response of soil bulk EC signature to CO2 leakage. Observations show that: (1) high soil CO2 concentration due to CO2 leakage enhances the dependence of bulk soil EC on soil moisture. The bulk soil EC is a linear multivariate function of soil moisture and soil temperature, the coefficient for soil moisture increased from 2.111dS for the non-leaking phase to 4.589dS for the CO2 leaking phase; and the coefficient for temperature increased from 0.003dS/°C for the non-leaking phase to 0.008dS/°C for the CO2 leaking phase. The dependence of bulk soil EC on soil temperature is generally weak, but leaked CO2 enhances the dependence, (2) after the CO2 release, the relationship between soil bulk EC and soil CO2 concentration observes three distinct CO2 decay modes. Rainfall events result in sudden changes of soil moisture and are believed to be the driving forcing for these decay modes, and (3) within each mode, increasing soil CO2 concentration results in higher bulk soil EC. Comparing the first 2 decay modes, it is found that the dependence of soil EC on soil CO2 concentration is weaker for the first decay mode than the second decay mode. [Copyright &y& Elsevier]

Abstract: Recombinant elastin-like protein (ELP) polymers display several favorable characteristics for tissue repair and replacement as well as drug delivery applications. However, these materials are derived from peptide sequences that do not lend themselves to cell adhesion, migration, or proliferation. This report describes the chemoselective ligation of peptide linkers bearing the bioactive RGD sequence to the surface of ELP hydrogels. Initially, cystamine is conjugated to ELP, followed by the temperature-driven formation of elastomeric ELP hydrogels. Cystamine reduction produces reactive thiols that are coupled to the RGD peptide linker via a terminal maleimide group. Investigations into the behavior of endothelial cells and mesenchymal stem cells on the RGD-modified ELP hydrogel surface reveal significantly enhanced attachment, spreading, migration and proliferation. Attached endothelial cells display a quiescent phenotype. [Copyright &y& Elsevier]

Abstract: Objective: We report our initial experience, and describe our technique, in performing laparoscopic ipsilateral ureteroureterostomy (IUU) in the pediatric population. Materials and methods: An IRB-approved, retrospective review of all patients undergoing laparoscopic IUU at our institution between 2006 and 2009 was performed. Demographic data, mode of presentation, underlying diagnosis, operative parameters, complications and follow-up data were analyzed. Cystoscopy, retrograde pyelograms and ureteral stent placement into the lower pole ureter were performed at the beginning of all cases. All were performed via a transperitoneal approach. An end-to-side ureteral anastamosis was carried out along the proximal lower pole ureter. No drains were left in place. Urethral catheters were left for 48 h. Results: There were seven patients in the series. All were female with a mean age of 84 months (11舐190). Diagnosis was an ectopic ureter in six patients and a ureterocele in one patient. No patient required conversion to an open approach. Mean total operative time was 187 min (140舐252). Mean hospital stay was 2 days (1舐4) with a mean follow up of 8 months (1舐15). No complications occurred postoperatively. Follow-up studies demonstrate decreased or resolved hydronephrosis in all cases. Conclusions: In our initial experience, laparoscopic IUU can be accomplished in a safe and effective manner with minimal complication. [Copyright &y& Elsevier]

Abstract: Background: The safety of laparoscopic bariatric procedures in superobese patients is still debatable. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program''s participant-use file, the patients who had undergone laparoscopic Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding for morbid obesity were identified. Several perioperative variables, including 30-day morbidity and mortality, were collected, and the data were compared within each procedure after dividing the patients according to the body mass index: <50 kg/m2 (morbidly obese group and ≥50 kg/m2 (superobese group). Results: A total of 29,323 patients who had undergone laparoscopic bariatric procedures from 2005 to 2008 were identified. Overall, compared with the morbidly obese group, the superobese group had more men (3:2), younger patients, a greater incidence of co-morbidities (e.g., hypertension and dyspnea), a significantly increased length of stay, and a greater rate of 30-day mortality (.26% versus .07%, odds ratio [OR] 4.38, P = .0001). In the gastric bypass group, the superobese group had a significantly greater incidence of postoperative complications, including superficial wound infections (2.45%, OR 1.68, P = .0001), reintubation (.61%, OR 1.97, P = .003), pulmonary embolism (.30%, OR 2.13, P = .032), myocardial infarction (.07%, P = .017), deep vein thrombosis (.49%, OR 2.06, P = .006), septic shock (.44%, OR 1.74, P = .04), and 30-day mortality (.28%, OR 2.26, P = .026). In the laparoscopic adjustable gastric banding group, the superobese group had a significantly greater incidence of postoperative complications, including superficial (1.65%, OR 2.18, P = .0013) and deep (.23%, OR 2.56, P = .035) wound infections, sepsis, septic shock and 30-day mortality (.17%, OR 13.4, P = .0219). Conclusion: Laparoscopic bariatric procedures in superobese patients have been associated with significantly increased complications, including 30-day mortality, compared with morbidly obese patients. However, overall, the procedures appear to be safe, with low complication and 30-day mortality rates. [Copyright &y& Elsevier]

