Shiga toxin-producing Escherichia coli clonal complex 32, including serotype O145:H28, in the UK and Ireland.

Introduction. Shiga toxin-producing Escherichia coli (STEC) O157:H7 has been the most clinically significant STEC serotype in the UK for over four decades. Over the last 10 years we have observed a decrease in STEC O157:H7 and an increase in non-O157 STEC serotypes, such as O145:H28.Gap Statement. Little is known about the microbiology and epidemiology of STEC belonging to CC32 (including O145:H28) in the UK. The aim of this study was to integrate genomic data with patient information to gain a better understanding of the virulence, disease severity, epidemic risk assessment and population structure of this clinically significant clonal complex.Methodology. Isolates of E. coli belonging to CC32 (n=309) in the archives of public health agencies in the UK and Ireland were whole-genome-sequenced, virulence-profiled and integrated with enhanced surveillance questionnaire (ESQ) data, including exposures and disease severity.Results. Overall, diagnoses of STEC belonging to CC32 (290/309, 94 %) in the UK have increased every year since 2014. Most cases were female (61 %), and the highest proportion of cases belonged to the 0-4 age group (53/211,25 %). The frequency of symptoms of diarrhoea (92 %), abdominal pain (84 %), blood in stool (71 %) and nausea (51 %) was similar to that reported in cases of STEC O157:H7, although cases of STEC CC32 were more frequently admitted to hospital (STEC CC32 48 % vs O157:H7  34 %) and/or developed haemolytic uraemic syndrome (HUS) (STEC CC32 9 % vs O157:H7 4 %).The majority of STEC isolates (268/290, 92 %) had the stx2a/eae virulence gene combination, most commonly associated with progression to STEC HUS. There was evidence of person-to-person transmission and small, temporally related, geographically dispersed outbreaks, characteristic of foodborne outbreaks linked to nationally distributed products.Conclusion. We recommend more widespread use of polymerase chain reaction (PCR) for the detection of all STEC serogroups, the development of consistent strategies for the follow-up testing of PCR-positive faecal specimens, the implementation of more comprehensive and standardized collection of epidemiological data, and routine sharing of sequencing data between public health agencies worldwide.

Genetic mechanism, baseline sensitivity and risk of resistance to oxathiapiprolin in oomycetes.

BACKGROUND: Oxathiapiprolin is a piperidinyl thiazole isoxazoline fungicide discovered by DuPont and commercialized by Corteva Agriscience. It acts by inhibiting a novel fungal target, an oxysterol binding protein (OSBP), and is intrinsically highly active against oomycetes including grape downy mildew (Plasmopara viticola) and potato late blight (Phytophthora infestans). Because the fungicide acts at a single site there is a need to determine the risk of resistance development. RESULTS: Oxathiapiprolin controlled European Plasmopara viticola and Phytophthora infestans isolates at very low concentrations with half maximal effective concentration (EC50 ) values ranging from 0.001 to 0.0264 mg L-1 and 0.001 to 0.03 mg L-1 , respectively. Laboratory mutagenesis studies performed with Phytophthora capsici using ultraviolet (UV) irradiation generated mutants with reduced sensitivity to oxathiapiprolin. All resistant mutants had a base pair change in the OSBP gene that resulted in an amino acid change. Most common substitutions were S768Y, G770V, G839W and L863W. Isolates of Plasmopara viticola and Phytophthora infestans with reduced sensitivity were also detected in field trial sites where oxathiapiprolin had been applied repeatedly each season over several consecutive years. CONCLUSIONS: The risk of oxathiapiprolin resistance development in Plasmopara viticola and Phytophthora infestans is medium to high and strict resistance management measures are required. Over-exposure of target populations to single-site fungicides during product development should be avoided.

Neurological involvement in children with hemolytic uremic syndrome.

