Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency.

ABSTRACT: A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6-T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior-posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.

Effect of trans-cinnamaldehyde nanoemulsion wash on chicken embryo development in fertilized eggs.

Cleanliness of eggs is critical in successful hatching egg operations. The objective of this study was to investigate the effect of trans-cinnamaldehyde nanoemulsion (TCNE) wash treatments, as a sanitation strategy, on embryonic development in fertilized eggs. Trans-cinnamaldehyde is a generally recognized as safe status phytochemical obtained from cinnamon bark. TCNE were prepared with emulsifiers Tween 80 (Tw.80) or gum Arabic and lecithin (GAL) by sonication. Day-old fertilized eggs were subjected to TCNE wash treatments at 34°C for 5 min, followed by 18 d of incubation at 37.7°C. Washing of fertilized eggs with TCNE-Tw.80 or GAL at 0.48% concentration did not significantly alter the egg weight at d 18 of incubation, as compared to baseline and control (P > 0.05). The egg weight loss (calculated as percentage) did not differ significantly between eggs subjected to nanoemulsion wash treatments and control eggs (P > 0.05). In case of embryo fertility and mortality, for baseline and control, ∼ 95% fertility rate was achieved, with combined early and midterm mortality at 16%. Likewise, TCNE-Tw.80 or TCNE-GAL resulted in 95% fertility (P > 0.05), with 11% and 17% combined early and midterm mortality, respectively. Furthermore, TCNE wash treatments did not differ significantly in yolk sac and embryo weight (as compared to control) and did not affect the length of the d 18 embryo (P > 0.05). Moreover, TCNE wash treatments did not alter tibia weight and length (P > 0.05). Results suggest that TCNE could potentially be used as a natural antimicrobial for fertilized egg sanitation. Further studies in industry settings are warranted.

Personalized Disease Prevention (PDP): study protocol for a cluster-randomized clinical trial.

BACKGROUND: The US Preventive Services Task Force recommends 25 primary preventive services for middle-aged adults, but it can be difficult to do them all. METHODS: The Personalized Disease Prevention (PDP) cluster-randomized clinical trial will evaluate whether patients and their providers benefit from an evidence-based decision tool to prioritize preventive services based on their potential to improve quality-adjusted life expectancy. The decision tool will be individualized for patient risk factors and available in the electronic health record. This Phase III trial seeks to enroll 60 primary care providers (clusters) and 600 patients aged 40-75 years. Half of providers will be assigned to an intervention to utilize the decision tool with approximately 10 patients each, and half will be assigned to usual care. Mixed-methods follow-up will include collection of preventive care utilization from electronic health records, patient and physician surveys, and qualitative interviews. We hypothesize that quality-adjusted life expectancy will increase by more in patients who receive the intervention, as compared with controls. DISCUSSION: PDP will test a novel, holistic approach to help patients and providers prioritize the delivery of preventive services, based on patient risk factors in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463887. Registered on July 19, 2022.

Association of Thoracic Aortic Aneurysm Size With Long-term Patient Outcomes: The KP-TAA Study.

Importance: The risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making. Objective: To evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system. Design, Setting, and Participants: The Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021. Exposures: TAA size. Main Outcomes and Measures: Aortic dissection (AD), all-cause death, and elective aortic surgery. Results: Of 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm. Conclusions and Relevance: In a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.

Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort.

BACKGROUND: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders. OBJECTIVES: We investigated whether higher intakes of periconceptional or midpregnancy folate, as recommended, were associated with a reduced risk of offspring cerebral palsy (CP). METHODS: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father, and Child Cohort Study [combined as MOthers and BAbies in Norway and Denmark (MOBAND-CP)]. A total of 190,989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22-25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairments, were our outcomes of interest. RESULTS: Periconceptional folic acid supplementation was not associated with CP [adjusted odds ratio (aOR), 1.02; 95% CI: 0.82-1.28]. However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR, 0.74; 95% CI: 0.57-0.96), and inverse associations were indicated for both the unilateral (aOR, 0.68; 95% CI: 0.46-1.02) and bilateral (aOR, 0.70; 95% CI: 0.49-1.02) spastic subtypes, although the associations were not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR, 0.49; 95% CI: 0.29-0.83), while for unilateral CP the aOR was 0.63 (95% CI: 0.34-1.22) for intakes of ≥500 compared to ≤199 dietary folate equivalents/day during midpregnancy. CONCLUSIONS: Our findings suggest that folate intakes in GWs 9 to 12 and midpregnancy were associated with lower risks of CP, while no association was observed for periconceptional supplementation.

