Using physiology to predict the responses of ants to climatic warming.
Physiological intolerance of high temperatures places limits on organismal responses to the temperature increases associated with global climatic change. Because ants are geographically widespread, ecologically diverse, and thermophilic, they are an ideal system for exploring the extent to which physiological tolerance can predict responses to environmental change. Here, we expand on simple models that use thermal tolerance to predict the responses of ants to climatic warming. We investigated the degree to which changes in the abundance of ants under warming reflect reductions in the thermal niche space for their foraging. In an eastern deciduous forest system in the United States with approximately 40 ant species, we found that for some species, the loss of thermal niche space for foraging was related to decreases in abundance with increasing experimental climatic warming. However, many ant species exhibited no loss of thermal niche space. For one well-studied species, Temnothorax curvispinosus, we examined both survival of workers and growth of colonies (a correlate of reproductive output) as functions of temperature in the laboratory, and found that the range of thermal tolerances for colony growth was much narrower than for survival of workers. We evaluated these functions in the context of experimental climatic warming and found that the difference in the responses of these two attributes to temperature generates differences in the means and especially the variances of expected fitness under warming. The expected mean growth of colonies was optimized at intermediate levels of warming (2-4°C above ambient); yet, the expected variance monotonically increased with warming. In contrast, the expected mean and variance of the survival of workers decreased when warming exceeded 4°C above ambient. Together, these results for T. curvispinosus emphasize the importance of measuring reproduction (colony growth) in the context of climatic change: indeed, our examination of the loss of thermal niche space with the larger species pool could be missing much of the warming impact due to these analyses being based on survival rather than reproduction. We suggest that while physiological tolerance of temperature can be a useful predictive tool for modeling responses to climatic change, future efforts should be devoted to understanding the causes and consequences of variability in models of tolerance calibrated with different metrics of performance and fitness.


Predicting climate effects on Pacific sardine.
For many marine species and habitats, climate change and overfishing present a double threat. To manage marine resources effectively, it is necessary to adapt management to changes in the physical environment. Simple relationships between environmental conditions and fish abundance have long been used in both fisheries and fishery management. In many cases, however, physical, biological, and human variables feed back on each other. For these systems, associations between variables can change as the system evolves in time. This can obscure relationships between population dynamics and environmental variability, undermining our ability to forecast changes in populations tied to physical processes. Here we present a methodology for identifying physical forcing variables based on nonlinear forecasting and show how the method provides a predictive understanding of the influence of physical forcing on Pacific sardine.


Words Can Shift: Dynamically Adjusting Word Representations Using Nonverbal Behaviors.
Humans convey their intentions through the usage of both verbal and nonverbal behaviors during face-to-face communication. Speaker intentions often vary dynamically depending on different nonverbal contexts, such as vocal patterns and facial expressions. As a result, when modeling human language, it is essential to not only consider the literal meaning of the words but also the nonverbal contexts in which these words appear. To better model human language, we first model expressive nonverbal representations by analyzing the fine-grained visual and acoustic patterns that occur during word segments. In addition, we seek to capture the dynamic nature of nonverbal intents by shifting word representations based on the accompanying nonverbal behaviors. To this end, we propose the Recurrent Attended Variation Embedding Network (RAVEN) that models the fine-grained structure of nonverbal subword sequences and dynamically shifts word representations based on nonverbal cues. Our proposed model achieves competitive performance on two publicly available datasets for multimodal sentiment analysis and emotion recognition. We also visualize the shifted word representations in different nonverbal contexts and summarize common patterns regarding multimodal variations of word representations.


Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.
Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring.


Fusing Partial Camera Signals for Noncontact Pulse Rate Variability Measurement.
Remote camera-based measurement of physiology has great potential for healthcare and affective computing. Recent advances in computer vision and signal processing have enabled photoplethysmography (PPG) measurement using commercially available cameras. However, there remain challenges in recovering accurate noncontact PPG measurements in the presence of rigid head motion. When a subject is moving, their face may be turned away from one camera, be obscured by an object, or move out of the frame resulting in missing observations. As the calculation of pulse rate variability (PRV) requires analysis over a time window of several minutes, the effect of missing observations on such features is deleterious. We present an approach for fusing partial color-channel signals from an array of cameras that enable physiology measurements to be made from moving subjects, even if they leave the frame of one or more cameras, which would not otherwise be possible with only a single camera. We systematically test our method on subjects ( N=25) using a set of six, 5-min tasks (each repeated twice) involving different levels of head motion. This results in validation across 25 h of measurement. We evaluate pulse rate and PRV parameter estimation including statistical, geometric, and frequency-based measures. The median absolute error in pulse rate measurements was 0.57 beats-per-minute (BPM). In all but two tasks with the greatest motion, the median error was within 0.4 BPM of that from a contact PPG device. PRV estimates were significantly improved using our proposed approach compared to an alternative not designed to handle missing values and multiple camera signals; the error was reduced by over 50%. Without our proposed method, errors in pulse rate would be very high, and estimation of PRV parameters would not be feasible due to significant data loss.


Follow your breath: respiratory interoceptive accuracy in experienced meditators.
Attention to internal bodily sensations is a core feature of mindfulness meditation. Previous studies have not detected differences in interoceptive accuracy between meditators and nonmeditators on heartbeat detection and perception tasks. We compared differences in respiratory interoceptive accuracy between meditators and nonmeditators in the ability to detect and discriminate respiratory resistive loads and sustain accurate perception of respiratory tidal volume during nondistracted and distracted conditions. Groups did not differ in overall performance on the detection and discrimination tasks; however, meditators were more accurate in discriminating the resistive load with the lowest ceiling effect. Meditators were also more accurate during the nondistracted tracking task at a lag time of 1 s following the breath. Results provide initial support for the notion that meditators have greater respiratory interoceptive accuracy compared to nonmeditators.


