Rapidly Dissolving Polymeric Microneedle Skin Patch of Naloxone for Opioid Overdose Treatment Tijani Akeemat1, Maria J. Peláez2, Prashant Dogra2,3, Ashana Puri1 1 Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614. 2 Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA 3 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA Worldwide opioid abuse affects over 16 million people. A major cause of death in abusers is overdosing. Naloxone (NAL) is an opioid inhibitor that reverses its respiratory depressing effect. The use of this drug is limited mostly to invasive delivery: intravenous (IV), intramuscular (IM) and subcutaneous (SC) due to its significant hepatic clearance and poor oral bioavailability (2%). These routes are painful and worse still is the need for frequent injections for patient stabilization due to the short half-life of NAL. Non-invasive intranasal forms exist but this is fraught with a couple of limitations such as nasal damage and epistaxis. The need for alternatives without these limitations is thus evident. The feasibility of the use of metal microneedles (MNs) for the transdermal delivery of NAL was demonstrated in-vitro and through in-vitro in-vivo correlation modeling in our lab. The goal of the current study was to design a rapidly dissolving polymeric MN patch with delivery and pharmacokinetic (PK) properties comparable to that seen with the commercially available NAL products, eliminating their highlighted limitations. NAL loaded rapidly dissolving polyvinyl pyrrolidone-based MN arrays (500 µm, 100 needles) were fabricated by the mold casting technique. The permeation profile of fabricated MNs over a predetermined time were assessed via an in-vitro permeation set up using porcine ear skin. Samples were analyzed via HPLC. To improve on drug flux and amount permeated, the effect of increasing MN length and density (no. of needles/unit area) were assessed by fabricating MNs 300 µm longer and those with density double that of the initial array. Factors such as drug load and polymer strength influenced the needle fabrication. Compared to passive permeation, a reduced lag time of about 15 min was observed with a significant drug flux of 15.09 ± 7.68 g/cm2/h seen in the first 1 h (pin-vitro in-vivocorrelation we were able to predict an optimized design of the patch that can reproduce the clinical PK of NAL obtained with commercial devices. Increasing needle density and/or patch area was found to be of greater significance. Overall, drug flux seen over 1 h depicts the applicability of fabricated needles in opioid overdose emergencies with delivery properties comparable to that with IM and IN delivery.

Many children in foster care have emotional or behavioral problems or are at risk for these problems. It is important to identify parents willing to foster children with these problems in order to ensure placement, care, stability and well-being of such children. This study presents a new 40-item self-report measure of the willingness of parents to foster children with emotional and behavioral problems, and two 20-item parallel forms of this measure. In addition, this study presents evidence of reliability and validity of scores derived from these measures with a national sample of 297 foster mothers. Coefficient alpha for these measures was 92 or greater, indicating excellent internal consistency reliability. Scores from these measures were unrelated to demographic characteristics, providing evidence of discriminant validity. In addition, scores from these measures were higher for foster mothers licensed to provide treatment foster care than for mothers only licensed to provide regular foster care, providing support for known groups validity. Finally, support for construct validity is provided by the fact that foster mothers with higher scores on these measures had fostered longer, were fostering more children at the time of this study, and had fewer children removed from their home at their request.

Schizophrenia (SZ) is a neurological disorder that presents with paranoia, hallucinations, and negative affect. A neurobiological hallmark of SZ is increased dopamine D2 receptor sensitivity. Antipsychotics that treat SZ have demonstrated limited efficacy as well as harmful and sometimes fatal side effects. Additionally, nicotine abuse is greatly increased in individuals diagnosed with SZ compared to the normal population. Treatment of this comorbidity is important, because cigarette smoking diminishes the quality of life in individuals with SZ and shortens their lifespan. The adenosine system is a potential novel target for SZ treatment. Adenosine A2a receptors form a heteromeric complex with dopamine D2 receptors that is mutually inhibitory, meaning each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study investigated the efficacy of an adenosine A2a agonist, CGS 21680, in alleviating the rewarding aspects of nicotine in the neonatal quinpirole rodent model of SZ. Rats were treated neonatally from postnatal (P)day 1 through 21 with the dopamine D2/D3 agonist quinpirole, raised to P41, and tested on conditioned place preference (CPP). CPP is a behavioral measure of the rewarding properties of a drug through temporal pairing of a drug with a distinct environmental context. Rats were given a drug free pre-conditioning preference test, and then conditioned to saline or nicotine (0.6 mg/kg base) from P43-51. Groups receiving CGS 21680 (0.03 or 0.09 mg/kg) were given the agonist 15 min before nicotine was administered. A drug-free post-conditioning test was administered on P52 to determine preference. The following day, brain tissue was analyzed for brain-derived neurotrophic factor (BDNF) and glial cell-lined neurotrophic factor (GDNF). BDNF is a ubiquitous neurotrophic factor involved in synaptic growth throughout the brain, whereas GDNF is important in dopamine plasticity. Results revealed that neonatal quinpirole enhanced nicotine CPP, replicating previous work, and both doses of CGS 21680 alleviated this enhancement. Nicotine resulted in a CPP in controls, and both doses of CGS 21680 also alleviated this preference. Therefore, CGS 21680 alleviated the rewarding aspects of nicotine. BDNF analyses in the nucleus accumbens (Nacc), a brain area that mediates drug reward, revealed that BDNF closely followed the behavioral results: CGS 21680 alleviated the enhancement in Nacc BDNF in neonatal quinpirole-treated animals, and eliminated the increase in Nacc BDNF produced by nicotine in controls. GDNF analyses revealed that neonatal quinpirole animals conditioned to nicotine resulted in an increase of GDNF in the NAacc, but this was eliminated by CGS 21680. This project revealed that an adenosine agonist with antispsychotic properties may have utility towards decreasing the rewarding aspects of nicotine and its accompanying neural plasticity changes in a model of SZ.

