Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth.
Homeobox genes murine Rhox5 and human RHOXF1 are expressed in early embryonic stages and then mostly restricted to germline tissues in normal adult, yet they are aberrantly expressed in cancer cells in vitro and in vivo . Here we study the epigenetic regulation and potential functions of Rhox5 gene. In Rhox5-silenced or extremely low expresser cells, we observed low levels of active histone epigenetic marks (H3ac, H4ac and H3K4me2) and high levels of repressive mark H3K9me2 along with DNA hypermethylation in the promoter. In Rhox5 low expresser cells, we typically observed modest levels of both active and repressive histone marks along with moderate DNA methylation. In Rhox5 highly expressed CT26 cancer cells, we observed DNA hypomethylation along with high levels of both active and repressive histone marks. Epigenetic drugs (retinoic acid and MS-275) induced F9 cell differentiation with enhanced Rhox5 expression and dynamic changes of epigenetic marks. Finally, Rhox5 knockdown by small hairpin RNA (shRNA) in CT26 colon cancer decreased cell proliferation and migration in vitro and tumor growth in vivo . Both DNA methylation and histone methylation/acetylation play key roles in modulating Rhox5 expression in various cell types. The stem cell-like "bivalent domain", an epigenetic feature originally identified in key differentiation genes within stem cells, exists in the Rhox5 gene promoter in not only embryonic stem cells but also cancer cells, cancer stem cells, and differentiated Sertoli cells. As Ras signaling-dependent Rhox5 expression promotes tumor growth, Rhox5 may be an ideal target for therapeutic intervention in cancer.


Severe babesiosis in Long Island: review of 34 cases and their complications.
Thirty-four consecutive patients were hospitalized with diagnosis of severe Babesia infection over the course of 13 years. The average time from onset of symptoms to diagnosis was 15 days. When compared with uninfected febrile control patients, affected patients complained significantly more often of malaise, arthralgias and myalgias, and shortness of breath (P<.05), and they more often had thrombocytopenia and abnormal liver function (P<.05). Forty-one percent of patients with Babesia developed complications such as acute respiratory failure, disseminated intravascular coagulation, congestive heart failure, and renal failure. Analysis of data revealed that complicated babesiosis was more commonly associated with the presence of severe anemia (hemoglobin level <10 g/dL; P=.01) and higher parasitemia levels (>10%; P=.08). Patients were treated with a combination of drugs that included clindamycin, quinine, atovaquone, or azithromycin. Despite treatment, parasitemia persisted for an average of 8.5 days (range, 3--21 days). Exchange transfusion was performed for 7 patients, and it effectively reduced the high levels of parasitemia. Three patients died. Improved outcomes may result with prompt recognition and treatment of babesiosis.


Miniports versus standard ports for laparoscopic cholecystectomy.
In conventional (standard) port laparoscopic cholecystectomy, four abdominal ports (two of 10 mm diameter and two of 5 mm diameter) are used. Recently, use of smaller ports, miniports, have been reported. To assess the benefits and harms of miniport (defined as ports smaller than the standard ports) laparoscopic cholecystectomy versus standard port laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013 to identify randomised clinical trials of relevance to this review. Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing miniport versus standard port laparoscopic cholecystectomy were considered for the review. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using RevMan analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI). We included 12 trials with 734 patients randomised to miniport laparoscopic cholecystectomy (380 patients) versus standard laparoscopic cholecystectomy (351 patients). Only one trial which included 70 patients was of low risk of bias. Miniport laparoscopic cholecystectomy could be completed successfully in more than 80% of patients in most trials. The remaining patients were mostly converted to standard port laparoscopic cholecystectomy but some were also converted to open cholecystectomy. These patients were included for the outcome conversion to open cholecystectomy but excluded from other outcomes. Accordingly, the results of the other outcomes are on 343 patients in the miniport laparoscopic cholecystectomy group and 351 patients in the standard port laparoscopic cholecystectomy group, and therefore the results have to be interpreted with extreme caution.There was no mortality in the seven trials that reported mortality (0/194 patients in miniport laparoscopic cholecystectomy versus 0/203 patients in standard port laparoscopic cholecystectomy). There were no significant differences between miniport laparoscopic cholecystectomy and standard laparoscopic cholecystectomy in the proportion of patients who developed serious adverse events (eight trials; 460 patients; RR 0.33; 95% CI 0.04 to 3.08) (miniport laparoscopic cholecystectomy: 1/226 (adjusted proportion 0.4%) versus standard laparoscopic cholecystectomy: 3/234 (1.3%); quality of life at 10 days after surgery (one trial; 70 patients; SMD -0.20; 95% CI -0.68 to 0.27); or in whom the laparoscopic operation had to be converted to open cholecystectomy (11 trials; 670 patients; RR 1.23; 95% CI 0.44 to 3.45) (miniport laparoscopic cholecystectomy: 8/351 (adjusted proportion 2.3%) versus standard laparoscopic cholecystectomy 6/319 (1.9%)). Miniport laparoscopic cholecystectomy took five minutes longer to complete than standard laparoscopic cholecystectomy (12 trials; 695 patients; MD 4.91 minutes; 95% CI 2.38 to 7.44). There were no significant differences between miniport laparoscopic cholecystectomy and standard laparoscopic cholecystectomy in the length of hospital stay (six trials; 351 patients; MD -0.00 days; 95% CI -0.12 to 0.11); the time taken to return to activity (one trial; 52 patients; MD 0.00 days; 95% CI -0.31 to 0.31); or in the time taken for the patient to return to work (two trials; 187 patients; MD 0.28 days; 95% CI -0.44 to 0.99) between the groups. There was no significant difference in the cosmesis scores at six months to 12 months after surgery between the two groups (two trials; 152 patients; SMD 0.13; 95% CI -0.19 to 0.46). Miniport laparoscopic cholecystectomy can be completed successfully in more than 80% of patients. There appears to be no advantage of miniport laparoscopic cholecystectomy in terms of decreasing mortality, morbidity, hospital stay, return to activity, return to work, or improving cosmesis. On the other hand, there is a modest increase in operating time after miniport laparoscopic cholecystectomy compared with standard port laparoscopic cholecystectomy and the safety of miniport laparoscopic cholecystectomy is yet to be established. Miniport laparoscopic cholecystectomy cannot be recommended routinely outside well-designed randomised clinical trials. Further trials of low risks of bias and low risks of random errors are necessary.


The psychological impact of chronic environmental adversity: Responding to prolonged drought.
The health effects of chronic environmental adversity have received insufficient attention, particularly those associated with the psychological impact of drought. Resilience or adaptive response to drought has received even less attention than vulnerability factors. This research examined factors associated with drought impact in rural and remote Australian communities. In 2008 postal surveys were completed by 302 adults (mean age 53 years; 57% female, 77% married) living in rural areas of prolonged drought exposure. Outcome measures were: (i) psychological distress (Kessler 10) and (ii) an index of concern or worry about drought. A range of predictor variables were assessed: adaptability (hopefulness, neuroticism), other adverse events, personal support and community connectedness, and sense of place, as a measure of connection to the local environment. Predictors of drought related worry differed from those associated with psychological distress levels. The former included socio-economic factors (living on a farm [Odds Ratio, OR 3.09], current employment [OR 3.64]), personal psychological characteristics (neuroticism [OR 1.29]), and greater connection with the environment (sense of place [OR 1.05]). On the other hand, psychological distress was associated chiefly with personal factors, such as higher neuroticism [OR 1.92], lower levels of hopefulness [OR 0.28], and lower perceived social support and community connectedness [OR 0.39]. Practical financial, employment and family factors were identified as important elements of drought impact, as to a lesser extent was sense of place, reflecting a confrontation with the consequences of chronic environmental degradation, while personal hopefulness may help mitigate the psychological impact of such adversity.


Confronting misconceptions of public housing communities: A qualitative report of community-informed narratives by community members and partners.
Objectives were (a) to understand a community-informed narrative, as told by community members (CMs) and community partners (CPs), about the strengths, experiences, and perspectives of public housing communities; and (b) to analyze similarities and differences between CMs' and CPs' experiences and perspectives. Qualitative interviews were conducted with 22 CMs of public housing (ages 26-58, 100% female caregivers, 96% Black, 4% multiethnic) and 43 CPs (ages 28-78, 67.4% female, 81.4% Black and African American). Four themes were derived from the CM and CP interviews: (1) counters to public narratives, (2) disinvestment begets disinvestment, (3) community conditions should be better, and (4) community cohesion and connection. Findings from this study present community-centered narratives and experiences that were counter to stereotyped public narratives and could influence public perceptions and behavior to inform policy changes related to improving living conditions and supporting CMs in public and low-income housing communities.


Parkinson disease loci in the mid-western Amish.
Previous evidence has shown that Parkinson disease (PD) has a heritable component, but only a small proportion of the total genetic contribution to PD has been identified. Genetic heterogeneity complicates the verification of proposed PD genes and the identification of new PD susceptibility genes. Our approach to overcome the problem of heterogeneity is to study a population isolate, the mid-western Amish communities of Indiana and Ohio. We performed genome-wide association and linkage analyses on 798 individuals (31 with PD), who are part of a 4,998 member pedigree. Through these analyses, we identified a region on chromosome 5q31.3 that shows evidence of association (p value < 1 × 10(-4)) and linkage (multipoint HLOD = 3.77). We also found further evidence of linkage on chromosomes 6 and 10 (multipoint HLOD 4.02 and 4.35 respectively). These data suggest that locus heterogeneity, even within the Amish, may be more extensive than previously appreciated.


