Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus.
The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of Δ(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior preoptic area, two hypothalamic regions that are richly innervated by GnRH1-containing fibers. This observation suggests that GnRH1 may regulate the formation of sulfated neurosteroids to control sexual activity. Double labeling of frog brain slices with HST and GnRH1 antibodies revealed that GnRH1-immunoreactive fibers are located in close vicinity of HST-positive neurons. The cDNAs encoding 3 GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned from the frog brain. RT-PCR analyses revealed that riGnRHR-1 is strongly expressed in the hypothalamus and the pituitary whereas riGnRHR-2 and -3 are primarily expressed in the brain. In situ hybridization histochemistry indicated that GnRHR-1 and GnRHR-3 mRNAs are particularly abundant in preoptic area and magnocellular nucleus whereas the concentration of GnRHR-2 mRNA in these 2 nuclei is much lower. Pulse-chase experiments using tritiated Δ(5)P and DHEA as steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate as a sulfonate moiety donor, showed that GnRH1 stimulates, in a dose-dependent manner, the biosynthesis of Δ(5)PS and DHEAS in frog diencephalic explants. Because Δ(5)PS and DHEAS, like GnRH, stimulate sexual activity, our data strongly suggest that some of the behavioral effects of GnRH could be mediated via the modulation of sulfated neurosteroid production.


Very low doses of heavy oxygen ion radiation induce premature ovarian failure.
Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET = 179 keV/µm). Adult female mice were irradiated with 0, 5, 30 or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA). Six-hour after irradiation, percentages of ovarian follicles immunopositive for γH2AX, a marker of DNA double strand breaks, 4-HNE, a marker of oxidative lipid damage and BBC3 (PUMA), a proapoptotic BCL-2 family protein, were dose dependently increased in irradiated mice compared to controls. One week after irradiation, numbers of primordial, primary and secondary follicles per ovary were dose dependently decreased, with complete absence of follicles in the 50 cGy groups. The ED50 for primordial follicle destruction was 4.6 cGy for oxygen compared to 27.5 cGy for iron in our previous study. Serum FSH and LH concentrations were significantly elevated in 50 cGy groups at 8 week. Supplementation with ALA mitigated the early effects, but not the ultimate depletion of ovarian follicles. In conclusion, oxygen charged particles are even more potent inducers of ovarian follicle depletion than charged iron particles, raising concern for premature ovarian failure in astronauts exposed to both particles during space travel.


Understanding European integration with bipartite networks of comparative advantage.
Core objectives of European common market integration are convergence and economic growth, but these are hampered by redundancy, and value chain asymmetries. The challenge is how to harmonize labor division to reach global competitiveness, meanwhile bridging productivity differences across the EU. We develop a bipartite network approach to trace pairwise co-specialization by applying the revealed comparative advantage method within and between the EU15 and Central and Eastern European (CEE). This approach assesses redundancies and the division of labor in the EU at the level of industries and countries. We find significant co-specialization among CEE countries but a diverging specialization between EU15 and CEE. Productivity increases in those CEE industries that have co-specialized with other CEE countries after EU accession, while co-specialization across CEE and EU15 countries is less related to productivity growth. These results show that a division of sectoral specialization can lead to productivity convergence between EU15 and CEE countries.


Psychological Factors Including Demographic Features, Mental Illnesses, and Personality Disorders as Predictors in Internet Addiction Disorder.
Objective: Problematic internet use is an important social problem among adolescents and has become a global health issue. This study identified predictors and patterns of problematic internet use among adult students. Method: In this study, 401 students were recruited using stratified sampling technique. Participants were selected among students from 4 universities in Tehran and Karaj, Iran, during 2016 and 2017. Internet Addiction Test (IAT), Millon Clinical Multiaxial Inventory - Third Edition (MCMI-III), Structured Clinical Interview for DSM (SCID-I), and semi-structured interview were used to diagnose internet addiction. Then, the association between main psychiatric disorders and internet addiction was surveyed. Data were analyzed using SPSS18 software by performing descriptive statistics and multiple logistic regression analysis methods. P- Values less than 0.05 were considered statistically significant. Results: After controlling the demographic variables, it was found that narcissistic personality disorder, obsessive- compulsive personality disorder, anxiety, bipolar disorders, depression, and phobia could increase the odds ratio (OR) of internet addiction by 2.1, 1.1, 2.6, 1.1, 2.2 and 2.5-folds, respectively (p-value<0.05), however, other psychiatric or personality disorders did not have a significant effect on the equation. Conclusion: The findings of this study revealed that some mental disorders affect internet addiction. Considering the sensitivity and importance of the cyberspace, it is necessary to evaluate mental disorders that correlate with internet addiction.


Marsupial genome sequences: providing insight into evolution and disease.
Marsupials (metatherians), with their position in vertebrate phylogeny and their unique biological features, have been studied for many years by a dedicated group of researchers, but it has only been since the sequencing of the first marsupial genome that their value has been more widely recognised. We now have genome sequences for three distantly related marsupial species (the grey short-tailed opossum, the tammar wallaby, and Tasmanian devil), with the promise of many more genomes to be sequenced in the near future, making this a particularly exciting time in marsupial genomics. The emergence of a transmissible cancer, which is obliterating the Tasmanian devil population, has increased the importance of obtaining and analysing marsupial genome sequence for understanding such diseases as well as for conservation efforts. In addition, these genome sequences have facilitated studies aimed at answering questions regarding gene and genome evolution and provided insight into the evolution of epigenetic mechanisms. Here I highlight the major advances in our understanding of evolution and disease, facilitated by marsupial genome projects, and speculate on the future contributions to be made by such sequences.


The elasticity of alpha-helices.
The elasticity of alpha-helices is examined using equilibrium molecular-dynamics simulations. From the statistics of curvatures and twists, we compute the elastic moduli of several representative alpha-helices, both in the presence and absence of aqueous solvent. We discover that the bending modulus (persistence length) of the helices is independent of the amino-acid sequence, although helices in water are slightly softer than in vacuum. The response of the helices under the action of an external force is also computed and compared with continuum mechanics predictions. Within the time scale of our simulation, we show that the properties of alpha-helices are well reproduced by an elastic and isotropic rod. The persistence length (bending modulus) of most alpha-helices in water or vacuum is approximately 100 nm, roughly twice that of DNA.


A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom.
A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable. Clinical and electrophysiological examination revealed a compression of the ulnar nerve in the ulnar sulcus and in Guyon's canal. Ultrasound evaluation showed a suspicious tumour proximal to the elbow close to the ulnar nerve. The ulnar sulcus was then released and an epineural and perineural lesion 3-4 cm proximal to the sulcus was excised under microscope. The histopathology confirmed the lesion as non-caseating sarcoid granulomas. The patient showed no other signs of systemic sarcoidosis, as neuropathy was the only symptom and the condition improved postoperatively. Sensory deficits and paraesthesia resolved fully. The extension of the minor finger remained slightly inferior compared with the not affected side. Sarcoid neuropathy is a rare neurological complication of sarcoidosis and has to be included in differential diagnosis of nerve conduction impairments.


Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease.
Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.


The negative association between traditional physical activities and the prevalence of glucose intolerance in Alaska Natives.
The once low prevalence of non-insulin-dependent (Type 2) diabetes (NIDDM) in Eskimos and Indians has risen approximately fourfold over the past 30 years, suggesting the presence of a non-genetic factor affecting NIDDM prevalence. At the same time, traditional physical activities required of a subsistence (self-sufficiency) lifestyle have diminished. Since physical activity has been shown to prevent NIDDM in other populations, we performed a case-control study of physical activity and glucose intolerance in 666 Yup'ik Eskimos and Athabaskan Indians > or = 40 years old in 15 villages in the Yukon Kuskokwim Delta in Alaska. Self-administered questionnaires were used to determine whether subjects participated in a number of traditional activities and/or their modern counterpart (for example, dog sledding and riding motorized vehicles). Intensity values and a score were defined for the activities. Cases included known or newly discovered impaired glucose tolerance or NIDDM. Newly discovered cases were defined by oral glucose tolerance testing of those individuals were screening blood glucose values > or = 6.7 mmol l-1 by random capillary blood glucose testing. Cases included 11 newly discovered (1 with a history of IGT) and 26 known cases of NIDDM, and 17 newly discovered and 1 known cases of IGT. The results showed that, compared to a reference group with low-level physical activity, moderate level physical activity (odds ratio, OR, 0.7, 95% confidence interval [CI] 0.4-1.3) and high level activity (OR 0.2, CI 0.1-0.6) were associated with a lower prevalence of glucose intolerance, adjusted for age, ethnicity, body mass index, and sex.


