[Non-gated vessel wall imaging of the internal carotid artery using radial scanning and fast spin echo sequence: evaluation of vessel signal Intensity by flow rate at 3.0 tesla].
Vessel wall imaging using radial scanning does not use a blood flow suppression pulse with gated acquisition. It has been proposed that there may not be a flow void effect if the flow rate is slow; however, this has yet to be empirically tested. To clarify the relationship between the signal intensity of the vessel lumen and the blood flow rate in a flow phantom, we investigated the usefulness of vessel wall imaging at 3.0 tesla (T). We measured the signal intensity while changing the flow rate in the flow phantom. Radial scanning at 1.5 T showed sufficient flow voids at above medium flow rates. There was no significant difference in lumen signal intensity at the carotid artery flow rate. The signal intensity of the vessel lumen decreased sufficiently using the radial scan method at 3.0 T. We thus obtained sufficient flow void effects at the carotid artery flow rate. We conclude this technique to be useful for evaluating plaque if high contrast can be maintained for fixed tissue (such as plaque) and the vessel lumen.


Hypophosphatemic rickets in opsismodysplasia.
Opsismodysplasia is a rare spondylo(epi)chondrodysplasia characteristized by delayed skeletal maturation and a constellation of dysplastic features. Although metaphyseal irregularities/cupping have been noted, neither renal phosphate wasting nor rickets have previously been reported. To evaluate hypophosphatemia and rickets in opsismodysplasia. Two girls with opsismodysplasia presenting with hypophoshpatemia by 3 years of age. Routine biochemistries to assess hypophosphatemia and renal phosphate wasting; radiographs (rachitic changes) and DEXA scan (BMD); FGF23 levels, PHEX and FGF23 gene analyses performed (Patient 1). Both children had hypophosphatemia, decreased TRP, and rickets. Oral phosphorus and calcitriol improved metaphyseal mineralization, yet serum phosphate levels remained relatively low and renal phosphate wasting persisted. PHEX and FGF23 gene analyses were negative, whereas serum FGF23 levels were markedly elevated in Patient 1. We now demonstrate an association between opsismodysplasia, hypophosphatemic rickets, and FGF23 elevation. Screening phosphorus levels may thus uncover a potentially treatable component of this disease.


[Heterogeneity of calcitonin in liver cirrhosis].
Elevated serum calcitonin (SC) levels have been observed in cirrhotic patients although the biological activity of this hormone in such patients is not known. Twenty one patients diagnosed histologically of alcoholic hepatic cirrhosis (AC) and 12 healthy controls were studied evaluating the degree of hepatocellular failure by means of clinical and biological criteria. Serum calcitonin was determined by means of a radioimmuno assay (RIA) and a radioimmunometric assay (IRMA) in which by combining two monoclonal antibodies, mature calcitonin is determined. These levels almost correspond to levels of biologically active calcitonin. The results obtained show a significant increase in SC in patients with AC when compared to controls, both by RIA (280 +/- 197 pg/ml, p less than 0.001) and IRMA (18 +/- 6 pg/ml, p less than 0.01). Control values were 57 +/- 23 pg/ml and 12 +/- 7 pg/ml respectively. Mean SC values in cirrhotic patients obtained by RIA were 4.9 times greater than their controls while the increase in SC in cirrhotics determined by IRMA was 1.5 times the control, thus obtaining a significant direct correlation between SC and severity of hepatic failure. According to our results, the elevated SC found in cirrhotics is mainly due to immature or non active forms directly related with the degree of severity of the hepatic failure and probably to high Molecular Weight molecules. The slight increase in mature SC in this type of patients is probably due to hormonal mechanism of bone regulation, defendants of hepatic osteodystrophy.


[Effect of prostaglandin E2, cAMP and histamine on glycoprotein synthesis in isolated cells of the rat gastric mucosa].
It was discovered that prostaglandin E2 (PGE2), but not histamine, increased the incorporation of 3H-N-acetyl-D-glucosamine and 14C-amino acids into the acid-insoluble protein fraction of isolated, mainly mucoid cells of rat gastric mucosa. The cAMP at the dose of 1 mM enhanced, like the PGE2, the synthesis of gastric mucoids. Cycloheximide inhibited the basal incorporation of labelled N-acetyl-D-glucosamine and the amino acid mixture by 28 and 72%, respectively, and blocked completely the PGE2 effect on glycoproteins formation. It is suggested that the PGE2, unlike histamine, enhances the biosynthesis of glycoproteins in the mucoid cells of rat gastric mucosa. The cAMP is believed to be a messenger of the PGE2 effect.


Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy.
Major depressive disorder (MDD) has been hypothesized to lead to impairments in empathy. Previous cross-sectional studies did not disentangle effects of MDD itself and antidepressant treatment. In this first longitudinal neuroimaging study on empathy in depression, 29 patients with MDD participated in two functional magnetic resonance imaging (fMRI) sessions before and after 3 months of antidepressant therapy. We compared their responses to an empathy for pain task to a group of healthy controls (N = 35). All participants provided self-report ratings targeting cognitive (perspective taking) and affective (unpleasant affect) aspects of empathy. To control for general effects on processing of negative affective states, participants additionally underwent an electrical pain task. Before treatment, we found no differences in empathic responses between controls and patients with MDD. After treatment, patients showed significant decreases in both affective empathy and activity of three a priori selected brain regions associated with empathy for pain. Decreases in affective empathy were moreover correlated with symptom improvement. Moreover, functional connectivity during the empathy task between areas associated with affective (anterior insula) and cognitive (precuneus) empathy decreased between sessions in the MDD group. Neither cognitive empathy nor responses to painful electrical shocks were changed after treatment. These findings contradict previous cross-sectional reports of empathy deficits in acute MDD. Rather, they suggest that antidepressant treatment reduces the aversive responses triggered by exposure to the suffering of others. Importantly, this cannot be explained by a general blunting of negative affect, as treatment did not change self-experienced pain.


Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study.
The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS) METHODS: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004-2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC. Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%. Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.


Treatment of a large segmental bone defect with allograft and autogenous bone marrow graft.
Management of segmental bone defects is a challenge to orthopedic surgeons. We report a 23-year-old man who sustained segmental bone loss of 9 cm in length in his left femur due to an open fracture. Open reduction and internal fixation with a 95 degrees angle blade plate and screws, supplemented with a composite of two femoral head allografts and a graft of 100 mL of autogenous bone marrow, was performed 3 weeks after the injury, when the soft tissues had healed. The postoperative rehabilitation program included delayed weight bearing (crutches for 3 months), a limited early range of motion of the left knee, and quadriceps muscle exercise. Callus bridging was noted on x-ray films 3 months postoperatively. Clinical and radiographic union were noted 6 months after the surgery. We suggest that this new and simple method can be applied to successfully treat segmental bone loss of more than 6 cm in length.


Selection from perceptual and conceptual representations.
The lateral prefrontal cortex has been implicated in a wide variety of functions that guide our behavior, and one such candidate function is selection. Selection mechanisms have been described in several domains spanning different stages of processing, from visual attention to response execution. Here, we consider two such mechanisms: selecting relevant information from the perceptual world (e.g., visual selective attention) and selecting relevant information from conceptual representations (e.g., selecting a specific attribute about an object from long-term memory). Although the mechanisms involved in visual selective attention have been well characterized, much less is known about the latter case of selection. In this article, we review the relevant literature from the attention domain as a springboard to understanding the mechanisms involved in conceptual selection.


Mediastinoscope: another use.
We describe a technique for the retrieval of left atrial pressure monitoring catheters using a mediastinoscope. The procedure is simple, safe and it can be accomplished quickly without re-opening the sternum.


Randomized trial of stents versus bypass surgery for left main coronary artery disease.
Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice. We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups. The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02). In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).


Abundance, spatial distribution and genetic diversity of Ostreococcus tauri viruses in two different environments.
Although large DNA viruses of eukaryotic algae represent a major force in shaping populations of plankton, knowledge about them is often limited to their overall diversity, abundance, and the flux of their constituent matter between ecosystem compartments. In order to gain insight about the genetics and structure of such populations, we used an easily cultivable model unicellular algal species, Ostreococcus tauri (Prasinophyceae), to monitor and compare populations of viruses in different marine environments. The abundance of O. tauri viruses showed very large temporal fluctuations, but remarkably was more than two orders of magnitude higher in lagoons than in coastal waters. We analysed 161 individual viruses found after plating out for lysis plaques on the host during a time series of water samplings. The haplotypes of viruses infecting our host strain were determined by sequence analysis of the partial DNA polymerase gene, permitting a spatiotemporal analysis of their population structure. We found 48 haplotypes, only the two most abundant ones being shared among all of the three study sites (lagoon, coastal and offshore), supporting the hypothesis that there is great diversity among the viruses infecting one host strain. However, our data suggest that the population structure differ between lagoons and coastal sea.