Visual evoked potentials in children prenatally exposed to methylmercury.
Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes. However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors. We evaluated the effect of prenatal methylmercury exposure on visual evoked potential (VEP) latencies in Faroese children with elevated prenatal methylmercury exposure. A cohort of 182 singleton term births was assembled in the Faroe Islands during 1994-1995. At age 7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of subjects with abnormal vision conditions. We used multiple regression analysis to evaluate the association of mercury concentrations in cord blood and maternal hair at parturition with VEP latencies after adjustment for potential confounders that included the cord-serum phospholipid concentration of n-3 polyunsaturated fatty acids (PUFAs) and the duration of breastfeeding. Unadjusted correlations between mercury exposure and VEP latencies were equivocal. Multiple regression models showed that increased mercury concentrations, especially in maternal hair, were associated with delayed latencies for VEP peak N145. After covariate adjustment, a delay of 2.22 ms (p=0.02) was seen for each doubling of the mercury concentration in maternal hair. In agreement with neuropsychological findings, the present study suggests that prenatal methylmercury exposure may have an adverse effect on VEP findings despite the absence of clinical toxicity to the visual system. However, this association was apparent only after adjustment for n-3 PUFA status.


Telehealthcare in COPD: a systematic review and meta-analysis on physical outcomes and dyspnea.
Only a minority of patients with chronic obstructive pulmonary disease (COPD) have access to pulmonary rehabilitation (PR). Home-based solutions such as telehealthcare, have been used in efforts to make PR more available. The aim of this systematic review was to investigate the effects of telehealthcare on physical activity level, physical capacity and dyspnea in patients with COPD, and to describe the interventions used. Randomized controlled trials were identified through database searches, reference lists and included authors. Articles were reviewed based on eligibility criteria by three authors. Risk of bias was assessed by two authors. Standardized mean differences (SMD) or mean differences (MD) with 95% CI were calculated. Forest plots were used to present data visually. Nine studies (982 patients) were included. For physical activity level, there was a significant effect favoring telehealthcare (MD, 64.7 min; 95% CI, 54.4-74.9). No difference between groups was found for physical capacity (MD, -1.3 m; 95% CI, -8.1-5.5) and dyspnea (SMD, 0.088; 95% CI, -0.056-0.233). Telehealthcare was promoted through phone calls, websites or mobile phones, often combined with education and/or exercise training. Comparators were ordinary care, exercise training and/or education. The use of telehealthcare may lead to improvements in physical activity level, although the results should be interpreted with caution given the heterogeneity in studies. This is an important area of research and further studies of the effect of telehealthcare for patients with COPD would be beneficial. In PROSPERO 2012: CRD42012003294. http://www.crd.york.ac.uk/PROSPEROFILES/3294_PROTOCOL_20121016.pdf.


Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer.
Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression-free survival (BPFS) over RP alone. Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS). In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, -0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone. The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.


The anatomy of absenteeism.
Based on comprehensive administrative register data from Norway, we examine the determinants of sickness absence behavior; in terms of employee characteristics, workplace characteristics, panel doctor characteristics, and economic conditions. The analysis is based on a novel concept of a worker's steady state sickness absence propensity, computed from a multivariate hazard rate model designed to predict the incidence and duration of sickness absence for all workers. Key conclusions are that (i) most of the cross-sectional variation in absenteeism is caused by genuine employee heterogeneity; (ii) the identity of a person's panel doctor has a significant impact on absence propensity; (iii) sickness absence insurance is frequently certified for reasons other than sickness; and (iv) the recovery rate rises enormously just prior to the exhaustion of sickness insurance benefits.


High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.
The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.


Purification and characterization of Escherichia coli DNA polymerase V.
Cell survival and genome rescue after UV irradiation in Escherichia coli depends on DNA repair mechanisms induced in response to DNA damage as part of the SOS regulon. SOS occurs in two phases. The first phase is dominated by accurate repair processes such as excision and recombinational DNA repair, while the second phase is characterized by a large approximately 100-fold increase in mutations caused by an error-prone replication of damaged DNA templates. SOS mutagenesis occurs as a direct result of the action of the UmuDC gene-products, which form the low fidelity Escherichia coli DNA polymerase V, a heterotrimeric complex composed of UmuD'(2)C. This chapter describes the preparation of highly purified native pol V that is suitable for a wide range of biochemical studies of protein-protein, protein-DNA interactions and translesion-synthesis (TLS) mechanisms.


The immunological and long-term atopic outcome of infants born to women following a milk-free diet during late pregnancy and lactation: a pilot study.
Infants born to atopic parents have been found to be at high risk of allergy development. The present study investigated the effect of a maternal milk-free diet during late pregnancy and lactation on the immune response and allergy incidence in at-risk and control infants. Atopic mothers were randomly allocated into an intervention group (n 12) or an unrestricted-diet group (n14) and compared with non-atopic mothers following an unrestricted diet (n 12). The intervention involved a maternal milk-free diet during late pregnancy and lactation. Infants were followed up for 18 months postnatally. A significant fall in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G (IgG) antibody levels (P < 0.05) was observed after a 7-week milk-exclusion diet. In maternal and cord serum samples the levels of beta-Lg-IgG and alpha-casein-IgG antibodies were significantly correlated (r 0.89, P < 0.0001 and r 0.71, P < 0.001 respectively). Higher levels of beta-Lg-IgG (P < 0.05) were observed in the cord serum samples compared with paired maternal serum samples. Single-blind allergy assessment by a paediatrician at 12 and 18 months showed that the infants born in the non-atopic group had a significantly lower allergy incidence compared with the infants born in the atopic group following an unrestricted diet (P < 0.008 and P < 0.02 respectively). The allergy incidence in the infants born in the atopic diet group was significantly lower compared with that of the atopic group following an unrestricted diet (P < 0.04). It was observed that the atopic nature of the parents significantly affected the allergy incidence in their children. A trend towards a beneficial effect of a maternal milk-free diet during late pregnancy and lactation was also observed in infants born to atopic parents.


Disturbance frequency and community structure in a twenty-five year intervention study.
Models of community regulation commonly incorporate gradients of disturbance inversely related to the role of biotic interactions in regulating intermediate trophic levels. Higher trophic-level organisms are predicted to be more strongly limited by intermediate levels of disturbance than are the organisms they consume. We used a manipulation of the frequency of hydrological disturbance in an intervention analysis to examine its effects on small-fish communities in the Everglades, USA. From 1978 to 2002, we monitored fishes at one long-hydroperiod (average 350 days) and at one short-hydroperiod (average 259 days; monitoring started here in 1985) site. At a third site, managers intervened in 1985 to diminish the frequency and duration of marsh drying. By the late 1990s, the successional dynamics of density and relative abundance at the intervention site converged on those of the long-hydroperiod site. Community change was manifested over 3 to 5 years following a dry-down if a site remained inundated; the number of days since the most recent drying event and length of the preceding dry period were useful for predicting population dynamics. Community dissimilarity was positively correlated with the time since last dry. Community dynamics resulted from change in the relative abundance of three groups of species linked by life-history responses to drought. Drought frequency and intensity covaried in response to hydrological manipulation at the landscape scale; community-level successional dynamics converged on a relatively small range of species compositions when drought return-time extended beyond 4 years. The density of small fishes increased with diminution of drought frequency, consistent with disturbance-limited community structure; less-frequent drying than experienced in this study (i.e., longer return times) yields predator-dominated regulation of small-fish communities in some parts of the Everglades.


