[Intracranial aneurysms and autosomal dominant polycystic kidney disease].
Three women aged 55, 47 and 40 years with polycystic kidney disease had several relatives with cystic kidneys, some of whom had died or been crippled after (presumably) a subarachnoid haemorrhage. Two of these patients had a haemorrhage from an aneurysm of a cerebral artery; after clipping of the vessel they recovered without sequelae. The third patient had magnetic resonance (MR) angiography performed, which revealed no aneurysm. The prevalence of intracranial, saccular aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) is about 10%. ADPKD patients with questions about the risk of a subarachnoid haemorrhage should be informed about the need of blood pressure control and the possibility of screening by MR angiography. Diagnosed aneurysms can be treated neurosurgically or endovascularly. Since aneurysms develop in the course of life, screening as a rule is only necessary from the age of 20 years, and its repetition every 5 years should be considered.


Diamagnetic Composites for High-Q Levitating Resonators.
Levitation offers extreme isolation of mechanical systems from their environment, while enabling unconstrained high-precision translation and rotation of objects. Diamagnetic levitation is one of the most attractive levitation schemes because it allows stable levitation at room temperature without the need for a continuous power supply. However, dissipation by eddy currents in conventional diamagnetic materials significantly limits the application potential of diamagnetically levitating systems. Here, a route toward high-Q macroscopic levitating resonators by substantially reducing eddy current damping using graphite particle based diamagnetic composites is presented. Resonators that feature quality factors Q above 450 000 and vibration lifetimes beyond one hour are demonstrated, while levitating above permanent magnets in high vacuum at room temperature. The composite resonators have a Q that is >400 times higher than that of diamagnetic graphite plates. By tuning the composite particle size and density, the dissipation reduction mechanism is investigated, and the Q of the levitating resonators is enhanced. Since their estimated acceleration noise is as low as some of the best superconducting levitating accelerometers at cryogenic temperatures, the high Q and large mass of the presented composite resonators positions them as one of the most promising technologies for next generation ultra-sensitive room temperature accelerometers.


The effect of soy food intake on mineral status in premenopausal women.
Soy foods have been substituted for meat in recent years because of proposed health benefits. Research indicates, however, that soy protein and phytate in soy products inhibit the absorption of divalent cations. Our study was primarily designed to determine the effect of consuming two to three servings per day of soy foods, providing ∼19 g protein and ∼36 mg isoflavones, on iron and zinc status in premenopausal women during a 10-weeks period. As secondary outcomes, we also tested the effect of soy foods on biochemical markers of bone and thyroid hormones. Nonsmoking women (18-28 years) without chronic disease, anemia, pregnancy, or irregular menstrual cycles were randomly assigned to either the soy food (SF, n=31) or animal food (AF, n=32) group. Blood and urine samples and 3-day dietary records were collected at baseline and postintervention. At baseline, iron and zinc status, bone markers, and thyroid hormones were not different between groups. After intervention, no significant changes were observed in hemoglobin, transferrin saturation, serum iron, ferritin, or transferrin receptor (TFR) concentrations. Plasma zinc, but not serum alkaline phosphatase, significantly decreased in both groups (-0.8 μmol/L). The change in bone-specific alkaline phosphatase was significant between SF (1.5 U/L) and AF (-0.7 U/L) groups. No significant changes were observed in bone resorption, thyroid-stimulating hormone (TSH), or free thyroxine after soy food intake. Incorporating ∼19 g soy protein from soy foods for 10 weeks had no significant effect on iron or zinc status, bone resorption or formation, or thyroid hormone status in premenopausal women.


[Cystic dysplasia in the seminal vesicle. Case report and literature review].
Contribution of one case report of cystic dysplasia of the seminal vesicle with ipsilateral renal agenesis in a 32 year-old male presenting with primary infertility. The seminograms showed moderate astenoteratospermia while in the abdominal-pelvic ultrasound there were changes in the right seminal vesicle and right renal agenesis, which was confirmed with further complementary tests: UIV, transrectal ultrasound, urethrocystoscopy, arteriography and renal scan.


Biology, Ecology, and Management of an Invasive Stink Bug, Bagrada hilaris, in North America.
The painted bug, Bagrada hilaris, native to eastern and southern Africa and Asia, was detected in California in 2008, and it has spread rapidly throughout several southwestern US states. A polyphagous insect, it is particularly damaging to the billion dollar cole crop industry. B. hilaris frequently causes damage when it migrates to newly planted crops from weedy hosts. Feeding produces circular or star-shaped chlorotic lesions that become necrotic, and infested plants may be distorted. Currently, no reliable sampling methods for B. hilaris exist, nor are there effective natural enemies in the United States. Therefore, management has relied on multiple applications of insecticides and cultural practices such as removal of weedy hosts, destruction of crop residues, timing of planting, and use of transplants. Several pyrethroid and neonicotinoid insecticides are most effective for controlling the insect. Reliable sampling methods and further development of integrated pest management strategies to manage this invasive pest are urgently needed as its range continues to expand.


[Heredity and the bimanual asymmetry of human finger and palm dermatoglyphs].
An attempt has been made to study the effect of hereditary factors on the asymmetry of morpho-functional quantitative traits, in particular, finger and palm dermatoglyphs (24 indices). The results of examination of 140 twin pairs (83 monozygotic and 57 dizygotic) are presented. The hereditary effects have been found for ten traits when an account is taken of the asymmetry direction, and for nine traits when asymmetry direction is not considered.


Ethical and legal considerations in psychobiography.
Despite psychobiography's long-standing history in the field of psychology, there has been relatively little discussion of ethical issues and guidelines in psychobiographical research. The Ethics Code of the American Psychological Association (APA) does not address psychobiography. The present article highlights the value of psychobiography to psychology, reviews the history and current status of psychobiography in the field, examines the relevance of existing APA General Principles and Ethical Standards to psychobiographical research, and introduces a best practice ethical decision-making model to assist psychologists working in psychobiography. Given the potential impact of psychologists' evaluative judgments on other professionals and the lay public, it is emphasized that psychologists and other mental health professionals have a high standard of ethical vigilance in conducting and reporting psychobiography. (PsycINFO Database Record


[Use of data bank on tuberculosis patients and of computer program for clinical and immunological analysis].
Three hundred and twenty patients with pulmonary tuberculosis were clinically and immunologically compared. The findings support the significance and prospects for using a personal computer while making clinical and laboratory comparisons in different groups of patients for a prompt and objective analysis of available data. Comparative evaluation of the informative value of immunologic tests have indicated that in relation to the major clinical parameters of a tuberculous process, differences are great in those characterizing both T- and B-cell, and specific antimycobacterial immunity. The clinical and immunological findings regarding the specific features of a tuberculosis process may serve as the basis for multidimensional analysis and development of criteria for computer-aided clinical and immunological diagnosis of tuberculosis.


Non-invasive sensing systems for acceleration-induced physiologic changes.
The status of a system under development for detection of gravity-induced loss of consciousness (G-LOC) and subsequent recovery is presented. The physiological factors under investigation for use in the loss-of-consciousness monitoring system (LOCOMS) effort are eye blink rate, head slumping, head-level arterial pulsations, and spectral shift in EEG frequency. Also being studied for inclusion in the LOCOMS are a means of detecting the presence/quality of the anti-G straining maneuver and anti-G suit functions, and a system for voice-synthesized query for interrogating the pilot prior to intervention in aircraft control. The possibility of reducing the length of the period of relative incapacitation that occurs after the pilot regains consciousness is considered.


Comparison of the Effects of Walking with and without Nordic Pole on Upper Extremity and Lower Extremity Muscle Activation.
[Purpose] The aim of this study was to assess the effect of Nordic pole walking on the electromyographic activities of upper extremity and lower extremity muscles. [Subjects and Methods] The subjects were randomly divided into two groups as follows: without Nordic pole walking group (n=13) and with Nordic pole walking group (n=13). The EMG data were collected by measurement while the subjects walking on a treadmill for 30 minutes by measuring from one heel strike to the next. [Results] Both the average values and maximum values of the muscle activity of the upper extremity increased in both the group that used Nordic poles and the group that did not use Nordic poles, and the values showed statistically significant differences. There was an increase in the average value for muscle activity of the latissimus dorsi, but the difference was not statistically significant, although there was a statistically significant increase in its maximum value. The average and maximum values for muscle activity of the lower extremity did not show large differences in either group, and the values did not show any statistically significant differences. [Conclusion] The use of Nordic poles by increased muscle activity of the upper extremity compared with regular walking but did not affect the lower extremity.


Epoxides--is there a human health problem?
The purpose of this review is to consider whether epoxides represent a hazard to human health. Possible means of occupational and non-occupational exposure are discussed with reference to the production and uses of industrially important compounds and other epoxides, such as naturally occurring plant and fungal products. In addition to epoxides themselves, unsaturated compounds that may be metabolised in vivo to epoxides are included, since this appears to be a further important means of exposure. The toxicology, in particular carcinogenicity and mutagenicity, is discussed, along with a brief outline of the biochemistry such as metabolism, binding to cell constituents, and DNA repair mechanisms. The question of interactions between different epoxides in vivo is also raised.


