Apology for the publication of Sheng et al. (2024).

Recently, Cultural Diversity & Ethnic Minority Psychology (CDEMP) published Sheng et al.'s (see record 2024-72017-001) article titled "The Development of Tibetan Children's Racial Bias in Empathy: The Mediating Role of Ethnic Identity and Wrongfulness of Ethnic Intergroup Bias." The article went through the standard peer review process. Subsequent to its publication, one of our readers expressed concerns regarding the biased language (e.g., "backwardness of education") and deficit-oriented interpretation of findings (e.g., "the geographical environment and traditional way of life in Tibet can also impact the development of [racial biases in empathy] in Tibetan children"). The reader rightly pointed out that this language and interpretation reinforce imperialism, particularly given the complex relations between Tibet and China. We sincerely apologize to our readers, and especially to our Tibetan colleagues, for failing to identify these issues prior to the publication of the article.Wetake accountability for the oversight and have followed due process to correct our mistakes in the publication of this article. We will also take action to prevent this from happening again. In this editorial, we describe the study, actions taken by the CDEMP Editorial Team, the authors' response, and future actions to be taken by the CDEMP Editorial Team. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Validation of a diet-induced Macaca fascicularis model of non-alcoholic steatohepatitis with dietary and pioglitazone interventions.

AIM: To develop an obese, insulin-resistant cynomolgus monkey model of non-alcoholic steatohepatitis (NASH) with fibrosis with a high fat/high cholesterol (HFHC) diet (with or without high fructose) and test its responsiveness to caloric restriction or pioglitazone. METHODS: First, two groups of monkeys (n = 24/group) with histologically proven NASH and fibrosis were fed the HFHC diet for 17 weeks. The treatment group was subjected to a 40% caloric restriction (CR) and had their diet switched from the HFHC diet to a chow diet (DSCR). Paired liver biopsies were taken before and 17 weeks after DSCR. Subsets of monkeys (nine/group) had whole liver fat content assessed by MRI. Next, two groups of monkeys with histologically proven NASH and fibrosis were treated with vehicle (n = 9) or pioglitazone (n = 20) over 24 weeks. RESULTS: The HFHC and DSCR groups lost 0.9% and 11.4% of body weight, respectively. After 17 weeks, non-alcoholic fatty liver disease activity score (NAS) improvement was observed in 66.7% of the DSCR group versus 12.5% of the HFHC group (P < .001). Hepatic fat was reduced to 5.2% in the DSCR group versus 23.0% in the HFHC group (P = .0001). After 24 weeks, NAS improvement was seen in 30% of the pioglitazone group versus 0% of the vehicle group (P = .08). CONCLUSIONS: Both weight loss induced by DSCR and treatment with pioglitazone improve the histological features of NASH in a diet-induced cynomolgus monkey model. This model provides a translational preclinical model for testing novel NASH therapies.

Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes.

Importance: Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited. Objective: To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes. Design, Setting, and Participants: Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017. Exposures: Self-reported cannabis exposure in pregnancy was ascertained through routine perinatal care. Main Outcomes and Measures: The primary outcome was preterm birth before 37 weeks' gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks' gestation (late preterm), 32 to 33 6/7 weeks' gestation, 28 to 31 6/7 weeks' gestation, and less than 28 weeks' gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding. Results: In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51% of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks' gestation was 6.1% among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95% CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98% (95% CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95% CI, 1.45-1.61]), placental abruption (1.6% vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3% vs 13.8%; RR, 1.40 [95% CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95% CI, 1.13-1.45]). Conclusions and Relevance: Among pregnant women in Ontario, Canada, reported cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.

Pharmacokinetics and immunogenicity investigation of a human anti-interleukin-17 monoclonal antibody in non-naïve cynomolgus monkeys.

