Search

Youth with autism spectrum disorders frequently experience significant symptoms of anxiety. Empirically supported psychosocial interventions exist, yet access is limited, especially for families in rural areas. Telehealth (i.e. videoconferencing) has potential to reduce barriers to access to care; however, little is known about the feasibility or efficacy of directly intervening with youth with autism spectrum disorders through this modality. This study details the pilot testing of a telehealth version of an empirically supported intervention targeting anxiety in youth with autism spectrum disorders. The primary focus of this study is on feasibility, with evaluation of outcomes as a starting point for future randomized trials. In all, 33 families of youth with autism spectrum disorders and significant anxiety symptoms participated in this study (Telehealth Facing Your Fears (FYF) Intervention: n = 17; Wait-list control: n = 16). Youth of all functioning levels were included. Acceptability was strong; however, the usability of the technology was problematic for some families and impeded some sessions significantly. Fidelity of the telehealth version to the critical elements of the original, in vivo version was excellent. More work is needed to improve delivery of exposure practices and parent coaching. Preliminary efficacy analyses are promising, with improvements observed in youth anxiety over time (relative to a comparison group waiting for live intervention) and parent sense of competence (within group). Clearly, stronger designs are necessary to evaluate efficacy sufficiently; however, this study does provide support for further investigation of clinic-to-home videoconferencing as a direct intervention tool for youth with autism spectrum disorders and their parents.

Rigorous environmental testing, with C-mode scanning acoustic microscopy (CSAM) inspection, was imposed on a sizeable set of exemplary commercial off-the-shelf plastic encapsulated microcircuits (PEMs) to demonstrate their suitability for dormant storage over extensive periods of time. After qualification testing of over 4800 samples of 39 standard manufacturer (mfr) part numbers from 18 world-class mfrs in 25 widely different PEM package types, indications of product discrepancies by CSAM were largely discounted based upon device reliability testing, including physical cross sectioning.

A dramatic increase in stress during adolescence is generally (and fortunately) accompanied by a concomitant increase in the sophistication and flexibility of a teen’s capacity to cope with stress. For teens living in the context of family poverty, both the experience of stress and the development of adaptive coping capacities are more complicated. First, poor teens often experience higher levels of stress created by life in poverty, such as noise pollution, crowding, and hunger. Second, this context of stress created by poverty amplifies the impact of normative adolescent stress. Third, high levels of stress compromise poor teens’ development and use of efficacious coping, and instead encourage disengagement coping, which has detrimental long-term effects on adolescent health and development. Finally, prevention programs targeting the development of efficacious coping during late childhood and early adolescence have the potential to better equip teens affected by poverty to face the challenges ahead.

Social support and vagal regulatory capacity (VRC), an index of flexible vagal responses during various types of stress, are linked to attenuated stress responding and positive health outcomes. Guided by the polyvagal perspective, we tested whether children's VRC is associated with attenuated sympathetic nervous system (SNS) stress reactivity in socially supportive conditions. Sixty-one 4- to 5-year-old children living in poverty underwent two standardized laboratory stress induction procedures. Cardiac vagal reactivity (respiratory sinus arrhythmia) to a first set of stressors (social, cognitive, physical, and emotional) indexed VRC. During a second set of stressors, participants were randomly assigned to a supportive or nonsupportive social context, and cardiac sympathetic reactivity (preejection period) was assessed. We hypothesized VRC would predict lower SNS stress reactivity, but only in the socially supportive context. Children with high VRC showed attenuated SNS stress reactivity in the socially supportive context compared to children with high VRC in the nonsupportive context and children with low VRC in either context. Individual differences in VRC predict attenuated SNS stress reactivity in socially supportive conditions. Understanding how social support and VRC jointly mitigate SNS stress reactivity may further efforts to prevent negative health outcomes. Implications for biological sensitivity to context and differential susceptibility theories are discussed.