The end of AIDS? HIV and the new landscape of illness in rural South Africa.
The global HIV/AIDS scientific community has begun to hail the dawn of 'the End of AIDS' with widespread anti-retroviral therapy (ART) and dramatic declines in AIDS-related mortality. Drawing on community focus groups and in-depth individual interviews conducted in rural South Africa, we examine the complex unfolding of the end of AIDS in a hard-hit setting. We find that while widespread ART has led to declines in AIDS-related deaths, stigma persists and is now freshly motivated. We argue that the shifting landscape of illness in the community has produced a new interpretive lens through which to view living with HIV and dying from AIDS. Most adults have one or more chronic illnesses, and ART-managed HIV is now considered a preferred diagnosis because it is seen as easier to manage, more responsive to medication, and less dangerous compared to diseases like cancer, hypertension, and diabetes. Viewed through this comparative lens, dying from AIDS elicits stigmatising individual blame. We find that blame persists despite community acknowledgement of structural barriers to ART adherence. Setting the ending of AIDS within its wider health context sheds light on the complexities of the epidemiological and health transitions underway in much of the developing world.


Signal transduction pathways alter the molecular cargo of extracellular vesicles: implications in regenerative medicine.
Extracellular vesicles (EVs) possess regenerative properties and are also considered as future vaccines. All types of cells secrete EVs; however, the amount of EVs secreted by the cells varies under various physiological as well as pathological states. Several articles have reviewed the molecular composition and potential therapeutic applications of EVs. Likewise, the 'sorting signals' associated with specific macromolecules have also been identified, but how the signal transduction pathways prevailing in the parent cells alter the molecular profile of the EVs or the payload they carry has not been sufficiently reviewed. Here, we have specifically discussed the implications of these alterations in the macromolecular cargo of EVs for their therapeutic applications in regenerative medicine.


The biomechanics of pedicle screw-based instrumentation.
There are three basic concepts that are important to the biomechanics of pedicle screw-based instrumentation. First, the outer diameter of the screw determines pullout strength, while the inner diameter determines fatigue strength. Secondly, when inserting a pedicle screw, the dorsal cortex of the spine should not be violated and the screws on each side should converge and be of good length. Thirdly, fixation can be augmented in cases of severe osteoporosis or revision. A trajectory parallel or caudal to the superior endplate can minimise breakage of the screw from repeated axial loading. Straight insertion of the pedicle screw in the mid-sagittal plane provides the strongest stability. Rotational stability can be improved by adding transverse connectors. The indications for their use include anterior column instability, and the correction of rotational deformity.


Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH.
Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown. To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age. In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis. 763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P < 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction < 0.001). In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.


A genetic counselor's reflections on lessons learned, challenges, and successes experienced during a one-year pilot integration in a primary care clinic.
This practice-related insight article describes the experience of a genetic counselor being integrated into a multidisciplinary primary care clinic that provides care for a predominantly marginalized patient population in Victoria, British Columbia, Canada. Reflections on the lessons learned, including challenges and successes during this one-year pilot integration are shared by the genetic counselor in the context of exploring the potential value a genetic counselor can provide while embedded in a primary care clinic. The relationship between clinical genetic counseling practice and a culturally safe and trauma informed approach in primary care is explored, and additional steps are described that can be taken to facilitate more equitable and inclusive access to genetic counseling services for underserved and vulnerable patient populations.


Five-year follow-up of participants in a randomised controlled trial showing benefits from exercise for breast cancer survivors during adjuvant treatment. Are there lasting effects?
In an earlier randomised controlled trial, we showed that early stage breast cancer patients who received a supervised exercise programme, with discussion of behaviour change techniques, had psychological and functional benefits 6 months after the intervention. The purpose of this study was to determine if benefits observed at 6 months persisted 18 and 60 months later. Women who were in the original trial were contacted at 18 and 60 months after intervention. Original measures were repeated. Of the 148 women from the original study who agreed to be contacted again, 114 attended for follow-up at 18 months and 87 at 60 months. Women in the original intervention group reported more leisure time physical activity and more positive moods at 60 months than women in the original control group. Irrespective of original group allocation, women who were more active consistently reported lower levels of depression and increased quality of life compared to those who were less active. We have shown that there are lasting benefits to an exercise intervention delivered during treatment to breast cancer survivors. Regular activity should be encouraged for women with early stage breast cancer as this can have lasting implications for physical and psychological functioning.


Fine mapping of the stem rust resistance gene SrTA10187.
SrTA10187 was fine-mapped to a 1.1 cM interval, candidate genes were identified in the region of interest, and molecular markers were developed for marker-assisted selection and Sr gene pyramiding. Stem rust (Puccinia graminis f. sp. tritici, Pgt) races belonging to the Ug99 (TTKSK) race group pose a serious threat to global wheat (Triticum aestivum L.) production. To improve Pgt host resistance, the Ug99-effective resistance gene SrTA10187 previously identified in Aegilops tauschii Coss. was introgressed into wheat, and mapped to the short arm of wheat chromosome 6D. In this study, high-resolution mapping of SrTA10187 was done using a population of 1,060 plants. Pgt resistance was screened using race QFCSC. PCR-based SNP and STS markers were developed from genotyping-by-sequencing tags and SNP sequences available in online databases. SrTA10187 segregated as expected in a 3:1 ratio of resistant to susceptible individuals in three out of six BC3F2 families, and was fine-mapped to a 1.1 cM region on wheat chromosome 6DS. Marker context sequence was aligned to the reference Ae. tauschii genome to identify the physical region encompassing SrTA10187. Due to the size of the corresponding region, candidate disease resistance genes could not be identified with confidence. Comparisons with the Ae. tauschii genetic map developed by Luo et al. (PNAS 110(19):7940-7945, 2013) enabled identification of a discrete genetic locus and a BAC minimum tiling path of the region spanning SrTA10187. Annotation of pooled BAC library sequences led to the identification of candidate genes in the region of interest-including a single NB-ARC-LRR gene. The shorter genetic interval and flanking KASP™ and STS markers developed in this study will facilitate marker-assisted selection, gene pyramiding, and positional cloning of SrTA10187.


[Summary of the practice guideline for the diagnosis and treatment of ADHD in adolescents and adults with addictions].
Various guidelines are available for the diagnosis and treatment of ADHD in adults, but not for patients with ADHD and a comorbid substance use disorder (SUD). In 2010, the Addiction Medicine Working Party, a division of the VAD (Verenigingvoor Alcohol- en andere Drugproblemen/Association for Alcohol and other Drug Problems) developed a practice guideline on how, when and by whom ADHD can be diagnosed in patients with an addiction, and how these patients should be treated. Given the high prevalence of ADHD in treatment-seeking SUD patients and the availability of valid screening instruments, all SUD patients should be screened for ADHD as soon as their drug use has stabilized. Acquiring information from external sources as well as clinical observation and questionnaires are important tools for the establishment of the diagnosis of ADHD. Integrated treatment primarily includes psycho-education, coaching and cognitive behavioural therapy in addition to pharmacotherapy. Evidence-based treatments for addiction may also be effective in patients with concomitant ADHD, provided the methods are adapted to the limitations that are associated with this condition.


Decorrelated neuronal firing in cortical microcircuits.
Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.


Separating the effects of hypobaria and hypoxia on lettuce: growth and gas exchange.
The objectives of this research were to determine the influence of hypobaria (reduced atmospheric pressure) and reduced partial pressure of oxygen (pO2) [hypoxia] on carbon dioxide (CO2) assimilation (C(A)), dark-period respiration (DPR) and growth of lettuce (Lactuca sativa L. cv. Buttercrunch). Lettuce plants were grown under variable total gas pressures [25 and 101 kPa (ambient)] at 6, 12 or 21 kPa pO2)(approximately the partial pressure in air at normal pressure). Growth of lettuce was comparable between ambient and low total pressure but lower at 6 kPa pO2 (hypoxic) than at 12 or 21 kPa pO2. The specific leaf area of 6 kPa pO2 plants was lower, indicating thicker leaves associated with hypoxia. Roots were most sensitive to hypoxia, with a 50-70% growth reduction. Leaf chlorophyll levels were greater at low than at ambient pressure. Hypobaria and hypoxia did not affect plant water relations. While hypobaria did not adversely affect plant growth or C(A), hypoxia did. There was comparable C(A) and a lower DPR in low than in ambient total pressure plants under non-limiting CO2 levels (100 Pa pCO2, nearly three-fold that in normal air). The C(A)/DPR ratio was higher at low than at ambient total pressure, particularly at 6 kPa pO2- indicating a greater efficiency of C(A)/DPR in low-pressure plants. There was generally no significant interaction between hypoxia and hypobaria. We conclude that lettuce can be grown under subambient pressure ( congruent with25% of normal earth ambient total pressure) without adverse effects on plant growth or gas exchange. Furthermore, hypobaric plants were more resistant to hypoxic conditions that reduced gas exchange and plant growth.


Metformin is synthetically lethal with glucose withdrawal in cancer cells.
Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased dependency on Warburg-like aerobic glycolysis (hyperglycolytic phenotype) is critical to sustain CSC stemness and immortality; (3) the microenvironment-mediated contextual synthetic lethality of metformin should be expected to enormously potentiate the anti-cancer effect of anti-angiogenesis agents that promote severe oxygen and glucose deprivation in certain areas of the tumor tissues.


Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial.
To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort. This study included 256 methotrexate (MTX)-naïve RA patients from a randomised placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd-5th metacarpophalangeal joints at 0, 12, 24, 52 and 104 weeks were obtained and scored using the RAMRIS system. Multivariable logistic regression examined if baseline and early change (weeks 12/24) in RAMRIS scores independently predicted progression of the van der Heijde-Sharp (vdHS) score and MRI erosion score at 1 and 2 years of follow-up. High baseline score and poor improvement over the first 24 weeks in synovitis (p=0.003 and p=0.003, respectively) and in bone oedema (p=0.02 and p=0.001, respectively) were independent predictors of X-ray progression at 1 year. Associations were significant or tended towards an association at 2 years. An increase in RAMRIS bone erosion >0.5 at weeks 12 and 24 also predicted X-ray progression (p<0.003). Poor 12-week improvement in bone oedema was associated with X-ray and MRI progression at 1 year (p<0.05). Regression models that incorporated baseline and 12-week and 24-week changes in MRI measures of synovitis (AUC=0.71) and bone oedema (AUC=0.70) improved the prediction of X-ray progression at 1 year above clinical disease activity alone (AUC=0.66, p<0.04). Baseline and early changes in MRI measures independently predicted X-ray and MRI progression at later time-points. The predictive validity established here supports potential use in shorter-duration studies to determine efficacy of RA therapies in preventing structural damage.