Adaptation reveals multi-stage coding of visual duration.
In conflict with historically dominant models of time perception, recent evidence suggests that the encoding of our environment's temporal properties may not require a separate class of neurons whose raison d'être is the dedicated processing of temporal information. If true, it follows that temporal processing should be imbued with the known selectivity found within non-temporal neurons. In the current study, we tested this hypothesis for the processing of a poorly understood stimulus parameter: visual event duration. We used sensory adaptation techniques to generate duration aftereffects: bidirectional distortions of perceived duration. Presenting adapting and test durations to the same vs different eyes utilises the visual system's anatomical progression from monocular, pre-cortical neurons to their binocular, cortical counterparts. Duration aftereffects exhibited robust inter-ocular transfer alongside a small but significant contribution from monocular mechanisms. We then used novel stimuli which provided duration information that was invisible to monocular neurons. These stimuli generated robust duration aftereffects which showed partial selectivity for adapt-test changes in retinal disparity. Our findings reveal distinct duration encoding mechanisms at monocular, depth-selective and depth-invariant stages of the visual hierarchy.


Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation.
Accumulation of advanced glycation endproducts (AGEs) in bone tissue occurs in ageing and in Diabetes mellitus, and is partly responsible for the increased risk of low-stress bone fractures observed in these conditions. In this study we evaluated whether the anti-osteoporotic agent strontium ranelate can prevent the deleterious effects of AGEs on bone cells, and possible mechanisms of action involved. Using mouse MC3T3E1 osteoblastic cells in culture we evaluated the effects of 0.1mM strontium ranelate and/or 100 μg/ml AGEs-modified bovine serum albumin (AGEs-BSA) on cell proliferation, osteogenic differentiation and pro-inflammatory cytokine production. We found that AGEs-BSA alone decreased osteoblastic proliferation and differentiation (P<0.01) while increasing IL-1β and TNFα production (P<0.01). On its own, strontium ranelate induced opposite effects: an increase in osteoblast proliferation and differentiation (P<0.01) and a decrease in cytokine secretion (P<0.01). Additionally, strontium ranelate prevented the inhibitory and pro-inflammatory actions of AGEs-BSA on osteoblastic cells (P<0.01). These effects of strontium ranelate were blocked by co-incubation with either the MAPK inhibitor PD98059, or the calcium channel blocker nifedipine. We also evaluated by Western blotting the activation status of ERK (a MAPK) and b-catenin. Activation of both signaling pathways was decreased by AGEs treatment, and this inhibitory effect was prevented if AGEs were co-incubated with strontium ranelate (P<0.01). On its own, strontium ranelate increased both pERK and activated b-catenin levels. In conclusion, this study demonstrates that strontium ranelate can prevent the deleterious in vitro actions of AGEs on osteoblastic cells in culture by mechanisms that involve calcium channel, MAPK and b-catenin activation.


Climate change, crop production and child under nutrition in Ethiopia; a longitudinal panel study.
The amount and distribution of rainfall and temperature influences household food availability, thus increasing the risk of child under nutrition. However, few studies examined the local spatial variability and the impact of temperature and rainfall on child under nutrition at a smaller scale (resolution). We conducted this study to evaluate the effect of weather variables on child under nutrition and the variations in effects across the three agro ecologies of Ethiopia. A longitudinal panel study was conducted. We used crop productions (cereals and oilseeds), livestock, monthly rainfall and temperature, and child under nutrition data for the period of 1996, 1998, 2000 and 2004. We applied panel regression fixed effects model. The study included 43 clusters (administrative zones) and 145 observations. We observed a spatio temporal variability of rainfall, stunting and underweight. We estimated that for a given zone, one standard deviation increase in rainfall leads to 0.242 standard deviations increase in moderate stunting. Additionally, a one standard deviation increase temperature leads to 0.216 standard deviations decrease in moderate stunting. However, wasting was found to be poorly related with rainfall and temperature. But severe wasting showed a positive relationship with the quadratic term of rainfall. We conclude that rainfall and temperature are partly predicting the variation in child stunting and underweight. Models vary in predicting stunting and underweight across the three agro ecologic zones. This could indicate that a single model for the three agro ecologies may not be not applicable.


A Functional Near-Infrared Spectroscopy Study of State Anxiety and Auditory Working Memory Load.
Cognitive studies have suggested that anxiety is correlated with cognitive performance. Previous research has focused on the relationship between anxiety level and the perceptual load within the frontal region, such as the dorsolateral prefrontal and anterior cingulate cortices. High-anxious individuals are predicted to have worse performance on cognitively-demanding tasks requiring efficient cognitive processing. A few functional magnetic resonance imaging studies have specifically discussed the performance and brain activity involving working memory for high-anxious individuals. This topic has been further explored with electroencephalography, although these studies have mostly provided results involving visual face-related stimuli. In this study, we used auditory stimulation to manipulate the working memory load and attempted to interpret the deficiency of cognitive function in high-anxious participants or patients using functional near infrared spectroscopy (fNIRS). The fNIRS signals of 30 participants were measured while they were performing an auditory working memory task. For the auditory n-back task, there were three experimental conditions, including two n-back task conditions of stimuli memorization with different memory load and a condition of passive listening to the stimuli. Hemodynamic responses from frontal brain regions were recorded using a wireless fNIRS device. Brain activation from the ventrolateral and orbital prefrontal cortex were measured with signals filtered and artifacts removed. The fNIRS signals were then standardized with statistical testing and group analysis was performed. The results revealed that there were significantly stronger hemodynamic responses in the right ventrolateral and orbital prefrontal cortex when subjects were attending to the auditory working memory task with higher load. Furthermore, the right lateralization of the prefrontal cortex was negatively correlated with the level of state anxiety. This study revealed the possibility of incorporating fNIRS signals as an index to evaluate cognitive performance and mood states given its flexibility regarding portable applications compared to other neuroimaging techniques.


[Flap endonuclease-1 and its role in the processes of DNA metabolism in eucaryotic cells].
Flap endonuclease-1 (FEN1) is a structure specific endonuclease. The natural substrates of FEN1 are 5'-flap structures formed by three DNA chains one of them has unannealed flapped 5'-end (flap). Flap structures are the intermediates of different processes of DNA metabolism, such as DNA recombination, Okazaki fragment maturation during replication of lagging strand, as well as strand displacement DNA synthesis in base excision repair. FEN1 also possesses 5'-exonuclease activity and newly discovered gap endonuclease activity. FEN1 is known to interact physically and functionally with a number of DNA replication and repair proteins such as the proliferating cell nuclear antigen, helicase/nuclease Dna2, WRN and BLM proteins, replication protein A, apurinic/apyrimidinic endonuclease 1, DNA polymerase beta, poly(ADP-riboso) polymerase 1, high mobility group protein 1, integrase of human immunodeficiency virus, transcription coactivator p300, chromatin proteins, cyclin-dependent kinases (Cdk1, Cdk2, Cyclin A). FEN1 activity is significant for maintaining the integrity of repeat sequences in genome. Recent data suppose the correlation between the abnormality of hFEN1 activity and arising/progression of neurodegenerative and cancer diseases. FEN1 has the dramatic effect on cell growth and development thereby attracting the interest to this enzyme.


Why Muslim women in Northern Ghana do not use skilled maternal healthcare services at health facilities: a qualitative study.
Muslim women are one sub-population in Ghana among whom the rate of skilled maternal health services accessibility and utilisation is very low. However, there are no studies in Ghana that explore the maternity needs and care experiences of Muslim women, and why they do not utilise maternal healthcare services at health facilities. The purpose of this paper is to explore the maternity healthcare needs and care experiences of Muslim women and the barriers to accessing and using maternal health services. Qualitative research was conducted with 94 Muslim women in three communities in northern Ghana between November 2011 and May 2012. Data were analysed using the Attride-Stirling's thematic network analysis framework. Findings suggest that although Muslim women do want to receive skilled care in a health facility, they often experience difficulties with accessing and using such services. These difficulties were often conditioned by a religious obligation to maintain bodily sanctity through modest dressing and the avoidance of unlawful bodily exposure or contact with certain people including male or alien caregivers. Other related access barriers include lack of privacy, healthcare providers' insensitivity and lack of knowledge about Muslim women's religious and cultural practices, and health information that lacked the cultural and religious specificity to meet Muslim women's maternity care needs. Maternal healthcare services designed to meet the needs of mainstream non-Muslim Ghanaian women might lack the flexibility and responsiveness to meet the unique maternity care needs of Muslim women. Recommendations for change include cultural competence training for healthcare providers and cultural/religious matching to meet Muslim women's care needs and to enhance their care experience.


