Detection of Pre-clinical Involvement of the Second Eye in Viral Acute Retinal Necrosis Using Optical Coherence Tomography.

PURPOSE: To report the detection of retinitis in the second eye of a patient with viral acute retinal necrosis (ARN), before the appearance of clinical change, using swept-source optical coherence tomography. RESULTS: A 63 year-old male developed right-sided varicella-zoster virus (VZV) ARN, confirmed with aqueous sampling. High-dose intravenous aciclovir caused renal impairment and was suspended for two-days. One day later, left eye macular SS-OCT revealed focal retinal thickening and disruption of retinal architecture without clinically detectable retinitis. The patient was asymptomatic. Aqueous sampling was VZV PCR positive. He received bilateral foscarnet injections and renal adjusted dose of aciclovir. The left OCT signs improved with full restoration of retinal layers. CONCLUSIONS: We report for the first time the use of OCT to detect pre-clinical second eye retinitis during ARN. Prompt diagnosis and combined systemic and intensive local antiviral therapy resulted in a favourable structural and functional outcome.

Management of Ganciclovir Resistant Cytomegalovirus Retinitis in a Solid Organ Transplant Recipient: A Review of Current Evidence and Treatment Approaches.

Purpose: Cytomegalovirus retinitis (CMVR) is a serious and potentially sight-threatening infection in immunocompromised individuals. Strategies for the management of drug-resistant CMVR are described. Methods: A case of severe bilateral CMVR in a single lung transplant patient, with UL97 mutation conferring ganciclovir-resistance, is presented. Treatment with standard antiviral agent and adjuvant leflunomide, immunosuppression modifications (calcineurin inhibitors and corticosteroid), intravitreal antiviral therapy and novel use of CMV-immunoglobulin is described. A literature review to support drug-resistant CMVR management is presented. Results: Severe and progressive CMV retinitis was refractory to intravitreal foscarnet and systemic leflunomide. Drug-toxicity restricted systemic antiviral therapy options. The use of combined leflunomide and CMV-immunoglobulins, in the absence of viremia, has not been previously reported. Loss of ganciclovir-resistance was eventually observed permitting successful treatment with systemic and intravitreal ganciclovir. Conclusions: Drug-resistant CMVR is a complex clinical challenge. Multiple systemic and local treatment strategies may be necessary but toxicity, resistance, and co-morbidities may severely restrict available options.

Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

Does oral carbohydrate supplementation improve labour outcome? A systematic review and individual patient data meta-analysis.

BACKGROUND: Labour is a period of significant physical activity. The importance of carbohydrate intake to improve outcome has been recognised in sports medicine and general surgery. OBJECTIVES: To assess the effect of oral carbohydrate supplementation on labour outcomes. SEARCH STRATEGY: MEDLINE (1966-2014), Embase, the Cochrane Library and clinical trial registries. SELECTION CRITERIA: Randomised controlled trials (RCT) of women randomised to receive oral carbohydrate in labour (<6 cm dilated), versus placebo or standard care. DATA COLLECTION AND ANALYSIS: Authors were contacted to provide data. Individual patient data meta-analyses were performed to calculate pooled risk ratios (RR) and 95% confidence intervals (CI). MAIN RESULTS: Eight RCTs met the inclusion criteria. Six authors responded, four supplied data (n = 691). Three studies used isotonic drinks (one placebo-controlled, two compared with standard care), and one an advice booklet regarding carbohydrate intake. The mean difference in energy intake between the intervention and control groups was small [three studies, 195 kilocalories (kcal), 95% CI 118-273]. There was no difference in the risk of caesarean section (RR 1.15, 95% CI 0.83- 1.61), instrumental birth (RR 1.26, 95% CI 0.96-1.66) or syntocinon augmentation (RR 0.99, 95% CI 0.86-1.13). Length of labour was similar (mean difference -3.15 minutes, 95% CI -35.14 to 41.95). Restricting the analysis to primigravid women did not affect the result. Oral carbohydrates did not increase the risk of vomiting (RR 1.09, 95% CI 0.78-1.52) or 1-minute Apgar score <7 (RR 1.23, 95% CI 0.82-1.83). AUTHORS' CONCLUSION: Oral carbohydrate supplements in small quantities did not alter labour outcome. TWEETABLE ABSTRACT: Oral carbohydrate does not affect labour. But the difference between intervention and control equals 10 teaspoons sugar.