The pharmacokinetics (PK) of biologic therapeutics, especially monoclonal antibodies (mAbs), in monkeys generally presents the most relevant predictive PK information for humans. However, human mAbs, xenogeneic proteins to monkeys, are likely to be immunogenic. Monkeys previously treated with a human mAb (non-naïve) may have developed antidrug antibodies (ADAs) that cross-react with another test mAb in subsequent studies. Unlike PK studies for small-molecule therapeutics, in which animals may be reused, naïve monkeys have been used almost exclusively for preclinical PK studies of biologic therapeutics to avoid potential pre-existing immunologic cross-reactivity issues. The propensity and extent of pre-existing ADAs have not been systematically investigated to date. In this study, the PK and immunogenicity of mAb A, a human anti-human interkeukin-17 mAb, were investigated in a colony of 31 cynomolgus monkeys previously exposed to other human mAbs against different targets. We screened the monkeys for pre-existing antibodies to mAb A prior to the PK study and showed that 44% of the monkeys had pre-existing cross-reactive antibodies to mAb A, which could affect the PK characterization of the antibody. In the subcolony of monkeys without measurable pre-existing ADAs, PK and immunogenicity of mAb A were successfully characterized. The impact of ADAs on mAb A PK was also demonstrated in the monkeys with pre-existing ADAs. Here we report the results and propose a pragmatic approach for the use of non-naïve monkeys when conducting PK studies of biologic therapeutics.

4ß-Hydroxycholesterol as an endogenous biomarker of CYP3A activity in cynomolgus monkeys.

It has been proposed that in humans 4ß-hydroxycholesterol is formed mainly by CYP3A-catalyzed metabolism of cholesterol and thus may serve as an endogenous marker for CYP3A activity. The cynomolgus monkey is widely used as one of the nonrodent preclinical safety species in pharmaceutical research. In the current study, the potential application of 4ß-hydroxycholesterol as an endogenous biomarker of CYP3A in response to drug treatment was evaluated in cynomolgus monkeys. Following multiple oral administration of rifampicin (a known CYP3A inducer) at 15 mg/kg/d in cynomolgus monkeys, the mean serum 4ß-hydroxycholesterol levels increased 4-fold from the baseline of 55.3 ± 21.7 to 221 ± 53.4 ng/ml. The mean concentration ratios of 4ß-hydroxycholesterol to cholesterol increased 5-fold. The data suggest that 4ß-hydroxycholesterol formation from cholesterol metabolism was induced by rifampicin treatment in monkeys. This observation correlated with the metabolism of midazolam (a probe substrate of CYP3A activity) monitored in the same study. The serum exposure (area under the curve) of midazolam was markedly decreased by ∼95%, confirming the induction of CYP3A catalytic activity by rifampicin treatment in monkeys. The formation of 4ß-hydroxycholesterol from cholesterol was specifically mediated by recombinant cynomolgus CYP3A8 and CYP3A5. The Km values of CYP3A8 and CYP3A5 for 4ß-hydroxycholesterol formation from cholesterol were 204 and 104 µM, respectively, and Vmax values were 0.600 and 0.310 pg/pmol/min, respectively. The results suggest that 4ß-hydroxycholesterol can be used as an endogenous biomarker to identify strong CYP3A inducers in cynomolgus monkeys, which may help to evaluate drug-drug interaction potential of drug candidates in preclinical settings.

Conceptualizing Educational Comparability in Distributed Health Professions Education: A Scoping Review.

PURPOSE: This study aimed to create greater clarity about the current understanding and formulate a model of how educational comparability has been used in the literature to inform practice. METHOD: The authors conducted a literature search of 9 online databases, seeking articles published on comparability in distributed settings in health professions education before August 2021, with an updated search conducted in May 2023. Using a structured scoping review approach, 2 reviewers independently screened articles for eligibility with inclusion criteria and extracted key data. All authors participated in the descriptive analysis of the extracted data. RESULTS: Twenty-four articles published between 1987 and 2021 met the inclusion criteria. Most articles were focused on medical education programs (n = 21) and located in North America (n = 18). The main rationale for discussing comparability was accreditation. These articles did not offer definitions or discussions about what comparability means. The program logic model was used as an organizing framework to synthesize the literature on practices that schools undertake to facilitate and demonstrate comparability in the design (inputs), implementation (activities), and evaluation (outcomes) of distributed education. Inputs include common learning objectives, identical assessment tools and policies, governance models that enable clear communication, and reporting structure that is supported by technological infrastructure. Activities include faculty planning meetings and faculty development training. Outcomes include student experiences and academic performances. CONCLUSIONS: This study demonstrated that a more complex understanding of the dynamics of educational processes and practices is required to better guide the practice of educational comparability within distributed education programs. In addition to highlighting the need to develop an accepted definition of educational comparability, further elucidation of the underlying dynamics among input, activities, and outcomes would help to better determine what drivers should be prioritized when considering educational change with attention to context within distributed education.