Electrocardiogram Changes with Acute Alcohol Intoxication: A Systematic Review.
Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature. Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes. A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review. Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions. The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.


Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied.


Prevalence, characteristics and a neurocognitive model of mirror-touch synaesthesia.
In so-called 'mirror-touch synaesthesia', observing touch to another person induces a subjective tactile sensation on the synaesthete's own body. It has been suggested that this type of synaesthesia depends on increased activity in neural systems activated when observing touch to others. Here we report the first study on the prevalence of this variant of synaesthesia. Our findings indicate that this type of synaesthesia is just as common, if not more common than some of the more frequently studied varieties of synaesthesia such as grapheme-colour synaesthesia. Additionally, we examine behavioural correlates associated with the condition. In a second experiment, we show that synaesthetic experiences are not related to somatotopic cueing--a flash of light on an observed body part does not elicit the behavioural or subjective characteristics of synaesthesia. Finally, we propose a neurocognitive model to account for these characteristics and discuss the implications of our findings for general theories of synaesthesia.


Novel nonparametric approach to canonical correlation analysis with applications to low CNR functional MRI data.
Detection of activation in functional MRI (fMRI) is often complicated by the low contrast-to-noise ratio (CNR) in the data. The primary source of the difficulty is the fact that for activities that are subtle the signal can be hidden inside the inherent noise in the data. Classical univariate methods based on t-test or F-test are susceptible to noise, as they fail to harness systematic correlations in evoked responses within neighboring voxels. Here the power of a multivariate statistical analysis tool known as canonical correlation analysis (CCA) in fMRI studies is demonstrated where the CNR is low. As a further illustration of the power of the method, a comparative study of CCA and ordinary correlation analysis using simulated data under various noise levels is also performed. A novel nonparametric approach is introduced to calculate the P-values from the distribution of the complicated test statistic. The circumstances under which CCA is a better performer as well as when it is not the case are discussed. As an example, this method is applied to detect hippocampal activation from memory-related tasks.


Mechanisms of exertional fatigue in muscle glycogenoses.
Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis, which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue.


Long-term isolation of a highly mobile seabird on the Galapagos.
The Galapagos Islands are renowned for their high degree of endemism. Marine taxa inhabiting the archipelago might be expected to be an exception, because of their utilization of pelagic habitats-the dispersal barrier for terrestrial taxa-as foraging grounds. Magnificent frigatebirds (Fregata magnificens) have a highly vagile lifestyle and wide geographical distribution around the South and Central American coasts. Given the potentially high levels of gene flow among populations, the species provides a good test of the effectiveness of the Galapagos ecosystem in isolating populations of highly dispersive marine species. We studied patterns of genetic (mitochondrial DNA, microsatellites and nuclear introns) and morphological variation across the distribution of magnificent frigatebirds. Concordant with predictions from life-history traits, we found signatures of extensive gene flow over most of the range, even across the Isthmus of Panama, which is a major barrier to gene flow in other tropical seabirds. In contrast, individuals from the Galapagos were strongly differentiated from all conspecifics, and have probably been isolated for several hundred thousand years. Our finding is a powerful testimony to the evolutionary uniqueness of the taxa inhabiting the Galapagos archipelago and its associated marine ecosystems.


Implementation of a risk-stratified opioid weaning protocol in a pediatric intensive care unit.
Opioids are important in the care of critically ill children. However, their use is associated with complications including delirium, dependence, withdrawal, and bowel dysfunction. Our aim was to implement a risk-stratified opioid weaning protocol to reduce the duration of opioids without increasing the incidence of withdrawal. A pre- and post-interventional prospective study was undertaken in a large children's hospital pediatric ICU where we implemented a risk-stratified opioid weaning protocol. Patients were included if exposed to ≥7days of scheduled opioids. The primary outcome was duration of opioids and secondary outcome was hospital LOS. One hundred seven critically ill children met the inclusion criteria (68 pre-, 39 post-intervention). Demographics, risk factors, and confounders did not differ between groups. Patients in the post-intervention group had shorter duration of opioids (17 vs. 22.5days, p=0.01) and opioid wean (12 vs. 18days, p=0.01). Despite the shorter duration of opioid wean, there was no increase in withdrawal incidence. There was no difference in the LOS (29 vs. 33days, p=0.06). We implemented a risk-stratified opioid weaning protocol for critically ill children that resulted in reduction in opioid exposure without an increase in withdrawal. There was no difference in the LOS.


A new role for FGF2 as an endogenous inhibitor of anxiety.
Human postmortem studies have demonstrated that fibroblast growth factor-2 (FGF2) expression is decreased in the brain of depressed individuals. It remained unclear, however, whether this is a consequence of the illness or whether FGF2 plays a primary role in the control of mood and emotions. In this series of studies, we first ask whether endogenous FGF2 expression correlates with spontaneous anxiety, a trait associated with vulnerability to severe mood disorders in humans. This is tested in two genetically distinct groups of rats selectively bred to differ dramatically in their response to novelty and anxiety-provoking conditions (HRs = low anxiety/high response to novelty vs LRs = high anxiety/low response to novelty). We demonstrate that high-anxiety LRs have significantly lower levels of hippocampal FGF2 mRNA relative to low-anxiety HRs. We then demonstrate that FGF2 expression is modifiable by environmental factors that alter anxiety--thus, environmental complexity reduces anxiety behavior and induces FGF2 expression in hippocampus, particularly in high-anxiety LRs. Finally, we directly test the role of FGF2 as an anxiolytic and show that a 3 week treatment regimen of peripherally administered FGF2 is highly effective at blunting anxiety behavior, specifically in high-anxiety LRs. This treatment is accompanied by an increase in survival of adult-born hippocampal cells, both neurons and astrocytes, most clearly in LRs. These findings implicate hippocampal FGF2 as a central integrator of genetic and environmental factors that modify anxiety, point to hippocampal neurogenesis and gliogenesis as key in this modulation, and underscore FGF2's potential as a new target for treatment of depression and anxiety disorders.


Costs, benefits and effectiveness of worksite physical activity counseling from the employer's perspective.
This study evaluated the impact of worksite physical activity counseling using cost-benefit and cost-effectiveness analyses. Civil servants (N = 299) were randomly assigned to an intervention (N = 131) or control (N = 168) group for 9 months. The intervention costs were compared with the monetary benefits gained from reduced sick leave. In addition, the intervention costs minus the monetary benefits from sick leave reduction were compared with the effects (percentage meeting the public health recommendation for moderate-intensity physical activity, energy expenditure, cardiorespiratory fitness, and upper extremity symptoms). The intervention costs were EUR 430 per participant, and the benefits were EUR 125 due to sick leave during the intervention period, for net total costs of EUR 305 for the intervention. During the same 9-month period the year after the intervention, the benefits from sick leave reduction were EUR 635. No statistically significant differences in costs and benefits were found between the groups. As to the cost-effectiveness, improvement in energy expenditure and cardiorespiratory fitness was observed at higher costs. The point estimates of the cost-effectiveness ratios were EUR 5.2 (without imputation of effect data) and EUR 2.7 (with imputation of effect data) per extra kilocalorie of energy expenditure per day and EUR 235 (without imputation of effect data) and EUR 45.9 (with imputation of effect data) per beat per minute of decrease in submaximal heart rate. This study does not provide a financial reason for implementing worksite counseling intervention on physical activity on the short-term. However, positive effects were shown for energy expenditure and cardiorespiratory fitness.


Noninvasive risk stratification of lung adenocarcinoma using quantitative computed tomography.
Lung cancer remains the leading cause of cancer-related deaths in the United States and worldwide. Adenocarcinoma is the most common type of lung cancer and encompasses lesions with widely variable clinical outcomes. In the absence of noninvasive risk stratification, individualized patient management remains challenging. Consequently a subgroup of pulmonary nodules of the lung adenocarcinoma spectrum is likely treated more aggressively than necessary. Consecutive patients with surgically resected pulmonary nodules of the lung adenocarcinoma spectrum (lesion size ≤3 cm, 2006-2009) and available presurgical high-resolution computed tomography (HRCT) imaging were identified at Mayo Clinic Rochester. All cases were classified using an unbiased Computer-Aided Nodule Assessment and Risk Yield (CANARY) approach based on the quantification of presurgical HRCT characteristics. CANARY-based classification was independently correlated to postsurgical progression-free survival. CANARY analysis of 264 consecutive patients identified three distinct subgroups. Independent comparisons of 5-year disease-free survival (DFS) between these subgroups demonstrated statistically significant differences in 5-year DFS, 100%, 72.7%, and 51.4%, respectively (p = 0.0005). Noninvasive CANARY-based risk stratification identifies subgroups of patients with pulmonary nodules of the adenocarcinoma spectrum characterized by distinct clinical outcomes. This technique may ultimately improve the current expert opinion-based approach to the management of these lesions by facilitating individualized patient management.


