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TMEM106B encodes a lysosomal membrane protein and was initially identified as a risk factor for frontotemporal lobar degeneration. Recently, a dominant D252N mutation in TMEM106B was shown to cause hypomyelinating leukodystrophy. However, how TMEM106B regulates myelination is still unclear. Here we show that TMEM106B is expressed and localized to the lysosome compartment in oligodendrocytes. TMEM106B deficiency in mice results in myelination defects with a significant reduction of protein levels of proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG), the membrane proteins found in the myelin sheath. The levels of many lysosome proteins are significantly decreased in the TMEM106B-deficient Oli-neu oligodendroglial precursor cell line. TMEM106B physically interacts with the lysosomal protease cathepsin D and is required to maintain proper cathepsin D levels in oligodendrocytes. Furthermore, we found that TMEM106B deficiency results in lysosome clustering in the perinuclear region and a decrease in lysosome exocytosis and cell surface PLP levels. Moreover, we found that the D252N mutation abolished lysosome enlargement and lysosome acidification induced by wild-type TMEM106B overexpression. Instead, it stimulates lysosome clustering near the nucleus as seen in TMEM106B-deficient cells. Our results support that TMEM106B regulates myelination through modulation of lysosome function in oligodendrocytes.

Objective The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. Methods We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. Results The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. Conclusions This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

Background Although Latinos, African-Americans, and American Indians/Alaska Natives comprise 34% of Americans, these under-represented minorities (URMs) account for only 7% of US medical-school faculty. Even when URMs become faculty, they face many substantial challenges to success. Little has been published, however, on keys to academic success for URM young faculty investigators. Methods The Research in Academic Pediatrics Initiative on Diversity (RAPID) goal is to enhance the professional advancement of URM junior faculty pursuing research careers in general academic pediatrics. One important RAPID component is the annual mentoring/career-development conference, which targets URM residents, fellows, and junior faculty, and has included 62 URM participants since its 2013 inception. A conference highlight is the panel discussion on keys to academic success for URM young investigators, conducted by the RAPID National Advisory Committee, a diverse group of leading senior researchers. The article aim was to provide a guide to academic success for URM young investigators using the 2018 RAPID Conference panel discussion. A modified Delphi technique was used to provide a systematic approach to obtaining answers to six key questions using an expert panel: the single most important key to success for URM young investigators; ensuring optimal mentorship; how to respond when patients/families say, “I don’t want you to see my child because you are ____”; best strategies for maximizing funding success; how to balance serving on time-consuming committees with enough time to advance research/career objectives; and the single thing you wish someone had told you which would have substantially enhanced your success early on. Results/Conclusions This is the first published practical guide on keys to academic success for URM young investigators. Identified keys to success included having multiple mentors, writing prolifically, being tenaciously persistent, having mentors who are invested in you, dealing with families who do not want you to care for their child because of your race/ethnicity by seeking to understand the reasons and debriefing with colleagues, seeking non-traditional funding streams, balancing committee work with having enough time to advance one’s research and career by using these opportunities to generate scholarly products, and asking for all needed resources when negotiating for new jobs.

Child welfare agencies have adopted assessment tools and instruments to inform the level of risk and guide the agency's level of intervention with the family. Actuarial assessments may be more uniform but inflexible with respect to practice wisdom whereas clinical or consensus-based assessments are more comprehensive and intuitive but lack objectivity. The purpose of the current study is to compare clinical and actuarial methods of risk assessment used by child welfare workers to make decisions about substantiation and services. The current study examined the (1) association between clinical and actuarial dimensions, (2) association between actuarial dimensions and outcomes, (3) association between clinical dimensions and outcomes, (4) caseworker primary use of actuarial dimensions, and (5) caseworker supplementary use of actuarial dimensions. Findings indicated that the actuarial may not be solely predictive of agency intensity with respect to case decision and service provision. Our findings suggest that dual-measurement does inform intensity, and we speculate from these findings that the measures may be involved with decision-making in a complex way. This study may be best viewed as a means by which researchers begin to parse how decisions are made; with this information, instruments may be better tailored to facilitate clinical, critical thought.

Introduction 26 million Americans have limited English proficiency (LEP). It is well established that language barriers adversely affect health and health care. Despite growing awareness of language barriers, there is essentially a void in the medical literature regarding the influence of language disparity on pediatric surgery patients. This study was designed to assess the impact of patient–provider language concordance on question-asking behavior and patient satisfaction for pediatric surgery patients. Methods Participants included families of patients in a General Pediatric Surgery Clinic categorized into 3 groups by patient–provider language concordance: concordant English-speaking, LEP concordant Spanish-speaking, and LEP discordant Spanish-speaking using an interpreter. Clinical visits were audio recorded and the number of patient-initiated questions and the length of clinical encounter were measured. Families were administered a surgery-specific, 5-point Likert scale questionnaire modeled after validated surveys concerning communication, trust, perceived discrimination and patient–provider language concordance. Regression models were performed to analyze associations between language concordance and patient's question-asking behavior and between language concordance and survey results. Results A total of 156 participants were enrolled including 57 concordant-English, 52 LEP concordant-Spanish and 47 LEP-discordant-Spanish. There was significant variation in the mean number of patient-initiated questions among the groups (p=0.002). Both the English and Spanish concordant groups asked a similar number of questions (p=0.9), and they both asked more questions compared to the Spanish-discordant participants (p=0.002 and p=0.001). Language discordance was associated with fewer questions asked after adjustment for socioeconomic status. Language concordant participants rated higher scores of communication. Both Spanish-concordant and Spanish-discordant patients reported significantly increased preference for, and value of language concordant care. Language discordant participants reported that they desired to ask more questions but were limited by a language barrier (p=0.001). Conclusions In a pediatric surgery clinic, language concordant care increases the number of patient-asked questions during a clinical visit and improves communication suggesting that discordant care is a potential source of disparities in access to information. Future efforts should focus on expanding access to language concordant providers in other surgery subspecialties as a step towards limiting disparities in surgical care for all patients.

Background: The internet’s low cost and potential for high reach makes Web-based channels prime for delivering evidence-based physical activity (PA) interventions. Despite the well-studied success of internet-based PA interventions in primarily non-Hispanic white populations, evidence on Spanish-speaking Latinas’ use of such interventions is lacking. The recent rise in technology use among Latinas in the United States, a population at heightened risk for low PA levels and related conditions, suggests that they may benefit from Web-based PA interventions tailored to their cultural and language preferences. Objective: The goal of the research was to examine participant engagement with various features of an internet-based PA intervention for Latinas and explore how use of these features was differentially associated with adoption and maintenance of PA behavior change. Method: Pasos Hacia la Salud tested a Spanish-language, culturally adapted, individually tailored, internet-based PA intervention versus a Spanish language, internet-based, Wellness Contact Control condition for underactive Latinas (N=205, mean age 39.2 [SD 10.5] years, 84% Mexican American). These analyses examined engagement with the website and explored how use was associated with adoption and maintenance of moderate to vigorous physical activity (MVPA) behavior. Results: Overall, participants logged on to the website an average of 22 times (SD 28) over 12 months, with intervention participants logging on significantly more than controls (29 vs 14.7, P