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The aim of this study is to explore and analyze the employee's experiences of using low arousal approach as a method in residential care homes. It is also done to better understand the employee's experiences, challenges and successes by using low arousal approach as a method with young people who show challenging behavior due to situations that makes them lose control over their behavior. The method used to answer the chosen questions is a qualitative method in the form of semi-structured interviews. This specific method was chosen because it allows for an in-depth exploration of our chosen topic. To answer the chosen questions, we have interviewed 6 employee's from one residential care home. These interviews provided a deeper understanding of their experiences with using the method and the advantages and disadvantages of applying it as a behavior management method. Their experiences with the method indicate that it is helpful when a child or young person with behavioral problems exhibits challenging behavior, as it helps to prevent the situation from escalating. Based on the interviews, we were able to conclude that there are more advantages than disadvantages. The method leads to strong relationships, greater understanding and positive behavioral change. The disadvantages include that over time, employee's may forget how to act in problem creating situations. The focus over time may shift more towards creating a calm working environment rather than helping the children or young people with behavioral problems who need assistance. In conclusion, with the help of the 6 semi structured interviews, the study was able to gain deeper insight into the employee's experiences, situations and the advantages and disadvantages of using the method while working with behavioral problems in residential care homes for children and young people.

This study was designed to determine the effectiveness of individual child-centered play therapy in the elementary school in: 1) enhancing the self-concept of kindergarten children who are experiencing adjustment difficulties; 2) decreasing the overall behavioral problems of kindergarten children experiencing adjustment difficulties 3) decreasing externalizing behavior problems such as aggression and delinquency of kindergarten children experiencing adjustment difficulties; 4) decreasing the internalizing behavior problems such as withdrawal, somatic complaints, anxiety and depression of kindergarten children experiencing adjustment difficulties; 5) increasing parental perception of change in the problematic behaviors of kindergarten children experiencing adjustment difficulties; and 6) enhancing self-control in kindergarten children experiencing adjustment difficulties. A secondary objective was to compare the participants involved in individual child-centered play therapy with participants in a previous study who were involved in child-centered group play therapy on the above named dimensions. The experimental group, consisting of 14 kindergarten children experiencing adjustment difficulties, received 10-12, 30-minute individual play therapy sessions in a 12 week period in their elementary school. The comparison group, utilized from the 1999 McGuire study, consisted of 15 children with adjustment problems and received 12-14, 45-minute group play therapy sessions in 14 weeks in their elementary school. The control group, consisting of 13 children experiencing adjustment problems, received no play therapy intervention over a 12 week period. An Analysis of Covariance revealed significant findings in 1 of the 6 hypotheses and one subscale hypothesis examining the effectiveness of individual play therapy versus the wait list control group. Specifically, children with adjustment problems in the experimental group exhibited a significant reduction in total behavior problems and a significant reduction in externalizing behavior problems as measured by the Child Behavior Checklist-Parent Form (CBCL). Additionally, an Analysis of Covariance revealed significant findings in 1 of the 6 hypotheses examining the comparison of the effectiveness of individual play therapy versus the group play therapy comparison group from McGuire (1999). Individual play therapy was significantly more effective than group play therapy in helping children maintain an acceptable level of classroom behaviors as perceived by teachers on the Early Childhood Behavior Scale (ECBS).

