Functional Evidence of CCDC186 as a New Disease-Associated Gene with Endocrine and Central Nervous System Alterations.

CCDC186 protein is involved in the maturation of dense-core vesicles (DCVs) in the trans-Golgi network in neurons and endocrine cells. Mutations in genes involved in DCV regulation, other than CCDC186, have been described in patients with neurodevelopmental disorders. To date, only one patient, within a large sequencing study of 1000 cases, and a single case report with variants in CCDC186, had previously been described. However, no functional studies in any of these two cases had been performed. We identified three patients from two gypsy families, unrelated to each other, with mutations in the CCDC186 gene. Clinically, all patients presented with seizures, frontotemporal atrophy, hypomyelination, recurrent infections, and endocrine disturbances such as severe non-ketotic hypoglycemia. Low levels of cortisol, insulin, or growth hormone could only be verified in one patient. All of them had a neonatal onset and died between 7 months and 4 years of age. Whole exome sequencing identified a homozygous variant in the CCDC186 gene (c.2215C>T, p.Arg739Ter) in the index patients of both families. Protein expression studies demonstrated that CCDC186 was almost undetectable in fibroblasts and muscle tissue. These observations correlated with the transcriptomic analysis performed in fibroblasts in one of the patients, which showed a significant reduction of CCDC186 mRNA levels. Our study provides functional evidence that mutations in this gene have a pathogenic effect on the protein and reinforces CCDC186 as a new disease-associated gene. In addition, mutations in CCDC186 could explain the combined endocrine and neurologic alterations detected in our patients.

Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis.

Vitamin D deficiency has been linked with adverse events in various liver diseases. The present study aimed to recognize the association between severe vitamin D deficiency and disease progression, hepatobiliary malignancies, liver-related mortality, and the need for liver transplantation in primary sclerosing cholangitis (PSC). Patients with a diagnosis of PSC (n = 354), followed by the autoimmune liver disease clinic at the University of Alberta, were included. Patients with vitamin D levels < 25 nmol/L were defined as severely deficient. Univariate and multivariate analyses were conducted using the Cox proportional hazards regression models. The mean vitamin D level was 59 ± 2 nmol/L, and 63 patients (18%) had a severe vitamin D deficiency. Patients with a severe vitamin D deficiency were 2.5 times more likely to experience hepatobiliary malignancies (HR 2.55, 95% CI, 1.02-6.40, p = 0.046). A severe vitamin D deficiency at diagnosis (HR 1.82, 95% CI, 1.05-3.15, p = 0.03) and persistent deficiencies over time (HR 2.26, 95% CI, 1.17-4.37, p = 0.02) were independently associated with a higher risk of poor clinical liver outcomes. A severe vitamin D deficiency at diagnosis and persistent deficiency at longitudinal assessments were associated with liver-related mortality or the need for liver transplantation.

Return to work of employees with low levels of education: The employers' role and perspective.

BACKGROUND: To achieve adequate return to work (RTW) after sickness absence, Dutch legislation prescribes cooperation between absent employees and employers. Yet, we lack insight into how employees with low levels of education exercise influence over (i.e. self-direct) RTW. OBJECTIVE: This study aimed to enhance our understanding of: (A) the role that employers play in the self-direction of employees with low levels of education over their RTW; (B) how employers perceive these employees' efforts (or lack thereof) to self-direct their own RTW; and (C) how employers understand and interpret the behaviours of these employees. Social cognitive theory served as a framework. METHODS: A qualitative study was conducted with 13 employer representatives using semi-structured interviews. Data were analysed in NVivo12 using a template approach. RESULTS: Employers tend to play a guiding, directive role in employees' RTW. According to employers, employees generally comply with the employers' decisions and suggestions, whether or not they have tried to realise their own preferences regarding mode and timing of RTW. Employers interpret such employee behaviours from the perspective of environmental (e.g. financial pressures to RTW) and person-related factors (e.g. sickness and RTW perceptions). CONCLUSIONS: Employers, rather than employees direct the employees' RTW. Employers should give voice to employees and enable them to have more control over their RTW. Future research should acquire more insight in the employees' perspective.