A time-dependent and voltage-sensitive K+ current in single cells from frog atrium.
A quantitative description of the time-dependent and voltage-sensitive outward currents in heart has been hampered by the complications inherent to the multicellular preparations previously used. We have used the whole-cell patch-clamp technique to record the delayed outward K+ current, IK, in single cells dissociated from frog atrium. Na+ currents were blocked with tetrodotoxin and Ca2+ currents with Mn2+ or Cd2+. After depolarizations from -50 mV to potentials positive to -30 mV, a time-dependent outward current was observed. This current has been characterized according to its steady state activation, kinetics, and ion transfer function. The current is well described as a single Hodgkin-Huxley conductance. The deactivation of the current is a single exponential. Activation of the current is sigmoid and is fitted well by raising the activation variable to the second power. The reversal potential of IK is near EK and shifts by 57 mV/10-fold change in [K+]o. This suggests that the current is carried selectively by K ions. The threshold for activation is near -30 mV. IK is maximally activated positive to +20 mV and shows no inactivation. The fully activated current-voltage relationship is linear between -110 and +50 mV. Neither Ba2+ (250 microM) nor Cd2+ (100 microM) affects IK.


Hendricks v. People: forcing the insanity defense on an unwilling defendant.
At least 17 jurisdictions permit insanity defenses to be entered over the objections of defendants. Those jurisdictions believe that society's interest in a just determination of the charges outweighs a competent defendant's choice. If competency includes the ability to rationally choose a plea, competent defendants should not be forced to enter insanity defenses against their wills.


A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior: Possible roles of direct receptor modulation.
Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A receptor agonist), CP-94253 (a 5-HT1B receptor agonist), or ondansetron (a 5-HT3 receptor antagonist). These selective ligands were chosen to simulate vortioxetine's direct modulation of these receptors. Paroxetine was also included in the male study. Acute and repeated treatment with vortioxetine at doses corresponding to clinical levels (based on serotonin transporter occupancy) had minimal effects on sexual behavior in male and female rats. High dose vortioxetine plus flesinoxan (to mimic predicted clinical levels of 5-HT1A receptor occupancy by vortioxetine) facilitated male rat sexual behavior (acutely) while inhibiting female rat proceptive behavior (both acutely and after 14 days treatment). The selective serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual behavior acutely while inhibiting female rat proceptive behavior after repeated administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male and female rats after repeated administration. Ondansetron had no effect on sexual behavior. These findings underline the complex serotonergic regulation of sexual behavior and indicate that the low sexual side effects of vortioxetine found in clinical studies are likely associated with its direct modulation of serotonin receptors.


A single-stage reconstruction of a complex Achilles wound with modified free composite lateral arm flap.
Composite defect of the posterior aspect of the heel, including the Achilles tendon, usually is very difficult to reconstruct as we face the problems of controlling infection, resurfacing the deficient skin defect, and restoring plantar flexion. With the latest advances in microsurgery, several free composite flaps have been used to reconstruct the defect in the Achilles tendon region to achieve stable and functional soft tissue coverage. We report such a single-stage reconstruction of a complex Achilles wound using the modified neurosensory lateral arm free flap including the triceps tendon strip and the posterior cutaneous nerve. Authors' rolled-up triceps tendon strip method is presented for the one-stage reconstruction of the Achilles tendon and soft tissue defect, providing good contour, strong tension, and protective sensation. The follow-up has proved a satisfactory outcome.


The efficacy of lumbar hybrid stabilization using the DIAM to delay adjacent segment degeneration: an intervention comparison study with a minimum 2-year follow-up.
Although posterior lumbar interbody fusion (PLIF) has a successful fusion rate, the long-term outcome of PLIF is occasionally below expectations because of adjacent segment degeneration (ASD). To evaluate the ability of hybrid stabilization using DIAM (Device for Interspinous Assisted Motion) to delay ASD. An intervention comparison study of 75 patients (hybrid, 25; PLIF, 50) was performed. The indications for hybrid stabilization were facet joint degeneration, Pfirrmann grade II to III, and stenosis at the rostral adjacent segment. The PLIF group consisted of patients matched for age, sex, and fusion. The hybrid stabilization procedure included traditional PLIF and DIAM installation at a superior adjacent segment. The outcomes were analyzed with a linear mixed model analysis. Conditional logistic regression was performed to calculate the odds ratio for the association of surgical methods. The hybrid group (24%) revealed fewer ASDs than the PLIF group (48%). Among ASDs, spondylolisthesis occurred more frequently in the PLIF group than the hybrid group. Hybrid surgery was significantly associated with ASD; the odds ratio for hybrid surgery was 0.28 compared with PLIF. Foraminal height of the PLIF group decreased more than the hybrid group (P = .01). Segmental mobility showed a greater increase in the PLIF group than the hybrid group (P = .04). However, the clinical outcomes did not show significant differences between the groups. Hybrid stabilization with DIAM and pedicle screws can be used for patients with facet degeneration at adjacent segments but should be further investigated.


New High-Resolution Analysis of the nu(3) Band of the (15)N(16)O(2) Isotopomer of Nitrogen Dioxide by Fourier Transform Spectroscopy.
New high-resolution Fourier transform absorption spectra of an (15)N(16)O(2) isotopic sample of nitrogen dioxide were recorded at the University of Bremen in the 6.3-µm region. Starting from the results of a previous study [Y. Hamada, J. Mol. Struct. 242, 367-377 (1991)], a new and more extended analysis of the nu(3) band located at 1582.1039 cm(-1) has been performed. The spin-rotation energy levels were satisfactorily reproduced using a theoretical model which takes into account both the Coriolis interactions between the spin-rotation energy levels of the (001) vibrational state with those of the (020) and (100) states and the spin-rotation resonances within each of the NO(2) vibrational states. Precise vibrational energies and rotational, spin-rotation, and coupling constants were obtained in this way for the first triad of (15)N(16)O(2) interacting states {(020), (100), (001)}. Finally, a comprehensive list of line positions and line intensities of the {nu(1), 2nu(2), nu(3)} interacting bands of (15)N(16)O(2) was generated, using for the line intensities the transition moment operators which were obtained previously for the main isotopic species. Copyright 2000 Academic Press.


Breast-Specific Epigenetic Regulation of DeltaNp73 and Its Role in DNA-Damage-Response of BRCA1-Mutated Human Mammary Epithelial Cells.
The function of BRCA1/2 proteins is essential for maintaining genomic integrity in all cell types. However, why women who carry deleterious germline mutations in BRCA face an extremely high risk of developing breast and ovarian cancers specifically has remained an enigma. We propose that breast-specific epigenetic modifications, which regulate tissue differentiation, could team up with BRCA deficiency and affect tissue susceptibility to cancer. In earlier work, we compared genome-wide methylation profiles of various normal epithelial tissues and identified breast-specific methylated gene promoter regions. Here, we focused on deltaNp73, the truncated isoform of p73, which possesses antiapoptotic and pro-oncogenic functions. We showed that the promoter of deltaNp73 is unmethylated in normal human breast epithelium and methylated in various other normal epithelial tissues and cell types. Accordingly, deltaNp73 was markedly induced by DNA damage in human mammary epithelial cells (HMECs) but not in other epithelial cell types. Moreover, the induction of deltaNp73 protected HMECs from DNA damage-induced cell death, and this effect was more substantial in HMECs from BRCA1 mutation carriers. Notably, when BRCA1 was knocked down in MCF10A, a non-malignant breast epithelial cell line, both deltaNp73 induction and its protective effect from cell death were augmented upon DNA damage. Interestingly, deltaNp73 induction also resulted in inhibition of BRCA1 and BRCA2 expression following DNA damage. In conclusion, breast-specific induction of deltaNp73 promotes survival of BRCA1-deficient mammary epithelial cells upon DNA damage. This might result in the accumulation of genomic alterations and allow the outgrowth of breast cancers. These findings indicate deltaNp73 as a potential modifier of breast cancer susceptibility in BRCA1 mutation carriers and may stimulate novel strategies of prevention and treatment for these high-risk women.


Does productivity drive diversity or vice versa? A test of the multivariate productivity-diversity hypothesis in streams.
The idea that productivity regulates species diversity is deeply ingrained in the field of ecology. Yet, over the past few decades, an increasing number of experiments have shown that species diversity controls, rather than simply responds to, biomass production. These contrasting perspectives have led to a seeming paradox: Is diversity the cause or the consequence of biological production? Here we present empirical evidence for the multivariate productivity-diversity (MPD) hypothesis, which argues that differing perspectives on productivity-diversity relationships can be resolved by recognizing that historical research has focused on how resource supply regulates both the productivity and richness of local competitors, whereas more recent studies have focused on how the richness of a colonist pool regulates the efficiency by which resources are captured and converted into new tissue. The MPD hypothesis predicts that three pathways operate concurrently to generate productivity diversity relationships in nature: (1) resource supply directly limits the standing biomass and/or rate of new production by primary producers, (2) producer biomass is directly influenced by the richness of species that locally compete for resources, and (3) resource supply rate indirectly affects producer biomass by influencing the fraction of species from a colonist pool that locally coexist. To examine whether this set of pathways explains covariation between productivity and diversity in natural streams, we used nutrient-diffusing agar "patches" to manipulate resource supply rates in 20 streams throughout the Sierra Nevada mountain range, California, USA. We then measured the fraction of periphyton species from the stream colonist pool co-occurring on each nutrient patch, as well as the standing biomass and rates of primary production. Natural patterns of covariation agreed with predictions of the MPD hypothesis. Algal biomass was an increasing function of nutrient supply, and an increasing function of local richness. The fraction of species from the colonist pool found co-occurring on a patch was a concave-down function of nutrient supply, causing nutrients to indirectly affect biomass via control over local richness. These results suggest that the MPD hypothesis is a viable explanation of patterns of diversity and productivity in natural stream ecosystems, and that it has potential to merge the historical view that productivity drives diversity with a parallel view that diversity drives productivity.


