Overdose risk perceptions and experience of overdose among heroin users in Cork, Ireland. Preliminary results from a pilot overdose prevention study

Background. Opioid overdose is the primary cause of death among injecting drug users (IDU). Overdose is generally not sudden, occurs over one to three hours, and often in the presence of bystanders. This presents a unique window of opportunity to intervene. Aim. Successful overdose prevention training includes appropriate clinical and non-clinical responses. The study aimed to investigate Irish IDU experience of overdose, and need for education and resuscitation skills programming. We report on pilot findings. Methods. Phase One assessed service user experience of overdose, substances used, setting for overdose, and awareness of appropriate non-clinical responses (n=52). Phase two implemented an educational intervention at two Cork addiction service sites. This involved assessing service user awareness of appropriate non-clinical methods to manage overdose and their interest in receiving resuscitation training (n=26). Phase three piloted a resuscitation skills training intervention for staff, family and IDU consisting of instruction on how to recognise and prevent overdose, appropriate response techniques; rescue breathing, and calling emergency services (n=26). Results. The findings illustrated the majority had experienced overdose, described the main substances involved, the settings, the responses employed, and the perceptions of risk. The need for education equipping IDU with overdose prevention and management skills was identified. Awareness of appropriate responses (correct emergency numbers, recovery and resuscitation skills) improved following the educational and skills training interventions Conclusions. Continued efforts in Ireland to integrate culturally specific overdose prevention into agonist opioid treatment services, prison discharge, homeless primary health and needle and syringe exchange are warranted

Neonatal epididymo-orchitis caused by Pseudomonas aeruginosa: a case report

Epididymitis and epididymo-orchitis are an uncommon causes of acute testicular pain in neonatal boys, epididymo-orchitis is infection or inflammation of epididymis and testis it's may be associated with urinary tract infections or reflux of urine predisposed by an underlying vasal anomaly. Pediatricians should examine the testicles meticulously after a baby is born

ARRAW: Anti-resonant reflecting acoustic waveguides

© 2020 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft. Development of acoustic and optoacoustic on-chip technologies calls for new solutions to guiding, storing and interfacing acoustic and optical waves in integrated silicon-on-insulator systems. One of the biggest challenges in this field is to suppress the radiative dissipation of the propagating acoustic waves, while co-localizing the optical and acoustic fields in the same region of an integrated waveguide. Here we address this problem by introducing anti-resonant reflecting acoustic waveguides (ARRAWs) - mechanical analogues of the anti-resonant reflecting optical waveguides. We discuss the principles of anti-resonant guidance and establish guidelines for designing efficient ARRAWs. Finally, we demonstrate examples of the simplest silicon/silica ARRAW platforms that can simultaneously serve as near-IR optical waveguides, and support strong backward Brillouin scattering

Oral drug delivery strategies for development of poorly water soluble drugs in paediatric patient population

Selecting the appropriate formulation and solubility-enabling technology for poorly water soluble drugs is an essential element in the development of formulations for paediatric patients. Different methodologies and structured strategies are available to select a suitable approach and guide formulation scientists for development of adult formulations. However, there is paucity of available literature for selection of technology and overcoming the challenges in paediatric formulation development. The need for flexible dosing, and the limited knowledge of the safety of many formulation excipients in paediatric subjects, impose significant constraints and in some instances require adaptation of the approaches taken to formulating these drugs for the adult population. Selection of the best drug delivery system for paediatrics requires an efficient, systematic approach that considers a drug's physical and chemical properties and the targeted patient population's requirements. This review is a step towards development of a strategy for the design of solubility enhancing paediatric formulations of highly insoluble drugs. The aim of this review is to provide an overview of different approaches and strategies to consider in order to assist development of paediatric formulation for poorly water-soluble drugs with the provision of examples of some marketed products. In addition, it provides recommendations to overcome the range of challenges posed by these strategies and adaptations of the adult approach/product presentation required to enable paediatric drug development and administration

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

PURPOSE: Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [(18)F]-flumazenil ([(18)F]-FMZ) PET could be used to non-invasively characterise GABA(A)/central benzodiazepine receptor (GABA(A)/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE. METHODS: Dynamic [(18)F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5–25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [(18)F]-FMZ PET scan (3.6–4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [(18)F]-FMZ PET data. KEY FINDINGS: The PSM was found to adequately model [(18)F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [(18)F]-FMZ binding. SIGNIFICANCE: Alterations to hippocampal GABA(A)/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [(18)F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [(18)F]-FMZ PET is useful for investigating the role that changes GABA(A)/cBZR density and binding affinity play in the pathogenesis of TLE

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Prevalence and determinants of the use of self-tests by members of the public: a mixed methods study

Background Self-tests can be used by members of the public to diagnose conditions without involving a doctor, nurse or other health professional. As technologies to design and manufacture diagnostic tests have developed, a range of self-tests have become available to the public to buy over-the-counter and via the Internet. This study aims to describe how many people have used self-tests and identify factors associated with their use. Methods A postal questionnaire will elicit basic information, including sociodemographic characteristics, and whether the person has used or would use specified self-tests. Consent will be sought to recontact people who want to participate further in the study, and interviews and focus groups will be used to develop hypotheses about factors associated with self-test use. These hypotheses will be tested in a case-control study. An in-depth questionnaire will be developed incorporating the identified factors. This will be sent to: people who have used a self-test (cases); people who have not used a self-test but would use one in the future (controls); and people who have not used and would not use a self-test (controls). Logistic regression analysis will be used to establish which factors are associated with self-test use. Discussion Self-tests do have potential benefits, for example privacy and convenience, but also potential harms, for example delay seeking treatment after a true negative result when the symptoms are actually due to another condition. It is anticipated that the outcomes from this study will include recommendations about how to improve the appropriate use of self-tests and existing health services, as well as information to prepare health professionals for patients who have used self-tests