Disentangling the genetics of lean mass.
Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.


Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial.
Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time. Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms. The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity. Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure. Australian New Zealand Clinical Trials Registry ACTRN12615000596505.


Gender, Assets, and Agricultural Development: Lessons from Eight Projects.
Ownership of assets is important for poverty reduction, and women's control of assets is associated with positive development outcomes at the household and individual levels. This research was undertaken to provide guidance for agricultural development programs on how to incorporate gender and assets in the design, implementation, and evaluation of interventions. This paper synthesizes the findings of eight mixed-method evaluations of the impacts of agricultural development projects on individual and household assets in seven countries in Africa and South Asia. The results show that assets both affect and are affected by projects, indicating that it is both feasible and important to consider assets in the design, implementation, and evaluation of projects. All projects were associated with increases in asset levels and other benefits at the household level; however, only four projects documented significant, positive impacts on women's ownership or control of some types of assets relative to a control group, and of those only one project provided evidence of a reduction in the gender asset gap. The quantitative and qualitative findings suggest ways that greater attention to gender and assets by researchers and development implementers could improve outcomes for women in future projects.


Correlates and Longitudinal Renal and Cardiovascular Implications of FGF23 Levels in HIV-Positive Individuals.
Fibroblast growth factor23 (FGF23), an early marker of kidney dysfunction, is associated with cardiovascular death. Its role in HIV-positive individuals is unknown. We measured FGF23 in 100 HIV-negative and 191 HIV-positive nondiabetic adults with normal baseline estimated glomerular filtration rate (GFR). We measured GFR by iohexol annually, albumin-creatinine ratio (ACR) every 6 months, as well as pulse wave velocity, carotid plaque, and carotid intima media thickness (IMT) at baseline and 2 years. Progressive albuminuria was defined as follow-up ACR ≥2-fold than baseline and ≥30 mg/g. Regression models assessed associations of FGF23 with baseline factors and longitudinal changes in disease markers. FGF23 levels were similar in HIV serostatus. Among HIV-positive persons, factors independently associated with higher baseline FGF23 levels included female (adjusted ratio of geometric means [95% CI],1.46 [1.21,1.76]), serum phosphorus (1.20 [1.03,1.40]), HCV (1.31 [1.10,1.56]) and non-suppressed HIV RNA (1.27 [1.01,1.76]). At baseline, FGF23 was not associated with GFR, albuminuria, carotid plaque, or carotid IMT in cross-sectionally adjusted analysis of HIV-positive individuals. However, higher baseline FGF23 was associated with progressive albuminuria (odds ratio1.48 [95% CI]:1.05,2.08) and a more rapid increase in IMT (13 μm/year, 95% CI,3,24). These findings suggest a role for FGF23 in HIV-positive populations in identifying patients at greater risk for cardiovascular and kidney disease.


Low-loss hybrid plasmonic waveguide with double low-index nano-slots.
A hybrid plasmonic waveguide with double low-index nano-slots is introduced. The fabrication is simple and compatible with the standard processes for SOI wafers. The theoretical investigation shows that the present hybrid plasmonic waveguide has a low loss and consequently a relatively long propagation distance (at the order of several tens of lambda). For TE polarization, there is a strong field enhancement in the double nano-slots. More power is confined in the low-index nano-slots for a smaller core width. For a 50 nm-wide hybrid plasmonic waveguide with double 10 nm-wide slots, the power confinement factor in the nano-slots is as high as 85% and the effective area is as small as 0.007 microm(2) at 1550 nm. Consequently, the power density in the nano-slots becomes very high, e.g., >120 microm(-2), which is very desired for many applications. For the present hybrid plasmonic waveguide, the lateral dimension could be less than 50 nm and the calculated decoupled separation for two parallel identical waveguides is only 0.62 microm, which is helpful to realize photonic integration circuits with ultra-high integration density.


Novel approach to optical profiler with gradient focal point methods.
Novel gradient focal point (GFP) methods by use of the gradient curvature cylindrical lens, the gradient thickness cylindrical lens and a tilted imaging sensor are proposed for the optical profiler. With the employed simple idea that the different divergence angle of an input beam to the lens generates the different focal position, the height information of one point can be obtained just in a single-shot by GFP approaches. The feasibility of the proposed system is demonstrated to be an alternative to optical profilers.


Does Chorionic Villus Sampling Increase the Risk of Preeclampsia or Gestational Hypertension?
Chorionic villus sampling (CVS) and amniocentesis are two methods for prenatal diagnosis. The goal of this study was to compare amniocentesis and CVS-related complications in a large sample of Iranian women. Medical records of 1624 women who underwent amniocentesis or CVS due to medical indications between 2008 and 2016 were reviewed. Data regarding age, gravidity, parity, gestational age, type of procedure, neonatal weight (and percentile), trisomia, abortion, intrauterine growth restriction (IUGR), severe IUGR, preeclampsia, and gestational hypertension were recorded. Finally, 1215 cases were evaluated. Mean maternal age, gravidity, and gestational age were significantly different between two groups. Preeclampsia, gestational hypertension, IUGR, severe IUGR, and intrauterine fetal death were not significantly different between two groups. Trisomy 18 and 21 were common in cases underwent amniocentesis. Women who underwent CVS are not at higher risk for developing hypertensive disorders than women underwent amniocentesis.


Outcomes associated with amphotericin B lipid complex (ABLC) prophylaxis in high-risk liver transplant patients.
Antifungal prophylaxis with liposomal amphotericin B in high-risk liver transplant recipients is recommended, but experience with amphotericin B lipid complex (ABLC, Abelcet(®)) in this setting is limited. Data from 615 liver transplants performed during 1999-2005 were analyzed retrospectively. High-risk patients (n = 146) received a mean cumulative ABLC dose of 955 ± 609 mg (mean duration of 23.3 ± 11.9 days). Low-risk patients (n = 469) received no prophylaxis. During a mean follow-up of 43.8 ± 29.2 months, fungal infections occurred in 32.2% of ABLC patients versus 43.5% of non-prophylaxis patients (P = 0.015). The overall rate of invasive fungal infection was 12.3% in the ABLC group versus 15.6% in the non-prophylaxis patients (P = 0.34). Any Candida infection (ABLC 29.5%, non-prophylaxis 41.2%, P = 0.011), probable or proven invasive Candida infection requiring systemic antifungal treatment (ABLC 18.5%, non-prophylaxis 32.4%, P = 0.001) and invasive abdominal candidiasis during the first 3 months (ABLC 4.1%, non-prophylaxis 9.2%, P = 0.049) were significantly less frequent in the ABLC group. There was no significant difference between groups in the incidence of Aspergillus infections. The ABLC group showed no evidence of nephrotoxicity. In conclusion, the marked and significant differences in infection rates and requirement for systemic treatment in this large population suggest that targeted use of low-dose ABLC therapy to high-risk patients is a valid prophylactic strategy following liver transplantation.


Bacterial community analysis of drinking water biofilms in southern Sweden.
Next-generation sequencing of the V1-V2 and V3 variable regions of the 16S rRNA gene generated a total of 674,116 reads that described six distinct bacterial biofilm communities from both water meters and pipes. A high degree of reproducibility was demonstrated for the experimental and analytical work-flow by analyzing the communities present in parallel water meters, the rare occurrence of biological replicates within a working drinking water distribution system. The communities observed in water meters from households that did not complain about their drinking water were defined by sequences representing Proteobacteria (82-87%), with 22-40% of all sequences being classified as Sphingomonadaceae. However, a water meter biofilm community from a household with consumer reports of red water and flowing water containing elevated levels of iron and manganese had fewer sequences representing Proteobacteria (44%); only 0.6% of all sequences were classified as Sphingomonadaceae; and, in contrast to the other water meter communities, markedly more sequences represented Nitrospira and Pedomicrobium. The biofilm communities in pipes were distinct from those in water meters, and contained sequences that were identified as Mycobacterium, Nocardia, Desulfovibrio, and Sulfuricurvum. The approach employed in the present study resolved the bacterial diversity present in these biofilm communities as well as the differences that occurred in biofilms within a single distribution system, and suggests that next-generation sequencing of 16S rRNA amplicons can show changes in bacterial biofilm communities associated with different water qualities.