An Endohyphal Bacterium (Chitinophaga, Bacteroidetes) Alters Carbon Source Use by Fusarium keratoplasticum (F. solani Species Complex, Nectriaceae).
Bacterial endosymbionts occur in diverse fungi, including members of many lineages of Ascomycota that inhabit living plants. These endosymbiotic bacteria (endohyphal bacteria, EHB) often can be removed from living fungi by antibiotic treatment, providing an opportunity to assess their effects on functional traits of their fungal hosts. We examined the effects of an endohyphal bacterium (Chitinophaga sp., Bacteroidetes) on substrate use by its host, a seed-associated strain of the fungus Fusarium keratoplasticum, by comparing growth between naturally infected and cured fungal strains across 95 carbon sources with a Biolog® phenotypic microarray. Across the majority of substrates (62%), the strain harboring the bacterium significantly outperformed the cured strain as measured by respiration and hyphal density. These substrates included many that are important for plant- and seed-fungus interactions, such as D-trehalose, myo-inositol, and sucrose, highlighting the potential influence of EHB on the breadth and efficiency of substrate use by an important Fusarium species. Cases in which the cured strain outperformed the strain harboring the bacterium were observed in only 5% of substrates. We propose that additive or synergistic substrate use by the fungus-bacterium pair enhances fungal growth in this association. More generally, alteration of the breadth or efficiency of substrate use by dispensable EHB may change fungal niches in short timeframes, potentially shaping fungal ecology and the outcomes of fungal-host interactions.


Experimental infection of lambs with C and S-type strains of Mycobacterium avium subspecies paratuberculosis: immunological and pathological findings.
The two main genotypes of recognized isolates of Mycobacterium avium subsp. paratuberculosis (Map) are cattle (C) and sheep (S) strains. An experimental infection was conducted to establish the effect of Map strain on the pathogenesis of ovine paratuberculosis. Twenty-four out of thirty 1.5-month-old Assaf lambs were divided into 4 groups of 6 and infected orally with three low passage field isolates, two of S- (22G and the pigmented Ovicap49) and one of C- (764) type, and the reference K-10 strain (C type). The remaining six animals were unchallenged controls. Animals were euthanized at 150 and 390 days post-infection (dpi). Throughout the experiment, the peripheral immune response was assessed and histological and molecular (PCR) studies were conducted on samples of intestine and related lymphoid tissue. Specific antibody and IFN-γ production was significantly higher in animals infected with the C strains, while no consistent IFN- γ responses were observed in the S-type strain infected groups. A positive intradermal skin test response was detected in all infected groups. Lambs infected with S-type strains had granulomatous lesions restricted to the lymphoid tissue with no differences in the lesion intensity over time. In both C-type strain groups, lesions were more severe at 150 dpi while at 390 dpi lesions, characterized by well-demarcated granulomas with fibrosis, decreased in severity. Only infected lambs were positive to PCR. These results suggest that the strain of Map has a strong influence over the immune and pathological responses developed by the host. Lesions induced by C-type strains in lambs show a regressive character and tend to decrease as the infection progresses.


Limited gains in native parasitoid performance on an invasive host beyond three generations of selection.
Co-evolved natural enemies provide sustainable and long-term control of numerous invasive insect pests, but the introduction of such enemies has declined sharply due to increasing regulations. In the absence of co-evolved natural enemies, native species may attack exotic invasive pests; however, they usually lack adaptations to control novel hosts effectively. We investigated the potential of two native pupal parasitoids, Pachycrepoideus vindemmiae and Trichopria drosophilae, to increase their developmental success on the invasive Drosophila suzukii. Replicated populations of the two parasitoids were subjected to 10 generations of laboratory selection on D. suzukii with Drosophila melanogaster serving as the co-evolved host. We assessed developmental success of selected and control lines in generations 0, 3, and 10. Changes in host preference, sex ratio, development time, and body size were measured to evaluate correlated responses with adaptation. Both parasitoid species responded rapidly to selection by significantly increasing their developmental success on the novel host within three generations, which remained constant for seven additional generations without further improvement. The generalist parasitoid species P. vindemmiae was able to reach similar developmental success as the control populations, while the performance of the more specialized parasitoid T. drosophilae remained lower on the novel than on the co-evolved host. There was no increase in preference towards the novel host over 10 generations of selection nor were there changes in development time or body size associated with adaptation in either parasitoid species. The sex ratio became less female-biased for both parasitoids after three generations of selection but rebounded in P. vindemmiae by generation 10. These results suggest that a few generations of selection may be sufficient to improve the performance of native parasitoids on invasive hosts, but with limits to the degree of improvement for managing invasive pests when exotic co-evolved natural enemies are not available.


The Ah receptor is a sensitive target of geldanamycin-induced protein turnover.
Geldanamycin (GA) binds directly to hsp90 and apparently disrupts certain hsp90 heterocomplexes. We have investigated the GA-hsp90 interaction and its effect on other associated proteins. Incubation of 2-[125I]-iodo-3-azido-7,8-dibromo-p-dioxin-labeled Hepa 1c1c7 cytosol with GA-coupled beads revealed a stable association of Ah receptor (AhR)/hsp90 complex with GA. In addition, sucrose gradient sedimentation analysis demonstrated that GA does not disrupt the 9S Ah receptor complex in vitro. HeLa and Hepa 1c1c7 cells were subjected to a dose-response and time-course treatment with GA and the level of the AhR was determined. A 75% depletion in AhR levels was observed within an hour of exposure to 100 nM GA. The relative stability of other proteins that associate with hsp90 was determined with the following rank order of sensitivity to GA exposure: AhR >> c-Raf-1 > glucocorticoid receptor > CDK4 >> p50. A series of hsp90 deletion mutants were used to map the domain that interacts with GA. Deletion of the first 221 amino acids in NH2-terminal domain resulted in loss of binding to solid-phase GA. Epitopes of monoclonal antibodies specific for hsp90 were also determined by direct immunoprecipitation with hsp90 mutants. Results indicated that monoclonal antibodies 8D3 and 3G3 interact with hsp90 via the first 221 amino acids in NH2-terminal region, whereas AC88 requires a COOH-terminal region between amino acids 661-677.


Anaphase B spindle dynamics in Drosophila S2 cells: Comparison with embryo spindles.
In the Drosophila melanogaster syncytial blastoderm stage embryo anaphase B is initiated by a cell cycle switch in which the suppression of microtubule minus end depolymerization and spatial reorganization of the plus ends of outwardly sliding interpolar microtubules triggers spindle elongation. RNA interference in Drosophila cultured S2 cells may present a useful tool for identifying novel components of this switch, but given the diversity of spindle design, it is important to first determine the extent of conservation of the mechanism of anaphase B in the two systems. The basic mechanism, involving an inverse correlation between poleward flux and spindle elongation is qualitatively similar in these systems, but quantitative differences exist. In S2 cells, poleward flux is only partially suppressed and the rate of anaphase B spindle elongation increases with the extent of suppression. Also, EB1-labelled microtubule plus ends redistribute away from the poles and towards the interpolar microtubule overlap zone, but this is less pronounced in S2 cells than in embryos. Finally, as in embryos, tubulin FRAP experiments revealed a reduction in the percentage recovery after photobleaching at regions proximal to the pole. The basic features of the anaphase B switch, involving the suppression of poleward flux and reorganization of growing microtubule plus ends, is conserved in these systems. Thus S2 cells may be useful for rapidly identifying novel components of this switch. The quantitative differences likely reflect the adaptation of embryonic spindles for rapid, streamlined mitoses.


The electrically evoked auditory change complex: preliminary results from nucleus cochlear implant users.
The purpose of this study was to determine if changes in the position of the stimulating electrode in the cochlea could be used to elicit the electrically evoked auditory change complex (EACC) from Nucleus cochlear implant users. Nine postlingually deafened adults participated in this study. Each study participant had been using his or her Nucleus CI24 cochlear implant for at least 3 mos before testing. The speech processor was bypassed and the output of the implanted receiver/stimulator was controlled directly. The stimulus was a 600 msec burst of a biphasic pulse train (1000 pps). In control conditions, the stimulating electrode was held constant and stimulation continued throughout the 600 msec recording interval. In experimental conditions, the EACC was elicited by introducing a change in the stimulating electrode 300 msec after the onset of the pulse train. The EACC was recorded using surface electrodes. Three recordings of 100 sweeps each were obtained for each stimulus condition. Bandpass filtering (1-100 Hz) was used to minimize contamination of the recordings by stimulus artifact. Averaged responses were then smoothed using a 40-msec wide boxcar filter and standard peak picking procedures were used to analyze these responses in the time domain. In each case, a clear onset response (P1-N1-P2) was recorded. In the experimental conditions, a second evoked potential, the EACC, was also recorded after the change in stimulating electrode. This second response had general morphological characteristics that were very similar to those of the onset response. Increasing the separation between the two stimulating electrodes in the experimental conditions resulted in a general trend toward increased EACC amplitudes. This report describes results of a set of experiments in which the speech processor of the cochlear implant was bypassed and the EACC was recorded in response to a change in stimulating electrode position. EACC amplitude was shown to increase as the separation between the two stimulating electrodes increased. Although preliminary in nature, these results demonstrate the feasibility of recording the EACC in response to changes in stimulating electrode position from individual cochlear implant users.


