Assessment and treatment of mental health conditions in children and adolescents: A systematic scoping review of how virtual reality environments have been used.

BACKGROUND: There is growing interest in the use of virtual reality environments (VREs) in psychological treatment and assessment. Most research has focused on the application of VREs in adult psychological disorders with fewer studies focusing on its applicability with children and adolescents. A systematic scoping review was undertaken of research assessing how VREs have been used in the treatment and assessment of childhood mental health disorders to provide an overview of the current state of the literature and identify future research directions. METHOD: Systematic searches of online databases were conducted in PsycInfo, PubMed, Embase, Scopus, and Web of Science. RESULTS: Eleven studies met eligibility criteria and were included in this review, with the majority focusing on VRE interventions for anxiety-related disorders. There is also emerging support for VRE deep breathing training for anxiety, VRE assisted treatment of internet gaming disorder and anorexia nervosa, and VRE assessment of body image evaluation in anorexia nervosa. Most studies were pilot and feasibility studies with only three randomised-controlled trials (RCT). CONCLUSIONS: The current literature shows some promise for the use of VRE assessments and interventions of childhood mental health problems, particularly for anxiety-related disorders such as social anxiety and specific phobias. However, high-quality RCTs are now needed to establish effectiveness of VREs in this population, and how it compares to existing evidence-based approaches, given its promise to improve both engagement and outcomes.

Reconsidering the relationship between health and income in the UK.

The present paper revisits and extends the examination of the long-run relationship between UK life expectancy and income provided by Tapia Granados (2012). Adopting a more detailed form of analysis, a clear break corresponding to the 1918-1919 Influenza Pandemic is identified in the long span of data examined. This finding of structural change, along with detected uncertainty regarding the orders of integration of the series examined, results in the application of split-sample analysis employing autoregressive distributed lag (ARDL) modelling. The results obtained reverse the 'no long-run relationship' conclusion of Tapia Granados (2012) with overwhelming evidence presented in support of a negative relationship between life expectancy and income. Our findings add to both health-income research and a burgeoning literature on the reproduction and replication of previously published empirical research.

Pre-clinical Formulation Development of an in situ Meglumine Salt of AZD5991: A Novel Macrocyclic Mcl-1 Inhibitor.

PURPOSE: AZD5991 is a potent and selective macrocyclic inhibitor of Mcl-1 in clinical development. Developing an intravenous solution formulation for AZD5991 proved to be challenging primarily due to the poor intrinsic solubility of AZD5991. In this article are described studies performed to select a suitable crystalline form and to assess physicochemical properties of AZD5991 to aid in the design of a solution formulation for preclinical studies. METHODS: It is preferable that the preclinical formulation has a line of sight for clinical formulation. For AZD5991, a concentration of at least 20 mg/ml was required for toxicology studies. Toward this goal, extensive pre-formulation characterization of AZD5991 including solid form analysis, pH-solubility profiling and solubility determination in cosolvents and other solubilizing media were carried out. RESULTS & DISCUSSION: Crystalline Form A, which is more stable in aqueous solution and possesses acceptable thermal stability, was selected for preclinical and clinical development of AZD5991. Extensive solubility evaluation revealed an interesting pH-solubility profile that significantly enhances solubilization at pH > 8.5 to allow solution concentrations of at least 30 mg/ml by in situ meglumine salt formation. CONCLUSION: Developing pre-clinical formulations to support in vivo studies requires a good understanding of the physicochemical properties of the drug candidates. Candidates with challenging pharmaceutic properties like the novel macrocycle molecule AZD5991, demand extensive characterization in its polymorph landscape, solubility profile and suitability evaluation of the excipients. Meglumine, a pH-adjusting and solubilizing agent, was found to be the best choice for formulating AZD5991 into an intravenous product to support preclinical studies.

The role of flavored electronic nicotine delivery systems in smoking cessation: A systematic review.