Uptake of heparin cofactor II and antithrombin into the aorta wall after a deendothelializing injury in vivo: comparison with the behaviors of prothrombin and fibrinogen.
The initiation of a denuding injury to the vascular endothelium rapidly leads to a deposition of platelets and fibrin at the site of injury. We have measured previously the responses of rabbit fibrinogen, prothrombin, and antithrombin to a deendothelializing balloon-catheter injury to the rabbit aorta in vivo. In this study, rabbit iodine 125-labeled HCII and iodine 125-labeled AT were coinjected intravenously into anesthetized rabbits 5 minutes before deendothelialization of the thoracic aorta. The rabbit was exsanguinated at 5 to 60 minutes after injury, the aorta was excised, and the accumulation of each radiolabeled protein in each layer of aorta wall was determined relative to the concentration of the respective native protein in circulating blood at exsanguination. The maximum flux rates into the aorta wall (i.e., platelet layer and intima-media) in the first minute after injury were calculated from the uptake data; approximately 2.8 molecules of AT accumulated for each HCII molecule. By comparison with previous measurements, the maximum flux rate of AT was similar to that of prothrombin. Further, the molar ratio of accumulated prothrombin/AT + HCII) in the aorta wall was 0.75. Detergent extracts of the injured aorta intima-media contained unreacted HCII and HCII complexes; the uninjured aorta contained only unreacted HCII. By contrast, high molecular weight AT complexes and unreacted AT were extracted from the uninjured, and in greater quantity from the injured, aorta wall. We conclude that, of the plasma antithrombins, AT accumulated more rapidly than HCII in vivo and appeared to be the more active inhibitor at the site of vascular injury. HCII may play a relatively minor role as an antithrombin and possibly only after injury.


Male suicide rates in German prisons and the role of citizenship.
Prisoners are at a particularly high risk of suicide. In contrast to other psychosocial risk factors it remains unclear to what degree the risk of suicide differs between prisoners with local citizenship and foreigners. In order to provide more detailed information for suicide prevention in prisons, this study aims to compare suicide rates (SR) between these populations in German criminal custody. Based on a German national database of completed suicide in custody, suicides by prisoners were analysed and compared with epidemiological data of the prison population and the general population, stratified for German and foreign citizenship. Data analysis was adjusted for differences in the age distribution of both populations by calculating standard mortality ratios (SMR) for suicide. SR were higher in prisoners with German citizenship than those with foreign citizenship (SR = 76.5 vs. SR = 42.8, P<0.01). This association was not specific to the prison population, as the higher SR in citizens compared to non-citizens (SR = 19.3 vs. SR = 9.0, P<0.01) were also found in the general population. The association between prison suicide and citizenship was comparable in juvenile and adult prisoners, indicating its relevance to both the juvenile and adult detention systems. Imprisonment is associated with a substantially increased risk of suicide in both German and non-German citizens, a finding which needs to be taken into consideration by the justice system. The lower suicide risk in non-German citizens is independent of whether or not they are in custody.


Spreading of liquids on highly curved surfaces.
Because of surface tension, liquid films coating fibers or the insides of capillary tubes are usually unstable and break up into a periodic array of droplets. However, if these films are very thin (of thickness in the range of tens of angstroms), they can be stabilized by long-range van der Waals forces. A simple method for making such wetting films consists of slowly drawing the fiber out of a bath of liquid; the thickness of the film is then measured using a method based on gas chromatography. If these liquid films are thick, and are forced to flow, they may then not break up: the instability becomes "saturated."


Combining SNP discovery from next-generation sequencing data with bulked segregant analysis (BSA) to fine-map genes in polyploid wheat.
Next generation sequencing (NGS) technologies are providing new ways to accelerate fine-mapping and gene isolation in many species. To date, the majority of these efforts have focused on diploid organisms with readily available whole genome sequence information. In this study, as a proof of concept, we tested the use of NGS for SNP discovery in tetraploid wheat lines differing for the previously cloned grain protein content (GPC) gene GPC-B1. Bulked segregant analysis (BSA) was used to define a subset of putative SNPs within the candidate gene region, which were then used to fine-map GPC-B1. We used Illumina paired end technology to sequence mRNA (RNAseq) from near isogenic lines differing across a ~30-cM interval including the GPC-B1 locus. After discriminating for SNPs between the two homoeologous wheat genomes and additional quality filtering, we identified inter-varietal SNPs in wheat unigenes between the parental lines. The relative frequency of these SNPs was examined by RNAseq in two bulked samples made up of homozygous recombinant lines differing for their GPC phenotype. SNPs that were enriched at least 3-fold in the corresponding pool (6.5% of all SNPs) were further evaluated. Marker assays were designed for a subset of the enriched SNPs and mapped using DNA from individuals of each bulk. Thirty nine new SNP markers, corresponding to 67% of the validated SNPs, mapped across a 12.2-cM interval including GPC-B1. This translated to 1 SNP marker per 0.31 cM defining the GPC-B1 gene to within 13-18 genes in syntenic cereal genomes and to a 0.4 cM interval in wheat. This study exemplifies the use of RNAseq for SNP discovery in polyploid species and supports the use of BSA as an effective way to target SNPs to specific genetic intervals to fine-map genes in unsequenced genomes.


Retinoids in the pancreas.
Retinoids (vitamin A and its natural and synthetic analogs) are required by most tissues for maintaining the normal health of the tissue. This is certainly true for the pancreas. The recent literature is convincing that retinoids are needed by the adult to assure normal pancreatic endocrine functions, especially those of the α- and β-cells. It is also well established that retinoids are required to insure normal pancreas development in utero, including the development of the endocrine pancreas. The actions of retinoids for maintaining normal pancreatic islet functions has drawn considerable research interest from investigators interested in understanding and treating metabolic disease. Pancreatic retinoids are also of interest to investigators studying the origins of pancreatic disease, including the development of pancreatic fibrosis and its sequelae. This research interest is focused on pancreatic stellate cells (PSCs) which store retinoids and possess the metabolic machinery needed to metabolize retinoids. The literature on pancreatic disease and retinoids suggests that there is an association between impairments in pancreatic retinoid storage and metabolism and the development of pancreatic disease. These topics will be considered in this review.


Guided wave propagation in a honeycomb composite sandwich structure in presence of a high density core.
A coordinated theoretical, numerical and experimental study is carried out in an effort to interpret the characteristics of propagating guided Lamb wave modes in presence of a high-density (HD) core region in a honeycomb composite sandwich structure (HCSS). Initially, a two-dimensional (2D) semi-analytical model based on the global matrix method is used to study the response and dispersion characteristics of the HCSS with a soft core. Due to the complex structural characteristics, the study of guided wave (GW) propagation in HCSS with HD-core region inherently poses many challenges. Therefore, a numerical simulation of GW propagation in the HCSS with and without the HD-core region is carried out, using surface-bonded piezoelectric wafer transducer (PWT) network. From the numerical results, it is observed that the presence of HD-core significantly decreases both the group velocity and the amplitude of the received GW signal. Laboratory experiments are then conducted in order to verify the theoretical and numerical results. A good agreement between the theoretical, numerical and experimental results is observed in all the cases studied. An extensive parametric study is also carried out for a range of HD-core sizes and densities in order to study the effect due to the change in size and density of the HD zone on the characteristics of propagating GW modes. It is found that the amplitudes and group velocities of the GW modes decrease with the increase in HD-core width and density.


The Effect of Nasal Obstruction after Different Nasal Surgeries Using Acoustic Rhinometry and Nasal Obstruction Symptom Evaluation Scale.
The efficiency of nasal surgeries can be determined by objective or subjective methods. We have assessed the effect of nasal obstruction after different nasal surgeries using Acoustic Rhinometry (AR) and Nasal Obstruction Symptom Evaluation (NOSE) Scale. Between May 2011 and May 2012, 40 young adult patients and 10 healthy volunteers as control group who referred to Otorhinolaryngology Clinic in Eskisehir Military Hospital due to nasal obstruction were enrolled. Depending on operation, patients were divided into four equal groups. Group 1: Septoplasty, Group 2: Septoplasty with sprader graft, Group 3: Septorinoplasty and Group 4: Septorhinoplasty with spreader graft. The patients completed NOSE scale, 1 week before and 1 month after the surgery and AR measurements. There were a significant improvement in mean NOSE scores of patients and statistical difference was found between pre and post-operational values for each group. There was a statistically significant change of the mean minimal cross section areas (MCA) of the deviated side of nasal passages measured by AR between pre and postoperative period. In patients with nasal obstruction, functional nasal surgeries which were performed after appropriate medical examination and with right operation methods had a positive impact on quality of life and patient satisfaction. We observed that nasal findings were correlated with NOSE scores and MCA values. So, we suggest that NOSE scale and AR to be used for evaluation of the efficiency of functional nasal surgeries.