Low Levels Matter: Clinical Relevance of Low Pru p 3 sIgE in Patients With Peach Allergy.

Many clinical lab settings still use 0.35 KUA/L as the cut-off for serum specific-IgE (sIgE) immunoassays, while the detection limit is 0.1 KUA/L. The clinical relevance of -low-level sIgE (0.1-0.35 KUA/L) remains controversial. Pru p 3 sIgE is considered to be the main routine tool for assessing lipid transfer protein (LTP) sensitization. We aimed to evaluate the clinical relevance of Pru p 3 sIgE low levels in a population diagnosed with LTP allergy. Adults diagnosed with LTP allergy and Pru p 3 sIgE ≥ 0.1 KUA/L between 2012 and 2019 were included. Clinical data were reviewed. nPru p 3 basophil activation test (BAT) was performed and basophil reactivity (BR) and sensitivity (BS) correlated with the peach allergy symptoms. Pru p 3 sIgE from 496 subjects was recorded, 114 (23.0%) between 0.1 and 0.34 KUA/L (grLOW), the rest ≥ 0.35 KUA/L (grB). A total of 44.7% in grLOW and 59.9% in grB were allergic. Urticaria was more frequent in grLOW. In grLOW, Pru p 3 sIgE was higher in patients with local compared with systemic symptoms. In grB, Pru p 3 sIgE was higher in allergic patients. Pru p 3/Total IgE ratios were higher in allergic vs. tolerant in both groups. In BAT, BR was similar in both groups. In grLOW, it was higher on allergic compared with tolerant (p = 0.0286), and on those having systemic vs. local symptoms (p = 0.0286). BS showed no significant difference between groups. Patients with low levels represent a non-negligible fraction and around 45% are peach allergic. BAT showed functional sIgE in them. Pru p 3 sensitizations should be carefully evaluated even when sIgE levels are low.

Analysis of pathological changes and related factors in liver tissue of HBeAg-negative patients with low HBsAg levels.

The relationship between pathological changes in liver tissue and the level of hepatitis B surface antigen (HBsAg) remains unclear. This study aimed to analyze the pathological changes in liver tissue and its related factors in patients with low-level HBsAg in order to provide a basis for judging the condition of these patients. A retrospective study was performed on 96 chronic hepatitis B patients with HBsAg levels < 1400 IU/ml and > 0.05 IU/ml. The histopathological examination of these patients was conducted. Univariate and multivariate analyses were used to determine risk factors for pathological changes. Among the 96 patients, 57.3% (55) had inflammatory events ≥ G2 and 33.4% (33) had fibrosis ≥ S2. HBV infection duration (p = 0.001) and splenic vein diameter (p = 0.001) were independent risk factors of liver inflammation (≥ G2) in patients with low-level HBsAg, while AST (p = 0.006) and PLT (p = 0.005) were independent risk factors of liver fibrosis (≥ S2). Moreover, HBV infection duration (p < 0.001) and spleen vein (p = 0.001) were independent factors of potential antiviral treatment. Liver inflammation and fibrosis are still common in patients with low-level HBsAg; thus, the monitoring and appropriate antiviral treatment cannot be ignored.

Low Levels of Air Pollution and Health: Effect Estimates, Methodological Challenges, and Future Directions.

PURPOSE OF REVIEW: Fine particle (PM2.5) levels have been decreasing in the USA over the past decades. Our goal was to assess the current literature to characterize the association between PM2.5 and adverse health at low exposure levels. RECENT FINDINGS: We reviewed 26 papers that examined the association between short- and long-term exposure to PM2.5 and cardio-respiratory morbidity and mortality. There is evidence suggesting that these associations are stronger at lower levels. However, there are certain methodological and interpretational limitations specific to studies of low PM2.5 levels, and further methodological development is warranted. There is strong agreement across studies that air pollution effects on adverse health are still observable at low concentrations, even well below current US standards. These findings suggest that US standards need to be reevaluated, given that further improving air quality has the potential of benefiting public health.

