Humidified and standard oxygen therapy in acute severe asthma in children (HUMOX): A pilot randomised controlled trial.

BACKGROUND: Oxygen (O2) is a mainstay of treatment in acute severe asthma but how it is administered varies widely. The objectives were to examine whether a trial comparing humidified O2 to standard O2 in children is feasible, and specifically to obtain data on recruitment, tolerability and outcome measure stability. METHODS: Heated humidified, cold humidified and standard O2 treatments were compared for children (2-16 years) with acute severe asthma in a multi-centre, open, parallel, pilot randomised controlled trial (RCT). Multiple outcomes were assessed. RESULTS: Of 258 children screened, 66 were randomised (heated humidified O2 n = 25; cold humidified O2 n = 21; standard O2 n = 20). Median (IQR) length of stay (hours) in hospital was 37.9 (29.1), 52 (35.4) and 49.1 (29.7) for standard, heated humidified and cold humidified respectively and time (hours) on O2 was 15.9 (9.4), 13.6 (14.9) and 13.1 (14.9) for the three groups respectively. The mean (standard deviation) time (hours) taken to step down nebulised to inhaled treatment was 5.6 (14.3), 35.1 (28.2) and 32.7 (20.1). Asthma Severity Score decreased in all three groups similarly, although missing data prevented complete analysis. Humidified O2 was least well tolerated with eight participants discontinuing their randomised treatment early. An important barrier to recruitment was research nurse availability. CONCLUSION: Although, the results of this pilot study should not be extrapolated beyond the study sample and inferential conclusions should not be drawn from the results, this is the first RCT to compare humidified and standard O2 therapy in acute severe asthmatics of any age. These findings and accompanying screening data show that a large RCT of O2 therapy is feasible. However, challenges associated with randomisation and data collection should be addressed in any future trial design.

Healthcare providers' and managers' knowledge, attitudes and perceptions regarding international medical volunteering in Uganda: a qualitative study.

OBJECTIVES: The study sought to explore the knowledge, attitudes and perceptions of healthcare providers and health programme managers regarding the benefits, challenges and impact of international medical volunteers' clinical placements. Views on how to better improve the work of international medical volunteers and the volunteer organisation Voluntary Service Overseas (VSO) for the benefit of local communities were also explored. SETTINGS: Public healthcare facilities, VSO offices in Gulu and VSO offices in Kampala, Uganda. PARTICIPANTS: Ugandan healthcare providers (n=11) and health programme managers (n=6) who had worked with or managed international medical volunteers. INTERVENTIONS: Data collection was conducted using key informant interviews. Transcribed interviews were coded by topic and grouped into categories. Thematic framework analysis using NVivo identified emerging themes. RESULTS: Both healthcare providers and managers reported a beneficial impact of volunteers and working with the volunteer organisation (clinical service provision, multidisciplinary teamwork, patient-centred care, implementation of audits, improved quality of care, clinical teaching and mentoring for local healthcare providers); identified challenges of working with volunteers (language barriers and unrealistic expectations) and the organisation (lack of clear communication and feedback processes); and provided recommendations to improve volunteer placements and working partnership with the organisation (more local stakeholder input and longer placements). Most healthcare providers were positive and recommended that volunteers are enabled to continue to work in such settings if resources are available to do so. CONCLUSIONS: Healthcare providers based in a low-resource setting report positive experiences and impacts of working with international medical volunteers. Currently, there is lack of local feedback processes, and the establishment of such processes that consider local stakeholder reflections requires further strengthening. These would help gain a better understanding of what is needed to ensure optimal effectiveness and sustainable impact of international medical volunteer placements.

The ASPET Mentoring Network: Enhancing Diversity and Inclusion through Career Coaching Groups within a Scientific Society.