Binding of vitronectin to opa-expressing Neisseria gonorrhoeae mediates invasion of HeLa cells.
Neisseria gonorrhoeae induces local infections in the human genitourinary tract and can disseminate to other organs to cause severe disease. Blood-derived factors present in the genital mucosa have been suggested to facilitate the spread of N. gonorrhoeae in disseminated gonococcal infections. Using gentamicin invasion assays and confocal microscopy, we observed a strong stimulatory effect of fetal calf serum (FCS) on the gonococcal invasion of HeLa cells. FCS-mediated invasion was dependent on the expression of the epithelial cell invasion-associated Opa protein (plasmid-encoded Opa50 or its chromosomal homolog Opa30), while N. gonorrhoeae expressing noninvasive Opa proteins (Opa(51-60)) or no Opa protein (Opa-) was not invasive even in the presence of FCS. Incubation of N. gonorrhoeae MS11 with biotinylated FCS revealed a 78-kDa protein as the prominent protein binding to Opa50- or Opa30-expressing gonococci. This protein was recognized by antibodies against vitronectin (VN) in Western blots. Purified human or bovine VN efficiently bound to Opa50-expressing gonococci, while binding to noninvasive Opa- or Opa52-expressing gonococci was significantly lower. Binding of VN was inhibited by heparin in a concentration-dependent manner, indicating that the heparin binding sites present in VN or Opa50 may play an essential role in this interaction. Based on gentamicin invasion assays and confocal microscopy studies, VN binding was associated with an increased invasion of Opa50- and Opa30-expressing gonococci into HeLa cells. The ability of VN to mediate entry into epithelial cells may constitute an important event in the pathogenesis of local as well as disseminated gonococcal infections.


Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune response and development of postischemic neuronal damage.
Consumption of fish has been shown to reduce risk of coronary heart disease and, possibly, of ischemic stroke. Because docosahexaenoic acid (DHA) is the most likely neuroactive component within fish oil, we hypothesized that exposing mice to a DHA-enriched diet may reduce inflammation and protect neurons against ischemic injury. To visualize the effects of DHA on neuroinflammation after stroke, TLR2-fluc-GFP transgenic mice were exposed to either a control diet, a diet depleted in n-3 polyunsaturated fatty acid, or a diet enriched in DHA during 3 months. Real-time biophotonic/bioluminescence imaging of the TLR2 response was performed before and after middle cerebral artery occlusion, whereas cytokines concentrations and stroke area analyses were performed at 3 and 7 days after middle cerebral artery occlusion, respectively. We show that a 3-month DHA treatment prevented microglial activation after ischemic injury, reduced the ischemic lesion size, and increased levels of the antiapoptotic molecule Bcl-2 in the brain. Additional analysis revealed a significant decrease in the levels of COX2 and IL-1β, but not in other proinflammatory cytokines. Importantly, long-term DHA supplementation significantly changed the n-3:n-6 polyunsaturated fatty acid ratio in the brain. Collectively, these data indicate that diet-induced accumulation of DHA in the brain protects against postischemic inflammation and injury. Because DHA is widely available at low cost and has an excellent safety profile, our data suggest that increased DHA intake may provide protection against acute immune response/brain damage in ischemic stroke.


Multicenter study of homocysteine measurement--performance characteristics of different methods, influence of standards on interlaboratory agreement of results.
After the demonstration that moderate hyperhomocysteinemia is associated with thrombosis, many hematological labs are becoming interested in total homocysteine (tHcy) measurement. This prompted us to organize a collaborative study to investigate the performance of methods used in this setting and to assess the between-lab comparability of results. Two pairs of pooled plasma (A1-A2 and B1-B2) were prepared at the coordinating Center. tHcy levels were normal in A1-A2 and moderately high in B1-B2. Within each pair tHcy levels were similar but not identical. Aliquots were taken from each pool to prepare sets of 100 samples (coded from 1 to 100). Each set consisted of 25 replicates for each pool. Samples were frozen and shipped in dry ice to 16 labs with a common frozen aqueous standard. Labs were asked to measure (in blind) tHcy with their methods and standards. Results were sent to the coordinating Center both as raw readings and as tHcy levels. The following methods were used: High Pressure Liquid Chromatography (HPLC) in 12 labs (home-made in 10 and commercial in 2); Enzyme Immuno Assays (EIA) in 2; Fluorescence Polarization Immunoassay (FPIA) in 2 and Capillary Electrophoresis (CE) in one. Results for paired pools (A1-A2 and B1-B2) were analyzed by the Student t test to assess for the ability to discriminate between similar but not identical tHcy levels. Results for each pool were used to assess within-lab reproducibility and between-lab comparability. Within-lab reproducibility expressed as median CV ranged from 12.6 to 13.9% (home-made HPLC); from 9.2 to 11.4% (commercial HPLC); from 21.8 to 24.2% (EIA); from 2.7 to 3.3% (FPIA) and from 11.2 to 22.0% (CE). All labs, except one using CE and 2 using home-made HPLC, were able to discriminate between similar tHcy levels in the normal range (pools A1-A2). Ten labs (4 using home-made HPLC, 2 commercial HPLC, 2 FPIA, one EIA and one CE) were able to discriminate between similar moderately high tHcy levels (pools B1-B2). Between-lab comparability expressed as CV was 14.0% 13.9%, 15.6% and 14.5% for pools A1, A2, B1, and B2. These values were considerably lower (CV values < 5.2%) when a common plasma standard was used for calculation of tHcy levels, while the use of a common aqueous standard failed to achieve the necessary harmonization. In conclusion, performance characteristics of the FPIA method compare favorably with the well-established HPLC methods. It is simpler and more suitable to be used by general hematological labs. Between-lab comparability of results is still a problem. The establishment of an international plasma standard would be of help to harmonize tHcy measurement across laboratories.


Describing ground and excited state potential energy surfaces for molecular photoswitches using coupled cluster models.
In this article, we use two extensively studied systems, a retinal model system and azobenzene, to explore the use of coupled cluster models for describing ground and singlet excited state potential energy surfaces of photoswitchable systems. While not being suitable for describing nuclear dynamics of photoisomerization, coupled cluster models have useful attributes, such as the inclusion of dynamical correlation, their black box nature, and the systematic improvement offered by truncation level. Results for the studied systems show that when triple excitations (here through the CC3 model) are included, ground and excited state potential energy surfaces for isomerization paths may reliably be generated, also for states of doubly excited character. For ground state equilibrium cis- and trans-azobenzene, the molecular geometry and basis set is seen to significantly impact the vertical excitation energies for the two lowest excited states. Efficient implementations of coupled cluster models can therefore constitute valuable tools for investigating photoswitchable systems and can be used for preliminary black box studies to gather information before more complicated excited state dynamics approaches are pursued.


Dialysis therapy for psoriasis. Report of three cases and review of the literature.
Three patients with psoriasis, who were resistant to all modes of accepted therapy, underwent 32 hours of peritoneal dialysis weekly for ten weeks. In two patients, there was a clearing of 80% of the psoriatic lesions after completion of therapy. In one of these patients, there was a recurrence of the lesions two months later, but the other patient is still in relative remission after 12 months. The third patient had clearing of 50% of the lesions, but there was recurrence two months after cessation of treatment. This experience as well as a review of the literature indicates that dialysis may have a positive effect on psoriasis and that the effect obtained is more prominent with peritoneal dialysis than with hemodialysis.


Construing benefits from adversity: adaptational significance and dispositional underpinnings.
The discovery of benefits from living with adversity has been implicated in psychological well-being in numerous investigations, is pivotal to several prominent theories of cognitive adaptation to threat, and can be predicted by personality differences. This article summarizes the prevalence and adaptive significance of finding benefits from major medical problems, locates the place of benefit-finding in stress and coping theories, and examines how it may be shaped by specific psychological dispositions such as optimism and hope and by broader personality traits such as Extraversion and Openness to Experience. The distinction between beliefs about benefits from adversity (benefit-finding) and the use of such knowledge as a deliberate strategy of coping with the problem (benefit-reminding) is underscored and illustrated by daily process research on coping with chronic pain.


Proteolytic degradation of intestinal mucosal extracellular matrix after lamina propria T cell activation.
Proteoglycans, consisting of glycosaminoglycan (GAG) side chains covalently linked to a protein core, are a major component of the extracellular matrix of the intestinal lamina propria. This study investigated the effects of lamina propria T cell activation on the proteoglycan component of the matrix. The high degree of sulphation of GAGs means that they are polyanionic and thus can be visualised in tissue sections by means of colloidal-gold labelled cationic probes. In human fetal small intestine there is a dense meshwork of anionic residues in the lamina propria and basement membrane. When explants of human fetal small intestine are cultured ex vivo, and resident lamina propria T cells are activated with pokeweed mitogen, mucosal destruction occurs within three days. This is associated with the rapid loss of anionic sites from the lamina propria. Dermatan sulphate proteoglycan is lost from the tissue and is present at increased concentrations in the organ culture supernatants, indicating that T cell activation has led to solubilisation of lamina propria proteoglycans. Tissue destruction and loss of anionic residues are inhibited in a dose dependent fashion by dexamethasone, and by the protease inhibitor, alpha 2 macroglobulin. Proteolytic degradation of the lamina propria may therefore be a mechanism by which T cell hypersensitivity injures the intestinal mucosa.