To assess the frequency and results of cataract surgery with concurrent vitrectomy due to zonule weakness in eyes with pseudoexfoliation (PXF).Private practice, Boston, Massachusetts, USA.This retrospective nonrandomized study assessed consecutive eyes with PXF having cataract surgery. High risk was defined as preoperative phacodonesis, iridodonesis, or lens subluxation (subgroup 1); preoperative anterior chamber depth or angle-depth asymmetry between eyes confirmed by slitlamp biomicroscopy or gonioscopy, respectively (subgroup 2); or complicated cataract extraction related to zonule weakness in the fellow eye (subgroup 3). Exclusion criteria were previous vitrectomy, scleral buckle, or trabeculectomy surgery and combined cataract-glaucoma surgery. A comparative analysis of outcome parameters was performed.Of the 1059 eyes evaluated, 38 had vitrectomy. Concurrent vitrectomy was required in 19 (15.6%) of 122 high-risk eyes and 19 (2.0%) of 937 non-high-risk eyes (P.00001). The need for concurrent vitrectomy was greatest in subgroup 3 (72.7%) and subgroup 1 (42.9%). There was no statistically significant difference between the vitrectomy group and the no-vitrectomy group in the mean improvement in logMAR corrected distance visual acuity (CDVA) (P = .38) or mean change in intraocular pressure (IOP) (mean decrease 2.6 mm Hg +/- 1.5 [SD] and 1.6 +/- 0.5 mm Hg, respectively) (P = .47).Despite the need for vitrectomy and the attendant increased demands in postoperative care, both the vitrectomy group and no-vitrectomy group had improved logMAR CDVA and IOP.No author has a financial or proprietary interest in any material or method mentioned.

The authors tested a theoretical model positing that poverty has an indirect effect on child and adolescent functioning through children's poverty-related stress. Path analyses with a multiethnic sample of 164 children aged 6 to 18 revealed that the stress associated with poverty, such as economic strain, family conflict, violence/trauma, and discrimination, is an important component of the experience of poverty for children. Poverty-related stress was associated with a wide range of correlates, including internalizing and externalizing syndromes, DSM-IV diagnostic symptoms, physical health, and deviant behavior such as pregnancy, legal problems, substance abuse, and school dropout. Most models fit equally well for adolescents and preadolescents, suggesting that poverty is stressful for children as young as 6. African American children's functioning was less strongly associated with poverty-related stress than was the functioning of Hispanic and Caucasian children. Implications of poverty-related stress a...

PURPOSE: Botulinum toxin type A (BTX-A), produced byClostridium botulinum,is a potent neurotoxin. The purpose of this study was to evaluate the efficacy of BTX-A for treatment of anismus. MATERIALS AND METHODS: All patients treated with BTX-A for anismus were evaluated. Eligibility criteria included a history of chronic assisted evacuation (laxatives, enemas, or suppositories), demonstration of anismus by cinedefecogram and electromyography, and failure of a minimum of three sessions of supervised biofeedback therapy (BF). Contingent on body mass, 6 to 15 units of BTX-A was injected bilaterally under electromyography guidance into the external sphincter or the puborectalis muscle. Treatment was repeated as necessary for a maximum of three sessions during a three-month period. Success was considered as discontinuation of evacuatory assistance and was evaluated between one and three months and again at up to one year. RESULTS: Between July 1994 and May 1995, four patients ranging from 29 to 82 years in age (2 females, 2 males) had anismus that failed to respond to between 3 and 15 biofeedback sessions. All patients improved between one and three months after BTX-A injection, and two had sustained improvement for a range of three months to one year. There was no morbidity or mortality associated with BTX-A injection. CONCLUSIONS: BTX-A is extremely successful for temporary treatment of anismus that is refractory to BF management. However, because the mechanism of action is short, longer term results are only 50 percent successful. Hopefully, modifications in the strain of BTX-A and dose administered will allow longer periods of success or a repeat trial of BF. Nonetheless, this preliminary report is very encouraging in offering a method of managing this recalcitrant condition.

This chapter discusses the relations between childhood adversity and autonomic nervous system measures. It begins with a discussion on poverty and adverse experiences early in life and then reviews autonomic nervous system (ANS) measures of children's basal and stress responses, the history of the ANS field, and ANS methodological developments. Two important theories about ANS are discussed: (1) biological embedding and how early experiences can fundamentally alter ANS regulation, and (2) biological sensitivity to context, which explains how children's psychobiological responses differ based on the child's exposure to adversity. Lastly, there is a summary of studies of early childhood on ANS as a mediator or moderator of the relations between poverty-related adverse conditions and mental or physical health. This chapter concludes with a discussion of future directions to address methodological gaps in the literature examining associations among poverty-related stress and adversity, ANS dysregulation, and physical and mental health outcomes.

Background Praziquantel (PZQ) is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism) screening with adult worms in vitro and/or animal models of disease—tools that limit automation and throughput with modern microtiter plate-formatted compound libraries. Methods A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to ‘reposition’ (re-profile) drugs as anti-schistosomals with potential savings in development timelines and costs. Findings Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of ‘hit’ drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource. Conclusions To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that interfaces schistosomula with microtiter plate-formatted compound libraries. The workflow has identified various compounds and drugs as hits in vitro and leads, with the prescribed oral efficacy, in vivo. Efforts to improve throughput, automation, and rigor of the screening workflow are ongoing., Author Summary The flatworm disease schistosomiasis infects over 200 million people with just one drug (praziquantel) available—a concern should drug resistance develop. Present drug discovery approaches for schistosomiasis are slow and not conducive to automation in a high-throughput format. Therefore, we designed a three-component screen workflow that positions the larval (schistosomulum) stage of S. mansoni at its apex followed by screens of adults in culture and, finally, efficacy tests in infected mice. Schistosomula are small enough and available in sufficient numbers to interface with automated liquid handling systems and prosecute thousands of compounds in short time frames. We inaugurated the workflow with a 2,160 compound library that includes known drugs in order to cost effectively ‘re-position’ drugs as new therapies for schistosomiasis and/or identify compounds that could be modified to that end. We identify a variety of ‘hit’ compounds (antibiotics, psychoactives, antiparasitics, etc.) that produce behavioral responses (phenotypes) in schistosomula and adults. Tests in infected mice of the most promising hits identified a number of ‘leads,’ one of which compares reasonably well with praziquantel in killing worms, decreasing egg production by the parasite, and ameliorating disease pathology. Efforts continue to more fully automate the workflow. All screen data are posted online as a drug discovery resource.

Families living with the burdens of poverty-related stress are at risk for developing a range of psychopathology. The present study examines the year-long prospective relationships among poverty-related stress, involuntary engagement stress response (IESR) levels, and anxiety symptoms and aggression in an ethnically diverse sample of 98 families (300 individual family members) living at or below 150% of the US federal poverty line. Hierarchical Linear Modeling (HLM) moderator model analyses provided strong evidence that IESR levels moderated the influence of poverty-related stress on anxiety symptoms and provided mixed evidence for the same interaction effect on aggression. Higher IESR levels, a proxy for physiological stress reactivity, worsened the impact of stress on symptoms. Understanding how poverty-related stress and involuntary stress responses affect psychological functioning has implications for efforts to prevent or reduce psychopathology, particularly anxiety, among individuals and families living in poverty.

The enhancer of rudimentary gene, e(r), encodes a 104‑amino‑acid, highly conserved transcription cofactor. Hypomorphic mutations of e(r) show an enhancement of a hypomorphic rudimentary mutant wing phenotype. These mutants in a wild‑type background are viable, fertile, and morphologically wild‑type. Since the only mutant alleles were hypomorphic, it was important to isolate null mutations to determine if any other phenotypes might be associated with a loss‑of‑function of e(r). We utilized a marked P element, P{SUPor‑P, y + }, located 895 bp upstream of the start of transcription of e(r) to generate nineteen deficiencies in the region. Deficiencies of e(r) enhance the mutant wing phenotype of a hypomorphic rudimentary allele, r hd1 . In a wild‑type background, the deficiencies of e(r), unlike the hypomorphic alleles, have a low viability and females have low fertility. The expression of e(r) in the nurse cells of the ovary is consistent with the low fertility, and suggests an ovarian function for e(r). Deficiencies of CG15352, the gene directly upstream of e(r), are not associated with any obvious mutant phenotypes and present the possibility that it encodes a nonvital or redundant function.