Quality of life and perceived financial implications among otorhinolaryngologists during the COVID-19 pandemic across India.
The changing trends in medical practice, uncertainties and monetary apprehensions due to the COVID-19 pandemic may influence the sense of well-being among otorhinolaryngologists. The present study was conducted to evaluate quality of life (QOL) and perceived financial implications in otorhinolaryngologists during the COVID-19 pandemic across India. A cross-sectional study was carried out among otorhinolaryngology specialists across India using WHOQOL-BREF and Consumer Financial Protection Bureau (CFPB) Financial Well-Being Scale questionnaires on Google Forms, which was kept open for the latter half of July 2020. A total of 358 responses were obtained; the response rate was 26.64%. Twenty-four percent of respondents worked exclusively in academic settings; 40.22% of specialists had over 10 years of work experience. Average monthly income in 2019 was between 1-3 lakhs Indian Rupees (INR) in 43.85%, while in 2020, 62.57% of the specialists had an average monthly income of below one lakh INR; this difference was statistically significant (p < 0.001). Mean WHOQOL-BREF scores for physical, psychological, social and environmental domains were 68.8 ± 1, 62.3 ± 0.75, 68.9 ± 1.17 and 65.8 ± 1.01, respectively; mean CFPB financial well-being scale score was 55.5 ± 0.66. QOL and financial well-being were better in otolaryngologists older than 60 years, male specialists and private consultants. There has been a tremendous impact on quality of life and financial well-being among otorhinolaryngologists in India during the COVID-19 pandemic. The study outcome may help otolaryngologists comprehend and perceive the extent to which it has affected their professional and personal lives, and explore ways to face and overcome the situation.


The 150 most important questions in cancer research and clinical oncology series: questions 6-14 : Edited by Chinese Journal of Cancer.
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, nine more questions are presented as followed. Question 6. Why do nasopharyngeal carcinomas rarely metastasize to the brain? Question 7. Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node? Question 8. What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis? Question 9. How does chronic hepatitis prevent liver metastasis from colorectal cancer? Question 10. How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis? Question 11. Why do cancers rarely metastasize to the small bowel? Question 12. Why do glioblastomas rarely metastasize outside the central nervous system? Question 13. Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas, these tumors are the most therapeutically refractory among all human cancers. What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy, since even a surgical resection of greater than 99% of tumor tissues is invariably associated with recurrence? Question 14. The blood-brain barrier (BBB) effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain. What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?


Respiratory effects of capsaicin occur beyond the lung vagi in anaesthetized rats.
The effects of an intravenous capsaicin challenge on the respiratory pattern and ventilation were studied in 15 urethane/chloralose-anaesthetized, spontaneously breathing rats. Bolus injection of capsaicin at a dose of 5 micrograms/kg into the right femoral vein evoked respiratory arrest in all animals (both prior to and after bilateral midcervical vagotomy), which effect was abolished by ruthenium red pretreatment. Breathing that followed the apnoea was of enlarged tidal volume and initially increased respiratory rate, which resulted in an augmented ventilation. The capsaicin-induced respiratory changes were independent of vagal integrity and may depend on stimulation of vanilloid receptors within the nodose ganglia.


Scoping Review of Oral Health-Related Birth Cohort Studies: Toward a Global Consortium.
The multidisciplinary nature and long duration of birth cohort studies allow investigation of the relationship between general and oral health and indicate the most appropriate stages in life to intervene. To date, the worldwide distribution of oral health-related birth cohort studies (OHRBCSs) has not been mapped, and a synthesis of information on methodological characteristics and outcomes is not available. We mapped published literature on OHRBCSs, describing their oral health-related data and methodological aspects. A 3-step search strategy was adopted to identify published studies using PubMed, Embase, Web of Science, and OVID databases. Studies with baseline data collection during pregnancy or within the first year of life or linked future oral health data to exposures during either of these 2 life stages were included. Studies examining only mothers' oral health and specific populations were excluded. In total, 1,721 articles were suitable for initial screening of titles and abstracts, and 528 articles were included in the review, identifying 120 unique OHRBCSs from 34 countries in all continents. The review comprised literature from the mid-1940s to the 21st century. Fifty-four percent of the OHRBCSs started from 2000 onward, and 75% of the cohorts were from high-income and only 2 from low-income countries. The participation rate between the baseline and the last oral health follow-up varied between 7% and 93%. Ten cohorts that included interventions were mostly from 2000 and with fewer than 1,000 participants. Seven data-linkage cohorts focused mostly on upstream characteristics and biological aspects. The most frequent clinical assessment was dental caries, widely presented as decayed, missing, and filled teeth (DMFT/dmft). Periodontal conditions were primarily applied as isolated outcomes or as part of a classification system. Socioeconomic classification, ethnicity, and country- or language-specific assessment tools varied across countries. Harmonizing definitions will allow combining data from different studies, adding considerable strength to data analyses; this will be facilitated by forming a global consortium.


[Compare stress and social support between adolescent and adult pregnant women during third trimester].
With the change of society, adolescent pregnancy is the issue for the professionals to face and be concerned about. The results of the study can be utilized to improve the prenatal care for adolescents. A total of 90 adolescents and 90 adults during third trimester were recruited to participate in this study. Three methods were used to collect data: the Demographic Data Form, the Pregnancy Stress Rating Scale, and the Interpersonal Support Evaluation List. Primiparas showed a significantly higher score on stress from seeking safe passage for herself and her child through pregnancy, labor and delivering than multiparas. Adult pregnant women had a higher score on social support than did pregnant adolescents. Results of the stepwise multiple regression indicated that the best subset to predict stress from identifying maternal role was social support and education. The best subset to predict stress from seeking safe passage for herself and her child through pregnancy, labor and delivery was parity and education, the best predictor of stress from altering body structure and body function was education.


Classification of lungs infected COVID-19 images based on inception-ResNet.
Nowadays, COVID-19 is spreading rapidly worldwide, and seriously threatening lives . From the perspective of security and economy, the effective control of COVID-19 has a profound impact on the entire society. An effective strategy is to diagnose earlier to prevent the spread of the disease and prompt treatment of severe cases to improve the chance of survival. The method of this paper is as follows: Firstly, the collected data set is processed by chest film image processing, and the bone removal process is carried out in the rib subtraction module. Then, the set preprocessing method performed histogram equalization, sharpening, and other preprocessing operations on the chest film. Finally, shallow and high-level feature mapping through the backbone network extracts the processed chest radiographs. We implement the self-attention mechanism in Inception-Resnet, perform the standard classification, and identify chest radiograph diseases through the classifier to realize the auxiliary COVID-19 diagnosis process at the medical level, all in an effort to further enhance the classification performance of the convolutional neural network. Numerous computer simulations demonstrate that the Inception-Resnet convolutional neural network performs CT image categorization and enhancement with greater efficiency and flexibility than conventional segmentation techniques. The experimental COVID-19 CT dataset obtained in this paper is the new data for CT scans and medical imaging of normal, early COVID-19 patients and severe COVID-19 patients from Jinyintan hospital. The experiment plots the relationship between model accuracy, model loss and epoch, using ACC, TPR, SPE, F1 score and G-mean to measure the image maps of patients with and without the disease. Statistical measurement values are obtained by Inception-Resnet are 88.23%, 83.45%, 89.72%, 95.53% and 88.74%. The experimental results show that Inception-Resnet plays a more effective role than other image classification methods in evaluation indicators, and the method has higher robustness, accuracy and intuitiveness. With CT images in the clinical diagnosis of COVID-19 images being widely used and the number of applied samples continuously increasing, the method in this paper is expected to become an additional diagnostic tool that can effectively improve the diagnostic accuracy of clinical COVID-19 images.


Sequential study on the influence of adriamycin on cell proliferation and ultrastructure of cultured mammary tumor cells.
The time-dependent cytocidal and growth inhibitory effects of Adriamycin (ADM) on monolayer cultures of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor cells were analyzed. The inhibitory effect on cell proliferation was assessed by colony formation in soft agar. Growth inhibition and [3H]thymidine labeling indices clearly demonstrate a dose-dependent antimitotic and cytotoxic effect of the drug. At low concentrations (10(-9)-10(-8) M), 90-100% of cells survived 24-hr exposure. At a higher concentration (10(-5) M), 75-80% of cells survived after 8-hr exposure; by 72 hr only 20-30% of the cells remained. Autoradiographic examination of the pulse-labeled cultures demonstrated no change in the proportion of cells in S-phase during the first 4 hr of treatment. Subsequently DNA synthesis was completely abolished and remained inhibited for the duration of the experiment (72 hr). Clonogenic assay revealed a complete arrest of growth in cells exposed to 10(-5) M ADM and greater than 60% inhibition of cell proliferation at 10(-7) M. Ultrastructural changes were not observed in cells during the first 4 hr of treatment; however, after 8 hr most surviving cells exhibited alterations in nuclear chromatin. The surviving cells showed mitochondrial degeneration, myelin body formation, and vacuolization of the endoplasmic reticulum. This study shows the potential usefulness of the primary culture system in drug evaluation. In addition, serial observation of the effects of ADM revealed a cell subpopulation of the primary culture with differential sensitivity to the drug.