Over the past decades, two persisting priorities in science, technology, engineering, and mathematics (STEM) training have been: 1) increasing the knowledge of and access to careers beyond academic scientist; and 2) increasing the diversity of the STEM workforce. Previous studies show that a uniquely constructed career coaching group provides strong support and progress for both priorities. This report extends this design into a more sustainable model that is positioned within the professional context of rising young scientists. This new model is based in the American Society for Pharmacology and Experimental Therapeutics (ASPET)-the ASPET Mentoring Network. Groups of PhD students and postdocs were assigned to an ASPET professional (academic or other career) member (the coach) with an initial meeting held the day before the society's annual meeting. The coaching groups interacted during the meeting and then virtually for a year. Extensive survey and interview evaluation data gathered from the first three cohorts (12 coaching groups) in 2016- 2018 provided strong evidence of the perceived and real benefits of the network. This new version of career coaching groups is both feasible and linked to career success due to its close association with a scientific society, peers, and coaches who share scientific identities and aspirations.

Featured counter trafficking program: The law enforcement first responder protocol.

This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficking children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes the Law Enforcement First Responder Protocol, which trained law enforcement to recognize youth engaged in sex work as survivors of commercial sexual exploitation, rather than as "prostitutes", and to connect these survivors immediately with social services, advocates, timely medical care and ongoing follow-up.

Pediatric Return Appointment Adherence for Child Welfare-Involved Children in Los Angeles California.

OBJECTIVES: This study of primarily Latino caregivers and Latino child welfare-involved children had the following aims: (1) explore the return appointment adherence patterns at a pediatric medical clinic; and (2) determine the relationship of adherence to return appointments and caregiver, child, and clinic variables. METHODS: The sample consisted of caregivers of child welfare-involved children who were asked to make a pediatric outpatient clinic return appointment (N = 87). Predictors included caregiver demographics, child medical diagnoses and age, and clinic/convenience factors including distance from the clinic to caregiver's home, days until the return appointment, reminder telephone call, Latino provider, and additional specialty appointment. Predictors were examined using χ(2) and t tests of significance. RESULTS: Thirty-nine percent of all caregivers were nonadherent in returning for pediatric appointments. When return appointments were scheduled longer after the initial appointment, caregivers were less likely to bring children back for medical care. CONCLUSIONS: The 39 % missed return appointment rate in this study is higher than other similar pediatric populations. Better coordination between pediatricians and caregivers in partnership with child welfare case workers is needed to ensure consistent follow-up regarding health problems, especially when appointments are not scheduled soon after the initial appointment.

Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice.

Diabetes in humans and animals is accompanied by chronic low-grade inflammation, which could be a possible mediator of developing neuropathology and neurobehavioral deficits. The objective of the present study determined if decreasing inflammation could reverse diabetes-induced decreases in hippocampal cell proliferation, one aspect of hippocampal neurogenesis. C57BL/6J mice were made diabetic by administering streptozotocin (STZ; 195 mg/kg). STZ mice or vehicle controls received chronic treatment with the non-steroidal anti-inflammatory drug indomethacin (2 mg/kg for 14 days). Levels of glucose, corticosterone and cytokines were measured from plasma, cell proliferation was measured using BrdU incorporation in the hippocampus and TNF-αR1 and TNF-αR2 mRNA was measured using real-time PCR. STZ-induced diabetes increased plasma levels of glucose and corticosterone and decreased body weight. Cell proliferation in the hippocampus was reduced in diabetic mice by 50 %. The decreased level of cell proliferation was reversed by chronic treatment with indomethacin without changes to corticosterone and glucose levels. Plasma TNF-α levels increased in diabetic mice and were normalized by indomethacin treatment whereas IL-1 and IL-6 levels were unchanged by diabetes or indomethacin. In contrast, plasma levels of the cytokines IL-10 and IFN-gamma decreased in diabetic mice and were not affected by indomethacin treatment. STZ-induced diabetes decreased hippocampal expression of TNF-αR2 but not TNF-αR1 mRNA. Indomethacin ameliorated the effects of STZ on hippocampal neurogenesis independent of corticosterone and glycemic control, possibly by mediating the proinflammatory cytokine TNF-α. Inflammation is a potential novel pharmacological target for alleviating neurobehavioral complications arising from diabetes.