Our objective was to establish the rate of neurological involvement in Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) and describe the clinical presentation, management and outcome. A retrospective chart review of children aged ≤ 16 years with STEC-HUS in Children's Health Ireland from 2005 to 2018 was conducted. Laboratory confirmation of STEC infection was required for inclusion. Neurological involvement was defined as encephalopathy, focal neurological deficit, and/or seizure activity. Data on clinical presentation, management, and outcome were collected. We identified 240 children with HUS; 202 had confirmed STEC infection. Neurological involvement occurred in 22 (11%). The most common presentation was seizures (73%). In the neurological group, 19 (86%) were treated with plasma exchange and/or eculizumab. Of the 21 surviving children with neurological involvement, 19 (91%) achieved a complete neurological recovery. A higher proportion of children in the neurological group had renal sequelae (27% vs. 12%, P = .031). One patient died from multi-organ failure.Conclusion: We have identified the rate of neurological involvement in a large cohort of children with STEC-HUS as 11%. Neurological involvement in STEC-HUS is associated with good long-term outcome (complete neurological recovery in 91%) and a low case-fatality rate (4.5%) in our cohort. What is Known: • HUS is associated with neurological involvement in up to 30% of cases. • Neurological involvement has been reported as predictor of poor outcome, with associated increased morbidity and mortality. What is New: • The incidence of neurological involvement in STEC-HUS is 11%. • Neurological involvement is associated with predominantly good long-term outcome (90%) and a reduced case-fatality rate (4.5%) compared to older reports.

Circumventricular Organ Apelin Receptor Knockdown Decreases Blood Pressure and Sympathetic Drive Responses in the Spontaneously Hypertensive Rat.

The central site(s) mediating the cardiovascular actions of the apelin-apelin receptor (APJ) system remains a major question. We hypothesized that the sensory circumventricular organs (CVOs), interfacing between the circulation and deeper brain structures, are sites where circulating apelin acts as a signal in the central nervous system to decrease blood pressure (BP). We show that APJ gene (aplnr) expression was elevated in the CVOs of spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto (WKY) controls, and that there was a greater mean arterial BP (MABP) decrease following microinjection of [Pyr1]apelin-13 to the CVOs of SHRs compared to WKY rats. Lentiviral APJ-specific-shRNA (LV-APJ-shRNA) was used to knockdown aplnr expression, both collectively in three CVOs and discretely in individual CVOs, of rats implanted with radiotelemeters to measure arterial pressure. LV-APJ-shRNA-injection decreased aplnr expression in the CVOs and abolished MABP responses to microinjection of [Pyr1]apelin-13. Chronic knockdown of aplnr in any of the CVOs, collectively or individually, did not affect basal MABP in SHR or WKY rats. Moreover, knockdown of aplnr in any of the CVOs individually did not affect the depressor response to systemic [Pyr1]apelin-13. By contrast, multiple knockdown of aplnr in the three CVOs reduced acute cardiovascular responses to peripheral [Pyr1]apelin-13 administration in SHR but not WKY rats. These results suggest that endogenous APJ activity in the CVOs has no effect on basal BP but that functional APJ in the CVOs is required for an intact cardiovascular response to peripherally administered apelin in the SHR.

Mutation in the Ciliary Protein C2CD3 Reveals Organ-Specific Mechanisms of Hedgehog Signal Transduction in Avian Embryos.