Mapping of two ugp genes coding for the pho regulon-dependent sn-glycerol-3-phosphate transport system of Escherichia coli.
Two genes, ugpA and ugpB, coding for a binding protein-dependent sn-glycerol-3-phosphate transport system, were mapped at 75.3 min on the Escherichia coli chromosome. A Tn10 insertion in ugpA resulted in loss of transport activity but still allowed the synthesis of the sn-glycerol-3-phosphate-binding protein. This Tn10 insertion was found to be linked by P1 transduction to pit, aroB, malA, asd, and livH with 2.5, 2.8, 25, 63.5, and 83% cotransduction frequency. An insertion of Mud (Ampr lac) in ugpB resulted in the loss of the binding protein. ugpB is closely linked to ugpA. It is either the structural gene for the binding protein or located proximal to it. The analysis of the crosses allowed the ordering of the markers in the clockwise direction as follows: aroB, malA, asd, ugpA, ugpB, livH, pit.


Functional analysis of GmCPDs and investigation of their roles in flowering.
The onset of floral development is a pivotal switch in the life of soybean. Brassinosteroids (BRs), a group of steroidal phytohormones with essential roles in plant growth and development, are associated with flowering induction. Genes involved in BR biosynthesis have been studied to a great extent in Arabidopsis, but the study of these genes has been limited in soybean. In this study, four CPD homologs (GmCPDs) catalyzing BR synthesis were isolated from soybean. Transcripts were mainly confined to cotyledons and leaves and were down-regulated in response to exogenous BR. Bioinformatic analysis showed strong sequence and structure similarity between GmCPDs and AtCPD as well as CPDs of other species. Overexpression of GmCPDs in an Arabidopsis BR-deficient mutant rescued the phenotype by restoring the biosynthesis pathway, revealing the functional roles of each GmCPDs in. Except for the rescue of root development, leaf expansion and plant type architecture, GmCPDs in expression also complemented the late flowering phenotype of Arabidopsis mutants deficient in CPD. Further evidence in soybean plants is that the expression levels of GmCPDs in are under photoperiod control in Zigongdongdou, a photoperiod-sensitive variety, and show a sudden peak upon floral meristem initiation. Together with increased GmCPDs in expression in the leaves and cotyledons of photoperiod-insensitive early-maturity soybean, it is clear that GmCPDs in contribute to flowering development and are essential in the early stages of flowering regulation.


Opposing systematic reviews: the effects of two quality rating instruments on evidence regarding t'ai chi and bone mineral density in postmenopausal women.
This article compares and contrasts two systematic reviews of t'ai chi (TC) interventions on bone mineral density in postmenopausal women. The aim is to examine how chosen quality rating instruments can impact systematic reviews of TC literature. The rating instruments in the reviews, the three-item scale of Jadad et al. and the ad hoc checklist of Wayne et al., were analyzed using Oxman's evaluation criteria for systematic reviews regarding inclusion of articles, interpretation of results, and overall implications for the efficacy of TC on bone mineral density. According to Oxman's criteria, the Jadad scale did not address advances in statistical methods and was not comprehensive enough to adapt to the clinical context or topic. In contrast, the checklist by Wayne et al. was comprehensive, adaptable to clinical context and topical relevance, and compatible with recent developments in statistics and experimental design. These quality rating instruments were critical in the inclusion of studies, analyses, and overall conclusions summarizing the TC literature. The conclusions from the two systematic reviews were starkly opposing; Lee et al. found no convincing evidence, dismissing TC studies as low quality, while Wayne et al. stated that TC may be an effective, safe, and practical intervention. Readers must exercise caution concerning high or low ratings from systematic reviews of TC studies because the choice of quality rating tool can dramatically influence the summary and conclusions of the reviews. There is no consensus on quality rating standards at this time. Of the two, the Jadad scale was not only inadequate but also inappropriate for reviewing TC studies, potentially misleading researchers, clinicians and policymakers. Future systematic reviews of TC should utilize instruments that are updated to current scientific standards, comprehensive, adaptable to clinical context, and relevant to the research topic.


Automated computer-derived prostate volumes from MR imaging data: comparison with radiologist-derived MR imaging and pathologic specimen volumes.
To compare prostate gland volume (PV) estimation of automated computer-generated multifeature active shape models (MFAs) performed with 3-T magnetic resonance (MR) imaging with that of other methods of PV assessment, with pathologic specimens as the reference standard. All subjects provided written informed consent for this HIPAA-compliant and institutional review board-approved study. Freshly weighed prostatectomy specimens from 91 patients (mean age, 59 years; range, 42-84 years) served as the reference standard. PVs were manually calculated by two independent readers from MR images by using the standard ellipsoid formula. Planimetry PV was calculated from gland areas generated by two independent investigators by using manually drawn regions of interest. Computer-automated assessment of PV with an MFA was determined by the aggregate computer-calculated prostate area over the range of axial T2-weighted prostate MR images. Linear regression, linear mixed-effects models, concordance correlation coefficients, and Bland-Altman limits of agreement were used to compare volume estimation methods. MFA-derived PVs had the best correlation with pathologic specimen PVs (slope, 0.888). Planimetry derived volumes produced slopes of 0.864 and 0.804 for two independent readers when compared with specimen PVs. Ellipsoid formula-derived PVs had slopes closest to one when compared with planimetry PVs. Manual MR imaging and MFA PV estimates had high concordance correlation coefficients with pathologic specimens. MFAs with axial T2-weighted MR imaging provided an automated and efficient tool with which to assess PV. Both MFAs and MR imaging planimetry require adjustments for optimized PV accuracy when compared with prostatectomy specimens.


Effects of feed enzymes on nutritive value of soyabean meal fed to broilers.
1. The effects of two enzyme products on the nutritive value of soyabean meal (SBM) were investigated with the emphasis on changes in composition of non-starch polysaccharides (NSP) along the digestive tract. Enzyme A was a commercially available product containing mainly hemicellulase, pectinase, beta-glucanase and some protease activities and Enzyme B was an experimental product with mainly beta-galactanase activity. 2. Enzymes were added at the recommended dosage (normal) and at 5 times the recommended dosage (high) to a semi-purified diet based on maize with SBM as the sole protein source. 3. The enzymes had no effect on digesta viscosity in the jejunum or ileum. 4. Enzyme A at the high dosage significantly (P<0.05) improved AMEN, reduced excreta moisture content and improved ileal protein digestibility. The addition of the same enzyme at the recommended dosage had no effect on any of the above parameters. 5. Analysis of the monosaccharide composition revealed that Enzyme A tended to reduce the amounts of rhamnose and galactose in the soluble and insoluble NSP fractions in thejejunal and ileal digesta. The reduction was significant (P<0.05) when the same enzyme was added at the high dosage. 6. Enzyme B significantly (P<0.05) improved AMEN of the diet but not the growth or the feed conversion ratio (FCR) of the birds. Enzyme B at the high dosage significantly reduced (P<0.05) ileal protein digestibility. 7. Enzyme B significantly (P<0.05) increased the amount of free sugars in thejejunum and reduced (P<0.05) the concentration of soluble NSP in the ileum. 8. Analysis of the monosaccharide composition in the jejunal and ileal digesta showed that this enzyme was highly effective in releasing galactose from both the soluble and insoluble NSP fractions. 9. It is concluded that glycanases with galactanase and pectinase activities supplemented at appropriate dosages can improve the digestibility of the NSP in SBM and increase the metabolisable energy content of the diet containing high levels of SBM. 10. Furthermore, the addition of Enzyme B at the high dosage significantly (P<0.05) reduced protein digestibility without any measurable reduction in growth performance.


Isolation of a new superantigen with potent mitogenic activity to murine T cells from Streptococcus pyogenes.
A mitogenic substance on murine lymphocytes was detected in the culture supernate of Streptococcus pyogenes type 12 strain. This substance had a molecular weight of 28,000 and pI 9.2, and was designated as S. pyogenes mitogen (SPM). The proliferative response of C3H/HeN spleen cells began at 1 ng ml-1 and reached a maximal response at 100 ng ml-1 of SPM for 4 days culture. Anti-Thy 1.2 mAb and complement-treated spleen cells abrogated the proliferative response to any dose of SPM. Although the anti-major histocompatibility complex class 1 mAbs had no blocking effect on proliferation by SPM, this proliferation was substantially inhibited by the addition of either anti-I-A or anti-I-E mAb, and complete inhibition was produced by the addition of both mAbs. Fixed antigen-presenting cells still induced T cell proliferation by SPM. A significant expansion of T cells bearing V beta 13 T-cell receptor was observed up to 73% among the Thy 1.2+ cells in cultures stimulated with SPM, indicating expansion in a V beta-specific manner. Immunoblotting of IEF-separated proteins showed that anti-streptococcal pyrogenic exotoxin (SPE) C reacted with a protein of pI 6.9 and anti-SPEB did not show any reactivity. SPEA was reported to expand V beta 8.1 and 8.2 bearing murine T cells, and SPM did not. SPM also exhibited potent mitogenic activity on human T cells and V beta 21+ T cells were selectively expanded. These results lead to the conclusion that SPM was neither SPEA, B nor C, but a new protein belonging to a group of streptococcal superantigens with activity on not only human but also murine lymphocytes.