Nonclinical safety assessment of a synthetic peptide thrombopoietin agonist: effects on platelets, bone homeostasis, and immunogenicity and the implications for clinical safety monitoring of adverse bone effects.

RWJ-800088 is a novel, potent polyethylene glycol (PEG)-conjugated thrombopoietin (TPO) mimetic that increases platelet levels and protects against thrombocytopenia. A nonclinical safety program was customized for this peptide that takes into account its protein-like structure, synthetic chemical nature, agonist pharmacologic activity, and mode of administration. In repeat-dose toxicity studies, the salient findings were dose-related increases in circulating platelet counts, mean platelet volume, and megakaryocytes in the bone marrow with no antibody formation. Reversible myelofibrosis and hyperostosis were observed in rats, but not dogs, when the circulating platelet levels exceeded 3× those of vehicle controls. The bone effects were due to the exaggerated pharmacologic effect and excessive stimulation and elevation of megakaryocytes by TPO, which results in intramedullary proliferation of fibroblasts and mesenchymal cells followed by osseous metaplasia. These findings support the use of platelet elevations of >3× as a stopping criterion to prevent potential adverse bone-related effects in humans.

Association of Maternal Opioid Use in Pregnancy With Adverse Perinatal Outcomes in Ontario, Canada, From 2012 to 2018.

Importance: A recent epidemic of opioid abuse has been described in many communities, although population-based data on trends in use in pregnancy and perinatal outcomes after in utero exposure remain limited. Objective: To assess trends in prenatal opioid use and the potential association between prenatal opioid use and preterm birth and adverse perinatal outcomes. Design, Setting, and Participants: This population-based retrospective cohort study covered live births and stillbirths among adolescents and women 15 years and older from April 1, 2012, to March 31, 2018, in Ontario, Canada. Data were analyzed from July 29 to October 15, 2019. Exposures: Any opioid use in pregnancy, ascertained through self-reporting and routine prenatal care. Main Outcome and Measures: The primary outcome was preterm birth before a gestational age of 37 weeks. Separate indicators for birth occurring at gestational ages of 34 to 36 weeks (plus 6 to 7 days; late preterm), 32 to 33 weeks (plus 6 to 7 days), 28 to 31 weeks (plus 6 to 7 days), and less than 28 weeks (very preterm birth). Secondary outcomes included small for gestational age, stillbirth, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference and relative risk (RR) of outcomes associated with cannabis exposure to control for confounding. Results: Among 710 911 women included in the analytic sample (mean [SD] age, 30.4 [5.3] years), 8059 used opioids (1.1%), with prevalence decreasing from 1.31% (95% CI, 1.25%-1.38%) in fiscal year 2012-2013 to 1.05% (95% CI, 0.99%-1.11%) in fiscal year 2017-2018 (P < .001 for trend). Use was highest among women in the lowest quintile of area-level income (2.36% vs 0.56% in the highest quintile; RR, 3.86; 95% CI, 3.58-4.15) and did not decrease over time in this group (from 2.63% [95% CI, 2.41%-2.87%] in 2012-2013 to 2.35% [95% CI, 2.14%-2.58%] in 2017-2018; P = .23 for trend). The crude rate of preterm birth at a gestational age of less than 37 weeks was 14.0% (n = 1127) among women with reported use in pregnancy and 6.0% (n = 42 226) among women who did not use opioids in the unmatched cohort. The adjusted RR for preterm birth before a gestational age of 37 weeks was 1.63 (95% CI, 1.52-1.75) among opioid users compared with nonusers and 1.77 (95% CI, 1.35-2.31) for preterm birth before 32 weeks. Among newborns, risk for neonatal intensive care was 40.5% with perinatal exposure to opioids compared with 13.9% in unexposed infants (RR, 2.91; 95% CI, 2.80-3.03). Conclusions and Relevance: Rates of opioid use in pregnancy have declined in recent years, although use remains significantly higher among lower-income women. In this large population-based cohort, opioid use in pregnancy was associated with an increased risk of preterm birth and admission to a neonatal intensive care unit.