Bioenergetic analysis of human peripheral blood mononuclear cells.

Leucocytes respond rapidly to pathogenic and other insults, with responses ranging from cytokine production to migration and phagocytosis. These are bioenergetically expensive, and increased glycolytic flux provides adenosine triphosphate (ATP) rapidly to support these essential functions. However, much of this work is from animal studies. To understand more clearly the relative role of glycolysis and oxidative phosphorylation in human leucocytes, especially their utility in a translational research setting, we undertook a study of human peripheral blood mononuclear cells (MNCs) bioenergetics. Glycolysis was essential during lipopolysaccharide (LPS)-mediated interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α production, as 2-deoxy-D-glucose decreased significantly the output of all three cytokines. After optimizing cell numbers and the concentrations of all activators and inhibitors, oxidative phosphorylation and glycolysis profiles of fresh and cryopreserved/resuscitated MNCs were determined to explore the utility of MNCs for determining the bioenergetics health profile in multiple clinical settings. While the LPS-induced cytokine response did not differ significantly between fresh and resuscitated cells from the same donors, cryopreservation/resuscitation significantly affected mainly some measures of oxidative phosphorylation, but also glycolysis. Bioenergetics analysis of human MNCs provides a quick, effective means to measure the bioenergetics health index of many individuals, but cryopreserved cells are not suitable for such an analysis. The translational utility of this approach was tested by comparing MNCs of pregnant and non-pregnant women to reveal increased bioenergetics health index with pregnancy but significantly reduced basal glycolysis and glycolytic capacity. More detailed analysis of discrete leucocyte populations would be required to understand the relative roles of glycolysis and oxidative phosphorylation during inflammation and other immune responses.

Rest and recuperation in the UK Armed Forces.

BACKGROUND: Recent epidemiological evidence suggests that military personnel commonly remain psychologically resilient in the face of adversity they face on deployment. However, the processes that promote resilience have not been well assessed within the UK military. For many years, the UK Armed Forces have operated a policy of rest and recuperation (R&R), which refers to the brief period during which troops return home when on an operational tour of duty. While R&R is thought to play an import ant role in promoting recovery and well-being, there is as yet no empirical evidence to support its effectiveness. AIMS: To explore whether R&R promotes well-being and recovery from the strains of deployment in military personnel. METHODS: Participants completed self-report measures of mental health and exposure to potentially traumatic events (PTEs), as well as an R&R Recovery Questionnaire (R&RRQ). RESULTS: Statistical analysis indicated that the R&RRQ was a reliable measure within the sample of 97 subjects. Participants who reported recovery following R&R reported fewer symptoms of mental health difficulties. However, increased deployment exposure to PTEs was associated with feeling less recovered at the end of R&R. CONCLUSIONS: These preliminary data suggest that R&R can be useful for troops if they can use the time to recover. This study's results are relevant to policymakers and leaders in the military and other groups placed in challenging environments but more work is needed to understand how R&R works and to maximize its capacity to promote well-being among military personnel.

Cannabidivarin is anticonvulsant in mouse and rat.

BACKGROUND AND PURPOSE: Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. EXPERIMENTAL APPROACH: The effect of CBDV (1-100 µM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg(2+) -free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg·kg(-1) ) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays. KEY RESULTS: CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg(2+) -free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg(-1) ), audiogenic (≥50 mg·kg(-1) ) and PTZ-induced seizures (≥100 mg·kg(-1) ). CBDV (200 mg·kg(-1) ) alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function. CONCLUSIONS AND IMPLICATIONS: These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti-epileptic in chronic epilepsy models. LINKED ARTICLES: This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8.

Towards a differentiated understanding of active travel behaviour: using social theory to explore everyday commuting.