Clinical studies results show that policosanol (20 mg/day) + aspirin therapy had benefits versus placebo + aspirin to patients with recent non-cardioembolic ischemic stroke.To analyze the policosanol treatment effects in the hypertensive patients included in two non-cardioembolic ischemic stroke recovery trials.Hypertensive patients with a modified Rankin Scale (mRS) score 2 to 4 were randomized, within 30 days of onset, to policosanol + aspirin or placebo + aspirin, for six months. The primary outcome was mRS score reduction.One hundred forty two hypertensive patients (mean age: 66 years) were included in the analysis. Policosanol + aspirin decreased significantly the mRS score mean from the first interim check-up. The policosanol treatment effect did not wear off, on the contrary, even improved after six months therapy. More over, policosanol + aspirin (80.3%) treatment achieved significant results (mRS= 1), whereas the placebo + aspirin did not (8.5%). Two patients discontinued and four (two from each group) referred mild adverse events.The treatment for six months with policosanol + aspirin in hypertensive patients who had suffered a non-cardioembolic ischemic stroke proved to be more effective than the placebo + aspirin treatment in the functional recovery of these patients.Efectos del policosanol en la recuperacion funcional de pacientes hipertensos con ictus isquemico no cardioembolico.Introduccion. Los resultados de los estudios clinicos muestran que el tratamiento con policosanol (20 mg/dia) + aspirina produce beneficios frente a placebo + aspirina en pacientes con ictus isquemico no cardioembolico reciente. Objetivo. Analizar los efectos del tratamiento con policosanol en pacientes hipertensos incluidos en dos ensayos de recuperacion de ictus isquemico no cardioembolico. Pacientes y metodos. Pacientes hipertensos que sufrieron un ictus en los 30 dias previos y que, con una puntuacion de 2 a 4 en la escala de Rankin modificada (mRS), se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + aspirina o placebo + aspirina durante seis meses. La variable primaria de eficacia fue la reduccion de la puntuacion en la mRS. Resultados. Se incluyo a un total de 142 pacientes hipertensos (edad media: 66 años) en el analisis. El policosanol + aspirina disminuyo significativamente la puntuacion de la mRS desde el primer chequeo intermedio. El efecto del tratamiento con policosanol no desaparecio, sino que incluso mejoro despues de seis meses de tratamiento. El numero de pacientes que alcanzaron valores de la mRS= 1 fue mayor en el grupo de policosanol + aspirina (80,3%) que en el de placebo + aspirina (8,5%). Dos pacientes causaron baja del estudio y cuatro (dos de cada grupo) refirieron efectos adversos leves. Conclusiones. El tratamiento durante seis meses con policosanol + aspirina a pacientes hipertensos que habian sufrido un ictus isquemico no cardioembolico demostro ser mas efectivo que el tratamiento con placebo + aspirina en su recuperacion funcional.

To ensure timely appropriate care for low-birth-weight (LBW) infants, healthcare providers must communicate effectively with parents, even when language barriers exist. We sought to evaluate whether non-English primary language (NEPL) and professional in-person interpreter use were associated with differential hospital length of stay for LBW infants, who may incur high healthcare costs. We analyzed data for 2047 infants born between 1 January 2008 and 30 April 2013 with weight &lt, 2500 g at one hospital with high NEPL prevalence. We evaluated relationships of NEPL and in-person interpreter use on length of stay, adjusting for medical severity. Overall, 396 (19%) had NEPL parents. Fifty-three percent of NEPL parents had documented interpreter use. Length of stay ranged from 1 to 195 days (median 11). Infants of NEPL parents with no interpreter use had a 49% shorter length of stay (adjusted incidence rate ratio (IRR) 0.51, 95% confidence interval (CI) 0.43&ndash, 0.61) compared to English-speakers. Infants of parents with NEPL and low interpreter use (&lt, 25% of hospital days) had a 26% longer length of stay (adjusted IRR 1.26, 95% CI 1.06&ndash, 1.51). NEPL and high interpreter use (&gt, 25% of hospital days) showed a trend for an even longer length of stay. Unmeasured clinical and social/cultural factors may contribute to differences in length of stay.

Background: Physical activity is markedly low in Latina adolescents, yet few physical activity interventions have been attempted in this population. Web-based interventions can incorporate theory-based components, be appealing to adolescents, and have potential for low-cost dissemination. Objective: This study aimed to assess the feasibility, acceptability, and potential efficacy of a Web-based physical activity intervention for Latina adolescents in a single-arm pilot trial. Methods: A total of 21 Latina adolescents (aged 12-18 years) who could read and write in English and were underactive (

BACKGROUND The metopic suture is unlike other cranial sutures in that it normally closes in infancy. Consequently, the diagnosis of metopic synostosis depends primarily on a subjective assessment of cranial shape. The purpose of this study was to create a simple, reproducible radiographic method to quantify forehead shape and distinguish trigonocephaly from normal cranial shape variation. METHODS Computed tomography scans were acquired for 92 control patients (mean age, 4.2 ± 3.3 months) and 18 patients (mean age, 6.2 ± 3.3 months) with a diagnosis of metopic synostosis. A statistical model of the normal cranial shape was constructed, and deformation fields were calculated for patients with metopic synostosis. Optimal and divergence (simplified) interfrontal angles (IFA) were defined based on the three points of maximum average deformation on the frontal bones and metopic suture, respectively. Statistical analysis was performed to assess the accuracy and reliability of the diagnostic procedure. RESULTS The optimal interfrontal angle was found to be significantly different between the synostosis (116.5 ± 5.8 degrees; minimum, 106.8 degrees; maximum, 126.6 degrees) and control (136.7 ± 6.2 degrees; minimum, 123.8 degrees; maximum, 169.3 degrees) groups (p < 0.001). Divergence interfrontal angles were also significantly different between groups. Accuracy, in terms of available clinical diagnosis, for the optimal and divergent angles, was 0.981 and 0.954, respectively. CONCLUSIONS Cranial shape analysis provides an objective and extremely accurate measure by which to diagnose abnormal interfrontal narrowing, the hallmark of metopic synostosis. The simple planar angle measurement proposed is reproducible and accurate, and can eliminate diagnostic subjectivity in this disorder. CLINICAL QUESTION/LEVEL OF EVIDENCE Diagnostic, IV.

BACKGROUND Few reports have described laparoscopy-assisted pancreaticoduodenectomy (LAPD) as an alternative to the conventional open approach for periampullary tumors. The safety and feasibility of this procedure remain to be determined. In this study, we compared the short-term clinical outcomes of LAPD with those of open pancreaticoduodenectomy (OPD). METHODS A retrospective review of patients who had undergone pancreaticoduodenectomy for periampullary tumors between June and December 2014 was conducted. Patient demographic data and their pathological and short-term clinical parameters were compared between the LAPD and OPD groups. RESULTS Fifty-two patients were included in the study: 18 had undergone LAPD and 34 had undergone OPD. The mean operation time was longer for LAPD than for OPD (531.1 vs. 383.2 min, P

Hispanics account for over 60% of the U.S. population growth and 25% speak little-to-no English. This language barrier adversely affects both access to and quality of care. Surgical specialties trail other medical fields in assessing the effects of language barriers to surgical clinical care and patient satisfaction. This study was designed to assess the effects of patient-provider language concordance on a pediatric surgery practice.A surgery-specific, 7-point Likert scale questionnaire was designed with 14 questions modeled after validated patient satisfaction surveys from the literature. Questions concerning provider-patient language concordance, quality of understanding, and general satisfaction were included. Surveys were administered to families of patients in the General Pediatric Surgery Clinic at our institution. Families were categorized into three groups: English-speaking, regardless of race/ethnicity; Spanish-speaking using interpreter services with an English-speaking medical team; and Spanish-speaking communicating directly with a Spanish-speaking medical team (Hispanic Center for Pediatric Surgery, HCPS). One-way analysis of variance was used to test for group differences.We administered 226 surveys; 49 were removed due to lack literacy proficiency. Families in the HCPS group reported a higher level of satisfaction than the interpreter and English groups (p0.01). The HCPS group also indicated improved understanding of the information from the visit (p0.001). Spanish-speaking only families felt that communicating directly with their health care team in their primary language was more important than their English-speaking counterparts (p0.001).In a pediatric surgery clinic, language concordant care improves patient satisfaction and understanding for Hispanic families in comparison to language discordant care. Other clinics in other surgery sub-specialties may consider using this model to eliminate language barriers and improve patient satisfaction and understanding of surgical care.

