The relationship between personality, supportive transactions and support satisfaction, and mental health of patients with early rheumatoid arthritis. Results from the Dutch part of the Euridiss study:results from the Dutch part of the Euridiss study

The relationships between two personality characteristics (neuroticism, extraversion), three types of supportive transactions (emotional support, social companionship, instrumental support) and satisfaction with these transactions, and two aspects of mental health (feelings of anxiety and depressive mood) were studied among 280 patients with early rheumatoid arthritis. Structural equation modeling of the relevant variables showed that people with a more neurotic personality profile showed more anxiety and depressed feelings. Extraversion had no direct effect on depression or anxiety. Companionship, both transactions and satisfaction, had an independent positive effect on depression but not on anxiety. The effect of emotional support ran via social companionship: more emotional support (both transactions and satisfaction) was expressed in companionship leading to a less depressed mood. Finally, more depressed people received more instrumental supportive transactions while more satisfaction with this type of supportive transactions was related to less anxiety. Apart from the disturbing effect of a neurotic personality profile on mental health, the results once more underscore the importance of social companionship as a multifunctional activity for people's mental health. Maintaining this type of relationships despite a disabling condition gives people the opportunity to derive rewards that otherwise could not or only with more difficulty be achieved

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Training pediatric health care providers in prevention of dental decay: results from a randomized controlled trial

Background: Physicians report willingness to provide preventive dental care, but optimal methods for their training and support in such procedures are not known. This study aimed to evaluate the effect of three forms of continuing medical education (CME) on provision of preventive dental services to Medicaid-enrolled children by medical personnel in primary care physician offices. Methods: Practice-based, randomized controlled trial. Setting: 1,400 pediatric and family physician practices in North Carolina providing care to an estimated 240,000 Medicaid-eligible children aged 0–3 years. Interventions: Group A practices (n = 39) received didactic training and course materials in oral health screening, referral, counseling and application of fluoride varnish. Group B practices (n = 41) received the same as Group A and were offered weekly conference calls providing advice and support. Group C practices (n = 41) received the same as Group B and were offered in-office visit providing hands-on advice and support. In all groups, physicians were reimbursed $38–$43 per preventive dental visit. Outcome measures were computed from reimbursement claims submitted to NC Division of Medical Assistance. Primary outcome measure: rate of preventive dental services provision per 100 well-child visits. Secondary outcome measure: % of practices providing 20 or more preventive dental visits. Results: 121 practices were randomized, and 107 provided data for analysis. Only one half of Group B and C practices took part in conference calls or in-office visits. Using intention-to-treat analysis, rates of preventive dental visits did not differ significantly among CME groups: GroupA = 9.4, GroupB = 12.9 and GroupC = 8.5 (P = 0.32). Twenty or more preventive dental visits were provided by 38–49% of practices in the three study groups (P = 0.64). Conclusion: A relatively high proportion of medical practices appear capable of adopting these preventive dental services within a one year period regardless of the methods used to train primary health care providers.Gary D Slade, R Gary Rozier, Leslie P Zeldin, and Peter A Margoli

Phocid Seal Leptin: Tertiary Structure and Hydrophobic Receptor Binding Site Preservation during Distinct Leptin Gene Evolution

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus

Severe MUPS in a sick-listed population: a cross-sectional study on prevalence, recognition, psychiatric co-morbidity and impairment

Background: Medically unexplained physical symptoms (MUPS) have a high prevalence in the general population and are associated with psychiatric morbidity. There are indications that MUPS are an important determinant of frequent and long-term disability. The primary objective was to assess the prevalence of MUPS in sick-listed-employees and its associations with depressive disorders, anxiety disorders, health anxiety, distress and functional impairment. Secondary objectives were to investigate the classification of the occupational health physicians (OHPs), their opinions about the causes as well as the attributions of the employee. Methods: In a cross- sectional study of 489 sick-listed employees from 5 OHP group practices, MUPS, depressive disorders, anxiety disorders, health anxiety, distress and functional impairment were assessed with the Patient Health Questionnaire (PHQ), the Whitely Index (WI), the Four-Dimensional Symptom Questionnaire (4DSQ) and the Short-Form 36 Health Survey (SF-36). We used a cut off score of 15 on the PHQ for the categorisation of severe MUPS. The opinions of the OHPs were evaluated by means of a separate questionnaire with regard to the presence of employees physical symptoms, and the symptoms attributions, and the diagnoses of the OHPs. Results: Severe MUPS had a prevalence of 15.1% in this population of sick-listed employees. These employees had 4-6 times more depressive and anxiety disorders, and were more impaired. Female gender and PHQ-9 scores were determinants of severe MUPS. Most of the time the OHPs diagnosed employees with severe MUPS as having a mental disorder. The employees attributed their physical symptoms in 66% to mental or to both mental and physical causes. Conclusion: The prevalence of severe MUPS is higher in long-term sick-listed employees than in the non-sick-listed working population and at least equals the prevalence in the general practice population. Severe MUPS are associated with psychiatric morbidity and functional impairment and must therefore be specifically recognised as such. Validated questionnaires, such as the PHQ-15, are useful instruments in order to help OHPs to recognise severe MUPS