Purpose To assess the effect of phacoemulsification with posterior chamber intraocular lens (IOL) implantation performed by a single surgeon on intraocular pressure (IOP) and glaucoma medication requirements in pseudoexfoliation (PFX) eyes with or without glaucoma. Setting Private practice, Boston, Massachusetts, USA. Methods This retrospective analysis comprised 1122 eyes with PFX having uneventful phacoemulsification with IOL implantation. Of the eyes, 882 did not have glaucoma (PFX group) and 240 had glaucoma (PXG group). A comparative outcomes analysis was performed; the analysis focused on IOP and change in glaucoma medication requirements between the 2 groups. Results The mean IOP was statistically significantly reduced through 7 years postoperatively compared with preoperatively in the PFX group. The PXG group had reduced mean IOP for 1 year and reduced glaucoma medication requirements at almost all postoperative time intervals. Higher mean preoperative IOP was associated with a greater reduction in mean IOP postoperatively in both groups. Intraocular pressure spikes (>30 mm Hg) 1 day postoperatively occurred in 4% in the PFX group and 17% in the PXG group. Postoperatively, 2.7% of PFX eyes progressed to a need for glaucoma medication and 3.7% of PXG eyes progressed to a need for laser and/or glaucoma surgery. Conclusions A long-term reduction in mean IOP occurred in PFX eyes with and without glaucoma. The IOP reduction was proportional to the preoperative IOP; higher preoperative IOP was associated with a greater reduction in IOP. Glaucoma progression in both groups was low, suggesting a protective effect of phacoemulsification on IOP in these eyes.

Chemotherapy against human African trypanosomiasis relies on four drugs that cause frequent and occasionally severe side-effects. Because human African trypanosomiasis is a disease of poor people in Africa, the traditional market-driven pathways to drug development are not available. One potentially rapid and cost-effective approach to identifying and developing new trypanocidal drugs would be high throughput-screening of existing drugs already approved for other uses, as well as clinical candidates in late development. We have developed an ATP-bioluminescence assay that could be used to rapidly and efficiently screen compound libraries against trypanosomes in a high throughput-screening format to validate this notion. We screened a collection of 2160 FDA-approved drugs, bioactive compounds and natural products to identify hits that were cytotoxic to cultured Trypanosoma brucei at a concentration of 1 mum or less. This meant that any hit identified would be effective at a concentration readily achievable by standard drug dosing in humans. From the screen, 35 hits from seven different drug categories were identified. These included the two approved trypanocidal drugs, suramin and pentamidine, several other drugs suspected but never validated as trypanocidal, and 17 novel trypanocidal drugs.

Individual differences in autonomic nervous system reactivity have been studied in relation to physical and mental health outcomes, but rarely among children with chronic disease. The purpose of this study was to examine the associations among autonomic reactivity, clinical severity, family stressors, and mental health symptoms in children with homozygous sickle cell disease. Nineteen children with homozygous sickle cell disease participated in a cross-sectional study involving parent-completed measures, medical record reviews and laboratory-based measures of autonomic nervous system responses to social, cognitive, physical and emotional challenges. Autonomic reactivity was significantly associated with both clinical severity and externalizing behavior symptoms. Children with greater parasympathetic withdrawal during challenges compared to rest had significantly more severe disease (r = -0.45, p0.05); greater sympathetic activation during challenges compared to rest was associated with more externalizing behavior symptoms ( r= 0.44, p0.05). Children experiencing major family stressors had internalizing behavior symptoms but no difference in autonomic reactivity or clinical severity compared to children experiencing fewer family stressors. Individual differences in autonomic reactivity may offer a new, biologically plausible account for observed variation in painful episodes, other physical complications and behavioral symptoms among children with sickle cell disease.