Sofrer bullying na infância e na adolescência se configura como fator de risco para a instalação e manutenção de problemas de comportamento e de transtornos psiquiátricos. A adversidade familiar, por sua vez, contribui para o envolvimento em situações de bullying. Os objetivos do presente estudo foram: (1) avaliar e comparar os escores de problemas de comportamento em dois grupos (vítimas e não vítimas de bullying), obtidos por meio do autorrelato e do relato dos professores e (2) verificar correlações entre os escores de adversidade familiar e de problemas de comportamento nos dois grupos. Participaram 154 adolescentes, dos quais 31 (20,1%) foram identificados como vítimas de bullying, por meio da Escala de Violência Escolar (EVE) e da versão traduzida do Peer Assessment. Para avaliar os problemas de comportamento foram utilizadas as versões brasileiras do Youth Self Report/11-18 (YSR) e do Teacher Report Form (TRF). O índice de adversidade familiar (IAF) avaliou o nível de adversidade familiar entre as famílias. Mais adolescentes vítimas de bullying foram avaliados com problemas de comportamento internalizantes, externalizantes e totais em nível clínico, quando comparados ao grupo de não vítimas. As maiores diferenças entre grupos foram verificadas na subescala de Depressão e Ansiedade, a partir do relato dos adolescentes, e na escala de Comportamento Agressivo, de acordo com os professores. Os alunos alvos de bullying relataram mais problemas de comportamento internalizantes (F=13,3 e p=0,001) e menos problemas de comportamento externalizantes (F=6,63 e p=0,013), quando comparados ao relato de seus professores. A presença de discórdia conjugal foi mais frequente em famílias de alunos vítimas de bullying, atingindo diferença estatisticamente significativa entre os grupos ( 2 =4,2 e p=0,04). Houve correlação positiva e ligeira entre os escores de problemas de comportamento, relatados pelos alunos, e os escores de adversidade familiar (=0,288 e p=0,001). Embora os escores de problemas de comportamento, sobretudo internalizantes, relatados por vítimas de bullying tenham sido significativamente superiores aos relatados por não vítimas, e tenham atingido níveis clínicos, os professores parecem não estarem sensíveis a estes indicadores. Identificar problemas de comportamento e características familiares adversas associadas à vitimização, assim como avaliar a percepção dos próprios envolvidos e de seus professores, contribui para o desenvolvimento de medidas preventivas de bullying em escolas brasileiras / Being bullied in childhood and adolescence is configured as a risk factor for the installation and maintenance of behavioral problems and psychiatric disorders. Family adversity, in turn, contributes to involvement in bullying situations. The aims of the study were: (1) to evaluate and compare the scores of behavior problems in two groups (victims and non-victims of bullying), obtained by self-report and by teachers report, and (2) examine correlations between the scores of family adversity and behavior problems of the two groups. Participated 154 adolescents, of whom, 31 (20.1%) were identified as victims of bullying, through the School Violence Scale (EVE) and through the translated version of the Peer Assessment. To assess the behavioral problems, the Brazilian versions of the Youth Self Report/11-18 (YSR) and the Teacher Report Form (TRF) were used. The family adversity index (LAI), from Rutter, assessed the level of family adversity among the families. Most adolescent victims of bullying were assessed with internalizing problems, externalizing, and total behavior at a clinical level, when compared with non-victims. The biggest differences between groups were found in the subscale of Depression and Anxiety, according to the teenagers and the Aggressive Behavior scale, according to teachers. The target of bullying students reported more internalizing behavior problems (F = 13.3, p = 0.001) and fewer externalizing behavior problems (F = 6.63, p = 0.013), when compared with their teachers. The presence of interparental conflict was more frequent in families of students bullied, reaching statistically significant difference between groups ( 2 = 4.2, p = 0.04). There was a slight and positive correlation between the scores of behavioral problems reported by students and the family adversity scores ( = 0.288, p = 0.001). While scores of behavior problems, especially internalizing, reported by victims of bullying were significantly higher than those reported by non-victims, and have reached clinical levels, the teachers do not seem to be sensitive to these indicators. Identify behavior problems and family characteristics associated with victimization, and to evaluate the perception of the involved and their teachers contribute to the development of preventive measures of bullying in Brazilian schools