Light-Oxygen-Voltage (LOV)-sensing Domains: Activation Mechanism and Optogenetic Stimulation.
The light-oxygen-voltage (LOV) domains of phototropins emerged as essential constituents of light-sensitive proteins, helping initiate blue light-triggered responses. Moreover, these domains have been identified across all kingdoms of life. LOV domains utilize flavin nucleotides as co-factors and undergo structural rearrangements upon exposure to blue light, which activates an effector domain that executes the final output of the photoreaction. LOV domains are versatile photoreceptors that play critical roles in cellular signaling and environmental adaptation; additionally, they can noninvasively sense and control intracellular processes with high spatiotemporal precision, making them ideal candidates for use in optogenetics, where a light signal is linked to a cellular process through a photoreceptor. The ongoing development of LOV-based optogenetic tools, driven by advances in structural biology, spectroscopy, computational methods, and synthetic biology, has the potential to revolutionize the study of biological systems and enable the development of novel therapeutic strategies.


Functional food and nutra-pharmaceutical perspectives of date (Phoenix dactylifera L.) fruit.
Date palm counts among the oldest fruit crops of the world and is mainly cultivated for its highly nutritious fruits consumed as a staple food in many countries, especially in the Gulf region. Dates are enriched with numerous therapeutic bioactives and functional compounds such as phenolics, flavonols, carotenoids, minerals, and vitamins that not only provide an appreciable amount of energy required for the human body but also act as an effective therapeutic agent against several diseases. This review aimed to provide a deep insight into the nutritional as well as phytochemicals profile of date fruit and its seeds in order to explore their biological (anti-cancer, anti-diabetic, cardio-protective, anti-inflammatory properties), functional food, and nutra-pharmaceutical attributes. PRACTICAL APPLICATIONS: This review provides updated information regarding the date fruits and seeds phytochemicals composition together with highlighting dates potential as a natural therapeutic agent against several diseases. The study also urges the importance of consuming dates as a great package to live a healthy life due to the functional food and nutraceutical properties of this valuable fruit. The study also provides information first time as recommending dates to cope with the hidden hunger or micronutrient deficiency faced by the third world inhabitants. Hence, the review may further help the industry and researchers to explore the potential of dates for future medicinal and nutra-pharmaceutical applications.


Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity.
Activation of Toll-like receptors (TLRs) is widely accepted as an essential event for defence against infection. Many TLRs utilize a common signalling pathway that relies on activation of the kinase IRAK4 and the transcription factor NFkappaB for the rapid expression of immunity genes. 21 K DNA microarray technology was used to evaluate LPS-induced (TLR4) gene responses in blood monocytes from a child with an IRAK4-deficiency. In vitro responsiveness to LPS was confirmed by real-time PCR and ELISA and compared to the clinical predisposition of the child and IRAK4-deficient mice to Gram negative infection. We demonstrated that the vast majority of LPS-responsive genes in IRAK4-deficient monocytes were greatly suppressed, an observation that is consistent with the described role for IRAK4 as an essential component of TLR4 signalling. The severely impaired response to LPS, however, is inconsistent with a remarkably low incidence of Gram negative infections observed in this child and other children with IRAK4-deficiency. This unpredicted clinical phenotype was validated by demonstrating that IRAK4-deficient mice had a similar resistance to infection with Gram negative S. typhimurium as wildtype mice. A number of immunity genes, such as chemokines, were expressed at normal levels in human IRAK4-deficient monocytes, indicating that particular IRAK4-independent elements within the repertoire of TLR4-induced responses are expressed. Sufficient defence to Gram negative immunity does not require IRAK4 or a robust, 'classic' inflammatory and immune response.


Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients.
Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively. The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.


One size fits all? Race, gender and body mass index among U.S. adults.
This study examined the extent to which factors presumed to be correlated with body mass index (BMI) vary across four race- and gender-specific groups. Data were drawn from the American Changing Lives Survey to estimate separate multivariate regression models for the total study sample that included African-American males, Caucasian males, African-American females and Caucasian females. The dependant variable of interest was BMI. Independent variables included age, human capital variables, relationship and support measures, health status and behavior measures, and stress and outlook measures. Results from the pooled model indicated that BMI was associated with a number of factors such as employment status, chronic illness, financial strain and religiosity. However, race- and gender-specific regression models revealed that predictors of BMI varied considerably for African-American men, Caucasian men, African-American women and Caucasian women. In other words, these models disentangled important correlations not observed in the pooled model. These findings suggest that addressing racial disparities in body weight-related outcomes requires health practitioners to modify obesity prevention and treatment efforts to incorporate a broader array of factors inherent to specific racial and gender populations.


Genetic Diversity in the Major Capsid L1 Protein of HPV-16 and HPV-18 in the Netherlands.
Intratypic molecular variants of human papillomavirus (HPV) type-16 and -18 exist. In the Netherlands, a bivalent vaccine, composed of recombinant L1 proteins from HPV-16 and -18, is used to prevent cervical cancer since 2009. Long-term vaccination could lead to changes in HPV-16 and -18 virus population, thereby hampering vaccination strategies. We determined the genetic diversity of the L1 gene in HPV-16 and -18 viral strains circulating in the Netherlands at the start of vaccination in order to understand the baseline genetic diversity in the Dutch population. DNA sequences of the L1 gene were determined in HPV-16 (n = 241) and HPV-18 (n = 108) positive anogenital samples collected in 2009 and 2011 among Dutch 16- to 24-year old female and male attendees of the sexually transmitted infection (STI) clinics. Phylogenetic analysis was performed and sequences were compared to reference sequences HPV-16 (AF536179) and HPV-18 (X05015) using BioNumerics 7.1. For HPV-16, ninety-five single nucleotide polymorphism (SNPs) were identified, twenty-seven (28%) were non-synonymous variations. For HPV-18, seventy-one SNPs were identified, twenty-nine (41%) were non-synonymous. The majority of the non-silent variations were located in sequences encoding alpha helix, beta sheet or surface loops, in particular in the immunodominant FG loop, and may influence the protein secondary structure and immune recognition. This study provides unique pre-vaccination/baseline data on the genetic L1 diversity of HPV-16 and -18 viruses circulating in the Netherlands among adolescents and young adults.


Bioassay for Determining the Concentrations of Caffeine and Individual Methylxanthines in Complex Samples.
Caffeine and other methylxanthines are stimulant molecules found in formulated beverages, including sodas and energy drinks, and in brewed beverages, such as coffee and teas. Previously, we developed a bioassay for caffeine that involves monitoring the growth of a ΔguaB mutant of Escherichia coli defective in de novo guanine biosynthesis. When supplemented with a plasmid expressing the genes for an N-demethylation pathway from Pseudomonas putida CBB5, these bacteria demethylate caffeine (1,3,7-trimethylxanthine) and other methylxanthines into xanthine, which is then converted into guanine to support cell growth. A major limitation of this bioassay was that it could only measure the total concentration of all methylxanthines in a mixture. Therefore, it could not be used to measure the caffeine content of beverages like teas, which contain substantial quantities of multiple methylxanthines. To overcome this limitation, we created seven new plasmids containing all subsets of the three demethylase genes (ndmA, ndmB, and ndmC). We show that strains of ΔguaBE. coli containing each plasmid are able to demethylate specific subsets of methylxanthines and that they can be used to determine the concentrations of individual methylxanthines in complex mixtures containing multiple methylxanthines, including coffee doped with an additional methylxanthine. While validating this assay, we also discovered an unexpected demethylation event at the 1-methyl position when NdmB and NdmC were expressed in the absence of NdmA. The improved cell-based bioassay is inexpensive, is easy to use, and gives results comparable to standard high-performance liquid chromatography methods for measuring methylxanthine concentrations.IMPORTANCE Caffeine (1,3,7-trimethylxanthine) is the dominant neurostimulant found in coffee, teas, sodas, and energy drinks. Measuring the amount of caffeine and other methylxanthines in these beverages is important for quality assurance and safety in food science. Methylxanthines are also used in medicine and as performance-enhancing drugs, two contexts in which accurately determining their concentrations in bodily fluids is important. Liquid chromatography is the standard method for measuring methylxanthine concentrations in a sample, but it requires specialized equipment and expertise. We improved a previous bioassay that links E. coli growth to methylxanthine demethylation so that it can now be used to determine the amounts of individual methylxanthines in complex mixtures or beverages, such as coffee.