Whitefly Endosymbionts: Biology, Evolution, and Plant Virus Interactions.

Whiteflies (Hemiptera: Aleyrodidae) are sap-feeding global agricultural pests. These piercing-sucking insects have coevolved with intracellular endosymbiotic bacteria that help to supplement their nutrient-poor plant sap diets with essential amino acids and carotenoids. These obligate, primary endosymbionts have been incorporated into specialized organs called bacteriomes where they sometimes coexist with facultative, secondary endosymbionts. All whitefly species harbor the primary endosymbiont Candidatus Portiera aleyrodidarum and have a variable number of secondary endosymbionts. The secondary endosymbiont complement harbored by the cryptic whitefly species Bemisia tabaci is particularly complex with various assemblages of seven different genera identified to date. In this review, we discuss whitefly associated primary and secondary endosymbionts. We focus on those associated with the notorious B. tabaci species complex with emphasis on their biological characteristics and diversity. We also discuss their interactions with phytopathogenic begomoviruses (family Geminiviridae), which are transmitted exclusively by B. tabaci in a persistent-circulative manner. Unraveling the complex interactions of these endosymbionts with their insect hosts and plant viruses could lead to advancements in whitefly and whitefly transmitted virus management.

Complications associated with surgical dehorning in goats: A retrospective study of 239 cases.

OBJECTIVE: This article describes complications following surgical dehorning of goats. STUDY DESIGN: Retrospective. Medical records of goats that underwent surgical dehorning were reviewed. ANIMALS: Two hundred thirty-nine goats. METHODS: The medical records of 239 goats, not previously dehorned by other methods, that were cosmetically dehorned between January 2006 and April 2016, were reviewed. Data retrieved from the medical records included breed, weight, the surgeon performing the procedure, intraoperative complications, and the occurrence of return visits to the teaching hospital because of complications related to the dehorning procedure. The owner of record then completed a standard questionnaire during a telephone interview. RESULTS: One or more complications following the surgical dehorning procedure were reported in 93/239 (38.91%) of goats. Complications were divided into major and minor categories. Eighty-four of 239 goats (35.14%) had minor complications, 3/239 goats (1.26%) experienced major complications, and 6/239 (2.51%) had both major and minor complications. The mean weight of goats with complications was 29.73 kg compared to 24.91 kg for goats without complications. This difference was statistically significant (P = .015). CONCLUSION: Surgical dehorning of goats results in a high rate of complications; however, the majority of these complications are minor and do not affect health and performance of the goats. Goats experiencing complications weighed significantly more than goats without complications. CLINICAL SIGNIFICANCE: Surgical dehorning of goats requires minimal aftercare and results in a low rate of serious complications.

Urban parks provide ecosystem services by retaining metals and nutrients in soils.

Urban greenspaces provide ecosystem services like more natural ecosystems do. For instance, vegetation modifies soil properties, including pH and soil organic matter content, yet little is known about its effect on metals. We investigated whether the accumulation and mobility of heavy metals, nutrients and carbon is affected by plant functional types (evergreen or deciduous trees, lawns) in urban parks of varying ages in southern Finland. Plant types modified soil physico-chemical parameters differently, resulting in diverging accumulation and mobility of metals and other elements in park soils. However, the effects of plant functional type depended on park age: lawns in parks of ca. 50 y old had the highest contents of Cr, Cu, Fe, Mn, Ni, and Zn, and in these, and older parks (>100 y old), contents of most metals were lowest under evergreen trees. The mobility of metals and other elements was influenced by the amount of water leached through the soils, highlighting the importance of vegetation on hydrology. Soils under evergreen trees in young parks and lawns in intermediately-aged parks were most permeable to water, and thus had high loads of Ca, Cr, Cu, Fe, Ni, tot-P and tot-N. The loads/concentrations of elements in the leachates was not clearly reflected by their content/concentration in the soil, alluding to the storage capacity of these elements in urban park soils. Our results suggest that in urban systems with a high proportion of impermeable surfaces, park soil has the potential to store nutrients and metals and provide an important ecosystem service particularly in polluted cities.

How optimal caseload midwifery can modify predictors for preterm birth in young women: Integrated findings from a mixed methods study.

