Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

A proposal for an updated staging system for LCHADD retinopathy.

OBJECTIVE: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology. METHODS: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity. RESULTS: Two independent experts first graded fundus photos and electrophysiology to classify the stage of chorioretinopathy based upon an existing published system. With newer imaging modalities and improved electrophysiology, many patients did not fit cleanly into a single traditional staging group. Therefore, we developed a novel staging system that better delineated the progression of LCHADD retinopathy. We maintained the four previous delineated stages but created substages A and B in stages 2 to 3 to achieve better differentiation. DISCUSSION: Previous staging systems of LCHADD chorioretinopathy relied on only on the assessment of standard 30 to 45-degree fundus photographs, visual acuity, fluorescein angiography (FA), and ffERG. Advances in recordings of ffERG and multimodal imaging with wider fields of view, allow better assessment of retinal changes. Following these advanced assessments, seven patients did not fit neatly into the original classification system and were therefore recategorized under the new proposed system. CONCLUSION: The new proposed staging system improves the classification of LCHADD chorioretinopathy, with the potential to lead to a deeper understanding of the disease's progression and serve as a more reliable reference point for future therapeutic research.

Amino acid ratio combinations as biomarkers for discriminating patients with pyruvate dehydrogenase complex deficiency from other inborn errors of metabolism.

BACKGROUND: Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial neurometabolic disorder of energy deficit, with incidence of about 1 in 42,000 live births annually in the USA. The median and mean ages of diagnosis of PDCD are about 12 and 31 months, respectively. PDCD is a major cause of primary lactic acidosis with concomitant elevation in blood alanine (Ala) and proline (Pro) concentrations depending on phenotypic severity. Alanine/Leucine (Ala/Leu) ≥4.0 and Proline/Leucine (Pro/Leu) ≥3.0 combination cutoff from dried blood spot specimens was used as a biomarker for early identification of neonates/infants with PDCD. Further investigations were needed to evaluate the sensitivity (SN), specificity (SP), and clinical utility of such amino acid (AA) ratio combination cutoffs in discriminating PDCD from other inborn errors of metabolism (IEM) for early identification of such patients. METHODS: We reviewed medical records of patients seen at UPMC in the past 11 years with molecularly or enzymatically confirmed diagnosis. We collected plasma AA analysis data from samples prior to initiation of therapeutic interventions such as total parenteral nutrition and/or ketogenic diet. Conditions evaluated included organic acidemias, primary mitochondrial disorders (MtDs), fatty acid oxidation disorders (FAOD), other IEMs on current newborn screening panels, congenital cardiac great vessel anomalies, renal tubular acidosis, and non-IEMs. The utility of specific AA ratio combinations as biomarkers were evaluated using receiver operating characteristic curves, correlation analysis, principal component analysis, and cutoff SN, SP, and positive predictive value determined from 201 subjects with broad age range. RESULTS: Alanine/Lysine (Ala/Lys) and Ala/Leu as well as (Ala + Pro)/(Leu + Lys) and Ala/Leu ratio combinations effectively discriminated subjects with PDCD from those with other MtDs and IEMs on current newborn screening panels. Specific AA ratio combinations were significantly more sensitive in identifying PDCD than Ala alone or combinations of Ala and/or Pro in the evaluated cohort of subjects. Ala/Lys ≥3.0 and Ala/Leu ≥5.0 as well as (Ala + Pro)/(Leu + Lys) ≥2.5 and Ala/Leu ≥5.0 combination cutoffs identified patients with PDCD with 100% SN and ~85% SP. CONCLUSIONS: With the best predictor of survival and positive cognitive outcome in PDCD being age of diagnosis, PDCD patients would benefit from use of such highly SN and SP AA ratio combination cutoffs as biomarkers for early identification of at-risk newborns, infants, and children, for early intervention(s) with known and/or novel therapeutics for this disorder.

Effect of progesterone infused controlled internal drug releasing (CIDR) device and timing of gonadotropin stimulation using P.G. 600 on reproductive success in ewes bred out of season.