Screw Pullout Strength After Pedicle Screw Reposition: A Finite Element Analysis.
Finite element analysis based on computed tomography images from the lumbar spine. Determined the pullout strength of unsatisfactorily placed screws and repositioned screws after unsatisfactory place in lumbar spine surgery. Pedicle screws are widely used to stabilize the spinal vertebral body. Unsatisfactory screws could lead to surgical complications, and may need to be repositioned. Screw removal and reposition, however, may decrease pullout strength. We conducted a three-dimensional finite element analysis based on high-resolution computed tomography images from a 39-year-old healthy woman. Pullout strength was determined with the screw placed in different orientations at the same entry point (as selected by the Magerl method), as well as after removal and reposition. The material properties of the vertebral body and the screw were simulated by using grayscale values and verified data, respectively. A load along the screw axis was applied to the end of the screw to simulate the pullout. The pullout strength was 1840.0 N with the Magerl method. For unsatisfactorily placed screws, the pullout strength was 1500.8 N at 20% overlap, 1609.6 N at 40% overlap, 1628.9 N at 60% overlap, and 1734.7 N at 80% overlap with the hypothetical screw path of the Magerl method. For repositioned screws, the pullout strength was 1763.6 N, with 20% overlap, 1728.3 N at 40% overlap, 1544.0 N at 60% overlap, and 1491.1 N at 80% overlap, with the original path. Comparison of repositioned screw with unsatisfactorily placed screw showed 14.04% decrease in pullout strength at 80% overlap, 5.21% decrease at 60% overlap, 7.37% increase at 40% overlap, and 17.51% increase at 20% overlap, with the screw path of the Magerl method. Removal and reposition increased the pullout strength at 20% and 40% overlap, but decreased the pullout strength at 60% and 80% overlap. For clinical translation, we recommend removal and reposition of the screw when the overlap is in the range of 20% to 40% or less. In vitro specimen studies are needed to verify these preliminary findings.


Multiple Sclerosis in a Multi-Ethnic Population in Houston, Texas: A Retrospective Analysis.
Multiple Sclerosis (MS) is a progressive neurodegenerative disease that affects more than 2 million people worldwide. Increasing knowledge about MS in different populations has advanced our understanding of disease epidemiology and variation in the natural history of MS among White and minority populations. In addition to differences in incidence, African American (AA) and Hispanic patients have greater disease burden and disability in earlier stages of disease compared to White patients. To further characterize MS in AA and Hispanic populations, we conducted a retrospective chart analysis of 112 patients treated at an MS center in Houston, Texas. Here, we describe similarities and differences in clinical presentation, MRI findings, treatment regimens, disability progression, and relapse rate. While we found several similarities between the groups regarding mean age, disability severity, and degree of brain atrophy at diagnosis, we also describe a few divergences. Interestingly, we found that patients who were evaluated by a neurologist at symptom onset had significantly decreased odds of greater disability [defined as Expanded Disability Status Scale (EDSS) > 4.5] at last presentation compared to patients who were not evaluated by a neurologist (OR: 0.04, 95% CI: 0.16-0.9). We also found that active smokers had significantly increased odds of greater disability both at diagnosis and at last clinical encounter compared to nonsmokers (OR: 2.44, 95% CI: 1.10-7.10, OR= 2.44, 95% CI: 1.35-6.12, p = 0.01, respectively). Additionally, we observed significant differences in treatment adherence between groups. Assessment of the degree of brain atrophy and progression over time, along with an enumeration of T1, T2, and gadolinium-enhancing brain lesions, did not reveal differences across groups.


Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women.
Common genetic variants, such as the brain-derived neurotrophic factor (BDNF) Val/66/Met polymorphism (rs6265), are known to interact with environmental factors such as early adversity to increase the risk of subsequent major depression. Much less is known about how they interact with individual differences in cortisol, although these also represent a risk for major depression. To determine whether this BDNF variant moderated the risk represented by higher levels of morning salivary cortisol in adult women. We recruited 279 premenopausal women who were at high risk of major depressive disorder because of either negative self-evaluation, unsupportive core relationship or chronic subclinical symptoms of depression or anxiety. Morning salivary cortisol was measured daily for up to 10 days at entry. Participants were followed up for about 12 months by telephone calls at 3-4 monthly intervals. Major depression and severe life events were assessed through interviews at baseline and follow-up; DNA was obtained from the saliva. There were 53 onsets (19%) of depressive episodes during follow-up. There was a significant U-shaped relationship between adjusted morning cortisol levels at baseline and the probability of depression onset during follow-up. In total, 51% experienced at least one severe life event/difficulty, and this strongly predicted subsequent onsets of depressive episodes. The BDNF Val/66/Met genotype was not directly associated with onsets of depression or with cortisol levels, but there was significant interaction between Val/66/Met and cortisol: the association between baseline cortisol and depression was limited to those with the Val/66/Val variant. There was no interaction between life events and either this BDNF polymorphism or cortisol levels. Morning salivary cortisol interacts with the BDNF Val/66/Met polymorphism in predicting new depressive episodes. This paper adds to the evidence that single gene polymorphisms interact with endogenous factors to predict depression.


Non-consensual condom removal, reported by patients at a sexual health clinic in Melbourne, Australia.
Non-consensual removal of condoms, colloquially referred to as 'stealthing', is the removal of a condom during sex by a sexual partner when consent has been given for sex with a condom only. We conducted a cross-sectional survey to determine how commonly women and men who have sex with men (MSM) attending Melbourne Sexual Health Centre had experienced stealthing, and analysed situational factors associated with the event. Responses were linked to demographic information extracted from patient files. 1189 of 2883 women (41.2%), and 1063 of 3439 MSM (30.9%) attending the clinic during the study period completed the survey. Thirty-two percent of women (95% CI: 29%,35%) and 19% of MSM (95% CI: 17%,22%) reported having ever experienced stealthing. Women who had been stealthed were more likely to be a current sex worker (Adjusted Odds Ratio [AOR] 2.87, 95% CI: 2.01,4.11, p <0.001). MSM who had experienced stealthing were more likely to report anxiety or depression (AOR 2.13, 95% CI: 1.25,3.60, p = 0.005). Both female and male participants who had experienced stealthing were three times less likely to consider it to be sexual assault than participants who had not experienced it (OR 0.29, 95% CI: 0.22,0.4 and OR 0.31, 95% CI: 0.21,0.45 respectively). A high proportion of women and MSM attending a sexual health service reported having experienced stealthing. While further investigation is needed into the prevalence of stealthing in the general community, clinicians should be aware of this practice and consider integrating this question into their sexual health consultation. Understanding situational factors would assist in the development of preventive strategies, particularly female sex workers and MSM.


The Paradox of Declining Female Work Participation in an Era of Economic Growth.
The past three decades have seen the advent of major transformations in the Indian economy. The economy has achieved average growth rates of 5-9 per cent, education has risen sharply for both men and women, fertility rates have declined, and infrastructure facilities, particularly access to electricity, cooking gas and piped water, have improved. All these factors are expected to reduce the demand for women's time spent in domestic chores and increase their opportunities for paid work. Paradoxically, however, the National Sample Surveys document a substantial decline in women's Work Participation Rates (WPRs), particularly for rural women. Optimistic interpretation of these trends suggests that increasing prosperity accounts for women's labour force withdrawal. For young women, rising school and college enrolment is incompatible with demands of the workforce. For both young and older women, rising prosperity allows for withdrawal from economic activities to focus on domestic duties. Pessimistic interpretations of these trends suggest that it is absence of suitable jobs rather than women's withdrawal from the labour force that accounts for declining female work participation. A third explanation focuses on increasing measurement errors in work participation data from the National Sample Surveys. This paper examines these diverse explanations using data from National Sample Surveys and India Human Development Surveys for 2004-5 and 2011-12 and finds that: (1) Decline in rural women's work participation recorded by National Sample Surveys may be overstated; (2) Supply factors explain a relatively small proportion of the decline in women's work participation rates; (3) Public policies such as improvement and transportation facilities and MGNREGS that enhance work opportunities for women are associated with increased participation by women in the work force.


Targeting Cellular Senescence for Age-Related Diseases: Path to Clinical Translation.
Beyond the palliative reach of today's medicines, medical therapies of tomorrow aim to treat the root cause of age-related diseases by targeting fundamental aging mechanisms. Pillars of aging include, among others, genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. The unitary theory of fundamental aging processes posits that by targeting one fundamental aging process, it may be feasible to impact several or all others given its interdependence. Indeed, pathologic accumulation of senescent cells is implicated in chronic diseases and age-associated morbidities, suggesting that senescent cells are a good target for whole-body aging intervention. Preclinical studies using senolytics, agents that selectively eliminate senescent cells, and senomorphics, agents that inhibit production or release of senescence-associated secretory phenotype factors, show promise in several aging and disease preclinical models. Early clinical trials using a senolytic combination (dasatinib and quercetin), and other senolytics including flavonoid, fisetin, and BCL-xL inhibitors, illustrate the potential of senolytics to alleviate age-related dysfunction and diseases including wound healing. Translation into clinical applications requires parallel clinical trials across institutions to validate senotherapeutics as a vanguard for delaying, preventing, or treating age-related disorders and aesthetic aging.


Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase.
Mitochondria are double-membrane-bounded organelles that depend critically on phospholipids supplied by the endoplasmic reticulum. These lipids must cross the outer membrane to support mitochondrial function, but how they do this is unclear. We identify the Voltage Dependent Anion Channel (VDAC), an abundant outer membrane protein, as a scramblase-type lipid transporter that catalyzes lipid entry. On reconstitution into membrane vesicles, dimers of human VDAC1 and VDAC2 catalyze rapid transbilayer translocation of phospholipids by a mechanism that is unrelated to their channel activity. Coarse-grained molecular dynamics simulations of VDAC1 reveal that lipid scrambling occurs at a specific dimer interface where polar residues induce large water defects and bilayer thinning. The rate of phospholipid import into yeast mitochondria is an order of magnitude lower in the absence of VDAC homologs, indicating that VDACs provide the main pathway for lipid entry. Thus, VDAC isoforms, members of a superfamily of beta barrel proteins, moonlight as a class of phospholipid scramblases - distinct from alpha-helical scramblase proteins - that act to import lipids into mitochondria.