Overweight and obesity among Hispanic children entering foster care: a preliminary examination of polyvictimization.

This retrospective medical chart review examined the prevalence of overweight/obesity (≥85th percentile) and obesity (≥95th percentile) in Hispanic foster children aged 2-18 years in Los Angeles, California. Logistic regression was used for boys and girls separately to analyze polyvictimization (i.e., one vs. two or more types of maltreatment), type of maltreatment (abuse vs. neglect), and age-group as risk factors for overweight and obesity. Almost 40% of participants were overweight/obese, with the highest prevalence (47.7%) observed among children aged 12-18. Children aged 6-18 were at an increased risk of overweight/obesity and obesity compared with children aged 2-5. Although polyvictimization has been shown to have adverse health effects, in this study, it was related to slightly lower odds of obesity for boys but was unrelated to high weight for girls. Addressing the obesity epidemic among Hispanic foster children is vital to preventing continued obesity and the development of obesity-related health problems, especially by focusing on important community and family influences.

Weight changes in children in foster care for 1 year.

OBJECTIVE: The aims of this study of predominately racial/ethnic minority children in foster care (N=360, birth to 19 years old) in Los Angeles, CA were to examine the (1) prevalence of obesity (≥ 95 percentile) and overweight/obese (≥ 85 percentile) upon entrance to foster care (T1) and after 1 year in foster care (T2); (2) comparison of high weight categories to national statistics; (3) relationship of changes in weight status to age, reason for entry into foster care, and placement. METHODS: Chi-square test and McNemar test comparing paired proportions were used to determine whether there were significant changes in the proportion of high weight categories between T1 and T2. Chi-square test or Fisher's exact test were used to evaluate the association between age, placement, and reason for foster care with the change in weight category. Changes in weight were categorized as (1) decreased in weight, (2) remained at overweight or obese, (3) increased in weight, or (4) remained normal. RESULTS: The proportion of obese and obese/overweight children between ages 2 and 5 were significantly lower at T2 than T1. There were no significant changes in the prevalence of obesity for the total population at T2. Children age 6 or older had a higher prevalence of obesity and overweight/obesity compared to national statistics. Of children at all ages, 64.7% of children of all ages entered foster care with a normal weight and stayed in the normal range during their first year in foster care, 12.2% decreased their weight, 15.4% remained overweight or obese, and 7.7% increased their weight. Age and parental substance use was related to change in weight category from T1 to T2. CONCLUSION: Children did not become more overweight or obese in foster care; however 28% of the children were obese or overweight upon entry into foster care. Children who are 6 years or older and obese upon entering foster care should be targeted for weight reduction. The pediatric community and child welfare system need to work together by including weight percentiles in the foster care file and training/monitoring child welfare caregivers in weight reduction interventions.

Modeling an Inflammation-Related Depressive Phenotype in Mice Using Bacille Calmette-Guérin.

The relationship between inflammation and neuropsychiatric symptoms is of interest to the scientific community for several reasons. A substantial subset of patients suffering from major depressive disorder also exhibit evidence of chronic inflammation including elevated levels of circulating pro-inflammatory cytokines. Immune-mediated inflammatory diseases and immunotherapy can result in depressive symptoms in some patients. Recent evidence suggests that the chronic inflammation may play a role in the pathophysiology of the depressive state, although the specific biological mechanisms are not clear. Herein we describe a model of an inflammation-related depressive phenotype in mice using the tuberculosis vaccine, bacille Calmette-Guérin, to induce chronic inflammation and a subsequent depressive phenotype which is assessed using the tail-suspension test. The model provides an avenue to study not only the molecular and biochemical changes that may be associated with the development of the depressive phenotype, but also pharmacological manipulations of the phenotype.

Demographic and placement variables associated with overweight and obesity in children in long-term foster care.