Decreased expression of Cyr61 is associated with prostate cancer recurrence after surgical treatment.
Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. Previous studies have suggested that Cyr61 may be a marker for a more aggressive phenotype. In this study, we evaluated the association between Cyr61 staining intensity and subsequent recurrence after surgical treatment of clinically localized prostate cancer. A study of 229 men with recurrence and 229 controls matched on age, race, pathologic stage, and Gleason sum nested in a cohort of men who underwent radical prostatectomy for clinically localized prostate cancer, utilizing immunohistochemistry analysis of tissue microarray (TMA) sections, was conducted. Odds ratios (OR) of recurrence and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Recurrence was identified in 12.2% of cases, and in 24.0% of controls that had at least 1 TMA spot containing cancer with a staining intensity of 3 (P = 0.001). Taking into account age, pathologic stage and grade, presurgery prostate-specific antigen concentration, and calendar of surgery as a measure of tissue block storage time, men with a Cyr61 staining intensity of 3 were 56% less likely to recur than men with a lower staining intensity (OR = 0.44, 95% CI = 0.22-0.90). High Cyr61 staining intensity in adenocarcinoma was associated with a lower risk of recurrence after surgical treatment of prostate cancer independent of pathologic tumor characteristics. If validated in other sample sets, Cyr61 may serve as a tissue biomarker for stratifying men for risk of recurrence and thus could inform treatment decision making.


[The HIV antibody test--answers from users].
The survey of the HIV test users interviewed at the AIDS/STD consultancy of the Bremen Health Department identifies that the test is mostly used by young, well-educated heterosexual people with a rather minor risk of a HIV infection (58%). But a cluster analysis also shows the test to be used by different groups with different risks: Young heterosexual people generally use the test, which is free of charge, pre-emptively at the begin of a new partnership so as to stop using condoms in the future. In this group, especially young men have the least potential of risk. Older heterosexual men seem to have a higher risk because of sexual affairs and less use of condoms. These men often live in long-lasting partnerships, so their wives may be infected with sexually transmitted diseases as well. The group of men who have sex with men (MSM) shows the highest risk factors (frequent change of partners, high rate of STDs in their anamnesis). At least this group often uses condoms. MSM use the test mostly after a high-risk situation to check to see if they are infected with HIV. They especially appreciate the anonymity of our test but also the consultation. The HIV test in our health department seems to be used mostly by those people who have already integrated the test into their strategies of prevention. It cannot be seen as an independent way of prevention. To reach less educated people, it is necessary to establish comprehensive concepts of prevention which reflect the cultures and the way of life of these people. Success will only be achieved in cooperation with other institutions outside the health department and also requires resources and patience. In the following we will present possible strategies.


Validation of an insulin infusion nomogram for intensive glucose control in critically ill patients.
To evaluate the effectiveness, safety, and associated patient outcomes of a simplified, nurse-directed insulin nomogram designed to achieve intensive blood glucose level control (target range 90-144 mg/dl). Prospective study with a retrospective control group. A medical-surgical intensive care unit (ICU) in a quaternary care, university-affiliated hospital in an urban center. Eighty-six critically ill adult patients (aged>or=18 yrs) requiring blood glucose control, with 42 in the retrospective control group and 44 in the prospective nomogram group. Control patients received insulin subcutaneously or intravenously based on ad hoc insulin sliding scales; nomogram patients received intravenous insulin at a rate specified by the nomogram, based on capillary blood glucose levels measured at the bedside. Insulin infusion in the prospective patient group was titrated by the bedside nurse based on a predefined nomogram to attain the target blood glucose level. The retrospective control group was used as a comparison to assess the safety and effectiveness of the nomogram. Fewer patients in the nomogram (32%) than control (67%) group had a diagnosis of diabetes mellitus on admission. Overall, blood glucose levels in the nomogram group were within the target range 52% of the time versus 20% in the control group (p<0.001). Morning blood glucose levels were significantly lower compared with the control group (mean+/-SD 128+/-32 vs 176+/-50 mg/dl, p<0.001). Nomogram patients achieved target blood glucose levels faster than control patients (median 15 vs 66 hrs, p<0.0001). This improved blood glucose control remained statistically significant after adjusting for baseline differences in diabetes status. Hyperglycemia occurred less often in the nomogram than the control group (14% vs 53%, p<0.0001), and hypoglycemia occurred more often (3.8% vs 2.2%, p=0.004). The frequency of severe hypoglycemia was similar in both groups (0.2% vs 0.4%, p=NS). Such control required slightly more blood glucose checks/day in the nomogram group (7.1+/-1.5 vs 5.8+/-1.1, p<0.001). No significant reduction was observed in duration of vasopressor or antibiotic therapy or in length of stay in the ICU. This study demonstrated that intensive blood glucose control is achievable using a nurse-directed nomogram. This improved control was achieved, regardless of diabetes status of the patient, without substantially compromising safety or increasing resource use.


Changes in the relative contribution of each leg to the control of quiet two-legged stance following unilateral plantar-flexor muscles fatigue.
We used unilateral plantar-flexor muscles fatigue to assess the capacity of the central nervous system to adapt quiet two-legged stance control to a unilateral ankle neuromuscular perturbation. Eighteen young healthy adults stood barefoot with their eyes closed and were asked to sway as little as possible. The Experimental group (n = 9) executed this postural task in two conditions, before (pre-test) and following the completion of a fatiguing exercise designed to induce a muscular fatigue in the plantar-flexor muscles of their dominant leg (post-test). For the Control group (n = 9), this fatiguing exercise was replaced with a standing rest period corresponding to the fatiguing exercise. Results of the Experimental group showed no significant difference between the weightbearing index measured in the pre-test condition and that observed in the post-test condition. Results further revealed that unilateral plantar-flexor muscles fatigue yielded different effects on the centre of foot pressure (CoP) displacements under the non-fatigued leg and under the fatigued leg: a wider surface area of the CoP displacements was observed under the non-fatigued than under the fatigued leg, and a higher mean speed of the CoP displacements was observed under the non-fatigued leg only in the post-test relative to the pre-test condition. These findings evidenced that the contribution of each leg to the control of quiet two-legged stance is modified as a result of muscle fatigue of unilateral plantar-flexor muscles. The greater contribution of the non-fatigued leg could be viewed as a fatigue-induced adaptive change in the control of quiet two-legged stance in response to an alteration of the unilateral ankle neuromuscular function induced by unilateral plantar-flexor muscles fatigue.


Is there equity in oral healthcare utilization: experience after achieving Universal Coverage.
To assess the socioeconomic-related (in)equality and horizontal (in)equity in oral healthcare utilization among Thai adults after Universal Coverage (UC) policy implemented nationwide, and to decompose the source of inequality in utilization. Further, to identify the determinants that effect to out-of-pocket payments for oral healthcare. Using the data of 32748, Thai adults aged 15 years and over from nationally representative Health and Welfare Survey and Socio-Economic Survey in 2006. This study employs concentration index (CI) and horizontal inequity index (HI) to measure the socioeconomic-related inequality and horizontal inequity in oral healthcare utilization, respectively. Further, employing decomposition method to identify the sources of inequality comprising of a contribution of income, need determinants (i.e. self-assessed oral health, demographic characteristics), non-need determinants (i.e.working status, educational level attainment, type of insurance entitlement, geographic characteristics and marital status) and residual term. Two-part model is used to determine the factors effect to out-of-pocket payments for oral healthcare. There are the pro-rich inequality and inequity in oral healthcare utilization among Thais as indicated by significantly positive values of CI (=0.199) and HI (=0.206). The poor are more likely to access and utilize services at subsidized public facility particularly community hospital, as opposed to the better-off who tend to utilize services at private facility. Income and non-need determinants principally contribute to the pro-poor in public sector utilization, unlike pro-rich in private sector utilization. Need factors account for most of the pro-poor utilization. Type of treatment obtained and insurance used in the last visit are the substantial determinants effect to incurring out-of-pocket payments for oral healthcare. Notwithstanding the UC policy implementation made impressive strides toward improving of welfare coverage and an increase in accessibility of health services among Thais, inequality and inequity in oral healthcare utilization persist even when the country achieved universal coverage. Decomposition analyses demonstrate the association of each determinant to inequality in utilization which provides information for policy amendment to achieve the goal of equity in healthcare system.


Stroke prevention with rivaroxaban in higher-risk populations with atrial fibrillation.
Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major risk factor for stroke. Rivaroxaban, an oral factor Xa inhibitor, is approved for the prevention of stroke in patients with non-valvular AF. In the pivotal phase III trial ROCKET AF, rivaroxaban demonstrated non-inferiority compared with warfarin for reducing the risk of stroke or systemic embolism (SE) in patients with AF (intention-to-treat analysis), without an increased risk of major bleeding. Superior efficacy vs. warfarin was achieved while patients were on study medication. Other direct oral factor Xa inhibitors have completed phase III clinical trials in this indication. Compared with warfarin, apixaban (in the ARISTOTLE trial) and edoxaban (in the ENGAGE-AF trial) were shown to be superior or non-inferior, respectively, for reduction in stroke or SE risk in patients with AF. Baseline stroke risk, as indicated by CHADS2 scores, was lower in patients in the ARISTOTLE and ENGAGE-AF trials than in ROCKET AF. This review discusses the main findings from ROCKET AF, specifically examining recent subgroup analyses investigating rivaroxaban use across various patient types at high risk for adverse outcomes, including those with prior stroke or transient ischaemic attack, reduced renal function, prior myocardial infarction, peripheral artery disease, heart failure or patients aged ≥ 75 years and those resident in East Asia. These subgroup analyses demonstrate that the treatment effect for rivaroxaban vs. warfarin is broadly consistent across a wide range of patient groups, with respect to both efficacy and safety.