Background: Electronic nicotine delivery systems (ENDS) come in numerous flavors and may aid smoking cessation. This systematic review examines evidence on the role of ENDS flavors in smoking cessation. Methods: We searched EMBASE OVID, PsychInfo, and Medline databases for studies that: 1) examined cigarette cessation outcomes for persons using ENDS (intent, attempts, and success) and 2) reported results separated by respondent's ENDS flavor used. We extracted crude and adjusted odds ratios for associations between cessation outcomes and types of ENDS flavors used (nontobacco vs. tobacco/unflavored; nontobacco and nonmenthol vs. tobacco/unflavored and menthol). We did not consider cessation outcomes among people not using ENDS. We evaluated the evidence using the GRADE approach, focusing on consistency and reliability of findings across studies. Results: 29 studies met inclusion criteria, producing 36 odds ratios (ORs) comparing cessation outcomes across ENDS flavor groups. Three ORs examined quit intent, five examined quit attempts, and 28 examined quit success. Using GRADE, we reached Low levels of certainty that there was not an association between ENDS flavor use and intention to quit smoking or making a quit attempt. There were Very Low levels of certainty that nontobacco flavored versus tobacco/unflavored ENDS use was not associated with smoking cessation success, with similar findings for nonmenthol and nontobacco compared to tobacco and menthol flavored ENDS. Conclusion: The evidence about the role of different flavored ENDS use and smoking cessation outcomes is inconclusive, reflecting highly heterogeneous study definitions and methodological limitations. More high-quality evidence, ideally from randomized controlled trials, is required.

Mediating a host cell signaling pathway linked to overwinter mortality offers a promising therapeutic approach for improving bee health.

INTRODUCTION: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. OBJECTIVES: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. METHODS: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. RESULTS: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. CONCLUSION: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.

Exploring the Gaps in Programming for Men and Women with a Gambling Disorder in the Correctional System in Canada.

The prevalence of problem gambling in the correctional system is about 10 times higher than in the general population, but programming for gambling problems in the correctional system is scarce. Examined barriers to treatment for problem gamblers in the correctional system, sex or gender differences, and options for program design. We conducted interviews with 16 experts who had worked with problem gamblers in the correctional system and analyzed the data in terms of themes. For barriers, the experts discussed a lack of awareness about problem gambling, as well as stigmatization and lockdowns. Experts described the content of current programs as equally applicable to both men and women, but that emotional components were more important for women. Finally, the experts had mixed views on whether programming should be integrated with other programs such as substance abuse. Programming implications for this population are discussed.

Executive functioning among first time and recidivist inmates in Uruguay.

Previous research has found association between antisocial behavior and deficits in executive functioning. However, research into a link between them accounting for criminal history has found divergent results in western countries. The present study sought to determine the severity of executive functioning deficits in offenders compared to a normative sample, and the differences between first time offenders as compared to recidivists in Uruguay using a cross-sectional design. The neuropsychological performance of 334 male adult inmates was assessed using the BRIEF- A and a normative sample of 377. Results indicated that offenders performed significantly worse than non-offenders in the global score and the subscales of the BRIEF-A. Moreover, first time offenders exhibited less performance deficits in cognitive functioning than recidivist offenders. Compared to first time offenders, recidivist showed executive dysfunction concerning behavioral regulation index and globally. These results enhance our knowledge about executive dysfunction associated with criminality and may help to tailor the offenders' programs to offenders with executive deficits.

Experimental design, development and evaluation of extended release subcutaneous thermo-responsive in situ gels for small molecules in drug discovery.

The objective of this work is to develop extended release subcutaneous thermo-responsive in situ gel-forming delivery systems using the following commercially available triblock polymers: poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA, copolymer A & B) and poly (lactide-co-caprolactone)-poly (ethylene glycol)-poly (lactide-co-caprolactone) (PLCL-PEG-PLCL, copolymer C). Performance of two optimized formulations containing ketoprofen as a model compound, was assessed by comparing in vitro drug release profiles with in vivo performance following subcutaneous administration in rats. This work employs a Design of Experiment (DoE) approach to explore first, the relationship between copolymer composition, concentration, and gelation temperature (GT), and second, to identify the optimal copolymer composition and drug loading in the thermo-responsive formulation. Furthermore, this work discusses the disconnect observed between in vitro drug release and in vivo pharmacokinetic (PK) profiles. In vitro, both formulations showed extended-release profiles for 5-9 days, while PK parameters and plasma profiles were similar in vivo without extended release observed. In conclusion, a clear disconnection is observed between in vitro ketoprofen drug release and in vivo performance from the two thermogel formulations tested. This finding highlights a remaining challenge for thermogel formulation development, that is, being able to accurately predict in vivo behavior from in vitro results.