Secondary traumatization in first responders: a systematic review.

Background: Finding precise definitions of secondary traumatic stress, vicarious traumatization, and compassion fatigue is not easy. While some researchers define these terms differentially, others use them interchangeably. In the present review, we refer to all three phenomena as secondary traumatization. Objectives: This systematic review aims to provide an overview of prevalence rates of secondary traumatization in first responders and to shed light on corresponding resilience and risk factors. Methods: After identifying 219 studies within the searched databases and 2192 references via hand searching, 31 studies were included in this review. We systematically searched the electronic databases PubMed, PsychINFO, and PSYNDEX (German database). The following inclusion criteria were applied: (1) participants had to be first responders working on-site: police officers, firefighters, search and rescue personnel, or emergency and paramedic team members; (2) secondary traumatization (secondary traumatic stress/vicarious traumatization/compassion fatigue) was assessed quantitatively with a validated questionnaire or subscale explicitly measuring secondary traumatization; and (3) English or German language original papers. Results: We found low levels of secondary traumatization in first responders. Several studies describe protective and risk factors for secondary traumatization, including pretraumatic (e.g. age, gender), peritraumatic (e.g. exposure, emotional exhaustion), and post-traumatic factors (e.g. social support, alcohol and tobacco use). Conclusion: Next to an immunizing effect, the low prevalence of secondary traumatization in first responders could be explained by social desirability and job-loss concerns. Therefore, we may be underestimating the prevalence of secondary traumatization in first responders. Some resilience (social support) and risk factors (female gender) are consistent with previous research in other populations. However, owing to the cross-sectional study designs, we must interpret resilience and risk factors with caution. Future research should focus on longitudinal study designs and preventive as well as curative interventions.

Antecedentes: No es fácil encontrar definiciones precisas de estrés traumático secundario, traumatización vicaria y fatiga de compasión. Mientras algunos investigadores definen estos términos de forma diferencial, otros los usan indistintamente. En esta revisión consideramos estos tres fenómenos como traumatización secundaria.Objetivos: Esta revisión sistemática tiene por objetivo proveer de una visión general de la prevalencia de tasas de traumatización secundaria en personal encargado de prestar primeros auxilios y aclarar los factores de riesgo y resiliencia relacionadas.Mtodos: Tras identificar 219 estudios en búsquedas en bases de datos y 2192 referencias identificadas a través de búsqueda manual, 31 estudios fueron incluidos en esta revisión. Sistemáticamente buscamos en las bases de datos electrónicas: PubMed, PsychInfo y PSYNDEX (base de datos alemana). Se aplicaron los siguientes criterios de inclusión: (1) los participantes tenían que ser personas encargadas de prestar primeros auxilios en terreno: oficiales de policía, bomberos, personal de búsqueda y socorristas, equipos paramédicos y de emergencia, (2) traumatización secundaria (estrés traumático secundario/traumatización vicaria/fatiga de compasión) evaluada cuantitativamente con un cuestionario o sub-escala validados para medir explícitamente traumatización secundaria, (3) artículos originales en inglés o alemán.Resultados: Encontramos bajos niveles de traumatización secundaria en personal encargado de prestar primeros auxilios. Varios estudios describen factores de protección y de riesgo para traumatización secundaria, incluyendo factores pre- (ej. edad, género), peri- (ej. exposición, agotamiento emocional), y post-traumáticos (ej. apoyo social, uso de tabaco y alcohol).Conclusión: Además de un efecto inmunizante, la baja prevalencia de traumatización secundaria en personal encargado de prestar primeros auxilios podría ser explicada por aceptación social y preocupaciones respecto a pérdida de empleo. Por lo tanto, podríamos estar subestimando la prevalencia de traumatización secundaria en esta población. Algunos factores de resiliencia (apoyo social) y de riesgo (género femenino) son consistentes con investigaciones previas en otras poblaciones. Sin embargo, al tratarse de diseños de estudios transversales, debemos interpretar la resiliencia y factores de riesgo con cautela. Investigaciones futuras deberían enfocarse en estudios de tipo longitudinal así como también en intervenciones preventivas y curativas.