Discrepancies in the evaluation of the safety of the human papillomavirus vaccine.
Despite being more than ten years since its introduction, global acceptance to the human papillomavirus (HPV) vaccine is still low. The immunogenetic background of the host, and HPV antigen recognition, are important in natural HPV infection, and should be taken into account in the understanding of adverse autoimmune reactions by the HPV vaccine in certain groups. There is no doubt of the benefit of vaccines in the reduction of the incidence of infectious diseases, and in the case of HPV, the prevention of persistent infection that would lead to cervical cancer. Side-effects, however, should be closely monitored and reported without any bias, to ensure that the benefits of vaccines outweigh the risks of adverse reactions. In this article we bring the attention on certain adverse effects of the vaccine against HPV that have not been well studied as they are not well defined. We also compare the different approaches on HPV vaccine policies regarding its adverse reactions in countries like Japan and Colombia, vs. the recommendations issued by the WHO.


Familial vitamin D resistant rickets: End-organ resistance to 1,25-dihydroxyvitamin D.
Rickets is softening of bones due to defective mineralization of cartilage in the epiphyseal growth plate, leading to widening of ends of long bones, growth retardation, and skeletal deformities in children. The predominant cause is deficiency or impaired metabolism of vitamin D. The observation that some forms of rickets could not be cured by regular doses of vitamin D, led to the discovery of rare inherited abnormalities of vitamin D metabolism or vitamin D receptor. Vitamin D dependent rickets (VDDR) is of two types: Type I is due to defective renal tubular 25-hydroxyvitamin D 1-α hydroxylase and type II is due to end-organ resistance to active metabolite of vitamin D. Typical signs are observed from the first month of life. The patient with rickets described below had markedly increased serum alkaline phosphatase and 1,25-dihydroxyvitamin D. We attribute these abnormalities to impaired end-organ responsiveness to 1,25-dihydroxyvitamin D.


Structure and spatial distribution of the Chironomidae community in mesohabitats in a first order stream at the Poço D'Anta Municipal Biological Reserve in Brazil.
The Chironomidae occupy different habitats along the lotic system with their distribution determined by different factors such as the substrate characteristics and water speed. The input of vegetable material from the riparian forest allows a higher habitat diversity and food to the benthic fauna. The main aim of this paper is to verify the structure and spatial distribution of the Chironomidae fauna in different mesohabitats in a first order stream located at a Biological Reserve in the southeast of Brazil. In the months of July, August, and September 2007, and in January, February, and March 2008, samples were collected with a hand net (250 µm) in the following mesohabitats: litter from riffles, litter from pools, and sediment from pools. The community structure of each mesohabitat was analyzed through the abundance of organisms, taxa richness, Pielou's evenness, Shannon's diversity, and taxa dominance. Similarity among the mesohabitats was obtained by Cluster analysis, and Chironomidae larvae distribution through the Correspondence analysis. Indicator species analysis was used to identify possible taxa preference for a determined mesohabitat. The analyzed mesohabitats showed high species richness and diversity favored by the large environmental heterogeneity. Some taxa were indicators of the type of mesohabitat. The substrate was the main factor that determined taxa distribution in relation to water flow differences (riffle and pool). Stream characteristics such as low water speed and the presence of natural mechanisms of retention may have provided a higher faunistic similarity between the areas with different flows. The results showed that the physical characteristics of each environment presented a close relationship with the structure and spatial distribution of the Chironomidae fauna in lotic systems.


A Review of 101 Consecutive Subcutaneous Mastectomies and Male Chest Contouring Using the Concentric Circular and Free Nipple Graft Techniques in Female-to-Male Transgender Patients.
Many techniques exist for subcutaneous mastectomy in female-to-male transgender patients. The authors review outcomes for two techniques and present an algorithm to aid surgeons in technique selection. One hundred one consecutive female-to-male transgender patients undergoing subcutaneous mastectomy using the concentric circular or free nipple graft technique were retrospectively reviewed. An algorithm for procedure selection was created using classification and regression tree analysis. Aesthetic results (nipple-areola complex, scar, and chest contour) were also independently reviewed. Two hundred two subcutaneous mastectomies were performed (concentric circular, 92 breasts; free nipple graft, 110 breasts). The overall complication rate was 21.3 percent, with 6.4 percent requiring operative intervention (free nipple graft, 1 percent; concentric circular, 13 percent; p < 0.001). The overall revision rate was 23.8 percent (free nipple graft, 12.7 percent; concentric circular, 37.0 percent; p < 0.001). In the concentric circular group, there were 3.3 times the odds of total complications (p = 0.03) and 4.0 times the odds of revision surgery (p < 0.001). Mean aesthetic scores for the concentric circular technique were superior to free nipple graft for scar (3.39 versus 2.62; p < 0.001) and contour (3.82 versus 3.34; p < 0.001). In patients who meet selection criteria, the concentric circular technique is preferred because of fewer scars, improved aesthetic contour, and potential for retained nipple sensation. These patients must be counseled regarding the higher rate of complications and revisions. It was determined that smokers and those with a nipple-to-inframammary fold distance greater than 7 cm or nipple-to-inframammary fold distance less than 7 cm and a body mass index greater than 27 kg/m should undergo the free nipple graft technique because of the increased risk of complications with the concentric circular technique. Therapeutic, III.


Current concept of photocarcinogenesis.
There is ample evidence demonstrating that solar ultraviolet light (UV) induces human skin cancers. First, epidemiological studies have demonstrated a negative correlation between the latitude of residence and incidence and mortality rates of both melanoma and non-melanoma skin cancers in homogeneous populations. Second, skin cancer can be produced in mice by UV irradiation; the action spectrum of photocarcinogenesis falls into UVB (280-320 nm). Third, patients with genetic disorders that lead to deficiencies in repairing UV-induced DNA damage are prone to develop cancers in sun-exposed areas of the skin. Photocarcinogenesis is a multistage process that involves initiation, promotion, and progression. In addition UV induced immunosuppression is closely involved in photocarcinogenesis. Accumulation of DNA lesions caused by UV in several cancer related genes plays a crucial role in carcinogenesis. Indeed, even in actinic keratosis, precancerous lesions, genetic alterations can be observed. A conventional knowledge demonstrated that UVB induced DNA lesion causes genetic mutation (initiation) and UVB-inflammation (sunburn) induces promotion. However recent findings revealed that the photocarcinogenesis pathway is more complex consequences where each of these processes, mediated by various cellular, biochemical, and molecular changes, are closely related to each other. The pyrimidine photoproducts that result from direct DNA damage induced by UV are involved in developing skin cancer through mutations that lead to the upregulation or downregulation of signal transduction pathways, cell cycle dysregulation, and depletion of antioxidant defenses. In addition pyrimidine dimers have been shown to trigger UV induced immunosuppression, which also plays an important role in photocarcinogenesis, partly by upregulation of IL-10, an immunosuppressive cytokine. UV also produces oxidative stress and oxidative DNA damage in skin cells, which cause alteration of the genes involved in the cell cycle, apoptosis and modification of cell signaling by redox regulation, resulting in inflammation. It has been shown that in Ogg1 knockout mice which are deficient in repairing 8-oxo-7, 8-dihydroguanine (8-oxoG), UVB irradiation up-regulates the inflammatory gene, implying that 8-oxoG is involved in triggering inflammation. In this review I summarize the state of the art knowledge regarding photocarcinogenesis including experimental data and implication for clinical viewpoints.


Traumatized index finger pollicization for thumb reconstruction.
When the index finger is injured or severed in conjunction with a traumatic amputation of the thumb, transfer of the injured index finger can restore the important function of the thumb. The purpose of this study is to evaluate the results of the transfer of an injured index finger for traumatic loss of the thumb. Seven patients treated by pedicled transfer of a traumatized index finger after amputation to the ipsilateral thumb were reviewed retrospectively. Postoperative evaluations included thumb range of motion, opposition and pinch function, grasp and pinch strength, sensation, a pick-up test, and a patient-rated appearance of the thumb and hand. Vascular patency of the traumatized index finger and thumb was evaluated in each patient prior to thumb reconstruction. After an average of 4 years of follow-up for surviving patients, all had excellent postoperative function and satisfactory results. The period between injury and thumb reconstruction ranged from 5 months to 4 years. All patients were men with a mean age of 43 years. Amputation levels included the metacarpophalangeal joint in 2 patients, the first metacarpal in 2 patients, and the proximal phalanx in 3 patients. All transferred traumatic index fingers survived without complications. Transfer of the injured index finger to the amputated thumb serves as an excellent adjunct for treatment of traumatic thumb amputations/crush injuries. Consistent results can be obtained while maintaining opposition and protective sensation after this procedure. However, technical demands are great, and initial injuries to the thumb and index finger ultimately determine the final outcomes. Therapeutic IV.


