Wearable inkjet-printed antenna performance for medical applications at 868/915 MHz

The use of biosensors attached to the body for health monitoring is now readily accepted, and the merits of such systems and their potential impact on healthcare receive much attention. Wearable medical systems used in clinical applications to monitor vital signs must be comfortable to wear, yet have robust performance to ensure reliable communications links. Additionally, and vital to the success of these innovations, is that these solutions are disposable to avoid risk of patient infection and this means that they must be ultra-low cost. Antennas optimized for printing using conductive inks offer new exciting advances in making a truly disposable solution.

Clozapine-induced liver injury and pleural effusion

Clozapine, whilst associated commonly with a transient and benign increase in liver enzymes, has also been associated with varying presentations of hepatitis in existing case reports. This report describes what we believe to be the first documented case of acute liver injury and pleural effusion associated with clozapine, resolving after cessation of the agent. The case supports existing literature in advocating a high index of suspicion, particularly in the 4-5 weeks following clozapine initiation, when considering nonspecific clinical symptoms and signs.

Presentation of lacrimo-auriculodento- digital (LADD) syndrome in a young female patient

BACKGROUND: Lacrimo-auriculo-dento-digital (LADD) syndrome (OMIM #149730) is an autosomal-dominant congenital disorder that can be caused by heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 (FGFR2) and 3 (FGFR3), and has been found in association with a mutation in the FGF10 gene, which encodes an Fgfr ligand. Clinical signs vary, but the condition is characterised by involvement of the lacrimal and salivary systems, cup-shaped ears, hearing loss and dental abnormalities. Additional features may include involvement of the hands and feet with other body systems particularly the kidneys.

CASE REPORT: Previous literature on the subject has been reviewed and this case is the first presentation of LADD syndrome in the Republic of Ireland, as a sporadic case in a 12-year-old girl who exhibited a range of dental and digital anomalies.

TREATMENT: Her general medical practitioner managed her medical care whilst her oral care necessitated a multidisciplinary approach involving restorative and orthodontic elements.

FOLLOW-UP: The initial restorative phase of treatment has successfully improved the appearance of the patient's anterior teeth using direct resin composite build-ups.

Periodontal Manifestations of Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE) Syndrome in an 11 Year Old Patient

Introduction: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) is an auto inflammatory syndrome caused by an autosomal recessive gene mutation. This very rare syndrome has been reported in only 14 patients worldwide. A number of clinical signs have been reported including joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced childhood lipodystrophy. Further symptoms include recurrent fevers, purpuric skin lesions, periorbital erythema and failure to thrive. This is the first reported case of periodontal manifestations associated with CANDLE syndrome. 
Case Presentation: An 11 year old boy was referred to Cork University Dental School and Hospital with evidence of severe periodontal destruction. The patient’s medical condition was managed in Great Ormond Street Children’s Hospital, London. The patient’s dental management included initial treatment to remove teeth of hopeless prognosis followed by prosthodontic rehabilitation using removable partial dentures. This was followed by further non-surgical periodontal treatment and maintenance. In the long term, the potential definitive restorative options, including dental implants, will be evaluated in discussion with the patient’s medical team.
Conclusion: Periodontitis as a manifestation of systemic disease is one of seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system. A number of systemic diseases have been associated with advanced periodontal destruction including Diabetes Mellitus, Leukaemia and Papillon-Lefevre Syndrome. In the case described, treatment necessitated a multidisciplinary approach with input from medical and dental specialities for a young patient with severe periodontal destruction associated with CANDLE syndrome.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study

Background: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.

Methods: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).

Findings: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min).

Interpretation: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.

Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets

The purpose of this study was to determine serum profiles of cytokines at a protein level and Creactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age. Four of the infected piglets developed severe PMWS at 14 to 21 days post-infection (d.p.i.) and died prior to termination of the experiment. The remaining six PCV2-infected piglets experienced transient fever, but did not display overt clinical signs of PMWS and were considered as subclinically infected. A bioassay was used to detect IL-6 and ELISAs were used to detect IFN-alpha, IL-10, and CRP. There were no significant differences in cytokine or CRP expression from 0 to 7 d.p.i. between the PMWS-affected and the subclinically infected piglets. Levels of IL-10 and CRP were elevated from 10 and 14 d.p.i. respectively in the PMWS-affected piglets compared to the subclinically infected piglets. There were no significant differences in IFN-alpha and IL-6 expression between the PMWS-affected piglets and the subclinically infected piglets. The present study shows that elevated levels of serum CRP and IL-10 were associated with PCV2-infected piglets that subsequently developed severe PMWS. This may help to provide further insight into the immunoaetiogenesis of this syndrome.

Legalizing physician-assisted suicide and/or euthanasia: Pragmatic implications

Objective: Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated-particularly around ethical and legal issues-and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community.

Method: We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized.

Results: We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered.

Significance of Results: Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.

Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review

Background: There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias. 

Objective: Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture. 

Design: Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria. 

Setting: Critical care departments within NHS hospitals in the north-west of England. 

Participants: Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation. 

Main outcome measures: SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard. 

Results: Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4–16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy. 

Conclusion: SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error.

Grazing under experimental hypercapnia and elevated temperature does not affect the radula of a chiton (Mollusca, Polyplacophora, Lepidopleurida)

Chitons (class Polyplacophora) are benthic grazing molluscs with an eight-part aragonitic shell armature. The radula, a serial tooth ribbon that extends internally more than half the length of the body, is mineralised on the active feeding teeth with iron magnetite apparently as an adaptation to constant grazing on rocky substrates. As the anterior feeding teeth are eroded they are shed and replaced with a new row. The efficient mineralisation and function of the radula could hypothetically be affected by changing oceans in two ways: changes in seawater chemistry (pH and pCO(2)) may impact the biomineralisation pathway, potentially leading to a weaker or altered density of the feeding teeth; rising temperatures could increase activity levels in these ectothermic animals, and higher feeding rates could increase wear on the feeding teeth beyond the animals' ability to synthesise, mineralise, and replace radular rows. We therefore examined the effects of pH and temperature on growth and integrity in the radula of the chiton Leptochiton asellus. Our experiment implemented three temperature (similar to 10, 15, 20 degrees C) and two pCO(2) treatments (similar to 400 mu atm, pH 8.0; similar to 2000 mu atm, pH 7.5) for six treatment groups. Animals (n = 50) were acclimated to the treatment conditions for a period of 4 weeks. This is sufficient time for growth of ca. 7-9 new tooth rows or 20% turnover of the mineralised portion. There was no significant difference in the number of new (non-mineralised) teeth or total tooth row count in any treatment. Examination of the radulae via SEM revealed no differences in microwear or breakage on the feeding cusps correlating to treatment groups. The shell valves also showed no signs of dissolution. As a lineage, chitons have survived repeated shifts in Earth's climate through geological time, and at least their radulae may be robust to future perturbations.

Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial?

Childhood wheezing is common particularly in children under the age of six years and in this age-group is generally referred to as preschool wheezing. Particular diagnostic and treatment uncertainties exist in these young children due to the difficulty in obtaining objective evidence of reversible airways narrowing and inflammation. A diagnosis of asthma depends on the presence of relevant clinical signs and symptoms and the demonstration of reversible airways narrowing on lung function testing, which is difficult to perform in young children. Few treatments are available and inhaled corticosteroids are the recommended preventer treatment in most international asthma guidelines. There is however considerable controversy about its effectiveness in children with preschool wheeze and a corticosteroid responder phenotype has not been established. These diagnostic and treatment uncertainties in conjunction with the knowledge of corticosteroid side-effects, in particular the reduction of growth velocity, has resulted in a variable approach to inhaled corticosteroid prescribing by medical practitioners and a reluctance in carers to regularly administer the treatment. Identifying children who are likely responders to corticosteroid therapy would be a major benefit in the management of this condition. Eosinophils have emerged as a promising biomarker of corticosteroid responsive airways disease and evaluation of this biomarker in sputum has successfully been employed to direct management in adults with asthma. Obtaining sputum from young children is time-consuming and difficult and it is hard to justify more invasive procedures such as a bronchoscopy in young children routinely. Recently, in children, interest has shifted to assessing the value of less invasive biomarkers of likely corticosteroid response and the biomarker 'blood eosinophils' has emerged as an attractive candidate. The aim of this review is to summarise the evidence for blood eosinophils as a predictive biomarker for corticosteroid responsive disease with a particular focus on the difficult area of preschool wheeze. 