Objectives of this study were to determine effects of exogenous progesterone (via controlled internal drug releasing devices; CIDR) in combination with exogenous gonadotropins (PMSG/hCG) use either at CIDR removal or 1 d before CIDR removal to induce estrus and cyclicity and subsequently enhance the proportion of ewes lambing, lambing rate, prolificacy, and days to lambing in ewes bred out of season. Multiparous ewes (n = 414) were randomly assigned to one of four treatments: untreated (U, n = 122), 7 d CIDR (C, n = 97), 7 d CIDR plus P.G. 600 (240 IU pregnant mare serum gonadotropin [PMSG] and 120 IU human chorionic gonadotropin [hCG]) at CIDR removal (CPG0, n = 97), and 7 d CIDR plus P.G. 600 (240 IU PMSG and 120 IU hCG) 1 d before CIDR removal (CPG-1, n = 98). Rams (n = 15) were joined with ewes immediately after CIDR removal and remained with ewes for a 21 d breeding period. Lambing data were summarized for the first 10 days of the lambing season and overall. Categorical data were analyzed using the GLIMMIX procedure of SAS whereas non-categorical data were analyzed using the mixed procedure. Proportion of ewes lambing in the first 10 d was greater (P < 0.05) for CPG0 and CPG-1 ewes compared with C ewes, which was greater (P < 0.0001) compared with U ewes. Overall proportion of ewes lambing was greater (P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences (P ≥ 0.84) due to P.G. 600 were detected compared with C. Lambing rate in the first 10 d was greater (P < 0.05) for CPG-1 than C, with CPGO being intermediate, and all CIDR-treated ewes being greater than U (P < 0.0001). Overall lambing rate increased (P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences (P ≥ 0.76) due to P.G. 600 were detected compared with C. Prolificacy was similar among all treatments both for the first 10 d of the lambing season (P = 0.86) and overall (P = 0.80). Day of lambing in the lambing season was reduced (P ≤ 0.03) for CPG0 and CPG-1 compared with CIDR-treated ewes, which was reduced (P < 0.0001) compared with U ewes (days 10.6, 9.0, 13.4, and 24.4 ± 0.9 for CPG0, CPG-1, CON, and U, respectively). Though timing of P.G. 600 did not influence results, the combination of CIDR and P.G. 600 enhanced the proportion of lambs born earlier in the lambing season, and incorporating a CIDR with or without P.G. 600 enhanced the overall proportion of ewes lambing and lambing rate in out-of-season breeding scenarios.

Using donor funding to catalyse investment in malaria prevention in Ghana: an analysis of the potential impact on public and private sector expenditure.

BACKGROUND: An estimated 1.5 billion malaria cases and 7.6 million malaria deaths have been averted globally since 2000; long-lasting insecticidal nets (LLINs) have contributed an estimated 68% of this reduction. Insufficient funding at the international and domestic levels poses a significant threat to future progress and there is growing emphasis on the need for enhanced domestic resource mobilization. The Private Sector Malaria Prevention (PSMP) project was a 3-year intervention to catalyse private sector investment in malaria prevention in Ghana. METHODS: To assess value for money of the intervention, non-donor expenditure in the 5 years post-project catalysed by the initial donor investment was predicted. Non-donor expenditure catalysed by this investment included: workplace partner costs of malaria prevention activities; household costs in purchasing LLINs from retail outlets; domestic resource mobilization (public sector financing and private investors). Annual ratios of projected non-donor expenditure to annualized donor costs were calculated for the 5 years post-project. Alternative scenarios were constructed to explore uncertainty around future consequences of the intervention. RESULTS: The total donor financial cost of the 3-year PSMP project was USD 4,418,996. The average annual economic donor cost per LLIN distributed through retail sector and workplace partners was USD 21.17 and USD 7.55, respectively. Taking a 5-year post-project time horizon, the annualized donor investment costs were USD 735,805. In the best-case scenario, each USD of annualized donor investment led to USD 4.82 in annual projected non-donor expenditure by the fifth-year post-project. With increasingly conservative assumptions around the project consequences, this ratio decreased to 3.58, 2.16, 1.07 and 0.93 in the "very good", "good", "poor" and "worst" case scenarios, respectively. This suggests that in all but the worst-case scenario, donor investment would be exceeded by the non-donor expenditure it catalysed. CONCLUSIONS: The unit cost per net delivered was high, reflecting considerable initial investment costs and relatively low volumes of LLINs sold during the short duration of the project. However, taking a longer time horizon and broader perspective on the consequences of this complex catalytic intervention suggests that considerable domestic resources for malaria control could be mobilized, exceeding the value of the initial donor investment.