Although survival rate in papillary thyroid cancer (PTC) is high, the risk of persistence and recurrence together with the dramatic rise in its incidence cannot be overemphasized. Filipinos are considered to be at greater risk for negative outcomes. A paradigm shift in the management of PTC introduces re-stratification based on response to therapy which was reported to have better correlation with long-term outcome. The study aimed to identify predictors of incomplete response after thyroidectomy and radioiodine therapy among patients with PTC. The results of the study may have important implications in our understanding of the disease process allowing more aggressive treatment and monitoring of certain subgroups of patients. Retrospective review of 225 patients with PTC (59 % ATA low risk, 30 % ATA intermediate risk and 11 % ATA high risk) who underwent thyroidectomy and radioiodine therapy was performed. Thirteen variables were considered (age, gender, histopathological variant, stage, extent of disease, MACIS score, AMES score, primary tumour size, lymph node, lymphovascular invasion, bilaterality, multifocality and preoperative TSH level). Logistic regression analysis using Backward Wald algorithm was used to identify independent predictors of incomplete response to therapy after 24 months. Of the 225 patients, 69 (31 %) had incomplete response. Biochemical and structural (predominantly thyroid bed, lung and bone) incomplete response was observed in 6 and 63 patients, respectively. Incomplete response was documented in 8, 54 and 92 % of low-, intermediate- and high-risk patients based on ATA recommendation. Incomplete response was significantly dependent on gender, lymph node involvement and location, extent of malignancy and multifocality taking into account the size of concurrent tumours (p

Objective. To evaluate an innovative curriculum meeting new pediatric residency education guidelines, Special Care Optimization for Patients and Education (SCOPE). Methods. Residents were randomized to intervention (n = 23) or control (n = 25) groups. Intervention residents participated in SCOPE, pairing them with a child with special health care needs (CSHCN) and faculty mentor to make a home visit, complete care coordination toolkits, and participate in case discussions. The primary outcome was resident self-efficacy in nine skills in caring for CSHCN. Secondary outcomes included curriculum feasibility/acceptance, resident attitudes, and family satisfaction. Results. Response rates were ≥65%. Intervention residents improved in their self-efficacy for setting patient-centered goals compared with controls (mean change on 4-point Likert-type scale, 1.36 vs 0.56, P < .05). SCOPE was feasible/acceptable, residents had improved attitudes toward CSHCN, and families reported high satisfaction. Conclusion. SCOPE may serve as a model for efforts to increase residents’ self-efficacy in their care of patients with chronic disease.

Currently, 28 states and the District of Columbia have legalized cannabis for medical use despite its remaining Schedule I federally. Benefits of medical cannabis (MC) have been demonstrated in nausea/vomiting associated with chemotherapy, cachexia associated with HIV/AIDS, and certain types of neuropathic pain. However, it is unclear how comfortable hospice providers are with the concept of MC.The aim of this study is to determine changes in knowledge, self-perceived skills, and attitudes (KSA) of hospice providers regarding MC after an online educational intervention.The educational intervention consisted of 3 learning modules covering information from 6 learning domains. Participants took a pre- and postcourse survey to assess changes in KSA. Participant demographics were analyzed using descriptive statistics. To detect any differences between pre- and postsurvey answers, a paired t test was used to reduce intersubject variability.Attitudes about the importance of cannabis knowledge were overall positive and did not change significantly after the intervention (N = 94). Both self-perceived skills and knowledge increased significantly, with providers reporting more positive skills, and75% of respondents answering questions correctly after the intervention. There was a significant difference in attitudes in all domains in the postsurvey between participants who have practiced in hospice3 years or ≥4 years, but no difference in perceived skills or knowledge.Providers' attitudes regarding the importance of MC knowledge were strong and the same before and after. Both the self-perception of skills and direct knowledge were significantly increased after the educational intervention.

Life under threat of deportation What is the effect on a child of having parents who are at risk of deportation as unauthorized immigrants? Hainmueller et al. developed a quasi-experimental protocol to address this complicated question. They selected mothers who had birthdates either just before or just after the cutoff for the United States' Deferred Action for Childhood Arrivals (DACA) program. Children whose mothers were protected from deportation by DACA had 50% fewer diagnoses of adjustment and anxiety disorder than children with mothers whose birthdates, by coincidence, preceded the cutoff and who thus were not protected. Science , this issue p. 1041

Gonadotropin releasing hormone(GnRH) as an adjunct to orchidopexy for the treatment of cryptorchidism is still controversial. Present evidences were studied through a meta-analysis of comparative clinical trials.Systematic literature search was done up to September 30, 2013. Studies were independently appraised by two reviewers. Continuous data of fertility indices were extracted as weighted mean difference (WMD) and standard deviation (SD); while nominal data of fertility indices were extracted as relative risk (RR). Random effects model was used to analyze the pooled effect estimates. Inter-study heterogeneity and publication bias were assessed. PROSPERO Protocol registration (CRD42013004922).Ten eligible studies were included. The pooled effect estimates showed that cryptorchid children treated with GnRH when compared with controls, have significantly increased germ cell per tubule (WMD: 0.35; 95% CI 0.07-0.62, P=0.01) and increased RR to have normal value of germ cell per tubule (RR: 2.86; 95% CI 1.73-4.71, P0.0001). Inter-study heterogeneity was noted, source identified with subgroup analysis. Publication bias was not evident. No GnRH related adverse events were reported in all studies.Evidence suggests that a subset of boys with cryptorchidism may benefit from GnRH as adjunctive to orchidopexy in improving the fertility index. However, future studies are recommended to specifically identify subgroup characteristics of cryptorchidism that will clearly benefit from the treatment.

Mobile technology is opening a wide range of opportunities for transforming the standard of care for chronic disorders. Using smartphones as tools for longitudinally tracking symptoms could enable personalization of drug regimens and improve patient monitoring. Parkinson's disease (PD) is an ideal candidate for these tools. At present, evaluation of PD signs requires trained experts to quantify motor impairment in the clinic, limiting the frequency and quality of the information available for understanding the status and progression of the disease. Mobile technology can help clinical decision making by completing the information of motor status between hospital visits. This paper presents an algorithm to detect PD by analyzing the typing activity on smartphones independently of the content of the typed text. We propose a set of touchscreen typing features based on a covariance, skewness, and kurtosis analysis of the timing information of the data to capture PD motor signs. We tested these features, both independently and in a multivariate framework, in a population of 21 PD and 23 control subjects, achieving a sensitivity/specificity of $0.81/0.81$ for the best performing feature and $0.73/0.84$ for the best multivariate method. The results of the alternating finger-tapping, an established motor test, measured in our cohort are $0.75/0.78$ . This paper contributes to the development of a home-based, high-compliance, and high-frequency PD motor test by analysis of routine typing on touchscreens.

