A polymorphism near MC4R gene (rs17782313) is associated with serum triglyceride levels in the general Japanese population: the J-MICC Study.
Previously reported associations of a common polymorphism near melanocortin-4 receptor (MC4R) gene (rs17782313) with BMI/obesity were inconsistent, especially in East Asia, and the associations of the polymorphism with serum lipid levels have not been fully elucidated. This study evaluated the association between rs17782313 and obesity-related traits and serum lipid levels in the general Japanese population. A total of 2,035 subjects (aged 35-69 years, 1,024 males and 1,011 females) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We examined the associations between near MC4R polymorphism (rs17782313) and obesity-related traits [height, weight, body mass index (BMI), weight change from 20 years old], serum lipid levels (triglycerides, total and HDL-cholesterol), and intake of nutrients (total energy and macronutrients). Polymorphism of rs17782313 (minor C allele) was positively associated with serum triglyceride levels (P for trend = 0.020) adjusted for age and sex. Analysis using a general linear model revealed that the number of minor C alleles was positively associated with serum triglyceride levels after adjustment for age, sex, and potential confounders (P for trend = 0.004). Statistical significance did not change after further adjustment for total energy intake and BMI. There was no significant association between rs17782313 and obesity-related traits including BMI. Interactions between rs17782313 and sex, BMI, or total energy intake for triglyceride levels were not significant. To our knowledge, this study demonstrated for the first time that rs17782313 was associated with serum triglyceride levels in Asian population. Further studies are needed to confirm this result.


Biocultural implications of oral pathology in an ancient Central California population.
Bioarchaeologists have long noted two unusual trends in the dentitions of prehistoric Native Californian populations: high rates of wear and low prevalence of caries. The Central California site of CA-CCO-548 offers a unique opportunity to examine the relationship between oral pathology and extreme dental wear in a large (n = 480), ancient (4,300–3,100 BP), and temporally well-defined population sample. This study specifically examines three interrelated processes of the oral cavity in this population: dental wear, dental caries, and periodontal disease. The results show high levels of dental wear (average of 6.1, Smith system), low frequencies of carious lesions (2.5%), low frequencies of periodontal disease (17.8%), and high frequencies of periapical abscesses (10.7%). The pathological processes examined here have complicated multifactorial etiologies. However, they all share the common primary etiological agents of facultative pathogenic bacteria proliferation in the oral biofilm. Integration of the current etiological explanations for infections of the oral cavity, information from the ethnographic record pertaining to subsistence and activity patterns in Native Californian populations, and statistical analysis of specific disease and wear patterns leads to a novel explanation for the observed pattern of oral pathology in this population sample. Specifically, the introduction of antibacterial compounds through dietary items and non-alimentary tooth use is suggested as the most likely explanation for the unusually low prevalence of dental caries and periodontal disease.


Bilateral hydronephrosis due to fecaloma in an elderly woman.
By computer search of the literature, we found few cases of hydronephrosis due to fecal impaction. Because such a complication is extremely rare, we describe an 81-year-old woman with dementia, gallstones, arterial hypertension, and diverticulosis of the sigma who was hospitalized for severe constipation, fecaloma, and bilateral hydronephrosis. Through simultaneous lavage by two rectal tubes and manual disimpaction of fecaloma, bilateral hydronephrosis was resolved. We also briefly review the appropriate literature.


Factors associated with injury severity in Oklahoma City bombing survivors.
Terrorist bombings are an increasing source of violent death and injury worldwide. Injuries in building bombings have been previously reported in descriptive studies, but no comparative analyses have quantitatively assessed factors influencing the severity of nonfatal bombing injuries. The objective of this study was to identify personal and environmental risk factors for injury severity in the Oklahoma City bombing, on April 19, 1995. We conducted a retrospective comparative analysis of 509 nonfatally injured occupants of four buildings surrounding the detonation site. The source of data was the 1995 Oklahoma City Bombing database, a registry of all injuries and fatalities related to the bombing. Multivariable logistic regression was used to assess two outcomes: (1) medically-attended injury among injured occupants; and (2) hospital admission among occupants with medically attended injuries. Increased odds of sustaining medically attended injuries were associated with being struck by flying glass (adjusted odds ratio [AOR], 5.3; 95% confidence interval [CI], 1.9-14.8) and location above the first floor of buildings (OR, 4.0; 95% CI, 1.4-11.7) after adjustment for other factors. Adjusted odds of hospital admission were associated with location in the collapsed region (AOR, 43.4; 95% CI, 4.4-434.1), being blown by the blast wind (AOR, 5.3; 95% CI, 2.1-13.8), and being trapped (AOR, 3.1; 95% CI, 1.2-7.7). The severity of nonfatal injury in the Oklahoma bombing was primarily associated with structural and environmental factors. Improved architectural design may prevent many injuries in building bombings. These finding provide evidence for future injury prevention activities.


UnReal? Investigating the Sense of Reality and Psychotic Symptoms with Virtual Reality.
Distortions of reality, such as hallucinations, are common symptoms of many psychiatric conditions. Accordingly, sense of reality (SoR), the ability to discriminate between true and false perceptions, is a central criterion in the assessment of neurological and psychiatric health. Despite the critical role of the SoR in daily life, little is known about how this is formed in the mind. Here, we propose a novel theoretical and methodological framework to study the SoR and its relation to psychotic symptoms. In two experiments, we employed a specialized immersive virtual reality (VR) environment allowing for well-controlled manipulations of visual reality. We first tested the impact of manipulating visual reality on objective perceptual thresholds (just noticeable differences). In a second experiment, we tested how these manipulations affected subjective judgments of reality. The results revealed that the objective perceptual thresholds were robust and replicable, demonstrating that SoR is a stable psychometric property that can be measured experimentally. Furthermore, reality alterations reduced subjective reality judgments across all manipulated visual aspects. Finally, reduced sensitivity to changes in visual reality was related to self-reported prodromal psychotic symptoms. These results provide evidence for the relevance of SoR in the assessment of psychosis and other mental disorders in which reality is distorted.


Market dynamics immediately before and after financial shocks: Quantifying the Omori, productivity, and Bath laws.
We study the cascading dynamics immediately before and immediately after 219 market shocks. We define the time of a market shock T{c} to be the time for which the market volatility V(T{c}) has a peak that exceeds a predetermined threshold. The cascade of high volatility "aftershocks" triggered by the "main shock" is quantitatively similar to earthquakes and solar flares, which have been described by three empirical laws-the Omori law, the productivity law, and the Bath law. We analyze the most traded 531 stocks in U.S. markets during the 2 yr period of 2001-2002 at the 1 min time resolution. We find quantitative relations between the main shock magnitude M≡log{10} V(T{c}) and the parameters quantifying the decay of volatility aftershocks as well as the volatility preshocks. We also find that stocks with larger trading activity react more strongly and more quickly to market shocks than stocks with smaller trading activity. Our findings characterize the typical volatility response conditional on M , both at the market and the individual stock scale. We argue that there is potential utility in these three statistical quantitative relations with applications in option pricing and volatility trading.


Selection of prime actor in humans during bimanual object manipulation.
In bimanual object manipulation tasks, people flexibly assign one hand as a prime actor while the other assists. Little is known, however, about the neural mechanisms deciding the role assignment. We addressed this issue in a task in which participants moved a cursor to hit targets on a screen by applying precisely coupled symmetrical opposing linear and twist forces on a tool held freely between the hands. In trials presented in an unpredictable order, the action of either the left or the right hand was spatially congruent with the cursor movements, which automatically rendered the left or right hand the dominant actor, respectively. Functional magnetic resonance imaging indicated that the hand-selection process engaged prefrontal cortical areas belonging to an executive control network presumed critical for judgment and decision-making and to a salience network attributed to evaluation of utility of actions. Task initiation, which involved switching between task sets, had a superordinate role with reference to hand selection. Behavioral and brain imaging data indicated that participants initially expressed two competing action representations, matching either mapping rule, before selecting the appropriate one based on the consequences of the initial manual actions. We conclude that implicit processes engaging the prefrontal cortex reconcile selections among action representations that compete for the establishment of a dominant actor in bimanual object manipulation tasks. The representation selected is the one that optimizes performance by relying on the superior capacity of the brain to process spatial congruent, as opposed to noncongruent, mappings between manual actions and desired movement goals.


Geometrically defined spin structures in ultrathin Fe3O4 with bulk like magnetic properties.
We have grown high quality magnetite microcrystals free from antiphase boundaries on Ru(0001) by reactive molecular beam epitaxy, conserving bulk magnetic properties below 20 nm thickness. Magnetization vector maps are obtained by X-ray spectromicroscopy and compared with micromagnetic simulations. The observed domain configurations are dictated purely by shape anisotropy, overcoming the possible influences of (magneto)crystalline anisotropy and defects, thus demonstrating the possibility of designing spin structures in ultrathin, magnetically soft magnetite at will.


Genetic and physical evidence for plasmid control of Shigella sonnei form I cell surface antigen.
Virulent Shigella sonnei synthesize a surface antigen (form I) which appears to be one of several requirements needed for this host to invade epithelial cells. Upon restreaking on agar media, form I cells readily and irreversibly generate form II cells that lack the form I antigen. All form II cells are avirulent. Plasmid deoxyribonucleic acid of form I and II cells of four different S. sonnei isolates, obtained from different areas of the world, was analyzed by agarose gel electrophoresis. A large plasmid (approximately 120 megadaltons in three of the strains) that is present in form I cells was always absent from form II derivatives. Attempts to transfer conjugally only this large plasmid from form I to genetically marked form II cells were unsuccessful. However, a composite molecule, apparently formed by recombination between the large form I plasmid and a self-transmissible plasmid, was found to transfer the form I trait. Transconjugant S. sonnei strains acquiring the form I antigen could retransfer this trait to S. sonnei, Shigella flexneri, or Salmonella typhi. These preliminary findings demonstrate that S. sonnei form I antigen synthesis is mediated by a large plasmid which is lost spontaneously at a relatively high frequency from S. sonnei strains.