Primary cilia are ubiquitous microtubule-based organelles that serve as signaling hubs for numerous developmental pathways, most notably the Hedgehog (Hh) pathway. Defects in the structure or function of primary cilia result in a class of diseases called ciliopathies. It is well known that primary cilia participate in transducing a Hh signal, and as such ciliopathies frequently present with phenotypes indicative of aberrant Hh function. Interestingly, the exact mechanisms of cilia-dependent Hh signaling transduction are unclear as some ciliopathic animal models simultaneously present with gain-of-Hh phenotypes in one organ system and loss-of-Hh phenotypes in another. To better understand how Hh signaling is perturbed across different tissues in ciliopathic conditions, we examined four distinct Hh-dependent signaling centers in the naturally occurring avian ciliopathic mutant talpid2 (ta2). In addition to the well-known and previously reported limb and craniofacial malformations, we observed dorsal-ventral patterning defects in the neural tube, and a shortened gastrointestinal tract. Molecular analyses for elements of the Hh pathway revealed that the loss of cilia impact transduction of an Hh signal in a tissue-specific manner at variable levels of the pathway. These studies will provide increased knowledge into how impaired ciliogenesis differentially regulates Hh signaling across tissues and will provide potential avenues for future targeted therapeutic treatments.

Pneumomediastinum in a child with severe COVID-19.

The current global pandemic of the novel coronavirus SARS-CoV2 is a threat to the health and lives of millions of people worldwide. The latest statistics from the World Health Organisation show that there have been 6,515,796 confirmed cases worldwide with 387,298 confirmed deaths (last update 5 June 2020, 10:41 CEST). The majority of critically unwell patients with SARS-CoV2 are adults and the radiological findings associated with them are consistent throughout the literature. However, the reported paediatric cases are few, and as such, there is a limited body of evidence available. More international data is needed, not only on the clinical presentation, but also the radiological findings, so that health-care providers are better able to understand and diagnose this pandemic disease. We describe a case of a previously healthy 9-year-old female who presented to the Emergency Department with symptoms suggestive of raised intracranial pressure. Her CT revealed a medulloblastoma and post-operatively she tested positive for SARS-CoV2. She had a rapid deterioration in her clinical condition and required admission to the intensive care unit (ICU). We provide the supporting radiology along her clinical course in order to demonstrate important insights into this disease in children, including the unusual pnemomediastinum complications which occurred as part of her clinical course. This case is the first reported of its kind.

Comparison and correlation of commercial SARS-CoV-2 real-time-PCR assays, Ireland, June 2020.

We report the performance of a variety of commercially available SARS-CoV-2 PCR kits, used in several different sites across Ireland to determine if Ct values across platforms are comparable. We also investigate whether a Ct value, a surrogate for calculated viral loads in the absence of viral culture of > 34 can be used to exclude SARS-CoV-2 infection and its complications. We found a variation in Ct values from different assays for the same calculated viral load; this should be taken into consideration for result interpretation.

Establishment of sentinel surveillance of human clinical campylobacteriosis in Ireland.

The aim of this work was the establishment of a national laboratory sentinel surveillance service for human clinical Campylobacter in Ireland. This included detailed genomic molecular epidemiology of Campylobacter for 2019. For February-December 2019, 24 clinical microbiology laboratories in Ireland submitted all PCR/culture-positive clinical Campylobacter spp. specimens to Public Health Laboratory (PHL) Dublin one week out of every four. Antimicrobial susceptibility testing (AST) according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria was carried out for Campylobacter spp. isolates for ciprofloxacin, tetracycline and erythromycin. Batch whole genome sequencing (WGS) was carried out on cultures and analysis was performed to determine species, genotype, identify antimicrobial resistance (AMR) and virulence determinants and identify clusters. A total of 75 isolates and 366 PCR-positive stools were received, and 277 isolates recovered (55.7% recovery from stools). Of 257 isolates characterized by WGS, 86.4% (n = 222) were Campylobacter jejuni, 11.7% (n = 30) Campylobacter coli and 1.9% (n = 5) Campylobacter lari. There were 20 clonal complexes with ST-21 clonal complex most prevalent at 26.8% (n = 69). 50.5% (n = 140) of isolates were susceptible to all three antimicrobials tested. 39.3% (n = 109) isolates were ciprofloxacin resistant, 26.3% (n = 73) tetracycline resistant and two isolates erythromycin resistant. Congruence between phenotypic and genotypic AST was observed. There was 95.9% and 95.6% sensitivity and specificity for WGS to predict ciprofloxacin sensitivity and 98.6% and 99.5% sensitivity and specificity for WGS to predict tetracycline sensitivity. Virulence factors flaA, racR, ciaB and cdtB were detected in all isolates. WGS identified 31 potential clusters for public health alert. This sentinel surveillance of human campylobacteriosis in Ireland establishes the basis for a national reference service. Linking with other partners in a 'One Health' framework will help us better understand sources of infection to reduce disease burden and the threat of AMR.