Stroke is a leading cause of mortality and disability. Policosanol has been effective in brain ischemia models. The aim of this study is to investigate whether policosanol, added to aspirin therapy within 30 days of stroke onset, is better than placebo + aspirine for the long-term recovery of non-cardioembolic ischemic stroke subjects.Randomized, double-blind, placebo-controlled study. Eighty patients (mean age: 69 years) within 30 days of onset, with a modified Rankin Scale score (mRS) 2 to 4, were included. They were randomized in two groups (policosanol + aspirine or placebo + aspirine) for 12 months.Policosanol + aspirine decreased significantly mean mRS from the first interim check-up (1.5 months). The treatment even improved after long-term therapy. More policosanol + aspirin (87.5%) than placebo + aspirine (0%) patients achieved mRSs= 1. Policosanol + aspirine increased significantly Barthel Index, lowered LDL-cholesterol and increased HDL-cholesterol versus placebo + aspirin.Long-term (12 months) administration of policosanol + aspirin given after suffering non-cardioembolic ischemic stroke was shown to be better than placebo + aspirin in improving functional outcomes when used among patients with non-cardioembolic ischemic stroke of moderate severity.Efecto a largo plazo del policosanol en la recuperacion funcional de pacientes con ictus isquemico no cardioembolico: estudio de un año.Introduccion. El ictus es una causa principal de mortalidad y discapacidad. El policosanol ha sido eficaz en modelos de isquemia cerebral. Este estudio investiga si el tratamiento a largo plazo con policosanol, añadido a la terapia con acido acetilsalicilico (AAS), dentro de los 30 dias posteriores a un ictus, es mejor que el placebo + AAS en la recuperacion de los pacientes. Pacientes y metodos. Estudio aleatorizado, doble ciego, controlado con placebo. Se incluyeron 80 pacientes (edad media: 69 años) que sufrieron un ictus en los 30 dias previos y con una puntuacion de 2-4 en la escala de Rankin modificada (mRS). Se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + AAS o placebo + AAS durante 12 meses. Resultados. El tratamiento con policosanol + AAS disminuyo significativamente la puntuacion en la mRS desde el primer control intermedio (1,5 meses). El efecto del tratamiento incluso mejoro con la terapia a largo plazo. El numero de pacientes que alcanzaron valores de mRS menores o iguales a 1 fue superior en el grupo de policosanol + AAS (87,5%) que en el de placebo + AAS (0%). El tratamiento con policosanol + AAS aumento significativamente el indice de Barthel, disminuyo el colesterol LDL y aumento el colesterol HDL frente a placebo + AAS. Conclusiones. El tratamiento a largo plazo (12 meses) con policosanol + AAS fue mas efectivo que el tratamiento con placebo + AAS en la recuperacion funcional de los pacientes despues de sufrir un ictus isquemico no cardioembolico de moderada gravedad.

Objective To describe the diversity of pediatric residents and examine relationships of cross-cultural training experiences with training satisfaction, perceived preparedness for providing culturally effective care, and attitudes surrounding care for underserved populations. Methods A cross-sectional survey was conducted of a national random sample of graduating pediatric residents and an additional sample of minority residents. Using weighted analysis, we used multivariate regression to test for differences in satisfaction, preparedness, and attitudes between residents with more and less cross-cultural experiences during residency, controlling for residents' characteristics and experiences before training. Results The survey response rate was 57%. Eleven percent were Hispanic, 61% white, 21% Asian, 9% African American, 9% other racial/ethnic groups; 34% grew up in a bi- or multilingual family. Ninety-three percent of residents were satisfied with their residency training, 81% with the instruction they received on health and health care disparities, and 54% on global health issues. Ninety-six percent of residents felt they were prepared to care for patients from diverse backgrounds, but fewer felt prepared to care for families with beliefs at odds with Western medicine (49%) and families who receive alternative or complementary care (37%). Residents with more cross-cultural experiences during residency reported being better prepared than those with less experience to care for families with limited English proficiency (adjusted odds ratio [aOR] 2.11; 95% confidence interval [CI] 1.40–3.17), new immigrants (aOR 1.91; 95% CI 1.32–2.75), and with religious beliefs that might affect clinical care (aOR 1.62; 95% CI 1.13–2.32). Conclusions Pediatric residents begin their training with diverse cross-cultural backgrounds and experiences. Residency experiences in cross-cultural care contribute to feelings of preparedness to care for diverse US children.

BACKGROUND AND OBJECTIVE: The diversifying US population of children necessitates assessing the diversity of the pediatric academic workforce and its level of cultural competency training. Such data are essential for workforce and educational policies. METHODS: An 8-question survey was sent to 131 US pediatric chairs to assess plans for diversity, targeted groups, departmental diversity, diversity measures, perceived success in diversity, and presence and type of cultural competency training. RESULTS: In all, 49.6% of chairs responded, and three-quarters of them reported having a plan for diversity, which targeted racial; ethnic; gender; lesbian, gay, bisexual, and transgender; disabled; and social class groups. Of the residents, 75% were women, as compared with 54% of faculty and 26% of chairs. Racial and ethnic diversity was limited among trainees, faculty, and leaders; CONCLUSIONS: Pipeline issues for minorities are ongoing challenges. Pediatric leadership needs more representation of racial and ethnic minorities, women, and LGBT. Suggestions for workforce and educational policies are made.

Latino families who express a higher degree of familism are characterized by positive interpersonal familial relationships, high family unity, social support, interdependence in the completion of daily activities, and close proximity with extended family members. Retention of cultural values, such as familism, may be linked to positive health outcomes; however, little is known about how families retain culture of origin values in the face of acculturation pressures. The current study explores acculturation influences as indexed by language preference and household education on maternal and child familism. Mothers and children of Mexican descent (fourth grade students) (n = 219) completed measures of demographics, household education, language preference, and familism. Three hypotheses were examined. First, we predicted that lower household education would be correlated with higher familism scores. However, contrary to our prediction, a higher familism score was significantly associated with a higher level of household education (p

Purpose To describe a novel use of high-dose-rate intravascular brachytherapy in the first reported case of macroscopic metastatic rectal adenocarcinoma within a peripheral vein. Methods and materials Following thrombolytic therapy to ablate an overlying venous thrombosis, a vascular stent was deployed across the entire length of the tumor. Using the stent as a target, 4300 cGy was delivered to the tumor via megavoltage external beam radiation. This was followed by two weekly intravascular high-dose-rate 192Ir brachytherapy applications of 400 cGy each. Results There is no evidence of recurrence in the treated vein at 43 months of follow-up. Conclusions In this unique case, a combination of external beam radiation therapy and intravascular brachytherapy provided effective control of a solitary intravascular metastasis from rectal carcinoma.

Laparoscopic distal pancreatectomy (LDP) is a treatment option for benign and borderline pancreatic tumors. However, pancreatic fistula (PF) remains a significant morbidity, contributing to the length of hospital stay and overall costs. In a consecutive series of 143 patients at a single institution, the predictive factors associated with PF after LDP were identified.A retrospective study of patients who had undergone LDP between January 2003 and December 2013 was conducted. Patient demographic data and clinicopathological parameters were analyzed to evaluate their correlation with the incidence of PF.Among the 143 patients, the indications for surgery were benign disease in 117 (82%) and malignant tumors in 26 (18%). PF occurred in 25 (17%) patients, 10 (40%) of whom had clinically significant (grade B) PF. No grade C PF was observed. Multivariable analysis showed that pancreatic thickness was a significant predictive factor for PF (P0.001). A 12-mm cutoff value was based on the median pancreatic thickness in this series. Pancreatic texture alone was not a significant risk factor (P = 0.30); however, it became significant in patients with pancreatic thickness exceeding 12 mm (P = 0.005).Pancreatic thickness exceeding 12 mm significantly increases the likelihood of PF after LDP. Pancreatic texture alone is not an independent risk factor for PF, but when combined with a thick parenchyma (12 mm), a soft pancreas is predictive of PF.