Psychological aspects in the perception of dyspnea in obstructive pulmonary diseases.
Dyspnea is an impairing symptom in obstructive pulmonary diseases. Besides multiple physiological pathways contributing to this sensation recent research has demonstrated an important role of psychological factors in the perception of dyspnea. The present review article synthesizes the research literature with regard to psychological aspects of the perception of dyspnea as well as other dyspnea-related issues such as course of disease, neuropsychological correlates and interventions that focus on psychological or behavioural changes. The available data show that inaccurate perception of dyspnea is related to poorer treatment outcome in obstructive pulmonary diseases and is impacted upon by emotional, attentional and learning processes. Neuropsychological deficits might further contribute to this association. Different psychological and behavioural interventions might reduce comorbid psychological disorders and thus improve the perception of dyspnea. However, future research is clearly required to substantiate current findings.


Insights about dying from the SUPPORT project. The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.
The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) project was a study of 9105 seriously ill patients, 4274 of whom died within 6 months. HELP, the Hospitalized Elderly Longitudinal Project, was an ancillary study, in four of the five SUPPORT hospitals, of 1286 persons aged 80 years and older, 321 of whom died within 6 months. This paper reviews the SUPPORT and HELP literature to bring together insights concerning the time near death of seriously ill patients. We reviewed published reports from SUPPORT and HELP, specifically, demographics of dying; characteristics of a prognostic model to estimate survival; patient symptoms near death; patient preferences and decision-making near death; ineffectiveness of the SUPPORT intervention; costs of dying while seriously ill; and the impact of serious illness on the family. We also compared and contrasted the experience of patients with different conditions. Patients in SUPPORT who died were typically younger than age 75. Most SUPPORT patients who died were male and most had an income of less than $11,000, although the older patients in HELP were even more likely to have had such low incomes. Patients with cirrhosis were much younger than most decedents, and patients with cancer were less often poor. Most had serious symptoms close to death. The place of death was more closely related to hospital bed supply than to decisions made by healthcare providers or individual patient preferences or characteristics. Prognosis near death was quite uncertain, especially in patients with heart and lung failure. Although SUPPORT aimed to describe and compare decision-making affecting seriously ill patients, it also illuminated many other aspects of their course near death.


The Singaporean public beliefs about the causes of mental illness: results from a multi-ethnic population-based study.
To identify the common causal beliefs of mental illness in a multi-ethnic Southeast Asian community and describe the sociodemographic associations to said beliefs. The factor structure to the causal beliefs scale is explored. The causal beliefs relating to five different mental illnesses (alcohol abuse, depression, obsessive-compulsive disorder (OCD), dementia and schizophrenia) and desire for social distance are also investigated. Data from 3006 participants from a nationwide vignette-based study on mental health literacy were analysed using factor analysis and multiple logistic regression to address the aims. Participants answered questions related to sociodemographic information, causal beliefs of mental illness and their desire for social distance towards those with mental illness. Physical causes, psychosocial causes and personality causes were endorsed by the sample. Sociodemographic differences including ethnic, gender and age differences in causal beliefs were found in the sample. Differences in causal beliefs were shown across different mental illness vignettes though psychosocial causes was the most highly attributed cause across vignettes (endorsed by 97.9% of respondents), followed by personality causes (83.5%) and last, physical causes (37%). Physical causes were more likely to be endorsed for OCD, depression and schizophrenia. Psychosocial causes were less often endorsed for OCD. Personality causes were less endorsed for dementia but more associated with depression. The factor structure of the causal beliefs scale is not entirely the same as that found in previous research. Further research on the causal beliefs endorsed by Southeast Asian communities should be conducted to investigate other potential causes such as biogenetic factors and spiritual/supernatural causes. Mental health awareness campaigns should address causes of mental illness as a topic. Lay beliefs in the different causes must be acknowledged and it would be beneficial for the public to be informed of the causes of some of the most common mental illnesses in order to encourage help-seeking and treatment compliance.


Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements.
We have recently demonstrated enhanced alpha-adrenergic responsiveness assessed electrophysiologically in ischemic and reperfused myocardium. This study was performed to determine whether ischemia alters alpha 1-adrenergic receptor number (Bmax) of affinity (KD) based on [3H]prazosin binding. Within 30 min after occlusion, Bmax increased in ischemic regions to 207% of control to 27 +/- 2 fmol/mg protein, with the increase persisting (+ 141% of control) during early reperfusion (2 min), before returning to control base-line values (13 +/- 1.6) after 15 min of reperfusion. KD was not altered at any interval studied. Beta receptor number of ([3H]dihydroalprenolol) and Na+-K+ ATPase activity were comparable in control compared to ischemic myocardium although beta-receptor Bmax and KD in both regions decreased during early reperfusion. Thus, the enhanced alpha-adrenergic responsivity previously recognized with ischemia and reperfusion is correlated with an increase in alpha 1-adrenergic receptors.


Neonatal adiposity is associated with microRNAs in adipocyte-derived extracellular vesicles in maternal and cord blood, a discovery analysis.
Maternal body size, nutrition, and hyperglycemia contribute to neonatal body size and composition. There is little information on maternal-fetal transmission of messages which influence fetal growth. We analyzed adipocyte-derived small extracellular vesicular (ADsEV) microRNAs in maternal and cord blood to explore their adipogenic potential. There were 279 mother-neonate pairs with all phenotypic data (normal glucose tolerant NGT = 148, gestational diabetes mellitus GDM = 131). Neonates with adiposity were those in the highest tertile (T3) of sex-specific sum of skinfolds and those without adiposity (lean) in the lowest tertile T1 of NGT pregnancies. We studied ADsEV miRNAs in 76 and 51 neonates with and without adiposity respectively and their mothers based on power calculations (68 NGT and 59 GDM pregnancies). ADsEV miRNAs from maternal and cord blood plasma samples were profiled on Agilent 8*60 K microarray. Differential expression (DE) of ADsEV miRNAs in adipose vs. lean groups was studied before and after adjustment for maternal GDM, adiposity, and vitamin B12-folate status. Multiple miRNAs were common in maternal and cord blood and positively correlated. We identified 24 maternal and 5 cord blood miRNAs differentially expressed (discovery p ≤ 0.1) in the adipose group in unadjusted, and 19 and 26, respectively, in the adjusted analyses. Even though DE miRNAs were different in maternal and cord blood, they targeted similar adipogenic pathways (e.g., the forkhead box O (FOXO) family of transcription factors, mitogen‑activated protein kinase (MAPK) pathway, transforming growth factor beta (TGF-β) pathway). Maternal GDM and adiposity were associated with many DE ADsEV miRNAs. Our results suggest that the ADsEV miRNAs in mothers are potential regulators of fetal adiposity. The expression and functionality of miRNAs appear to be influenced by maternal adiposity, hyperglycemia, and micronutrient status during pregnancy.


The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment.
Several studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. To determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). In this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. The serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. Our study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.


Translational regulation of oskar mRNA occurs independent of the cap and poly(A) tail in Drosophila ovarian extracts.
Translational regulation plays a prominent role in Drosophila body patterning. Progress in elucidating the underlying mechanisms has been limited by the lack of a homologous in vitro system that supports regulation. Here we show that extracts prepared from Drosophila tissues are competent for translation. Ovarian extracts, but not embryonic extracts, support the Bruno response element- and Bruno-dependent repression of oskar mRNA translation, which acts in vivo to prevent protein synthesis from transcripts not localized to the posterior pole of the oocyte. Consistent with suggestive evidence from in vivo experiments, regulation in vitro does not involve changes in poly(A) tail length. Moreover, inhibition studies strongly suggest that repression does not interfere with the process of 5' cap recognition. Translational regulation mediated through the Bruno response elements is thus likely to occur via a novel mechanism.


Factors linking suicidal ideation with drinking to cope and alcohol problems in emerging adult college drinkers.
There is a well-established association between suicidal behavior and alcohol misuse. However, few studies have applied relevant theory and research findings in the areas of both alcohol and suicidal behavior to aid in the understanding of why these may be linked. The current study examined whether three variables (problem-solving skills, avoidant coping, and negative urgency) suggested by theory and previous findings in both areas of study help to account for the previously found association of suicidal ideation with drinking to cope and alcohol problems. Participants were 381 college women (60.4%) and men (39.6%) between the ages of 18 and 25 who were current drinkers and had a history of (at a minimum) passive suicidal ideation. Structural equation modeling was used to examine hypothesized associations among problem-solving skills, avoidant coping, drinking to cope (DTC), impulsivity in response to negative affect (i.e., negative urgency), severity of suicidal ideation, heavy alcohol use, and alcohol problems. Model results revealed that problem-solving skills deficits, avoidant coping, and negative urgency were each directly or indirectly associated with greater severity of suicidal ideation, DTC, heavy alcohol use, and alcohol problems. The results suggest that the positive association between suicidal ideation and DTC found in this and other studies may be accounted for by shared associations of these variables with problem-solving skills deficits, avoidant coping, and negative urgency. Increasing at-risk students' use of problem-solving skills may aid in reducing avoidance and negative urgency, which in turn may aid in reducing suicidal ideation, DTC, and alcohol misuse. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Comprehensive phylogeographic and phylodynamic analyses of global Senecavirus A.
Senecavirus A (SVA) is a member of the genus Senecavirus in the family Picornaviridae that infects pigs and shows symptoms similar to foot and mouth diseases and other vesicular diseases. It is difficult to prevent, thus, causing tremendous economic loss to the pig industry. However, the global transmission routes of SVA and its natural origins remain unclear. In this study, we processed representative SVA sequences from the GenBank database along with 10 newly isolated SVA strains from the field samples collected from our lab to explore the origins, population characteristics, and transmission patterns of SVA. The SVA strains were firstly systematically divided into eight clades including Clade I-VII and Clade Ancestor based on the maximum likelihood phylogenetic inference. Phylogeographic and phylodynamics analysis within the Bayesian statistical framework revealed that SVA originated in the United States in the 1980s and afterward spread to different countries and regions. Our analysis of viral transmission routes also revealed its historical spread from the United States and the risk of the global virus prevalence. Overall, our study provided a comprehensive assessment of the phylogenetic characteristics, origins, history, and geographical evolution of SVA on a global scale, unlocking insights into developing efficient disease management strategies.


Phosphoproteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function.
Thrombin, a procoagulant protease, cleaves and activates protease-activated receptor-1 (PAR1) to promote inflammatory responses and endothelial dysfunction. In contrast, activated protein C (APC), an anticoagulant protease, activates PAR1 through a distinct cleavage site and promotes anti-inflammatory responses, prosurvival, and endothelial barrier stabilization. The distinct tethered ligands formed through cleavage of PAR1 by thrombin versus APC result in unique active receptor conformations that bias PAR1 signaling. Despite progress in understanding PAR1 biased signaling, the proteins and pathways utilized by thrombin versus APC signaling to induce opposing cellular functions are largely unknown. Here, we report the global phosphoproteome induced by thrombin and APC signaling in endothelial cells with the quantification of 11,266 unique phosphopeptides using multiplexed quantitative mass spectrometry. Our results reveal unique dynamic phosphoproteome profiles of thrombin and APC signaling, an enrichment of associated biological functions, including key modulators of endothelial barrier function, regulators of gene transcription, and specific kinases predicted to mediate PAR1 biased signaling. Using small interfering RNA to deplete a subset of phosphorylated proteins not previously linked to thrombin or APC signaling, a function for afadin and adducin-1 actin binding proteins in thrombin-induced endothelial barrier disruption is unveiled. Afadin depletion resulted in enhanced thrombin-promoted barrier permeability, whereas adducin-1 depletion completely ablated thrombin-induced barrier disruption without compromising p38 signaling. However, loss of adducin-1 blocked APC-induced Akt signaling. These studies define distinct thrombin and APC dynamic signaling profiles and a rich array of proteins and biological pathways that engender PAR1 biased signaling in endothelial cells.


Relation of Fontan Baffle Stroke Volume to Fontan Failure and Lower Exercise Capacity in Patients With an Atriopulmonary Fontan.
Fontan failure remains a significant problem, especially in patients with an atriopulmonary Fontan. Fontan baffle volume change during the cardiac cycle (Fontan baffle stroke volume) may affect outcomes in Fontan circulation. Assuming that increased Fontan baffle stroke volume is associated with increased energy loss in the baffle, we hypothesized that higher baffle stroke volume is associated with worse exercise capacity and increased incidence of Fontan failure. Patients from 6 centers with an atriopulmonary or lateral tunnel Fontan operation were included if they had a cardiac magnetic resonance (CMR) study and an adequate cardiopulmonary exercise test. Fontan baffle stroke volume was defined as the difference between maximum and minimum Fontan baffle volumes. Fontan failure was defined as death, listing for transplantation, heart failure symptoms requiring medications, or peak VO2 below 16 ml/kg/min. The study group consisted of 107 patients (median age 19 years, interquartile range, 14 to 29 years). Most patients (84%) had lateral tunnel procedure. During a median follow-up period of 6.8 [interquartile range: 3.2 to 8.8] years after the CMR, 25 (23%) patients had Fontan failure (7 deaths, 3 listed for transplantation, and 15 with heart failure symptoms). Predictors of Fontan failure on multivariable analysis were ventricular tachycardia, protein losing enteropathy, and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. Predictors of lower peak VO2 on multivariable analysis were older age at CMR and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. In conclusion, larger Fontan baffle stroke volume was independently associated with lower peak VO2 and Fontan failure in atriopulmonary Fontan.


Effects of age and larval nutrition on phenotypic expression of insecticide-resistance in Anopheles mosquitoes.
Insecticide-resistance threatens the control of mosquito-borne diseases like malaria or dengue fever. To ensure sustainable vector control we need a full understanding of the factors driving the evolution of resistance. We test the hypothesis that the expression of insecticide-resistance depends on the available resources by rearing genetically DDT-resistant and sensitive larvae of Anopheles mosquitoes at three diet regimes, which correspond to 40%, 70% and 100% of the normal diet and exposing the adult females to DDT 5, 10 and 15 days after emergence. In both colonies post-exposure survival decreased with age at exposure. Additionally, the food levels and DDT-resistance were positively correlated in both colonies, although only in the DDT-resistant one was this relationship statistically significant. The impact of larval diet was smaller than the effect of age at exposure. We discuss our results and explain the implication of this study to resistance monitoring for public health and vector management.


Revision eDCR using a superior pedicled mucosal flap.
Endoscopic dacryocystorhinostomies (eDCRs) show patency rates between 81% and 94%. However, dacryocystorhinostomy (DCR) failure and the need for revision remain a significant challenge. One of the principal challenges in revision eDCR is the need to surgically identify the correct osteotomy site and maintain long-term patency in the setting of previously instrumented and potentially scarred tissue. At the same time, the surgeon must assume that the blood supply to the commonly described anterior and posteriorly pedicled flaps has been compromised. The objective of the study is to describe a novel flap technique for revision eDCR. The superior based mucosal flap is a novel technique that provides a vascularized mucosa preserving technique in revision eDCR despite previous instrumentation of the lacrimal system. This technique provides wide exposure of the revision osteotomy site while simultaneously allowing a viable mucosal flap to be replaced at the conclusion of the procedure, thereby minimizing bone exposure and cicatricial restenosis. The authors have utilized this technique in 13 procedures with 100% positive identification of the lacrimal sac, a 0% complication rate, and a 100% success rate after a mean follow-up of 26.93 ± 10.33 months (range 6-35 months). The eDCR using the superior pedicled mucosal flap provides excellent exposure of the maxillary bone and the lacrimal sac. This method preserves vascularity of the flap using a superiorly based pedicle which is typically inviolate during both open and endoscopic primary DCR. The mucosal flap can then be replaced, thereby minimizing bone exposure and optimizing patency.


Genomic and antigenic characterization of monomeric autotransporters of Haemophilus parasuis: an ongoing process of reductive evolution.
The genome of the highly pathogenic Haemophilus parasuis Nagasaki strain (serovar 5) was sequenced to 99 % completion. A genomic comparison with two other pathogenic serovar 5 H. parasuis strains identified six genes per genome (bmaA1-bmaA6) encoding β-barrel monomeric autotransporters, bmaA2 and bmaA3 being pseudogenes in at least one strain. The remaining encoded proteins were predicted to belong to the subtilisin (BmaA1 and BmaA4) and cysteine (BmaA5 and BmaA6) protease families. Allelic polymorphism was detected in other H. parasuis strains by comparative genomic hybridization using microarrays. Recombination events were observed, some of them leading to gene disruption in one of the three strains, although synteny around bmaA genes was conserved. These results suggest that bmaA genes are undergoing a process of reductive evolution. To evaluate their use as potential vaccine antigens, the products of the passenger domains of bmaA1, bmaA4, bmaA5 and bmaA6 were produced in Escherichia coli as recombinant proteins. They were detected by immunoblotting using sera of colostrum-deprived piglets recovering from a sublethal infection with H. parasuis (Nagasaki). The existence of specific antibodies after infection with H. parasuis also demonstrated in vivo expression. Using proteomics, only BmaA6 was detected in the in vitro-grown Nagasaki strain. Interestingly, the translocator domain was found in the outer membrane, while the passenger domain was located in supernatants. These results indicate that BmaA proteins could be considered as immunogen candidates to improve H. parasuis vaccines. However, their capacity to confer protective immunity needs to be studied further.


Pharmacological treatment of severe psychiatric disorders in the developing world : lessons from India.
Severe psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) cause much morbidity and disability in developing countries. Most of the evidence on the efficacy and effectiveness of drug treatments for these disorders is based on trials conducted in Western countries. Cultural, biological and health system factors may profoundly influence the applicability of such evidence in developing countries. Attitudes towards, and concepts about, psychiatric disorders vary across cultures, and these may influence the acceptability of drug treatments. Genetic and environmental factors may lead to variations in the pharmacodynamics and pharmacokinetics of psychotropic drugs across ethnic groups. This may explain why lower doses of psychotropic drugs tend to be used for non-Caucasian patients. There is a dearth of mental health professionals and care facilities in developing countries, especially in rural areas. Epidemiological studies show that, despite this lack of services, the outcome of schizophrenia is favourable in developing countries. This suggests that cultural, genetic or environmental factors may play as much of a role in influencing outcome as access to antipsychotic treatment. Regional drug policies may influence the availability and cost of psychotropic drugs. In particular, the Indian experience, where drugs are manufactured by several local pharmaceutical firms, thus bringing their cost down, may represent a unique deregulated drug industry. However, the impending impact of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement, with the strict enforcement of patent laws, will almost certainly lead to a rise in drug costs in the coming years. This may influence the choice and cost effectiveness of various drugs. The implications of these cross-cultural variations for policy and practice are the need to ensure a reliable supply of affordable psychotropic drugs in developing countries, trained healthcare professionals to use these drugs rationally, a concerted advocacy campaign to exclude drugs for severe psychiatric disorders from patent protection, and the development of psychosocial programmes to improve global outcomes.