Electron spin relaxation of P1 centers in synthetic diamonds with potential as B1 standards for DNP enhanced NMR.

The microwave magnetic field, B1, in the non-resonant structures typically used for DNP-enhanced NMR is relatively small, so calibration via continuous wave (CW) power saturation requires a sample with longer spin lattice relaxation times than the samples used as CW standards in X-band cavities. HPHT diamonds have strong, easily observed EPR signals from P1 centers (nitrogen defects), and are indefinitely stable. This makes HPHT diamonds attractive as secondary standards for calibration of electron B1 field strength in a variety of experimental arrangements. The concentrations of P1 centers is also typically in the 30-200 ppm range, or equivalently 10-60 mM, and therefore the EPR relaxation observed is relevant to DNP enhanced NMR employing free radical polarizing agents at similar concentrations. Pulsed and CW saturation relaxation measurements T1 and T2 are compared at X-band. Under CW conditions the relevant T1T2 product of time constants in our samples at room temperature is found to be dominated by electron-electron spin diffusion, and the product is large enough that saturation will be possible with the B1 of typical DNP systems. The similarity of T1 and T2 values obtained by pulse measurements at X-band and Q-band suggests that the X-band results can be extrapolated to the higher EPR frequencies used for DNP experiments. The electron spin dynamics observed here in HPHT diamond samples identify them as useful model systems to better delineate the interplay of electron spin relaxation, magic angle spinning, and inhomogeneous microwave irradiation as they affect DNP enhancement.

Increased apelin receptor gene expression in the subfornical organ of spontaneously hypertensive rats.

The vascular organ of the lamina terminalis, subfornical organ (SFO), and area postrema comprise the sensory circumventricular organs (CVO) which are central structures that lie outside the blood brain barrier and are thought to provide an interface between peripherally circulating signals and the brain through their projections to central autonomic structures. The SFO expresses mRNA for the G protein-coupled apelin receptor (APJ, gene name aplnr) and exogenous microinjection of the neuropeptide apelin (apln) to the SFO elicits a depressor effect. Here we investigated the expression and cellular distribution of aplnr, apln and the recently described ligand apela (apela) in the CVOs and investigated whether differences in the levels of expression of apelinergic gene transcripts in these regions might underlie the chronic elevated blood pressure seen in hypertension. We carried out multiplex in situ hybridization histochemistry on CVO tissue sections from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. Confocal immunofluorescent images indicated strong aplnr expression, with lower levels of apln and modest apela expression, in the CVOs of both WKY rats and SHRs, in both neurons and glia. The expression level of aplnr transcripts was increased in the SFO of SHRs compared to WKY rats. Our data may highlight a potential dysfunction in the communication between CVOs and downstream signalling pathways in SHRs, which may contribute to its different phenotype/s.

Rapid diffusion-weighted MRI for the investigation of recurrent temporal bone cholesteatoma.