Identification of an aquaculture poriferan "Pest with Potential" and its phylogenetic implications.

Correct identification and classification of sponges is challenging due to ambiguous or misleading morphological features. A particular case is a blue keratose sponge occasionally referred to as the "Blue Photo Sponge" among aquarists, which appears frequently (and in several cases unintended) in private aquaria. This spicule-less species, occasionally specified as Collospongia auris Bergquist, Cambie & Kernan 1990, not only displays a high phenotypic plasticity in growth form and colour, it also proliferates in aquacultures under standard conditions unlike most other sponges. Therefore, this species is regarded as a pest for most aquarists. In turn, the ease of cultivation and propagation in aquacultures qualifies this species as a model organism for a wide array of scientific applications. For these purposes, correct identification and classification are indispensable. We reconstructed ribosomal gene trees and determined this species as Lendenfeldia chondrodes (De Laubenfels, 1954) (Phyllospongiinae), distant to Collospongia auris, and corroborated by skeletal features. Additionally, the resulting phylogeny corroborated major shortcomings of the current Phyllospongiinae classification-its consequences are discussed.

Quality assurance in diabetic retinal screening in South Africa.

BACKGROUND: Diabetic retinopathy (DR) is an important biomarker for microvascular disease and blindness. Digital fundus photography is a cost-effective way of screening for DR. Access to DR screening is difficult for many South Africans with diabetes. OBJECTIVE: To perform external quality assurance (EQA) on graders registered in the Ophthalmological Society of South Africa DR screening programme. METHODS: Graders registered on the South African (SA) Diabetic Register website were invited to participate in the study. The Scottish EQA software system was used to enable on-line grading of 100 retinal photographs. Expert National Health Service graders provided the consensus expert grading for the image set. RESULTS: Two hundred and sixty-one participants completed the EQA process, including nine ophthalmologists, 243 optometrists, and nine other graders. A wide range of outcomes were demonstrated, with a mean sensitivity of 0.905 (range 0.286 - 1.000) and mean specificity of 0.507 (0.000 - 0.935). The mean diagnostic odds ratio was calculated to be 12.3 (range 0.147 - 148.2). CONCLUSIONS: This is the first quality assurance study conducted with SA healthcare professionals. The outcomes are of interest to all stakeholders dealing with the diabetes epidemic. The disparity in grader performance indicates room for improvement. The results demonstrate a high referral rate to ophthalmology, suggesting that on average graders are performing safely, but with a high number of inappropriate referrals.

A single-blinded randomized clinical trial comparing polymyxin B-trimethoprim and moxifloxacin for treatment of acute conjunctivitis in children.

OBJECTIVE: To perform a randomized controlled trial comparing moxifloxacin hydrochloride with polymyxin B-trimethoprim for the treatment of acute conjunctivitis. STUDY DESIGN: Patients ages 1-18 years old with acute conjunctivitis had cultures performed and were randomized to receive either moxifloxacin hydrochloride or polymyxin B-trimethoprim ophthalmic solution for 7 days. Response to treatment was determined by phone query on day 4-6 and by examination with post-treatment conjunctival culture on day 7-10. RESULTS: One hundred and twenty-four patients were enrolled. Eighty patients (65%) had recognized pathogens (55 Haemophilus influenzae, 22 Streptococcus pneumoniae, 4 Moraxella catarrhalis) isolated from their conjunctiva. One hundred fourteen (56/62 moxifloxacin and 58/62 polymyxin B-trimethoprim) completed the 4-6 day evaluation, with 43/56 (77%) of the moxifloxacin group and 42/58 (72%) of the polymyxin B-trimethoprim group clinically cured according to parents (noninferiority test P = .04). Eighty-nine (39/56 moxifloxacin and 50/58 polymyxin B-trimethoprim) patients completed the 7-10 day evaluation. Clinical cure was observed in 37/39 (95%) of the moxifloxacin and 49/51 (96%) of the polymyxin B-trimethoprim treated groups (noninferiority test P ≤ .01). Clinical cure rates for culture positive and negative conjunctivitis were not different. There was no statistically significant difference in bacteriologic cure rates between the 2 groups. CONCLUSIONS: Polymyxin B-trimethoprim continues to be an effective treatment for acute conjunctivitis with a clinical response rate that does not differ from moxifloxacin. Use of polymyxin B-trimethoprim for the treatment of conjunctivitis would result in significant cost savings compared with fluoroquinolones.