Low Levels of Physical Activity and Sedentary Behavior in Adults with Intellectual Disabilities.

Adults with intellectual disabilities (ID) are more likely to lead sedentary lifestyles and have low levels of physical activity (LLPA). The present study investigated the prevalence of reported LLPA and time spent watching TV in adults with ID and identified the associated factors for these behaviors. The proxy informants of 1618 adults with ID completed the surveys regarding their health behaviors. Multiple logistic regressions were employed for LLPA and multiple linear regressions for time spent watching TV. About 60% of adults with ID had LLPA and average time spent watching TV was 3.4 h a day. Some characteristics and health and function variables were identified as associated factors. While engaging in community activities and involvement in Special Olympics were inversely associated with LLPA, they were not associated with time spent watching TV. Attending day/educational programs or being employed were associated with spending less time watching TV. Findings highlight differential factors associated with LLPA versus TV-watching behavior in adults with ID. Hence, a key strategy aimed at increasing physical activity includes promoting participation in social and community activities, while targeted activities for reducing sedentary behavior might focus on providing day programs or employment opportunities for adults with ID.

Depression as a moderator of STAIR Narrative Therapy for women with post-traumatic stress disorder related to childhood abuse.

Background: Depression among those who have experienced childhood abuse is associated with earlier onset, more persistent and severe symptoms, more frequent relapse, and poorer treatment outcomes across a variety of psychiatric disorders. In addition, individuals with a history of childhood abuse are more likely to develop post-traumatic stress disorder (PTSD) co-occurring with depression. Objective: This study evaluated whether severity of depression moderated the outcome in a PTSD treatment for childhood abuse survivors. Specifically, we assessed whether individuals with significant depression obtained better outcomes when provided with a two-module treatment which included a skills training component with behavioral activation interventions, Skills Training in Affective and Interpersonal Regulation (STAIR) followed by a trauma-focused component, Narrative Therapy, as compared to two control conditions where one component (STAIR or Narrative Therapy) was replaced with Supportive Counseling. Method: Participants were 104 women with PTSD related to childhood abuse. Participants were randomized into three conditions: (1) STAIR plus Narrative Therapy (SNT), (2) STAIR plus Supportive Counseling (SSC), and (3) Supportive Counseling plus Narrative Therapy (SCNT). Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) PTSD symptom severity was assessed at pre-treatment, post-treatment, and 3 and 6 month follow-up. Results: Participants with severe depression showed superior PTSD symptom reduction following SNT, while those in the other two conditions experienced a loss of improvement after treatment ended. A similar finding was obtained among those with moderate depression, while among those with low levels of depression, outcomes did not differ across the three treatment conditions. Conclusions: Childhood abuse survivors with severe depression obtained superior outcomes in a treatment that combined skills training with trauma-focused work. Skills packages which contain behavioral activation interventions in combination with trauma-focused work may be particularly beneficial for patients with childhood abuse and severe depression.