Elicitation of health state utilities associated with differing durations of morning stiffness in rheumatoid arthritis.
Specific symptoms of rheumatoid arthritis (RA), including joint stiffness and functional disability, are most severe in the morning. 'Morning stiffness' has a negative impact on health-related quality-of-life (HRQoL); however, how HRQoL is correlated to morning stiffness duration is unknown. The objective of this study was to obtain population-based utility values associated with different durations of morning stiffness in RA. The time-trade-off (TTO) approach was used to elicit utility values for four different health states (HS), which differed in morning stiffness duration. One hundred and nine members of the UK general public rated each HS in individual face-to-face interviews with trained investigators. TTO scores were converted into utility values. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. On a scale of 0 (death) to 1 (full health), a mean utility value of 0.45±0.29 was elicited for ∼3 h of morning stiffness (anchor HS), 0.50±0.28 for 2-3 h of morning stiffness (HS1), 0.61±0.25 for 1-2 h of morning stiffness (HS2) and 0.78±0.20 for <1 h of morning stiffness (HS3). The difference between each HS was statistically significant (p<0.01). Mean VAS utility scores followed the same trend. Utility incrementally increased with each HS associated with a shorter duration of morning stiffness. Limitations of this research include potential bias from the TTO method due to the discounting effect of time, scale compatibility, and loss aversion. The UK population-based utility values show a reduction in morning stiffness duration in RA is associated with improved HRQoL. Despite the impact of morning stiffness on HRQoL, it is rarely evaluated and little is known as to how it is affected by current treatments. The results of this study can be applied in future cost-utility analyses of healthcare interventions which target an improvement in morning stiffness duration for RA patients.


Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women: the Iowa Women's Health Study.
Recent epidemiological studies suggest that there is an inverse association between the frequent consumption of nuts and the risk of coronary heart disease (CHD), and clinical investigations suggest that diets high in nuts may reduce serum cholesterol levels. This study assessed whether the risk of death due to CHD and all causes is reduced in postmenopausal women who frequently consume nuts. In 1986, 34,111 postmenopausal women with no known cardiovascular disease reported the frequency of their consumption of nuts and other foods, as well as other CHD risk factors. During approximately 12 years of follow-up, 3726 women died, 657 from CHD. After adjustment for multiple risk factors for CHD and dietary variables, there was an inverse but not statistically significant association between frequent nut consumption (two or more 28.5 g servings per week compared with less than one serving per month) and death from CHD (relative risk 0.81; 95% confidence interval: 0.60-1.11). There was also a weak inverse association between frequent nut intake and all-cause mortality (relative risk 0.88; 95% confidence interval: 0.77-0.99, p for trend = 0.047). Frequent nut consumption may offer postmenopausal women modest protection against the risk of death from all causes and CHD.


Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population.
Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.


Role of volatile fatty acids in colonization resistance to Clostridium difficile.
The in vitro inhibition of Clostridium difficile by volatile fatty acids was correlated with the pH and concentrations of volatile fatty acids in the ceca of hamsters of different ages. The concentrations of cecal volatile fatty acids increased with the age of the animals. Maximum concentrations of individual volatile fatty acids were attained when the animals were ca. 19 days old, with acetic, propionic, and butyric acids occurring in the highest concentrations (72, 16, and 32 microequivalents/g of cecum, respectively). The cecal pH was approximately the same in hamsters of all ages (pH 6.6 to 7.0). Only butyric acid reached a concentration in the ceca of hamsters which was inhibitory to the in vitro multiplication of C. difficile. This inhibitory concentration was attained when the animals were ca. 19 days of age. When mixtures of volatile fatty acids were prepared at concentrations equal to those present in the ceca of hamsters, there was a direct correlation between the in vitro inhibitory activity of the volatile fatty acids and the susceptibility of hamsters 4 days of age or older to C. difficile intestinal colonization. The resistance of hamsters less than 4 days of age to C. difficile intestinal colonization appears to be due to factors other than volatile fatty acids.


Interferometric optical vortex array generator.
Two new interferometric configurations for optical vortex array generation are presented. These interferometers are different from the conventional interferometers in that they are capable of producing a large number of isolated zeros of intensity, and all of them contain optical vortices. Simulation and theory for optical vortex array generation using three-plane-wave interference is presented. The vortex dipole array produced this way is noninteracting, as there are no attraction or repulsion forces between them, leading to annihilation or creation of vortex pairs.


De Novo Transcriptome Characterization of a Sterilizing Trematode Parasite (Microphallus sp.) from Two Species of New Zealand Snails.
Snail-borne trematodes represent a large, diverse, and evolutionarily, ecologically, and medically important group of parasites, often imposing strong selection on their hosts and causing host morbidity and mortality. Even so, there are very few genomic and transcriptomic resources available for this important animal group. We help to fill this gap by providing transcriptome resources from trematode metacercariae infecting two congeneric snail species, Potamopyrgus antipodarum and P. estuarinus This genus of New Zealand snails has gained prominence in large part through the development of P. antipodarum and its sterilizing trematode parasite Microphallus livelyi into a textbook model for host-parasite coevolutionary interactions in nature. By contrast, the interactions between Microphallus trematodes and P. estuarinus, an estuary-inhabiting species closely related to the freshwater P. antipodarum, are relatively unstudied. Here, we provide the first annotated transcriptome assemblies from Microphallus isolated from P. antipodarum and P. estuarinus We also use these transcriptomes to produce genomic resources that will be broadly useful to those interested in host-parasite coevolution, local adaption, and molecular evolution and phylogenetics of this and other snail-trematode systems. Analyses of the two Microphallus transcriptomes revealed that the two trematode types are more genetically differentiated from one another than are the M. livelyi infecting different populations of P. antipodarum, suggesting that the Microphallus infecting P. estuarinus represent a distinct lineage. We also provide a promising set of candidate genes likely involved in parasitic infection and response to salinity stress.


[Treatment of hot flashes in women with a previous diagnosis of breast cancer].
Due to the huge prescription of adjuvant chemotherapy and hormonotherapy, the number of breast cancer survivors with hot flashes is to raise. Hormone replacement therapy is typically withheld from women with previous breast cancer. Treatment should begin with a careful patient history, with specific attention to the frequency and severity of hot flashes and their effect on the individual's function. For mild symptoms that do not interfere with sleep or daily activity, behavioural changes or treatments like soy phyto-oetrogens or vitamin E could be a reasonable initial approach. For more severe symptoms, several alternative substances have therefore been investigated. The use of clonidine and gabapentine should be discouraged because of their modest efficacy and adverse effects. Newer antidepressants (selective serotonin reuptake inhibitors) that are the best studied drugs to date, appear promising as therapy for women with hot flashes. The decrease in hot flashes achieved with progestational agents is similar to that seen with oestrogen therapy but there is debate about the safety of long term use of progestational agents in patients with a history of breast cancer. If hot flashes are particularly troublesome and do not respond to alternative approaches, quality of life must be balanced against theoretical risk of tumour promotion before choosing to use hormone replacement therapy to control these symptoms.


Splashing Threshold of Oblique Droplet Impacts on Surfaces of Various Wettability.
Oblique drop impacts were performed at high speeds (up to 27 m/s, We > 9000) with millimetric water droplets, and a linear model was applied to define the oblique splashing threshold. Six different sample surfaces were tested: two substrate materials of different inherent surface wettability (PTFE and aluminum), each prepared with three different surface finishes (smooth, rough, and textured to support superhydrophobicity). Our choice of surfaces has allowed us to make several novel comparisons. Considering the inherent surface wettability, we discovered that PTFE, as the more hydrophobic surface, exhibits lower splashing thresholds than the hydrophilic surface of aluminum of comparable roughness. Furthermore, comparing oblique impacts on smooth and textured surfaces, we found that asymmetrical spreading and splashing behaviors occurred under a wide range of experimental conditions on our smooth surfaces; however, impacts occurring on textured surfaces were much more symmetrical, and one-sided splashing occurred only under very specific conditions. We attribute this difference to the air-trapping nature of textured superhydrophobic surfaces, which lowers the drag between the spreading lamella and the surface. The reduced drag affects oblique drop impacts by diminishing the effect of the tangential component of the impact velocity, causing the impact behavior to be governed almost exclusively by the normal velocity. Finally, by comparing oblique impacts on superhydrophobic surfaces at different impact angles, we discovered that although the pinning transition between rebounding and partial rebounding is governed primarily by the normal impact velocity, there is also a weak dependence on the tangential velocity. As a result, pinning is inhibited in oblique impacts. This led to the observation of a new behavior in highly oblique impacts on our superhydrophobic surfaces, which we named the stretched rebound, where the droplet is extended into an elongated pancake shape and rebounds while still outstretched, without exhibiting a recession phase.