OBJECTIVE: to identify possible mechanisms by which caseload midwifery reduces preterm birth for young childbearing women. DESIGN: a mixed methods triangulation, convergence design was used to answer the research question 'How does the way maternity care is provided affect the health and well-being of young women and their babies?' The project generated quantitative and qualitative findings which were collected and analysed concurrently then separately analysed and published. The research design enabled integration of the quantitative and qualitative findings for further interpretation through a critical pragmatic lens. SETTING: a tertiary maternity hospital in Australia providing care to approximately 500 pregnant young women (aged 21 years or less) each year. Three distinct models of care were offered: caseload midwifery, young women's clinic, and standard 'fragmented' care. PARTICIPANTS: a cohort study included data from 1971 young women and babies during 2008-2012. An ethnographic study included analysis of focus group interviews with four caseload midwives in the young women's midwifery group practice; as well as ten pregnant and postnatal young women receiving caseload midwifery care. FINDINGS: integrated analysis of the quantitative and qualitative findings suggested particular features in the model of care which facilitated young women turning up for antenatal care (at an earlier gestation and more frequently) and buying in to the process (disclosing risks, engaging in self-care activities and accepting referrals for assistance). We conceptualised that Optimal Caseload Midwifery promotes Synergistic Health Engagement between midwife and the young woman. KEY CONCLUSIONS: optimal Caseload Midwifery (which includes midwives with specific personal attributes and philosophical commitments, along with appropriate institutional infrastructure and support) facilitates midwives and young clients to develop trusting relationships and engage in maternity care. Health engagement can modify predictors for preterm birth that are common amongst pregnant adolescents by promoting earlier maternity booking, sufficient antenatal care, greater emotional resilience, ideal gestational weight gain, less smoking/drug use, and fewer untreated genito-urinary infections. IMPLICATIONS FOR PRACTICE: the institutional infrastructure and managerial support for caseload midwifery should value and prioritise the philosophical commitments and personal attributes required to optimise the model. Furthermore the location of visits, between appointment access to primary midwife, and back-up system should be organised to optimise the midwife-woman relationship in order to promote the young woman's engagement with maternity care.

Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International Population-Based Study.

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.

A randomized pilot study on the effect of niacin on pulmonary arterial pressure.

BACKGROUND: Niacin induces the release of vasodilating prostaglandins, for which receptors are present within the pulmonary arterial circulation. We hypothesized that immediate-release niacin would reduce right ventricular systolic pressure in patients with pulmonary hypertension in a randomized, double-blinded, single-dose provocation study. METHODS: We recruited inpatient subjects with a Doppler echocardiogram showing a peak tricuspid regurgitation (TR) jet velocity of 2.7 m/s or greater, and who were free of known pulmonary vascular disease. Subjects were randomized in a 1:2:2 ratio to receive a single dose of either placebo, niacin 100 mg or niacin 500 mg, respectively. TR jet velocities were measured immediately before, and 1 hour post dose, corresponding to peak niacin absorption and prostaglandin release. The primary endpoint was the change in mean TR jet velocity measured over ten successive cardiac cycles. RESULTS: The baseline mean estimated right ventricular systolic pressure (RVSP) for all 49 subjects (25 male) was 51.9 ± 12.1 mm Hg. The primary endpoint of mean change in TR jet velocity was 0.016 ± 0.065 m/s in the placebo group, compared to -0.017 ± 0.065 m/s with niacin 100 mg, and -0.063 ± 0.038 m/s with niacin 500 mg (P = 0.63). The change in maximum estimated RVSP across the three drug groups was 0.2 ± 1.6 mm Hg, -1.3 ± 1.8 mm Hg and -2.2 ± 1.2 mm Hg (P = 0.62). In exploratory pairwise analysis in the high-dose niacin group (500 mg), the reduction in mean RVSP was from 50.9 ± 9.4 mm Hg to 48.7 ± 10.0 mm Hg (P = 0.09). CONCLUSIONS: A single dose of immediate-release niacin (100 mg or 500 mg) had no significant effect on RVSP 1 hour post administration. A nonsignificant dose-dependent trend for a modest reduction in RVSP, most notable in the 500 mg group, was noted. (ISRCTN number 12353191, registered April 23, 2015).

Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial.

IMPORTANCE: Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. OBJECTIVE: To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. INTERVENTIONS: Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. RESULTS: Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement. CONCLUSIONS AND RELEVANCE: Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01052116.

Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer.

BACKGROUND: To determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Patients with Magnetic resonance imaging (MRI) or ultrasound defined T3 or T4 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6-9 weeks following the completion of chemoradiation. RESULTS: Thirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease-free survival at 3 years is 75.5% (confidence interval: 55.1-87.6%). CONCLUSIONS: Erlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR.

Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design.

Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms.

State-of-the-art and future directions in multilevel interventions across the cancer control continuum.

We conducted literature searches and analyses to describe the current state of multilevel intervention (MLI) research and to identify opportunities to advance cancer control and prevention. We found single-level studies that considered other contextually important levels, and multilevel health-care systems research and community-wide studies. This literature is characterized by limited reporting of theoretical, contextual, temporal, and implementation factors. Most MLIs focus on prevention and screening, rather than diagnosis, treatment, or survivorship. Opportunities relate to 1) dynamic, adaptive emergent interventions and research designs that evolve over time by attending to contextual factors and interactions across levels; 2) analyses that include simulation modeling, or multimethod approaches that integrate quantitative and qualitative methods; and 3) translation and intervention approaches that locally reinvent MLIs in different contexts. MLIs have great potential to reduce cancer burden by using theory and integrating quantitative, qualitative, participatory, and transdisciplinary methods that continually seek alignment across intervention levels, pay attention to context, and adapt over time.

Mindfulness and problem gambling: a review of the literature.

This article reviews the literature with respect to mindfulness and its potential for reducing the severity of problem gambling behaviour. Interest in the role of mindfulness as a treatment for problem gambling has gained the attention of researchers across Australia, the United States, and Canada. However, the literature is limited and current studies have severe methodological limitations. Despite this issue, investigations have revealed that dispositional mindfulness is related to less severe problem gambling outcomes and that psychological distress, overconfidence and risk willingness, myopic focus on reward and ego involvement may act as mediators in this relationship. Moreover, the literature indicates that the inverse relationship between dispositional mindfulness and psychological distress may be mediated by factors such as values clarification; emotional, cognitive, and behavioural flexibility; non-attachment; emotion dysregulation/distress intolerance; thought suppression; and rumination. This article discusses the theoretical and clinical implications of these relationships with respect to mindfulness-based interventions for problem gambling. It is recommended that the approach be considered with cautious optimism.

ACCF/AHA methodology for the development of quality measures for cardiovascular technology: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures.

Consistent with the growing national focus on healthcare quality, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have taken a leadership role over the past decade in developing measures of the quality of cardiovascular care by convening a joint ACCF/AHA Task Force on Performance Measures. The Task Force is charged with identifying the clinical topics appropriate for the development of performance measures and with assembling writing committees composed of clinical and methodological experts in collaboration with appropriate subspecialty societies. The Task Force has also created methodology documents that offer guidance in the development of process, outcome, composite, and efficiency measures. Cardiovascular performance measures using existing ACCF/AHA methodology are based on Class I or Class III guidelines recommendations, usually with Level A evidence. These performance measures, based on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures for both internal quality improvement and public reporting. However, many of the tools for diagnosis and treatment of cardiovascular disease involve advanced technologies, such as cardiac imaging, for which there are often no underlying guideline documents. Because these technologies affect the quality of cardiovascular care and also have the potential to contribute to cardiovascular health expenditures, there is a need for more critical assessment of the use of technology, including the development of quality and performance measures in areas in which guideline recommendations are absent. The evaluation of quality in the use of cardiovascular technologies requires consideration of multiple parameters that differ from other healthcare processes. The present document describes methodology for development of 2 new classes of quality measures in these situations, appropriate use measures and structure/safety measures. Appropriate use measures are based on specific indications, processes, or parameters of care for which high level of evidence data and Class I or Class III guideline recommendations may be lacking but are addressed in ACCF appropriate use criteria documents. Structure/safety measures represent measures developed to address structural aspects of the use of healthcare technology (e.g., laboratory accreditation, personnel training, and credentialing) or quality issues related to patient safety when there are neither guidelines recommendations nor appropriate use criteria. Although the strength of evidence for appropriate use measures and structure/safety measures may not be as strong as that for formal performance measures, they are quality measures that are otherwise rigorously developed, reviewed, tested, and approved in the same manner as ACCF/AHA performance measures. The ultimate goal of the present document is to provide direction in defining and measuring the appropriate use-avoiding not only underuse but also overuse and misuse-and proper application of cardiovascular technology and to describe how such appropriate use measures and structure/safety measures might be developed for the purposes of quality improvement and public reporting. It is anticipated that this effort will help focus the national dialogue on the use of cardiovascular technology and away from the current concerns about volume and cost alone to a more holistic emphasis on value.

ACCF/AHA methodology for the development of quality measures for cardiovascular technology: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures.