Which way up? Recognition of homologous DNA segments in parallel and antiparallel alignments.
Homologous gene shuffling between DNA molecules promotes genetic diversity and is an important pathway for DNA repair. For this to occur, homologous genes need to find and recognize each other. However, despite its central role in homologous recombination, the mechanism of homology recognition has remained an unsolved puzzle of molecular biology. While specific proteins are known to play a role at later stages of recombination, an initial coarse grained recognition step has, however, been proposed. This relies on the sequence dependence of the DNA structural parameters, such as twist and rise, mediated by intermolecular interactions, in particular, electrostatic ones. In this proposed mechanism, sequences that have the same base pair text, or are homologous, have lower interaction energy than those sequences with uncorrelated base pair texts. The difference between the two energies is termed the "recognition energy." Here, we probe how the recognition energy changes when one DNA fragment slides past another, and consider, for the first time, homologous sequences in antiparallel alignment. This dependence on sliding is termed the "recognition well." We find there is a recognition well for anti-parallel, homologous DNA tracts, but only a very shallow one, so that their interaction will differ little from the interaction between two nonhomologous tracts. This fact may be utilized in single molecule experiments specially targeted to test the theory. As well as this, we test previous theoretical approximations in calculating the recognition well for parallel molecules against MC simulations and consider more rigorously the optimization of the orientations of the fragments about their long axes upon calculating these recognition energies. The more rigorous treatment affects the recognition energy a little, when the molecules are considered rigid. When torsional flexibility of the DNA molecules is introduced, we find excellent agreement between the analytical approximation and simulations.


Network Topology in Soft Gels: Hardening and Softening Materials.
The structural complexity of soft gels is at the origin of a versatile mechanical response that allows for large deformation, controlled elastic recovery, and toughness in the same material. A limit to exploiting the potential of such materials is the insufficient fundamental understanding of the microstructural origin of the bulk mechanical properties. Here we investigate the role of the network topology in a model gel through 3D numerical simulations. Our study links the topology of the network organization in space to its nonlinear rheological response preceding yielding and damage: our analysis elucidates how the network connectivity alone could be used to modify the gel mechanics at large strains, from strain-softening to hardening and even to a brittle response. These findings provide new insight for smart material design and for understanding the nontrivial mechanical response of a potentially wide range of technologically relevant materials.


Forecasting Japan's physician shortage in 2035 as the first full-fledged aged society.
Japan is rapidly becoming a full-fledged aged society, and physician shortage is a significant concern. The Japanese government has increased the number of medical school enrollments since 2008, but some researchers warn that this increase could lead to physician surplus in the future. It is unknown how many physicians will be required to accommodate future healthcare needs. We simulated changes in age/sex composition of the population, fatalities (the number of fatalities for the consecutive five years), and number of physicians from 2010 to 2035. Two indicators were defined: fatalities per physician and fatalities by physician working hour, based on the data of the working hours of physicians for each tuple of sex and age groups. We estimated the necessary number of physicians in 2035 and the number of new physicians to maintain the indicator levels in 2010. The number of physicians per 1,000 population is predicted to rise from 2·00 in 2010 to 3·14 in 2035. The number of physicians aged 60 years or older is expected to increase from 55,375 (20% of physicians) to 141,711 (36%). In 2010 and 2035, fatalities per physician were 23·1 and 24·0 for the total population, and 13·9 and 19·2 for 75 years or older, respectively. Fatalities per physician working hour are predicted to rise from 0·128 to 0·138. If working hours are limited to 48 hours per week in 2035, the number of fatalities per physician working hour is expected to be 0·196, and the number of new physicians must be increased by 53% over the current pace. The number of physicians per population continues to rise, but the estimated supply will not fulfill the demand for healthcare in the aging society. Strategies to increase the number of physicians and improve working conditions are urgently needed.


[Gastrectomy with spleen preservation in patients with stomach cancer].
It was analyzed the results of surgical treatment of 118 patients with stomach cancer. Lymphadenectomy and gastrectomy were done in all cases. All patients were divided into two groups. Gastrectomy and splenectomy were performed in the first group, gastrectomy with preservation of spleen was done in the second group. It was revealed that splenectomy is not an independent prognostic factor influencing on prolonged survival of patients with stomach cancer. Preservation of spleen permits to reduce the number of early postoperative complications.


Seeking for Optimal Excited States in Photoinduced Electron-Transfer Processes─The Case Study of Brooker's Merocyanine.
Material design enters an era in which control of electrons in atoms, molecules, and materials is an essential property to be predicted and thoroughly understood in view of discovering new compounds with properties optimized toward specific optical/optoelectronic applications. π-electronic delocalization and charge separation/recombination enter notably into the set of features that are highly desirable to tailor. Diverse domains are particularly relying on photoinduced electron-transfer (PET), including fields of paramount importance such as energy production through light-harvesting, efficient chemoreceptive sensors, or organic field-effect transistors. In view of completing the arsenal of strategies in this area, we selected Brooker's merocyanine─a typical [D-π-A] compound─as the case study and examined from time-dependent density functional theory the opportunity offered by selected excited states to reach a suited manipulation of the charge transfer (CT) extent. In addition to the consideration of diagnostic tools able to spot the charge amount (i.e., magnitude of electron fraction) transferred upon excitation (qCT), the spatial extent associated with such an electronic transition or CT length (DCT), as well as the corresponding variation in dipole moment between the ground and the excited states (μCT), further analysis of the excitation process was undertaken. The advantage of going beyond the above-mentioned molecular indicators─which can be considered as PET global indices─was explored on the basis of a partitioning of the electron density. Relevant insight was gained on the relation these global indices have with the evolution of (local) features characterizing either chemical bond or electron delocalization upon vertical excitations.


Comparison of immunological detection of 5-hydroxytryptamine by monoclonal antibodies with standard silver stains as an aid to diagnosing carcinoid tumours.
Immunoreactivity to a monoclonal antibody against 5-hydroxytryptamine (5HT) was compared with Churukian Schenk argyrophilia and Masson Fontana argentaffin staining as an aid to the diagnosis of 53 carcinoid tumours. Thirty four tumours were argentaffin positive, 50 were argyrophil positive, and 43 contained immunologically detectable 5HT. In general, argentaffin staining and immunological detection of 5HT failed to pick up tumours derived from the foregut of type B or type D morphology. Argentaffin negative tumours usually showed only focal immunoreactivity for 5HT. If immunological detection of 5HT is used alone as a marker for carcinoid tumours problems arise in the differentiation of carcinoid tumours from adenocarcinomas which may also contain 5HT. These results were compared with those culled from other reported techniques used as an aid to the diagnosis of carcinoid tumours.


Effective Conformational Sampling in Explicit Solvent with Gaussian Biased Accelerated Molecular Dynamics.
In this Article, a user-friendly Gaussian biased accelerated molecular dynamics (GbAMD) method is presented that uses a sum of Gaussians of potential energies as the biased force to accelerate the conformational sampling. The easy parameter setting of GbAMD is demonstrated in a variety of simulation tests for the conformational transitions of proteins with various complexity including the folding of Trpcage, GB1p, and HP35 peptides as well as the functional conformational changes of nCaM and HIV-1 PR proteins. Additionally, the ability of GbAMD in conformational sampling and free-energy evaluation is quantitatively assessed through the comparison of GbAMD simulations on the folding of α-helical Trpcage and β-hairpin GB1p with the accompanying standard dual boost AMD and conventional MD (cMD) simulations. While GbAMD can fold both peptides into their native structures repeatedly in individual trajectories, AMD can only fold Trpcage and cMD fails the folding in both cases. As a result, only GbAMD can quantitatively measure the properties of the equilibrium conformational ensemble of protein folding consistent with experimental data. Also notable is that the structural properties of the indispensable unfolded and transition states in the folding pathways of Trpcage and GB1p characterized by GbAMD simulations are in great agreement with previous simulations on the two peptides. In summary, GbAMD has an effective conformational sampling ability that provides a convenient and effective access for simulating the structural dynamics of biomolecular systems.


Organization of stigma surface components in Brassica: a cytochemical study.
The nature of secretion products forming the pellicle of the dry-type stigma surface has been investigated in Brassica by an electron-microscopic cytochemical study. In order to determine whether the pellicle is organized like a membrane, we used a series of cytochemical methods to visualize cell membranes. Three groups of techniques presenting different degrees of specificity in terms of cell surface markers have been used: non-specific labelling of cell-surface components, characterization of glycoconjugates and localization of enzymic activities. We demonstrated that the pellicle of Brassica stigmas, although not possessing a trilamellar structure, presents numerous characteristics encountered in biological membranes. In particular, it possesses cytochemically demonstrable enzyme activities, including ATPase and adenylate cyclase, whose role remains to be elucidated in relation to the pollen-stigma interactions.


Penetrating injury of the vertebral artery: a unique management approach.
We have reported a case of traumatic vertebral artery transection discovered during an emergency neck exploration for penetrating injury with acute hemorrhage. Knowledge of the surgical anatomy of this vessel and awareness of the treatment alternatives that must be considered for its acute injury are important. A cooperative approach between the surgeon, anesthesiologist, and radiologist in this case, using a combination of anesthetic hypotension, surgical tamponade, and angiographic embolization, resulted in a successful outcome in this difficult case.