3-Methylpiperidinium ionic liquids

A wide range of room temperature ionic liquids based on the 3-methylpiperdinium cation core were produced from 3-methylpiperidine, which is a derivative of DYTEK® A amine. First, reaction with 1-bromoalkanes or 1-bromoalkoxyalkanes generated the corresponding tertiary amines (Rmβpip, R = alkyl or alkoxyalkyl); further quaternisation reactions with the appropriate methylating agents yielded the quaternary [Rmmβpip]X salts (X(-) = I(-), [CF3CO2](-) or [OTf](-); Tf = -SO2CF3), and [Rmmβpip][NTf2] were prepared by anion metathesis from the corresponding iodides. All [NTf2](-) salts are liquids at room temperature. [Rmmβpip]X (X(-) = I(-), [CF3CO2](-) or [OTf](-)) are low-melting solids when R = alkyl, but room temperature liquids upon introduction of ether functionalities on R. Neither of the 3-methylpiperdinium ionic liquids showed any signs of crystallisation, even well below 0 °C. Some related non-C-substituted piperidinium and pyrrolidinium analogues were prepared and studied for comparison. Crystal structures of 1-hexyl-1,3-dimethylpiperidinium tetraphenylborate, 1-butyl-3-methylpiperidinium bromide, 1-(2-methoxyethyl)-1-methylpiperidinium chloride and 1-(2-methoxyethyl)-1-methylpyrrolidinium bromide are reported. Extensive structural and physical data are collected and compared to literature data, with special emphasis on the systematic study of the cation ring size and/or asymmetry effects on density, viscosity and ionic conductivity, allowing general trends to be outlined. Cyclic voltammetry shows that 3-methylpiperidinium ionic liquids, similarly to azepanium, piperidinium or pyrrolidinium counterparts, are extremely electrochemically stable; the portfolio of useful alternatives for safe and high-performing electrolytes is thus greatly extended.

Phytoremediation assessment of Gomphrena globosa and Zinnia elegans grown in arsenic-contaminated hydroponic conditions as a safe and feasible alternative to be applied in arsenic-contaminated soils of the Bengal Delta

Several agricultural fields show high contents of arsenic because of irrigation with arsenic- contaminated groundwater. Vegetables accumulate arse- nic in their edible parts when grown in contaminated soils. Polluted vegetables are one of the main sources of arsenic in the food chain, especially for people living in rural arsenic endemic villages of India and Bangladesh. The aim of this study was to assess the feasibility of floriculture in the crop rotation system of arsenic en- demic areas of the Bengal Delta. The effects of different arsenic concentrations (0, 0.5, 1.0, and 2.0 mg As L−1) and types of flowering plant (Gomphrena globosa and Zinnia elegans) on plant growth and arsenic accumula- tion were studied under hydroponic conditions. Total arsenic was quantified using atomic absorption spec- trometer with hydride generation (HG-AAS). Arsenic was mainly accumulated in the roots (72 %), followed by leaves (12 %), stems (10 %), and flowers (<1 %). The flowering plants studied did not show as high phytoremediation capacities as other wild species, suchas ferns. However, they behaved as arsenic tolerant plants and grew and bloomed well, without showing any phytotoxic signs. This study proves that floriculture could be included within the crop rotation system in arsenic-contaminated agricultural soils, in order to im- prove food safety and also food security by increasing farmer’s revenue.