Pathogenic CD8(+) T cells in multiple sclerosis.
Traditionally, autoimmune pathogeneses have been attributed to CD4(+) T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens to CD4(+) T cells. Because few autoimmune diseases show stronger associations with major histocompatibility complex class I alleles (ankylosing spondylitis, Behçet's disease, and psoriasis), CD8(+) T cells, which interact with major histocompatibility complex class I molecules, have been largely ignored in autoimmunity research. However, a variety of findings has recently revived interest in this population, particularly in MS. First, it shows associations with major histocompatibility complex class I alleles. Second, its lesions show a predominance of CD8(+) T cells. Third, these represent effectors that can directly damage central nervous system target cells. Furthermore, several clinical trials of monoclonal antibodies specifically against CD4(+) T cells, or the polarizing cytokines on which they depend, have failed to show any therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T cells. Here, we review the evidence that CD8(+) T cells play a role in MS pathogenesis.


Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer's disease.
A growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer's disease (AD). With a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive impairment (MCI-AD; n = 25) or at the stage of early dementia (ADD; n = 33), and in nondemented controls (n = 41); in all patients, the clinical diagnoses were in accordance with the results of the four core cerebrospinal fluid (CSF) biomarkers (amyloid β (Aβ)1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm. The influence of preanalytical storage procedures on the NfL in plasma was tested on samples exposed to six different conditions. NfL concentrations significantly increased in the samples exposed to more than one freezing/thawing cycle, and in those stored for 5 days at room temperature or at 4 °C. Compared with the control group of nondemented subjects (22.0 ± 12.4 pg/mL), the unadjusted plasma NfL concentration was highly significantly higher in the MCI-AD group (38.1 ± 15.9 pg/mL, p < 0.005) and even further elevated in the ADD group (49.1 ± 28.4 pg/mL; p < 0.001). A significant association between NfL and age (ρ = 0.65, p < 0.001) was observed; after correcting for age, the difference in NfL concentrations between AD and controls remained significant (p = 0.044). At the cutoff value of 25.7 pg/mL, unconditional sensitivity, specificity, and accuracy were 0.84, 0.78, and 0.82, respectively. Unadjusted correlation between plasma NfL and Mini Mental State Examination (MMSE) across all patients was moderate but significant (r = -0.49, p < 0.001). We observed an overall significant correlation between plasma NfL and the CSF biomarkers, but this correlation was not observed within the diagnostic groups. This study confirms increased concentrations of plasma NfL in patients with Alzheimer's disease compared with nondemented controls.


DBSolve Optimum: a software package for kinetic modeling which allows dynamic visualization of simulation results.
Systems biology research and applications require creation, validation, extensive usage of mathematical models and visualization of simulation results by end-users. Our goal is to develop novel method for visualization of simulation results and implement it in simulation software package equipped with the sophisticated mathematical and computational techniques for model development, verification and parameter fitting. We present mathematical simulation workbench DBSolve Optimum which is significantly improved and extended successor of well known simulation software DBSolve5. Concept of "dynamic visualization" of simulation results has been developed and implemented in DBSolve Optimum. In framework of the concept graphical objects representing metabolite concentrations and reactions change their volume and shape in accordance to simulation results. This technique is applied to visualize both kinetic response of the model and dependence of its steady state on parameter. The use of the dynamic visualization is illustrated with kinetic model of the Krebs cycle. DBSolve Optimum is a user friendly simulation software package that enables to simplify the construction, verification, analysis and visualization of kinetic models. Dynamic visualization tool implemented in the software allows user to animate simulation results and, thereby, present them in more comprehensible mode. DBSolve Optimum and built-in dynamic visualization module is free for both academic and commercial use. It can be downloaded directly from http://www.insysbio.ru.


Sterile testis complementation with spermatogonial lines restores fertility to DAZL-deficient rats and maximizes donor germline transmission.
Despite remarkable advances in assisted reproductive capabilities approximately 4% of all couples remain involuntarily infertile. In almost half of these cases, a lack of conception can in some measure be attributed to the male partner, wherein de novo Y-chromosomal deletions of sperm-specific Deleted-in-Azoospermia (DAZ) genes are particularly prevalent. In the current study, long-term cultures of rat spermatogonial stem cells were evaluated after cryo-storage for their potential to restore fertility to rats deficient in the DAZ-like (DAZL) gene. Detailed histological analysis of DAZL-deficient rat testes revealed an apparently intact spermatogonial stem cell compartment, but clear failure to produce mature haploid gametes resulting in infertility. After proliferating >1 million-fold in cell number during culture post-thaw, as few as 50,000 donor spermatogonia transplanted into only a single testis/recipient effectively restored fecundity to DAZL-deficient rats, yielding 100% germline transmission to progeny by natural mating. Based on these results, the potency and efficacy of this donor stem cell line for restoring fertility to azoospermic rodents is currently unprecedented. Prospectively, similar successes in humans could be directly linked to the feasibility of obtaining enough fully functional spermatogonial stem cells from minimal testis biopsies to be therapeutically effective. Thus, regeneration of sperm production in this sterile recipient provides an advanced pre-clinical model for optimizing the efficacy of stem cell therapies to cure a paradoxically increasing number of azoospermic men. This includes males that are rendered infertile by cancer therapies, specific types of endocrine or developmental defects, and germline-specific de novo mutations; all of whom may harbor healthy sources of their own spermatogonial stem cells for treatment.


Estimating age from recapture data: integrating incremental growth measures with ancillary data to infer age-at-length.
Estimating the age of individuals in wild populations can be of fundamental importance for answering ecological questions, modeling population demographics, and managing exploited or threatened species. Significant effort has been devoted to determining age through the use of growth annuli, secondary physical characteristics related to age, and growth models. Many species, however, either do not exhibit physical characteristics useful for independent age validation or are too rare to justify sacrificing a large number of individuals to establish the relationship between size and age. Length-at-age models are well represented in the fisheries and other wildlife management literature. Many of these models overlook variation in growth rates of individuals and consider growth parameters as population parameters. More recent models have taken advantage of hierarchical structuring of parameters and Bayesian inference methods to allow for variation among individuals as functions of environmental covariates or individual-specific random effects. Here, we describe hierarchical models in which growth curves vary as individual-specific stochastic processes, and we show how these models can be fit using capture-recapture data for animals of unknown age along with data for animals of known age. We combine these independent data sources in a Bayesian analysis, distinguishing natural variation (among and within individuals) from measurement error. We illustrate using data for African dwarf crocodiles, comparing von Bertalanffy and logistic growth models. The analysis provides the means of predicting crocodile age, given a single measurement of head length. The von Bertalanffy was much better supported than the logistic growth model and predicted that dwarf crocodiles grow from 19.4 cm total length at birth to 32.9 cm in the first year and 45.3 cm by the end of their second year. Based on the minimum size of females observed with hatchlings, reproductive maturity was estimated to be at nine years. These size benchmarks are believed to represent thresholds for important demographic parameters; improved estimates of age, therefore, will increase the precision of population projection models. The modeling approach that we present can be applied to other species and offers significant advantages when multiple sources of data are available and traditional aging techniques are not practical.


The person trade-off method and the transitivity principle: an example from preferences over age weighting.
The person trade-off (PTO) is increasingly being used to elicit preferences in health. This paper explores the measurement properties of the PTO method in the context of a study about how members of the public prioritise between patients of different ages. In particular, it considers whether PTO responses satisfy the transitivity principle; that is, whether one PTO response can be inferred from two other PTO responses. The results suggest that very few responses to PTO questions satisfy cardinal transitivity condition. However, this study has produced results that suggest that cardinal transitivity will hold, on average, when respondents who fail to satisfy the ordinal transitivity condition have been excluded from the analysis. This suggests that future PTO studies should build in checks for ordinal transitivity.


Probiotics, symptoms, and gut microbiota: what are the relations? A randomized controlled trial in subjects with irritable bowel syndrome.
Introduction. Knowledge of the mechanism of action of probiotics in subjects with irritable bowel syndrome (IBS) is imperfect. Objective. This trial aimed at discriminating between a direct effect on the gut wall and an indirect effect caused by modulation of the fecal microbiota. Design. Randomized, double-blind, crossover trial. Material and Methods. Patients with IBS were given one capsule of 10(10) CFU L. plantarum MF 1298 or placebo once daily. Symptoms were registered (score 0-15) and feces collected at the end of each period. The gut microbiota was analyzed with 16S rRNA gene analyses and results reported as proportions of Bacteroides, Faecalibacterium, and Lachnospiraceae and Simpson's D diversity score. Results. Sixteen participants (11 women) with a mean age of 50 years (SD 11) were available for the analyses. Intake of L. plantarum MF 1298 was associated with a significant aggravation of symptoms, but neither intake of L. plantarum MF 1298 nor symptoms were associated with the composition of the fecal microbiota (P values >0.10). Conclusions. The trial indicates that the symptomatic aggravation related to intake of L. plantarum MF 1298 was a direct effect of the microbe on the gut wall and not caused by changes in the fecal microbiota.