The effectiveness of substance use interventions for homeless and vulnerably housed persons: A systematic review of systematic reviews on supervised consumption facilities, managed alcohol programs, and pharmacological agents for opioid use disorder.

BACKGROUND: Substance use is disproportionately high among people who are homeless or vulnerably housed. We performed a systematic overview of reviews examining the effects of selected harm reduction and pharmacological interventions on the health and social well-being of people who use substances, with a focus on homeless populations. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, PsycINFO, Joanna Briggs Institute EBP, Cochrane Database of Systematic Reviews and DARE for systematic reviews from inception to August 2019. We conducted a grey literature search and hand searched reference lists. We selected reviews that synthesized evidence on supervised consumption facilities, managed alcohol programs and pharmacological interventions for opioid use disorders. We abstracted data specific to homeless or vulnerably housed populations. We assessed certainty of the evidence using the GRADE approach. Our search identified 483 citations and 30 systematic reviews met all inclusion criteria, capturing the results from 442 primary studies. This included three reviews on supervised consumption facilities, 24 on pharmacological interventions, and three on managed alcohol programs. Supervised consumption facilities decreased lethal overdoses and other high risk behaviours without any significant harm, and improved access to care. Pharmaceutical interventions reduced mortality, morbidity, and substance use, but the impact on retention in treatment, mental illness and access to care was variable. Managed alcohol programs reduced or stabilized alcohol consumption. Few studies on managed alcohol programs reported deaths. CONCLUSIONS: Substance use is a common chronic condition impacting homeless populations. Supervised consumption facilities reduce overdose and improve access to care, while pharmacological interventions may play a role in reducing harms and addressing other morbidity. High quality evidence on managed alcohol programs is limited.

Maternal cannabis use in pregnancy and child neurodevelopmental outcomes.

Cannabis use in pregnancy has increased1,2, and many women continue to use it throughout pregnancy3. With the legalization of recreational cannabis in many jurisdictions, there is concern about potentially adverse childhood outcomes related to prenatal exposure4. Using the provincial birth registry containing information on cannabis use during pregnancy, we perform a retrospective analysis of all live births in Ontario, Canada, between 1 April 2007 and 31 March 2012. We link pregnancy and birth data to provincial health administrative databases to ascertain child neurodevelopmental outcomes. We use matching techniques to control for confounding and Cox proportional hazards regression models to examine associations between prenatal cannabis use and child neurodevelopment. We find an association between maternal cannabis use in pregnancy and the incidence of autism spectrum disorder in the offspring. The incidence of autism spectrum disorder diagnosis was 4.00 per 1,000 person-years among children with exposure compared to 2.42 among unexposed children, and the fully adjusted hazard ratio was 1.51 (95% confidence interval: 1.17-1.96) in the matched cohort. The incidence of intellectual disability and learning disorders was higher among offspring of mothers who use cannabis in pregnancy, although less statistically robust. We emphasize a cautious interpretation of these findings given the likelihood of residual confounding.

Nanocellulose-Based Conductive Membranes for Free-Standing Supercapacitors: A Review.

There is currently strong demand for the development of advanced energy storage devices with inexpensive, flexibility, lightweight, and eco-friendly materials. Cellulose is considered as a suitable material that has the potential to meet the requirements of the advanced energy storage devices. Specifically, nanocellulose has been shown to be an environmentally friendly material that has low density and high specific strength, Young's modulus, and surface-to-volume ratio compared to synthetic materials. Furthermore, it can be isolated from a variety of plants through several simple and rapid methods. Cellulose-based conductive composite membranes can be assembled into supercapacitors to achieve free-standing, lightweight, and flexible energy storage devices. Therefore, they have attracted extensive research interest for the development of small-size wearable devices, implantable sensors, and smart skin. Various conductive materials can be loaded onto nanocellulose substrates to endow or enhance the electrochemical performance of supercapacitors by taking advantage of the high loading capacity of nanocellulose membranes for brittle conductive materials. Several factors can impact the electronic performance of a nanocellulose-based supercapacitor, such as the methods of loading conductive materials and the types of conductive materials, as will be discussed in this review.