Planteamiento: La depresión entre los que han sufrido malos tratos en la infancia se asocia con un inicio más temprano, síntomas más persistentes y graves, recaídas más frecuentes y peores resultados de tratamiento en una variedad de trastornos psiquiátricos. Además, las personas con abuso infantil son más propensas a desarrollar un TEPT concurrente con la depresión. Objetivo: Este estudio evaluó si la gravedad de la depresión moderaba el resultado en un tratamiento de TEPT para sobrevivientes de maltrato infantil. Específicamente, evaluamos si los individuos con depresión significativa obtenían mejores resultados cuando se les proporcionaba un tratamiento de dos módulos que incluía un componente de entrenamiento en habilidades con intervenciones de activación conductual, Entrenamiento de habilidades en regulación afectiva e Interpersonal (STAIR, siglas en inglés de Skills Training in Affective and Interpersonal Regulation), seguido de un componente centrado en el trauma, Terapia Narrativa (TN), en comparación con dos condiciones de control en las que un componente (el STAIR o la TN) se sustituía por terapia de apoyo (TA). Métodos: Los participantes fueron 104 mujeres con TEPT relacionado con maltrato infantil. Los participantes fueron asignados al azar a tres condiciones: (1) STAIR más Terapia Narrativa (STN) (2) STAIR más terapia de apoyo (STA) y (3) terapia de apoyo más Terapia Narrativa (TATN). Se evaluó la gravedad de los síntomas de TEPT con el CAPS-IV al inicio del tratamiento, después del tratamiento y en el seguimiento a los 3 y 6 meses. Resultados: Los participantes con depresión grave mostraron una mayor reducción de los síntomas de TEPT después de la Terapia Narrativa de STAIR, mientras que los de las otras dos condiciones experimentaron una pérdida de mejoría una vez finalizado el tratamiento. Se encontró un resultado similar entre los que tenían depresión moderada, mientras que entre los que tenían un nivel bajo de depresión, los resultados no difirieron entre las tres condiciones de tratamiento. Conclusión: Los supervivientes de maltrato infantil con depresión grave obtuvieron resultados superiores en un tratamiento que combina entrenamiento de habilidades con el trabajo centrado en el trauma. Los paquetes de habilidades que contienen intervenciones de activación conductual en combinación con el trabajo centrado en el trauma pueden ser particularmente beneficiosos para pacientes con abuso infantil y depresión grave.

Mediation of effects of the level of response to alcohol and impulsivity 15 years later in 36-year-old men: Implications for prevention efforts.

BACKGROUND: Although the prevalence of alcohol use disorders (AUDs) has increased in older individuals in the recent decade, there are few programs to mitigate that increase. The current analyses evaluate the feasibility of applying to older drinkers elements of an approach to prevent heavier drinking in young adults by focusing on mediators of effects of two risk factors for alcohol problems, low levels of response to alcohol (low LRs) and higher impulsivity. METHODS: Data were extracted from the San Diego Prospective Study (SDPS). Structural Equation Models evaluated relationships among age 36 low LRs and higher impulsivity; age 46 perceived peer drinking, alcohol expectancies, and drinking to cope; and age 51 alcohol problems, even after controlling for age 36 alcohol problems. RESULTS: Relationships of age 36 low LRs to later alcohol problems was both direct and linked to age 46 heavy drinking peers. LR also operated indirectly through peer drinking to alcohol expectancies and drinking to cope. Age 36 impulsivity had no direct path to later alcohol problems and operated primarily through mediation by alcohol expectancies and via expectancies to drinking to cope. After controlling for age 36 alcohol problems, the low LR and impulsivity results remained robust. CONCLUSIONS: Programs for mitigating increases in alcohol problems in middle-age drinkers should consider identifying individuals with low LRs and/or higher impulsivity and implementing prevention approaches similar to a program used in young adults. The approach should emphasize some different mediators for older drinkers with low LRs and those with higher impulsivity.

Concentrations of Trace Elements in Hemodialysis Patients: A Prospective Cohort Study.