Proton pump inhibitor-responsive esophageal eosinophilia: still a valid diagnosis?
To update rapidly evolving concepts regarding the controversial entity of 'proton pump inhibitor (PPI)-responsive esophageal eosinophilia,' referring to patients with clinical, endoscopic and histologic features of eosinophilic esophagitis (EoE) who achieve remission on PPI therapy. Up to half of pediatric and adult patients with typical EoE symptoms and histology achieve clinico-pathologic remission on PPI therapy, irrespective of whether esophageal pH monitoring demonstrates abnormal acid reflux. In patients with clinical and histologic features of EoE, genotypic and phenotypic features of PPI responders and nonresponders are virtually indistinguishable, and different from those of patients with gastroesophageal reflux disease. In PPI responders, PPIs effects on esophageal Th2 inflammation and gene expression are similar to those of topical steroids in PPI nonresponders. These therapies, along with diets, recently have been shown to be potentially interchangeable in two small series. Proton pump inhibitor-responsive esophageal eosinophilia is an inappropriate disease descriptor, arbitrarily based on a response to a single drug, and should be abandoned. Patients who have esophageal eosinophilia and esophageal symptoms that resolve with PPI therapy have phenotypic, molecular, mechanistic, and therapeutic features indistinguishable from similar patients who do not respond to PPIs. These patients with PPI responsiveness should be considered within the spectrum of EoE.


Proteomic mapping of atrial and ventricular heart tissue in patients with aortic valve stenosis.
Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. To overcome these issues this study used high resolution mass spectrometry in combination with a stem cell-derived cardiac specific protein quantification-standard to profile the proteomes of 17 atrial and 29 left ventricular myocardial FFPE human myocardial tissue samples from AVS-patients. In our proteomic analysis we quantified a median of 1980 (range 1495-2281) proteins in every single sample and identified significant upregulation of 239 proteins in atrial and 54 proteins in ventricular myocardium. We compared the proteins with published data. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. In summary, we provide both a workflow for quantitative proteomics of human FFPE heart tissue and a comprehensive proteomic resource for AVS induced changes in the human myocardium.


Diagnosis and management of skin and soft-tissue infections (SSTI): a literature review and consensus statement on behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy.
Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges and resulting in significant morbidity and mortality among patients as well as increased healthcare costs. eight members of the SSTI working group of the Italian Society of infectious Diseases prepared a draft of the statements, grading the quality of each piece of evidence after a careful review of the current literature using MEDLINE database and their own clinical experience. Statements were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America (IDSA). The manuscript was successively reviewed by seven members of the SSTI working group of the international Society of Chemotherapy, and ultimately re-formulated by all e xperts. the microbiological and clinical aspects together with diagnostic features were considered for uncomplicated and complicated SSTIs. Antimicrobial therapy was considered as well -both empirical and targeted to methicillin-resistant Staphylococcus aureus (MRSA) and/or other main pathogens.


Characterization of beta-adrenoreceptors on smooth muscle cells from guinea pig stomach.
To characterize the beta-adrenergic receptors on guinea pig gastric smooth muscle cells, we examined the effects of beta-adrenergic agonists and antagonists on biological activity, cellular adenosine 3',5'-cyclic monophosphate (cAMP), and radioligand binding. Adrenergic agonists, isoproterenol (ISO), epinephrine (EPI), and norepinephrine (NE), inhibited carbachol-stimulated contraction of muscle cells, with relative potencies (IC50S) of ISO (0.1 microM) greater than EPI (1.4 microM) greater than NE (11 microM). Each agonist increased cellular cAMP, with relative potencies (IC50S) of ISO (0.5 microM) greater than EPI (6.3 microM) greater than NE (56 microM). Binding of the nonselective beta-antagonist 125I-pindolol was temperature-dependent, saturable, reversible, and specific. 125I-pindolol binding was inhibited by the three agonists, with relative potencies (IC50S) of ISO (0.9 microM) greater than EPI (9.6 microM) greater than NE (112 microM). Pindolol inhibited binding of 125I-pindolol with an IC50 of 100 nM. The IC50 for inhibition of binding of 125I-pindolol by the relatively beta 2-selective antagonist ICI 118,551 was 70 nM and for the relatively beta 1-selective antagonist betaxolol was 1,000 nM. Computer analysis of the dose-inhibition curves for binding of 125I-pindolol for the antagonists indicated that gastric smooth muscle cells possess exclusively beta 2-adrenergic receptors of two classes, one class with a high affinity for ICI 118,551 (Kd = 50 nM) and the other with a low affinity for ICI 118,551 (Kd = 30 microM). Our results indicate that beta-adrenergic agonists interact with beta 2-adrenergic receptors on gastric smooth muscle cells to increase cellular cAMP and inhibit muscle contraction.


What breaks a melody: perceiving F0 and intensity sequences with a cochlear implant.
Pitch perception has been extensively studied using discrimination tasks on pairs of single sounds. When comparing pitch discrimination performance for normal-hearing (NH) and cochlear implant (CI) listeners, it usually appears that CI users have relatively poor pitch discrimination. Tasks involving pitch sequences, such as melody perception or auditory scene analysis, are also usually difficult for CI users. However, it is unclear whether the issue with pitch sequences is a consequence of sound discriminability, or if an impairment exists for sequence processing per se. Here, we compared sequence processing abilities across stimulus dimensions (fundamental frequency and intensity) and listener groups (NH, CI, and NH listeners presented with noise-vocoded sequences). The sequence elements were firstly matched in discriminability, for each listener and dimension. Participants were then presented with pairs of sequences, constituted by up to four elements varying on a single dimension, and they performed a same/different task. In agreement with a previous study (Cousineau et al., 2009) fundamental frequency sequences were processed more accurately than intensity sequences by NH listeners. However, this was not the case for CI listeners, nor for NH listeners presented with noise-vocoded sequences. Intensity sequence processing was, nonetheless, equally accurate in the three groups. These results show that the reduced pitch cues received by CI listeners do not only elevate thresholds, as previously documented, but also affect pitch sequence processing above threshold. We suggest that efficient sequence processing for pitch requires the resolution of individual harmonics in the auditory periphery, which is not achieved with the current generation of implants.


Genetic linkage analysis of 14 candidate gene loci in a family with autosomal dominant osteoarthritis without dysplasia.
The role of various gene loci was investigated in a family in which familial osteoarthritis (FOA), with onset at an early age, is transmitted as an autosomal dominant mendelian trait. The absence of clinical and radiographic signs of dysplasia and calcium pyrophosphate deposition disease (CPDD) indicates that the basic disease process in this family is osteoarthritis (OA). Genetic linkage analysis of 14 candidate genes resulted in the exclusion of 10 important genes (COL2A1, COL9A1, COL9A2, COL11A1, COL11A2, COMP, the CPDD region, CRTL-1, CRTM, and MMP3). Other relevant genes were not informative in this family. The candidate loci previously identified in FOA and heritable skeletal disorders associated with OA are clearly not involved in the development of the primary FOA phenotype in the family investigated, indicating genetic heterogeneity.


The prevalence of conversion symptoms in women from a general Turkish population.
Conversion symptoms have historically be seen to be related to dissociative disorders and early trauma. This study sought to determine the prevalence of conversion symptoms among women in the general Turkish population. Participants (N=628) were administered The Dissociative Disorders Interview Schedule, the Borderline Personality Disorder section of the Structured Clinical Interview for DSM-III-R Personality Disorders, and the PTSD Module of the Structured Clinical Interview for DSM-III-R; 48.7% of participants had a lifetime history of a conversion symptom. They reported various types of childhood abuse and neglect more frequently than nonconversion subjects. Lifetime diagnosis of major depression, dissociative disorder, and childhood physical abuse predicted a conversion symptom. Effects of childhood neglect and emotional and sexual abuse among subjects with conversion symptoms were mediated by comorbid lifetime diagnosis of major depression and dissociative disorders. The authors suggest revisions to the DSM-V regarding conversion and somatization disorders.


Emotional Pathways to the Biological Embodiment of Racial Discrimination Experiences.
Racial discrimination experiences are common among youth with an ethnic minority background, and such experiences affect health. Stress-sensitive systems like the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as one mechanism. HPA-axis activity, measured through daily patterns of salivary cortisol, is altered among individuals who experience discrimination. We know little about the day-to-day processes by which discrimination experiences become embodied in stress biology. The HPA axis is responsive to negative social-evaluative (NSE) emotion. The present study investigated whether NSE emotions are a pathway by which discrimination dysregulates HPA-axis functioning as measured by cortisol levels. Perceived discrimination, diurnal cortisol, and changes in NSE emotion were assessed in a sample of 102 young adults. Emotions and cortisol were measured across the day for seven consecutive days in naturalistic settings. Multilevel modeling and regression analyses were used to examine average and day-to-day associations between discrimination, NSE emotion, and cortisol. Mediation and specificity analyses were conducted. Discrimination was associated with NSE emotion (β = 0.34, p = .001). Day-to-day changes (β = 0.10, p = .002) and average levels (β = 0.03, p = .013) of NSE emotion were associated with dysregulated cortisol. NSE emotion mediated the association between discrimination and diurnal cortisol slopes (β = 0.10 [95% confidence interval = 0.01-0.21]). Findings were robust for covariates including stressful life events, more pronounced for NSE emotion compared with negative affect at the day level, similar for NSE emotion and general negative affect at the person level, and specific to cortisol slopes. Findings suggest that daily NSE and average negative emotions are important pathways by which racial discrimination gets under the skin, or is embodied, in stress biology.