Tongue entrapment in aluminum water bottle: discussion of removal and airway management.

Tongue entrapment in a bottle neck is rare, with few cases reported in the literature. Reported here is the case of a child who presented to the Emergency Department with her tongue entrapped in an aluminum bottle. This case is unique in that the patient had a delayed presentation resulting in significant tongue edema, requiring advanced methods for removal and airway management. These include sedated mechanical removal of the strangulating object and transnasal fiberoptic intubation. We review published cases and the options for removal of an entrapped tongue from a bottle neck, and we discuss the importance of airway management.

Horny sponges and their affairs: on the phylogenetic relationships of keratose sponges.

The demosponge orders Dictyoceratida and Dendroceratida are historically assigned to the keratose (or "horny") sponges, which are mostly devoid of primary skeletal elements, but possess an elaborate skeleton of organic fibres instead. This paucity of complex mineral skeletal elements makes their unambiguous classification and phylogenetic reconstruction based on morphological features difficult. Here we present the most comprehensive molecular phylogeny to date for the Dendroceratida, Dictyoceratida, and also other sponge orders that largely lack a mineral skeleton or skeletal elements at all (i.e. Verongida, Halisarcida, Chondrosida), based on independent mitochondrial and nuclear markers. We used molecular data to validate the coherence of all recognised orders, families and subfamilies that are currently defined using morphological characteristics. We discussed the significance of morphological and chemotaxonomic characters for keratose sponges, and suggested adapted definitions for the classification of dendroceratid, dictyoceratid, and verongid higher taxa. Also, we found that chondrosid sponges are non-monophyletic with respect to Halisarcida. Verongida and Dendroceratida were monophyletic, however most of their classically recognised families were not recovered. This indicated that the current distinction between dendritic and mesh-like fibre skeletons is not significant at this level of classification. Dysideidae were found to be the sister-group to the remaining Dictyoceratida. Irciniidae formed a distinct clade, however Thorectidae and Spongiidae could not be separated with the molecular markers used. Finally, we are establishing the name Verongimorpha for the clade combining verongid, chondrosid and halisarcid taxa and readjust the content of its sister-clade Keratosa.

Identification of Staphylococcus aureus and determination of methicillin resistance directly from positive blood cultures by isothermal amplification and a disposable detection device.

A simple, rapid, and user-friendly procedure has been developed to identify Staphylococcus aureus and determine its methicillin resistance directly from gram-positive cocci in cluster-containing blood culture medium. The specimens were diluted and heated prior to amplification of the nuc and mecA genes with isothermal helicase-dependent amplification. Amplicons were detected using a disposable detection device. The analytical sensitivity of the assays was 50 CFU per reaction, and the clinical sensitivity and specificity were both 100% for S. aureus detection and 100% and 98% for methicillin resistance determination, respectively.