BACKGROUND: Suspected cholesteatoma recurrence is commonly investigated with magnetic resonance imaging (MRI) of the temporal bone. Non-echo planar diffusion-weighted imaging (non-EP DWI) has become the sequence of choice. PURPOSE: To assess the agreement between an MRI protocol incorporating both non-EP DWI and contrast-enhanced sequences, and a shortened protocol without contrast-enhanced sequences in the assessment of suspected cholesteatoma recurrence. MATERIALS AND METHODS: One hundred consecutive MRIs, consisting of T2-weighted, non-EP DWI and pre- and post-contrast T1-weighted sequences, were reviewed by two radiologists at a tertiary referral centre. Agreement between the two protocols was assessment by means of a weighted Cohen kappa coefficient. RESULTS: We found a near perfect agreement between the two protocols (kappa coefficient with linear weighting 0.98; 95% confidence interval 0.95-1.00). There were two cases in which the two protocols were discordant. In both cases, the lesion measured <3 mm and images were degraded by artefact at the bone-air interface. The shortened protocol without post-contrast sequences yielded a 32% reduction in acquisition time. CONCLUSION: When non-EP DWI is available, contrast-enhanced sequences can be omitted in the vast majority of cases without compromising diagnostic accuracy. Contrast-enhanced sequences may provide additional value in equivocal cases with small (<3 mm) lesions or in cases where images are degraded by artefact.

Discovering and Reflecting on Bias: A Discussion about Challenges and Benefits of Culturally Centered Patient Care with Women Physicians of the East Bay.

Implicit or unconscious bias is a lens through which we see our world based on our past experiences and learned stereotypes. Within health care, this lens of bias has typically had a negative impact on patient care, particularly for marginalized populations. We sat down with 3 physicians within Kaiser Permanente East Bay to learn about their personal experiences of bias in patient care. We also discuss the importance of acknowledging bias and practicing cultural humility in order to best ally with our patients. We are hopeful our conversation with these physicians will inspire more of the same, leading to improved health care for those that have suffered from bias in the past.

Polar Ocean Observations: A Critical Gap in the Observing System and Its Effect on Environmental Predictions From Hours to a Season.

There is a growing need for operational oceanographic predictions in both the Arctic and Antarctic polar regions. In the former, this is driven by a declining ice cover accompanied by an increase in maritime traffic and exploitation of marine resources. Oceanographic predictions in the Antarctic are also important, both to support Antarctic operations and also to help elucidate processes governing sea ice and ice shelf stability. However, a significant gap exists in the ocean observing system in polar regions, compared to most areas of the global ocean, hindering the reliability of ocean and sea ice forecasts. This gap can also be seen from the spread in ocean and sea ice reanalyses for polar regions which provide an estimate of their uncertainty. The reduced reliability of polar predictions may affect the quality of various applications including search and rescue, coupling with numerical weather and seasonal predictions, historical reconstructions (reanalysis), aquaculture and environmental management including environmental emergency response. Here, we outline the status of existing near-real time ocean observational efforts in polar regions, discuss gaps, and explore perspectives for the future. Specific recommendations include a renewed call for open access to data, especially real-time data, as a critical capability for improved sea ice and weather forecasting and other environmental prediction needs. Dedicated efforts are also needed to make use of additional observations made as part of the Year of Polar Prediction (YOPP; 2017-2019) to inform optimal observing system design. To provide a polar extension to the Argo network, it is recommended that a network of ice-borne sea ice and upper-ocean observing buoys be deployed and supported operationally in ice-covered areas together with autonomous profiling floats and gliders (potentially with ice detection capability) in seasonally ice covered seas. Finally, additional efforts to better measure and parameterize surface exchanges in polar regions are much needed to improve coupled environmental prediction.

Molecular characterization of Campylobacter causing human clinical infection using whole-genome sequencing: Virulence, antimicrobial resistance and phylogeny in Ireland.