Overweight and obesity is a growing problem for children in foster care. This study describes the prevalence of overweight and obesity in an urban, ethnic minority population of children ages 2-19 in long-term foster care (N = 312) in Los Angeles, California. It also investigates whether demographics or placement settings are related to high body mass index. The estimates of prevalence of overweight/obesity (≥85th percentile) and obesity (≥95th percentile) were presented for gender, age, ethnicity, and placement type. Multiple logistic regression was used to examine potential associations between demographic and placement variables and weight status. The prevalence of overweight/obesity was almost 40 % and obesity was 23 % for the study population. Children placed in a group home had the highest prevalence of overweight/obesity (60 %) and obesity (43 %) compared to other types of placement. Within this study, older children (ages 12-19) were more likely to be overweight/obese than normal weight compared to children between 2 and 5 years old when controlling for gender, ethnicity and placement (OR = 2.10, CI = 1.14-3.87). These findings suggest that older age and long-term foster care in general may be risk factors for obesity. Child welfare agencies and health care providers need to work together to train caregivers with children in long-term foster care in obesity treatment interventions and obesity prevention strategies.

A depressive phenotype induced by Bacille Calmette Guérin in 'susceptible' animals: sensitivity to antidepressants.

RATIONALE: The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized. OBJECTIVES: This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam. MATERIALS AND METHODS: CD-1 mice were dosed with Bacille Calmette-Guérin (BCG) and measures of body weight, locomotor activity, and immobility in the tail suspension test (TST) were made. Spleen weight, plasma cytokines, and lung indoleamine-2,3-dioxygenase mRNA assessments were made at experiment termination. Pharmacological studies with acute fluoxetine and desipramine were done in naïve CD-1 mice to establish doses using the TST and in a locomotor assay to establish a nonsedating dose of diazepam. Characterization of the pharmacological sensitivity of the BCG model was done by assessing locomotor activity 6 days post BCG treatment and measuring immobility at 7 days post treatment in the presence or absence of fluoxetine (56 mg/kg), desipramine (20 mg/kg), or diazepam (1 mg/kg). RESULTS: Ten to 30 % of BCG-treated mice did not exhibit an increase in immobility and were termed "resilient" to BCG-induced behavioral changes despite evidence of an activated immune system. BCG-"susceptible" mice exhibited increased immobility in TST and deficits in locomotor activity. The increased immobility in BCG-susceptible mice was attenuated by acute fluoxetine and desipramine, and exacerbated by diazepam. CONCLUSIONS: The depressive phenotype in this BCG model of chronic inflammation is sensitive to antidepressants and consistent with clinical reports showing that paroxetine pretreatment prior to immunotherapy can prevent the development of psychiatric symptoms.

T-type calcium channel antagonism produces antipsychotic-like effects and reduces stimulant-induced glutamate release in the nucleus accumbens of rats.

T-type calcium channels are important in burst firing and expressed in brain regions implicated in schizophrenia. Therefore, we examined the effects of novel selective T-type calcium channel antagonists in preclinical assays predictive of antipsychotic-like activity. TTA-A2 blocked the psychostimulant effects of amphetamine and MK-801 and decreased conditioned avoidance responding. These effects appeared mechanism based, rather than compound specific, as two structurally dissimilar T-type antagonists also reduced amphetamine-induced psychomotor activity. Importantly, the ability to reduce amphetamine's effects was maintained following 20 days pre-treatment with TTA-A2. To explore the neural substrates mediating the observed behavioral effects, we examined the influence of TTA-A2 on amphetamine-induced c-fos expression as well as basal and stimulant-evoked dopamine and glutamate release in the nucleus accumbens. TTA-A2 decreased amphetamine-induced c-fos expression as well as MK-801-induced, but not basal, glutamate levels in the nucleus accumbens. Basal, amphetamine- and MK-801-induced dopamine efflux was altered. These findings suggest that T-type calcium channel antagonism could represent a novel mechanism for treating schizophrenia.