Fostering physical activity is an established public health priority for the primary prevention of a variety of chronic diseases. One promising population approach is to seek to embed physical activity in everyday lives by promoting walking and cycling to and from work ('active commuting') as an alternative to driving. Predominantly quantitative epidemiological studies have investigated travel behaviours, their determinants and how they may be changed towards more active choices. This study aimed to depart from narrow behavioural approaches to travel and investigate the social context of commuting with qualitative social research methods. Within a social practice theory framework, we explored how people describe their commuting experiences and make commuting decisions, and how travel behaviour is embedded in and shaped by commuters' complex social worlds. Forty-nine semi-structured interviews and eighteen photo-elicitation interviews with accompanying field notes were conducted with a subset of the Commuting and Health in Cambridge study cohort, based in the UK. The findings are discussed in terms of three particularly pertinent facets of the commuting experience. Firstly, choice and decisions are shaped by the constantly changing and fluid nature of commuters' social worlds. Secondly, participants express ambiguities in relation to their reasoning, ambitions and identities as commuters. Finally, commuting needs to be understood as an embodied and emotional practice. With this in mind, we suggest that everyday decision-making in commuting requires the tactical negotiation of these complexities. This study can help to explain the limitations of more quantitative and static models and frameworks in predicting travel behaviour and identify future research directions.

Integrating children's services in England: national evaluation of children's trusts.

BACKGROUND: Poor co-ordination of services can have severe consequences for disadvantaged children with complex needs. Since 2003 national and local governments in England embarked on sweeping reforms aimed at improving and integrating local health, education and social services for children. These were to be organized locally by children's trusts and piloted by 35 children's trust pathfinders. METHODS: This study described and compared the experience of integrating children's services in all 35 children's trust pathfinders, covering 20% of children in England. It had a prospective mixed-methods design. Over 3 years we interviewed 147 managers and professionals working in the children's trusts, including 172 semi-structured interviews, carried out two questionnaire surveys of the 35 children's trusts and analysed official documents. RESULTS: In most areas different agencies jointly commissioned children's services, especially for mental health, disabilities and multi-purpose children's centres, and increasingly pooled finances. Provision of multi-agency and multi-professional services was increasing. Professionals generally supported these changes but found them stressful. All children's trusts appointed directors of children's services and established boards representing multiple agencies. Systems for sharing information about individual children were mostly in place but were still underused. Health services were generally less involved in joint work than were local authorities' education and social care services, with notable exceptions. Areas where local authorities and health authorities shared geographical boundaries made most progress. Some children's trusts made few changes beyond their statutory obligations. CONCLUSION: Children's trusts enabled major changes to services in areas where local actors and organizations were motivated and empowered. In other areas the remit of children's trusts was often too broad and vague to overcome entrenched organizational and professional divisions and interests. Policymakers need to balance facilitation of change in areas with dynamic change agents with methods for ensuring that dormant areas and agencies are not left behind.

Distribution and clearance of bioadhesive formulations from the olfactory region in man: effect of polymer type and nasal delivery device.

There is an increasing need to identify novel approaches by which to improve the efficiency of drug transport from the nasal cavity (olfactory region) to the CNS, especially for treatment of central nervous system disorders. It is suggested, that one approach is the combination of active targeting of a bioadhesive formulation, that will retain the drug at the absorption site, potentially in combination with, an absorption enhancer. Two low methylated pectins, LM-5 and LM-12 were selected for evaluation as drug delivery systems, due to their ability to gel in the nasal cavity and their bioadhesive characteristics, together with chitosan G210, which acts both as a bioadhesive material and as an efficient absorption enhancer. It was found that all of the bioadhesive formulations were able to reach the olfactory region in the nasal cavity of human volunteers when delivered using a simple nasal drop device. Furthermore, the formulations displayed a significantly increased residence time on the epithelial surface. This was in contrast to a non-bioadhesive control delivered with the same device. In contrast, a pectin formulation administered with a nasal spray system did not show an increase in residence time in the olfactory region. It was further shown that the reproducibility of olfactory delivery of a polymer formulation was significantly better intra-subject than inter-subject.

Cocaine: what role does it have in current ENT practice? A review of the current literature.