Trends and correlates of cannabis use in pregnancy: a population-based study in Ontario, Canada from 2012 to 2017.

OBJECTIVE: Forthcoming legislative changes will legalize and make cannabis widely available in Canada. We conducted an analysis of Ontario's birth registry to determine recent trends and correlates of cannabis use in pregnancy. METHODS: We conducted a population-based retrospective cohort study assembled from the Better Outcomes Registry & Network (BORN) Ontario database, covering live births and stillbirths in Ontario between April 2012 and December 2017. Trends in self-reported cannabis use in pregnancy were analyzed according to maternal age and area-level socio-economic status (SES) using log binomial regression analysis. RESULTS: A total of 10,731 women reported cannabis use in pregnancy. Prevalence increased from 1.2% in 2012 to 1.8% in 2017 (p-trend, < 0.001), equivalent to a relative increase of 61% (relative risk [RR] 1.61, 95% confidence interval [CI] 1.51 to 1.72). The crude prevalence of cannabis use in pregnancy among women aged 15 to 24 years and in the lowest two area-level income quintiles was 6.7%, compared to 0.3% among women aged 35 years and over in the highest three income quintiles (RR 24.59, 95% CI 21.98 to 27.52). A majority (52.0%) of cannabis users were aged 15-24 years and 54.7% of users were in the lowest two income quintiles. CONCLUSION: Cannabis use in pregnancy has increased since 2012 in Ontario and was reported in about 2% of pregnancies in 2017. Increases were predominately among women of younger ages and those of lower SES, and these groups account for half of users. Promoting cannabis cessation in pregnancy could lead to improved perinatal and later childhood outcomes and reduce health inequalities.

The regional medical campus model and rural family medicine practice in British Columbia: a retrospective longitudinal cohort study.

BACKGROUND: Regional medical campuses have been implemented across North America to address gaps in the physician workforce. We report findings from a study that examined the association between a combined model of regional medical campuses and students' decision to enter rural family medicine practice. METHODS: In 2004, the University of British Columbia added 2 regional medical campuses, 1 in a large population centre in a rural and coastal context and 1 in a medium-sized population centre in an isolated northern and rural context. Data were extracted from the University of British Columbia's Medical Education Database. Multivariable logistic regression examined the relationship of age, sex, rural background and campus location to students' choice of rural family medicine practice. RESULTS: There was an association between campus location and choice of family medicine versus other specialties. A rural background (odds ratio [OR] 2.59, 95% confidence interval [CI] 1.08-6.21) and training at either of the 2 regional medical campuses (OR 3.24, 95% CI 1.19-8.83 and OR 5.38, 95% CI 2.24-12.91) predicted rural family practice. INTERPRETATION: Choosing to practise family medicine in a rural location was associated with having a rural background and having trained at a regional medical campus. These early results suggest that a combined regional campus model in medical education contributes to the rural family practice workforce.

Tobacco Point-of-Purchase marketing in school neighbourhoods and school smoking prevalence: a descriptive study.

BACKGROUND: Point of Purchase (PoP) promotional and advertising activities are a sophisticated tobacco marketing strategy. This study describes tobacco PoP activities in school neighbourhoods and compares PoP activities in retail stores between schools with high and low smoking prevalence. METHODS: A cross-sectional study was conducted in 81 randomly selected schools across five provinces. Students in grades 10-11 completed a questionnaire on smoking. Observations were made in all retail stores located within a one-kilometre radius around the school. ANOVA tests were used to detect differences on PoP variables between high (> 20.6%) and low (< or = 20.6%) smoking prevalence schools, defined as percentage of students reporting at least a few puffs on > 2 days in the last 30 days. RESULTS: Approximately half of retail stores in each school neighbourhood exhibited tobacco PoP activities. Average school smoking prevalence was 20.99%. There were significant main effects on PoP variables between schools with high and low smoking prevalence, Wilk's lambda = 0.81, F (6,74) = 2.89, p < 0.01, eta2 = 0.19. Stores near schools with high smoking prevalence had significantly lower prices per cigarette (F (1,79) = 15.34, p < 0.01, eta2 = 0.16), more in-store promotions (F (1,79) = 6.73, p < 0.01, eta2 = 0.08), and fewer government-sponsored health warnings (F (1,79) = 6.26, p < 0.01, eta2 = 0.07) compared to schools with low smoking prevalence. CONCLUSION: Higher levels of PoP activities in stores located in the school neighbourhood are related to school smoking prevalence. Schools with low smoking prevalence had more stores that posted government health warning signs and higher cigarette prices. Legislation regulating PoP activities and health warnings in school neighbourhoods should be considered.