Target and Non-Target Processing during Oddball and Cyberball: A Comparative Event-Related Potential Study.
The phenomenon of social exclusion can be investigated by using a virtual ball-tossing game called Cyberball. In neuroimaging studies, structures have been identified which are activated during social exclusion. But to date the underlying mechanisms are not fully disclosed. In previous electrophysiological studies it was shown that the P3 complex is sensitive to exclusion manipulations in the Cyberball paradigm and that there is a correlation between P3 amplitude and self-reported social pain. Since this posterior event-related potential (ERP) was widely investigated using the oddball paradigm, we directly compared the ERP effects elicited by the target (Cyberball: "ball possession") and non-target (Cyberball: "ball possession of a co-player) events in both paradigms. Analyses mainly focused on the effect of altered stimulus probabilities of the target and non-target events between two consecutive blocks of the tasks. In the first block, the probability of the target and non-target event was 33% (Cyberball: inclusion), in the second block target probability was reduced to 17%, and accordingly, non-target probability was increased to 66% (Cyberball: exclusion). Our results indicate that ERP amplitude differences between inclusion and exclusion are comparable to ERP amplitude effects in a visual oddball task. We therefore suggest that ERP effects--especially in the P3 range--in the Oddball and Cyberball paradigm rely on similar mechanisms, namely the probability of target and non-target events. Since the simulation of social exclusion (Cyberball) did not trigger a unique ERP response, the idea of an exclusion-specific neural alarm system is not supported. The limitations of an ERP-based approach will be discussed.


Genomic organization of the human myocilin gene (MYOC) responsible for primary open angle glaucoma (GLC1A).
Myocilin is a newly found cytoskeletal protein involved in the morphogenesis of the basal body, a major microtubule organizing center, of the ciliated epithelium. It was recently realized that myocilin is virtually identical to the independently reported protein TIGR (trabecular meshwork-induced glucocorticoid response), which is responsible for the pathogenesis of chromosome 1q-linked primary open angle glaucoma (GLC1A). In this paper, we determined the genomic organization of the myocilin (MYOC/TIGR) gene by analyzing the nucleotide sequence of the BAC clones containing the MYOC/TIGR gene. The MYOC/TIGR gene consists of three exons. Each of the two splice donor and acceptor sites agrees well with the GT/AG rule. Primer sets to amplify each of the three exons are designed. The 5'-flanking region of MYOC gene contains the TGTTCT sequence overlapped with a palindromic sequence TTCTTTTTAAAAAGAA, which appears to be a glucocorticoid responsive element. There is also a unique sequence of dinucleotide repeat [(GT)2AA(GT)4AC(GT)13] which may also serve as a regulatory element. These results should aid in further detection of the MYOC/TIGR gene mutation and in depth understanding of the tissue-specific MYOC gene regulation.


BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells.
Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7.


Acetophenone Mannich bases: study of ionic liquid catalysed synthesis and antioxidative potential of products.
Three-component Mannich reaction of acetophenone or 4-iodoacetophenone with a variety of substituted anilines and benzaldehyde, catalysed with diethanolammonium chloroacetate, was performed under mild conditions. Mannich bases (MBs), of which five are new, were obtained in good to excellent yields. All compounds were characterized using elemental analysis, NMR and IR. In addition, detailed experimental and simulated UV-Vis spectral characterization of these compounds is presented here for the first time. In vitro antioxidative potential of synthetized MBs was evaluated using 2,2-diphenyl-1-picryl-hydrazyl radical and density functional theory (DFT) thermodynamical study. It was shown that compounds with anisidine moiety express moderate antioxidative activity. Mechanism of the organocatalysed Mannich reaction was thoroughly inspected by means of DFT. The reaction undergoes the hydrogen bonding-assisted mechanism. Moreover, the proposed rate determining step of the overall reaction is water elimination in the process of iminium ion formation. To the extent of our knowledge, this is the first detailed report on the influence of this type of catalyst on the formation of iminium ion, as a crucial intermediate for the whole reaction.


Unilateral elbow arthrodesis: the preferred position.
Twenty-five volunteers had unilateral elbow immobilization for 24 hours in each of two positions of flexion, 45 degrees and 90 degrees . Twenty-two of the 25 volunteers preferred a position of 90 degrees of flexion. Standard functional testing revealed significant limitations in each position of immobilization, confirming that there is no single optimal position of elbow arthrodesis. This study suggests that, for most individuals, 90 degrees is the preferred position of elbow arthrodesis for activities of daily living. However, factors such as age, sex, occupation, and dominance of the extremity should be considered when choosing a position of arthrodesis.


Effect of LiCl on gastric acid secretion and mucosal barrier function.
Lithium chloride (LiCl) has been shown to decrease gastric acid secretion and protect against ethanol-induced hemorrhagic gastritis in the rat. To further investigate these properties, two sets of experiments were performed in dogs with chronic Heidenhain pouches to study the effect of LiCl on histamine-stimulated gastric acid secretion and bile-induced disruption of the gastric mucosal barrier. In the first experiments the effect of LiCl on intravenous histamine-stimulated gastric secretion (40 micrograms/kg . hr) was determined. LiCl (30 mg/kg . hr) significantly reduced gastric acid secretion when compared to normal saline control (457 +/- 87 mueq H+/10 min versus 637 +/- 112 mueq H+/10 min, P less than 0.05). Serum and gastric lithium levels were determined and a significant inverse linear correlation existed between acid output and serum and gastric lithium levels. In the second set of experiments the effect of LiCl on bile-induced disruption of the gastric mucosal barrier was determined. Heidenhain pouches were continuously perfused with a pH 2 acid test solution and indices of mucosal barrier function (net acid back-diffusion and potential difference) were determined. LiCl (30 mg/kg . hr) significantly reduced both the increase in acid-back diffusion and the fall in potential difference with bile injury (5 mM taurodeoxycholate). In conclusion, these studies indicate that LiCl (1) decreases histamine-stimulated gastric acid secretion, and (2) diminishes bile-induced disruption of the gastric mucosal barrier in the canine Heidenhain pouch.


Topography-Mediated Fibroblast Cell Migration Is Influenced by Direction, Wavelength, and Amplitude.
Biophysical stimuli including topography play a crucial role in the regulation of cell morphology, adhesion, migration, and cytoskeleton organization and have been known to be important in biomaterials design for tissue engineering. However, little is known about the individual effects of topographic direction, structure repetition, and feature size of the substrate on which wound healing occurs. We report on the design of a topographical gradient with wavelike features that gradually change in wavelength and amplitude, which provides an efficient platform for an in vitro wound healing assay to investigate fibroblast migration. The wound coverage rate was measured on selected areas with wavelength sizes of 2, 5, and 8 μm in perpendicular and parallel orientations. Furthermore, a method was developed to produce independently controlled wavelength and amplitude and study which parameter has greater influence. Cell movement was guided by topographical properties, with a lower wrinkle wavelength (2 μm) eliciting the fastest migration speed, and the migration speed increased with decreasing amplitude. However, when the amplitudes were matched, cells migrated faster on a larger wavelength. This study also highlights the sensitivity of fibroblasts to the topographic orientation, with cells moving faster in the parallel direction of the topography. The overall behavior indicated that the wavelength and amplitude both play an important role in directing cell migration. The collective cell migration was found not to be influenced by altered cell proliferation. These findings provide key insights into topography-triggered cell migration and indicate the necessity for better understanding of material-directed wound healing for designing bio-inductive biomaterials.


Sarcopenia and Its Impact on Quality of Life.
Sarcopenia is recognized as a major health problem among older adults. This syndrome is associated with serious health consequences in terms of frailty, disability, morbidity and mortality. The aim of this study is to review sarcopenia and its impact on quality of life (QoL). MEDLINE database was searched from January to March 2016 using predefined search terms "sarcopenia", quality of life". Based on extensive literature search, 32 articles were identified while only 6 studies met the inclusion criteria and were associated with sarcopenia and QoL. Quality of life level was measured using generic self-reported tools; the Medical Outcomes Survey Short-form General Health Survey (SF-36) in 4 studies and EuroQol-5D instrument (EQ-5D) in 2 studies. Subjects with sarcopenia demonstrated a significantly high proportion of problems relating to several dimensions of QoL. More studies based on Sarcopenia and QoL are needed. Although the impact of sarcopenia on QoL was assessed in all studies with QoL generic instruments, it would be more insightful to utilise a disease-specific quality of life questionnaire, such as the SarQoL for sarcopenic subjects.


Additional genetic risk factors for venous thromboembolism in carriers of the factor V Leiden mutation.
Only a minority of subjects with factor V (FV) Leiden mutation develop venous thromboembolism (VTE), suggesting that additional genetic risk factors may be present in symptomatic carriers. We screened 157 unrelated carriers of the FV Leiden mutation with a first episode of VTE and 291 unrelated asymptomatic FV carriers for the presence of two frequent mutations, i.e. G20210A of the prothrombin gene and C677T of the methylenetetrahydrofolate reductase gene. Carriers with other inherited or acquired thrombophilia-associated abnormalities were excluded from analysis. Heterozygotes for the G20210A mutation were more prevalent among symptomatic carriers than in asymptomatic carriers (10.8% v 2.7%, P<0.0001); homozygotes for the C677T mutation were also more prevalent in symptomatic carriers (21.6% v 14.4%, P = 0.05). Factor V Leiden carriers who had had a VTE episode during oral contraceptive intake were more frequently carriers of the G20210A mutation (14.3%, P = 0.03). These results further support the idea that VTE in carriers of FV Leiden results from interaction with additional genetic or circumstantial risk factors, and that an accurate search for such factors is required to identify carriers at risk.


