Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling

Anemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the inflammatory context is still not understood completely. In the present study, we show that activin B has an unexpected but crucial role in the induction of hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding the activin β(B)-subunit, in the livers of mice challenged with lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma-derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates hepcidin expression markedly, an observation confirmed in mouse primary hepatocytes. Pretreatment with a bone morphogenic protein type I receptor inhibitor showed that the effect of activin B on hepcidin expression is entirely attributable to its effect on bone morphogenetic protein signaling, most likely via activin receptor-like kinase 3. Activin B is therefore a novel and specific target for the treatment of anemia of inflammation.     

Pandemic A/H1N1 influenza: Transmission of the first cases in Spain

Introduction

Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe.

Methods

Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases.

Results

On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1–16.1) and their contacts (13.2%; CI: 4.4–22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel.

Conclusion

The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO.     

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets

Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and na?ve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.     

The dimensionality of between‐person differences in white matter microstructure in old age

Between‐person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion‐tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60–87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract‐specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age‐related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Effects of dietary inorganic nitrate on static and dynamic breath-holding in humans

Inorganic nitrate has been shown to reduce oxygen cost during exercise. Since the nitrate-nitrite-NO pathway is facilitated during hypoxia, we investigated the effects of dietary nitrate on oxygen consumption and cardiovascular responses during apnea. These variables were measured in two randomized, double-blind, placebo-controlled, crossover protocols at rest and ergometer exercise in competitive breath-hold divers. Subjects held their breath for predetermined times along with maximum effort apneas after two separate 3-day periods with supplementation of potassium nitrate/placebo.     

Predictors of signs and symptoms of temporomandibular disorders: a 20-year follow-up study from childhood to adulthood

The aim of this study was to find possible predictors of signs and symptoms of temporomandibular disorders (TMD) in a long-term perspective. Baseline questionnaire and clinical examinations focusing on function and dysfunction of the masticatory system were performed in a sample of 402 subjects 7, 11, and 15 years old. After 20 years, 320 subjects (80% of the original sample) completed a similar questionnaire as at baseline. From the oldest age group, now aged 35 years, 100 subjects (74% of the original sample) also attended a clinical examination. Three variables from the 20-year follow-up were chosen as dependent variables in logistic regression analyses, with independent variables selected from the baseline examinations. Three variables at baseline were significant predictors for reported TMJ clicking at the 20-year follow-up, tooth wear index being the strongest (odds ratio = 4.3). Reported TMJ clicking at the start was the only significant predictor for TMD symptoms without clicking 20 years later (odds ratio = 2.3). The third logistic regression model, using the Helkimo Clinical Dysfunction Score as dependent variable, resulted in four significant predictors from the baseline examinations (bruxism, oral parafunctions, TMJ clicking, and deep bite). The results indicated that some signs and symptoms might predict TMD signs and symptoms in a long-term perspective. However, it cannot be concluded from this study whether these symptoms recorded in childhood - oral parafunction, tooth wear, TMJ clicking, and deep bite - can be used for predicting manifest TMD in adult age.     

Signs and Symptoms of Mandibular Dysfunction in Complete Denture Wearers Five Years after Receiving New Dentures

Studies have shown that signs and symptoms of mandibular dysfunction are a common finding in complete denture wearers. There is, however, a low representation of these patients in clinical series, probably due to their lower propensity to seek help and their greater willingness to accept a certain degree of dysfunction compared to other patients.

The author of this article examined a group of complete denture wearers five years after treatment with new complete dentures. These findings are compared with the situation before treatment and at a six-month follow-up. Clinical signs of dysfunction were a common finding on all three occasions. The favorable decrease of clinical signs that was noted at the six- month follow-up was generally followed by some relapse after five years.

The author stresses that a recall system, including correction of the dentures when needed, is important. This will not only preserve good comfort and extend the life of the dentures, but will also prevent or delay the development of signs and symptoms of mandibular dysfunction.     

Laparoscopic-assisted pull-through for Hirschsprung's disease,a prospective repeated evaluation of functional outcome

Aim of the study

To evaluate the functional outcome of laparoscopic-assisted endorectal pull-through (LAP) for Hirschsprung's disease (HSCR) over time.

Methods

Thirty-five children with HSCR underwent laparoscopic-assisted pull-through at our institution between 1998 and 2009. The diagnosis was histologically confirmed in all cases. Clinical data was extracted from the case records. A prospective assessment of the functional outcome was performed in 2009 and 2012. Exclusion criteria were a follow-up of less than 6 months after treatment (1 case) and total colonic aganglionosis (1 case). An independent examiner, not involved in the clinical care of the patients, performed interviews using a semi-structured questionnaire. Four patients could not be traced for the first interview. Two cases were lost for the second interview. Altogether twenty-seven patients completed the study. Data from the two interviews were compared. The regional ethical review board approved the study.

Main Results

The median patient age was 4 years old (range 2–16) at the time of the first interview and 7 years old (range 5–19) at the time of the second interview . There were 23 males and 4 females in the study group. The median age at laparoscopic-assisted pull-through was 104 days old (range 29 days–8 years). In the first interview 11 patients reported constipation, 18 patients reported soiling more frequently than once per week when they had loose stools and 16 patients when they had solid stools. Laxatives or irrigations were used by 13 of the patients. In the second interview 4 patients reported constipation, 16 patients reported soiling when they had loose stools and 15 patients reported soiling when they had solid stools. Eight patients used laxatives or irrigations. The decrease in constipation was statistically significant (p = 0,023).

Conclusions

Our study shows a statistically significant reduction of constipation over time. There is a high risk of incontinence after laparoscopic-assisted pull-through, with few signs of short-term improvement.     

Pulmonary arterial hypertension associated with systemic sclerosis in the Czech Republic

Background  

Systemic sclerosis (SSc) is an important cause of pulmonary arterial hypertension (PAH), with an estimated prevalence of 7.85–26.7%.