Pramipexole in patients with early Parkinson's disease (PROUD): a randomised delayed-start trial.

BACKGROUND: In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). METHODS: Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30-79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. FINDINGS: Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (-0·4 points, 95% CI -2·2 to 1·4, p=0·65). 62 patients in the early pramipexole group and 61 patients in the delayed pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal (123)I-FP-CIT binding was -15·1% (SE 2·1) for early and -14·6% (2·0) for delayed pramipexole (difference -0·5 percentage points, 95% CI -5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early pramipexole and 179 (84%) patients given delayed pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early pramipexole group and 17 (8%) in the delayed pramipexole group had serious events, two of which (hallucinations and orthostatic hypotension) were deemed related to study drug. INTERPRETATION: By clinical and neuroimaging measures, pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6-9 months. The results do not support the hypothesis that pramipexole has disease-modifying effects. FUNDING: Boehringer Ingelheim GmbH.

Novel potential drug against T. cruzi and its interaction with surfactant micelles.

The interaction of 5-nitro-2-furfurilylidene benzhydrazide (5NFB), potential anti-trypanosomal compound, with micellar solutions was studied. The results indicated that 50 mug of 5NFB completely kills 20 million T. cruzi epimastigote cells within 3 days, whereas the same amount of benznidazole kills 30% of the cells after 4 days. 5NFB solubility in surfactants solutions (SDS, DTAB, C12EO8) increased linearly with surfactant concentration. According to small angle X-ray scattering (SAXS), 5NFB does not affect micellar structural features. A comparison between C12EO8 effects on T. cruzi epimastigote cells and on erythrocytes showed that surfactant lytic effect is stronger in parasite cells, enlightening the potential of 5NFB micellar formulations.

Inadequate follow-up of abnormal screening mammograms: findings from the race differences in screening mammography process study (United States).

OBJECTIVE: Despite relatively high mammography screening rates, there are reports of inadequate follow-up of abnormal results. Our objective was to identify factors associated with inadequate follow-up, and specifically, to determine if this outcome differed by race/ethnicity. METHODS: We studied 176 subjects with abnormal or inconclusive mammograms identified from a prospective cohort study of African-American (n = 635) and White (n = 816) women who underwent screening in five hospital-based facilities in Connecticut, October 1996 through January 1998. Using multivariate logistic regression, we identified independent predictors of inadequate follow-up of an abnormal mammogram. RESULTS: Over 28% of women requiring immediate or short-term follow-up did not receive this care within three months of the recommended return date. African-American race/ethnicity, pain during the mammogram, and lack of a usual provider were significant independent predictors of inadequate follow-up. Although many factors were examined, the observed race difference was unexplained. CONCLUSIONS: While inadequate follow-up of abnormal exams undermines the potential benefits of mammography screening for all women, the observed race difference in this study may have implications for the persistent race difference in breast cancer stage at diagnosis and survival. More research is needed to identify factors that contribute to poor follow-up among African-American women.

Micellar solubilization of ibuprofen - influence of surfactant head groups on the extent of solubilization

An important property of micells with particular significance in pharmacy is their ability to increase the solubility of poorly soluble drugs in water, thus increasing their bioavailability. In this work, the solubilization of ibuprofen (IBU) was studied in micellar solutions of there surfactants possessing the same hydrocarbon tail but different hydrophilic head groups, namely sodium dodecyl sulphate (SDS), dodecyltrimethylammonium bromide (DTAB), and n-dodecyl octa(ethylene oxide) (`C IND. 12´ E`O IND. 8´). The results showed that, irrespective of the surfactant type, the solubility of IBU increased linearly with increasing surfactant concentration, as a consequence of the association between the drug and the micelles...