Importance Medical errors and adverse events (AEs) are common among hospitalized children. While clinician reports are the foundation of operational hospital safety surveillance and a key component of multifaceted research surveillance, patient and family reports are not routinely gathered. We hypothesized that a novel family-reporting mechanism would improve incident detection. Objective To compare error and AE rates (1) gathered systematically with vs without family reporting, (2) reported by families vs clinicians, and (3) reported by families vs hospital incident reports. Design, Setting, and Participants We conducted a prospective cohort study including the parents/caregivers of 989 hospitalized patients 17 years and younger (total 3902 patient-days) and their clinicians from December 2014 to July 2015 in 4 US pediatric centers. Clinician abstractors identified potential errors and AEs by reviewing medical records, hospital incident reports, and clinician reports as well as weekly and discharge Family Safety Interviews (FSIs). Two physicians reviewed and independently categorized all incidents, rating severity and preventability (agreement, 68%-90%; κ, 0.50-0.68). Discordant categorizations were reconciled. Rates were generated using Poisson regression estimated via generalized estimating equations to account for repeated measures on the same patient. Main Outcomes and Measures Error and AE rates. Results Overall, 746 parents/caregivers consented for the study. Of these, 717 completed FSIs. Their median (interquartile range) age was 32.5 (26-40) years; 380 (53.0%) were nonwhite, 566 (78.9%) were female, 603 (84.1%) were English speaking, and 380 (53.0%) had attended college. Of 717 parents/caregivers completing FSIs, 185 (25.8%) reported a total of 255 incidents, which were classified as 132 safety concerns (51.8%), 102 nonsafety-related quality concerns (40.0%), and 21 other concerns (8.2%). These included 22 preventable AEs (8.6%), 17 nonharmful medical errors (6.7%), and 11 nonpreventable AEs (4.3%) on the study unit. In total, 179 errors and 113 AEs were identified from all sources. Family reports included 8 otherwise unidentified AEs, including 7 preventable AEs. Error rates with family reporting (45.9 per 1000 patient-days) were 1.2-fold (95% CI, 1.1-1.2) higher than rates without family reporting (39.7 per 1000 patient-days). Adverse event rates with family reporting (28.7 per 1000 patient-days) were 1.1-fold (95% CI, 1.0-1.2; P = .006) higher than rates without (26.1 per 1000 patient-days). Families and clinicians reported similar rates of errors (10.0 vs 12.8 per 1000 patient-days; relative rate, 0.8; 95% CI, .5-1.2) and AEs (8.5 vs 6.2 per 1000 patient-days; relative rate, 1.4; 95% CI, 0.8-2.2). Family-reported error rates were 5.0-fold (95% CI, 1.9-13.0) higher and AE rates 2.9-fold (95% CI, 1.2-6.7) higher than hospital incident report rates. Conclusions and Relevance Families provide unique information about hospital safety and should be included in hospital safety surveillance in order to facilitate better design and assessment of interventions to improve safety.

Modern digital devices and appliances are capable of monitoring the timing of button presses, or finger interactions in general, with a sub-millisecond accuracy. However, the massive amount of high resolution temporal information that these devices could collect is currently being discarded. Multiple studies have shown that the act of pressing a button triggers well defined brain areas which are known to be affected by motor-compromised conditions. In this study, we demonstrate that the daily interaction with a computer keyboard can be employed as means to observe and potentially quantify psychomotor impairment. We induced a psychomotor impairment via a sleep inertia paradigm in 14 healthy subjects, which is detected by our classifier with an Area Under the ROC Curve (AUC) of 0.93/0.91. The detection relies on novel features derived from key-hold times acquired on standard computer keyboards during an uncontrolled typing task. These features correlate with the progression to psychomotor impairment (p < 0.001) regardless of the content and language of the text typed, and perform consistently with different keyboards. The ability to acquire longitudinal measurements of subtle motor changes from a digital device without altering its functionality may allow for early screening and follow-up of motor-compromised neurodegenerative conditions, psychological disorders or intoxication at a negligible cost in the general population., Comunidad de Madrid

OBJECTIVE: This study examined the early developmental context of children in immigrant families (CIF), measured by the frequency with which parents share books with their children. METHODS: Trends in the frequency with which parents report book sharing, defined in this analysis as reading or sharing picture books with their young children, were analyzed across immigrant and nonimmigrant households by using data from the 2005, 2007, and 2009 California Health Interview Survey. Stepwise multivariate logistic regression assessed the likelihood that CIF shared books with parents daily. RESULTS: In this study, 57.5% of parents in immigrant families reported daily book sharing (DBS), compared with 75.8% of native-born parents. The lowest percentage of DBS was seen in Hispanic families with 2 foreign-born parents (47.1%). When controlling for independent variables, CIF with 2 foreign-born parents had the lowest odds of sharing books daily (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.54–0.68). When stratified by race/ethnicity, separate multivariate logistic regressions revealed CIF status to be associated with lower odds of DBS for Asian (OR: 0.56; 95% CI: 0.38–0.81) and Hispanic CIF (OR: 0.49; 95% CI: 0.42–0.58). CONCLUSIONS: There is an association between the lower odds of DBS and parental immigrant status, especially for Hispanic and Asian children. This relationship holds after controlling for variables thought to explain differences in literacy-related practices, such as parental education and income. Because book sharing is central to children’s development of early literacy and language skills, this disparity merits further exploration with the aim of informing future interventions.

Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction.To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers.Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use.Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P0.005).Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.

In this paper we present a segmentation method for ultrasound (US) images of the pediatric kidney, a difficult and barely studied problem. Our method segments the kidney on 2D sagittal US images and relies on minimal user intervention and a combination of improvements made to the Active Shape Model (ASM) framework. Our contributions include particle swarm initialization and profile training with rotation correction. We also introduce our methodology for segmentation of the kidney's collecting system (CS), based on graph-cuts (GC) with intensity and positional priors. Our intensity model corrects for intensity bias by comparison with other biased versions of the most similar kidneys in the training set. We prove significant improvements (p0.001) with respect to classic ASM and GC for kidney and CS segmentation, respectively. We use our semi-automatic method to compute the hydronephrosis index (HI) with an average error of 2.67 +/- 5.22 percentage points similar to the error of manual HI between different operators of 2.31 +/- 4.54 percentage points.

The majority of drug abusing offenders who need substance abuse treatment do not receive it. Although interventions like drug court increase the probability of offender success, little is known about how co-occurring psychological symptoms impact drug court treatment outcomes. Based on previous research, we hypothesized that co-occurring psychological symptoms would have a significant relationship with successful drug court completion. Using a sample of suburban drug court enrollees (n = 122), multivariate logistic regression was conducted with successful drug court completion as the outcome variable. Predictor variables included symptom counts of depression, post-traumatic stress, obsessive-compulsive disorder, panic disorder, psychosis, generalized anxiety, and social phobia. Results indicated that participants with fewer symptoms of depression were more likely to successfully complete drug court than participants with more symptoms. The present study extends previous research by demonstrating that symptoms of depression are related to poorer outcomes for drug court enrollees. Accordingly, drug courts need to address participants' symptoms of depression to maximize success.