[Calculated pulmonary vascular resistance, is definitively a worthless variable. Current methods for a better definition].
The term pulmonary vascular resistance [PVR] describes, in part, the forces opposing the flow across the pulmonary vascular bed. The equation traditionally used is based on the assumption that the pulmonary capillaries, as well as some others vessels in series behave like a Poiseuille resistance. This assumption implies a laminar type of flow of a homogeneous Newtonian fluid, however blood is not a Newtonian fluid and flow is pulsatile in the pulmonary circulation. Neglecting these factors [which only slightly undermines the application of the equation] and others as well [like distension and recruitment of the vessels], will, however, not give us a true clinically practical solution for the calculation of PVR, because the concept of the equation is only true or partially true for part of the pulmonary circulation. In other parts of the lung, flow depends mainly on the behaviour of capillaries as a Starling resistor. If we considered always pulmonary venous pressure [measured clinically as left atrial pressure or pulmonary wedge pressure] as the effective downstream pressure for the calculation of PVR and we ignore or disregard the existence of a significant "critical closing pressure" [whatever the cause] in the lung it will lead to additional erroneous concept regarding PVR calculations and, in addition for the real hemodynamic conditions of the pulmonary vascular bed. Because, at least two different models of perfusion exist in the lung it is inadmissible from a theoretical point of view to calculate PVR, based on only in one of these models. According to the present knowledge of the pulmonary circulation hemodynamics, an improved definition for the PVR could be obtained: 1. by a multipoint pulmonary vascular pressure/flow plot at high flows and 2. with the use of the pulmonary artery occlusion pressure [PAOP] in addition to the determination of the pulmonary wedge pressure technique [PWP], in order to establish the estimated downstream pressure of the pulmonary circulation at zero flow. Therefore, pulmonary hemodynamic determinations of the PVR are better defined with the analysis of the pressure-flow relationships in addition to the information derived from the PAOP/PWP measurements. However, if none of the previous pressure-flow relationships [in order to obtain the slope = PVR at high flows] or the effective downstream pressure measurements [in order to estimate the critical closing pressure at zero flow] are applied for the analysis of the pulmonary circulation, a cautious interpretation of the measured variables [mean pulmonary artery pressure and cardiac output] is preferable to wrong conclusions made from a meaningless variable, the "calculated PVR".


The effect of mouthrinses on oral malodor: a systematic review.
The objective of this study is to systematically review the literature regarding the impact of mouthrinses on oral malodor and present evidence for the treatment effects of mouthrinses on oral malodor. PubMed-MEDLINE, the Cochrane-CENTRAL and EMBASE were searched through February 10, 2012 to identify appropriate studies. Volatile sulphur compound measurements, organoleptic measurements and tongue coating were selected as outcome variables. SEARCH RESULTS: The independent screenings of 333 unique titles and paper abstracts revealed 12 publications (12 experiments) that met the eligibility criteria. Means and standard deviations were extracted. The results were separated into short-term (<3 weeks) and longer-term (≥3 weeks) studies. In this review, nearly all mouthwashes with active ingredients had beneficial effects in reducing oral malodor in both short- and longer-term studies. The most compelling evidence was provided for chlorhexidine mouthwashes, and those that contained a combination of cetyl pyridinum chloride and zinc provided the best evidence profile on oral malodor. Little data with respect to tongue coating were available, and none of the studies showed a beneficial effect for this parameter.


Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial cancer but rarely silenced in pancreatic cancer with microsatellite instability.
Disruption of the DNA mismatch repair (MMR) system has been found to play an important role in sporadic human cancers of several organs such as colorectum, stomach, endometrium, and pancreas. In cancers of the former three organs, disruption of the MMR system is mainly caused by hypermethylation of the hMLH1 gene. We investigated the expression of the hMLH1 and hMSH2 proteins immunohistochemically in pancreatic and endometrial cancers with high frequency microsatellite instability (MSI-H). Loss of expression of hMLH1 was found in none of seven pancreatic cancer, whereas eight (57%) of 14 endometrial cancer showed loss of expression of hMLH1. On the other hand, one (14%) of seven pancreatic cancers and two (14%) of 14 endometrial cancers showed loss of hMSH2 expression. We further analyzed the methylation status at the promoter region of the hMLH1 and hMSH2 genes and found hypermethylation of hMLH1 at the promoter region in the great majority of endometrial cancers with loss of expression. However, no pancreatic cancer showed hypermethylation. We then further analyzed 22 pancreatic cancer cell lines and obtained similar results. These results suggested that MSI-H in pancreatic cancer is probably caused by different mechanisms from those of other sporadic cancers with MSI-H.


2-Aminoimidazole facilitates efficient gene delivery in a low molecular weight poly(amidoamine) dendrimer.
Functional groups have shown great potential in gene delivery. However, a number of the reported functional groups can only overcome one certain physiological barrier, resulting in limited transfection efficiencies. Based on the structure-activity relationships of both imidazolyl and guanidyl, we designed a novel multifunctional group, 2-aminoimidazole (AM), for gene delivery. On modifying with the AM group, the transfection efficiency of low molecular weight poly(amidoamine) (G2) was 200 times greater than the parent dendrimer in vitro. In contrast, the transfection efficiency of G2 showed a decreasing trend when it was grafted with imidazole. Assays revealed that the AM group played multiple roles in gene delivery, including condensing DNA into monodisperse nanoparticles of 80-90 nm in diameter, achieving nearly ten times higher cellular-uptake efficacy, and enhancing the abilities of endosome/lysosome escape and nuclear localization. What's more, AM showed low toxicity. These results demonstrate that the AM group could be a promising tool in non-viral gene delivery.


Disparities in amputations in minorities.
As a result of the impact of health disparities on the healthcare system such as their influence on arenas significant to healthcare distribution, including cost, quality, and access, identification and resolution of health disparities is a primary national agenda item. Resolution of disparities in amputation is an area of opportunity that warrants further consideration. The purposes of our review are to highlight current data on disparities in amputation in minorities and to consider future goals related to an elimination of this disparity. Studies on disparities in amputation were accessed using the following databases: PubMed, Cinahl, OVID/Medline, Embase, and Cochrane databases. In each database, a search of title/abstract was performed for the search terms "disparities and amputation," "race and amputation," and "diabetes and amputation." Each search was limited by human and English language. Where are we now? A disparity exists in both frequency and level of amputation in minorities both in the presence and absence of a diagnosis of diabetes. Where do we need to go? A need exists for future research involving a more deliberate examination of the use of preventive screening for patients at high risk for amputation across medical settings. How do we get there? Research in this area would benefit from funding, large-scale data collection, and physician exposure to education on high-risk patients and preventive screening opportunities.


Association of Ixodes pacificus (Acari: ixodidae) with the spatial and temporal distribution of equine granulocytic ehrlichiosis in California.
This study was conducted to determine if the biology of certain ticks associated with horses regulates the spatial and temporal distribution of equine granulocytic ehrlichiosis (EGE) in California north of Monterey County. We compared the spatial and temporal distribution of EGE cases with the seasons of activity and life histories of ticks that infest horses. Spatially, cases collected from equine veterinarians clustered around each other in a manner different from the way in which control cities of practice were distributed, with foci limited to the Sierra Nevada and coastal foothills. Cases also clustered seasonally: most were diagnosed between November and April. The spatial and temporal pattern of EGE cases closely parallels the well-characterized life history and distribution of Ixodes pacificus Cooley & Kohls, but not other ticks commonly associated with horses. Building on previous studies, there is compelling evidence that this tick has the vectorial capacity to transmit Ehrlichia equi to horses. Based on the life history and distribution of I. pacificus in relation to EGE cases, we reason that this tick is the only biologically plausible vector of E. equi in California, and provide evidence for a tightly linked association between I. pacificus and the epidemiology of EGE.