A retail audit of mosquito control products in Busia County, western Kenya.

BACKGROUND: Approximately 70% of Kenya's population is at risk for malaria. The core vector control methods in Kenya are insecticide-treated mosquito nets (ITNs) and indoor residual spraying, with supplementary larval source management. In 2015, 21% of ITNs were accessed through the private retail sector. Despite the private sector role in supplying mosquito control products (MCPs), there is little evidence on the availability, sales trends, and consumer preferences for MCPs other than ITNs. This study, a component of a larger research programme focused on evaluating a spatial repellent intervention class for mosquito-borne disease control, addressed this evidence gap on the role of the private sector in supplying MCPs. METHODS: A cross-sectional survey was deployed in a range of retail outlets in Busia County to characterize MCP availability, sales trends, and distribution channels. The questionnaire included 32 closed-ended and four open-ended questions with short answer responses. Descriptive analysis of frequency counts and percentages was carried out to glean insights about commercially available MCPs and the weighted average rank was used to determine consumer preferences for MCPs. Open-ended data was analysed thematically. RESULTS: Retail outlets that stocked MCPs commonly stocked mosquito coils (73.0%), topical repellents (38.1%), aerosol insecticide sprays (23.8%) and ITNs (14.3%). Overall, retailers reported the profits from selling MCPs were adequate and they overwhelmingly planned to continue stocking the products. Of respondents who stocked MCPs, 96.8% responded that sales increased during long rains and 36.5% that sales also surged during short rains. ITNs and baby-size nets were often delivered by the wholesaler. Retailers of aerosol sprays, mosquito coils, and topical repellents either collected stock from the wholesaler or products were delivered to them. Other commercially available MCPs included insecticide incense sticks, electric mosquito strikers, insecticide soaps, electrically heated insecticide mats, and electric insecticide emanators, indicating a well-established market. CONCLUSIONS: The wide range of MCPs in local retail outlets within the study area suggests the need and demand for mosquito control tools, in addition to ITNs, that are affordable, easy to use and effective. The presence of a wide range of MCPs, is a promising sign for the introduction of a spatial repellent intervention class of products that meets consumer needs and preferences.

Species diversity of fungal endophytes across a stress gradient for plants.

Foliar fungal endophytes are one of the most diverse guilds of symbiotic fungi found in the photosynthetic tissues of every plant lineage, but it is unclear how plant environments and leaf resource availability shape their diversity. We explored correlations between leaf nutrient availability and endophyte diversity among Pinus muricata and Vaccinium ovatum plants growing across a soil nutrient gradient spanning a series of coastal terraces in Mendocino, California. Endophyte richness decreased in plants with higher leaf nitrogen-to-phosphorus ratios for both host species, but increased with sodium, which may be toxic to fungi at high concentrations. Isolation frequency, a proxy of fungal biomass, was not significantly predicted by any of the same leaf constituents in the two plant species. We propose that stressed plants can exhibit both low foliar nutrients or high levels of toxic compounds, and that both of these stress responses predict endophyte species richness. Stressful conditions that limit growth of fungi may increase their diversity due to the suppression of otherwise dominating species. Differences between the host species in their endophyte communities may be explained by host specificity, leaf phenology, or microclimates.

Exploring HIV concern in a population of Dominican American women midlife and older.