Topical cocaine is used by many otorhinolaryngologists because of its good local anaesthetic and vasoconstrictive properties. A review of the available literature suggests a risk/benefit analysis would suggest that in the out-patient setting local anaesthetic agents which do not contain cocaine should be used. For rhinosurgical procedures, preparations containing cocaine and adrenaline in the appropriate concentrations and doseage are safe in the vast majority of patients without previous cardiac disease. The relative benefit of using cocaine in relation to other topical analgesics and vasoconstrictors in surgery remains unproven and alternative preparations should be used wherever there is concern over the cardiac status of the patient. It is important to be alert to the possibility that patients presenting with a septal perforation or destructive midfacial lesions may be suffering from an addiction to cocaine. It is important to arrive at the correct diagnosis in a destructive process and even in the presence of raised antineutrophilic cytoplasmic antibodies (ANCA) a diagnosis of cocaine abuse should actively be excluded.

What are children's trusts? Early findings from a national survey.

BACKGROUND: The Children Act 2004 and National Service Framework for Children, Young People and Maternity Services require fuller integration of health, education and social services for children and young people in England and Wales. The UK government supported the establishment of 35 experimental children's trust pathfinders (henceforth called children's trusts) in England. METHODS: A questionnaire was completed by managers in all 35 children's trusts a year after their start. Children's trust documents were examined. Census and performance indicators were compared between children's trust areas and the rest of England. RESULTS: Children's trust areas had demographic and social characteristics typical of England. All children's trusts aimed to improve health, education and social services by greater managerial and service integration. All had boards representing the three sectors; other agencies' representation varied. Two-thirds of children's trusts had moved towards pooling budgets in at least some service areas. At this stage in their development, some had prioritized joint procurement or provision of services, with formal managerial structures, while others favoured an informal strategic planning, co-ordination and information sharing approach. The commonest priorities for services development were for disabled children (16 children's trusts), followed by early intervention (11) and mental health services (8). CONCLUSIONS: The diverse strategies adopted by these 35 children's trusts during their first year is due to their own characteristics and to the way government strategy developed during this period. Whilst some prioritized organizational development, joint financing and commissioning, and information sharing, others laid more emphasis on mechanisms for bringing front-line professionals closer together. Their experiences are of value to others deciding how best to integrate children's services.

Al cluster superatoms as halogens in polyhalides and as alkaline earths in iodide salts.

Two classes of gas-phase aluminum-iodine clusters have been identified whose stability and reactivity can be understood in terms of the spherical shell jellium model. Experimental reactivity studies show that the Al13I-x clusters exhibit pronounced stability for even numbers of I atoms. Theoretical investigations reveal that the enhanced stability is associated with complementary pairs of I atoms occupying the on-top sites on the opposing Al atoms of the Al13- core. We also report the existence of another series, Al14I-x, that exhibits stability for odd numbers of I atoms. This series can be described as consisting of an Al14I-3 core upon which the I atoms occupy on-top locations around the Al atoms. The potential synthetic utility of superatom chemistry built upon these motifs is addressed.

'Entopy': localized mucosal allergic disease in the absence of systemic responses for atopy.

BACKGROUND: The Th2 immune response in the nasal mucosa of subjects with allergic rhinitis is mediated by allergen-specific IgE. Moreover, these subjects show positive responses for markers of systemic atopy, including allergen-specific skin sensitivity and raised serum IgE titres. In contrast, idiopathic rhinitis (IR) subjects with similar histological nasal mucosal features differ in being defined as non-allergic because they have negative atopic responses. OBJECTIVE: We hypothesized that it is possible to have an allergic Th2 disease pathway localized in the nasal mucosa of 'non-allergic' rhinitis subjects despite an absence of atopic responses. METHODS: The presence of house dust mite and grass pollen-specific IgE antibodies was investigated in non-atopic (n=10) and atopic (n=11) subjects with persistent rhinitis and compared to normal (n=12) control subjects. Biotin-labelled allergen was used to localize specific allergen-binding antibodies in situ in sections of nasal mucosa. RESULTS: Grass pollen allergen binding was detected in the nasal mucosa of 3/10 non-atopic IR subjects but, in contrast, dust mite-specific antibodies were not detected. Specific antibodies were present in a total of 8/11 mucosal samples from the allergic group, but none was detected in normal control tissues. CONCLUSION: These findings support the concept of localized nasal allergy in 'non-atopic' rhinitis subjects. We propose the term 'entopy' to define this phenomenon and believe that this concept has a wider implication for localized allergic responses in other mucosal sites.

Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?

BACKGROUND: The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. METHODS: Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. RESULTS: All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. CONCLUSION: A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests 'localized allergy' may exist in the absence of systemic atopic markers.

Antimicrobial activity of extracts of eastern North American hardwood trees and relation to traditional medicine.

Wood and bark extracts of 14 eastern North American hardwood tree species which were used traditionally as medicine by First Nation's people were screened for antimicrobial activities with eight strains of bacteria and six strains of fungi. Eighty-six percent of the bark extracts were active against methicillin sensitive Staphylococcus aureus; 71% against Bacillus subtilus and 79% against Mycobacterium phlei. The bark extract of Juglans cinerea was active against Pseudomonas aeruginosa 187, Salmonella typhiumurium, and Klebsiella pneumoniae. The wood extracts were less active: 72% were active against S. aureus (methicillin-sensitive), 36% against B. subtilus and 43% against M. phlei. Results from antifungal tests indicated that 36% of the extracts were active against at least one fungal strain and that bark extracts were more active than wood extracts. The bark extract from Juglans cinerea had the broadest spectrum of activities against Candida albicans, Saccharomyces cerevisiae, Cryptococcus neoformans, Trichophyton mentagrophytes, Microsporum gypseum, and Aspergillus fumigatus. In general, the extracts were more active against gram positive bacteria than gram negative bacteria and against filamentous fungi than yeast-like fungi. The study also demonstrated a correlation between frequency of traditional medicinal use by the First Nations people and antimicrobial activity of extracts indicating that the traditional knowledge encompasses an understanding of aspects of chemical ecology.

Antifungal activity of extracts from medicinal plants used by First Nations Peoples of eastern Canada.

From literature describing medicinal usage of plants by First Nations Peoples in eastern Canada, 18 eastern Canadian plants were selected and tested for their antifungal activities. Eight randomly selected tropical plants were also tested for comparative purposes. Four groups of plants were obtained: popular antimicrobial-remedy (n=6), popular non-antimicrobial-remedy (n=6), random temperate (n=6) and random tropical (n=8). Extracts from these plants were tested in disk assays as growth inhibitors of six fungi known to be opportunistic human pathogens (Saccharomyces cerevisiae, Cryptococcus neoformans, Candida albicans, Aspergillus fumigatus, Microsporum gypseum and Trichophyton mentagrophytes). Of the four plant groups tested, extracts from the popular antimicrobial-remedy group were significantly more effective at inhibiting fungal growth based on both overall antifungal activity and number of fungal species inhibited.

Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist: investigations into possible mechanism of action in vivo.

The mechanisms underlying the neuroprotective effects of the group II metabotropic glutamate receptor (mGluR) agonist LY379268 were investigated in a gerbil model of global ischemia. LY379268 (10 mg/kg i.p.) 30 or 60 min after 5-min bilateral carotid artery occlusion (BCAO) attenuated the ischemia-induced hyperactivity and provided protection in the CA1 hippocampal cells. This neuroprotective effect was maintained (P <.001) when histological analysis was performed 14 and 28 days after BCAO. Furthermore, 24- or 48-h pretreatment with LY379268, 10 mg/kg i.p., before 5-min BCAO markedly reduced (P <.001 and P <.05, respectively) the damage to CA1 hippocampal neurons. This result is consistent with the induction of neuroprotective factors or a very long brain half-life. To study the possible induction of neuroprotective factors as contributing to this action of LY379268, brains were examined for expression of neurotrophic factors. Results indicated that LY379268 (10 mg/kg i.p.) failed to alter the expression of transforming growth factor-beta, brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor in the hippocampal regions of brains taken from gerbils sacrificed at 6, 24, 72, and 120 h postinjection. The new group II mGlu antagonist, LY341495, administered 1 h before 5-min BCAO, attenuated the neuroprotective effect of LY379268 administered 24 h before 5-min BCAO. Complementary pharmacokinetic studies showed that a significant receptor-active concentration persisted in the brain 24 h after LY379268 10 mg/kg i.p. We conclude that group II mGluR occupancy, rather than induction of neuroprotective factors, explains the long-lasting neuroprotective effect of LY379268 in the gerbil model of global ischemia.