Dopamine receptor genes and evolutionary differentiation in the domestication of fighting cocks and long-crowing chickens.
The chicken domestication process represents a typical model of artificial selection, and gives significant insight into the general understanding of the influence of artificial selection on recognizable phenotypes. Two Japanese domesticated chicken varieties, the fighting cock (Shamo) and the long-crowing chicken (Naganakidori), have been selectively bred for dramatically different phenotypes. The former has been selected exclusively for aggressiveness and the latter for long crowing with an obedient sitting posture. To understand the particular mechanism behind these genetic changes during domestication, we investigated the degree of genetic differentiation in the aforementioned chickens, focusing on dopamine receptor D2, D3, and D4 genes. We studied other ornamental chickens such as Chabo chickens as a reference for comparison. When genetic differentiation was measured by an index of nucleotide differentiation (NST) newly devised in this study, we found that the NST value of DRD4 for Shamo (0.072) was distinctively larger than those of the other genes among the three populations, suggesting that aggressiveness has been selected for in Shamo by collecting a variety of single nucleotide polymorphisms. In addition, we found that in DRD4 in Naganakidori, there is a deletion variant of one proline at the 24th residue in the repeat of nine prolines of exon 1. We thus conclude that artificial selection has operated on these different kinds of genetic variation in the DRD4 genes of Shamo and Naganakidori so strongly that the two domesticated varieties have differentiated to obtain their present opposite features in a relatively short period of time.


Natural variation of chronological aging in the Saccharomyces cerevisiae species reveals diet-dependent mechanisms of life span control.
Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae, mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control. Two major Quantitative Trait Loci (QTLs) were identified within a biparental population obtained by crossing two natural isolates with contrasting aging behavior. Detection of these QTLs was dependent upon the nature and concentration of the carbon sources available for growth. In the first QTL, the RIM15 gene was identified as major regulator of aging under low glucose condition, lending further support to the importance of nutrient-sensing pathways in longevity control under calorie restriction. In the second QTL, we could show that the SER1 gene, encoding a conserved aminotransferase of the serine synthesis pathway not previously linked to aging, is causally associated with CLS regulation, especially under high glucose condition. These findings hint toward a new mechanism of life span control involving a trade-off between serine synthesis and aging, most likely through modulation of acetate and trehalose metabolism. More generally it shows that genetic linkage studies across natural strains represent a promising strategy to further unravel the molecular basis of aging.


Pairwise joint modeling of clustered and high-dimensional outcomes with covariate missingness in pediatric pneumonia care.
Multiple outcomes reflecting different aspects of routine care are a common phenomenon in health care research. A common approach of handling such outcomes is multiple univariate analyses, an approach which does not allow for answering research questions pertaining to joint inference. In this study, we sought to study associations among nine pediatric pneumonia care outcomes spanning assessment, diagnosis and treatment domains of care, while circumventing the computational challenge posed by their clustered and high-dimensional nature and incompletely recorded covariates. We analyzed data from a cluster randomized trial conducted in 12 Kenyan hospitals. There were varying degrees of missingness in the covariates of interest, and these were multiply imputed using latent normal joint modeling. We used the pairwise joint modeling strategy to fit a correlated random effects joint model for the nine outcomes. This entailed fitting 36 bivariate generalized linear mixed models and deriving inference for the joint model using pseudo-likelihood theory. We also analyzed the nine outcomes separately before and after multiple imputation. We observed joint effects of patient-, clinician- and hospital-level factors on pneumonia care indicators before and after multiple imputation of missing covariates. In both pairwise joint modeling and separate univariate analysis methods, enhanced audit and feedback improved documentation and adherence to recommended clinical guidelines over time in six and five pneumonia care indicators, respectively. Additionally, multiple imputation improved precision of parameter estimates compared to complete case analysis. The strength and direction of association among pneumonia outcomes varied within and across the three domains of pneumonia care.


AIRE1A might be involved in cyclin B2 degradation in testicular lysates.
The autoimmune regulator gene Aire shows predominant expression in thymus and other immunologically relevant tissues, and is assigned the major function of programming autoreactive T-cell deletion. However, the expression of this gene in tissues outside the immune system raises a question about its possible function beyond the T-cell deletion dogma. We detected Aire in mouse testis, and the expression of AIRE protein was remarkably high in postmeiotic germ cells. Sequencing results indicate that testis expressed Aire variant 1a. AIRE could be detected in spermatozoa, with heavy localization on the principal acrosomal domains. Mouse oocytes stained negatively for AIRE before fertilization, but stained positively for AIRE 30 min after fertilization. In the zygote, the levels of AIRE correlated negatively with cyclin B2 levels. Goat testicular lysates spiked with recombinant human AIRE exhibited augmented cyclin B2 degradation in the presence of protease inhibitors, which was inhibited by MG-132, indicating the operation of proteasomal pathways. Thus, this study identifies a correlation between the presence of AIRE and proteasomal breakdown of cyclin B2, which leads us to speculate that cyclin B2 could be a target of AIRE's E3-ubiquitin ligase activity.


Anemia in Intensive Care: A Review of Current Concepts.
Anemia in patients admitted to an intensive care unit is common and affects almost all critically ill patients. The intensivist is faced with the challenge of treating multifactorial etiologies, mainly bleeding and blood loss due to phlebotomy and decreased erythropoiesis. Red cell transfusion, the most common treatment for anemia, comes with associated risks, which may further reduce the chance of survival of these patients. The best evidence suggests the practice of restrictive RBC transfusion (transfusion at Hb<7 g/dl). In this article, the etiopathogenesis of the anemia in critically ill is reviewed, and current opinion on the pros and cons of various management strategies are discussed with emphasize on restrictive transfusion policy.