BACKGROUND: The feminization and ethnic diversification of HIV infection, has resulted in a call for gender- and culture-specific prevention strategies for at-risk groups including Latinos in the United States. The steadily changing demographic profile of the AIDS epidemic challenges prevention strategies to remain relevant and up-to-date, particularly in populations of women midlife and older where an understanding of risk remains under explored. As the CDC requests country-specific HIV risk profiles for Latino communities in the US, understanding the socio-economic, behavioral and personal risk reasons of HIV risk for older Dominican women is critical for prevention. METHODS: We conducted focus group discussions informed by the Theory of Gender and Power (TGP). The three constructs of the TGP: 1) Affective influences/social norms; 2) Gender-specific norms and. 3) Power and Authority guided the thematic analysis and identified themes that described the socio-cultural and contextual reasons that that contribute to perceptions of HIV risk. RESULTS: Sixty Dominican American women ages 57-73 participated in our focus group discussions. Sexual Division of Labour: 1) Economic Dependence; 2) Financial Need and 3) Education and Empowerment. Sexual Division of Power: 4) HIV Risk and 5) Relationship Dynamics. Cathexis: Affective Influences/Social Norms: 6) HIV/AIDS Knowledge and 7) Prevention and Testing. Importantly, participants were concerned about partner fidelity when visiting the Dominican Republic, as the country accounts for the second highest HIV rates in the Caribbean. CONCLUSIONS: Our results confirm previous findings about perceptions of HIV risk and provide additional insight into aging-related aspects of HIV risk for Latino women midlife and older.

Correlates and aetiological factors associated with hedonic well-being among an ageing population of US men and women: secondary data analysis of a national survey.

OBJECTIVE: To understand the gender-specific factors that uniquely contribute to successful ageing in a US population of men and women, 57-85 years of age. This was achieved through the examination of the correlates of subjective well-being defined by health-related quality of life (HRQoL), across several biological and psychosocial determinants of health. DESIGN: Cross-sectional study. SETTING: The National Social Life, Health and Ageing Project (NSHAP), 2010-2011 a representative sample of the US population. PARTICIPANTS: 3377 adults aged 57-85 (1538 men, 1839 women) from the NSHAP. MAIN OUTCOME MEASURES: The biopsychosocial factors of biological/physiological function, symptom status, functional status, general health perceptions and HRQoL happiness. METHOD: HRQoL was measured using the NSHAP wave 2 multistage, stratified area probability sample of US households (n=3377). Variable selection was guided by the Wilson and Cleary model (WCM) that classifies health outcomes at five main levels and characteristics. RESULTS: Our findings indicate differences in biopsychosocial factors comprised in the WCM and their relative importance and unique impact on HRQoL by gender. Women reported significantly lower HRQoL than men (t=3.5, df=3366). The most significant contributors to HRQoL in women were mental health (B=0.31; 0.22, 0.39), loneliness (B=-0.26; -0.35, -0.17), urinary incontinence (B=-0.22; -0.40, -0.05) and support from spouse/partner (B=0.27; 0.10, 0.43) and family B=0.12; 0.03, 0.20). Men indicated mental health (B=0.21; 0.14, 0.29), physical health (B=0.17; 0.10, 0.23), functional difficulties (B=0.38; 0.10, 0.65), loneliness (B=-0.20; -0.26, -0.12), depression (B=-0.36; -0.58, -0.15) and support from friends (B=0.06; 0.10, 0.11) as significant contributors. Those with greater social support had better HRQoL (F=4.22, df=4). Lack of companionship and reliance on spouse/partner were significant HRQoL contributors in both groups. CONCLUSION: Our findings offer insight into ageing, gender and subjective well-being. The results provide an opportunity to identify biopsychosocial factors to inform interventions to support successful ageing.

The future and promise of cognitive behavioral therapy: a commentary.