Abstract: The focus of this paper is twofold: (1) to examine the non-linear relationship between pedestrian crashes and predictor variables such as demographic characteristics (population and household units), socio-economic characteristics (mean income and total employment), land use characteristics, road network characteristics (the number of lanes, speed limit, presence of median, and pedestrian and vehicular volume) and accessibility to public transit systems, and (2) to develop generalized linear pedestrian crash estimation models (based on negative binomial distribution to accommodate for over-dispersion of data) by the level of pedestrian activity and spatial proximity to extract site specific data at signalized intersections. Data for 176 randomly selected signalized intersections in the City of Charlotte, North Carolina were used to examine the non-linear relationships and develop pedestrian crash estimation models. The average number of pedestrian crashes per year within 200 feet of each intersection was considered as the dependent variable whereas the demographic characteristics, socio-economic characteristics, land use characteristics, road network characteristics and the number of transit stops were considered as the predictor variables. The Pearson correlation coefficient was used to eliminate predictor variables that were correlated to each other. Models were then developed separately for all signalized intersections, high pedestrian activity signalized intersections and low pedestrian activity signalized intersections. The use of 0.25mile, 0.5mile and 1mile buffer widths to extract data and develop models was also evaluated. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Postoperative hydrocele development is a frustrating complication of varicocele surgical repair. To avoid this complication, we began to offer percutaneous embolization as a treatment option. We present our initial experience with this technique. Methods: A retrospective review of all patients who underwent percutaneous embolization and sclerotherapy of a varicocele at our institution was performed. Results: There were 27 patients with a mean age of 16 years (range 13–19 years). Indications included pain (48%), varicocele size (30%) and persistent testicular asymmetry (22%). Four patients had experienced failure of a previous surgical repair. Follow-up data were available for 21 patients (mean 9 months). The varicocele resolved in 19 patients (91%) with no evidence of hydrocele formation in any of the boys. There was resolution of pain in all patients for whom this was the indication for the procedure. In the two failures, access to the lower spermatic vein was not possible owing to the number and tortuosity of the vessels. Conclusions: Percutaneous embolization and sclerotherapy represent a truly minimally invasive treatment with low morbidity, minimal pain and rapid recovery. In our early experience, since lymphatic channels are completely avoided, there appears to be no risk of hydrocele formation. [ABSTRACT FROM AUTHOR]

Abstract: Selectins (L, E, and P) are vascular endothelial molecules that play an important role in the recruitment of leukocytes to inflamed tissue. In this regard, P-Selectin glycoprotein-1 (PSGL-1) has been identified as a ligand for P-Selectin. PSGL-1 binds to P-Selectin through the interaction of core-2 O-glycan expressing sialyl Lewis x oligosaccharide and the three tyrosine sulfate residues. Herein, we report the synthesis of threonine-linked core-2 O-glycan as an amino acid building block for the synthesis of PSGL-1. This building block was further incorporated in the Fmoc-assisted solid-phase peptide synthesis to provide a portion of the PSGL-1 glycopeptide. [Copyright &y& Elsevier]