The present study on the main olfactory system (MOS) and the accessory olfactory system (AOS) documents the functional morphology of the rodent olfactory region and that of the vomeronasal organ (VNO) using light and electron microscopical techniques. Special attention is given to the cytoarchitecture of the sensory epithelia, i. e. the olfactory epithelium (OE) of the regio olfactoria and the neuroepithelium of the VNO (VNO-NE). Both sensory epithelia consist of a pseudostratified columnar epithelium composed of three types of cells, i. e. receptor cells, supporting cells and progenitor cells. Even at the light microscopical level, however, distinctive morphological features can be distinguished which illustrate important differences between the two sensory epithelia. For example, the height of the respective epithelia differs considerably, the VNO-NE is approximately 170 microns tall and the OE is only about 90 microns. The receptors of the VNO-NE lack olfactory knobs which are typically found in the sensory cells of the OE. The perikarya of the receptor cells of the VNO-NE are very large when compared to those of the sensory cells of the OE. In contrast to the OE, blood vessels are found within the neuroepithelial layer of the VNO. The progenitor cells of the OE are located in a clearly distinguishable cell layer which is lacking in the rodent VNO-NE. The differences between the two epithelial layers become more obvious at the electron microscopical level. The olfactory knobs of the sensory cell dendrites of the OE reach the nasal cavity with numerous cilia. These olfactory hairs, on average 11 per knob, consist of a short proximal segment and a long and thin distal segment. This distal segment runs parallel to the epithelial surface and is embedded in the neuroepithelial mucosal layer. The dendrites of the receptor cells of the VNO-NE reach the lumen of the VNO with numerous branched microvilli which are also embedded in the mucous layer. Horizontal ultrathin sections through the apical portion of the OE reveal that each supporting cell completely envelopes several dendrites. This glia-like relationship is not found in the corresponding layer of the VNO-NE. The sensory cell perikarya of the OE contain only a few endoplasmatic reticulum (ER) profiles while the receptor cells of the VNO are characterized by an extensive smooth endoplasmatic reticulum (SER). In contrast to the fila olfactoria, numerous axons within the vomeronasal nerve show ellipsoidal varicosities without synaptic vesicles which may indicate the existence of at least two vomeronasal nerve fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Filipino Americans have more adolescent pregnancies than other Asian-Pacific Islanders (APIs). Few community-academic collaborations have addressed adolescent pregnancy prevention in this community.We sought to describe the lessons learned from and impact of a community-based teen pregnancy prevention program for Filipino Americans implemented by a Filipina pediatrics resident.We formed a community-academic partnership between the Filipino Youth Coalition, a community-based organization (CBO) in San Jose, California, and the Stanford School of Medicine's Pediatric Advocacy Program. We developed a culturally tailored parent-teen conference addressing adolescent pregnancy prevention in Filipino Americans. We qualitatively and quantitatively evaluated this intervention by collecting both pre- and post-conference data using a convenience sample design.Engaging particular aspects of Filipino culture (i.e., religion and intergenerational differences) helped to make this community-academic partnership successful. For physicians-in-training who are conducting community-based participatory research (CBPR), project challenges may include difficulties in building and maintaining academic- community relationships, struggles to promote sustainability, and conflicting goals of "community insiders" and "academic outsiders." Authors offer insights and implications for residents interested in practicing CBPR.CBPR is a key tool for exploring health issues in understudied populations. CBPR experiences can provide meaningful educational opportunities for physicians-in-training and can build sustained capacity in CBOs. They can also help residents to develop analytic skills, directly affect the health of the communities they serve, and, for minority physicians, give back to the communities they call home.

To compare health care access, utilization, and perceived health status for children with SHCN in immigrant and nonimmigrant families. This cross-sectional study used data from the 2003 California Health Interview Survey to identify 1404 children (ages 0–11) with a special health care need. Chi-square and logistic regression analyses were used to examine relations between immigrant status and health access, utilization, and health status variables. Compared to children with special health care needs (CSHCN) in nonimmigrant families, CSHCN in immigrant families are more likely to be uninsured (10.4 vs. 4.8%), lack a usual source of care (5.9 vs. 1.9%), report a delay in medical care (13.0 vs. 8.1%), and report no visit to the doctor in the past year (6.8 vs. 2.6%). They are less likely to report an emergency room visit in the past year (30.0 vs. 44.0%), yet more likely to report fair or poor perceived health status (33.0 vs. 16.0%). Multivariate analyses suggested that the bivariate findings for children with SHCN in immigrant families largely reflected differences in family socioeconomic status, parent’s language, parental education, ethnicity, and children’s insurance status. Limited resources, non-English language, and limited health-care use are some of the barriers to staying healthy for CSHCN in immigrant families. Public policies that improve access to existing insurance programs and provide culturally and linguistically appropriate care will likely decrease health and health care disparities for this population.

Background: Transfusion-transmitted infections (TTIs) constitute a major health problem worldwide where routine screening of blood or blood products is improperly done, and where non-medical injecting medications and/or drug use are prevalent. Prevalence and risk factors vary by geographic location and by the specific TTI (including HIV-1, HBV, HCV and HTLV-I). Objective: To determine theprevalence and risk factors associated with TTIs among a sample of multi-transfused adult patients in Peru. Study design: A cross-sectionalmulti-center study was conducted across seven major hospitals in Peru from February 2003 to September 2004. Self-reported behavior information (medical procedures, number of sexual partners, and drug use history) was analyzed, along with a review of exposure history from hospital medical records. Prevalences were calculated by TTI for different exposures, along with unadjusted and adjusted odds ratios for infection risk. Results: Overall, 192 (54.7%) of 351 multi-transfused patients were found infected with one or more TTIs.Number of transfusion units, years of transfusion history (6 or more), and number of treatment facilities (2 or more) were associated with HCV infection. Hemodialysis history was a common risk factor associated with HBV, HCV and HTLV-I infection. HIV infection was associated only with total number of transfusion units received. Conclusions: High prevalences of HBV and HCV infection were foundamong Peruvian multi-transfused patients and were associated with a past history and number of blood transfusions, as well as with past hemodialysis procedures. TTIs continue to represent a significant public health problem in Peru. Continued vigilant attention to blood safety procedures, including universal screening and health care provider education, is recommended.

The main goal of hypercholesterolemia management for coronary prevention is to reduce serum low-density lipoprotein cholesterol (LDL-C) levels. D-003 is a mixture of high molecular weight aliphatic acids purified from sugarcane wax, while policosanol is a cholesterol-lowering drug purified from the same source, consisting in a mixture of higher aliphatic alcohols. No previous comparative study of both drugs in humans has been reported. This randomized, double-blind study compares the efficacy and tolerability of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia. After a baseline period, 100 patients were randomized to D-003 or policosanol both at 5 mg/day and 10 mg/day, for 8 weeks. D-003 and policosanol 5 mg/day reduced (p0.0001) LDL-C by 26.9% and 20.9%, respectively. These reductions increased with 10 mg/day (35.1% for D-003, 25.1% for policosanol. The reductions of LDL-C achieved with D-003 5 mg/day and 10 mg/day were greater (p0.05 and p0.001, respectively) than with policosanol. The frequency of patients treated with D-003 (5 mg/day) reaching LDL-C reductionsor = 15% (22/25, 88%) was greater (p0.01) than with policosanol (5 mg/day) (19/25, 76%), and the same was true for D-003 10 mg/day (25/25, 100%) and policosanol (22/25, 88%; p0.01). D-003 and policosanol (5 mg/day) also lowered (p0.001) total cholesterol (TC) (16.2% and 13.5%, respectively), and increased high-density lipoprotein cholesterol (HDL-C) by 15.3% (D-003) and 6.7% (policosanol). At 10 mg/day, D-003 and policosanol reduced (p0.001) TC (21.3% and 16.0%, respectively), while HDL-C was increased by 17.3% and 9.8%, respectively, D-003 being more effective than policosanol. Treatments did not affect triglycerides. Both drugs were well tolerated, with D-003 tolerated as well as policosanol. Three patients discontinued the study, none due to adverse events (AEs). Seven patients (three from the D-003 group and four from the policosanol group) experienced mild AEs. In conclusion, D-003 (5 and 10 mg/day) administered to patients with type II hypercholesterolemia was more effective than policosanol in lowering LDL-C and TC, and in increasing HDL-C. D-003 could be useful for treating type II hypercholesterolemia, but this subject deserves further clinical research.