OBJECTIVES: We characterized clinical isolates of Campylobacter using whole-genome sequencing (WGS) for detection of virulence genes, antimicrobial resistance markers and phylogenetic analysis in order to increase the knowledge on the molecular epidemiology of Campylobacter in Ireland, where there are significant gaps due to the widespread in the use of culture independent methods for the diagnosis of campylobacteriosis. METHODS: WGS was applied to 122 Campylobacter human isolates collected over a 10-years period, from diarrhoeal stool samples submitted for routine enteric screening. RESULTS: Genes associated with cytotoxin production such as cdtA, cdtB and cdtC were found in 88%, 89% and 89% isolates, respectively; adherence, colonization and invasion genes such as cadF, dnaJ, racR, iam, virB11 and ciaB were found in 99%, 99%, 98%, 99%, 1% and 80% isolates, respectively. Genetic markers associated with resistance to quinolones (C257T in gyrA), beta-lactams (blaoxa-61) and tetracycline (tet(O)) were present in 43%, 71% and 25% isolates, respectively. The cmeABC operon was present in 94% of isolates. No macrolide or aminoglycoside resistance markers were detected. Phylogenetic analysis showed that 112 isolates were assigned to 29 sequence types grouped into 17 clonal complexes. Four clusters previously unidentified were detected. These results shown the similarity of Irish data compared to what has been described globally. CONCLUSIONS: WGS has shown a high discriminatory power for cluster detection, demonstrating that its integration in routine laboratory surveillance could improve the detection and management of outbreaks. In addition we were able to demonstrate that virulence genes in clinical Campylobacter infections in Ireland were similar to those known previously. High prevalence of quinolone resistance markers has been found, which has implications for antimicrobial stewardship.

Blockade of Rostral Ventrolateral Medulla Apelin Receptors Does Not Attenuate Arterial Pressure in SHR and L-NAME-Induced Hypertensive Rats.

Dysfunction of the apelinergic system, comprised of the neuropeptide apelin mediating its effects via the G protein-coupled apelin receptor (APJ), may underlie the onset of cardiovascular disease such as hypertension. Apelin expression is increased in the rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs) compared to Wistar-Kyoto (WKY) normotensive rats, however, evidence that the apelinergic system chronically influences mean arterial blood pressure (MABP) under pathophysiological conditions remains to be established. In this study we investigated, in conscious unrestrained rats, whether APJ contributes to MABP and sympathetic vasomotor tone in the progression of two models of hypertension - SHR and L-NAME-treated rats - and whether APJ contributes to the development of hypertension in pre-hypertensive SHR. In SHR we showed that APJ gene (aplnr) expression was elevated in the RVLM, and there was a greater MABP increase following microinjection of [Pyr1]apelin-13 to the RVLM of SHR compared to WKY rats. Bilateral microinjection of a lentiviral APJ-specific-shRNA construct into the RVLM of WKY, SHR, and L-NAME-treated rats, chronically implanted with radiotelemeters to measure MABP, decreased aplnr expression in the RVLM and abolished acute [Pyr1]apelin-13-induced increases in MABP. However, chronic knockdown of aplnr in the RVLM did not affect MABP in either SHR or L-NAME-treated rats. Moreover, knockdown of aplnr in the RVLM of prehypertensive SHR did not protect against the development of hypertension. These results show that endogenous apelin, acting via APJ, is not involved in the genesis or maintenance of hypertension in either animal model used in this study.

Evolutionary Context of Non-Sorbitol-Fermenting Shiga Toxin-Producing Escherichia coli O55:H7.

In July 2014, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 in England involved 31 patients, 13 (42%) of whom had hemolytic uremic syndrome. Isolates were sequenced, and the sequences were compared with publicly available sequences of E. coli O55:H7 and O157:H7. A core-genome phylogeny of the evolutionary history of the STEC O55:H7 outbreak strain revealed that the most parsimonious model was a progenitor enteropathogenic O55:H7 sorbitol-fermenting strain, lysogenized by a Shiga toxin (Stx) 2a-encoding phage, followed by loss of the ability to ferment sorbitol because of a non-sense mutation in srlA. The parallel, convergent evolutionary histories of STEC O157:H7 and STEC O55:H7 may indicate a common driver in the evolutionary process. Because emergence of STEC O157:H7 as a clinically significant pathogen was associated with acquisition of the Stx2a-encoding phage, the emergence of STEC O55:H7 harboring the stx2a gene is of public health concern.