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play central roles in metabolism and inflammation. Although a variety of compounds have been shown to activate PPARs, identification of physiologically relevant ligands has proven difficult. In silico studies of lipid derivatives reported here identify specific 5-lipoxygenase products as candidate physiologically relevant PPAR-α activators. Subsequent studies show both in vitro and in a murine model of inflammation that 5-lipoxygenase stimulation induces PPAR-α signaling and that this results specifically from production of the inflammatory mediator and chemoattractant leukotriene B4 (LTB4). Activation of PPAR- α is a direct effect of intracellularly generated LTB4 binding to the nuclear receptor and not of secreted LTB4 acting via its cell-surface receptors. Activation of PPAR-α reduces secretion of LTB4 by stimulating degradation of this fatty acid derivative. We also show that the LTB4 precursors leukotriene A4 (LTA4) and 5-hydroperoxyeicosatetrenoic acid (5- HPETE) activate PPAR-α but have no significant endogenous effect independent of conversion to LTB4. We conclude that LTB4 is a physiologically relevant PPAR-α activator in cells of the immune system. This, together with previous findings, demonstrates that different types of lipids serve as endogenous PPAR-α ligands, with the relevant ligand varying between functionally different cell types. Our results also support the suggestion that regulation of inflammation may involve balancing proinflammatory effects of LTB4, exerted through cell-surface receptors, and anti-inflammatory effects exerted through PPAR-α activation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We describe a salvage technique for urinary diversion in the face of an obstructed, undilated upper urinary tract utilized in the management of a premature newborn infant with bilateral renal candidiasis, namely cutaneous calicostomy. Methods: An 850-g 24weeks'' gestation premature male infant developed obstructive nephropathy as a result of renal candidiasis. Systemic therapy with bilateral nephrostomy drainage and amphotericin B irrigations was repeatedly unsuccessful in eradicating the candiduria and fungal balls. Underlying bilateral proximal collecting system obstructions complicated the situation by rendering ureterostomy or pyelostomy impossible. Subsequent flank exploration was performed bilaterally, and bilateral cutaneous calicostomies were performed. Results: The patient''s urinary tract was successfully diverted and the fungal balls eradicated. Renal ultrasounds and antegrade nephrostograms through the cutaneous calicostomy stomas revealed the procedure to be successful. Unfortunately, the patient eventually died from overwhelming non-urologic sepsis approximately 3months postoperatively. Conclusions: Although systemic antifungal therapy with bilateral nephrostomy drainage has been shown to be successful in the treatment of obstructive uropathy due to renal candidiasis, surgical intervention is necessary when recurrent sepsis with candiduria persists. In the event that underlying collecting system obstruction is also present, cutaneous calicostomy is an option to consider in the treatment of this disease. [Copyright &y& Elsevier]

Abstract: Aryl sulfonamide-based endothelin antagonists were synthesized and covalently linked to the reactive lysine of the m38C2 antibody to create a series of CovX-Bodies. These chemically programmed antibodies behaved as potent endothelin receptor antagonists in vitro and had antitumor efficacy in a prostate cancer xenograft model which, on a molar basis, far exceeded the activity of the parent small molecule. [Copyright &y& Elsevier]

• Health experts and clinicians are relying on results of recent randomised controlled trials (RCTs) for COVID-19 treatment. • Randomisation methodologies were suboptimal for matching the studied groups based on disease severity. • The authors have failed to show that the data of these trials are without fatal sampling errors and sampling biases. • There is a definite need for validation of data in the completed trials and the improvement of randomisation methodologies. • Only double-blind placebo-controlled RCTs when done with robust randomisation methodologies can yield high-quality data. During the emerging COVID-19 (coronavirus disease 2019) pandemic, initially there were no proven treatment options. With the release of randomised controlled trial (RCT) results, we are beginning to see possible treatment options for COVID-19. The RECOVERY trial showed an absolute risk reduction in mortality by 2.8% with dexamethasone, and the ACTT-1 trial showed that treatment with remdesivir reduced the time to recovery by 4 days. Treatment with hydroxychloroquine (HCQ) and lopinavir/ritonavir did not show any mortality benefit in either the RECOVERY or World Health Organization (WHO) Solidarity trials. The National Institutes of Health (NIH) and Brazilian HCQ trials did not show any benefit for HCQ based on the seven-point ordinal scale outcomes. The randomisation methodologies utilised in these controlled trials and the quality of published data were reviewed to examine their adaptability to treat patients. We found that the randomisation methodologies of these trials were suboptimal for matching the studied groups based on disease severity among critically-ill hospitalised COVID-19 patients with high mortality rates. The published literature is very limited regarding the disease severity metrics among the compared groups and failed to show that the data are without fatal sampling errors and sampling biases. We also found that there is a definite need for the validation of data in these trials along with additional important disease severity metrics to ensure that the trials' conclusions are accurate. We also propose proper randomisation methodologies for the design of RCTs for COVID-19 as well as guidance for the publication of COVID-19 trial results. [ABSTRACT FROM AUTHOR]