Consistent with the growing national focus on healthcare quality, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have taken a leadership role over the past decade in developing measures of the quality of cardiovascular care by convening a joint ACCF/AHA Task Force on Performance Measures. The Task Force is charged with identifying the clinical topics appropriate for the development of performance measures and with assembling writing committees composed of clinical and methodological experts in collaboration with appropriate subspecialty societies. The Task Force has also created methodology documents that offer guidance in the development of process, outcome, composite, and efficiency measures. Cardiovascular performance measures using existing ACCF/AHA methodology are based on Class I or Class III guidelines recommendations, usually with Level A evidence. These performance measures, based on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures for both internal quality improvement and public reporting. However, many of the tools for diagnosis and treatment of cardiovascular disease involve advanced technologies, such as cardiac imaging, for which there are often no underlying guideline documents. Because these technologies affect the quality of cardiovascular care and also have the potential to contribute to cardiovascular health expenditures, there is a need for more critical assessment of the use of technology, including the development of quality and performance measures in areas in which guideline recommendations are absent. The evaluation of quality in the use of cardiovascular technologies requires consideration of multiple parameters that differ from other healthcare processes. The present document describes methodology for development of 2 new classes of quality measures in these situations, appropriate use measures and structure/safety measures. Appropriate use measures are based on specific indications, processes, or parameters of care for which high level of evidence data and Class I or Class III guideline recommendations may be lacking but are addressed in ACCF appropriate use criteria documents. Structure/safety measures represent measures developed to address structural aspects of the use of healthcare technology (e.g., laboratory accreditation, personnel training, and credentialing) or quality issues related to patient safety when there are neither guidelines recommendations nor appropriate use criteria. Although the strength of evidence for appropriate use measures and structure/safety measures may not be as strong as that for formal performance measures, they are quality measures that are otherwise rigorously developed, reviewed, tested, and approved in the same manner as ACCF/AHA performance measures. The ultimate goal of the present document is to provide direction in defining and measuring the appropriate use-avoiding not only underuse but also overuse and misuse-and proper application of cardiovascular technology and to describe how such appropriate use measures and structure/safety measures might be developed for the purposes of quality improvement and public reporting. It is anticipated that this effort will help focus the national dialogue on the use of cardiovascular technology and away from the current concerns about volume and cost alone to a more holistic emphasis on value.

Modulation of NMDA receptor function by inhibition of D-amino acid oxidase in rodent brain.

Observations that N-Methyl-D-Aspartate (NMDA) antagonists produce symptoms in humans that are similar to those seen in schizophrenia have led to the current hypothesis that schizophrenia might result from NMDA receptor hypofunction. Inhibition of D-amino acid oxidase (DAAO), the enzyme responsible for degradation of D-serine, should lead to increased levels of this co-agonist at the NMDA receptor, and thereby provide a therapeutic approach to schizophrenia. We have profiled some of the preclinical biochemical, electrophysiological, and behavioral consequences of administering potent and selective inhibitors of DAAO to rodents to begin to test this hypothesis. Inhibition of DAAO activity resulted in a significant dose and time dependent increase in D-serine only in the cerebellum, although a time delay was observed between peak plasma or brain drug concentration and cerebellum D-serine response. Pharmacokinetic/pharmacodynamic (PK/PD) modeling employing a mechanism-based indirect response model was used to characterize the correlation between free brain drug concentration and D-serine accumulation. DAAO inhibitors had little or no activity in rodent models considered predictive for antipsychotic activity. The inhibitors did, however, affect cortical activity in the Mescaline-Induced Scratching model, produced a modest but significant increase in NMDA receptor-mediated synaptic currents in primary neuronal cultures from rat hippocampus, and resulted in a significant increase in evoked hippocampal theta rhythm, an in vivo electrophysiological model of hippocampal activity. These findings demonstrate that although DAAO inhibition did not cause a measurable increase in D-serine in forebrain, it did affect hippocampal and cortical activity, possibly through augmentation of NMDA receptor-mediated currents.

Stem cell therapy for cardiac disease: what can be learned from oncology.

Hematopoietic stem cells (HSCs) are the most well-characterized and studied stem cells. They have been used to treat various benign and malignant hematologic disorders. Most stem cell transplant recipients survive more than 5 years without any evidence of their original clinical disease. Early animal trials have demonstrated the ability to improve cardiac function by transfer of HSCs into the myocardium, and early human studies have demonstrated the feasibility and safety of this approach. Trials in patients after myocardial infarction and with chronic heart failure have seen limited and mixed success, probably because of the various cell types and methods used.