Expression and functional implications of the renal apelinergic system in rodents.

Apelin binds to the G protein-coupled apelin receptor (APJ; gene name aplnr) to modulate diverse physiological systems including cardiovascular function, and hydromineral and metabolic balance. Recently a second endogenous ligand for APJ, named apela, has been discovered. We confirm that apela activates signal transduction pathways (ERK activation) in cells expressing the cloned rat APJ. Previous studies suggest that exogenous apela is diuretic, attributable wholly or in part to an action on renal APJ. Thus far the cellular distribution of apela in the kidney has not been reported. We have utilized in situ hybridization histochemistry to reveal strong apela labelling in the inner medulla (IM), with lower levels observed in the inner stripe of the outer medulla (ISOM), of rat and mouse kidneys. This contrasts with renal aplnr expression where the converse is apparent, with intense labelling in the ISOM (consistent with vasa recta labelling) and low-moderate hybridization in the IM, in addition to labelling of glomeruli. Apelin is found in sparsely distributed cells amongst more prevalent aplnr-labelled cells in extra-tubular regions of the medulla. This expression profile is supported by RNA-Seq data that shows that apela, but not apelin or aplnr, is highly expressed in microdissected rat kidney tubules. If endogenous tubular apela promotes diuresis in the kidney it could conceivably do this by interacting with APJ in vasculature, or via an unknown receptor in the tubules. The comparative distribution of apela, apelin and aplnr in the rodent kidney lays the foundation for future work on how the renal apelinergic system interacts.

Comparative Effectiveness of Imaging Modalities for the Diagnosis and Treatment of Intussusception: A Critically Appraised Topic.

RATIONALE AND OBJECTIVES: The purpose of this study was to critically appraise and compare the diagnostic performance of imaging modalities that are used for the diagnosis of intussusception and methods used in the treatment of ileocolic intussusception. METHODS: A focused clinical question was constructed and the literature was searched using the patient, intervention, comparison, outcome (PICO) method comparing radiography, ultrasound, and computed tomography in the detection of intussusception. The same methods were used to compare pneumatic (gas) reduction and hydrostatic (liquid) reduction using saline, water-soluble contrast, and barium. Retrieved articles were appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-Based Medicine hierarchy of validity for diagnostic studies. RESULTS: The retrieved sensitivity for the diagnosis of intussusception using plain radiography is 48% (95% confidence interval [CI], 44%-52%), with a specificity of 21% (95% CI, 18%-24%). The retrieved sensitivity for the diagnosis of intussusception using ultrasound is 97.9% (95% CI, 95%-100%), with a specificity of 97.8% (95% CI, 97%-99%). Based on a good quality meta-analysis, the combined success rate of gas enema reduction was shown to be 82.7% (95% CI, 79.9%-85.6%) compared to a combined success rate of 69.6% (95% CI, 65.0%-74.1%) for liquid enema reduction. CONCLUSIONS: The best available evidence recommends ultrasound as the diagnostic modality of choice for the diagnosis of ileocolic intussusception in children. In stable children without signs of peritonism, nonoperative reduction is the treatment of choice. Pneumatic (gas) reduction enema has been shown to be superior to hydrostatic (liquid) enema reduction.

Vasopressin V1a receptors mediate the hypertensive effects of [Pyr1 ]apelin-13 in the rat rostral ventrolateral medulla.