Early intervention can improve outcomes in acute kidney injury

Acute Kidney Injury(AKI) is common, costly to manage and associated with high mortality. AKI can occur either in the community or in hospitalised patients and may be challenging to recognise because it is typically asymptomatic.Opportunities for prevention of AKI are frequently missed and in the absence of symptoms or signs there is often a delay in recognition ofestablished AKI.Approximately two thirds of hospitalised patients admitted with AKI have developed AKI in the community. AKI in hospitalised patients is associated with a substantial mortality rate > 20%. AKI is a potentially reversible process so improvements in recognition and early interventions could have a major impact on patient outcomes.

Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis

BACKGROUND: Seasonal/perennial allergic conjunctivitis is the most common allergic conjunctivitis, usually with acute manifestations when a person is exposed to allergens and with typical signs and symptoms including itching, redness, and tearing. The clinical signs and symptoms of allergic conjunctivitis are mediated by the release of histamine by mast cells. Histamine antagonists (also called antihistamines) inhibit the action of histamine by blocking histamine H1 receptors, antagonising the vasoconstrictor, and to a lesser extent, the vasodilator effects of histamine. Mast cell stabilisers inhibit degranulation and consequently the release of histamine by interrupting the normal chain of intracellular signals. Topical treatments include eye drops with antihistamines, mast cell stabilisers, non-steroidal anti-inflammatory drugs, combinations of the previous treatments, and corticosteroids. Standard treatment is based on topical antihistamines alone or topical mast cell stabilisers alone or a combination of treatments. There is clinical uncertainty about the relative efficacy and safety of topical treatment.

OBJECTIVES: The objective of this review was to assess the effects of topical antihistamines and mast cell stabilisers, alone or in combination, for use in treating seasonal and perennial allergic conjunctivitis.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2014), EMBASE (January 1980 to July 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 17 July 2014. We also searched the reference lists of review articles and relevant trial reports for details of further relevant publications.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing topical antihistamine and mast cell stabilisers, alone or in combination, with placebo, no treatment or to any other antihistamine or mast cell stabiliser, or both, that examined people with seasonal or perennial allergic conjunctivitis, or both. The primary outcome was any participant-reported evaluation (by questionnaire) of severity of four main ocular symptoms: itching, irritation, watering eye (tearing), and photophobia (dislike of light), both separately and, if possible, by an overall symptom score. We considered any follow-up time between one week and one year.

DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. Disagreements were resolved by discussion among review authors and the involvement of a third review author. We followed standard methodological approaches used by Cochrane.

MAIN RESULTS: We identified 30 trials with a total of 4344 participants randomised, with 17 different drugs or treatment comparisons. The following antihistamines and mast cell stabilisers were evaluated in at least one RCT: nedocromil sodium or sodium cromoglycate, olopatadine, ketotifen, azelastine, emedastine, levocabastine (or levocabastine), mequitazine, bepotastine besilate, combination of antazoline and tetryzoline, combination of levocabastine and pemirolast potassium. The most common comparison was azelastine versus placebo (nine studies).We observed a large variability in reporting outcomes. The quality of the studies and reporting was variable, but overall the risk of bias was low. Trials evaluated only short-term effects, with a range of treatment of one to eight weeks. Meta-analysis was only possible in one comparison (olopatadine versus ketotifen). There was some evidence to support that topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo. There were no reported serious adverse events related to the use of topical antihistamine and mast cell stabilisers treatment.

AUTHORS' CONCLUSIONS: It seems that all reported topical antihistamines and mast cell stabilisers reduce symptoms and signs of seasonal allergic conjunctivitis when compared with placebo in the short term. However, there is no long-term data on their efficacy. Direct comparisons of different antihistamines and mast cell stabilisers need to be interpreted with caution. Overall, topical antihistamines and mast cell stabilisers appear to be safe and well tolerated. We observed a large variability in outcomes reported. Poor quality of reporting challenged the synthesis of evidence.

The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance

Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1β expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1β. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1β expression with implications for diseases like type 2 diabetes.