BACKGROUND: Low concentrations and excessive concentrations of trace elements have been commonly reported in hemodialysis patients, but available studies have several important limitations. STUDY DESIGN: Random sample of patients drawn from a prospective cohort. SETTING & PARTICIPANTS: 198 incident hemodialysis patients treated in 3 Canadian centers. MEASUREMENTS: We used mass spectrometry to measure plasma concentrations of the 25 elements at baseline, 6 months, 1 year, and 2 years following enrollment in the cohort. We focused on low concentrations of zinc, selenium, and manganese and excessive concentrations of lead, arsenic, and mercury; low and excessive concentrations of the other 19 trace elements were treated as exploratory analyses. Low and excessive concentrations were based on the 5th and 95th percentile plasma concentrations from healthy reference populations. RESULTS: At all 4 occasions, low zinc, selenium, and manganese concentrations were uncommon in study participants (≤5.1%, ≤1.8%, and ≤0.9% for zinc, selenium, and manganese, respectively) and a substantial proportion of participants had concentrations that exceeded the 95th percentile (≥65.2%, ≥74.2%, and ≥19.7%, respectively). Almost all participants had plasma lead concentrations above the 95th percentile at all time points. The proportion of participants with plasma arsenic concentrations exceeding the 95th percentile was relatively constant over time (9.1%-9.8%); the proportion with plasma mercury concentrations that exceeded the 95th percentile varied between 15.2% and 29.3%. Low arsenic, platinum, tungsten, and beryllium concentrations were common (>50%), as were excessive cobalt, manganese, zinc, vanadium, cadmium, selenium, barium, antimony, nickel, molybdenum, lead, and chromium concentrations. CONCLUSIONS: There was no evidence that low zinc, selenium, or manganese concentrations exist in most contemporary Canadian hemodialysis patients. Some patients have excessive plasma arsenic and mercury concentrations, and excessive lead concentrations were common. These findings require further investigation.

Correlations betweenintrahepatic HBsAg and HBcAg levels and serum HBsAg and HBV DNA levels in low-level HBsAg patients / 实用医学杂志

Objective To analyze the relationship between intrahepatic expression of HBsAg and HBcAg and the serum HBsAg and the load of HBV DNA in low-level HBsAg.To provide the basis for the diagnosis of low-level HBsAg.Methods A total of 63 patients with HBsAg lower than 1 400 IU/mL and higher than 0.05 IU/mL were enrolled in the study.All the 63 patients with low level HBsAg were collected for liver biopsy from January 2013 to December 2015.Serum HBsAg was detected by Roche cobas e601 automatic electrochemiluminescence immunoas-say system and supporting reagents.HBV DNA was detected using ROCHE automatic AmpliPrep/cobas TaqMan 48 system detector and supporting reagents.Results Among the 63 patients,the HBsAg in liver tissue was negative in 5 cases(7.94%),+in 47 cases(74.60%),++in 8 cases(12.70%),+++in 2 cases(3.17%),and++++was found in 1 case.The expression of HBcAg were negative in 30 cases(47.62%),+in 28 cases(44.44%),++in 4 cases(6.35%),+++in 1 case(1.59%),and++++in 0 cases.There was a significant positive correlation between HBsAg expression and serum HBsAg level by spearman and kendall correlation analysis(spearman analysis:r = 0.261,P=0.039;kendall analysis:r=0.217,P=0.036).HBcAg expression was significantly correlated with serum HBV DNA load with spearman and kendall correlation analysis(spearman analysis:r=0.305,P=0.015;kendall analysis:r=0.259,P=0.017).Conclusions The expression of HBsAg in liver tissue of in the patients with low level of HBsAg is positively correlated with the level of serum HBsAg,but not with the load of HBV DNA. There is significant positive correlation between HBcAg expression and serum HBV DNA load.

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salar L.) fed diets with graded levels of plant ingredients.

Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

Sucrose Transporter AtSUC9 Mediated by a Low Sucrose Level is Involved in Arabidopsis Abiotic Stress Resistance by Regulating Sucrose Distribution and ABA Accumulation.