Associations of Variability in Blood Pressure, Glucose and Cholesterol Concentrations, and Body Mass Index With Mortality and Cardiovascular Outcomes in the General Population.
Variability in metabolic parameters, such as fasting blood glucose and cholesterol concentrations, blood pressure, and body weight can affect health outcomes. We investigated whether variability in these metabolic parameters has additive effects on the risk of mortality and cardiovascular outcomes in the general population. Using nationally representative data from the Korean National Health Insurance System, 6 748 773 people who were free of diabetes mellitus, hypertension, and dyslipidemia and who underwent ≥3 health examinations from 2005 to 2012 were followed to the end of 2015. Variability in fasting blood glucose and total cholesterol concentrations, systolic blood pressure, and body mass index was measured using the coefficient of variation, SD, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (eg, a score of 4 indicated high variability in all 4 metabolic parameters). Cox proportional hazards models adjusting for age, sex, smoking, alcohol, regular exercise, income, and baseline levels of fasting blood glucose, systolic blood pressure, total cholesterol, and body mass index were used. There were 54 785 deaths (0.8%), 22 498 cases of stroke (0.3%), and 21 452 myocardial infarctions (0.3%) during a median follow-up of 5.5 years. High variability in each metabolic parameter was associated with a higher risk for all-cause mortality, myocardial infarction, and stroke. Furthermore, the risk of outcomes increased significantly with the number of high-variability metabolic parameters. In the multivariable-adjusted model comparing a score of 0 versus 4, the hazard ratios (95% CIs) were 2.27 (2.13-2.42) for all-cause mortality, 1.43 (1.25-1.64) for myocardial infarction, and 1.41 (1.25-1.60) for stroke. Similar results were obtained when modeling the variability using the SD, variability independent of the mean, and average real variability, and in various sensitivity analyses. High variability of fasting blood glucose and total cholesterol levels, systolic blood pressure, and body mass index was an independent predictor of mortality and cardiovascular events. There was a graded association between the number of high-variability parameters and cardiovascular outcomes.


Elucidation of the Na(2/3)FePO₄ and Li(2/3)FePO₄ intermediate superstructure revealing a pseudouniform ordering in 2D.
Based on TEM, synchrotron X-ray diffraction, DFT calculations, and Mössbauer spectroscopy, a unified understanding of the Na and Li intercalation process in FePO4 is proposed. The key to this lies in solving the highly sought-after intermediate A(2/3)FePO4 (A = Na, Li) superstructures that are characterized by alkali ions as well as Fe(II)/Fe(III) charge orderings in a monoclinic three-fold supercell. Formation energies and electrochemical potential calculations confirm that Na(2/3)FePO4 and Li(2/3)FePO4 are stable and metastable, respectively, and that they yield insertion potentials in fair agreement with experimental values. The 2/3 Na(Li) and 1/3 vacancy sublattice of the intermediate phases forms a dense (101)(Pnma) plane in which the atom/vacancy ordering is very similar to that predicted for the most uniform distribution of 1/3 of vacancies in a 2D square lattice. Structural analysis strongly suggests that the key role of this dense plane is to constrain the intercalation in the diffusion channels to operate by cooperative filling of (bc)(Pnma). From a practical point of view, this generalized mechanism highlights the fact that an interesting strategy for obtaining high-rate FePO4 materials would consist in designing grains with an enhanced (101) surface area, thereby offering potential for substantial improvements with respect to the performance of rechargeable Li and Na batteries.


Human herpesvirus-8 (Kaposi's sarcoma-associated virus) ORF50 increases in vitro cell susceptibility to human immunodeficiency virus type 1 infection.
ORF50, an immediate-early gene of human herpesvirus-8 (HHV-8), encodes a transactivating protein necessary for virus reactivation and lytic replication. ORF50 was reported recently to synergize with human immunodeficiency virus type 1 (HIV-1) tat at a post-transcriptional level. To study the effects of these molecular interactions on HIV replication and biology, cellular clones stably transformed with ORF50 were obtained by transfection of cell lines of different origin. These clones were infected subsequently with HIV. Experiments showed that ORF50 enhances HIV replication in T and B cells (Jurkat and BC-3 cells) and induces susceptibility and transient permissiveness in non-susceptible glial (A172) cells. Upregulation of viral receptors and co-receptors did not account for increased sensitivity to HIV infection and therefore the action of ORF50 might be modulated by the intracellular environment. Interestingly, non-susceptible cells transformed with ORF50 showed transient production of HIV particles that could spread to adjacent cells by direct contact. These findings show that HHV-8 ORF50 has an enhancing effect on HIV replication in vitro and suggest that the two viruses might interact in co-infected patients.


The zebrafish as a model for behavioral studies.
Zebrafish genetics is developing at a rapid pace, and this opens up new approaches to understanding genetic control. This short review discusses recent results obtained in behavioral studies in this species, and also shows some promising ways of combining behavioral studies with modern genetic techniques. The zebrafish could provide behavioral models for understanding the neural and genetic control of species-specific behavioral patterns associated with feeding and predator avoidance. Careful experimentation may also reveal the genetic underpinning of simple cognitive processes such as habituation and memory, or lateralized control of behavior.


30-day readmissions after coronary artery bypass graft surgery in New York State.
The aim of this study was to identify reasons for and predictors of readmission. Short-term readmissions have been identified as an important cause of escalating health care costs, and coronary artery bypass graft (CABG) surgery is 1 of the most expensive procedures. We retrospectively analyzed 30-day readmissions for 33,936 New York State patients who underwent CABG surgery between January 1, 2005, and November 30, 2007. The main reasons for readmission (principal diagnoses) and the significant independent predictors of readmission were identified. The hospital-level relationship between risk-adjusted mortality rate and risk-adjusted readmission rate was explored to determine the value of readmission rate as a complementary measure of quality. The most common reasons for readmission were post-operative infection (16.9%), heart failure (12.8%), and "other complications of surgical and medical care" (9.8%). Increasing age, female sex, African-American race, higher body mass index, numerous comorbidities, 2 post-operative complications (renal failure and unplanned cardiac reoperation), Medicare or Medicaid status, discharges to a skilled nursing facility, saphenous vein grafts, and longer lengths of stay were all associated with higher rates of readmission. The correlation between the risk-adjusted 30-day readmission rate of hospitals and risk-adjusted in-hospital/30-day mortality rate was 0.32 (p = 0.047). The range across hospitals in the readmission rate was from 8.3% to 21.1%. The 30-day readmission rate for CABG surgery remains high, despite decreases in short-term mortality. Patients with any of the numerous risk factors for readmission should be closely monitored. Hospital readmission rates are not highly correlated with mortality rates and might serve as an independent quality measure.


Plantar injection of formalin in rats reduces the expression of a potassium chroride cotransporter KCC2 in the spinal cord and a kinase inhibitor suppresses this reduction.
Brain-derived neurotrophic factor (BDNF) is released from activated microglia during neuropathic pain and is hypothesized to downregulate the expression of the potassium chloride cotransporter 2 (KCC2) via the TrkB receptor. Previous studies reported that KCC2 is downregulated 5 min after the plantar injection of formalin in rats; however, the mechanism behind this decrease in KCC2 expression during acute inflammatory pain remains unknown. In this study, we determined whether the TrkB receptor contributes to the expression of KCC2 during the acute pain. Five minutes after the plantar injection of formalin in rats, the ratio of KCC2-immunoreactive area in layer II of the spinal cord significantly decreased on the stimulated side compared to the unaffected side. On the other hand, this response was inhibited by the injection of a kinase inhibitor, K252a, in the subarachnoid space 15 min before the formalin injection. These findings suggest that in acute pain, the TrkB receptor may contribute to the decrease in the expression of KCC2.


Visual capture of gait during redirected walking.
Redirected walking allows users of virtual reality applications to explore virtual environments larger than the available physical space. This is achieved by manipulating users' walking trajectories through visual rotation of the virtual surroundings, without users noticing this manipulation. Apart from its applied relevance, redirected walking is an attractive paradigm to investigate human perception and locomotion. An important yet unsolved question concerns individual differences in the ability to detect redirection. Addressing this question, we administered several perceptual-cognitive tasks to healthy participants, whose thresholds of detecting redirection in a virtual environment were also determined. We report relations between individual thresholds and measures of multisensory weighting (visually-assisted postural stability (Romberg quotient), subjective visual vertical (rod-and-frame test) and illusory self-motion (vection)). The performance in the rod-and-frame test, a classical measure of visual dependency regarding postural information, showed the strongest relation to redirection detection thresholds: The higher the visual dependency, the higher the detection threshold. This supports the interpretation of users' neglect of redirection manipulations as a "visual capture of gait". We discuss how future interdisciplinary studies, merging the fields of virtual reality and psychology, may help improving virtual reality applications and simultaneously deepen our understanding of how humans process multisensory conflicts during locomotion.


An overview on preclinical and clinical experiences with photodynamic therapy for bladder cancer.
Photodynamic therapy (PDT) is one of the most interesting methods of photo treatment. In general, PDT is a modality for the treatment of non-muscle invasive tumors. PDT is very well suited in managing bladder cancer, as the bladder is accessible by endoscopy and the tumors are most often limited to the mucosa or sub-mucosa. PDT is likely more useful for patients with recurrent tumors after conventional therapies, as well as for patients with diffuse non-muscle invasive bladder carcinomas that are refractory to standard treatments before the commitment to radical extirpative surgery, particularly in patients at surgical high risk. The treatment of tumors with PDT includes three major parameters: presence of oxygen in tumor tissue, administration of a photosensitizer, and subsequent exposure to light. The PDT mechanism relies on the in situ generation of cytotoxic agents by the activation of a light-sensitive drug, resulting in cell death. In this review, we present past and current advances in the use of PDT with urinary bladder cancer and discuss the future roles for this type of therapy in the treatment of bladder cancer.


Transfer hydrogenation of aldehydes and ketones catalyzed using an aminophosphinite POCNH pincer complex of Ni(ii).
The aminophosphinite pincer complex (POCNH)NiBr was found to effectively catalyze the transfer hydrogenation of aldehydes and ketones with 2-propanol and KOtBu as a base, presenting a rare example of bifunctional nickel transfer hydrogenation catalysts. The transfer hydrogenation of aldehydes and ketones was found to be selective, tolerating a wide range of other functional groups, including those prone to reduction, such as esters, amides, alkenes, pyridines, and nitriles. The reactions were suggested to proceed via the metal-ligand cooperative mechanism with an intermediacy of an amido (POCN)NiII species.


Faith after an earthquake: a longitudinal study of religion and perceived health before and after the 2011 Christchurch New Zealand Earthquake.
On 22 February 2011, Christchurch New Zealand (population 367,700) experienced a devastating earthquake, causing extensive damage and killing one hundred and eighty-five people. The earthquake and aftershocks occurred between the 2009 and 2011 waves of a longitudinal probability sample conducted in New Zealand, enabling us to examine how a natural disaster of this magnitude affected deeply held commitments and global ratings of personal health, depending on earthquake exposure. We first investigated whether the earthquake-affected were more likely to believe in God. Consistent with the Religious Comfort Hypothesis, religious faith increased among the earthquake-affected, despite an overall decline in religious faith elsewhere. This result offers the first population-level demonstration that secular people turn to religion at times of natural crisis. We then examined whether religious affiliation was associated with differences in subjective ratings of personal health. We found no evidence for superior buffering from having religious faith. Among those affected by the earthquake, however, a loss of faith was associated with significant subjective health declines. Those who lost faith elsewhere in the country did not experience similar health declines. Our findings suggest that religious conversion after a natural disaster is unlikely to improve subjective well-being, yet upholding faith might be an important step on the road to recovery.


Examining consumer behavior toward genetically modified (GM) food in Britain.
This study examined behavior toward genetically modified (GM) food in a British community-based sample. We used an equivalent gain task in which participants actually received the options they chose to encourage truthful responding. In conjunction with this, theory of planned behavior (TPB) components were evaluated so as to examine the relative importance of behavioral influences in this domain. Here, the TPB was extended to include additional components to measure self-identity, moral norms, and emotional involvement. Results indicated that the monetary amounts participants accepted in preference to GM food were significantly lower than those accepted in preference to non-GM food. However, the vast majority of participants were indifferent between GM and non-GM food options. All TPB components significantly predicted behavioral intentions to try GM food, with attitudes toward GM being the strongest predictor. Self-identity and emotional involvement were also found to be significant predictors of behavioral intentions but moral norms were not. In addition, behavioral intentions significantly predicted behavior; however, PBC did not. An additional measure of participants' propensity to respond in a socially desirable manner indicated that our results were not influenced by self-presentation issues, giving confidence to our findings. Overall, it appears that the majority of participants (74.5%) would purchase GM food at some price.


Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages.
Fes is a protein tyrosine kinase with cell autonomous oncogenic activities that are well established in cell culture and animal models, but its involvement in human cancer has been unclear. Abundant expression of Fes in vascular endothelial cells and myeloid cell lineages prompted us to explore roles for Fes in the tumor microenvironment. In an orthotopic mouse model of breast cancer, we found that loss of Fes in the host correlated with reductions in engrafted tumor growth rates, metastasis, and circulating tumor cells. The tumor microenvironment in Fes-deficient mice also showed reduced vascularity and fewer macrophages. In co-culture with tumor cells, Fes-deficient macrophages also poorly promoted tumor cell invasive behavior. Taken together, our observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, in part by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages.


Biophysical characterization of copolymer-protected gene vectors.
A copolymer-protected gene vector (COPROG) is a three-component gene delivery system consisting of a preformed DNA and branched polyethylenimine (bPEI) complex subsequently modified by the addition of a copolymer (P6YE5C) incorporating both poly(ethylene glycol) (PEG) and anionic peptides. Using fluorescence correlation spectroscopy (FCS) and atomic force microscopy (AFM), we characterized and compared the self-assembly of bPEI/DNA particles and COPROG complexes. In low salt buffer, both bPEI/DNA and COPROG formulations form stable nanoparticles with hydrodynamic radii between 60-120 nm. COPROG particles, as compared to bPEI/DNA, show greatly improved particle stability to both physiological salt as well as low pH conditions. Binding stoichiometry of the three-component COPROG system was investigated by dual-color fluorescence cross-correlation spectroscopy (FCCS). It was found that a significant fraction of P6YE5C copolymer aggregates with excess bPEI forming bPEI/P6YE5C "ghost complexes" with no DNA inside. The ratio of ghost particles to COPROG complexes is about 4:1. In addition, we find a large fraction of excess P6YE5C copolymer, which remains unbound in solution. We observe a 2-4-fold enhanced reporter gene expression with COPROG formulations at various equivalents as compared to bPEI-DNA alone. We believe that both complex stabilization as well as the capture of excess bPEI into ghost particles induced by the copolymer is responsible for the improvement in gene expression.


Vandetanib (ZD6474) induces antiangiogenesis through mTOR-HIF-1 alpha-VEGF signaling axis in breast cancer cells.
Vandetanib, also known as ZD6474, has recently been proved to be a clinical drug for cancer by targeting vascular endothelial growth factor receptor 2 (VEGFR2), EGFR, and RET tyrosine kinases. We hypothesized that vandetanib will be a drug candidate for breast cancer treatment by targeting angiogenesis. Vandetanib was used to treat different breast cancer cell lines, and its effect on growth, apoptosis, and cell cycle was studied by MTT assay and flow cytometry. VEGF level in culture medium was measured by ELISA. Gene expression of mechanistic target of rapamycin (mTOR), hypoxia-inducible factor (HIF)-1 alpha, and VEGF at mRNA and protein level were analyzed by quantitative real-time-PCR and Western blot. The cellular behavior variations were investigated by using wound healing assay, transwell invasion assay, and tubular formation assay as well as experiments in vivo. We found that vandetanib can inhibit breast cancer cell line growth via apoptosis and cell cycle regulation. VEGF secretion decreases upon treatment. Vandetanib can reduce both mRNA and protein level of mTOR, HIF-1 alpha, and VEGF. Angiogenesis assays showed that vandetanib can inhibit wound healing, invasion, and tubular formation in culture. Furthermore, vandetanib inhibited the growth of breast tumor in vivo. In short, our study showed that vandetanib can control angiogenesis of breast cancer in culture via mTOR, HIF-1 alpha, and VEGF signaling pathway.


SPICY: towards automated phenotyping of large pepper plants in the greenhouse.
Most high-throughput systems for automated plant phenotyping involve a fixed recording cabinet to which plants are transported. However, important greenhouse plants like pepper are too tall to be transported. In this research we developed a system to automatically measure plant characteristics of tall pepper plants in the greenhouse. With a device equipped with multiple cameras, images of plants are recorded at a 5cm interval over a height of 3m. Two types of features are extracted: (1) features from a 3D reconstruction of the plant canopy; and (2) statistical features derived directly from RGB images. The experiment comprised 151 genotypes of a recombinant inbred population of pepper, to examine the heritability and quantitative trait loci (QTL) of the features. Features extracted from the 3D reconstruction of the canopy were leaf size and leaf angle, with heritabilities of 0.70 and 0.56 respectively. Three QTL were found for leaf size, and one for leaf angle. From the statistical features, plant height showed a good correlation (0.93) with manual measurements, and QTL were in accordance with QTL of manual measurements. For total leaf area, the heritability was 0.55, and two of the three QTL found by manual measurement were found by image analysis.


Early response of cartilage to abnormal factors as seen in the meniscus of the dog knee after cruciate ligament section.
Ultrastructural changes in the medial meniscus of the knee were studied following section of the anterior cruciate ligament in 7 dogs. As compared with the contralateral control knee, collagen fibrils became abnormally widely spaced and disoriented from 1 month after operation and amorphous material on the (femoral) articular surface increased in thickness. In superficial cells, granular endoplasmic reticulum and Golgi membranes were more profuse and lipid droplets increased in number from 1 week. Both superficial and deeper cells were very active at 1 and 2 months after operation and the nuclear fibrous lamina had increased in thickness. Some cell degeneration occurred in the superficial zone from 1 month. At 15 months both matrix and cells appeared to have returned to normal. These changes are compared with those in articular cartilage after cruciate ligament section and with the effects of intravenous papain on cartilage.


Motion of hydrogen bonds in diluted HDO/D2O solutions: direct probing with 150 fs resolution
An experiment is described to study temporal variations of the hydrogen bond length in diluted HDO/D2O solutions. The principles of this laser spectroscopic experiment are explained first. The construction of a laser source generating 150 fs pulses in the 2.5-4.5 microns spectral region at a 10 microJ power level is detailed next. The OH stretching band is reproduced for different excitation frequencies and different pump-probe delay times. A theory, based on statistical mechanics of nonlinear optical processes, is proposed to calculate the lowest two spectral moments. An effect is reported, the delay dependent vibrational solvatochromism. It is shown how this effect can be exploited to follow temporal variations of the OH...O bond length directly, in real time. The corresponding time scales are of the order of 700 fs. No bond oscillations are observed.


Validation techniques for logistic regression models.
This paper presents a comprehensive approach to the validation of logistic prediction models. It reviews measures of overall goodness-of-fit, and indices of calibration and refinement. Using a model-based approach developed by Cox, we adapt logistic regression diagnostic techniques for use in model validation. This allows identification of problematic predictor variables in the prediction model as well as influential observations in the validation data that adversely affect the fit of the model. In appropriate situations, recommendations are made for correction of models that provide poor fit.


QFib: Fast and Efficient Brain Tractogram Compression.
Diffusion MRI fiber tracking datasets can contain millions of 3D streamlines, and their representation can weight tens of gigabytes of memory. These sets of streamlines are called tractograms and are often used for clinical operations or research. Their size makes them difficult to store, visualize, process or exchange over the network. We propose a new compression algorithm well-suited for tractograms, by taking advantage of the way streamlines are obtained with usual tracking algorithms. Our approach is based on unit vector quantization methods combined with a spatial transformation which results in low compression and decompression times, as well as a high compression ratio. For instance, a 11.5GB tractogram can be compressed to a 1.02GB file and decompressed in 11.3 seconds. Moreover, our method allows for the compression and decompression of individual streamlines, reducing the need for a costly out-of-core algorithm with heavy datasets. Last, we open a way toward on-the-fly compression and decompression for handling larger datasets without needing a load of RAM (i.e. in-core handling), faster network exchanges and faster loading times for visualization or processing.


Adenoma Detection Rate Benchmarks: An Updated Analysis.
Early-onset colorectal cancer prompted organizations to reduce the recommended screening initiation age from 50 to 45 years. The American Society for Gastrointestinal Endoscopy Quality Assurance in Endoscopy Committee recommends 3 priority quality indicators for colonoscopy services. The adenoma detection rate is considered the most important measure with the established benchmark based upon studies of patients 50 years or older. The incidence of polyps increases with age, so this change has an as-yet-unknown effect on the new benchmark. Five studies were reviewed. Based upon the results, 45- to 50-year-old patients should be included in facilities' adenoma detection rate calculations using the currently recommended benchmarks of 25% for women and men combined, or 20% for women and 30% for men when the genders are calculated separately. Males consistently had more adenomas than females in each of the 3 studies that separated genders, a detail that might merit gender-based adenoma detection rate determinations in some practices. One study indicated caution is advised; it recommends males and females be calculated separately and different benchmarks be used for each gender. The adenoma detection rate has been shown to increase over time. More studies are needed to guide screening quality metrics.


The bereavement experience of spousal caregivers to persons with dementia: Reclaiming self.
Spouses of persons living with dementia both anticipate future loss and grieve for multiple losses occurring with caregiving and this ultimately influences their bereavement experience. Little research has been conducted regarding the bereavement experience in the caregiving journey with dementia and what does exist is mostly quantitative in nature. The purpose of this study is to describe the bereavement experience of spousal caregivers ( n = 10) utilizing Thorne's interpretive description. Thematic analysis revealed the features and facilitators of the bereavement process for spousal caregivers to persons with dementia. The unique contribution of this study to the dementia literature is the finding that the overall process of reclaiming self is significant to the bereavement journey. Future work should investigate identity as understood by spousal caregivers to persons with dementia, and further explore the processes, facilitators, and barriers to healthy bereavement in this population.


Benziodoxole-based hypervalent iodine reagents for atom-transfer reactions.
In the last decades, hypervalent iodine reagents have raised from chemical curiosities to mainstream reagents in organic synthesis. The use of benziodoxole-derived reagents has been especially successful in oxidation methods, whereas non-cyclic iodinanes have been used both for oxidation and atom-transfer reactions. On the other hand, the exceptional properties of benziodoxole reagents for atom-transfer reactions have only started to attract the attention of the synthetic community more recently. In this review, progress in the use of these compounds for C-X and C-C bond formations will be presented. In particular, recent breakthroughs in trifluoromethylation and alkynylation reactions have been realized since 2006 based on benziodoxole-derived reagents and these results are the main focus of this article.


Versatile (bio)functionalization of bromo-terminated phosphonate-modified porous aluminum oxide.
Porous aluminum oxide (PAO) is a nanoporous material used for various (bio)technological applications, and tailoring its surface properties via covalent modification is a way to expand and refine its application. Specific and complex chemical modification of the PAO surface requires a stepwise approach in which a secondary reaction on a stable initial modification is necessary to achieve the desired terminal molecular architecture and reactivity. We here show that the straightforward initial modification of the bare PAO surface with bromo-terminated phosphonic acid allows for the subsequent preparation of PAO with a wide scope of terminal reactive groups, making it suitable for (bio)functionalization. Starting from the initial bromo-terminated PAO, we prepared PAO surfaces presenting various terminal functional groups, such as azide, alkyne, alkene, thiol, isothiocyanate, and N-hydroxysuccinimide (NHS). We also show that this wide scope of easily accessible tailored reactive PAO surfaces can be used for subsequent modification with (bio)molecules, including carbohydrate derivatives and fluorescently labeled proteins.


Time-lapse analysis and microdissection of living 3D melanoma cell cultures for genomics and proteomics.
A novel technique is presented for the monitoring and morphological characterization of 3D cell cultures targeted for laser capture microdissection (LCM). A custom-made chamber enables time-lapse topography and pre-selection of cell targets in order to minimize microdissection time, optimizing the quality of biomolecules for downstream analyses. The method complements the recently presented novel application of LCM in living 3D cultures, whose compatibility with standard genomics and proteomics assays such as microarrays, real-time PCR, and 2D gel electrophoresis is further corroborated here. Specifically, the above techniques are employed in tandem to study, as a proof of principle, the dynamics of in vitro vasculogenic mimicry. It was shown previously that aggressive melanoma cells spontaneously differentiate on collagen gels into vascular-like networks with strong endogenous angiogenic potential. Here the evolution of vasculogenic mimicry was quantified by three time-dependent variables: the distribution of the vascular-like network lengths, widths, and area coverage. Based on these morphological descriptors the networks were locally classified over time as "early" or "mature" stage. LCM of networks and randomly oriented cells followed by real-time PCR for select genes revealed that differential expression was time-dependent and increased with network maturity. The method is widely applicable for microgenomics and microproteomics analyses in phenotypically evolving 3D cultures (i.e., of stem cells), under spontaneous or directed differentiation. Therefore beyond enabling future rigorous analyses on the mechanistics of vasculogenic mimicry, it provides a practical discovery engine for a range of developmental studies and tissue regenerative engineering applications.


Villous tumors of the duodenum. Report of two cases.
Two cases of duodenal villous adenoma are reported, bringing the total reported in the world literature to 51. The tumors are of importance despite their rarity because of the frequency of focal or occult malignant changes in the tumors, the nonspecific symptoms and radiographic findings and the potential surgical complications. Therefore, atypical lesions of the duodenum should be investigated endoscopically and all duodenal villous tumors should be surgically resected. Local excision is usually adequate treatment even when microinvasive cancer or carcinoma in situ are present.


At-risk children in Christian families concerning alcohol use.
Health educators proposing alcohol prevention programs for a church setting face a variety of problems. "Information only" preventive types of alcohol programs are being increasingly criticized. The purpose of this study was to identify variables that best predict use of alcohol for children in fundamentalist Protestant Christian families. Three hundred and two students currently enrolled in a mandatory health course at a fundamentalist Protestant Christian university responded to a questionnaire designed to identify contextual or environmental risk factors for alcohol use. A significant difference was found in five of 15 established environmental factors. This paper suggests that an alcohol education program that focused on these differences would be advantageous for the health educator to carry out in the church setting.


Comparison of unipedicular and bipedicular kyphoplasty on the stiffness and biomechanical balance of compression fractured vertebrae.
Percutaneous kyphoplasty (PKP) has been used to treat osteoporotic vertebral compression fractures for over 10 years; however, clinically speaking it is still controversial as to whether the use of unipedicular PKP or bipedicular PKP is best. Our study aimed to compare the different effects of unipedicular PKP and bipedicular PKP on the stiffness of compression fractured vertebral bodies (VBs), as well as to assess how cement distribution affect the bilateral biomechanical balance of the VBs. During this study, 30 thoracic VBs were compressed, creating vertebral compression fracture models; then they were augmented by unipedicular (group A and B) PKP and bipedicular (group C) PKP. In group A (unipedicular PKP), the cement was injected into one side and the augmentation was limited to the same side of the VB. In group B (unipedicular PKP), the cement was injected at only one side but the augmentation extended across the midline and filled both sides of the VB. In group C (bipedicular PKP), the cement was injected into both sides and thus achieved the bilateral augmentation. For the unipedicular PKP, the amount of cement injected was 15% of the original VB volume; while in bipedicular PKP, the amount of cement injected was a total of 20% of the original VB volume (10% was injected into each side). Using a MTS-858, we examined three phases of the VBs (intact, pre-augmented, post-augmented), by applying loads axially to the total vertebra and bilateral sides of the vertebra for each of three cycles, respectively. The changes of force and displacement were then recorded and the stiffness of the total vertebra and bilateral sides of the vertebra were calculated. For the pre-augmentation stage, the total VB stiffness of groups A, B and C significantly decreased when the compression fracture models were established (P < 0.05). After the cement augmentation (the post-augmentation stage), both groups A and B, showed that the stiffness could be restored to the initial, intact state; however, in group C, the stiffness was significantly higher than the initial, intact state (P < 0.01). The stiffness of the augmented side of group A was significantly higher than the non-augmented side (P < 0.001). In groups B and C, no significant differences were observed in the stiffness between total VB and each individual side. Thus, we can conclude that both unipedicular PKP and bipedicular PKP significantly increase the total VB stiffness. Bipedicular PKP creates stiffness uniformly across both sides of the vertebrae, while unipedicular PKP, creates a biomechanical balance depending on the distribution of cement. If bone cement is augmented only on one side, the stiffness of non-augmented side will be significantly lower than the augmented side, which might lead to an imbalance of stress on the VB. However, when cement augmentation crosses the midline, stiffness of both sides increase comparatively and biomechanical balance is thus achieved.