Reduced Mature MicroRNA Levels in Association with Dicer Loss in Human Temporal Lobe Epilepsy with Hippocampal Sclerosis

Hippocampal sclerosis (HS) is a common pathological finding in patients with temporal lobe epilepsy (TLE) and is associated with altered expression of genes controlling neuronal excitability, glial function, neuroinflammation and cell death. MicroRNAs (miRNAs), a class of small non-coding RNAs, function as post-transcriptional regulators of gene expression and are critical for normal brain development and function. Production of mature miRNAs requires Dicer, an RNAase III, loss of which has been shown to cause neuronal and glial dysfunction, seizures, and neurodegeneration. Here we investigated miRNA biogenesis in hippocampal and neocortical resection specimens from pharmacoresistant TLE patients and autopsy controls. Western blot analysis revealed protein levels of Dicer were significantly lower in certain TLE patients with HS. Dicer levels were also reduced in the hippocampus of mice subject to experimentally-induced epilepsy. To determine if Dicer loss was associated with altered miRNA processing, we profiled levels of 380 mature miRNAs in control and TLE-HS samples. Expression of nearly 200 miRNAs was detected in control human hippocampus. In TLE-HS samples there was a large-scale reduction of miRNA expression, with 51% expressed at lower levels and a further 24% not detectable. Primary transcript (pri-miRNAs) expression levels for several tested miRNAs were not different between control and TLE-HS samples. These findings suggest loss of Dicer and failure of mature miRNA expression may be a feature of the pathophysiology of HS in patients with TLE

Identification and characterization of microRNAs expressed in the African malaria vector Anopheles funestus life stages using high throughput sequencing

Background: Over the past several years, thousands of microRNAs (miRNAs) have been identified in the genomes of various insects through cloning and sequencing or even by computational prediction. However, the number of miRNAs identified in anopheline species is low and little is known about their role. The mosquito Anopheles funestus is one of the dominant malaria vectors in Africa, which infects and kills millions of people every year. Therefore, small RNA molecules isolated from the four life stages (eggs, larvae, pupae and unfed adult females) of An. funestus were sequenced using next generation sequencing technology. Results: High throughput sequencing of four replicates in combination with computational analysis identified 107 mature miRNA sequences expressed in the An. funestus mosquito. These include 20 novel miRNAs without sequence identity in any organism and eight miRNAs not previously reported in the Anopheles genus but are known in non-anopheles mosquitoes. Finally, the changes in the expression of miRNAs during the mosquito development were determined and the analysis showed that many miRNAs have stage-specific expression, and are co-transcribed and co-regulated during development. Conclusions: This study presents the first direct experimental evidence of miRNAs in An. funestus and the first profiling study of miRNA associated with the maturation in this mosquito. Overall, the results indicate that miRNAs play important roles during the growth and development. Silencing such molecules in a specific life stage could decrease the vector population and therefore interrupt malaria transmission.IS

Use of beneficial bacteria and their secondary metabolites to control grapevine pathogen diseases

Grapevine is one of the most important economic crops yielding berries, wine products as well as derivates. However, due to the large array of pathogens inducing diseases on this plant, considerable amounts of pesticides—with possible negative impact on the environment and health—have been used and are currently used in viticulture. To avoid negative impacts of such products and to ensure product quality, a substantial fraction of pesticides needs to be replaced in the near future. One solution can be related to the use of beneficial bacteria inhabiting the rhizo- and/or the endosphere of plants. These biocontrol bacteria and their secondary metabolites can reduce directly or indirectly pathogen diseases by affecting pathogen performance by antibiosis, competition for niches and nutrients, interference with pathogen signaling or by stimulation of host plant defenses. Due to the large demand for biocontrol of grapevine diseases, such biopesticides, their modes of actions and putative consequences of their uses need to be described. Moreover, the current knowledge on new strains from the rhizo- and endosphere and their metabolites that can be used on grapevine plants to counteract pathogen attack needs to be discussed. This is in particular with regard to the control of root rot, grey mould, trunk diseases, powdery and downy mildews, pierce’s disease, grapevine yellows as well as crown gall. Future prospects on specific beneficial microbes and their secondary metabolites that can be used as elicitors of plant defenses and/or as biocontrol agents with potential use in a more sustainable viticulture will be further discussed

Endocrine Disruptor Regulation of MicroRNA Expression in Breast Carcinoma Cells

Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer