Depression and Antidepressant Use Among Asian and Hispanic Adults: Association with Immigrant Generation and Language Use.
This research investigates the psychological well-being and usage of medical treatments by Asian and Hispanic immigrant descendants. Using data from all four waves of Add Health study, this paper focuses on two outcomes: (1) depression and (2) levels of antidepressant use by race/ethnicity, immigrant generation, and linguistic acculturation levels during adulthood. Findings reveal that depression is prevalent among Mexican Americans, other Hispanics, and Asian Americans. Furthermore, Mexican Americans and Asian Americans have reported a lower level of antidepressant use than whites, with Asian Americans attaining the lowest level when immigrant generation, language acculturation levels, and other socioeconomic factors are held constant. We also find that those who are linguistically less acculturated have much lower levels of antidepressant use than their monolingual English-speaking counterparts.


Properties of in situ generated gold nanoparticles in the cellular context.
Gold nanostructures that serve as probes for nanospectroscopic analysis of eukaryotic cell cultures can be obtained by the in situ reduction of tetrachloroauric acid (HAuCl4). To understand the formation process of such intracellularly grown particles depending on the incubation medium, the reaction was carried out with 3T3 fibroblast cells in three different incubation media, phosphate buffer, Dulbecco's Modified Eagle Medium (DMEM), and standard cell culture medium (DMEM with fetal calf serum). The size, the optical properties, the biomolecular corona, and the localization of the gold nanoparticles formed in situ vary for the different conditions. The combination of surface-enhanced Raman scattering (SERS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) microscopic mapping and transmission electron microscopy (TEM) provides complementary perspectives on plasmonic nanoparticles and non-plasmonic gold compounds inside the cells. While for the incubation with HAuCl4 in PBS, gold particles provide optical signals from the nucleus, the incubation in standard cell culture medium leads to scavenging of the toxic molecules and the formation of spots of high gold concentration in the cytoplasm without formation of SERS-active particles inside the cells. The biomolecular corona of nanoparticles formed in situ after incubation in buffer and DMEM differs, suggesting that different intracellular molecular species serve for reduction and stabilization. Comparison with data obtained from ready-made gold nanoparticles suggests complementary application of in situ and ex situ generated nanostructures for optical probing.


HIV-1 Vpu represents a minor target for cytotoxic T lymphocytes in HIV-1-infection.
We have previously shown that Vpu is rarely targeted by HIV-1-specific cytotoxic T lymphocytes (CTL). The present report extends these findings and describes the characterization of the first CTL epitope within HIV-1 Vpu, identified in an individual with long-term non-progressive HIV-1 infection. The epitope was shown to be highly conserved among HIV clade B sequences and is restricted by HLA-A*3303, an HLA allele commonly seen in Asian and west-African populations.


Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma.
Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue-specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms (SNPs) in the genes for claudin 1 and claudin 7 in colon cancer (CC) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN1 SNP rs9869263 (c.369C>T), and the CLDN7 SNPs rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded (FFPE) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN1 genotype CC in tumor samples and a higher risk of colon cancer development (OR 3.0, p < 0.001). We also found that the CLDN7 rs4562 (c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN7. The CLDN1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.


Prospective study of the value of transbronchial lung biopsy after lung transplantation.
Transbronchial lung biopsy (TBB) has become the gold standard for the diagnosis of acute rejection and cytomegalovirus (CMV) pneumonia in lung transplant recipients. The aim of this study was to assess the value of regular surveillance TBB in stable asymptomatic patients and to establish the role of TBB as a follow-up procedure 1 month after a previous pathological biopsy result. We prospectively evaluated 76 TBBs performed in 17 lung transplant recipients. A definite pathological results was found in 14 of 15 TBBs performed for clinical indications: CMV pneumonia (5), acute rejection grade > or = A2 according to the criteria of the International Society for Heart and Lung Transplantation (ISHLT) (4), bronchiolitis obliterans (3), and desquamative interstitial pneumonitis (2). Fifteen of 45 surveillance TBBs performed in asymptomatic patients revealed significant abnormalities. Ten episodes of acute rejection ISHLT grade > or = A2 and three episodes of CMV pneumonia detected by TBB had direct therapeutic consequences. Nine of 16 follow-up TBBs performed 1 month after a pathological biopsy result again showed relevant pathological findings. With the exception of one severe haemorrhage, no life-threatening complications occurred. Our results suggest that transbronchial lung biopsies performed on a regular basis after lung transplantation are important for the detection of asymptomatic and/or persistent acute rejection or injection. In the long-term, this strategy might be the most effective tool in reducing the incidence of bronchiolitis obliterans, which is still the main obstacle for further improvement of long-term survival after lung transplantation.


Selected essential oils inhibit key physiological enzymes and possess intracellular and extracellular antimelanogenic properties in vitro.
Essential oils (EOs) extracted from six medicinal herbs and food plants [Cinnamomum zeylanicum (CZ), Psiadia arguta (PA), Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), and Citrus reticulata (CR)] were studied for any inhibitory potential against key physiological enzymes involved in diabetes (α-glucosidase), skin aging (collagenase and elastase), and neurodegenerative disorders (acetylcholinesterase). Kinetic studies of the active EOs on the aforementioned enzymes were determined using Lineweaver-Burk plots. The intracellular and extracellular antimelanogenic potential of the EOs were evaluated on B16F10 mouse melanocytes. CH and CR were found to significantly inhibit (2.476 ± 0.13 μg/mL and 3.636 ± 0.10 μg/mL, respectively) acetylcholinesterase, compared with galantamine (3.989 ± 0.16 μg/mL). CH inhibited collagenase (50% inhibitory concentration 28.71 ± 0.16 μg/mL) compared with the control (24.45 ± 0.19 μg/mL). The percentage inhibition in the elastase assay of CH was 63.21% compared to the positive control (75.09%). In addition, CH, CR, CGp, CZ, and PT were found to significantly inhibit α-glucosidase (276.70 ± 0.73 μg/mL, 169.90 ± 0.58 μg/mL, 240.60 ± 6.50 μg/mL, 64.52 ± 0.69 μg/mL, and 313.0 ± 5.0 μg/mL, respectively), compared to acarbose (448.80 ± 0.81 μg/mL). Active EOs showed both uncompetitive and competitive types of inhibition. The EOs also inhibited intracellular (50% inhibitory concentration 15.92 ± 1.06 μg/mL, 23.75 ± 4.47 μg/mL, and 28.99 ± 5.70 μg/mL for CH, CR, and CGp, respectively) and extracellular (< 15.625 μg/mL for CH, CR, CGp, and PT) melanin production when tested against B16F10 mouse melanocytes. Results from the present study tend to show that EOs extracted from these medicinal plants can inhibit key enzymes and may be potential candidates for cosmetic and pharmaceutical industries.


Is the inherent potential of maize roots efficient for soil phosphorus acquisition?
Sustainable agriculture requires improved phosphorus (P) management to reduce the overreliance on P fertilization. Despite intensive research of root adaptive mechanisms for improving P acquisition, the inherent potential of roots for efficient P acquisition remains unfulfilled, especially in intensive agriculture, while current P management generally focuses on agronomic and environmental concerns. Here, we investigated how levels of soil P affect the inherent potential of maize (Zea mays L.) roots to obtain P from soil. Responses of root morphology, arbuscular mycorrhizal colonization, and phosphate transporters were characterized and related to agronomic traits in pot and field experiments with soil P supply from deficiency to excess. Critical soil Olsen-P level for maize growth approximated 3.2 mg kg(-1), and the threshold indicating a significant environmental risk was about 15 mg kg(-1), which represented the lower and upper levels of soil P recommended in current P management. However, most root adaptations involved with P acquisition were triggered when soil Olsen-P was below 10 mg kg(-1), indicating a threshold for maximum root inherent potential. Therefore, to maintain efficient inherent potential of roots for P acquisition, we suggest that the target upper level of soil P in intensive agriculture should be reduced from the environmental risk threshold to the point maximizing the inherent potential of roots.


Radial Basis Function Neural Network with Localized Stochastic-Sensitive Autoencoder for Home-Based Activity Recognition.
Over the past few years, the Internet of Things (IoT) has been greatly developed with one instance being smart home devices gradually entering into people's lives. To maximize the impact of such deployments, home-based activity recognition is required to initially recognize behaviors within smart home environments and to use this information to provide better health and social care services. Activity recognition has the ability to recognize people's activities from the information about their interaction with the environment collected by sensors embedded within the home. In this paper, binary data collected by anonymous binary sensors such as pressure sensors, contact sensors, passive infrared sensors etc. are used to recognize activities. A radial basis function neural network (RBFNN) with localized stochastic-sensitive autoencoder (LiSSA) method is proposed for the purposes of home-based activity recognition. An autoencoder (AE) is introduced to extract useful features from the binary sensor data by converting binary inputs into continuous inputs to extract increased levels of hidden information. The generalization capability of the proposed method is enhanced by minimizing both the training error and the stochastic sensitivity measure in an attempt to improve the ability of the classifier to tolerate uncertainties in the sensor data. Four binary home-based activity recognition datasets including OrdonezA, OrdonezB, Ulster, and activities of daily living data from van Kasteren (vanKasterenADL) are used to evaluate the effectiveness of the proposed method. Compared with well-known benchmarking approaches including support vector machine (SVM), multilayer perceptron neural network (MLPNN), random forest and an RBFNN-based method, the proposed method yielded the best performance with 98.35%, 86.26%, 96.31%, 92.31% accuracy on four datasets, respectively.


TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.
Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to "cytokine-cytokine receptor interaction." Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.


Family Caregivers' Experiences of Within-Hospital Handoffs for Older Adults in Acute Care.
Family caregivers' experiences during within-hospital handoffs between acute care units are not well understood. Qualitative description methodology was employed to describe family caregivers' experiences during their loved ones' handoffs. Semistructured interviews were conducted with 10 caregivers of hospitalized older adults. Three themes emerged: Lack of care coordination, Muddling through handoffs alone, and Wariness toward the care delivery system. Findings can help clinicians shape their interactions with caregivers to maximize their involvement in post-hospital care.


Total substitution of dietary fish oil by vegetable oils stimulates muscle hypertrophic growth in Senegalese sole and the upregulation of fgf6.
The long term effects of fish oil (FO) substitution by increasing the levels of vegetable oils (VO), 0% (CTR), 50% (VO50) and 100% (VO100), in diets for Senegalese sole were evaluated in terms of skeletal muscle cellularity and expression of related genes. After 140 days of feeding, all fish had similar body weight and length. The inclusion of 50% VO did not result in differences in muscle cellularity, but dorsal muscle cross-sectional area and fast-twitch fibre diameter increased in fish fed total FO substitution, whilst fibre density was reduced (P < 0.05) in relation to CTR. The total number of fibres was similar in all treatments. FO substitution did not affect the transcript levels of myogenic genes (myf5, mrf4, myog, myod1, myod2), but resulted in a two-fold increase of fgf6 transcript levels compared to CTR (P < 0.05). The relative expression of igf-I was higher in VO100 than in VO50, but was similar to CTR. FO substitution resulted in cellularity changes related to the stimulation of muscle hypertrophic growth, but not hyperplastic growth, and associated with a nutritional modulation of fgf6 by dietary VO. This study indicates that 50% VO does not affect the muscle phenotype, but total FO substitution stimulates muscle hypertrophy.


Degeneracy: a link between evolvability, robustness and complexity in biological systems.
A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology.This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present evidence that degeneracy is a fundamental source of robustness, it is intimately tied to multi-scaled complexity, and it establishes conditions that are necessary for system evolvability.


Fast and Slow Oscillations Recruit Molecularly-Distinct Subnetworks of Lateral Hypothalamic Neurons In Situ.
Electrical signals generated by molecularly-distinct classes of lateral hypothalamus (LH) neurons have distinct physiological consequences. For example, LH orexin neurons promote net body energy expenditure, while LH non-orexin neurons [VGAT, melanin-concentrating hormone (MCH)] drive net energy conservation. Appropriate switching between such physiologically-opposing LH outputs is traditionally thought to require cell-type-specific chemical modulation of LH firing. However, it was recently found that, in vivo, the LH neurons are also physiologically exposed to electrical oscillations of different frequency bands. The role of the different physiological oscillation frequencies in firing of orexin vs non-orexin LH neurons remains unknown. Here, we used brain-slice whole-cell patch-clamp technology to target precisely-defined oscillation waveforms to individual molecularly-defined classes LH cells (orexin, VGAT, MCH, GAD65), while measuring the action potential output of the cells. By modulating the frequency of sinusoidal oscillatory input, we found that high-frequency oscillations (γ, ≈30-200 Hz) preferentially silenced the action potential output orexinLH cells. In contrast, low frequencies (δ-θ, ≈0.5-7 Hz) similarly permitted outputs from different LH cell types. This differential control of orexin and non-orexin cells by oscillation frequency was mediated by cell-specific, impedance-unrelated resonance mechanisms. These results substantiate electrical oscillations as a novel input modality for cell-type-specific control of LH firing, which offers an unforeseen way to control specific cell ensembles within this highly heterogeneous neuronal cluster.


Radically promoted formation of a molecular lasso.
Two potential viologen-based molecular lasso precursors-both composed of a 4,4'-bipyridinium (BIPY2+) unit as part of a rope appended to a cyclobis(paraquat-p-phenylene) (CBPQT4+) loop-that have been designed to mimic the threading/unthreading motion of lasso peptides, have been synthesised and characterised. Solution and solid-state experiments reveal that, when the BIPY2+ unit in the rope and the CBPQT4+ loop are connected by a bulky linker, no lasso-like conformational transformation is observed between the different redox states on account of steric effects. In sharp contrast, when the linker size is small, the molecule can be switched between (i) a free rope-like conformation in its fully oxidised state and (ii) a self-entangled lasso-like conformation under reducing conditions employing either chemical or electrochemical stimuli: the BIPY˙+ unit in the rope resides inside the cavity of the CBPQT2(˙+) loop, forming a pseudo[1]rotaxane. The switching process is reversible and stereochemically unambiguous. This research shows how tiny structural differences can induce significantly different self-complexing properties and sheds light on designing functional artificial actuators.


Urinary tract infections in a South American population: dynamic spread of class 1 integrons and multidrug resistance by homologous and site-specific recombination.
One hundred four bacterial strains mediating urinary tract infections in separate individuals from a Uruguayan community were isolated. Forty-six strains conferred a multidrug resistance phenotype. All 104 strains were examined for the presence of class 1, 2, and 3 integrons. Class 1 integrons were found in 21 isolates across four distinct bacterial genera. A large class 1 integron in a Klebsiella pneumoniae strain was fully sequenced and was 29,093 bp in length. This integron probably arose by homologous recombination since it was embedded in a hybrid Tn21-like transposon backbone which comprised a Tn5036-like tnp transposition module at the IRi integron end and a Tn21 mer module at the IRt integron end. The parent integron/transposon that contributed the Tn5036 module was not related to Tn1696 since the integron insertion points in the transposon backbones were 16 bases apart. Examination of the other 20 class 1 integron-containing strains revealed further evidence of genetic exchange. This included a strain that possessed a Tn5036 module at the IRt end but not at the IRi end and another that possessed a tnp module beyond IRi that was a hybrid of Tn21 and Tn5051 and that is presumed to have arisen by site-specific recombination. This study highlights the ability of different genetic elements to act cooperatively to spread and rearrange antibiotic resistance in a community.


Sleep Patterns and Alertness in an Elite Super Rugby Team During a Game Week.
Sleep is a vital component of preparation, performance and recovery for a Super Rugby game. The purpose of this study was to quantify sleep behaviours and alertness of professional rugby union players during training and a game. Thirty-six rugby union players from a Super Rugby team wore a wrist-activity device (Readiband™) to measure sleep for 3 days before, 3 days after and on the night of an evening game. Players were separated into those selected to play the game (n = 23) and those who were not (n = 13). Alertness was assessed for all training and game times using bio-mathematical modelling. Alertness measures ≤90% were considered to reflect impaired reaction time. Those selected to play in the game progressively increased sleep duration over the nights prior to the game (by 92 min p ≤ 0.05) by delaying wake time. Players went to bed later after the game (02:20 ± 114 min vs 22:57 ± 60 min; p ≤ 0.001) which resulted in decreased sleep duration on game night compared to pre-game nights (296 ± 179 min vs 459 ± 78 min; p ≤ 0.05). Four players did not achieve any sleep on game night. Sleep duration appeared to be truncated by early morning training sessions (before 08:00) on the second and third mornings after the game. Alertness was >90% for all training and game times for all players. In conclusion, in the days leading into a Super Rugby game, players delay morning time at wake and consequently increase sleep duration with post-game sleep reduced in some.


Quantitative comparison of the hydrogen bond network of A-state and native ubiquitin by hydrogen bond scalar couplings.
The backbone hydrogen bond (H-bond) network of the partially folded A-state of ubiquitin (60% methanol, 40% water, pH 2) has been characterized quantitatively by (h3)J(NC)(') H-bond scalar couplings between the (15)N nuclei of amino acid H-bond donors and the (13)C carbonyl nuclei of the acceptors. Results on (h3)J(NC)(') couplings and the amide proton ((1)H(N)) chemical shifts for the A-state are compared quantitatively to the native state. The (h3)J(NC)(') correlations of the A-state show intact, nativelike H-bonds of the first beta-hairpin beta1/beta2 and the alpha-helix, albeit at lower strength, whereas the H-bonds in the C-terminal part change from a pure beta-structure to an all alpha-helical H(N)(i)-->O(i-4) connectivity pattern. A residue-specific analysis reveals that the conformations within the conserved secondary structure segments are much more homogeneous in the A-state than in the native state. Thus, the strong asymmetry of (h3)J(NC)(') couplings and (1)H(N) chemical shifts between the interior and exterior sides of the native state alpha-helix vanishes in the A-state. This indicates that the bend of this helix around the native state hydrophobic core is released in the homogeneous solvent environment of the A-state. Similarly, an irregularity in the behavior of H-bond I3-->L15 in hairpin beta1/beta2, which results from strong contacts to strand beta5 in the native state, is absent in the A-state. These findings rationalize the behavior of the (1)H(N) chemical shifts in both states and indicate that the A-state is in many aspects similar to the onset of thermal denaturation of the native state.


There is no defence for 'Conscientious objection' in reproductive health care.
A widespread assumption has taken hold in the field of medicine that we must allow health care professionals the right to refuse treatment under the guise of 'conscientious objection' (CO), in particular for women seeking abortions. At the same time, it is widely recognized that the refusal to treat creates harm and barriers for patients receiving reproductive health care. In response, many recommendations have been put forward as solutions to limit those harms. Further, some researchers make a distinction between true CO and 'obstructionist CO', based on the motivations or actions of various objectors. This paper argues that 'CO' in reproductive health care should not be considered a right, but an unethical refusal to treat. Supporters of CO have no real defence of their stance, other than the mistaken assumption that CO in reproductive health care is the same as CO in the military, when the two have nothing in common (for example, objecting doctors are rarely disciplined, while the patient pays the price). Refusals to treat are based on non-verifiable personal beliefs, usually religious beliefs, but introducing religion into medicine undermines best practices that depend on scientific evidence and medical ethics. CO therefore represents an abandonment of professional obligations to patients. Countries should strive to reduce the number of objectors in reproductive health care as much as possible until CO can feasibly be prohibited. Several Scandinavian countries already have a successful ban on CO.


'These are not luxuries, it is essential for access to life': Disability related out-of-pocket costs as a driver of economic vulnerability in South Africa.
With the dawn of the new sustainable development goals, we face not only a world that has seen great successes in alleviating poverty but also a world that has left some groups, such as persons with disabilities, behind. Middle-income countries (MICs) are home to a growing number of persons with disabilities. As these countries strive to achieve the new goals, we have ample opportunity to include persons with disabilities in the emerging poverty alleviation strategies. However, a lack of data and research on the linkages between economic vulnerability and disability in MICs hampers our understanding of the factors increasing economic vulnerability in people with disabilities. This article aims to present data related to elements of this vulnerability in one MIC, South Africa. Focusing on out-of-pocket costs, it uses focus group discussions with 73 persons with disabilities and conventional content analysis to describe these costs. A complex and nuanced picture of disability-driven costs evolved on three different areas: care and support for survival and safety, accessibility of services and participation in community. Costs varied depending on care and support needs, accessibility (physical and financial), availability, and knowledge of services and assistive devices. The development of poverty alleviation and social protection mechanisms in MICs like South Africa needs to better consider diverse disability-related care and support needs not only to improve access to services such as education and health (National Health Insurance schemes, accessible clinics) but also to increase the effect of disability-specific benefits and employment equity policies.


Evaluating minimal clinically important differences for the acne-specific quality of life questionnaire.
The Acne-Specific Quality of Life Questionnaire (Acne-QoL) is a responsive, reliable and valid instrument developed to measure the impact of facial acne across four dimensions of patient QOL. Score changes on this instrument have been used to report statistically significant treatment advantages for a low-dose oral contraceptive (Estrostep, containing norethisterone (norethindrone) acetate (NA) 1mg and ethinylestradiol (EE) [20, 30, 35 mg] as compared with placebo in women with moderate acne vulgaris. However, the question remained if these statistically significant results were also clinically meaningful. To evaluate the statistically significant Acne-QoL benefits observed with NA/EE in terms of their clinical significance, and to compare the three different approaches for defining a minimal clinically important difference (MCID) for the Acne-QoL instrument. Since the optimum method for estimating MCIDs has yet to be established, three different published approaches for determining MCIDs were applied and compared using data from two randomised, double-blind, placebo- controlled studies of the efficacy of NA/EE in the treatment of facial acne. Although the approaches differed substantially, the resulting MCID estimates were comparable. Specifically, the MCID estimates ranged from 0.50-10.3 mean change per item, depending on the domain. The results showed that the statistically significant treatment advantages for NA/EE were also clinically significant. When applied to the change scores present, the results showed that the statistically significant treatment advantages for NA/EE were also clinically significant.


The effect of mechanical traction on low back pain in patients with herniated intervertebral disks: a systemic review and meta-analysis.
To evaluate the effectiveness of traction in improving low back pain, functional outcome, and disk morphology in patients with herniated intervertebral disks. PubMed, Scopus, Embase, and the Cochrane Library were searched from the earliest record to July 2019. We included randomized control trials which (1) involved adult patients with low back pain associated with herniated disk confirmed by magnetic resonance imaging or computed tomography, (2) compared lumbar traction to sham or no traction, and (3) provided quantitative measurements of pain and function before and after intervention. Methodological quality was assessed using the physiotherapy evidence database (PEDro) scale and Cochrane risk of bias assessment. Initial searches for literature yielded 3015 non-duplicated records. After exclusion based on the title, abstract, and full-text review, 7 articles involving 403 participants were included for quantitative analysis. Compared with the control group, the participants in the traction group showed significantly greater improvements in pain and function in the short term, with standard mean differences of 0.44 (95% confidence interval (CI): 0.11-0.77) and 0.42 (95% CI: 0.08-0.76), respectively. The standard mean differences were not significant to support the long-term effects on pain and function, nor the effects on herniated disk size. Compared with sham or no traction, lumbar traction exhibited significantly more pain reduction and functional improvements in the short term, but not in the long term. There is insufficient evidence to support the effect of lumbar traction on herniated disk size reduction.


Applicability of Moyers analysis in mixed dentition: A systematic review.
Moyers analysis is widely used for analyzing mixed dentition, however, the accuracy of its theoretical probability tables has been recently questioned. Taking into consideration the fact the mixed dentition analysis is of paramount importance to precisely determine the space needed for alignment of canines and premolars, this research aimed at objectively assessing in the literature such an important step for orthodontic diagnosis. A computerized search involving articles published on PubMed and Lilacs between 1990 and September, 2011 was conducted in accordance with the method described in the Cochrane 5.1.0 handbook. The research resulted in a sample composed of 629 articles. The inclusion criteria were: Articles using the Moyers analysis with a sample greater or equal to 40 patients. Conversely, the exclusion criteria were: Dental casts of patients with syndromes or oral cleft, researches conducted with a literature review, only, or clinical case reports and researches conducted before 1990. For this systematic review, 19 articles were selected. Based on the literature available, we can conclude that Moyers mixed dentition analysis must be carefully used, since the majority of the articles analyzed showed that the probability of 75% was not as accurate as expected, leading to the need of adapting the probability levels depending on the study population.


The Influence of Ultrafiltration of Citrus limon L. Burm. cv Femminello Comune Juice on Its Chemical Composition and Antioxidant and Hypoglycemic Properties.
Membrane separation has brought about a significant change in the food processing industry because it could operate separation at low temperature without a reduction of nutrients and bioactive compounds. Citrus limon L. Burm. cv Femminello comune juice, an Italian IGP (Protected Geographical Indication) product, was subjected to the ultrafiltation (UF) process using a cellulose acetate membrane, with a cut-off of 100 kDa, subjected to different transmembrane pressures (TMP, 05⁻1.5 bar). Untreated and ultra-filtrated (UF) juices were investigated for physicochemical parameters including pH, titratable acidity (TA), total soluble solids (TSS) and ascorbic acid content. Total phenols (TPC) and flavonoids (TFC) contents were also determined. Rutin, hesperidin, eriocitrin, and neohesperidin were selected as markers and quantified by HPLC. Antioxidant potential was investigated by using DPPH, ABTS, and FRAP tests. RACI was used to identify the sample with highest antioxidant potential. The hypoglycemic activity was examined using carbohydrates hydrolyzing enzymes assay. The application of increasing pressures across the membrane led to a reduction in TSS without causing a loss of bioactive compounds in terms of TPC and TFC. UF juice obtained with TMP of 1.5 bar (J3) showed a significant amount of eriocitrin and hesperidin with concentrations of 15.8 and 10.5 mg/100 mL, respectively. This sample showed the highest antioxidant potential and exhibited a promising α-amylase and α-glucosidase inhibitory activity with IC50 values of 31.1 and 35.3 mg/mL, respectively. Collectively our results support the use of cellulose acetate membrane to obtain an ultra-filtered juice with significant health potential.


Object detection techniques applied on mobile robot semantic navigation.
The future of robotics predicts that robots will integrate themselves more every day with human beings and their environments. To achieve this integration, robots need to acquire information about the environment and its objects. There is a big need for algorithms to provide robots with these sort of skills, from the location where objects are needed to accomplish a task up to where these objects are considered as information about the environment. This paper presents a way to provide mobile robots with the ability-skill to detect objets for semantic navigation. This paper aims to use current trends in robotics and at the same time, that can be exported to other platforms. Two methods to detect objects are proposed, contour detection and a descriptor based technique, and both of them are combined to overcome their respective limitations. Finally, the code is tested on a real robot, to prove its accuracy and efficiency.


Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling.
Diminished ovarian reserve (DOR) is one of the causes of infertility in young women. In this prospective study, gene expression profiling (GEP) of corona radiata cells (CRC) was performed to identify genes deregulated in DOR patients. Microarray-based GEP of CRC isolated from eight women undergoing IVF was performed to identify genes differentially expressed between patients with normal ovarian reserve and DOR patients. Microfluidic-based quantitative RT-PCR assays were used to validate selected transcripts on 40 independent patients. A principal component analysis was used to identify more homogeneous subgroups of DOR patients. In silico analyses focusing on cis-regulation were performed to refine the interactions between patient's biological characteristics and their GEP. Forty-eight transcripts were differentially expressed, including CXXC finger protein 5 (CXXC5), forkhead box C1 (FOXC1) (down-regulated in DOR) as well as connective tissue growth factor (CTGF), follistatin-like 3 (FSTL3), prostaglandin-endoperoxide synthase 2 (PTGS2) and suppressor of cytokine signaling 2 (SOCS2) (up-regulated in DOR). According to these transcripts, two DOR patients' subgroups (DOR Gr1 and Gr2) were identified. In DOR Gr2 patients, C-terminal domain 2 (CITED2), CTGF, growth arrest-specific 1 (GAS1), insulin receptor substrate 2 (IRS2), PTGS2, SOCS2 and Versican (VCAN) were expressed at significantly higher levels and CXXC5, FOXC1, guanylate-binding protein 2 (GBP2) and zinc finger MIZ-domain containing 1 (ZMIZ1) at significantly lower levels. Higher baseline estradiol (E(2)) levels were observed in DOR Gr2 patients (P < 0.006). The in silico analyses suggested that all 11 genes differentially expressed between DOR Gr1 and DOR Gr2 subgroups could be transcriptional targets of estrogen. Despite small sample size limitations, 12 genes deregulated in the CRC of DOR patients were identified, which could be involved in DOR pathogenesis. A DOR patient's subgroup with high baseline E(2) levels and deregulated estrogen-responsive genes was also identified.


Method for morphophysiological study of specific pial microvessels.
A method is described whereby specific segments of the pial vasculature of cats can be both physiologically and morphologically studied. This is accomplished by the insertion of a cranial window through which specific pial vessels can be visualized, illustrated, numbered in a simple sketch, and physiologically evaluated under both control and experimental conditions. Following these procedures, perfusion of aldehydes is initiated and the pia and associated vasculature are stripped from the cortical mantle. The thin velum of pia so obtained permits the direct visualization of the pial vasculature whose unchanged configuration can be matched to the appropriate previously sketched vessels whose individual physiological status is known. In turn these vessels are divided into alternate segments and are prepared for either scanning or transmission electron microscopy. The advantages of this methodology is exemplified by the fact that it provides the physiological status and morphological characteristics of the same microvascular segment. Although designed for the pial vasculature, this protocol may also prove of use in the study of other superficially coursing microvascular beds.


Explanation of the mechanism for acousto-optically induced unidirectional operation of a ring laser.
A mechanism is proposed for the nonreciprocal behavior of a traveling-wave acousto-optic Q switch, whose use can provide an effective way to enforce unidirectional and hence single-frequency operation of a ring laser. Simple energy and momentum conservation considerations show that the Bragg condition is satisfied at different angles of incidence for the two counterpropagating beams, which leads to a difference in their diffraction losses. The loss difference, measured directly for a diode-pumped Nd:YAG ring laser, yielded values in close agreement with calculated values. Implications of these results for both single-frequency cw and Q-switched operation of diode-pumped solid-state ring lasers are discussed.


Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice.
Real time in vivo methods are needed to better understand the interplay between diet and the gastrointestinal microbiota. Therefore, a rodent indirect calorimetry system was equipped with hydrogen (H2) and methane (CH4) sensors. H2 production was readily detected in C57BL/6J mice and followed a circadian rhythm. H2 production was increased within 12 hours after first exposure to a lowly-digestible starch diet (LDD) compared to a highly-digestible starch diet (HDD). Marked differences were observed in the faecal microbiota of animals fed the LDD and HDD diets. H2 was identified as a key variable explaining the variation in microbial communities, with specific taxa (including Bacteroides and Parasutterella) correlating with H2 production upon LDD-feeding. CH4 production was undetectable which was in line with absence of CH4 producers in the gut. We conclude that real-time in vivo monitoring of gases provides a non-invasive time-resolved system to explore the interplay between nutrition and gut microbes in a mouse model, and demonstrates potential for translation to other animal models and human studies.


Oxygen or carbogen breathing before simulated submarine escape.
Raised internal pressure in a distressed submarine increases the risk of bubble formation and decompression illness after submarine escape. The hypothesis that short periods of oxygen breathing before submarine escape would reduce decompression stress was tested, using Doppler-detectable venous gas emboli as a measure. Twelve goats breathed oxygen for 15 min at 0.1 MPa before exposure to a simulated submarine escape profile to and from 2.5 MPa (240 m/seawater), whereas 28 control animals underwent the same dive without oxygen prebreathe. No decompression sickness (DCS) occurred in either of these two groups. Time with high bubble scores (Kisman-Masurel >or=3) was significantly (P < 0.001) shorter in the prebreathe group. In a second series, 30 goats breathed air at 0.2 MPa for 6 h. Fifteen minutes before escape from 2.5 MPa, animals were provided with either air (n = 10), oxygen (n = 12), or carbogen (97.5% O(2) and 2.5% CO(2)) gas (n = 8) as breathing gas. Animals breathed a hyperoxic gas (60% O(2)-40% N(2)) during the escape. Two animals (carbogen group) suffered oxygen convulsions during the escape but recovered on surfacing. Only one case of DCS occurred (carbogen group). The initial bubble score was reduced in the oxygen group (P < 0.001). The period with bubble score of Kisman-Masurel >or=3 was also significantly reduced in the oxygen group (P < 0.001). Oxygen breathing before submarine escape reduces initial bubble scores, although its significance in reducing central nervous system DCS needs to be investigated further.


Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells.
Inactivation of phosphatase and tensin homolog (PTEN) is a critical step during tumorigenesis, and PTEN inactivation by genetic and epigenetic means has been well studied. There is also evidence suggesting that PTEN negative regulators (PTEN-NRs) have a role in PTEN inactivation during tumorigenesis, but their identity has remained elusive. Here we have identified shank-interacting protein-like 1 (SIPL1) as a PTEN-NR in human tumor cell lines and human primary cervical cancer cells. Ectopic SIPL1 expression protected human U87 glioma cells from PTEN-mediated growth inhibition and promoted the formation of HeLa cell-derived xenograft tumors in immunocompromised mice. Conversely, siRNA-mediated knockdown of SIPL1 expression inhibited the growth of both HeLa cells and DU145 human prostate carcinoma cells in vitro and in vivo in a xenograft tumor model. These inhibitions were reversed by concomitant knockdown of PTEN, demonstrating that SIPL1 affects tumorigenesis via inhibition of PTEN function. Mechanistically, SIPL1 was found to interact with PTEN through its ubiquitin-like domain (UBL), inhibiting the phosphatidylinositol 3,4,5-trisphosphate (PIP3) phosphatase activity of PTEN. Furthermore, SIPL1 expression correlated with loss of PTEN function in PTEN-positive human primary cervical cancer tissue. Taken together, these observations indicate that SIPL1 is a PTEN-NR and that it facilitates tumorigenesis, at least in part, through its PTEN inhibitory function.


Treatment adherence to olfactory training: a real-world observational study.
Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT. In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (≥5.5) and NRS (≥1) scores. Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up. Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.


Revealing the paradox of drug reward in human evolution.
Neurobiological models of drug abuse propose that drug use is initiated and maintained by rewarding feedback mechanisms. However, the most commonly used drugs are plant neurotoxins that evolved to punish, not reward, consumption by animal herbivores. Reward models therefore implicitly assume an evolutionary mismatch between recent drug-profligate environments and a relatively drug-free past in which a reward centre, incidentally vulnerable to neurotoxins, could evolve. By contrast, emerging insights from plant evolutionary ecology and the genetics of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved function, stabilizing selection, and population-specific selection of human cytochrome P450 genes indicate recent evolutionary exposure to plant toxins, including those that affect animal nervous systems. Thus, the human propensity to seek out and consume plant neurotoxins is a paradox with far-reaching implications for current drug-reward theory. We sketch some potential resolutions of the paradox, including the possibility that humans may have evolved to counter-exploit plant neurotoxins. Resolving the paradox of drug reward will require a synthesis of ecological and neurobiological perspectives of drug seeking and use.


CO2 fixation kinetics of Halothiobacillus neapolitanus mutant carboxysomes lacking carbonic anhydrase suggest the shell acts as a diffusional barrier for CO2.
The widely accepted models for the role of carboxysomes in the carbon-concentrating mechanism of autotrophic bacteria predict the carboxysomal carbonic anhydrase to be a crucial component. The enzyme is thought to dehydrate abundant cytosolic bicarbonate and provide ribulose 1.5-bisphosphate carboxylase/oxygenase (RubisCO) sequestered within the carboxysome with sufficiently high concentrations of its substrate, CO(2), to permit its efficient fixation onto ribulose 1,5-bisphosphate. In this study, structure and function of carboxysomes purified from wild type Halothiobacillus neapolitanus and from a high CO(2)-requiring mutant that is devoid of carboxysomal carbonic anhydrase were compared. The kinetic constants for the carbon fixation reaction confirmed the importance of a functional carboxysomal carbonic anhydrase for efficient catalysis by RubisCO. Furthermore, comparisons of the reaction in intact and broken microcompartments and by purified carboxysomal RubisCO implicated the protein shell of the microcompartment as impeding diffusion of CO(2) into and out of the carboxysome interior.


Diet Quality Index for older adults (DQI-65): development and use in predicting adherence to dietary recommendations and health markers in the UK National Diet and Nutrition Survey.
Diet quality indexes (DQI) are useful tools for assessing diet quality in relation to health and guiding delivery of personalised nutritional advice; however, existing DQI are limited in their applicability to older adults (aged ≥ 65 years). Therefore, this research aimed to develop a novel evidence-based DQI specific to older adults (DQI-65). Three DQI-65 variations were developed to assess the impacts of different component quantitation methods and inclusion of physical activity. These were Nutrient and Food-based DQI-65 (NFDQI-65), NFDQI-65 with Physical Activity (NFDQI-65+PA) and Food-based DQI-65 with Physical Activity (FDQI-65+PA). To assess their individual efficacy, the NFDQI-65, NFDQI-65+PA and FDQI-65+PA were explored alongside the validated Healthy Eating Index-2015 (HEI-2015) and Alternative Healthy Eating Index-2010 (AHEI-2010) using data from the cross-sectional UK National Diet and Nutrition Survey (NDNS) rolling programme. Scores for DQI-65 variations, the HEI-2015 and AHEI-2010 were calculated for adults ≥ 65 years from years 2-6 of the NDNS (n 871). Associations with nutrient intake, nutrient status and health markers were analysed using linear and logistic regression. Higher DQI-65 and HEI-2015 scores were associated with increased odds of meeting almost all our previously proposed age-specific nutritional recommendations, and with important health markers of importance for older adults, including lower BMI, lower medication use and lower C-reactive protein (P < 0·01). Few associations were observed for the AHEI-2010. This analysis suggests value of all three DQI-65 as measures of dietary quality in UK older adults. However, methodological limitations mean further investigations are required to assess validity and reliability of the DQI-65.


Expression of the HGF receptor c-met by macrophages in experimental autoimmune encephalomyelitis.
Hepatocyte growth factor (HGF) is a pleiotropic cytokine able to evoke a wide array of cellular responses including proliferation, migration, and survival through activation of its receptor c-met. Various types of leukocytes have been described to express c-met suggesting that HGF/c-met signaling may directly influence leukocyte responses in inflammation. We have investigated the HGF/c-met pathway in experimental autoimmune encephalomyelitis (EAE), a common mouse model of multiple sclerosis (MS), in which macrophages play a dual role, contributing directly to CNS damage at disease onset but promoting recovery during remission by removing myelin debris. Here we show that during EAE both HGF and c-met are expressed in the CNS and that c-met is activated. We subsequently demonstrate that c-met is primarily expressed in inflammatory lesions by macrophages and a small number of dendritic cells (DCs) and oligodendrocyte progenitor cells (OPCs) but not by microglia or T cells. Complementary in vitro experiments show that only LPS and TNFalpha, but not IL-6, IL-10, or IL-13, are able to induce c-met expression in macrophages. In addition, using TNF signaling deficient macrophages we demonstrate that LPS and TNFalpha induce c-met through distinct pathways. Furthermore, TNFalpha- and LPS-induced c-met is functional because treatment of macrophages with recombinant HGF results in rapid phosphorylation of c-met. Interestingly, HGF/c-met signaling does not modulate cytokine expression, phagocytosis, or antigen presentation but promotes proliferation of activated macrophages. Taken together, our data indicate a pro-inflammatory role for the HGF/c-met pathway in EAE rather than a role in the initiation of repair mechanisms.


A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage.
The transition from multipotent mesodermal precursor to committed myoblast and its differentiation into a mature myocyte involve molecular events that enable the cell to activate muscle-specific genes. Among the participants in this process is the myocyte-specific enhancer factor 2 (MEF2) family of tissue-restricted transcription factors. These factors, which share a highly conserved DNA-binding domain including a MADS box, are essential for the expression of multiple muscle genes with cognate target MEF2 sites in cis. We report here a new human MEF2 factor, hMEF2D, which is unique among the members of this family in that it is present not only in myotubes but also in undifferentiated myoblasts, even before the appearance of myogenin. hMEF2D comprises several alternatively spliced products of a single gene, one of which is the human homolog of the Xenopus SRF-related factor SL-1. Like its relatives, cloned hMEF2D is capable of activating transcription via sequence-specific binding to the MEF2 site, recapitulating endogenous tissue-specific MEF2 activity. Indeed, while MEF2D mRNAs are ubiquitous, the protein is highly restricted to those cell types that contain this activity, implicating posttranscriptional mechanisms in the regulation of MEF2D expression. Alternative splicing may be important in this process: two alternative MEF2D domains, at least one of which is specifically included during myogenic differentiation, also correlate precisely with endogenous MEF2 activity. These findings provide compelling evidence that MEF2D is an integral link in the regulatory network for muscle gene expression. Its presence in undifferentiated myoblasts further suggests that it may be a mediator of commitment in the myogenic lineage.


Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse.
Down syndrome (DS) is the most common genetic cause of mental retardation and affects many aspects of brain development. DS individuals exhibit an overall reduction in brain size with a disproportionately greater reduction in cerebellar volume. The Ts65Dn mouse is segmentally trisomic for the distal 12-15 Mb of mouse chromosome 16, a region that shows perfect conserved linkage with human chromosome 21, and therefore provides a genetic model for DS. In this study, high resolution magnetic resonance imaging and histological analysis demonstrate precise neuro- anatomical parallels between the DS and the Ts65Dn cerebellum. Cerebellar volume is significantly reduced in Ts65Dn mice due to reduction of both the internal granule layer and the molecular layer of the cerebellum. Granule cell number is further reduced by a decrease in cell density in the internal granule layer. Despite these changes in Ts65Dn cerebellar structure, motor deficits have not been detected in several tests. Reduction in granule cell density in Ts65Dn mice correctly predicts an analogous pathology in humans; a significant reduction in granule cell density in the DS cerebellum is reported here for the first time. The candidate region of genes on chromosome 21 affecting cerebellar development in DS is therefore delimited to the subset of genes whose orthologs are at dosage imbalance in Ts65Dn mice, providing the first localization of genes affecting a neuroanatomical phenotype in DS. The application of this model for analysis of developmental perturbations is extended by the accurate prediction of DS cerebellar phenotypes.


Ischemic burden by 3-dimensional myocardial perfusion cardiovascular magnetic resonance: comparison with myocardial perfusion scintigraphy.
The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with (99m)Tc-tetrofosmin MPS. Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45). 3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia.


Mild Telomere Dysfunction as a Force for Altering the Adaptive Potential of Subtelomeric Genes.
Subtelomeric regions have several unusual characteristics, including complex repetitive structures, increased rates of evolution, and enrichment for genes involved in niche adaptation. The adaptive telomere failure hypothesis suggests that certain environmental stresses can induce a low level of telomere failure, potentially leading to elevated subtelomeric recombination that could result in adaptive mutational changes within subtelomeric genes. Here, we tested a key prediction of the adaptive telomere failure hypothesis-that telomere dysfunction mild enough to have little or no overall effect on cell fitness could still lead to substantial increases in the mutation rates of subtelomeric genes. Our results show that a mutant of Kluyveromyces lactis with stably short telomeres produced a large increase in the frequency of mutations affecting the native subtelomeric β-galactosidase (LAC4) gene. All lac4 mutants examined from strains with severe telomere dysfunction underwent terminal deletion/duplication events consistent with being due to break-induced replication. In contrast, although cells with mild telomere dysfunction also exhibited similar terminal deletion and duplication events, up to 50% of lac4 mutants from this background unexpectedly contained base changes within the LAC4 coding region. This mutational bias for producing base changes demonstrates that mild telomere dysfunction can be well suited as a force for altering the adaptive potential of subtelomeric genes.


Talking with hands: body representation in British Sign Language users.
Body representation (BR) refers to the mental representation of motor, sensory, emotional and semantic information about the physical body. This cognitive representation is used in our everyday life, continuously, even though most of the time we do not appreciate it consciously. In some cases, BR is vital to be able to communicate. A crucial feature of signed languages (SLs), for instance, is that body parts such as hands are used to communicate. Nevertheless, little is known about BR in SL: is the communicative function of the body overwriting the physical constraints? Here, we explored this question by comparing twelve British Sign Language (BSL) learners to seventeen tango dancers (body expertise but not for communication) and fourteen control subjects (no special body expertise). We administered the Body Esteem Scale (BES), the Hand Laterality Task (HLT) and the Mental Motor Chronometry (MMC). To control for visual imagery, we administered ad hoc control tasks. We did not identify parameters able to differentiate between SL users and the other groups, whereas the more implicit parameters distinguished clearly tango dancers from controls. Importantly, neither tasks on visual imagery nor the BES revealed differences. Our findings offer initial evidence that linguistic use of the body not necessarily influences the cognitive components we explored of body representation.


Expression and function of a novel variant of estrogen receptor-α36 in murine airways.
Evidence suggests that estrogen signaling is involved in sex differences in the prevalence rates and control of asthma, but the expression patterns of estrogen receptor variants and estrogen function in the lung are not well established. We investigated the expression of major estrogen receptor variants occurring naturally and after the development of allergen-induced airway hyperreactivity in a murine model of allergic asthma, along with the role of estrogen signaling in small-airway ciliary motion and smooth muscle contraction. Female BALB/c mice were sensitized with ovalbumin, and estrogen receptor expression patterns were examined by immunofluorescence and Western blot analysis. Time-lapse video and photodiode-based displacement measurement systems were used to assess the effects of estrogen signaling on airway ciliary beat frequency and smooth muscle contraction. We found that a novel variant of estrogen receptor (ER)-α, ER-α36, is expressed in airway epithelial and smooth muscle cells. ER-α36 was predominately localized on the plasma membranes of airway cells. After sensitization to allergen, the expression levels of ER-α36 increased significantly (P < 0.01), whereas the expression of ER-β and ER-α66 did not significantly change. Estrogen treatment in vitro resulted in a rapid increase in airway cilia motion in a dose-dependent fashion, but did not exert any effect on airway smooth muscle contraction. We speculate that the up-regulation of estrogen receptor expression associated with allergen-induced airway hyperresponsiveness may constitute a protective mechanism to facilitate the clearance of mucus. The identification and localization of specific estrogen receptor subtypes in the lung could lead to newer therapeutic avenues aimed at addressing sex differences of asthma susceptibility.


Schistura larketensis, a new cavernicolous fish (Teleostei: Nemacheilidae) from Meghalaya, Northeast India.
Schistura larketensis, a new species of cavernicolous loach, is described from Khung, a limestone cave in Meghalaya, India. The species differs from Schistura papulifera, its only troglomorphic congener from northeast India, in having a smooth ventral surface of the head, the presence of a small cylindrical axillary pelvic lobe, and the presence of three pores in the supratemporal canal of the cephalic lateral-line system. Apart from these differences, the species can be immediately distinguished from all other species of Schistura from the Brahmaputra River and neighboring basins by the complete absence (or only vestigial presence) of eyes.


Impact of biochar on mobilization, methylation, and ethylation of mercury under dynamic redox conditions in a contaminated floodplain soil.
Mercury (Hg) is a highly toxic element, which is frequently enriched in flooded soils due to its anthropogenic release. The mobilization of Hg and its species is of ultimate importance since it controls the transfer into the groundwater and plants and finally ends in the food chain, which has large implications on human health. Therefore, the remediation of those contaminated sites is an urgent need to protect humans and the environment. Often, the stabilization of Hg using amendments is a reliable option and biochar is considered a candidate to fulfill this purpose. We tested two different pine cone biochars pyrolyzed at 200 °C or 500 °C, respectively, with a view to decrease the mobilization of total Hg (Hgt), methylmercury (MeHg), and ethylmercury (EtHg) and/or the formation of MeHg and EtHg in a contaminated floodplain soil (Hgt: 41 mg/kg). We used a highly sophisticated automated biogeochemical microcosm setup to systematically alter the redox conditions from ~-150 to 300 mV. We continuously monitored the redox potential (EH) along with pH and determined dissolved organic carbon (DOC), SUVA254, chloride (Cl-), sulfate (SO42-), iron (Fe), and manganese (Mn) to be able to explain the mobilization of Hg and its species. However, the impact of biochar addition on Hg mobilization was limited. We did not observe a significant decrease of Hgt, MeHg, and EtHg concentrations after treating the soil with the different biochars, presumably because potential binding sites for Hg were occupied by other ions and/or blocked by biofilm. Solubilization of Hg bound to DOC upon flooding of the soils might have occurred which could be an indirect impact of EH on Hg mobilization. Nevertheless, Hgt, MeHg, and EtHg in the slurry fluctuated between 0.9 and 52.0 μg/l, 11.1 to 406.0 ng/l, and 2.3 to 20.8 ng/l, respectively, under dynamic redox conditions. Total Hg concentrations were inversely related to the EH; however, ethylation of Hg was favored at an EH around 0 mV while methylation was enhanced between -50 and 100 mV. Phospholipid fatty acid profiles suggest that sulfate-reducing bacteria may have been the principal methylators in our experiment. In future, various biochars should be tested to evaluate their potential in decreasing the mobilization of Hg and to impede the formation of MeHg and EtHg under dynamic redox conditions in frequently flooded soils.


Peripheral biomarkers of endometriosis: a systematic review.
Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage. We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine. We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful. Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.


Renal manifestations in HIV-infected Jamaican children.
Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children. A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications. Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years. HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.


The influence of elastic upstream artery length on fluid-structure interaction modeling: a comparative study using patient-specific cerebral aneurysm.
Fluid-structure interaction (FSI) simulations using a patient-specific geometry are carried out to investigate the influence the length of elastic parent artery and the position of constraints in the solid domain on the accuracy of patient-specific FSI simulations. Three models are tested: Long, Moderate, and Short, based on the length of the elastic parent artery. All three models use same wall thickness (0.5 mm) and the elastic modulus (5 MPa). The maximum mesh displacement is the largest for the Long model (0.491 mm) compared to other models (0.3 mm for Moderate, and 0.132 mm for Short). The differences of hemodynamic and mechanical variables, aneurysm volume and cross-sectional area between three models are all found to be minor. In addition, the Short model takes the least amount of computing time of the three models (11h compared to 21 h for Long and 19 h for Moderate). The present results indicate that the use of short elastic upstream artery can shorten the time required for pati ent-specific FSI simulations without impacting the overall accuracy of the results.


Opioid growth factor modulates angiogenesis.
Induced angiogenesis has recently been attempted as a therapeutic modality in patients with occlusive arterial atherosclerotic disease. We investigated the possible role of endogenous opioids in the modulation of angiogenesis. Chick chorioallantoic membrane was used as an in vivo model to study angiogenesis. Fertilized chick eggs were incubated for 3 days, explanted, and incubated for an additional 2 days. Three-millimeter methylcellulose disks were placed on the surface of the chorioallantoic membrane; each disk contained opioid growth factor ([Met(5)]-enkephalin; 5 microgram), the short-acting opioid receptor antagonist naloxone (5 microgram), opioid growth factor and naloxone together (5 microgram of each), the long-acting opioid antagonist naltrexone (5 microgram), or distilled water (control). A second series of experiments was performed with distilled water, the angiogenic inhibitor retinoic acid (1 microgram), and vascular endothelial growth factor (1 microgram) to further evaluate our model. The developing vasculature was imaged 2 days later with a digital camera and exported to a computer for image analysis. Total number of blood vessels, total vessel length, and mean vessel length were measured within a 100-mm(2) region surrounding each applied disk. Immunocytochemical analysis was performed with antibodies directed against opioid growth factor and its receptor (OGFr). Opioid growth factor had a significant inhibitory effect on angiogenesis, both the number of blood vessels and the total vessel length being decreased (by 35% and 20%, respectively) in comparison with control levels (P <.005). The simultaneous addition of naloxone and opioid growth factor had no effect on blood vessel growth, nor did naloxone alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51% and 24% in blood vessel number and length, respectively, in comparison with control specimens (P <.005). These results indicate that the opioid growth factor effects are receptor mediated and tonically active. Immunocytochemistry demonstrated the presence of both opioid growth factor and OGFr within the endothelial cells and mesenchymal cells of the developing chorioallantoic membrane vessel wall. Retinoic acid significantly reduced the number and the total length of blood vessels, whereas vascular endothelial growth factor increased both the number and the length of blood vessels in comparison with the controls (P <.0001). The magnitude of opioid growth factor's effects were comparable to those seen with retinoic acid, whereas inhibition of opioid growth factor with naltrexone induced an increase in total vessel length comparable to that for vascular endothelial growth factor. These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells.


Realizing any central projection with a mirror pair.
We show that, for any rotationally symmetric projection with a single virtual viewpoint, it is possible to design a two-mirror rotationally symmetric system that realizes the projection exactly. These mirror pairs are derived from two coupled differential equations. We give examples in which the projections from the sphere at infinity are stereographic, perspective, and equiresolution.


Inhaled corticosteroid therapy reduces the early morning peak in cortisol and aldosterone.
1. As mineralocorticoid and adrenocorticoid activity are both under the diurnal control of adrenocorticotropic hormone secretion, we aimed to evaluate whether the normal circadian rhythm of cortisol and aldosterone secretion was suppressed by inhaled corticosteroid therapy.2.Ten normotensive patients with mild-moderate asthma, mean age 24.0 (S.D. 9.8) years and mean arterial pressure 90.7 (9.8) mmHg, were studied in a double-blind, randomized crossover design comparing placebo with fluticasone propionate, 1000 microgram administered twice daily at 08:00 h and 20:00 h. After 5 days of repeated dosing at steady state, measurements were made of plasma cortisol and aldosterone at midnight and 08:00 h.3. With placebo there was a significant (P<0.05) difference between cortisol values at 08:00 h (588.6+/-83.8 nmol/l) and midnight (109.6+/-35.0 nmol/l), whereas after treatment with fluticasone propionate there was no significant difference between levels at 08:00 h (143.3+/-57.4 nmol/l) and midnight (64.3+/-22.3 nmol/l). For cortisol at 08:00 h there was also a significant (P<0.05) difference between placebo and fluticasone propionate. The same pattern was observed for aldosterone. Plasma aldosterone levels at 08:00 h after treatment with placebo (129.6+/-30.9 nmol/l) were significantly different (P<0. 05) to those seen at midnight (40.4+/-6.2 nmol/l). After treatment with fluticasone propionate, there was no significant difference between levels at midnight (55.4+/-11.7 nmol/l) and 08:00 h (64. 8+/-12.7 nmol/l).4. These results show that inhaled corticosteroid therapy abolishes the circadian rhythm of aldosterone and cortisol secretion. This may have possible implications for patients taking inhaled corticosteroids in terms of the beneficial cardiac effects of suppressing early morning aldosterone.


Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected].
Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to different glycolipid Ags, with distinct functional outcomes. Biochemical parameters controlling iNKT cell function are partly defined. However, the impact of iNKT cell receptor beta-chain repertoire and how alpha-galactosylceramide (alpha-GalCer) analogues induce distinct functional responses have remained elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire of iNKT cells impacts recognition and Ag avidity, and that stimulation with suboptimal avidity Ag results in preferential expansion of high-affinity iNKT cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT cell receptor down-regulation, are induced within narrow biochemical thresholds. Multimers of CD1d1-alphaGalCer- and alphaGalCer analogue-loaded complexes demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose structure and/or organization appear distinct from conventional alphabeta TCR. Our findings demonstrate that iNKT cell functions are controlled by affinity thresholds for glycolipid Ags and reveal a novel property of their Ag receptor apparatus that may have an important role in iNKT cell activation.


Dynamic buckling of actin within filopodia.
Filopodia are active tubular structures protruding from the cell surface which allow the cell to sense and interact with the surrounding environment through repetitive elongation-retraction cycles. The mechanical behavior of filopodia has been studied by measuring the traction forces exerted on external substrates.(1) These studies have revealed that internal actin flow can transduce a force across the cell surface through transmembrane linkers like integrins. In addition to the elongation-retraction behavior filopodia also exhibit a buckling and rotational behavior. Filopodial buckling in conjunction with rotation enables the cell to explore a much larger 3-dimensional space and allows for more complex, and possibly stronger, interactions with the external environment.(2) Here we focus on how bending of the filopodial actin dynamically correlates with pulling on an optically trapped microsphere which acts like an external substrate attached to the filopodial tip. There is a clear correlation between presence of actin near the tip and exertion of a traction force, thus demonstrating that the traction force is transduced along the actin shaft inside the filopodium. By extending a filopodium and holding it while measuring the cellular response, we also monitor and analyze the waiting times for the first buckle observed in the fluorescently labeled actin shaft.


Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.
While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher overall burden of mutations in all cancer genes. We identified several pathogenic variants that likely predispose to at least one of the tumours in patients with multiple cancers. We additionally present evidence that there may be a higher burden of variants of unknown significance in 'cancer genes' in patients with multiple cancer types. Further screens of this nature need to be carried out to build evidence to show if the cancers observed in these patients form part of a cancer spectrum associated with single germline variants in these genes, whether multiple layers of susceptibility exist (oligogenic or polygenic), or if the occurrence of multiple different cancers is due to random chance.


The prevalence of metabolic syndrome in drug-naïve bipolar II disorder patients before and after twelve week pharmacological intervention.
Accumulating evidence indicates a high prevalence rate of metabolic disturbance in bipolar disorder (BP) patients. However, the prevalence across BP subtypes has been investigated to a lesser degree. In the current study, we surveyed the prevalence of metabolic syndrome among drug-naïve bipolar II patients. Moreover, the effects of pharmacological treatment on metabolic indexes were also evaluated. This study recruited fifty-six drug-naïve BP II patients diagnosed according to the DSM-IV criteria. Among them, forty-four patients completed a 12-week pharmacological intervention with valproic acid, fluoxetine and lorazepam. Metabolic profiles and body mass index (BMI) were measured at baseline and 2 weeks, 8 weeks, and 12 weeks after receiving medication. The mean age of the 56 patients was 30.3±11.1. Before receiving medication, 6.5% of the patients met the ATP III criterion for metabolic syndrome. Among the 44 patients who completed the 12-week pharmacological intervention, the prevalence of metabolic syndrome increased from 7% to 10%. Repeated measurements showed that the changes in metabolic indexes were not significant, with the exceptions of BMI, waist circumference, and buttock circumference. In addition, the interaction between the improvement of hypomanic symptoms and BMI change was significant. The study was limited by the follow-up duration and sample size. In drug-naïve BP II patients, the prevalence of metabolic syndrome was significantly lower than that observed before in BP I patients. However, medications use was also associated with an increased risk of metabolic disturbance, although the impact was lesser. Clinical evidence suggests that metabolism and emotion homeostasis might share common mechanisms.


Remote powering platform for implantable sensor systems at 2.45 GHz.
Far-field remotely powered sensor systems enable long distance operation for low-power sensor systems. In this work, we demonstrate a remote powering platform with a miniaturized antenna and remote powering base station operating at 2.45 GHz. The rectenna, which is the energy receiving and conversion element of the sensor system, is designed and measured. The measurements for the tag are performed within 15 cm distance from the remote powering base station. The realized gain of the tag antenna is measured as -3.3 dB, which is 0.5 dB close to the simulations, where simulated realized gain is -2.8 dB.


First Graders' Stationary Behavior in Norwegian After-School Programs: A Mixed Methods Investigation.
After-school programs (ASPs) might influence the activities and behaviors of children. The aim of the reported study was to investigate how stationary behavior unfolds during ASP time in a sample of Norwegian first graders. A total of 42 first graders from 14 ASPs were observed during one entire ASP day. ActiGraph accelerometers were used to measure the intensity of their physical activity (PA). Children were found to be involved in stationary behavior for 54.9% of the studied ASP time-a median of 79.5 min (IQR = 62.0). However, there was considerable variation among the children in the sample. Most stationary behavior-63.5% of all stationary behavior during ASP time-was accumulated when the children were sitting indoors. The proportion of stationary behavior was significantly higher indoors than outdoors, during adult-managed time than child-managed time, and during time spent together with other children than time spent alone (p < 0.05). In child-managed physical activity play outdoors, stationary behavior commonly occurred during short periods of standing still. Stationary behavior was usually rapidly broken up by longer periods of PA. Stationary periods involved activities in close relationship with other children and appeared to be important for social interaction and friendship building. The researchers suggest that ASP staff members should actively promote physical activity play that breaks up sedentary time and replaces some stationary behaviors with PA, especially among the least active children.


Frequency of Arthritis-Like MRI Findings in the Forefeet of Healthy Volunteers Versus Patients With Symptomatic Rheumatoid Arthritis or Psoriatic Arthritis.
The objective of the present study is to evaluate arthritis-like findings on MRI studies of the forefeet of healthy volunteers versus patients with symptomatic rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Two observers analyzed MR images of the forefeet of 31 healthy volunteers, 30 patients with symptomatic RA, and 30 patients with symptomatic PsA, to identify MRI patterns of RA or PsA (e.g., bone marrow edema [BME], erosions, tenosynovitis, joint effusion, periarticular soft-tissue edema, or bony proliferations) on the basis of the Outcome Measures in Rheumatoid Arthritis Clinical Trial RA MRI scoring system and the PsA MRI scoring system. The Mann-Whitney test with Bonferroni correction was used for statistical analysis. Reader 1 found BME in 14 healthy volunteers (45%), whereas reader 2 found BME in 10 volunteers (32%). Tenosynovitis was observed by reader 1 in three healthy volunteers (10%). Joint effusion was found by reader 1 in seven healthy volunteers (23%) and by reader 2 in three volunteers (10%); the mean intensity grades for these findings were low (range, 1-1.33). Erosions, soft-tissue edema, and bony proliferations were not found in the forefeet of healthy volunteers. Reader 1 and reader 2 observed all arthritis-like features on the MR images of patients with RA. The percentages of patients with RA who had such MRI features, as identified by reader 1 and reader 2, respectively, were as follows: BME, 83% and 80%; erosions, 40% and 40%; tenosynovitis, 33% and 17%; effusion, 87% and 53%; soft-tissue edema, 20% and 27%; and bony proliferations, 3% and 3%. The percentages of patients with PsA who were found to have arthritis-like findings on MR images, as determined by reader 1 and reader 2, respectively, were as follows: BME, 70% and 67%; erosions, 20% and 20%; tenosynovitis, 57% and 50%; effusion, 70% and 37%; and soft-tissue edema, 60% and 53%. Bony proliferations were observed by reader 2 only in 7% of patients with PsA. The mean minimum intensity grade was 1 (for tenosynovitis in patients with RA, as observed by reader 2), whereas the maximum intensity grade was 2.53 (for erosions in patients with RA, as observed by reader 1). Tenosynovitis and soft-tissue edema were observed more frequently in patients with PsA than in patients with RA (p = 0.001-0.059). On the forefoot of healthy volunteers, mild BME is a common finding, and tenosynovitis and joint effusion are occasional findings. The frequency and intensity of arthritis-like findings on MRI are similar in patients with RA and PsA, with the exception of tenosynovitis and soft-tissue edema, which are more frequently observed in patients with PsA than in patients with RA.