Secretory Expression of an Alkaline Alginate Lyase With Heat Recovery Property in Yarrowia lipolytica.
Alginate lyase possesses wide application prospects for the degradation of brown algae and preparation of alginate oligosaccharides, and its degradation products display a variety of biological activities. Although many enzymes of this type have been reported, alginate lyases with unique properties are still relatively rare. In the present work, an alginate lyase abbreviated as Alyw203 has been cloned from Vibrio sp. W2 and expressed in food-grade Yarrowia lipolytica. The Alyw203 gene consists of an open reading frame (ORF) of 1,566 bp containing 521 amino acids, of which the first 17 amino acids are considered signal peptides, corresponding to secretory features. The peak activity of the current enzyme appears at 45°C with a molecular weight of approximately 57.0 kDa. Interestingly, Alyw203 exhibits unique heat recovery performance, returning above 90% of its initial activity in the subsequent incubation for 20 min at 10°C, which is conducive to the recovery of current enzymes at low-temperature conditions. Meanwhile, the highest activity is obtained under alkaline conditions of pH 10.0, showing outstanding pH stability. Additionally, as an alginate lyase independent of NaCl and resistant to metal ions, Alyw203 is highly active in various ionic environments. Moreover, the hydrolyzates of present enzymes are mainly concentrated in the oligosaccharides of DP1-DP2, displaying perfect product specificity. The alkali suitability, heat recovery performance, and high oligosaccharide yield of Alyw203 make it a potential candidate for industrial production of the monosaccharide and disaccharide.


[On pseudomonas aerugenosa immunity to microwave energies].
Experiments were performed to investigate immunity of a variety of water-suspended Pseudomonas aerugenosa to microwave energies. The objectives were to determine lethal temperatures for different Pseudomonas aerugenosa strains in water stream and to test whether Pseudomonas aerugenosa are adaptable to repeated microwave exposure.In the experiments, Pseudomonas aerugenosa died when water temperature was in the interval from 60 to 65 degrees C. It was also shown that Pseudomonas aerugenosa do not adapt to microwave energies. Therefore, we obtained evidence that microwave energies can be effectively used for water decontamination and heating in advanced life support systems.


[Evaluation of cutaneous necrosis risk in peripheral arterial diseases].
In the last years the surgical and pharmacological treatment of critical limb ischaemia has been significantly modified, increasing the reduction of amputation and/or the increase of limbs recovery. However, neither survival nor incidence of amputations changed. This, probably has been related to an inadequate therapy after revascularization procedures or to an increase of complications. The assessment of cutaneous necrosis risk and of the recovery possibility of the ischemic limb can positively influence the therapeutic strategy, in these patients. The aim of this paper is to identify the reference parameters that can represent objectively the limit for cutaneous ischemic suffering, improving the physiological knowledges of critical limb ischemia. In the first phase of our study 56 patients, in different stages of peripheral arterial disease have been, submitted to microcirculatory assessment measuring the pattern of TcPO2 and TcPCO2 in correlation with walking performance expressed as ACD at treadmill test (2.5 Km/h gradient 12.5%). The second phase assesses the clinical outcome after three months of 12 among 19 patients with critical limb ischemia, measuring the changes of TcPO2 and TcPCO2 with postural test and after infusion with prostanoids of two weeks. A reduction of the TcPO2 and an increase of the acidosis from stable to invalidant claudication have been observed, with a progressive loss of direct correlation between ACD and TcPO2, and an increase of the inverse correlation of the ACD with TcPCO2. In the CLI we found a very low TcPO2 levels with a TcPCO2 levels ( about 120 mmHg) with no correlation of ACD with TcPO2 and TcPCO2. The good clinical outcome was related to an increase of the TcPO2 and to a reduction of the TcPCO2 after postural stimulation and after therapy. In the patients with a bad response to the postural test, a possibility of recovery was observed only in those with a positive answer to therapeutic treatment. The invalidant claudication phase can be considered a point of physiopathological change from relative to absolute ischemia that is clinically equivalent to early sign of ischemia. The identification of recoverable patients seems to be related to postural test and pharmacological treatment with an increased values. Viceversa, it is still difficult to identify as non-responders, those patients with a bad postural test, or with a little improvement after pharmacological treatment, as those with an indication to primary amputation. More observations, evaluation data will contribute to a better definition of a negative trend.


Educational differences in the intention to stop smoking: explanations based on the Theory of Planned Behaviour.
At this time, the mechanisms by which socioeconomic differences in smoking develop are not completely understood. In this paper the Theory of Planned Behaviour as a potential explanatory framework for socioeconomic differences in smoking is tested. It was hypothesized that components of the Theory of Planned Behaviour may be unequally distributed over educational groups and therefore contribute to the explanation of socioeconomic differences in smoking. Educational differences in the intention to quit smoking are described and attempts are made to understand these in the light of educational patterns in attitude towards smoking cessation, perceived subjective norm concerning quitting smoking, and self-efficacy. This cross-sectional study was part of the longitudinal GLOBE study on socioeconomic differences in The Netherlands. Components of the Theory of Planned Behaviour were measured in 1997 among 602 Dutch daily smokers. No educational differences in the intention to quit smoking were found. Persons with a more positive attitude towards smoking cessation and a high subjective norm significantly more often intended to quit smoking. But, positive attitude and high subjective norm were not related to education, which explains the lack of educational differences in intention to quit smoking. Higher educated respondents reported significantly higher self-efficacy to refrain from smoking, which, however, was not related to the intention to quit smoking. It is anticipated that, from all components of the Theory of Planned Behaviour, only the direct effect of self-efficacy on behaviour may contribute to educational differences in smoking cessation.


Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration.
Lung cancer is one of the most common fatal diseases in the developed world. The disease is rarely cured by currently available therapies, with an overall survival rate of ∼10%. Characterizing novel proteins that offer crucial insights into the processes of lung tumour invasion and metastasis may therefore provide much-needed prognostic markers, and influence therapeutic strategies. Aberrant function of the integrin family of heterodimeric cell surface receptors is a common theme in cancer--investigation into novel integrin activity regulators may offer crucial insights into the processes of tumour invasion and metastasis and may reveal insights into potential therapeutic targets. We previously described that depletion of the novel multi-transmembrane domain protein Fam38A, located at the endoplasmic reticulum (ER), inactivates endogenous beta1 integrin affinity, reducing cell adhesion. We now show that depletion of Fam38A, also now known as Piezo1, causes anchorage independence and a switch to a reduced integrin-dependent mode of cell migration/invasion, a novel phenotype for this integrin-regulating protein. Normal lung epithelial cells show increased rates of migration by 2D time-lapse microscopy and increased capacity to invade into matrigel, despite having decreased integrin affinity. We confirm greatly depleted Fam38A expression in small cell lung cancer (SCLC) lines where a form of reduced integrin-dependent migration, i.e. amoeboid migration, is a known phenotype. We propose that loss of Fam38A expression may cause increased cell migration and metastasis in lung tumours.


Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema.
Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known. We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography. The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02). Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.


Intimate partner violence during pregnancy and adverse neonatal outcomes in low-income women.
Intimate partner violence (IPV) affects an estimated 1.5 million U.S. women annually. IPV impacts maternal and neonatal health with higher rates of depression and low birth weight (LBW). Less studied is experiencing IPV and delivering a small for gestational age (SGA) baby. SGA neonates are at increased risk of developmental and behavioral problems. The negative sequelae persist into adulthood with increased rates of diabetes mellitus and coronary heart disease. In a sample of 239 pregnant women experiencing IPV, in urban and rural settings, we examined cross-sectional associations of severity of IPV and neonatal outcomes (i.e., birth weight and gestational age). Severity of IPV was measured by the Conflict Tactics Scale 2 and neonatal outcomes were collected at the time of delivery. Outcomes were collected on 194 neonates; 14.9% (n=29) were classified as LBW, 19.1% (n=37) classified as SGA, and 9.8% (n=19) as LBW and SGA. Women reporting higher severity of IPV during pregnancy had a greater likelihood of delivering an SGA neonate (odds ratio [OR] 4.81; 95% confidence interval [95% CI] 1.86-12.47), and LBW neonate (OR 4.20; 95% CI 1.46-12.10). In a sample of pregnant women experiencing perinatal IPV, women experiencing greater severities of IPV were more likely to deliver a neonate with an adverse outcome. Early recognition and intervention of IPV is essential to reduce disparities in birth outcomes and long-term health outcomes for these neonates.


Probing Limits of Information Spread with Sequential Seeding.
We consider here information spread which propagates with certain probability from nodes just activated to their not yet activated neighbors. Diffusion cascades can be triggered by activation of even a small set of nodes. Such activation is commonly performed in a single stage. A novel approach based on sequential seeding is analyzed here resulting in three fundamental contributions. First, we propose a coordinated execution of randomized choices to enable precise comparison of different algorithms in general. We apply it here when the newly activated nodes at each stage of spreading attempt to activate their neighbors. Then, we present a formal proof that sequential seeding delivers at least as good spread coverage as the single stage seeding does. Moreover, we also show that, under modest assumptions, sequential seeding performs provably better than the single stage seeding using the same number of seeds and node ranking. Finally, we present experimental results comparing single stage and sequential approaches on directed and undirected graphs to the well-known greedy approach to provide the objective measure of the sequential seeding benefits. Surprisingly, applying sequential seeding to a simple degree-based selection leads to higher coverage than achieved by the computationally expensive greedy approach currently considered to be the best heuristic.