Virtual reconstruction of paranasal sinuses from CT data: A feasibility study for forensic application.
The purpose of this study was to report the feasibility of computed modelization and reconstitution of the paranasal sinuses, before and after trauma, from CT data. We modeled and reconstructed the paranasal sinuses of two patients (A and B), before and after trauma, using two different softwares (3DSlicer® and Blender®). Both patients had different numbers and locations of fractures. The 3DSlicer® software was used to create a 3D model from CT data. We then imported the 3D data into the Blender® software, to reconstruct and compare the dimensions of the paranasal sinuses before and after trauma. The 3 fragments of patient A and the 7 fragments of patient B could be repositioned in the pre-traumatic configuration. Distance measurements proved to be similar between pre- and post-traumatic 3D volumes. After simple trauma, bone facial anatomy reconstruction is manually feasible. The whole procedure could benefit from automatization through machine learning. However, this feasibility must be confirmed on more severely fractured paranasal sinuses, to consider an application in forensic identification.


POSTOPERATIVE CHANGES IN INTESTINAL MICROBIOTA AND USE OF PROBIOTICS IN ROUX-EN-Y GASTRIC BYPASS AND SLEEVE VERTICAL GASTRECTOMY: AN INTEGRATIVE REVIEW.
Studies suggest that weight loss induced by bariatric surgery and the remission of some comorbidities may be related to changes in the microbiota profile of individuals undergoing this procedure. In addition, there is evidence that manipulation of the intestinal microbiota may prove to be a therapeutic approach against obesity and metabolic diseases. To verify the changes that occur in the intestinal microbiota of patients undergoing bariatric surgery, and the impact of the usage of probiotics in this population. Articles published between 2007 and 2017 were searched in Medline, Lilacs and Pubmed with the headings: bariatric surgery, microbiota, microbiome and probiotics, in Portuguese, English and Spanish. Of the 166 articles found, only those studies in adults subjected to either Roux-en-Y gastric bypass or sleeve vertical gastrectomy published in original articles were enrolled. In the end, five studies on the change of intestinal microbiota composition, four on the indirect effects of those changes and three on the probiotics administration on this population were enrolled and characterized. Bariatric surgery provides changes in intestinal microbiota, with a relative increase of the Bacteroidetes and Proteobacteria phyla and reduction of Firmicutes. This is possibly due to changes in the gastro-intestinal flux, coupled with a reduction in acidity, in addition to changes in eating habits. The usage of probiotics seems to reduce the gastro-intestinal symptoms in the post-surgery, favor the increase of vitamin B12 synthesis, as well as potentiate weight loss.


REM sleep, dream variables and suicidality in depressed patients.
To examine the relationship between the emotional quality of dreams, REM sleep variables and suicidal tendency in depressed individuals, 26 depressed volunteers (10 males and 16 females) were assessed with the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and underwent 3 nights of polysomnography. There was a significant negative correlation between suicidality scores and REM latency and a positive correlation between suicidality and REM percent. Suicidal subjects had a significantly shorter mean REM latency and a higher mean REM percentage than the non-suicidal subjects. As expected in normal subjects, 20 subjects had an increase in dream-like quality (DLQ) of REM reports between the first and second halves of the night. The six subjects with a negative DLQ difference also scored as suicidal. A reduction in dream-like quality of the REM content reports between the first and second halves of the night was found to be associated with suicidal tendency. The findings may indicate that these subjects fail to self-regulate mood and integrate affect into long-term memory networks during sleep. Theoretical and clinical implications of these findings in depression are discussed.


A porous tantalum trabecular metal: basic science.
Conventional materials used for orthopedic reconstruction implants limit the design of new and improved implants. Solid metal is rigid. Porous fixation surfaces have low volumetric porosity available for biologic ingrowth and low frictional characteristics for initial implant stability and have to be bonded to solid-metal substrates. New porous structural biomaterials have been developed to help advance the current generation of prostheses and address unresolved clinical applications. Tantalum trabecular metal offers several advantages over other current conventional materials used for implants by its uniformity and structural continuity, strength, low stiffness, high porosity, and high coefficient of friction.


Female resistance to invading males increases infanticide in langurs.
Infanticide by adult male occurs in many mammalian species under natural conditions, and it is often assumed to be a goal-directed action and explained predominately by sexual selection. Motivation of this behavior in mammals is limitedly involved. We used long-term reproductive records and direct observation in captivity and in the field of two snub-nosed langur species on the basis of individual identification to investigate how infanticide happened and to be avoided in nonhuman primates. Our observations suggested that infanticide by invading males might be more accidental than goal-directed. The invading male seemed to monopolize all the females including lactating mothers during takeovers. Multiparous mothers who accepted the invading male shortly after takeovers avoided infanticide in most cases. Our results conjectured primiparous mothers would decrease infanticidal possibility if they sexually accepted the invading male during or immediately after takeovers. In the studied langur species, voluntary abortion or mating with the invading male was evidently adopted by females to limit or avoid infanticide by takeover males. The objective of the invading male was to monopolize all adult females after his takeover. It appeared that the mother's resistance to accepting the new male as a mating partner was the primary incentive for infanticide. Motivation analysis might be helpful to further understand why infanticide occurs in primate species.


Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease.
The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has also been used in strategies aimed at enhancing drug absorption due to its high expression in the intestine. Other MCT isoforms are less well characterized, but ongoing studies indicate that MCT6 transports xenobiotics such as bumetanide, nateglinide, and probenecid, whereas MCT7 has been characterized as a transporter of ketone bodies. MCT8 and MCT10 transport thyroid hormones, and recently, MCT9 has been characterized as a carnitine efflux transporter and MCT12 as a creatine transporter. Expressed at the blood brain barrier, MCT8 mutations have been associated with an X-linked intellectual disability, known as Allan-Herndon-Dudley syndrome. Many MCT isoforms are associated with hormone, lipid, and glucose homeostasis, and recent research has focused on their potential roles in disease, with MCTs representing promising novel therapeutic targets. This review will provide a summary of the current literature focusing on the characterization, function, and regulation of the MCT family isoforms and on their roles in drug disposition and in health and disease. SIGNIFICANCE STATEMENT: The 14-member solute carrier family 16 of monocarboxylate transporters (MCTs) plays a fundamental role in maintaining intracellular concentrations of a broad range of important endogenous molecules in health and disease. MCTs 1, 2, and 4 (L-lactate transporters) are overexpressed in cancers and represent a novel therapeutic target in cancer. Recent studies have highlighted the importance of MCTs in glucose, lipid, and hormone homeostasis, including MCT8 in thyroid hormone brain uptake, MCT12 in carnitine transport, and MCT11 in type 2 diabetes.


Family history and survival of patients with gastric cancer: a meta-analysis.
Previous studies have generated conflicting evidence regarding associations between family history and survival after gastric cancer surgery. In this study, we investigated this question using a meta-analysis. To identify relevant studies, PubMed and Embase databases were searched up to June 2013. Two reviewers independently assessed search results and data extraction of included studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were calculated based on fixed- or random- effects models. Homogeneity of effects across studies was assessed using x2 test statistics and quantified by I2. A total of five studies were selected according to the inclusion criteria. The total number of patients included was 2,030, which ranged from 145 to 598 per study. There was no significant difference in OS by family history of cancer (HR=0.83, 95%CIs=0.50-1.38), but subgroup analysis of patients with a first-degree family history of cancer (HR=0.74, 95%CIs=0.60-0.93) and gastric cancer family history (HR=0.56, 95%CIs=0.41-0.76) tended to show better OS in these patients. This meta-analysis suggests that a first-degree family history of cancer or gastric cancer family history is associated with better survival of gastric cancer patients after surgery, after a systematic review of five previous studies. These results can be applied by clinicians when counselling patients regarding their risk of death from gastric cancer. Further study is needed to investigate the underlying mechanism between family history and survival in gastric cancer patients.


Value of superb microvascular imaging ultrasonography in the diagnosis of carpal tunnel syndrome: Compared with color Doppler and power Doppler.
The aim of this study was to compare the value of superb microvascular imaging (SMI) in carpal tunnel syndrome (CTS) with that of color Doppler ultrasonography (CDUS) and power Doppler ultrasonography (PDUS).Fifty patients with symptomatic CTS and 25 healthy volunteers were enrolled. The cross-sectional area (CSA), CDUS score, PDUS score, and SMI score of the median nerve (MN) at the carpal tunnel were recorded. The value of different ultrasonography (US) diagnostic strategies was calculated.The blood flow display ratio in the MN of the healthy volunteers had no statistical difference between CDUS, PDUS, and SMI (20%, 32%, and 48%, respectively, P >.05). The blood flow display ratio for SMI in patients was significantly higher than that of CDUS and PDUS (90%, 52%, and 60%, respectively, P <.005). The accuracy of SMI score ≥2 (79%) was much higher than that of CDUS and PDUS (61% and 63%, respectively, P <.05). Comprehensive consideration of SMI and CSA, CSA≥10.5 mm, and/or SMI score ≥2 has the highest accuracy (83%), significantly higher than that of CSA combination with CDUS or PDUS (68% and 69%, respectively, P <.05).SMI is more sensitive to display the blood flow in the MN with CTS than CDUS and PDUS. It might significantly improve the diagnosis value for CTS.