The Academy for Psychological Clinical Science and the independent accrediting entity it created, the Psychological Clinical Science Accreditation system, have recently launched a movement aimed at reforming all of clinical psychology. If this movement is successful, it will result in a greater emphasis on empirical science in the practice of clinical psychology. As cognitive behavioral therapy (CBT) is the approach that currently has the greatest number of controlled scientific studies supporting it, this should be an impetus for CBT to grow. The very same scientific evidence that supports the efficacy of CBT, however, also shows that CBT is far from fully efficacious. Several recent trends that hold great promise to enhance the effectiveness of CBT are discussed, such as greater integration of CBT with biological approaches, cognitive science, systemic approaches, motivational interviewing, and strengths-based approaches.

Comparison of interventions to reduce sun exposure.

Exposure to ultraviolet (UV) light is the leading behavioral cause of skin cancer. This study evaluated the efficacy of 2 interventions to reduce UV exposure in college students prior to an opportunity for high-intensity exposure. Participants of 1 college campus were assigned randomly to 1 of 2 interventions prior to their spring holiday spent in a warm, sunny location: (1) a community-based informational campaign, or (2) a combination of the campaign and a cognitive-behavioral small group intervention. Participants of a second college campus served as a comparison group. The cognitive-behavioral group exhibited increased knowledge, more positive attitudes toward UV protection, greater advancement through stages of change, and greater protective clothing use relative to the comparison or community-education groups. The informational campaign had little apparent impact in this study.

Youth sport parenting styles and practices.

The purpose of this study was to examine parenting styles and associated parenting practices in youth sport. Following a season-long period of fieldwork, primary data were collected via interviews with 56 parents and supplemented by interviews with 34 of their female children. Data analysis was guided by Grolnick's (2003) theory of parenting styles. Analyses produced five findings: (1) Autonomy-supportive parents provided appropriate structure for their children and allowed them to be involved in decision making. These parents were also able to read their children's mood and reported open bidirectional communication. (2) Controlling parents did not support their children's autonomy, were not sensitive to their children's mood, and tended to report more closed modes of communication. (3) In some families, there were inconsistencies between the styles employed by the mother and father. (4) Some parenting practices varied across different situations. (5) Children had some reciprocal influences on their parents' behaviors. These findings reveal information about the multiple social interactions associated with youth sport parenting.

Levels of social complexity and dimensions of peer experiences in youth sport.

We assessed young adolescent female soccer players' perceptions of their peer group experiences. Data were collected via interviews with 34 girls from two youth soccer teams (M age = 13.0 years). Following inductive discovery analysis, data were subjected to an interpretive theoretical analysis guided by a model of peer experiences (Rubin, Bukowski, & Parker, 2006). Five categories of peer experiences were identified across three levels of social complexity. At the interaction level players integrated new members into the team and learned to interact with different types of people. At the relationship level players learned about managing peer conflict. At the group level a structure of leadership emerged and players learned to work together. Findings demonstrated interfaces between peer interactions, relationships, and group processes while also simplifying some apparently complex systems that characterized peer experiences on the teams studied.

Intervention programs for perpetrators of intimate partner violence: conclusions from a clinical research perspective.

In this article, the authors consider the empirical status of batterer intervention programs (BIPs) for male perpetrators of intimate partner violence (IPV). Recent reviews have reported only small average effect sizes for BIPs, with the small number of randomized trials showing little benefit of BIP attendance in preventing future abuse. The most widely adopted BIP intervention model has little empirical justification to support this dominance, yet states with standards governing the content of BIPs often mandate this approach as a contingency for state funding. Little data exist concerning the moderators and mediators of BIP effects on IPV recidivism, and a variety of factors threaten to impede future design advancements, including "turf" battles regarding the causes of IPV and limited funding outlets. Given this discouraging summary, the authors argue that research efforts concerning BIP effectiveness should borrow the design strategies and programmatic research efforts that have proven successful in psychotherapy research, in which significant advances have been made with regard to the evaluation and validation of empirically supported treatments for a wide variety of mental health problems. They conclude by calling for a new generation of IPV researchers to work across professional boundaries in a multidisciplinary manner to design the sophisticated evaluation studies that funding agencies would readily support, and that would provide the substantive answers to the many IPV-related public health questions that remain.