Oral glutamine supplementation relieves muscle loss in immobilized rats, altering p38MAPK and FOXO3a signaling pathways.
Skeletal muscle synthesizes, stores, and releases body L-glutamine (GLN). Muscle atrophy due to disabling diseases triggers the activation of proteolytic and pro-apoptotic cell signaling, thus impairing the body's capacity to manage GLN content. This situation has a poor therapeutic prognosis. Evaluating if oral GLN supplementation can attenuate muscle wasting mediated by elevated plasma cortisol and activation of caspase-3, p38MAPK, and FOXO3a signaling pathways in soleus and gastrocnemius muscles of rats submitted to 14-day bilateral hindlimbs immobilization. Animals were randomly distributed into six groups: non-immobilized rats (Control), control orally supplemented with GLN (1 g kg-1) in solution with L-alanine (ALA: 0.61 g kg-1; GLN+ALA), control orally supplemented with dipeptide L-alanyl-L-glutamine (DIP; 1.49 g kg-1), hindlimbs immobilized rats (IMOB), IMOB orally GLN+ALA supplemented (GLN+ALA-IMOB), and IMOB orally DIP supplemented (DIP-IMOB). Plasma and muscle GLN concentration, plasma cortisol level, muscle caspase-3 activity, muscle p38MAPK and FOXO3a protein content (total and phosphorylated forms), and muscle cross-sectional area (CSA) were measured. Compared to controls, IMOB rats presented: a) increased plasma cortisol levels; b) decreased plasma and muscle GLN concentration; c) increased muscle caspase-3 activity; d) increased total and phosphorylated p38MAPK protein content; e) increased FOXO3a and decreased phosphorylated FOXO3a protein content; f) reduced muscle weight and CSA befitting to atrophy. Oral supplementation with GLN+ALA and DIP was able to significantly attenuate these effects. These findings attest that oral GLN supplementation in GLN+ALA solution or DIP forms attenuates rats' skeletal muscle mass wasting caused by disuse-mediated muscle atrophy.


Prediction of response to plasma exchange in chronic relapsing polyneuropathy. A clinico-pathological correlation.
The clinical features, results of nerve conduction studies and sural nerve biopsy findings have been compared in 5 patients with chronic relapsing polyneuropathy in whom plasma exchange was used in treatment. In 2 patients who consistently responded to plasma exchange, the dominant pathological findings was segmental demyelination without prominent onion bulb formation, whereas axonal degeneration was more prominent in the cases which did not respond. It is concluded that in cases of chronic relapsing polyneuritis where the clinical, electrophysiological and histological features suggest primary demyelination, plasma exchange may provide a useful adjunct to therapy.


Prevention of experimental autoimmune thyroiditis through the anti-idiotypic network.
The central goal in the therapy of autoimmune diseases is to develop potent tools able to exert specific control of the immune response to self Ag. Anti-Id may provide such specific immunodulators because the relevance of the idiotypic network in autoimmunity is well documented. We now describe the protective immunity against experimental autoimmune thyroiditis induced exclusively by a thyroglobulin (Tg)-specific cytotoxic T cell clone and show that this down-regulation occurs through the generation of anti-Id antibodies (Ab) (Ab2Beta) which recognize the paratope of a anti-Tg mAb (Ab1) specific to the pathogenic epitope of the Tg molecule. We further analyze the various steps of the Ab responses (Ab1, Ab2, and Ab3) in terms of poly-, mono-, and autospecificities for the pathogenic epitope of the Tg molecule and for the idiotope of the related Ab.


Removal of residual nuclei following a cavitation event using low-amplitude ultrasound.
Microscopic residual bubble nuclei can persist on the order of 1 s following a cavitation event. These bubbles can limit the efficacy of ultrasound therapies such as shock wave lithotripsy and histotripsy, because they attenuate pulses that arrive subsequent to their formation and seed repetitive cavitation activity at a discrete set of sites (cavitation memory). Here, we explore a strategy for the removal of these residual bubbles following a cavitation event, using low-amplitude ultrasound pulses to stimulate bubble coalescence. All experiments were conducted in degassed water and monitored using high-speed photography. In each case, a 2-MHz histotripsy transducer was used to initiate cavitation activity (a cavitational bubble cloud), the collapse of which generated a population of residual bubble nuclei. This residual nuclei population was then sonicated using a 1 ms pulse from a separate 500-kHz transducer, which we term the bubble removal pulse. Bubble removal pulse amplitudes ranging from 0 to 1.7 MPa were tested, and the backlit area of shadow from bubbles remaining in the field following bubble removal was calculated to quantify efficacy. It was found that an ideal amplitude range exists (roughly 180 to 570 kPa) in which bubble removal pulses stimulate the aggregation and subsequent coalescence of residual bubble nuclei, effectively removing them from the field. Further optimization of bubble removal pulse sequences stands to provide an adjunct to cavitation-based ultrasound therapies such as shock wave lithotripsy and histotripsy, mitigating the effects of residual bubble nuclei that currently limit their efficacy.


Deep immunophenotyping reveals endometriosis is marked by dysregulation of the mononuclear phagocytic system in endometrium and peripheral blood.
Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single-cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages. A case-control study was designed. Endometrial biopsies and blood (n = 60 total) were obtained from women with (n = 20, n = 17, respectively) and without (n = 14, n = 9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed: one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed. The broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91+ macrophages overexpressed SIRPα (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease. A greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.


New equipment and new technique for measuring activity coefficients and Henry's constants at infinite dilution.
New equipment is presented along with various experimental procedures and setups to cover a large range of applications. It represents a considerable improvement in terms of speed, accuracy, and simplicity with respect to classical gas stripping methods known as "dilutor techniques." Furthermore, range of conditions of its use is larger in terms of: temperatures (from 90 to 600 K), corrosive power, and toxicity of handled compounds. Solutes that could adsorb inside sampling valves or on the walls of transfer lines between sampling valve and GC detector are now studied easily; thanks to new design and procedure. Activity coefficients of one solute into one solvent at five temperatures, several repeatability tests included, are obtained in worst cases in less than 3 h. One accurate activity coefficient measurement (toluene in water) at one temperature can be realized in less than 2 min, after loading of the dilutor cell, instead of more than half an hour for unreliable results with previous equipment. It must be pointed out that the slope determination (slope of the logarithm of the exponential decay of solute composition in vapor phase which is in equilibrium with liquid phase) is the highest source of errors (flow rate, temperature, number of moles of solute are known with high accuracy with respect to slopes); they are now determined within few ‰ instead of up to tens of % in the most difficult cases leading to higher accuracies of measured activity coefficients, Henry's constants at infinite dilutions or solubility data. Successful comparisons with literature data and reproducibility tests are presented herein.


Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements.
Previous cohort studies of fat intake and risk of coronary heart disease (CHD) have been inconsistent, probably due in part to methodological differences and various limitations, including inadequate dietary assessment and incomplete adjustment for total energy intake. The authors analyzed repeated assessment of diet from the Nurses' Health Study to examine the associations between intakes of four major types of fat (saturated, monounsaturated, polyunsaturated, and trans fats) and risk of CHD during 14 years of follow-up (1980-1994) by using alternative methods for energy adjustment. In particular, the authors compared four risk models for energy adjustment: the standard multivariate model, the energy-partition model, the nutrient residual model, and the multivariate nutrient density model. Within each model, the authors compared four different approaches for analyzing repeated dietary measurements: baseline diet only, the most recent diet, and two different algorithms for calculating cumulative average diets. The substantive results were consistent across all models; that is, higher intakes of saturated and trans fats were associated with increased risk of CHD, while higher intakes of monounsaturated and polyunsaturated fats were associated with reduced risk. When nutrients were considered as continuous variables, the four energy-adjustment methods yielded similar associationS. However, the interpretation of the relative risks differed across models. In addition, within each model, the methods using the cumulative averages in general yielded stronger associations than did those using either only baseline diet or the most recent diet. When the nutrients were categorized according to quintiles, the residual and the nutrient density models, which gave similar results, yielded statistically more significant tests for linear trend than did the standard and the partition models.


The curry spice curcumin attenuates beta-amyloid-induced toxicity through beta-catenin and PI3K signaling in rat organotypic hippocampal slice culture.
Accumulating evidence indicates that curcumin potently protects against beta-amyloid (Abeta) due to its oxygen free radicals scavenging and anti-inflammatory properties. However, cellular mechanisms that may underlie the neuroprotective effect of curcumin in Abeta-induced toxicity are not fully understood yet. The present study was undertaken to investigate the mechanisms involved in neuroprotective effects of curcumin, particularly involving Wnt/beta-catenin and PI3K pathways. Organotypic hippocampal slice cultures were treated with curcumin and exposed to Abeta1-42 for 48 hours. Synaptic dysfunction, cell death, ROS formation, neuroinflammation and beta-catenin, Akt, and GSK-3beta phosphorylation were measured to determine the effects of curcumin against Abeta toxicity. Curcumin significantly attenuated Abeta-induced cell death, loss of synaptophysin, and ROS generation. Furthermore, curcumin was able to decrease IL-6 release and increase IL-10 release, and prevented glial activation. The phosphorylation of beta-catenin was avoided and the levels of free beta-catenin were increased by curcumin to promote cell survival upon treatment with Abeta. Curcumin, in the presence of Abeta, activated Akt which in turn phosphorylates GSK-3beta, and resulted in the inhibition of GSK-3beta. The presence of LY294002, an inhibitor of PI3K pathway, blocked the pro-survival effect of curcumin. These results reinforce the neuroprotective effects of curcumin on Abeta toxicity and add some evidence that its mechanism may involve beta-catenin and PI3K signaling pathway in organotypic hippocampal slice culture.