Clinical oncology in resource-limited settings.
Infectious Agents and Cancer is introducing a new section of Clinical Oncology with the main objective of stimulating debate through articles published in the section. Infectious diseases have been the major causes of morbidity and mortality in human populations, and have dominated the medical approach to clinical and public health. Successful efforts to control mortality from acute infections have paved the way for chronic, mostly indolent, infections to become major causes of morbidity. Cancer, hitherto thought to be rare in resource-limited settings, is becoming a major contributor. The changes in mortality patterns are due, in part, to diseases linked to rapid changes in lifestyle, urbanization, and pollution. These diseases include many of the non-infection associated cancers. However, there is a dearth of information about the burden, pathogenesis, and therapeutic approaches about cancer in resource-limited countries. There are also substantial other challenges, including economic, infrastructure, technology, and personnel. The Journal advocates for interactive local-global (lo-bal) efforts to generate relevant knowledge about cancer burden, pathogenesis, and therapeutic approaches using a bottom-up approach to sharpen the focus on local and global relevance of research and clinical and public practice, particularly in resource-limited countries. The section on Clinical Oncology in Infectious Agents and Cancer will harness these "lo-bal" strategies to reduce substantially the time from concept, discovery, and development and implementation of locally and globally applicable diagnostic and therapeutic technologies.


Cyclin A1 protein shows haplo-insufficiency for normal fertility in male mice.
In higher eukaryotes, the cyclins constitute a family of proteins involved in progression through the cell cycle. The cyclin A1 gene (Ccna1) is expressed during meiosis and is required for spermatogenesis. Targeted disruption of the Ccna1 gene with a LacZ reporter gene has allowed us to study the expression pattern of this gene in more detail. We have confirmed expression in mouse pre-meiotic spermatocytes and also detected expression in the accessory olfactory bulb, hippocampus and amygdala of the adult brain. We have also found that the amount of cyclin A1 protein influences the fertility of male mice and its action is modulated by genetic background. On an outbred genetic background (129S6/SvEv x MF1), Ccna1 (tm1Col) -/- animals are sterile due to spermatogenic arrest prior to the first meiotic division while Ccna1 (tm1Col) +/- mice show reduced sperm production and fertility. This is even more pronounced on an inbred genetic background (129S6/SvEv) where Ccna1 (tm1Col) +/- male mice are sterile due to a severe reduction in the total number of sperm.


2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection.
Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world. Through large-scale deworming programs, World Health Organization aims to reduce moderate-to-heavy intensity infections below 1%. Current diagnosis and monitoring of these control programs are solely based on the detection of worm eggs in stool. Here we describe how metabolome analysis was used to identify the A. lumbricoides-specific urine biomarker 2-methyl pentanoyl carnitine (2-MPC). This biomarker was found to be 85.7% accurate in determining infection and 90.5% accurate in determining a moderate-to-heavy infection. Our results also demonstrate that there is a correlation between 2-MPC levels in urine and A. lumbricoides DNA detected in stool. Furthermore, the levels of 2-MPC in urine were shown to rapidly and strongly decrease upon administration of a standard treatment (single oral dose of 400 mg albendazole). In an Ascaris suum infection model in pigs, it was found that, although 2-MPC levels were much lower compared to humans, there was a significant association between urinary 2-MPC levels and both worm counts (p = 0.023) and the number of eggs per gram (epg) counts (p < 0.001). This report demonstrates that urinary 2-MPC can be considered an A. lumbricoides-specific biomarker that can be used to monitor infection intensity.


[Effect of gentle nursing care of premature infants on bonding and emotional development of the child. Follow-up of premature infants in Dr. Marina Marcovich's study].
The study was set out to investigate whether the Marcovich model of a "soft treatment" of premature infants encourages the parent-infant-relationship to such an extent that, at school age, the Marcovich-children would be found to differ significantly from children treated with standard care with regard to the quality of their attachment and the prevalence of emotional and behavioural disorders. The Marcovich-children of the present sample had been discharged from hospital much earlier than the standard group, they were less frequently treated with artificial respiration, infant-parent body contact was encouraged significantly earlier, and, although they were less frequently breast-fed, those who were breast-fed were allowed to do so at a much earlier stage. The Marcovich-children were found to display higher social competence, more emotional openness, more emotional coherence, less dismissal of attachment and less preoccupied anger. The two samples did not differ with regard to their total attachment quality as well as their emotional and behavioural problems. The fact that no significant differences could be established with regard to the quality of the attachment suggests that the complex life-saving attachment system is not irreversibly affected by the early separation and distress and that the months and years after the hospital stay have the power to make up with any experienced trauma. It seems, however, that special aspects of the attachment system, such as the communication and interaction, are positively encouraged and enhanced by the soft treatment of the premature infant, which leads to greater emotional openness and social competence, as well as less preoccupied anger against the attachment figures.


Genomic expansion of domain archaea highlights roles for organisms from new phyla in anaerobic carbon cycling.
Archaea represent a significant fraction of Earth's biodiversity, yet they remain much less well understood than Bacteria. Gene surveys, a few metagenomic studies, and some single-cell sequencing projects have revealed numerous little-studied archaeal phyla. Certain lineages appear to branch deeply and may be part of a major phylum radiation. The structure of this radiation and the physiology of the organisms remain almost unknown. We used genome-resolved metagenomic analyses to investigate the diversity, genomes sizes, metabolic capacities, and potential roles of Archaea in terrestrial subsurface biogeochemical cycles. We sequenced DNA from complex sediment and planktonic consortia from an aquifer adjacent to the Colorado River (USA) and reconstructed the first complete genomes for Archaea using cultivation-independent methods. To provide taxonomic context, we analyzed an additional 151 newly sampled archaeal sequences. We resolved two new phyla within a major, apparently deep-branching group of phyla (a superphylum). The organisms have small genomes, and metabolic predictions indicate that their primary contributions to Earth's biogeochemical cycles involve carbon and hydrogen metabolism, probably associated with symbiotic and/or fermentation-based lifestyles. The results dramatically expand genomic sampling of the domain Archaea and clarify taxonomic designations within a major superphylum. This study, in combination with recently published work on bacterial phyla lacking cultivated representatives, reveals a fascinating phenomenon of major radiations of organisms with small genomes, novel proteome composition, and strong interdependence in both domains.


HDAC inhibitors - new generation of target specific treatment.
Histone Deacetylases (HDACs) enzymes are critical in regulating gene expression and transcription. They also play a fundamental role in regulating cellular activities such as cell proliferation, survival and differentiation. Inhibition of HDACs has generated many fascinating results including a new strategy in human cancer therapy. HDAC Inhibitors (HDACIs) like SAHA, TSA are emerging as new promising drugs for various anti-inflammatory and CNS-disorders. This review, along with chemical classification, emphasizes on the therapeutic potential of various HDACIs against different diseases.


Assessing the prevalence of paranasal sinuses anatomical variants in patients with sinusitis using Cone Beam Computer Tomography.
To asses, by using the Cone Beam CT (CBCT) reformatted images, the presence of anatomical variants of the sinonasal cavities and to determine the correlation of these variations with the onset of maxillary sinus inflammations. The study is a retrospective one and consists of the investigation of 130 patients with CBCT imaging, patients that were referred to the Maxillo-Facial Clinic, Radiology Department of the Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca, for clinical symptoms of sinusitis within a period of 24 months. The images were analyzed for the presence of different anatomical variations and sinus inflammation. The CBCT images were obtained using a NewTom 3G scanner and the data acquired were statistically analyzed using Chi-square test, Odds ratio data and confidence intervals, with a determined p<0.05 considered to be statistically significant. The anatomical variants were detected both in the inflammation and control group. From the spectrum of variations concha bullosa, deviation of uncinate process and asymmetrical ethmoid roof presented significant association with sinusitis. The deviated position of the uncinate process appeared in more than 50% of patients in the positive group [OR=2.55] compared with a third of the control group. Concha bullosa was observed in 31% cases, 23% in the control group and 34% in the positive group [OR=1.73]. Haller cells showed a small difference between groups [OR=1.14] whereas the ethmoid roof asymmetry was evidently more prevalent in the inflammation group. The anatomical variants of the paranasal sinuses are not incidental, being found in a large number of patients and may be a predisposing factor in the onset and recurrence of sinuses inflammation. The CBCT technique, due to the finest multiplanar reconstruction, permits a very good pre-therapeutic assessment of these predisposing conditions.


Bilateral periprosthetic stress fractures in a juvenile chronic arthritis patient secondary to bilateral genu valgum.
Lateral insufficiency fractures following total hip replacement have been reported with the femoral stems positioned in varus, together with osteopenia of the lateral femoral cortex. Any abnormal alignment of the lower limbs, such as genu valgum, will alter the load distribution across the femoral cortices, and repetitive loading during walking will predispose the bones to stress fractures at any stress riser point, such as the tip of a femoral component. Bilateral femoral stress fractures post total hip replacements have not been previously described. We present a 55-year-old woman, diagnosed with juvenile idiopathic arthritis, who had undergone bilateral total hip replacements and bilateral knee replacements. The knees 15 years postoperatively were in valgus and the left knee was extremely stiff, flexing to just 5. The patient presented with bilateral thigh pain, with plain radiographs confirming bilateral periprosthetic fractures of the femur at the tip of well-fixed femoral components. There was no history of injury and her hips were functioning well up to this time. The patient required revision of both hips to long-stem uncemented components, bypassing the fractures, and revision of both knees to stemmed semi-constrained implants, thereby correcting the alignment of both lower limbs. Both fractures healed and the patient is currently pain-free and mobile with walking aids. Surgeons must remain aware that when implants are in situ, abnormal alignments will lead to abnormal forces, and stress fractures are likely to occur at any stress riser around the implant. Avoiding malalignment will avoid this complication.