D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous studies showed that D-003 (10-20 mg/day) administered for a short time inhibits platelet aggregation, 14 days being the longest duration investigated. This study was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days on platelet aggregation in normocholesterolemic subjects. This report shows the effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM), collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at baseline and at treatment completion. Fifty-four subjects were randomized to placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA, collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly but modestly inhibited (p0.01) platelet aggregation to AA (5.0%) and (p0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p0.001) platelet aggregation to AA and collagen (p0.01) by 20.3% and 14.7%, respectively. ADP-induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5 mg/day, lowered (p0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low-density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5 mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%. Triglycerides, however, were unchanged with D-003. No disturbances in safety indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the study and four patients (three taking D-003 and one taking placebo) reported adverse effects (AE) (headache in two patients taking D-003 and one patient taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003 (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but not to ADP Therefore, the antiplatelet effect was present with the longer treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003 were consistent with those expected for such a short treatment. In addition, D-003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well tolerated.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p0.01 and p0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.

D-003 is a mixture of very high molecular weight aliphatic acids purified from sugar cane wax showing cholesterol-lowering and antiplatelet effects proven in experimental and clinical studies. Experimental evidence indicates that inhibition of platelet aggregation induced by D-003 is associated with a reduction of thromboxane B2 (TxB2) and an increase of prostacyclin (Pgl2) serum levels. This double-blinded, randomized, placebo-controlled study was undertaken to investigate whether D-003 (20 mg/day) modifies serum levels of TxB2 and Pgl2 and inhibits platelet aggregation in human healthy volunteers. Thirty-one subjects were randomized to placebo or D-003 at 20 mg/day for 14 days. Serum levels of TxB2 and Pgl2 and platelet aggregation to arachidonic acid (AA) (1.75 mM) and collagen (1 microg/ml) were assessed. D-003 (20 mg/day) significantly reduced (p0.001) TxB2by 36.4% and increased Pgl2 serum levels by 31% compared with baseline, and these changes were different from placebo. As expected, D-003 significantly inhibited (p0.001) platelet aggregation to AA (81.9-65.6%) and to collagen (75.3-62.3%). No subject withdrew from the study. No drug-related disturbances were observed. We conclude that D-003 at 20 mg/day for 14 days significantly inhibited platelet aggregation to AA and collagen and reduced TxB2 and increased Pgl2 serum levels. These results are consistent with those observed in experimental models, indicating that the antiplatelet effect of D-003 is associated with the observed changes on the levels of AA metabolites. Further studies, however, should explore the mechanism involved in this action in greater depth.

D-003 is a mixture of long-chain aliphatic primary acids isolated from sugar cane wax with cholesterol-lowering effects proven in animals and healthy human volunteers. D-003 reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in rabbits, while it increased high-density lipoprotein cholesterol (HDL-C) and did not affect triglycerides. D-003 inhibits cholesterol synthesis by regulating, instead of directly inhibiting, hydroxamethylglutaryl-CoA (HMGCoA) reductase activity. Although the ways in which D-003 and statins inhibit cholesterol biosynthesis are not identical, the strong competitive inhibition of cholesterol biosynthesis induced by statins suggests that an enhanced decrease of LDL-C and TC caused by the combined therapy D-003 plus statins is not expected. Nevertheless, taking into account the differential effects of D-003 and statins in HDL-C and triglycerides in rabbits, potential benefits of such combined therapy on other lipid variables cannot been discarded. Fluvastatin is a statin that inhibits competitively HMGCoA reductase, like other members of this class. This study was undertaken to compare the cholesterol-lowering effects of D-003, fluvastatin and the combined therapy of D-003 plus fluvastatin in normocholesterolemic rabbits. Animals were randomly distributed into four groups of eight. One control group received the vehicle, two groups were treated with D-003 or fluvastatin at 5 mg/kg/day each, and the fourth group received the combined therapy of both drugs at 5 mg/kg/day each. Treatments were orally administered for 30 days. Body weight, food consumption and overall animal behavior were recorded to detect any warning sign resulting from combined therapy. After treatment, it was found that both D-003 and fluvastatin had significantly lowered LDL-C - D-003 by 81.5% (p0.01) and fluvastatin by 61.4% (p0.05). Combined therapy reduced LDL-C values (75.9%). Final values and percent changes reached in all groups were different from the control (p0.01). The reductions of TC were consistent with LDL-C decreases, so that D-003, fluvastatin and combined therapy significantly lowered TC by 48.4% (p0.01), 39.7% (p0.05) and 45.3%, respectively, values being different from those of the control (p0.01). The responses of LDL-C and TC to combined therapy were statistically similar, but less pronounced than those reached by D-003 alone. D-003 and combined therapy, but not fluvastatin alone, increased HDL-C (+21.5% and + 19.0%, respectively), these changes being significant versus the control (p0.05). In turn, fluvastatin and combined therapy, but not D-003 alone, lowered triglycerides (13.6% and 13.0%, respectively, p0.05 versus control). The effects of combined therapy on HDL-C were similar to those of D-003 alone, and the effects of combined therapy on triglycerides were similar to those of fluvastatin alone. The only advantage of combined therapy appears to be that it shows better effects on HDL-C than those of fluvastatin alone and better effects on triglycerides than D-003 alone. No significant changes in lipid profile were observed in the control group. All groups showed similar food consumption and body weight gain, health status being unaffected by the treatments. It is concluded that D-003 and fluvastatin at 5 mg/kg/day administered orally for 30 days to normocholesterolemic rabbits lowered LDL-C and TC, D-003 being more effective in increasing HDL-C and fluvastatin in lowering triglycerides. Combined therapy did not improve the response of LDL-C and TC with respect to monotherapies, but induced better responses of HDL-C and triglycerides than fluvastatin alone had on HDL-C or D-003 alone had on triglycerides.

D-003 is a mixture of very high molecular weight aliphatic primary acids purified from sugar cane (Saccharum officinarum, L) wax, in which the most abundant component is octacosanoic acid. Experimental studies have shown that D-003 not only shows cholesterol-lowering and antiplatelet effects, but also offers strong protection against plasma lipoprotein oxidation. Previous studies demonstrated that D-003 protected against the histological changes characteristic of Cl4C-induced hepatic injury in rats. The aim of the present study was to investigate the effects of D-003 in acute hepatotoxicity induced by paracetamol in rats. Male Sprague Dawley rats were randomly distributed in two experimental series of three experimental groups as follows: group 1--positive control rats (paracetamol-treated); groups 2 and 3--rats with liver damage induced by paracetamol and treated with D-003 at 5 and 25 mg/kg, respectively, and which also received paracetamol to induce liver injury. In experimental series 1, animals received paracetamol orally (600 mg/kg). In series 2, paracetamol was administered through the intraperitoneal route (200 mg/kg). Eighteen hours after paracetamol dosing, rats were anesthetized with ether and livers were removed for histopathological studies. In the two experimental series, D-003 at 5 and 25 mg/kg significantly (p0.01) decreased the percentage of turgent cells and hepatocytes with necrosis and increased the percentage of normal hepatocytes with respect to positive controls in a dose-dependent manner. Necrotic areas and inflammatory infiltrates were observed in the liver of nine out of ten (90%) positive controls. In turn, D-003 dramatically reduced both necrotic areas and inflammatory infiltrate and was present in only one out of ten (10%) animals treated in the two experimental series. No histological alterations in liver sections of negative controls were found. D-003 protected against the histological changes characteristic of paracetamol-induced hepatic injury in rats, in which the process of lipid peroxidation plays a major role. The relationship between this protective action of D-003 in this experimental model and its antioxidant effects needs to be further investigated before definitive conclusions are drawn.

D-003 is a mixture of very high molecular weight aliphatic primary acids purified from sugar cane (Saccharum officinarum, L.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies have shown that D-003 not only shows cholesterol-lowering and antiplatelet effects, but also offers strong protection against plasma lipoprotein oxidation. Acute hepatotoxicity induced by CCL4 in rats has been related to an increased rate of lipid peroxidation, and different antioxidant compounds have been revealed to be effective in this model. The aim of this study was to investigate the effects of D-003 in acute hepatotoxicity induced by CCL4 in rats. Male Sprague Dawley rats were randomly distributed in four experimental groups as follows: group 1: negative control rats; group 2: positive control rats (CCL4-treated); groups 3 and 4 rats with liver damage induced by CCL4 and treated with D-003 at 25 and 100 mg/kg, respectively. Acute liver injury was induced by CCL4 suspended in olive oil and intraperitoneally administered at 1 ml/kg. Eighteen hours after CCL4 dosing, the rats were anesthetized with ether and their livers were removed for histopathological studies. D-003 at 25 and 100 mg/kg significantly (p0.01) decreased the percentage of ballooned cells and hepatocytes with lipidic inclusions and increased the percentage of normal hepatocytes compared with that in positive controls in a dose-dependent manner. The percent inhibitions of the occurrence of ballooned cells and hepatocytes with lipids were marked (75% and 50%, respectively) with the high dose (100 mg/kg). The percent of turgent hepatocytes was also significantly reduced compared with that in positive controls, but this effect was not dose-dependent. No histological alterations in the liver sections of negative controls were found. Necrotic areas and inflammatory infiltrate were observed in the liver of 7/8 (87.5%) of positive controls. In turn, D-003 dramatically reduced both necrotic areas and inflammatory infiltrate and was present in only 1/8 (12.5%) animals treated with D-003 25 mg/kg and in none (0%) of the animals treated with 100 mg/kg. D-003 protected against the histological changes characteristic of CCL4-induced hepatic injury in rats, in which the process of lipid peroxidation plays the main role. The relationship between this protective action of D-003 on this experimental model and its antioxidant effects needs to be further investigated before definitive conclusions are drawn.

Background: We hypothesized that children’s perceptions of more neighborhood hazards would be associated with less physical activity, less aerobic fitness, and a higher body mass index. Objective: To examine the association between a hazardous neighborhood context and physical activity in children. Methods: Fourth-grade students (n=796) of diverse ethnic and economic backgrounds completed measures of neighborhood hazards, self-reported physical activity, physical fitness, height, and weight. Parents (n=518) completed telephone interviews and provided data on their education level and occupation. Results: As expected, children from families of lower socioeconomic status perceived significantly more neighborhood hazards. Contrary to our hypothesis, the perception of more hazards was significantly associated with more reported physical activity. This finding was not explained by school heterogeneity, alteration of the hazards measure, or differences in socioeconomic status. Conclusion: To further examine the relationship between neighborhood hazards and physical activity, we suggest that future studies include assessments of sedentary behavior, parental fear of violence, parental regulation of children’s leisure activities, and cost and quality of available play areas and organized sports. Arch Pediatr Adolesc Med. 2001;155:1143-1148

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects proved in experimental models and healthy volunteers. This study reports the results of a 4-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation in type II hypercholesterolemic patients. Patients started or continued on a step-one cholesterol-lowering therapy for 4 weeks and those with total cholesterol5.0 mmol/L despite dietary conditions were randomized to receive under double-blind conditions placebo or policosanol (10 mg/day) for 30 days. Both groups were similar at randomization. Effects of policosanol on platelet aggregation induced by arachidonic acid (3.2 mM), collagen (0.5-1 microgram/ml) and ADP (0.5-1 uM) were determined at baseline and after 30 days of treatment. Policosanol significantly reduced platelet aggregation induced by arachidonic acid and collagen, meanwhile it only inhibited significantly the platelet aggregation induced by the lowest doses of ADP (0.5 uM). No adverse events occurred during the trial. Only one patient (placebo) discontinued from the study because of arthralgia.

The key role of p53 and Rb alterations in human osteosarcoma is clear. For example, osteosarcoma is common in individuals inheriting mutant p53 or Rb genes. Osteosarcoma in dogs is similar to humans by histology, site, gender ratio and several other biological parameters. To study whether this similarity extends to the molecular level, 21 canine osteosarcomas were analyzed for alterations of p53, Rb and MDM2. MDM2 is a normal cell protein which antagonizes p53, amplification is seen in some human sarcomas. The gross structure of the p53, Rb and MDM2 genes was examined by Southern blotting. No deletions or rearrangements of the p53 or Rb genes were detected. The absence of gross gene alterations affecting these tumor suppressor genes is a significant difference between the disease in dogs and humans, since rearrangements or deletions of the p53 or Rb genes occur in 20-30 per cent of human osteosarcomas. The MDM2 gene appeared to be duplicated in one canine tumor but no cases of significant amplification were detected. Expression of normal Rb was detected in all cases. Mutations of the p53 gene were found in 38 percent of canine osteosarcomas. Analysis of mutations revealed a predominance of spontaneous mutation. These finding emphasize the key role that alterations of p53 have in the development of osteosarcoma in dogs and humans.

394 patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine 150 bid o ranitidine 300 mg bid in a prospective double-blind multicenter trial conducted in seven LatinoAmerican countries. Endoscopy at 4 weeks showed complete ulcer healing en 171 of 196 patients (87.2%) treated with ranitidine 150 mg bid and 178 of 198 (89.9%) treated with ranitidine 300 mg bid. Both treatment regimens were equally effective at rapidly reducing the incidence of ulcer-related symptoms. It is possible that higher dosage regimen of ranitidine would be useful in patients with more severe duodenal ulcer disease.

The present investigation reports light and electron microscopical aspects of the main olfactory epithelium (MOE) of the insectivorous bat Scotophilus heathi. Serial frontal sections of the nose and associated structures reveal: 1) that the MOE is located on most of the ethmoturbinals and on the proximal upper portion of the nasal septum; and 2) that the vomeronasal organ is absent in this species. The ultrastructure of the MOE of Scotophilus heathi is similar to that observed in other vertebrates. Moreover, we did not observe significant morphological differences between the MOE of male and female animals. Nevertheless, the supra-nuclear region of the supporting cells of males and females shows a different amount and distribution of "lysosome-like" cell organelles at the two times of the year investigated.

The present electron-microscopical study reports ultrastructural changes occurring in the supranuclear region of the supporting cells of the rat olfactory epithelium during the first 16 days of postnatal life. These changes are concerned with the enclosure of receptor cell dendrites and an increase in the amount of smooth endoplasmic reticulum, which has a specific distribution in the supporting cell. An increase in microvillous projections at the free cell surface is also observed. Moreover, this report demonstrates that the cytoarchitecture of the apical portion of the olfactory epithelium at the 16th day of postnatal life is similar, with respect to the relationship between supporting cells and receptor cell dendrites, to that of adult animals.