[Demonstration of the tonographic effect in YAG laser trabeculoplasty in chronic glaucoma].
In a pilot study comprising 16 eyes of 16 patients with chronic open-angle glaucoma the tonographic outflow facility was examined before and after Nd-YAG laser treatment of the trabecular meshwork. For evaluation of the facility effect of laser trabeculoplasty, the tonographic record between the third and seventh minute according to the tonography test of Leydhecker was used. An improvement in outflow facility was established which correlated with the postoperative fall in IOP.


Brimonidine-timolol fixed combination induced granulomatous inflammation of the eye.
We report on two cases of granulomatous conjunctivitis and uveitis related with the use of a brimonidine-timolol fixed combination. Case report and a review of medical literature. A 64-year-old man was diagnosed with marked granulomatous uveitis and a 57-year-old woman was diagnosed with granulomatous conjunctivitis. Both patients were using a topical fixed combination of brimonidine 0.2 %-timolol 0.5 % for open angle glaucoma. Bilateral granulomatous uveitis and conjunctivitis were diagnosed after 16 months of treatment with a fixed combination of brimonidine-timolol in both cases. Granulomatous inflammation resolved with the cessation of antiglaucomatous drugs and topical corticosteroid treatment. When the inflammation had resolved completely, both patients were rechallenged with topical brimonidine in one eye only to determine causality. Conjunctival hyperemia is a common side effect of glaucoma medications and is sometimes overlooked. Hyperemia may be associated with other signs such as iritis and keratic precipitates or conjunctival inflammation. In such cases, granulomatous inflammation may be considered in the differential diagnosis. The fixed-combination of brimonidine-timolol may cause this clinical picture.


Treatment of impetigo: oral antibiotics most commonly prescribed.
Impetigo is a highly contagious, superficial skin disease that is frequently seen in children. While data support the use of topical antibiotics for treatment, the medications actually prescribed in practice are not well documented. To determine the prescribing pattern of dermatologists and nondermatologists when treating impetigo and the demographics of the patients treated. National Ambulatory Medical Care Survey data on office visits for impetigo were analyzed from 1997 to 2007. Patient demographics and the treatments for impetigo were recorded. During this 10-year period, dermatologists managed an estimated 274,815 impetigo visits and nondermatologists an estimated 3,722,462 visits. Both dermatologists and nondermatologists most frequently prescribed oral antibiotics to treat impetigo. Topical antibiotics were second most common, and a variety of combination treatments were used. Oral antibiotics are the most common class of medications used to treat impetigo. There is an opportunity for physicians to take advantage of the equally efficacious topical antibiotics for treating impetigo. A shift towards topical antibiotics would likely decrease morbidity (resulting from adverse effects) associated with use of oral agents.


The role of Gamma Knife Radiosurgery in the management of unresectable gross disease or gross residual disease after surgery in ependymoma.
To evaluate the efficacy and the toxicity of Gamma Knife (GK)-based stereotactic radiosurgery (SRS) in the management of gross disease in ependymoma. Eight patients with 13 ependymomas were treated with GK-based SRS in our institution for gross disease. Five patients were treated for recurrent disease that developed after surgery and external beam radiotherapy (EBRT), two received SRS to the gross disease after surgery and EBRT, and one received SRS alone (in a 1.3 year old child). Median EBRT dose was 54.4 Gy (range 50-55.8 Gy). Median SRS dose was 14 Gy (range 12-20 Gy). Seven of eight (87.5%) patients had SRS to a single lesion and one of eight (12.5%) patients had treatment to six tumors in three different sessions. The median follow up was 30.2 months (range 8-65.4 months). Out of the eight patients treated with SRS, six (75%) were alive, four (50%) were alive with no recurrence, two (25%) were alive with recurrence, and two (25%) died of recurrent disease. Both patients treated with SRS as a boost were alive and without recurrence. Out of the five patients who received SRS as salvage treatment, three (60%) were alive, two (40%) were alive without recurrence, two (40%) developed distant failure, and three (60%) had in-field control. Two patients who received SRS to their brainstem lesions developed symptoms related to radionecrosis and were successfully treated with steroid with good control of symptoms. GK-based SRS appears to be a feasible and safe treatment modality for patients with ependymoma with unresectable gross disease or gross residual disease after surgery. SRS provides reasonable local control but out-of-field tumor progression remains an issue. For patients who receive SRS as a boost, the local control appears to be excellent.


Immune restoration with antiretroviral therapies: implications for clinical management.
Recent dramatic decreases in acquired immunodeficiency syndrome-related mortality are largely due to the introduction of highly active antiretroviral therapy (HAART). Although immune restoration due to suppression of human immunodeficiency virus (HIV) replication is a critical determinant of these trends, the magnitude of immune restoration seen after treatment with HAART varies substantially among treated persons and is generally incomplete. Nonetheless, even partial immune restoration is sufficient to provide protection from most major opportunistic infections; these risks can be largely predicted by the number of circulating CD4 cells. Limited data suggest that treatment earlier during the course of HIV infection may result in greater preservation of immune function, though this has not been studied in great detail. Preliminary studies performed among persons with multidrug-resistant virus whose treatment regimens are failing suggest that there is likely a benefit to continuation of therapy that may be related to diminished pathogenicity of drug-resistant virus. As deaths related to opportunistic infections diminish, the spectrum of causes of mortality in HIV infection is changing. Except for Kaposi sarcoma, there is insufficient information to conclude that the risks of non-Hodgkin lymphoma and other malignancies are diminishing among persons with HIV infection. How much immune restoration will be enough to ensure long-term survival in persons with HIV infection remains an open question. JAMA. 2000;284:223-228


Contact Force-Sensing versus Standard Catheters in Non-Fluoroscopic Radiofrequency Catheter Ablation of Idiopathic Outflow Tract Ventricular Arrhythmias.
Adequate contact between the catheter tip and tissue is important for optimal lesion formation and, in some procedures, it has been associated with improved effectiveness and safety. We evaluated the potential benefits of contact force-sensing (CFS) catheters during non-fluoroscopic radiofrequency catheter ablation (NF-RFCA) of idiopathic ventricular arrhythmias (VAs) originating from outflow tracts (OTs). A group of 102 patients who underwent NF-RFCA (CARTO, Biosense Webster Inc., Irvine, CA, USA) of VAs from OTs between 2014 to 2018 was retrospectively analyzed. We included 52 (50.9%) patients in whom NF-RFCA was performed using CFS catheters and 50 (49.1%) who were ablated using standard catheters. Arrhythmias were localized in the right and left OT in 70 (68.6%) and 32 (31.4%) patients, respectively. The RFCA acute success rate was 96.1% (n = 98) and long-term success during a minimum 12-month follow-up (mean 51.3 ± 21.6 months) was 85.3% (n = 87), with no difference between CFS and standard catheters. There was no difference in complications rate between CFS (n = 1) and standard catheter (n = 2) ablations. There is no additional advantage of CFS catheters use over standard catheters during NF-RFCA of OT-VAs in terms of procedural effectiveness and safety.


Treatment of Hypertrophic Burn Scars With Laser Therapy: A Review of Adverse Events.
Hypertrophic scarring, characterized by excessive scar tissue formation, is a debilitating outcome that significantly impairs physical and psychosocial recovery after burn injury. Hypertrophic scarring affects a substantial proportion of burn survivors, with reported prevalence as high as 70%. Fractional CO 2 laser (FCL) therapy, a therapy commonly used in acne scar treatment or skin rejuvenation, has become popular in treating hypertrophic scars. Little is known regarding FCL's adverse events for burn scar treatment. We hypothesize that FCL is a safe treatment modality with minimal adverse events in the management of hypertrophic burn scars. This is a retrospective chart review of adverse events after FCL at 2 centers within a single institution. Burn patients undergoing FCL between May 1, 2019, and June 1, 2021 were included. Demographics, injury etiology, laser treatment details, and adverse events were collected. A total of 170 patients, 77 (45.3%) males and 93 (54.7%) females, underwent 544 FCL therapies for burn scars. The average number of treatments per patient was 3 ± 2.23, with a range of 1 to 17 sessions. From the total 544 laser therapy sessions, 13 adverse events (2.4%) were reported. There were 5 reports (0.9%) of increased postprocedural pain and 1 report (0.2%) of increased paresthesia/numbness to laser site. Three instances (0.6%) of increased erythema and 4 reports (0.7%) of epidermal sloughing or blistering were reported. All but 5 patients (2.9%) reported improvements to scar symptoms. This study demonstrates minimal adverse events associated with FCL for hypertrophic burn scar treatment.