Neural overlap of L1 and L2 semantic representations in speech: A decoding approach.
Although research has now converged towards a consensus that both languages of a bilingual are represented in at least partly shared systems for language comprehension, it remains unclear whether both languages are represented in the same neural populations for production. We investigated the neural overlap between L1 and L2 semantic representations of translation equivalents using a production task in which the participants had to name pictures in L1 and L2. Using a decoding approach, we tested whether brain activity during the production of individual nouns in one language allowed predicting the production of the same concepts in the other language. Because both languages only share the underlying semantic representation (sensory and lexical overlap was maximally avoided), this would offer very strong evidence for neural overlap in semantic representations of bilinguals. Based on the brain activation for the individual concepts in one language in the bilateral occipito-temporal cortex and the inferior and the middle temporal gyrus, we could accurately predict the equivalent individual concepts in the other language. This indicates that these regions share semantic representations across L1 and L2 word production.


Relationship of mesenteric panniculitis with visceral and subcutaneous adipose tissue
Mesenteric panniculitis (MP) is an idiopathic benign disease characterized by fat necrosis, chronic inflammation, and fibrosis. The relationship between obesity and chronic low-grade inflammation has been reported. This study investigated the relationship of MP diagnosed using multidetector computed tomography (MDCT) with visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas. We retrospectively enrolled 104 patients with no radiological findings other than MP. Additionally, 76 individuals without any indicative radiological findings were included as controls. VAT and SAT were separately calculated (cm2) using a 3-dimensional workstation. The abdominal circumference was measured (cm). The mean abdominal circumference was 99.9 ± 7.9 cm, SAT was 195.3 ± 89.1 cm2, and VAT was 203.9 ± 72.8 cm2 in the MP group. The abdominal circumference, VAT, and SAT were significantly higher in the MP group than in the control group (P < 0.001). According to the receiver operating characteristic (ROC) analysis, cut-off level VAT and SAT were 167.5 cm2 (sensitivity 71%, specificity 69%) and 117.5 cm2 (sensitivity 78%, specificity 51 %), respectively. Increased VAT and SAT were associated with MP, suggesting their role in the etiology of MP.


Influence of a Pilates exercise program on the quality of life of sedentary elderly people: A randomized clinical trial.
This study evaluated the influence of a Pilates exercise program on the quality of life (QOL) of sedentary elderly women. Twenty-four elderly women (aged 64.8 ± 3 years) participated in this study. Participants were divided into two groups: a Pilates Group (PG) and a Control Group (CG). The women in the PG performed 30-min sessions of Pilates (on the ground and using appliances) twice a week over six months. To evaluate the QOL, the SF-36 survey was used. The PG achieved significant improvements in 7 out of 8 domains in the survey: functional capacity (p = 0.00), physical aspects (p = 0.03), pain (p = 0.00), general health condition (p = 0.04), vitality (p = 0.02), social aspects (p = 0.03) and mental health (p = 0.05). Our results showed that implementation of a Pilates program can improve QOL of sedentary elderly women.


How is gambling related to perceived parenting style and/or family environment for college students?
Background and aims The relationship between college student gambling, parenting styles, and family environments is a neglected area of gambling research. Do parenting styles indirectly influence problem gambling behaviors via family environments? Do poor family environments, characterized by high levels of conflict and low levels of cohesion, increase the likelihood of problem gambling among youth? This study explored the interrelationships among college students' current gambling behaviors and a) having an emotionally close and supportive family environment, b) having nagging and critical parents, c) having an authoritative mother, and d) frequency of alcohol consumption. Methods and results Survey data were collected from 450 undergraduate students enrolled in introductory psychology classes at two state universities in a southern state. Feeling that one has nagging and critical parents was associated with gambling in more venues, while the opposite was true for having emotionally close and supportive families. However, perceptions of having authoritative mothers were not related to gambling. The results also showed that more frequent alcohol consumption was associated with higher odds of gambling in casinos, playing cards for money, betting on sports, gambling on the Internet, higher gambling losses, and a larger number of gambling venues. Conclusions As with any exploratory research, there are several unique lines of inquiry that can, and should, follow from these findings, including more research on how college students' attitudes toward gambling activities may have begun prior to college and been influenced by their feelings about their homes and parents.


Immunology of psoriasis.
The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases.


In search of the 'problem family': public health and social work in England and Wales 1940-70.
Recent attempts to explain the decline of public health in England and Wales after 1948 have suggested that services had developed steadily but haphazardly in the interwar period, and that the lack of an underlying philosophy left Medical Officers of Health and their empires vulnerable to a range of forces that included the decline of infectious disease, the rise of hospital medicine, the growth of general practice, and the increasing professionalism of social work. Yet the argument that public health practitioners lagged behind contemporary thinking on social work in the 1950s deserves closer examination, and this article uses the rise and decline of the concept of the 'problem family' to examine the changing relationship between the two professional groups. It traces the emergence of the concept of the 'social problem group' in the 1930s, and considers why and how Medical Officers of Health and the Eugenics Society took up the idea of the 'problem family' after the Second world War. It charts how the Ministry of Health encouraged local authorities to use home helps and health visitors to tackle the 'problem family', and contrasts this medical approach with the casework methods developed by voluntary organizations and subsequently adopted by the social work profession. The article concludes that in revealing how Medical Officers of Health were out of touch with contemporary research and practice in social work, the issue of the 'problem family' helps to explain the decline of public health under the early National Health Service.