Sucrose (Suc) transporters (SUCs or SUTs) are important regulators in plant growth and stress tolerance. However, the mechanism of SUCs in plant abiotic stress resistance remains to be dietermined. Here, we found that AtSUC9 expression was induced by abiotic stress, including salt, osmotic and cold stress conditions. Disruption of AtSUC9 led to sensitive responses to abiotic stress during seed germination and seedling growth. Further analyses indicated that the sensitivity phenotype of Atsuc9 mutants resulted from higher Suc content in shoots and lower Suc content in roots, as compared with that in wild-type (WT) plants. In addition, we found that the expression of AtSUC9 is induced in particular by low levels of exogenous and endogenous Suc, and deletion of AtSUC9 affected the expression of the low Suc level-responsive genes. AtSUC9 also showed an obvious response to treatments with low concentrations of exogenous Suc during seed germination, seedling growth and Suc distribution, and Atsuc9 mutants hardly grew in abiotic stress treatments without exogenous Suc. Moreover, our results illustrated not only that deletion of AtSUC9 blocks abiotic stress-inducible ABA accumulation but also that Atsuc9 mutants had a lower content of endogenous ABA in stress conditions than in normal conditions. Deletion of AtSUC9 also inhibited the expression of many ABA-inducible genes (SnRk2.2/3/6, ABF2/3/4, ABI1/3/4, RD29A, KIN1 and KIN2). These results indicate that AtSUC9 is induced in particular by low Suc levels then mediates the balance of Suc distribution and promotes ABA accumulation to enhance Arabidopsis abiotic stress resistance.

Ganho de peso, consumo de ração e histologia de órgãos de leitões alimentados com rações contendo baixos níveis de fumonisina B1 / Weight gain, feed consumption and histology of organs from piglets fed rations containing low levels of fumonisin B1

A fumonisina B1 (FB1) é um metabólito secundário produzido principalmente por Fusarium verticilioides em diversos tipos de alimentos, principalmente o milho, o qual constitui a base para composição de rações para várias espécies de animais domésticos. A FB1é particularmente tóxica para suínos, cujas manifestações clínicas são evidentes em animais expostos a altas concentrações de FB1 na ração (em geral, acima de 30mg/kg). No entanto, são escassos os estudos sobre os efeitos da FB1em suínos alimentados com rações contendo baixas concentrações de fumonisinas, as quais são mais prováveis de serem encontradas em condições de campo. O objetivo do estudo foi avaliar os efeitos da exposição de leitões a baixos níveis de FB1 na ração, durante 28 dias, sobre o ganho de peso, consumo de ração, peso relativo de órgãos e aspectos histológicos do baço, fígado, pulmões, rins e coração. Vinte e quatro leitões foram distribuídos em 4 grupos experimentais e alimentados com rações contendo 0mg (controle), 3,0mg, 6,0mg ou 9,0mg FB1/kg de ração. As diferentes dietas não afetaram (P>0,05) o ganho de peso e nem o peso relativo dos órgãos analisados. Não foram constatadas lesões macroscópicas ou histopatológicas no baço, fígado, rins e coração. No entanto, foram observadas lesões histopatológicas nos pulmões de todos os suínos alimentados com rações contaminadas com fumonisinas, indicando que nenhum dos níveis de FB1 usados no experimento poderia ser considerado como seguro para suínos. São necessários novos estudos sobre os mecanismos de ação tóxica da FB1 em suínos, sobretudo em condições de exposição prolongada a baixos níveis de contaminação na ração.