[Metabolic profiling of the short-term responses of Nicotiana tabacum leaves cultivated under different LED lights].
The physiologically mature tobacco (Nicotiana tabacum) leaves was exposed to different light-emitting diode (LED) lights, i.e. ultraviolet A (UV-A), blue, green, yellow, red, white, to investigate their short-term response. Results showed that: 1) 68 GC/MS-stable metabolites were detected by non-targeted method. In the PLS-DA score plot, tobacco leaf samples showed clear grouping in each light cultivating condition. 61 metabolites were identified in mass spectra library. Besides, 45 metabolites, mainly including organic acids, carbohydrates, TCA cycle intermediate metabolites and amino acids, showed significant differences among the six light treatments. Hierarchical cluster analysis (HCA) and heat map showed that differential metabolites could be divided into five groups, and there were significant differences among the six treatments, especially under red and blue lights. Except for the metabolites of group B, almost all other metabolites contents in tobacco leaves treated with red light were higher than those under blue light. 2) Contents of solanesol, 3 alkaloids and 5 polyphenols were measured with targeted method. 4 alkaloids, including nicotine detected by non-targeted method, showed similar variation among all treatments, of which red and yellow light increased alkaloid accumulation significantly. The kaempferol-3-O-rutinoside and rutin showed similar variation among the six treatments, with the lowest content under blue light and the highest content under yellow light, nevertheless, 3 other polyphenols were differently affected by light qualities. The aolanesol accumulation was significantly repressed by yellow light, but showed highest content under blue light. In conclusion, light quality affected many metabolic pathways significantly in tobacco, such as fatty acid metabolism, glycometabolism, alkaloid metabolism, amino acid metabolism, tricarboxylic acid cycle and shikimate pathway.


Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM.
The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM.


[Clinical management of anorexia nervosa in a hospital ward].
The Lou-Andréas-Salomé unit, which specializes in behavioral addictions, is part of the addictology department of the Nantes university hospital center, and offers inpatient care for people suffering from eating disorders. It manages, prevents or limits the consequences of this addictive pathology, based on the work carried out by a multi-professional team focusing on different areas: somatic, psychological, cognitive, social and family.


Registry of the Spanish network for systemic sclerosis: clinical pattern according to cutaneous subsets and immunological status.
To investigate the incidence of clinical and immunological characteristics of a large cohort of Spanish patients with scleroderma (SSc) and identifying factors associated with particular organ manifestations assessed by a nationwide cross-sectional analysis. We classified SSc patients in 4 subsets using a modification of LeRoy and Medsger classification that included: "prescleroderma" (pre-SSc), limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (ssSSc). Fourteen Spanish centers participated in patient recruitment. On January 2008, the database included 916 consecutive Spanish SSc patients, 801 women (87.4%) and 115 men (12.6%), all of whom fulfilled the classification criteria proposed by LeRoy and Medsger. Epidemiological, clinical, and laboratory data were collected according to a standard protocol. Mean age at diagnosis was 51.2 ± 15.1 years and mean age at disease onset was 44.9.0 ± 15.8 years. lcSSc was the most frequent subset (61.8%) followed by dcSSc (26.5%), ssSSc (7.5%), and preSSc (4%) subsets. Gender ratios were as follows: dcSSc subset, 200 women and 43 men (4.7:1); lcSSc subset, 503 women and 63 men (ratio 7.9:1), and ssSSc subset, 62 women and 7 men (ratio 8.9:1). Digital ulcers, interstitial lung disease (ILD), musculoeskeletal and esophageal involvement, and scleroderma renal crisis were more frequent in dcSSc than lcSSc and ssSSc subsets. The incidence of pulmonary arterial hypertension assessed by echocardiography was similar in all subsets but mean estimated systolic pulmonary arterial pressure was higher in ssSSc than in lcSSc subset (47.3 ± 23.9 mm Hg vs 39.6 ± 19.2 mm Hg; P < 0.03). Cardiac involvement was identified more frequently in ssSSc than in dcSSc and lcSSc subsets (49.3% vs 32.5% and 31.1%, respectively; P = 0.015 and P = 0.004 for both comparisons). Acro-osteolysis (8.2% vs 2.4%, P = 0.049), calcinosis (19.8% vs 7.2%, P < 0.05), and sicca syndrome (37.5% vs 14.5%, P < 0.0001) were more frequent in lcSSc than in ssSSc subsets. The frequency of clinical manifestations related to the presence of anticentromere antibodies or antitopoisomerase I antibodies was very similar to that identified in patients categorized to lcSSc and dcSSc, respectively. However, in multivariate studies, the ranking of the variables according to their overall explanatory effect on the model showed that the contributory effect of the antibody status was not greater than that of the clinical categorization into lcSSc and dcSSc for the majority of disease manifestations, but, in important manifestations, as ILD, absence of anticentromere antibodies was an independent predictor factor. The classification of SSc into dcSSc, lcSSc, and ssSSc subsets is the one that most closely reflects the natural history of the disease, as they presented clear clinical differences. The immunological profile helps to define important visceral alteration as ILD. Finally, to improve early diagnosis of SSc, patients with preSSc should be considered both to trace the true evolution of the disease and to define which patients could benefit from therapeutic measures able to prevent the appearance of visceral involvements.


Patterns of East Asian pig domestication, migration, and turnover revealed by modern and ancient DNA.
The establishment of agricultural economies based upon domestic animals began independently in many parts of the world and led to both increases in human population size and the migration of people carrying domestic plants and animals. The precise circumstances of the earliest phases of these events remain mysterious given their antiquity and the fact that subsequent waves of migrants have often replaced the first. Through the use of more than 1,500 modern (including 151 previously uncharacterized specimens) and 18 ancient (representing six East Asian archeological sites) pig (Sus scrofa) DNA sequences sampled across East Asia, we provide evidence for the long-term genetic continuity between modern and ancient Chinese domestic pigs. Although the Chinese case for independent pig domestication is supported by both genetic and archaeological evidence, we discuss five additional (and possibly) independent domestications of indigenous wild boar populations: one in India, three in peninsular Southeast Asia, and one off the coast of Taiwan. Collectively, we refer to these instances as "cryptic domestication," given the current lack of corroborating archaeological evidence. In addition, we demonstrate the existence of numerous populations of genetically distinct and widespread wild boar populations that have not contributed maternal genetic material to modern domestic stocks. The overall findings provide the most complete picture yet of pig evolution and domestication in East Asia, and generate testable hypotheses regarding the development and spread of early farmers in the Far East.


Perivascular Adipose Tissue Oxidative Stress in Obesity.
Perivascular adipose tissue (PVAT) adheres to most systemic blood vessels in the body. Healthy PVAT exerts anticontractile effects on blood vessels and further protects against cardiovascular and metabolic diseases. Healthy PVAT regulates vascular homeostasis via secreting an array of adipokine, hormones, and growth factors. Normally, homeostatic reactive oxygen species (ROS) in PVAT act as secondary messengers in various signalling pathways and contribute to vascular tone regulation. Excessive ROS are eliminated by the antioxidant defence system in PVAT. Oxidative stress occurs when the production of ROS exceeds the endogenous antioxidant defence, leading to a redox imbalance. Oxidative stress is a pivotal pathophysiological process in cardiovascular and metabolic complications. In obesity, PVAT becomes dysfunctional and exerts detrimental effects on the blood vessels. Therefore, redox balance in PVAT emerges as a potential pathophysiological mechanism underlying obesity-induced cardiovascular diseases. In this review, we summarise new findings describing different ROS, the major sources of ROS and antioxidant defence in PVAT, as well as potential pharmacological intervention of PVAT oxidative stress in obesity.


Aspects of sexual precocity and morphometry of uterus, placenta and embryos/fetuses in Piau breed and Commercial line gilts.
In view of the importance of the genetic material of local breeds in the swine industry and the lack of information about reproductive performance of Piau females, two experiments were conducted to evaluate puberty and sexual maturity as well as the morphometry of embryos/fetuses, placenta and uterus during the first 90 days of gestation in Piau breed and Commercial line gilts. In experiment I, 37 Piau and 25 commercial line gilts were used. From the 120 days of age, detection of estrus was performed using mature boars from the first to third estrus of each gilt. Data regarding to age, body weight and estrus duration were recorded. After third estrus, females were slaughtered and ovaries were collected to determine ovulation rate. In experiment II, 36 Piau and 18 commercial line gilts were distributed into three groups according to the mating: Commercial, commercial line females x commercial line male; cross-mated, Piau females x commercial line male; and Piau, Piau females x Piau male. Gilts were slaughtered at 7, 15, 30, 45, 60 and 90 days of pregnancy. Piau females reached puberty and sexual maturity at the same age as commercial line females, but with lower weight; moreover, Piau group showed negative correlations of birth weight with puberty (-0.27) and sexual maturity (-0.29). Commercial gilts presented higher ovulation rate, weight and length of uterus, and length and thoracic circumference of fetuses. Nevertheless, number of fetuses was similar in all groups at 90 days of gestation suggesting that Piau females present higher survival rates of the conceptuses. The results showed differences between the genetic groups related to fetal and placental development, gestational losses, number of ovulations and uterine development. In addition, an intermediate status of fetal weight was observed in Piau/Commercial line crossbred conceptuses; thus, the selection of Piau females on reproductive traits to be mated with commercial line males would be an alternative to contribute to improvement of intramuscular fat content.