[Case report of introducing MMF and steroids as an immunosuppressive therapy after living-donor liver transplantation for a patient with the diabetic nephropathy].
Calcineurin inhibitor (CNI) combined with mycophenolate mofetil (MMF) and steroid is mainly used as immunosuppressive therapy after the living-donor liver transplantation (LDLT). However, the nephrotoxicity caused by CNI remains a critical problem for patients with chronic renal failure, especially on early postoperative period. A 62-year-old woman with decompensated liver cirrhosis secondary to hepatitis B (Child-Pugh C, MELD score 11 points) and chronic renal failure due to diabetic nephropathy (Cr 1.56 mg/dl, GFR 27 ml/min/1.73 m2) experienced LDLT. During the reconstruction of hepatic vein, the supra-and infra-hepatic vena cava was totally clamped. The estimated right lobe liver graft volume was 540 g, representing 51.3% of the standard liver volume of the recipient. Because of the perioperative renal dysfunction due to diabetic nephropathy and the total clamping the vena cava which induced the congestion kidney, MMF (1500 mg/day) and steroid (250 mg/day converted into predonisolone) were mainly introduced as an immunosuppressive therapy after LDLT. The low-dose CNI, tacrolimus also induced the nephrotoxicity and was given for only a short time. Finally, according to the postoperative renal function, the low-dose CNI, cyclosporin (50 mg/day) was able to be added to the introduced immunosuppressive therapy. After having left the hospital, MMF (1500 mg/day), steroid (20 mg/day converted into predonisolone) and cyclosporin (75 mg/day) continued to be given as the immunosuppressive therapy and neither acute graft rejection nor drug-induced renal dysfunction was occurred. This is a case report of introducing with mainly MMF and steroid as an immunosuppressive therapy after LDLT for a patient with perioperative renal dysfunction.


Deduction plans: a basis for intelligent backtracking.
A proof procedure is described that relies on the construction of certain directed graphs called ``deduction plans.'' Plans represent the structure of proofs in such a way that problem reduction may be used without imposing any ordering on the solution of subproblems, as required by other systems. The structure also allows access to all clauses deduced in the course of a proof, which may then be used as lemmas. Economy of representation is the maximum attainable, consistent with this unrestricted availability of lemmas. Restricted versions of this deduction system correspond to existing linear deduction procedures, but do not suffer from some of their shortcomings, such as redundant representation, strict ordering of subproblems, and explicit substitution. One of the rules for constructing plans, however, allows a subproblem to be factored to a previously solved one: this has no equivalent in existing system. A further economy is obtained by making it unnecessary to perform substitutions and calculate most general unifiers. The source of unification failure can be located when a subproblem is found to be unsolvable, so that exact backtracking can be performed rather than the blind backtracking performed by existing systems. Therefore, a deduction system based on the construction of plans can avoid the wasteful search of irrelevant areas of the search space that results from the usual backtracking methods.


Sodium Iodate Produces a Strain-Dependent Retinal Oxidative Stress Response Measured In Vivo Using QUEST MRI.
We identify noninvasive biomarkers that measure the severity of oxidative stress within retina layers in sodium iodate (SI)-atrophy vulnerable (C57BL/6 [B6]) and SI-atrophy resistant (129S6/SvEvTac [S6]) mice. At 24 hours after administering systemic SI to B6 and S6 mice we measured: (1) superoxide production in whole retina ex vivo, (2) excessive free radical production in vivo based on layer-specific 1/T1 values before and after α-lipoic acid (ALA) administration while the animal was inside the magnet (QUEnch-assiSTed MRI [QUEST MRI]), and (3) visual performance (optokinetic tracking) ± antioxidants; control mice were similarly assessed. Retinal layer spacing and thickness in vivo also were evaluated (optical coherence tomography, MRI). SI-treated B6 mice retina had a significantly higher superoxide production than SI-treated S6 mice. ALA-injected SI-treated B6 mice had reduced 1/T1 in more retinal layers in vivo than in SI-treated S6 mice. Uninjected and saline-injected SI-treated B6 mice had similar transretinal 1/T1 profiles. Notably, the inner segment layer 1/T1 of SI-treated B6 mice was responsive to ALA but was unresponsive in SI-treated S6 mice. In both SI-treated strains, antioxidants improved contrast sensitivity to similar extents; antioxidants did not change acuity in either group. Retinal thicknesses were normal in both SI-treated strains at 24 hours after treatment. QUEST MRI uniquely measured severity of excessive free radical production within retinal layers of the same subject. Identifying the mechanisms underlying genetic vulnerabilities to oxidative stress is expected to help in understanding the pathogenesis of retinal degeneration.


Dimensional control of supramolecular assemblies of diacetylene-derived peptide gemini amphiphile: from spherical micelles to foamlike networks.
Peptide amphiphiles capable of assembling into multidimensional nanostructures have attracted much attention over the past decade due to their potential applications in materials science. Herein, a novel diacetylene-derived peptide gemini amphiphile with a fluorenylmethyloxycarbonyl (Fmoc) group at the N-terminus is reported to hierarchically assemble into spherical micelles, one-dimensional nanorods, two-dimensional foamlike networks and lamellae. Solvent polarity shows a remarkable effect on the self-assembled structures by changing the balance of four weak noncovalent interactions (hydrogen-bonding, π-π stacking, hydrophobic interaction, and electrostatic repulsion). We also show the time-evolution not only from spherical micelles to helical nanofibers in aqueous solution, but also from branched wormlike micelles to foamlike networks in methanol solution. In this work, the presence of the Fmoc group plays a key role in the self-assembly process. This work provides an efficient strategy for precise morphological control, aiding the future development in materials science.


When the decision is what to decide: using evidence inventory reports to focus health technology assessments.
Health systems frequently make decisions regarding acquisition and use of new technologies. It is desirable to base these decisions on clinical evidence, but often these technologies are used for multiple indications and evidence of effectiveness for one indication does not prove effectiveness for all. Here, we describe two examples of evidence inventory reports that were performed for the purposes of identifying how much and what type of published clinical evidence was available for a given technology, and the contexts in which those technologies were studied. The evidence inventory reports included literature searches for systematic reviews and health technology assessment (HTA) reports, and systematic searches of the primary literature intended to count and categorize published clinical studies. The reports did not include analysis of the primary literature. The inventory reports were completed in 3 to 4 days each and were approximately ten pages in length, including references. Reports included tables listing the number of reported studies by specific indication for use, and whether or not there were randomized trials. Reports also summarized findings of existing systematic reviews and HTA reports, when available. Committees used the inventory reports to decide for which indications they wanted a full HTA report. Evidence inventory reports are a form of rapid HTA that can give decision makers a timely understanding of the available evidence upon which they can base a decision. They can help HTA providers focus subsequent reports on topics that will have the most influence on healthcare decision making.


Tethering Innate Surface Receptors on Dendritic Cells: A New Avenue for Immune Tolerance Induction?
Dendritic cells (DCs) play a key role in immunity and are highly potent at presenting antigens and orienting the immune response. Depending on the environmental signals, DCs could turn the immune response toward immunity or immune tolerance. Several subsets of DCs have been described, with each expressing various surface receptors and all participating in DC-associated immune functions according to their specific skills. DC subsets could also contribute to the vicious circle of inflammation in immune diseases and establishment of immune tolerance in cancer. They appear to be appropriate targets in the control of inflammatory diseases or regulation of autoimmune responses. For all these reasons, in situ DC targeting with therapeutic antibodies seems to be a suitable way of modulating the entire immune system. At present, the field of antibody-based therapies has mainly been developed in oncology, but it is undergoing remarkable expansion thanks to a wide variety of antibody formats and their related functions. Moreover, current knowledge of DC biology may open new avenues for targeting and modulating the different DC subsets. Based on an update of pathogen recognition receptor expression profiles in human DC subsets, this review evaluates the possibility of inducing tolerant DCs using antibody-based therapeutic agents.