Can Mandibular Condylar Mobility Sonography Measurements Predict Difficult Laryngoscopy?
Limited mandibular condylar mobility plays an important role in difficult laryngoscopy. Indirect assessment methods, such as mouth opening, have been proven to be useful predictors of difficult laryngoscopy. Sonography is a new direct assessment method for the limited mandibular condylar mobility. However, whether this method could be used in predicting difficult laryngoscopy still remains unknown. This study aimed to observe its ability to predict difficult laryngoscopy. Adult patients who were administered tracheal intubations for elective surgery under general anesthesia were enrolled in the study. Mandibular condylar mobility was assessed by sonography through condylar translation measurements. Beside mouth opening, other indirect variables that correlated with temporomandibular joint mobility, such as mandibular protrusion distance, upper lip bite test, and whether the condyle-tragus distance was <1 finger breadth, were also evaluated before anesthesia. The primary outcome was difficult laryngoscopy defined as the Cormack-Lehane level 3 or 4. A total of 484 patients were prospectively included, and difficult laryngoscopy was reported in 41 patients. The condylar translation prediction criterion for difficult laryngoscopy was ≤10 mm. The condylar translation was correlated with Cormack-Lehane level (Spearman correlation coefficient, -0.46; 99% confidence interval [CI], -0.55 to -0.36) and owned the highest area under the receiver operating characteristic curve (0.93; 99% CI, 0.90 to 0.96, compared with that of the other predictors, P < .001) with difficult laryngoscopy. The condylar translation ≤10 mm was with a considerable κ value (κ = 0.52; 99% CI, 0.37 to 0.67) to difficult laryngoscopy and proved to be an independent predictor by a multivariate logistic regression. Compared with indirect assessments, such as mouth opening and other parameters, mandibular condylar mobility, as assessed directly using sonography, was correlated with difficult laryngoscopy and demonstrated an independent and notably predictive property.


Physiologic and dosimetric considerations for limiting electric fields induced in the body by movement in a static magnetic field.
Movement in a strong static magnetic field induces electric fields in a human body, which may result in various sensory perceptions such as vertigo, nausea, magnetic phosphenes, and a metallic taste in the mouth. These sensory perceptions have been observed by patients and medical staff in the vicinity of modern diagnostic magnetic resonance (MR) equipment and may be distracting if they were to affect the balance and eye-hand coordination of, for example, a physician carrying out a medical operation during MR scanning. The stimulation of peripheral nerve tissue by a more intense induced electric field is also theoretically possible but has not been reported to result from such movement. The main objective of this study is to consider generic criteria for limiting the slowly varying broadband (<10 Hz) electric fields induced by the motion of the body in the static magnetic field. In order to find a link between the static magnetic flux density and the time-varying induced electric field, the static magnetic field is converted to the homogeneous equivalent transient and sinusoidal magnetic fields exposing a stationary body. Two cases are considered: a human head moving in a non-uniform magnetic field and a head rotating in a homogeneous magnetic field. Then the electric field is derived from the magnetic flux rate (dB/dt) of the equivalent field by using computational dosimetric data published in the literature for various models of the human body. This conversion allows the plotting of the threshold electric field as a function of frequency for vertigo, phosphenes, and stimulation of peripheral nerves. The main conclusions of the study are: The basic restrictions for limiting exposure to extremely low frequency magnetic fields recommended by the International Commission on Non-Ionizing Radiation Protection ICNIRP in 1998 will prevent most cases of vertigo and other sensory perceptions that result from induced electric fields above 1 Hz, while limiting the static magnetic field below 2 T, as recently recommended by ICNIRP, provides sufficient protection below 1 Hz. People can experience vertigo when moving in static magnetic fields of between 2 and 8 T, but this may be controlled to some extent by slowing down head and/or body movement. In addition, limiting the static magnetic field below 8 T provides good protection against peripheral nerve stimulation.


Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) found insufficient evidence to recommend testing for predictive variants in 28 variants (listed in Table 1) to assess risk for type 2 diabetes in the general population, on the basis of studies in populations of northern European descent. The EWG found that the magnitude of net health benefit from the use of any of these tests alone or in combination is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.The EWG found insufficient evidence to recommend testing for the TCF7L2 gene to assess risk for type 2 diabetes in high-risk individuals. The EWG found that the magnitude of net health benefit from the use of this test is close to zero. The EWG discourages clinical use unless further evidence supports improved clinical outcomes.On the basis of the available evidence for both the scenarios, the overall certainty of net health benefit is deemed "low." It has been suggested that genomic profiling in the general population or in high-risk populations for type 2 diabetes might lead to management changes (e.g., earlier initiation or higher rates of medical interventions, or targeted recommendations for behavioral change) that improve type 2 diabetes outcomes or prevent type 2 diabetes. The EWG found no direct evidence to support this possibility; therefore, this review sought indirect evidence aimed at documenting the extent to which genomic profiling alters type 2 diabetes risk estimation, alone and in combination with traditional risk factors, and the extent to which risk classification improves health outcomes. Assay-related evidence on available genomic profiling tests was deemed inadequate. However, on the basis of existing technologies that have been or may be used, the analytic sensitivity and specificity of tests for individual gene variants might be at least satisfactory. Twenty-eight candidate markers were evaluated in the general population. Evidence on clinical validity was rated inadequate for 24 of these associations (86%) and adequate for 4 (14%). Inadequate grades were based on limited evidence, poor replication, existence of possible biases, or combinations of these factors. Type 2 diabetes genomic profiling provided areas under the receiver operator characteristics curve of 55%-57%, with 4, 8, and 28 genes. Only TCF7L2 had convincing evidence of an association with type 2 diabetes with an odds ratio of 1.39 (95% confidence interval: 1.33-1.46).TCF7L2 was evaluated for high-risk populations, and the overall odds ratio was 1.66 (95% confidence interval: 1.22-2.27) for association with progression to type 2 diabetes. No studies were available to provide direct evidence on the balance of benefits and harms for genetic profiling for type 2 diabetes alone or in addition to traditional risk factors in the general population.Evidence for high-risk populations and TCF7L2 was inadequate on the basis of two identified studies. These studies found close to zero additional benefit with the addition of genomic markers to traditional risk factors (diet, body mass index, and glucose tolerance). Prevention of type 2 diabetes is a public health priority. Improvements in the outcomes associated with genomic profiling could have important impacts. Traditional risk factors (e.g., body mass index, weight, fat mass, and exercise) have an advantage in clinical screening and risk assessment strategies because they measure the actual targets for therapy (e.g., fasting plasma glucose and medical interventions). To be useful in predicting disease risk, genomic testing should improve the predictive value of these traditional risk factors. Some issues important for clinical utility remain unknown, such as the level of risk that changes intervention, whether long-term disease outcomes will improve, how individuals being tested will understand/respond to test results and interact with the health-care system, and whether testing will motivate behavior change or amplify potential harms.