"Best care on home ground" versus "elitist healthcare": concerns and competing expectations for medical tourism development in Barbados.
Many countries have demonstrated interest in expanding their medical tourism sectors because of its potential economic and health system benefits. However, medical tourism poses challenges to the equitable distribution of health resources between international and local patients and private and public medical facilities. Currently, very little is known about how medical tourism is perceived among front line workers and users of health systems in medical tourism 'destinations'. Barbados is one such country currently seeking to expand its medical tourism sector. Barbadian nurses and health care users were consulted about the challenges and benefits posed by ongoing medical tourism development there. Focus groups were held with two stakeholder groups in May, 2013. Nine (n = 9) citizens who use the public health system participated in the first focus group and seven (n = 7) nurses participated in the second. Each focus group ran for 1.5 hours and was digitally recorded. Following transcription, thematic analysis of the digitally coded focus group data was conducted to identify cross-cutting themes and issues. Three core concerns regarding medical tourism's health equity impacts were raised; its potential to 1) incentivize migration of health workers from public to private facilities, 2) burden Barbados' lone tertiary health care centre, and 3) produce different tiers of quality of care within the same health system. These concerns were informed and tempered by the existing a) health system structure that incorporates both universal public healthcare and a significant private medical sector, b) international mobility among patients and health workers, and c) Barbados' large recreational tourism sector, which served as the main reference in discussions about medical tourism's impacts. Incorporating these concerns and contextual influences, participants' shared their expectations of how medical tourism should locally develop and operate. By engaging with local health workers and users, we begin to unpack how potential health equity impacts of medical tourism in an emerging destination are understood by local stakeholders who are not directing sector development. This further outlines how these groups employ knowledge from their home context to ground and reconcile their hopes and concerns for the impacts posed by medical tourism.


Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor.
Dilated cardiomyopathy (DCM) is characterized by a dilated left ventricular cavity with systolic dysfunction manifested by heart failure. It has been revealed that mutations in genes for cytoskeleton or sarcomere proteins cause DCM. However, the disease-causing mutations can be found only in far less than half of patients with a family history, indicating that there should be other disease genes for DCM. Formin homology 2 domain containing 3 (FHOD3) is a sarcomeric protein expressed in the heart that plays an essential role in sarcomere organization during myofibrillogenesis. The purpose of this study was to explore a possible novel disease gene for DCM. We analyzed 48 Japanese familial DCM patients for mutations in FHOD3, and a missense variant, Tyr1249Asn, which was predicted to modify the 3D structure and damage protein function, was found in a case with adult-onset DCM. Functional studies revealed that the DCM-associated mutation significantly reduced the ability to induce actin dynamics-dependent activation of serum response factor, although no remarkable change in the cellular localization was induced in neonatal rat cardiomyocytes transfected with a mutant construct of FHOD3. The DCM-associated FHOD3 variant may cause DCM by interfering with actin filament assembly.


Mucin biosynthesis: identification of the cis-regulatory elements of human C2GnT-M gene.
Mucin glycan is the primary determinant of mucin functions. These functions are expanded by three branch structures, including core 2, core 4, and blood group I, which are synthesized by core 2 beta1,6 N-acetylglucosaminyltransferase-M (C2GnT-M). Alteration of C2GnT-M gene expression is expected to have a profound effect on mucin functions, which prompted us to study the regulation of this gene. Quantitative real-time PCR analysis of the expression of this gene in 24 human tissues and airway epithelial cells showed that this gene was expressed primarily in mucus-secretory tissues. 5' Rapid amplification of cDNA ends analysis, coupled with sequence alignment with human genome database, revealed that this gene was comprised of three exons and two introns. Northern blotting using exon 1 probe showed the presence of this exon in all transcripts, suggesting the presence of cis-regulatory elements in the proximal region upstream of and/or near the transcription initiation site (+1). Analysis of this DNA region (-417/+187) by a promoter-reporter transient transfection assay, coupled with serial deletion and linker scanning mutagenesis, revealed two positive regulatory regions, including -291/-282, and -62/-43. Further, the promoter activity was enhanced by all-trans retinoic acid (ATRA) and IL-13. Thus, the promoter region is specific to hC2GnT-M gene and subject to regulation by ATRA and IL-13. These cis-regulatory elements may be useful for construction of a mucus cell-specific vector for therapy of mucus hypersecretory diseases.


Bioactive chemical compounds in Eremurus persicus (Joub. & Spach) Boiss. essential oil and their health implications.
The genus Eremurus is native to Eastern Europe and temperate Asia. Particularly, Eremurus persicus (Joub. & Spach) Boiss. is highly valued in traditional foods and medicine. Scientific knowledge about E. persicus chemical composition and bioactivity is required. Therefore, the present study is aimed to determine the volatile composition of E. persicus essential oil (EO) by means of gas chromatography coupled to flame ionization/mass spectrometry detection. Moreover, the antioxidant, antimicrobial, anticancer, and acetylcholinesterase inhibitory activities of the EO were tested. Interestingly, the anti-dermatophyte potency was close to that of the drug griseofulvin, with minimum fungicidal concentration ranging between 0.7 and 4.5% depending on the fungi strain. The EO was also effective against hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) human cancer cell lines in a concentration (200-1500 ng/mL)-dependent manner, with a decrease of the cell viability up to 65% and 52%, respectively. The E. persicus EO was rich in terpenes and oxygenated terpene derivatives. Individually, limonene (16.25%), geranylgeraniol (15.23%), n-nonanal (9.48%), geranyl acetone (9.12%), benzene acetaldehyde (8.51%), linalool (7.93%), α-pinene (6.89%), and 1,8-cineol (5.22%) were the most abundant volatile compounds and could be chosen as analytical markers of this essential oil. In conclusion, our results suggested that this EO possesses a wide range of bioactive properties that could be useful in nutraceutical, functional foods and cosmeceutical formulations.


Leptin regulates the expression of angiopoietin-like 6.
Angiopoietin-like 6 (ANGPTL6) is a hepatokine that antagonizes obesity and insulin resistance by increasing energy expenditure. Despite its beneficial effects on metabolism, human studies have shown a paradoxical increase in ANGPTL6 level in the serum of patients with metabolic diseases, which has been interpreted as a compensatory upregulation. However, the regulatory mechanism of ANGPTL6 remains unclear. Since upregulation of ANGPTL6 is induced on metabolic stress, we investigated the hepatic expression of ANGPTL6 by leptin, a representative adipokine of obesity. Mice on a high-fat diet showed increased serum leptin levels and hepatic Angptl6 expression, which were attenuated by exercise training. A single leptin injection also induced hepatic ANGPTL6 expression and increased serum ANGPTL6 levels. In an in vitro model using primary hepatocytes, leptin treatment significantly upregulated ANGPTL6 expression at the mRNA and protein levels, as well as the amount of secreted ANGPTL6 protein in conditioned media. Similarly, exercise training on human participants also showed diminished serum levels of leptin and ANGPTL6. Altogether, these results strongly indicated that hepatic ANGPTL6 expression was determined by leptin.


Signals are informative but slow down responses when drivers meet bicyclists at road junctions.
Three experiments used a laboratory analogue to the task of driving to look at drivers' responses to encounters with a bicyclist at a T-junction. In particular, a comparison was made between the bicyclist indicating an upcoming turn with an arm signal, an informal signal of intent, or no signal. Overall, arm signals worked relatively well to inform drivers of the bicyclist's intentions and were easier to perceive than informal signals. It was also found that simple failures to react to the bicyclist in time were more common at shorter thinking times whereas incorrect positive responses were unaffected by thinking time. Most interestingly, these experiments showed that arm signals often slowed down the participants' decision-making processes, leading to a lower probability of their stopping in time when the bicyclist was at risk. Moreover, the same was true for informal signals in which there was eye-contact between the bicyclist and the participant. It is suggested that these effects come about because both arm signals and eye-contact are communicative acts and therefore invoke extra stages of involuntary cognitive processing in the drivers, thereby slowing their reactions.


Abortion in amsterdam.
Abstract Mortality from abortion is low in the Netherlands to-day, and approximately equal to mortality at delivery. Calculations suggest that about 4,000 abortions occur in Amsterdam every year, of which about 2,100 are induced. The abortion rate shows a very gradual decline after the Second World War. An investigation of the social background of women with induced abortion showed no relationship between occupational group and the incidence of abortion, but a strong negative correlation between religion and abortion. Abortion was more common among women with disturbed relationships in their own or parental families. Induced abortion usually occurred in pregnancies resulting from failure of contraception; these failures were caused not by lack of knowledge of good contraceptives, but by ineffective practice of contraception. The inability to use contraceptive methods in an effective way is related to a lack of communication between the two partners, and to a negative attitude of the women towards sex. An attempt has been made to formulate a theory of the causes of induced abortion among the women interviewed in Amsterdam.


Atmospheric Concentrations of New Persistent Organic Pollutants and Emerging Chemicals of Concern in the Group of Latin America and Caribbean (GRULAC) Region.
A special initiative was run by the Global Atmospheric Passive Sampling (GAPS) Network to provide atmospheric data on a range of emerging chemicals of concern and candidate and new persistent organic pollutants in the Group of Latin America and Caribbean (GRULAC) region. Regional-scale data for a range of flame retardants (FRs) including polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs), and a range of alternative FRs (novel FRs) are reported over 2 years of sampling with low detection frequencies of the novel FRs. Atmospheric concentrations of the OPEs were an order of magnitude higher than all other FRs, with similar profiles at all sites. Regional-scale background concentrations of the poly- and perfluoroalkyl substances (PFAS), including the neutral PFAS (n-PFAS) and perfluoroalkyl acids (PFAAs), and the volatile methyl siloxanes (VMS) are also reported. Ethyl perfluorooctane sulfonamide (EtFOSA) was detected at highly elevated concentrations in Brazil and Colombia, in line with the use of the pesticide sulfluramid in this region. Similar concentrations of the perfluoroalkyl sulfonates (PFAS) were detected throughout the GRULAC region regardless of location type, and the VMS concentrations in air increased with the population density of sampling locations. This is the first report of atmospheric concentrations of the PFAAs and VMS from this region.