Evaluating in-home water purification methods for communities in Texas on the border with Mexico

This study evaluated user preferences among three alternative in-home water treatment technologies suitable for households relying on trucked water in El Paso County, Texas, which is on the border with Mexico. The three technologies were: chlorination of household storage tanks, small-scale batch chlorination, and point-of-use ultraviolet disinfection. Fifteen households used each of the three technologies in succession for roughly four weeks each during April through June of 2004. Data were collected on treated water quality, and a face-valid survey was administered orally to assess user satisfaction with the technologies on a variety of attributes. Treatment with a counter-top ultraviolet disinfection system received statistically significantly higher ratings for taste and odor and likelihood of future use than the other two approaches. Ultraviolet disinfection and small-scale batch chlorination both received significantly higher ratings for ease of use than did storage tank chlorination. Over-chlorination was a common problem with both batch chlorination and storage tank chlorination. Water quality in the households using trucked water is now higher than was reported by a previous study, suggesting that water quality has improved over time.

Este estudio evaluó las preferencias de los consumidores de tres tecnologías domésticas para el tratamiento del agua, apropiadas para viviendas del condado de El Paso, Texas, situado en la frontera con México, que dependen del agua transportada en camiones. Las tres tecnologías fueron cloración de los tanques domésticos de almacenamiento, cloración de pequeños lotes de agua y desinfección mediante luz ultravioleta en el punto de dispensación. Quince viviendas utilizaron sucesivamente cada una de las tres tecnologías durante aproximadamente cuatro semanas entre abril y junio de 2004. Se registraron los datos sobre la calidad del agua tratada y se realizó una encuesta oral aceptada por los expertos para medir el grado de satisfacción de los usuarios con relación a diversos atributos de esas tecnologías. El tratamiento con el sistema de desinfección mediante luz ultravioleta instalado sobre la barra de la cocina tuvo una mejor valoración según el gusto y el olor del agua y una mayor probabilidad de uso futuro que los otros dos métodos. La desinfección mediante luz ultravioleta y la cloración de pequeños lotes recibieron mayor puntuación por su facilidad de uso con respecto a la cloración de los tanques de almacenamiento. La cloración excesiva fue un problema frecuente, tanto en la cloración de pequeños lotes como de los tanques de almacenamiento. La calidad del agua en las viviendas que utilizan agua transportada en camiones es ahora superior que la encontrada en estudios anteriores, lo que parece indicar que la calidad del agua ha mejorado.

A feasibility study on direct assay of an aqueous formulation by chiral supercritical fluid chromatography (SFC).

Supercritical fluid chromatography (SFC) has gained considerable importance in the area of Separation Science in pharmaceutical analysis over the past few years. The synthesis of chiral compounds is of particular significance in the pursuit of new drug entities. SFC is rapidly replacing high performance liquid chromatography (HPLC) in many pharmaceutical and biotechnological companies as the standard screening and method development tool for chiral compounds. Analysis of pharmaceutical formulations of research compounds is an area where SFC is recently being explored as a possible alternate or complementary technique to HPLC in limited scope. A feasibility study was carried out to perform direct assay of a chiral drug compound AZM in 100% aqueous formulations by SFC. The results indicated that this approach has the potential to significantly reduce the typical sample processing time prior to analysis. The method was reproducible, linear over a wide dynamic range, and sensitive enough to detect the minor enantiomeric impurity in the chiral drug compound investigated here. Further application will be pursued for other research compounds in the future to illustrate the broader applicability of this approach.

Evaluating in-home water purification methods for communities in Texas on the border with Mexico.

This study evaluated user preferences among three alternative in-home water treatment technologies suitable for households relying on trucked water in El Paso County, Texas, which is on the border with Mexico. The three technologies were: chlorination of household storage tanks, small-scale batch chlorination, and point-of-use ultraviolet disinfection. Fifteen households used each of the three technologies in succession for roughly four weeks each during April through June of 2004. Data were collected on treated water quality, and a face-valid survey was administered orally to assess user satisfaction with the technologies on a variety of attributes. Treatment with a counter-top ultraviolet disinfection system received statistically significantly higher ratings for taste and odor and likelihood of future use than the other two approaches. Ultraviolet disinfection and small-scale batch chlorination both received significantly higher ratings for ease of use than did storage tank chlorination. Over-chlorination was a common problem with both batch chlorination and storage tank chlorination. Water quality in the households using trucked water is now higher than was reported by a previous study, suggesting that water quality has improved over time.