Growth hormone- and testosterone-dependent regulation of glutathione transferase subunit A5 in rat liver.
The class Alpha glutathione S-transferase (GST) subunit A5 is expressed in the livers of young male and female rats. After sexual maturation, this protein is no longer detectable in the livers of male rats, but is still expressed in female rats. We have previously demonstrated that the sexually dimorphic secretion of growth hormone regulates the levels of certain class Mu GSTs in rat liver, and this study was designed to investigate the hormonal regulation of GSTA5. Control and hypophysectomized rats of both sexes were used to study the role of growth hormone in the regulation of hepatic GSTA5; and the influence of testosterone on the expression of this same subunit was investigated in intact females and castrated males. Liver cytosols were subjected to SDS/PAGE and immunoblotting using antibodies directed towards rat (r)GSTA5, and to affinity purification on glutathione-Sepharose followed by reverse-phase HPLC in order to quantify the relative levels of rGSTA1, A2, A3, A4, M1 and M2 subunits. These analyses revealed that the expression of rGSTA5 is, indeed, regulated by both growth hormone and testosterone.


Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks.
The purpose of this study is to estimate the level of healthcare use and costs incurred by postmenopausal women overall and for these selected conditions: cardiovascular disease, osteoporosis, breast cancer, and gynecological cancers. National healthcare survey and discharge data were used to estimate healthcare use by women aged 45 and older. Clinical Classification for Health Policy Research (CCHPR) codes were used to identify patients whose primary diagnosis or procedure corresponded with the selected conditions. National weights were used to estimate resource use. Treatment costs were estimated using cost/charge ratios or the Medicare fee schedule to calculate costs for each individual procedure. Estimated total annual medical care treatment costs for women 45 and older were about $186 billion in 1997 dollars, including about $60.4 billion for cardiovascular disease, $12.9 billion for osteoporosis, and $5.0 billion for breast and gynecological cancers. For each condition, estimated resource use and costs are reported for hospitalization, outpatient, nursing home, and home healthcare services. Resource use and costs are also reported by age and expected source of payment. The economic burden of disease for conditions commonly affecting postmenopausal women is substantial. Prior research establishes that hormone replacement therapy (HRT) may be effective in reducing the burden of disease among women who continue preventive therapy for many years, but few at-risk women do so. New alternatives for prevention, such as selective estrogen receptor modulators (SERMs), may be effective in reducing the burden of disease among postmenopausal women.


New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond.
Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it's prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.


Genomic prediction with a maize collaborative panel: identification of genetic resources to enrich elite breeding programs.
Collaborative diversity panels and genomic prediction seem relevant to identify and harness genetic resources for polygenic trait-specific enrichment of elite germplasms. In plant breeding, genetic diversity is important to maintain the pace of genetic gain and the ability to respond to new challenges in a context of climatic and social expectation changes. Many genetic resources are accessible to breeders but cannot all be considered for broadening the genetic diversity of elite germplasm. This study presents the use of genomic predictions trained on a collaborative diversity panel, which assembles genetic resources and elite lines, to identify resources to enrich an elite germplasm. A maize collaborative panel (386 lines) was considered to estimate genome-wide marker effects. Relevant predictive abilities (0.40-0.55) were observed on a large population of private elite materials, which supported the interest of such a collaborative panel for diversity management perspectives. Grain-yield estimated marker effects were used to select a donor that best complements an elite recipient at individual loci or haplotype segments, or that is expected to give the best-performing progeny with the elite. Among existing and new criteria that were compared, some gave more weight to the donor-elite complementarity than to the donor value, and appeared more adapted to long-term objective. We extended this approach to the selection of a set of donors complementing an elite population. We defined a crossing plan between identified donors and elite recipients. Our results illustrated how collaborative projects based on diversity panels including both public resources and elite germplasm can contribute to a better characterization of genetic resources in view of their use to enrich elite germplasm.


Health Promotion in Socially Vulnerable Youth: Sports as a Powerful Vehicle?
Community sport has emerged in the past decades and uses sports as a lever to improve health and well-being among socially disadvantaged youth. Despite this premise, we do not know whether and to what extent health promotion aims are achieved within community sports practice. Measurable actions are needed, but it can be hard for researchers or practitioners to know how to approach this. This study aimed at developing a health-promoting intervention targeting youth attending community sports. To this aim, we used a planned approach for intervention design within a community-based participatory research design. The result is a group-based program promoting health-supportive behavior among community sport coaches, as we found coaches to be quintessential in fostering motivation toward health behavior change in vulnerable youth attending community sports. The design of such a complex intervention is difficult, yet tractable, when using a planned approach. Of importance, community engagement was the core of our work and we provide the reader with detailed examples on the combined use of participatory research and planned intervention design. This article provides an exemplar of how to approach the development of a health-promoting intervention in hard-to-reach populations.


Telemonitoring increases patient awareness of health and prompts health-related action: initial evaluation of the TELE-ERA study.
Telemonitoring is being increasingly used for chronic disease monitoring. Understanding elderly patients' feelings and perspectives toward telemonitoring is important to minimize any barriers to implementation in this population. Twenty Tele-Era Trial participants completed qualitative interviews assessing opinions about their telemonitoring experience. Participants also rated telemonitoring on burden, communication with clinicians, impact on medical condition knowledge, and confidence in using the monitor. On an average, participants rated telemonitoring as minimally burdensome, rated themselves confident in using the monitor, and positively rated telemonitoring for clinical communication. Qualitative analysis revealed a predominant theme that telemonitoring increases patient awareness of their health and also that telemonitoring prompts action. Elderly patients find home telemonitoring to be an acceptable and satisfying experience that can increase their awareness of their health and provide a sense of safety in their home. Home telemonitoring can lead to earlier evaluation of decline in health status.


Influence of fear-avoidance beliefs on disability in patients with subacromial shoulder pain in primary care: a secondary analysis.
Little information exists about the role of fear-avoidance beliefs and catastrophizing in subacromial pain syndrome. The purpose of this study was to investigate the associations among pain, catastrophizing, fear, and disability and the contribution of fear-avoidance beliefs to disability at baseline and at 3-month follow-up. A cross-sectional and longitudinal analysis was conducted. Baseline demographic and clinical data, including fear-avoidance beliefs and catastrophizing, of 90 patients were assessed for this analysis. Disability was measured with the Shoulder Pain and Disability Index at baseline and at 3-month follow-up. First, bivariate and partial correlations were calculated among pain, fear-avoidance beliefs, catastrophizing, and disability, based on the fear-avoidance model. Second, the contribution of fear-avoidance beliefs to disability at baseline and at 3-month follow-up was examined with hierarchical regression analyses. Correlations between clinical variables and disability were largely in line with the fear-avoidance model. Regression analyses identified a significant contribution of fear-avoidance beliefs to baseline disability but not to disability at 3 months. Patients with subacromial pain syndrome were studied; therefore, the results should be transferred with caution to other diagnoses. A modified version of the Fear-Avoidance Beliefs Questionnaire was used, which was not validated for this patient group. Fear-avoidance beliefs contribute significantly to baseline disability but not to disability change scores after 3-month follow-up. Duration of complaints and baseline disability were the main factors influencing disability change scores. Although the results help to improve understanding of the role of fear-avoidance beliefs, further studies are needed to fully understand the influence of psychological and clinical factors on the development of disability in patients with subacromial shoulder pain.


Selectivity in mammalian extinction risk and threat types: a new measure of phylogenetic signal strength in binary traits.
The strength of phylogenetic signal in extinction risk can give insight into the mechanisms behind species' declines. Nevertheless, no existing measure of phylogenetic pattern in a binary trait, such as extinction-risk status, measures signal strength in a way that can be compared among data sets. We developed a new measure for phylogenetic signal of binary traits, D, which simulations show gives robust results with data sets of more than 50 species, even when the proportion of threatened species is low. We applied D to the red-list status of British birds and the world's mammals and found that the threat status for both groups exhibited moderately strong phylogenetic clumping. We also tested the hypothesis that the phylogenetic pattern of species threatened by harvesting will be more strongly clumped than for those species threatened by either habitat loss or invasive species because the life-history traits mediating the effects of harvesting show strong evolutionary pattern. For mammals, our results supported our hypothesis; there was significant but weaker phylogenetic signal in the risk caused by the other two drivers (habitat loss and invasive species). We conclude that D is likely to be a useful measure of the strength of phylogenetic pattern in many binary traits.


Functional genomics and networks: new approaches in the extraction of complex gene modules.
The engine that makes the cell work is made of an intricate network of molecular interactions. Nowadays, the elements and relationships of this complex network can be studied with several types of high-throughput techniques. The dream of having a global picture of the cell from different perspectives that can jointly explain cell behavior is, at least technically, feasible. However, this task can only be accomplished by filling the gap between data and information. The availability of methods capable of accurately managing, integrating and analyzing the results from these experiments is crucial for this purpose. Here, we review the new challenges raised by the availability of different genomic data, as well as the new proposals presented to cope with the increasing data complexity. Special emphasis is given to approaches that explore the transcriptome trying to describe the modules of genes that account for the traits studied.