Clinical relationships tested by iatrogenicity: the case of haemophiliac patients faced with the epidemic of transfusional AIDS.
After being victims of a serious iatrogenous damage, what kind of relationship can patients rebuild with the world of medicine? In this article, I examine this question in terms of the contaminated blood affair in France. Using a qualitative study of haemophiliac patients and their families as a base, I looked at the changes in their modes of commitment to medicine, from the period preceding contamination with AIDS through blood transfusion, until the present day. It would seem that the experience of iatrogenous injustice was at the root of a major reconfiguration: all of the patients looked back over their trajectories, examined their relationship with the medical world and changed their positions, but without necessarily drawing the same conclusions or taking the same stances. This article looks at the change from relationships essentially based on cooperation to relationships that are more negotiated. It also shows the current diversity in forms of commitment: they are the fruit of critical work, carried out by patients and their families, which reassesses both the cognitive and moral bases of medical legitimacy. The analysis of the reconfiguration of the relationships that haemophiliac patients have had with the medical world in the aftermath of the contaminated blood affair is enlightening in two ways. First of all, the current medical world would appear to be deeply marked by health scandals and the victims have become prime actors. Secondly, the experience of iatrogenicity asks, with especial acuteness, the question of confidence that is at the core of any clinical relationship. It thus has a heuristic value of general scope.


Managed care and its impact on American urology.
America's health care is undergoing a revolution. A previous private, fee-for-service, delivery system chiefly centered around hospital specialty care is rapidly being replaced by a commercialized system of managed care, controlled by businessmen whose prime motive is profit. Increasing emphasis of these managed care organizations is upon primary physicians who function as gatekeepers. While this new commercialized method of health care has been attended with reductions in the previous omnipresent health care inflation our country has experienced for the past several decades, its impact on quality of care and patient choice of physician remain a great concern. Especially vulnerable in this new system are our nation's academic centers, which, burdened with responsibility for education and research, are at a disadvantage in the competitive cost-based bidding for managed care contracts. Urology work force issues and the number of urologists in our nation remain another concern for urologists as they compete for access to patients in this new highly competitive environment. In a 1995 survey of a cohort of urologists in seven states, the respondents reported 35.8% of gross income came from managed care contracts, 86% reported the need for preservice approval for many diagnostic and therapeutic undertakings, 87% reported an inability to refer complex cases outside the Managed Care Organization (MCO) network, and 23% reported they were required to retain patients for treatment who they would have otherwise referred to a more qualified urologist. The majority of American urologists are reporting dropping gross revenues and increasing overhead in their dealings with managed care contracts. The advent of managed care is being attended with dropping gross revenues, increasing overhead costs and interference with the practice patterns of American urologists.


Is elevation of N-terminal pro-B-type natriuretic peptide at discharge associated with 2-year composite endpoint of all-cause mortality and heart failure hospitalisation after transcatheter aortic valve implantation? Insights from a multicentre prospective OCEAN-TAVI registry in Japan.
The aim of this study was to investigate the 2-year prognostic impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at discharge following transcatheter aortic valve implantation (TAVI). Multicentre prospective observational study. Seven institutions from multicentre, observational registry of symptomatic patients with severe aortic stenosis who undergo TAVI. We enrolled 500 consecutive patients who underwent TAVI with measurements of NT-proBNP at discharge between 2013 and 2016. Study patients were stratified into two groups according to survival classification and regression tree (CART) analysis: high versus low NT-proBNP groups. The impact of high NT-proBNP on a 2-year composite endpoint consisting of all-cause mortality and heart failure hospitalisation was evaluated using a multivariable Cox model. Median age was 86 years (quartile 82-89), and 24.2% of the study population were men. Median Society of Thoracic Surgeon score was 7.1 (5.1-9.8), and NT-proBNP at discharge was 1381 (653-3136) pg/mL. The composite endpoint incidence was 13.0% (95% CI 9.5% to 16.3%) at 1 year and 22.3% (95% CI 16.1%-27.9%) at 2 years. The survival CART analysis revealed that the NT-proBNP level required to discern the 2-year composite endpoint was 4288 pg/mL. Elevated NT-proBNP had a statistically significant impact on outcomes, with adjusted HR of 2.21 (95% CI 1.21 to 4.04, p=0.010), and with a significant sex difference (P for interaction=0.003). Elevation of NT-proBNP at discharge is associated with higher incidence of the 2-year composite endpoint after TAVI. 000020423.


Differential expression and internal feedback regulation of 1-aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, and ethylene receptor genes in tomato fruit during development and ripening.
We investigated the feedback regulation of ethylene biosynthesis in tomato (Lycopersicon esculentum) fruit with respect to the transition from system 1 to system 2 ethylene production. The abundance of LE-ACS2, LE-ACS4, and NR mRNAs increased in the ripening fruit concomitant with a burst in ethylene production. These increases in mRNAs with ripening were prevented to a large extent by treatment with 1-methylcyclopropene (MCP), an ethylene action inhibitor. Transcripts for the LE-ACS6 gene, which accumulated in preclimacteric fruit but not in untreated ripening fruit, did accumulate in ripening fruit treated with MCP. Treatment of young fruit with propylene prevented the accumulation of transcripts for this gene. LE-ACS1A, LE-ACS3, and TAE1 genes were expressed constitutively in the fruit throughout development and ripening irrespective of whether the fruit was treated with MCP or propylene. The transcripts for LE-ACO1 and LE-ACO4 genes already existed in preclimacteric fruit and increased greatly when ripening commenced. These increases in LE-ACO mRNA with ripening were also prevented by treatment with MCP. The results suggest that in tomato fruit the preclimacteric system 1 ethylene is possibly mediated via constitutively expressed LE-ACS1A and LE-ACS3 and negatively feedback-regulated LE-ACS6 genes with preexisting LE-ACO1 and LE-ACO4 mRNAs. At the onset of the climacteric stage, it shifts to system 2 ethylene, with a large accumulation of LE-ACS2, LE-ACS4, LE-ACO1, and LE-ACO4 mRNAs as a result of a positive feedback regulation. This transition from system 1 to system 2 ethylene production might be related to the accumulated level of NR mRNA.


Variable In Vivo Hepatitis D Virus (HDV) RNA Editing Rates According to the HDV Genotype.
Human hepatitis delta virus (HDV) is a small defective RNA satellite virus that requires hepatitis B virus (HBV) envelope proteins to form its own virions. The HDV genome possesses a single coding open reading frame (ORF), located on a replicative intermediate, the antigenome, encoding the small (s) and the large (L) isoforms of the delta antigen (s-HDAg and L-HDAg). The latter is produced following an editing process, changing the amber/stop codon on the s-HDAg-ORF into a tryptophan codon, allowing L-HDAg synthesis by the addition of 19 (or 20) C-terminal amino acids. The two delta proteins play different roles in the viral cell cycle: s-HDAg activates genome replication, while L-HDAg blocks replication and favors virion morphogenesis and propagation. L-HDAg has also been involved in HDV pathogenicity. Understanding the kinetics of viral editing rates in vivo is key to unravel the biology of the virus and understand its spread and natural history. We developed and validated a new assay based on next-generation sequencing and aimed at quantifying HDV RNA editing in plasma. We analyzed plasma samples from 219 patients infected with different HDV genotypes and showed that HDV editing capacity strongly depends on the genotype of the strain.


[Hepatic dysfunction correction in patients with obturation jaundice].
Comparative analysis of results of examination and treatment of 54 patients, suffering obturation jaundice syndrome, is presented. The presence and severity of hepatic dysfunction was determined in accordance to indices of cytolysis and cholestasis syndromes, and its severity--in accordance to V. P. Zinevich criteria (1986). There was established, that timely elimination of obturation jaundice, using miniinvasive interventions and subsequent conduction of complex hepatotropic therapy, using L-ornitin L-aspartate, permits to correct hepatic dysfunction effectively.


Ultrasound-induced lung hemorrhage is not caused by inertial cavitation.
In animal experiments, the pathogenesis of lung hemorrhage due to exposure to clinical diagnostic levels of ultrasound has been attributed to an inertial cavitation mechanism. The purpose of this article is to report the results of two experiments that directly contradict the hypothesis that ultrasound-induced lung hemorrhage is caused by inertial cavitation. Elevated hydrostatic pressure was used to suppress the involvement of inertial cavitation. In experiment one, 160 adult mice were equally divided into two hydrostatic pressure groups (0.1 or 1.1 MPa), and were randomly exposed to pulsed ultrasound (2.8-MHz center frequency, 1-kHz PRF, 1.42-micros pulse duration, 10-s exposure duration). For the two hydrostatic pressure groups (80 mice each), 8 in situ peak rarefactional pressure levels were used that ranged between 2.82 and 11.8 MPa (10 mice/group). No effect of hydrostatic pressure on the probability of hemorrhage was observed. These data lead to the conclusion that lung hemorrhage is not caused by inertial cavitation. Also, the higher hydrostatic pressure enhanced rather than inhibited the impact of ultrasonic pressure on the severity (hemorrhage area, depth, and volume) of lesions. These counterintuitive findings were confirmed in a second experiment using a 2 x 5 factorial design that consisted of two ultrasonic pressure levels and five hydrostatic pressure levels (100 mice, 10 mice/group). If inertial cavitation were the mechanism responsible for lung hemorrhage, then elevated hydrostatic pressures should have resulted in less rather than more tissue damage at each ultrasonic pressure level. This further supports the conclusion that the pathogenesis of ultrasound-induced lung hemorrhage is not caused by inertial cavitation.