KEY POINTS: Dysfunctions in CNS regulation of arterial blood pressure lead to an increase in sympathetic nerve activity that participates in the pathogenesis of hypertension. The apelin-apelin receptor system affects arterial blood pressure homeostasis; however, the central mechanisms underlying apelin-mediated changes in sympathetic nerve activity and blood pressure have not been clarified. We explored the mechanisms involved in the regulation of [Pyr1 ]apelin-13-mediated cardiovascular control within the rostral ventrolateral medulla (RVLM) using selective receptor antagonists. We show that [Pyr1 ]apelin-13 acts as a modulating neurotransmitter in the normotensive RVLM to affect vascular tone through interaction with the vasopressin V1a receptor but that [Pyr1 ]apelin-13-induced sympathoexcitation is independent of angiotensin II receptor type 1, oxytocin, ionotropic glutamate and GABAA receptors. Our data confirm a role for the apelin peptide system in cardiovascular regulation at the level of the RVLM and highlight that this system is a possible potential therapeutic target for the treatment of hypertension. ABSTRACT: Apelin is a ubiquitous peptide that can elevate arterial blood pressure (ABP) yet understanding of the mechanisms involved remain incomplete. Bilateral microinjection of [Pyr1 ]apelin-13 into the rostral ventrolateral medulla (RVLM), a major source of sympathoexcitatory neurones, increases ABP and sympathetic nerve activity. We aimed to investigate the potential involvement of neurotransmitter systems through which the apelin pressor response may occur within the RVLM. Adult male Wistar rats were anaesthetized and ABP was monitored via a femoral arterial catheter. Bilateral RVLM microinjection of [Pyr1 ]apelin-13 significantly increased ABP (9 ± 1 mmHg) compared to saline (-1 ± 2mmHg; P < 0.001), which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 ± 1 mmHg; P < 0.01). The rise in ABP was associated with an increase in the low frequency spectra of systolic BP (13.9 ± 4.3% total power; P < 0.001), indicative of sympathetic vasomotor activation. The [Pyr1 ]apelin-13-mediated pressor response and the increased low frequency spectra of systolic BP response were fully maintained despite RVLM pretreatment with the angiotensin II type 1 receptor antagonist losartan, the oxytocin receptor antagonist desGly-NH2 , d(CH2 )5 [D-Tyr2 ,Thr4 ]OVT, the ionotropic glutamate receptor antagonist kynurenate or the GABAA antagonist bicuculline (P > 0.05). By contrast, the [Pyr1 ]apelin-13 induced pressor and sympathoexcitatory effects were abolished by pretreatment of the RVLM with the vasopressin V1a receptor antagonist, SR 49059 (-1 ± 1 mmHg; 1.1 ± 1.1% total power, respectively; P < 0.001). These findings suggest that the pressor action of [Pyr1 ]apelin-13 in the RVLM of normotensive rats is not mediated via angiotensin II type 1 receptor, oxytocin, ionotropic glutamate or GABAA receptors but instead involves a close relationship with the neuropeptide modulator vasopressin.

Housing Instability and Children's Health Insurance Gaps.

OBJECTIVE: To assess the extent to which housing instability is associated with gaps in health insurance coverage of preschool-age children. METHODS: Secondary analysis of data from the Early Childhood Longitudinal Study-Birth Cohort, a nationally representative study of children born in the United States in 2001, was conducted to investigate associations between unstable housing-homelessness, multiple moves, or living with others and not paying rent-and children's subsequent health insurance gaps. Logistic regression was used to adjust for potentially confounding factors. RESULTS: Ten percent of children were unstably housed at age 2, and 11% had a gap in health insurance between ages 2 and 4. Unstably housed children were more likely to have gaps in insurance compared to stably housed children (16% vs 10%). Controlling for potentially confounding factors, the odds of a child insurance gap were significantly higher in unstably housed families than in stably housed families (adjusted odds ratio 1.27; 95% confidence interval 1.01-1.61). The association was similar in alternative model specifications. CONCLUSIONS: In a US nationally representative birth cohort, children who were unstably housed at age 2 were at higher risk, compared to their stably housed counterparts, of experiencing health insurance gaps between ages 2 and 4 years. The findings from this study suggest that policy efforts to delink health insurance renewal processes from mailing addresses, and potentially routine screenings for housing instability as well as referrals to appropriate resources by pediatricians, would help unstably housed children maintain health insurance.