Uma vez que atraves do uso do alarme de urina nem todas as criancas com enurese obtem os criterios definidos para o sucesso (14 noites secas consecutivas), buscou--se investigar procedimentos complementares para potencializar o seu efeito: a) o diario miccional, utilizado como um instrumento de avaliacao diagnostica da enurese e como uma medida dos efeitos de tratamentos e b) a uroterapia, que consiste de um conjunto de medidas comportamentais que tem como objetivo corrigir dificuldades provavelmente relacionadas a enurese nao corrigidas pelo uso do alarme. O diario miccional e o registro do volume de liquidos ingeridos e eliminados no periodo de dois dias pela crianca, que pode indicar, dentre outros padroes, urgencia miccional, hiperatividade detrusora, poliuria, bem como ingestao irregular de liquidos. As medidas comportamentais que compoe a uroterapia podem ser exemplificadas por: miccoes em horarios regulares; aumento da ingesta de liquidos e evitacao de irritantes vesicais. Neste estudo participaram 65 criancas e adolescentes com enurese distribuidas em dois grupos de tratamento. O primeiro grupo foi exposto a uroterapia e ao tratamento com alarme (grupo Uroterapia), enquanto o segundo grupo foi exposto somente ao tratamento com alarme (grupo Alarme). Por volta de 70% dos participantes de ambos os grupos obtiveram sucesso no tratamento, independentemente da realizacao da uroterapia. Os participantes do grupo Uroterapia apresentaram uma melhora mais acentuada no inicio do tratamento, mas esta nao se manteve como tendencia ao longo do tempo. Os participantes de ambos os grupos tiveram um aumento significativo da porcentagem da capacidade volumetrica da bexiga utilizada. Os participantes do grupo Uroterapia tiveram um aumento significativamente maior dos volumes de ingesta de liquidos e miccional / Not all children with enuresis reach 14 consecutive dry nights thought the use of the bell and pad alarm. That considered, we aimed to investigate additional procedures to enhance its success rate: a) the voiding diary, used as a diagnostic tool for evaluating enuresis and to measure overall treatments effects and b) urotherapy, consisting of a set of behavioral measures that aims at problems probably related to enuresis not corrected by the use of the bell and pad alarm. The voiding diary is a two--day record of fluid intake and micturition habits. It may indicate, among other patterns, urgency, detrusor overactivity, polyuria and irregular fluid intake. Urotherapy is composed of behavioral measures such: voiding at regular times; increased fluid intake; and avoidance of bladder irritants. 65 children and adolescents participated in this study. They were assigned to two treatment groups. The first group was exposed to urotherapy and to an alarm treatment (Urotherapy group), while the second was exposed only to an alarm treatment (Alarm group). Around 70% of participants became dry, regardless of the group they were assigned to. Participants from the Urotherapy group showed a more marked improvement early in treatment, but this trend was not maintained over time. Participants from both groups had a significant increase in the percentage of volumetric bladder capacity used and participants from the Urotherapy group had a significantly greater increase of fluid intake and voided volume

O diagnóstico de uma doença crônica na infância, como é o caso da doença de Charcot-Marie-Tooth (CMT), pode desencadear grandes mudanças em aspectos físicos, psicológicos e sociais, comprometendo a qualidade de vida e podendo desencadear problemas de comportamento. Neste sentido, este estudo buscou avaliar a qualidade de vida e indicadores comportamentais de pacientes com CMT. Foram avaliadas 34 crianças com CMT através dos instrumentos CHQPF-50 e SDQ e constatou-se que as crianças com CMT apresentaram uma qualidade de vida significativamente inferior a seus pares saudáveis não apenas nos aspectos físicos, mas também em aspectos emocionais. Em relação aos indicadores comportamentais, verificou-se uma taxa elevada de problemas tanto internalizantes quanto externalizantes das crianças com CMT. Características da própria doença, tais como realização de tratamento e gravidade da neuropatia, foram fatores que influenciaram diretamente tanto na qualidade de vida quanto nos problemas de comportamento das crianças. As variáveis antecedentes familiares e tipo de CMT não impactaram a qualidade nem acarretaram dificuldades de comportamento nas crianças deste estudo. Os resultados evidenciam a necessidade de se pensar em estratégias de saúde mental, que favoreçam a identificação de condições emocionais associadas ao quadro de saúde física destas criança. / The diagnosis of a chronic illness in childhood, such as Charcot-Marie-Tooth disease (CMT), can bring changes in physical, psychological and social aspects, decreasing the quality of life and result in behavioral problems. This study intends to evaluate the quality of life and behavior aspects of patients with CMT. Thirty-four children with CMT were evaluated through the CHQPF-50 and SDQ instruments. The results showed that children with CMT had a significantly lower quality of life than their healthy peers, not only in physical aspects but also in emotional aspects. Children with CMT presents both internalizing and externalizing behavioral problems. Characteristics of the disease, such as treatment and severity of neuropathy, were factors that impacts quality of life and behavioral problems in children. To have relatives with this disease and type of CMT did not affect the quality of life or behavior of the children of this study. The results leads to think about mental health strategies that improves the identification of emotional conditions associated to the physical health of these children