The effects of breed, neonatal age and pregnancy on the plasma copper status of goats in Oman.
There is a history of copper deficiency in grazing Omani livestock and the copper status of three economically important goat breeds, Jabal Akhdar (JA), Batina (B) and Dhofari (D) were therefore compared in October/November (cool season) and June (dry season) in a penned flock given a plentiful dietary supply of copper. In the cool season, 62 lactating does (5 JA, 12 B and 33 D), their 0-5-day-old kids (17 JA, 19 B and 22 D) and 25 dry does (17 JA, 5 B and 3 D) were blood sampled. In the dry season, the does sampled were either barren (15 JA, 16 B and 13 D) or pregnant (9 JA, 13 B and 33 D). The samples were analysed for total copper (TCu) and trichloroacetic acid (TCA)-soluble copper (TCA-sol Cu). There were no effects of breed on TCu or TCA-sol Cu in the cool season, the overall means being 0.75 (SE 0.049) and 0.59 (SE 0.052) mg/L. The mean TCu was low in kids at birth (0.59 mg/L) but had increased to 0.86 mg/L by 4 days of age (p < 0.001); breed differences were found (p < 0.002), the pooled values for JA, B and D being 0.77, 0.59 and 0.68 (SE 0.033-0.044) mg/L, respectively. By the dry season, the mean TCu had risen in barren does to 0.96 (0.045) mg/L but not in pregnant does (0.76 (0.047) mg/L: p < 0.002) and breed differences had emerged, the mean for D being 20% lower than those for JA and B (p < 0.05). The highest TCu values were found in the 7-month-old kids in June ( 1.17 (0.039) mg/L) but the breeds did not then differ. Some effects on TCA solubility were found but were considered unreliable. Breed effects may have been diminished by the generous supply of copper and early stage of lactation studied.


Timing of conversion to cervical malalignment and proximal junctional kyphosis following surgical correction of adult spinal deformity: a 3-year radiographic analysis.
The goal of this study was to assess the conversion rate from baseline cervical alignment to postoperative cervical deformity (CD) and the corresponding proximal junctional kyphosis (PJK) rate in patients undergoing thoracolumbar adult spinal deformity (ASD) surgery. The operative records of patients with ASD with complete radiographic data beginning at baseline up to 3 years were included. Patients with no baseline CD were postoperatively stratified by Ames CD criteria (T1 slope-cervical lordosis mismatch [TS-CL] > 20°, cervical sagittal vertical axis [cSVA] > 40 mm), where CD was defined as fulfilling one or more of the Ames criteria. Severe CD was defined as TS-CL > 30° or cSVA > 60 mm. Follow-up intervals were established after ASD surgery, with 6 weeks postoperatively defined as early; 6 weeks-1 year as intermediate; 1-2 years as late; and 2-3 years as long-term. Descriptive analyses and McNemar tests identified the CD conversion rate, PJK rate (< -10° change in uppermost instrumented vertebra and the superior endplate of the vertebra 2 levels superior to the uppermost instrumented vertebra), and specific alignment parameters that converted. Two hundred sixty-six patients who underwent ASD surgery (mean age 59.7 years, 77.4% female) met the inclusion criteria; 103 of these converted postoperatively, and the remaining 163 did not meet conversion criteria. Thirty-eight patients converted to CD early, 26 converted at the intermediate time point, 29 converted late, and 10 converted in the long-term. At conversion, the early group had the highest mean TS-CL at 25.4° ± 8.5° and the highest mean cSVA at 33.6 mm-both higher than any other conversion group. The long-term group had the highest mean C2-7 angle at 19.7° and the highest rate of PJK compared to other groups (p = 0.180). The early group had the highest rate of conversion to severe CD, with 9 of 38 patients having severe TS-CL and only 1 patient per group converting to severe cSVA. Seven patients progressed from having only malaligned TS-CL at baseline (with normal cSVA) to CD with both malaligned TS-CL and cSVA by 6 weeks. Conversely, only 2 patients progressed from malaligned cSVA to both malaligned cSVA and TS-CL. By 1 year, the former number increased from 7 to 26 patients, and the latter increased from 2 to 20 patients. The revision rate was highest in the intermediate group at 48.0%, versus the early group at 19.2%, late group at 27.3%, and long-term group at 20% (p = 0.128). A higher pelvic incidence-lumbar lordosis mismatch, lower thoracic kyphosis, and a higher thoracic kyphosis apex immediately postoperatively significantly predicted earlier rather than later conversion (all p < 0.05). Baseline lumbar lordosis, pelvic tilt, and sacral slope were not significant predictors. Patients with ASD with normative cervical alignment who converted to CD after thoracolumbar surgery had varying radiographic findings based on timing of conversion. Although the highest number of patients converted within 6 weeks postoperatively, patients who converted in the late or long-term follow-up intervals had higher rates of concurrent PJK and greater radiographic progression.


Shifting the treatment model: impact on engagement in outpatient therapy.
Attrition in youth outpatient mental health clinics ranges from 30 to 70 % and often occurs early in treatment. We implemented specific treatment planning strategies designed to reduce early attrition. Following implementation, 14.3 % of clients dropped out during the first five sessions compared to 26.1 % in the historical control (p < 0.001). During treatment, 33.6 % of clients dropped out in the intervention compared to 55.5 % in the historical control (p < 0.001). Engagement is central to the therapeutic process and may be particularly relevant early in treatment. Implementing evidence-based strategies to promote a collaborative relationship between the family and the clinician may increase engagement and decrease attrition.


To Stay in or Leave an Abusive Relationship: Losses and Gains Experienced by Battered Filipino Women.
The present study aimed to describe and analyze the losses and gains experienced by battered Filipino women as a result of their decision to stay in or leave an abusive relationship. In-depth, semistructured interviews were conducted with 60 battered women, 30 of the women were still living with their abusive husbands/partners and 30 have left their abusive husbands/partners. Results from the phenomenological data analysis of the qualitative data revealed that the women who stayed in and left their abusive partners experienced both losses and gains. For the women who stayed in an abusive relationship, they lost a sense of self, the opportunity for a better life, peace of mind, psychological well-being, and love for their partners. However, these women had the benefits of having a complete family and a partner to help raise their children. In contrast, despite not having a complete family or a partner to help them raise their children, women who left an abusive relationship gained back their sense of self, peace of mind, freedom, inner strength, and hope. Implications for counseling practice were discussed.


Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding.
Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains (TADs) is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventional 3C-based methods by using high-resolution Micro-C to probe links between 3D genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregates TAD regions into various finer-scale structures with distinct regulatory features including stripes, dots, and domains linking promoters-to-promoters (P-P) or enhancers-to-promoters (E-P) and bundle contacts between Polycomb regions. E-P stripes extending from the edge of domains predominantly link co-expressed loci, often in the absence of CTCF and cohesin occupancy. Acute inhibition of transcription disrupts these gene-related folding features without altering higher-order chromatin structures. Our study uncovers previously obscured finer-scale genome organization, establishing functional links between chromatin folding and gene regulation.


Stir bar sorptive extraction applied to the determination of dicarboximide fungicides in wine.
The dicarboximide fungicides vinclozolin, iprodione and procymidone were analyzed in white wines using stir bar sorptive extraction (SBSE) in combination with thermal desorption-capillary GC-MS analysis (TD-cGC-MS). The method was optimized using spiked water samples in a concentration range between 0.5 and 100 microg/l. Iprodione was measured as its degradation product 3,5-dichlorophenyl hydantoin. Limits of quantification in the full scan MS mode are 0.5 microg/l for vinclozolin and procymidone and 5 microg/l for iprodione. In the ion monitoring mode, concentrations 100 times lower can be dosed. Because of wine matrix effects on the recoveries, quantification of the target fungicides in wine had to be carried out by standard addition. For the thermolabile iprodione, the accuracy of SBSE-TD-cGC-MS was verified using SBSE followed by liquid desorption and analysis by liquid chromatography-atmospheric pressure chemical ionization mass spectroscopy. Procymidone and iprodione were detected in wines in concentrations up to 65 microg/l while the highest concentration of vinclozolin detected was smaller than 3 microg/l.