Fumonisin B1 (FB1) is a secondary metabolite produced mainly by Fusarium verticilioides in several types of foods, particularly corn, which is the basis for composition of feed for several domestic animals. FB1 is particularly toxic to pigs, being the clinical manifestations evident in animals exposed to high concentrations of FB1 in the diet (generally above 30mg/kg). However, there are few studies on the effects of FB1 on pigs fed rations containing low concentrations of fumonisin, which are most probably found under field conditions. The aim of the study was to evaluate the effects of a 28-day exposure of piglets to low levels of FB1 in the feed on the weight gain, feed consumption, organ weights and histological aspects of the spleen, liver, lungs, kidneys and heart. Twenty-four pigs were assigned into 4 experimental groups and fed diets containing 0mg (control), 3.0mg, 6.0mg or 9.0mg FB1/kg diet. The different diets did not affect (P>0.05) the weight gain or the weight of organs examined. There were no macroscopic or histological lesions in the spleen, liver, kidneys and heart. However, histological lesions were found in the lungs from all animals fed rations containing fumonisin, hence indicating that none of the FB1 levels used in the experiment could be considered as safe for piglets. Further studies on the mechanisms of toxic action of FB1 in pigs are needed, particularly under conditions of prolonged exposure to low contamination levels in the diet.

Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer.

The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24-84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC.

Niveles de vitamina D en mujeres posmenopáusicas con osteoporosis primaria / Levels of vitamin D in posmenopausal women with primary osteoporosis

La osteoporosis es un problema de salud pública a nivel mundial, particularmente en mujeres posmenopáusicas, jugando la deficiencia de vitamina D un importante rol en su génesis. Objetivo: Determinar los niveles de Vitamina D en mujeres posmenopáusicas con osteoporosis primaria. Material y métodos: Estudio descriptivo tipo serie de casos. Se incluyeron 40 mujeres posmenopáusicas con diagnóstico de osteoporosis primaria; se excluyeron las que habían recibido suplemento de calcio o vitamina D, terapia para osteoporosis o tenían alguna causa de osteoporosis secundaria. A todas las mujeres incluidas se les determinó el nivel sérico de 25 OH vitamina D. Resultados: La edad promedio fue 65,9 ± 10,22 años, y el promedio del Score T L1-L4 fue -2,82 ± 0,71, Score T en Cadera Total -1,59 ±1,05 y el Score T en radio 33% -3,10 ± 0,97 en la densitometría ósea. El nivel de vitamina D sérico fue 13,98 ± 5,95 ng/ml; 87,5% (35 pacientes) tuvieron niveles de vitamina D deficientes, 7,5% (3 pacientes) tenían niveles insuficientes y sólo 2 pacientes tuvieron niveles normales de vitamina D. Conclusión: La mayoría de mujeres posmenopáusicas con osteoporosis primaria tuvieron niveles de vitamina D en rangos de deficiencia e insuficiencia. Podría ser necesario dar suplementos de calcio y vitamina D a todas las pacientes posmenopáusicas con osteoporosis.

Osteoporosis is a public health problem in the world, mostly in postmenopausal women, low levels of vitamin D play an important role in its origin. Objective: To get the levels of vitamin D in postmenopausal women with primary osteoporosis. Material and methods: Descriptive study case series. We included a total of 40 postmenopausal women with diagnosis of primary osteoporosis, we excluded those women who received calcium and/or vitamin D supplement, treatment for osteoporosis or those women with a secondary osteoporosis. The serum level of 25 OH vitamin D was determined in all women. Results: 40 patients with primary osteoporosis were included, average age was 65.9 ± 10.22 years old, and with average T score L1-L4 of -2.82 ±0.71, T Score in total hip of -1.59 ±1.05 and a T score in radius 33% of -3.10 ± 0.97 by bone densitometry. The average level of serum vitamin D was 13.98 ± 5.95 ng/ml, 87.5% (35 patients) had deficient levels of vitamin D, 7.5% (3 patients) had insufficient levels and only the 5% (2 patients) had normal levels of vitamin D. Conclusion: Most postmenopausal women with primary osteoporosis had low levels of vitamin D; 87.5%. It could be necessary to supplement with calcium and vitamin D to all postmenopausal women patients with osteoporosis.