Pediatric health assessments of young children in child welfare by placement type.

OBJECTIVES: To describe health-related problems across placement types (unrelated foster, kin foster, in-home with birth parent); to examine the association of placement and demographic/child welfare variables (child gender, age, race/ethnicity; caregiver language; type of maltreatment, and length of time receiving services from child welfare) with health-related problems. METHODS: This study utilized a retrospective medical chart review of children less than 6 years old (n=449) seen at an outpatient child welfare pediatric clinic. Logistic regression modeling was used to estimate odds of having a weight, medical, or provisional developmental delay problem by placement and demographic/child welfare characteristics. RESULTS: Almost 13% of children in the sample were obese (≥95% age-gender specific percentile) and more than a quarter were overweight/obese (≥85%) while only 7% were underweight (≤5%). Most children (78%) had a physical health diagnosis and 25% were provisionally identified with a developmental delay. No differences between weight diagnoses, type of medical diagnoses, and provisional developmental delay by placement type were found, although children with 3 or more medical diagnoses were more likely to be with kin (p<.05). Children 2 years old or older were more likely to be overweight/obese than children under 2 years old (p<.05) and Hispanic children were more likely to be overweight/obese than non-Hispanic children (p<.01). Length of stay in child welfare was positively related with a medical diagnosis or provisional developmental delay (p<.01). CONCLUSIONS: Results argue for careful assessment of weight, medical, and developmental problems in children active to child welfare, whether residing in their home of origin, with kin, or with unrelated foster parents. The increasing problem of obesity among young children in child welfare warrants further investigation and intervention. PRACTICE IMPLICATIONS: The comprehensive health examination and enhanced health maintenance schedule for children in foster care should be extended to children who remain at home with child welfare services as child welfare involvement rather than placement is related to health-related problems.

Characterization of a cerebellar granule progenitor cell line, EtC.1, and its responsiveness to 17-beta-estradiol.

Mouse cerebellar development occurs at late embryonic stages and through the first few weeks of postnatal life. Hormones such as 17-beta-estradiol (E2) have been implicated in cerebellar development, through the expression of E2 receptors (ER). However, the role of E2 in the development and function of cerebellar neurons has yet to be fully elucidated. To gain insight into E2's actions on the developing cerebellum, we characterized a cloned neuronal cell line, E(t)C.1, derived from late embryonic cerebellum for its neural properties and responsiveness to E2. Our results revealed that E(t)C.1 cells express markers characteristic of neural progenitor cells such as Nestin, Musashi, and Doublecortin (DCX), and of the granule cell lineage such as Math1 and Zipro1. The ER alpha and beta (ERalpha and ERbeta) were also identified in this cell line. Functionality of ERs was verified using an Estrogen Response Element (ERE)-Luciferase reporter plasmid. E2 modulated ERalpha, FMRP, and IL-6, which were expressed in these cells. However, E2 did not induce changes in neural proteins nor induce maturation of E(t)C.1 cells. CREB and ERK(1/2) protein kinases were not modulated by E2 either. Interestingly, E(t)C.1 expressed active p450 Aromatase (P450arom), which was confirmed by the aromatization of androstenedione (AD) to E2 and other estrogen metabolites. Collectively, our results show that the E(t)C.1 cell line may serve as a model to study early development of cerebellar progenitor granule cells, and their responsiveness to E2.

A prototype for an economical vertical microstomia orthosis.

One of the complications of thermal injury is the development of scars and contractures during the healing process. This scarring can be devastating, especially when it involves the mouth. The purpose of this report is to describe the construction of an alternative vertical mouth stretching orthosis for vertical microstomia. By using thermoplastic splinting material and a long thread screw, a vertical mouth-stretching orthosis can be custom-fit to any patient's mouth. The device can be fabricated for a pediatric or adult patient for the rehabilitation of a circumferential mouth burn, especially targeting the vertical diameter. When using this device, patients gave positive feedback for comfort and ease of use, with increased mouth mobility and range of motion. This vertical orthotic device provides an economical and comfortable alternative for vertical mouth diameter enlargement to the current five devices available in the literature.

Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study.

OBJECTIVES: To determine the prevalence, diagnostic patterns, and management of prostatitis, interstitial cystitis, and epididymitis (PIE) in Canadian urology outpatient practice. METHODS: Representative urologists were randomly selected from the Canadian and Quebec Urological Associations. Each patient identified with a PIE diagnosis during a typical 2-consecutive-week period during April 2004 to July 2004 was requested to complete a corresponding Chronic Prostatitis Symptom Index (CPSI), O'Leary-Sant Symptom Index (OSSI), or a Chronic Epididymitis Symptom Index (CESI). Each day the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations, and treatments associated with each PIE patient. RESULTS: Sixty-five urologists were invited to participate. Fifty-seven (88%) agreed, and 48 (74%) completed the audit. Of the 8712 patients seen in outpatient practice (average 182 per urologist), 2675 were female and 6037 male. Prostatitis was identified in 2.7% of the men (n = 166; mean age 50 years; mean duration 3.1 years; mean CPSI score 19.7), interstitial cystitis in 2.8% of patients (n = 242; 211 women [7.9%], 26 men [0.4%]; mean age 50.2 years, mean duration 4.5 years, mean OSSI score 11.8), and epididymitis in 0.9% of men (n = 57; mean age 41.1 years, mean duration 2.5 years, mean CESI score 15.5). There was wide variance in investigations and treatments. CONCLUSIONS: This prospective audit indicates that prostatitis might not be as common as frequently believed and that interstitial cystitis is more common, and it represents the first estimate of the prevalence of epididymitis in urologic practice. The wide variance in investigations and treatments confirms the need for practice management guidelines.

Estrogen receptor-beta regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe.

BACKGROUND: Distinct expression patterns of estrogen receptor (ER)-alpha and ER-beta are displayed in the murine central nervous system. ER-beta is the predominant form of the receptor expressed in the murine midbrain dorsal raphe nucleus (DRN). Tryptophan hydroxylase (TPH) is abundantly expressed in the serotonergic neurons of the DRN and is regulated by estrogen in both the monkey and the guinea pig. METHODS: In this study we used immunocytochemistry to show that ER-beta and TPH are colocalized in the serotonergic cells of the murine DRN. We utilized the ER-alpha and ER-beta gene deletion mouse models and in situ hybridization to demonstrate that ER-beta is responsible for regulating TPH1 mRNA expression. RESULTS: Estrogen increased TPH1 mRNA expression in the DRN of wild type and ER-alpha knockout mice (alpha-ERKO) but not ER-beta knockouts (beta-ERKO). CONCLUSIONS: These data indicate that ER-beta is responsible for mediating estrogen regulated TPH1 expression in the murine DRN.

Differential hormonal regulation of tryptophan hydroxylase-2 mRNA in the murine dorsal raphe nucleus.

BACKGROUND: Recently a novel tryptophan hydroxylase isoform (TPH2) was identified and shown to be highly expressed in the central nervous system (CNS). Hormonal effects on TPH2 mRNA expression in the rodent dorsal raphe nucleus (DRN) are unknown. METHODS: In situ hybridization histochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the effects of dexamethasone or estradiol on TPH2 mRNA levels in the DRN of C57/Bl6 mice. RESULTS: Dexamethasone reduced TPH2 mRNA levels in the DRN of both ovx female and intact male mice. Reduction of TPH2 mRNA in the DRN was blocked by co-administration of mifepristone. Estradiol had no detectable effect on TPH2 mRNA levels in the DRN. CONCLUSIONS: TPH2 mRNA is regulated by glucocorticoids but not estradiol in the mouse DRN. Glucocorticoid-mediated reduction of TPH2 message may have relevance to the etiology of major depression, psychotic major depression in particular, where elevated glucocorticoids are one hallmark of the disease.