[Mortality from neural tube defects in Mexico, 1980-1997].
To describe the mortality due to neural tube defects (NTD) in Mexico for the 1980-1997 period. The annual NTD mortality rates per 10000 liveborn infants were calculated by state and for the country. The time trend was evaluated with the annual percent change (APC) obtained using a Poisson regression model. The NTD mortality ratio was calculated using the average national rate as reference. NTD mortality rates and ratios were graphically displayed on maps. During the 1980-1997 period the gross NTD mortality rate was 5.8 per 10000 live-born infants. Anencephaly (International Classification of Diseases ICD-9 740.0) was the most frequent type of NTD (37.7%), followed by spina bifida without hydrocephaly (CIE9 741.9) (31.6%). The national trend of NTD mortality increased between 1980 and 1990 (APC 7.5 95% CI 6.5, 8.6) and decreased between 1990 and 1997 (APC-2.3 95% CI-3.6, -0.9). The high NTD mortality rates were related to the high frequency of anencephaly. Also, the increase observed is not only attributable to diagnostic factors or to improved reporting. In Mexico, the influence of some NTD-associated factors such as specific genetic polymorphisms, folic acid deficit, maternal obesity, occupational exposure to pesticides, and poverty, should be assessed in specific studies.


Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men.
To evaluate the relationship between changes in physical fitness and risk of mortality in men. Prospective study, with two clinical examinations (mean interval between examinations, 4.9 years) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination (mean follow-up from subsequent examination, 5.1 years). Preventive medicine clinic. Participants were 9777 men given two preventive medical examinations, each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status. All cause (n = 223) and cardiovascular disease (n = 87) mortality. The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations (122.0/10,000 man-years); the lowest death rate was in men who were physically fit at both examinations (39.6/10,000 man-years). Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10,000 man-years. This is a reduction in mortality risk of 44% (95% confidence interval, 25% to 59%) relative to men who remained unfit at both examinations. Improvement in fitness was associated with lower death rates after adjusting for age, health status, and other risk factors of premature mortality. For each minute increase in maximal treadmill time between examinations, there was a corresponding 7.9% (P = .001) decrease in risk of mortality. Similar results were seen when the group was stratified by health status, and for cardiovascular disease mortality. Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men. Physicians should encourage unfit men to improve their fitness by starting a physical activity program.


Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis.
Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (PUFAs) to measures of atherosclerosis are sparse. We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis. A cross-sectional study was conducted in a multiethnic group of 5,488 adults aged 45-84 y and free of clinical cardiovascular disease. Diet was assessed by using self-administered food-frequency questionnaires. Subclinical atherosclerosis was determined by measurements of common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC score, >0), or ankle-brachial index (ABI, <0.90). After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and nonfried (broiled, steamed, baked, or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not by iCIMT, CAC score, or ABI. The multivariate odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; P for trend < 0.01) for n-3 PUFA intake; 0.80 (95% CI: 0.64, 1.01; P = 0.054) for nonfried fish consumption; and 0.90 (95% CI: 0.73, 1.11; P = 0.38) for fried fish consumption. This study indicates that the dietary intake of long-chain n-3 PUFAs or nonfried fish is associated with a lower prevalence of subclinical atherosclerosis classified by cCIMT, although significant changes in iCIMT, CAC score, and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis.


High speed light choppers.
Mechanical light choppers are used in many optical systems with a great deal of success. At high PRF's, however, designers often tend to avoid their use because of stress and torque limitations. This article attempts to provide an optical engineer with sufficient information to compute the maximum stresses in a chopper wheel. It also provides curves for estimating the torque required to drive the wheel as well as general design guidelines. An example is shown of a 10-kHz chopper that was designed from the data presented and is now in use.


Cancer in patients with ulcerative colitis, Crohn's disease and coeliac disease: record linkage study.
The objective of this study was to determine the risk of cancers in cohorts of patients with ulcerative colitis, Crohn's disease, or coeliac disease, compared with the risk in a control cohort. The method used was the analysis of a linked statistical database of hospital and mortality data in an area in southern England. Rate ratios for cancer (excluding cases occurring within the first year of follow-up), compared with the value of 1 in the control cohort, were 1.25 [95% confidence interval (CI), 1.13-1.39] in patients with ulcerative colitis, 1.27 (95% CI, 1.11-1.45) with Crohn's disease, and 1.16 (95% CI, 0.94-1.43) with coeliac disease. In patients with ulcerative colitis or Crohn's disease, there was a significantly high risk of cancer of the colon [2.22 (95% CI, 1.71-2.83) and 1.64 (95% CI, 1.09-2.39), respectively]. In patients with ulcerative colitis there was a significantly high risk of cancer of the rectum [1.84 (95% CI, 1.27-2.58)]. In patients with ulcerative colitis or Crohn's disease, who did not undergo partial or total colectomy for it, the rate ratios for colon cancer were, respectively, 5.52 (95% CI, 4.39-6.71) and 4.81 (95% CI, 3.52-6.47). In ulcerative colitis, there was an elevated risk of cancer of the rectum, liver and ovary. The rate ratio for lung cancer was low, but of borderline significance [0.72 (95% CI, 0.50-0.98)]. In Crohn's disease, the rate ratio was high for cancer of the cervix [2.63 (95% CI, 1.12-5.29)]. In patients with coeliac disease, the high-risk cancer was non-Hodgkin's lymphoma [rate ratio 3.28 (95% CI, 1.49-6.28)]. All three diseases carry an increased risk of cancer overall when the first year cases are included, though fairly modest in scale, and the increased risk seen in coeliac disease reduces when first year cases are excluded. Each has a distinctive pattern of individual high-risk cancers.


Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood.
Mutations in the COL1A1 and COL1A2 genes, encoding the proalpha1 and 2 chains of type I collagen, cause osteogenesis imperfecta (OI) or Ehlers-Danlos syndrome (EDS) arthrochalasis type. Although the majority of missense mutations in the collagen type I triple helix affect glycine residues in the Gly-Xaa-Yaa repeat, few nonglycine substitutions have been reported. Two arginine-to-cysteine substitutions in the alpha1(I)-collagen chain are associated with classic EDS [R134C (p.R312C)] or autosomal dominant Caffey disease with mild EDS features [R836C (p.R1014C)]. Here we show alpha1(I) R-to-C substitutions in three unrelated patients who developed iliac or femoral dissection in early adulthood. In addition, manifestations of classic EDS in Patient 1 [c.1053C>T; R134C (p.R312C); X-position] or osteopenia in Patients 2 [c.1839C>T; R396C (p.R574C); Y-position] and 3 [c.3396C>T; R915C (p.R1093C); Y-position] are seen. Dermal fibroblasts from the patients produced disulfide-bonded alpha1(I)-dimers in approximately 20% of type I collagen, which were efficiently secreted into the medium in case of the R396C and R915C substitution. Theoretical stability calculations of the collagen type I heterotrimer and thermal denaturation curves of monomeric mutant alpha1(I)-collagen chains showed minor destabilization of the collagen helix. However, dimers were shown to be highly unstable. The R134C and R396C caused delayed procollagen processing by N-proteinase. Ultrastructural findings showed collagen fibrils with variable diameter and irregular interfibrillar spaces, suggesting disturbed collagen fibrillogenesis. Our findings demonstrate that R-to-C substitutions in the alpha1(I) chain may result in a phenotype with propensity to arterial rupture in early adulthood. This broadens the phenotypic range of nonglycine substitutions in collagen type I and has important implications for genetic counseling and follow-up of patients carrying this type of mutation.


Early mitochondrial dysfunction in glycolytic muscle, but not oxidative muscle, of the fructose-fed insulin-resistant rat.
Although evidence that type 2 diabetes mellitus (T2DM) is accompanied by mitochondrial dysfunction in skeletal muscle has been accumulating, a causal link between mitochondrial dysfunction and the pathogenesis of the disease remains unclear. Our study focuses on an early stage of the disease to determine whether mitochondrial dysfunction contributes to the development of T2DM. The fructose-fed (FF) rat was used as an animal model of early T2DM. Mitochondrial respiration and acylcarnitine species were measured in oxidative (soleus) and glycolytic [extensor digitorum longus (EDL)] muscle. Although FF rats displayed characteristic signs of T2DM, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, mitochondrial content was preserved in both muscles from FF rats. The EDL muscle had reduced complex I and complex I and II respiration in the presence of pyruvate but not glutamate. The decrease in pyruvate-supported respiration was due to a decrease in pyruvate dehydrogenase activity. Accumulation of C14:1 and C14:2 acylcarnitine species and a decrease in respiration supported by long-chain acylcarnitines but not acetylcarnitine indicated dysfunctional β-oxidation in the EDL muscle. In contrast, the soleus muscle showed preserved mitochondrial respiration, pyruvate dehydrogenase activity, and increased fatty acid oxidation, as evidenced by overall reduced acylcarnitine levels. Aconitase activity, a sensitive index of reactive oxygen species production in mitochondria, was reduced exclusively in EDL muscle, which showed lower levels of the antioxidant enzymes thioredoxin reductase and glutathione peroxidase. Here, we show that the glycolytic EDL muscle is more prone to an imbalance between energy supply and oxidation caused by insulin resistance than the oxidative soleus muscle.


Monetary valuation of illnesses in Costa Rica: a subjective well-being approach.
This report aims to 1) explain and illustrate the use of the subjective well-being (SWB) approach as an alternative health-valuation methodology by estimating the monetary value of five general categories of illness in Costa Rica, and 2) foster comparative research on the advantages and limitations of alternative approaches to health valuation. Use of the SWB valuation approach to measure the monetary value of illness (MVI), based on empirical data from a representative survey in Costa Rica carried out in 2004. The MVI is defined as the estimated percentage of monthly income that would be required to compensate for the loss in life satisfaction (LS)--a primary SWB conception-that is expected to occur with the onset of illness. The five general categories of illnesses studied were cancer, cardiovascular disease, thyroid disease, arthritis, and infectious disease. There was wide disparity in the monetary values of the different illnesses. Some illnesses had relatively high monetary value compared to persons' mean income, indicating the high value of good health and of programs that aim to prevent the emergence of illnesses or abate their negative impact on people's well-being. The SWB valuation approach can be used to estimate illnesses' monetary value and thus can contribute to the design of health policies related to resource allocation and compensation, and revenue-generating schemes.


Prevalence of Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder in Workers With Upper Extremity Complaints.
Study Design Cross-sectional cohort study. Background Symptoms of depression, panic disorder (PD), and posttraumatic stress disorder (PTSD) have been associated with musculoskeletal complaints and could represent barriers to recovery in injured workers. Objectives To determine the prevalence of symptoms of depression, PD, and PTSD utilizing the Patient Health Questionnaire (PHQ) in a cohort of patients presenting to an upper extremity injured-worker clinic; secondarily, to identify any relationships between patients screening positive and patient-reported outcome measures. Methods In 2010, 418 patients completed the PHQ during their initial evaluation. Patients with PHQ scores exceeding threshold values for symptoms of depression, PD, or PTSD were compared based on patient-reported outcome scores, including the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The prevalence of symptoms, and their relationship with presenting complaints and patient-reported outcomes, were calculated. Results Thirty-one percent of patients scored above thresholds for symptoms of at least 1 mental health disorder. Of those who screened positive, 67% screened positive for depression, 44% for PTSD, and 50% for PD, with 43% of patients positive for multiple symptoms. Patients experiencing neck pain had significantly higher screening rates of depressive symptoms (62.5% versus 20.1%, P = .004) and PD (37.5% versus 12.9%, P = .044) compared with other presenting complaints. Similarly, patients with chronic pain had higher rates of depression (54.5% versus 20.1%, P = .006), PD (63.6% versus 12%, P<.001), and PTSD (36.4% versus 14.8%, P = .05) compared with other presenting complaints. Patients endorsing depressive symptoms had significantly lower SF-36 mental component summary scores (26.3 ± 10.7 versus 37.6 ± 9.9, P<.001) and higher shortened-version DASH (72.3 ± 16.7 versus 61.5 ± 11.1, P = .003) and DASH work scores (86.5 ± 19.2 versus 82.1 ± 20.1, P = .007) compared to patients endorsing other items on the PHQ. Conclusion In this prospective cohort study of injured workers, we identified a relatively high prevalence of symptoms of psychological disorders utilizing the PHQ, with one third of injured workers screening positive for symptoms of depression, PD, or PTSD. Further longitudinal follow-up is necessary to determine the impact on treatment outcomes. Level of Evidence Symptom prevalence, level 1b. J Orthop Sports Phys Ther 2016;46(7):590-595. Epub 12 May 2016. doi:10.2519/jospt.2016.6265.


Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.
The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients. 16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose. Only one patient lost HBsAg. 48 and 44 amino acid mutations were found before and after vaccine therapy in the vaccine group respectively, 51 of which (55.4%) occurred in immune epitopes: 5 were in B cell, 21 in T helper (Th), and 25 in cytotoxic T-lymphocyte (CTL) epitopes. In the control group, 35 and 41 amino acid substitutions were found before and after therapy, respectively. 32 (42%) of 76 amino acid changes occurred within immune epitopes. There were no differences in age, gender, and duration of chronicity in both patient and control groups in terms of the frequency and the patterns of mutations. In chronic carriers who already had HBsAg variants selected by the host-immune response, any immune stimulation by the vaccine had no effect on the chronic state of these patients or selected any remarkable escape mutants. Newer strategies should be considered based on third generation or the use of DNA vaccines or new adjuvants.


Pragmatics in action: indirect requests engage theory of mind areas and the cortical motor network.
Research from the past decade has shown that understanding the meaning of words and utterances (i.e., abstracted symbols) engages the same systems we used to perceive and interact with the physical world in a content-specific manner. For example, understanding the word "grasp" elicits activation in the cortical motor network, that is, part of the neural substrate involved in planned and executing a grasping action. In the embodied literature, cortical motor activation during language comprehension is thought to reflect motor simulation underlying conceptual knowledge [note that outside the embodied framework, other explanations for the link between action and language are offered, e.g., Mahon, B. Z., & Caramazza, A. A critical look at the embodied cognition hypothesis and a new proposal for grouding conceptual content. Journal of Physiology, 102, 59-70, 2008; Hagoort, P. On Broca, brain, and binding: A new framework. Trends in Cognitive Sciences, 9, 416-423, 2005]. Previous research has supported the view that the coupling between language and action is flexible, and reading an action-related word form is not sufficient for cortical motor activation [Van Dam, W. O., van Dijk, M., Bekkering, H., & Rueschemeyer, S.-A. Flexibility in embodied lexical-semantic representations. Human Brain Mapping, doi: 10.1002/hbm.21365, 2011]. The current study goes one step further by addressing the necessity of action-related word forms for motor activation during language comprehension. Subjects listened to indirect requests (IRs) for action during an fMRI session. IRs for action are speech acts in which access to an action concept is required, although it is not explicitly encoded in the language. For example, the utterance "It is hot here!" in a room with a window is likely to be interpreted as a request to open the window. However, the same utterance in a desert will be interpreted as a statement. The results indicate (1) that comprehension of IR sentences activates cortical motor areas reliably more than comprehension of sentences devoid of any implicit motor information. This is true despite the fact that IR sentences contain no lexical reference to action. (2) Comprehension of IR sentences also reliably activates substantial portions of the theory of mind network, known to be involved in making inferences about mental states of others. The implications of these findings for embodied theories of language are discussed.


New perspectives on molecular and cellular mechanisms of neuroprotection and neuroregeneration: part II.
Recent developments in the rapidly advancing area of neuroprotection and neuroregeneration necessitated the need to gather over 50 of the world's leading experts under the umbrella of the Global College of Neuroprotection and Neuroregeneration in its 7th Annual Meeting in Stockholm, Sweden. In this meeting, top policy-makers, together with world leaders in pharmaceutical industries, discussed the urgent need to develop new pharmaceuticals, as well as using a combination of existing ones, to treat CNS disorders in order to improve the current status of healthcare. In addition, nanobiotechnologists proposed the use of a new formulation of drugs using nanotechnologies for enhanced drug delivery to the brain for better therapeutic efficacy of the neuroprotective agents. The deliberations in this meeting provide new perspectives on the molecular and cellular mechanisms of neuroprotection and neuroregeneration that could be utilized to improve the existing healthcare for the benefit of mankind.


The Nutrition Society Medical Lecture. Obesity: from molecules to man.
Obesity is now a major public health problem in both developed and developing countries. In the UK over 16% men and 17.5% women are obese, an increase of more than 100% since 1980. However, interventions to prevent and treat obesity are hampered by an inadequate understanding of the aetiology of this condition. The present paper considers the current state of knowledge regarding the causes of obesity, including some of the genetic, metabolic, behavioural and environmental factors which influence energy balance. The present paper comprises The Nutrition Society Medal Lecture and focuses in particular on the research carried out at the MRC Dunn Nutrition Centre in Cambridge. It argues that despite decades of intensive research there is relatively little evidence of genetic or metabolic defects to explain the majority of cases of human obesity. Instead we must look to behavioural and/or environmental factors which may be underpinning the current epidemic of obesity.


Unequally ageing regions of Europe: Exploring the role of urbanization.
Since young adults tend to move from rural to urban regions, whereas older adults move from urban to rural regions, we may expect to see increasing differences in population ageing across urban and rural regions. This paper examines whether trends in population ageing across urban and rural NUTS-2 regions of the EU-27 have diverged over the period 2003-13. We use the methodological approach of convergence analysis, quite recently brought to demography from the field of economic research. Unlike classical beta and sigma approaches to convergence, we focus not on any single summary statistic of convergence, but rather analyse the whole cumulative distribution of regions. Such an approach helps to identify which specific group of regions is responsible for the major changes. Our results suggest that, despite expectations, there was no divergence in age structures between urban and rural regions; rather, divergence happened within each of the groups of regions.


Differential expression of glucose-metabolizing enzymes in multiple sclerosis lesions.
Demyelinated axons in multiple sclerosis (MS) lesions have an increased energy demand in order to maintain conduction. However, oxidative stress-induced mitochondrial dysfunction likely alters glucose metabolism and consequently impairs neuronal function in MS. Imaging and pathological studies indicate that glucose metabolism is altered in MS, although the underlying mechanisms and its role in neurodegeneration remain elusive. We investigated expression patterns of key enzymes involved in glycolysis, tricarboxylic acid (TCA) cycle and lactate metabolism in well-characterized MS tissue to establish which regulators of glucose metabolism are involved in MS and to identify underlying mechanisms. Expression levels of glycolytic enzymes were increased in active and inactive MS lesions, whereas expression levels of enzymes involved in the TCA cycle were upregulated in active MS lesions, but not in inactive MS lesions. We observed reduced expression and production capacity of mitochondrial α-ketoglutarate dehydrogenase (αKGDH) in demyelinated axons, which correlated with signs of axonal dysfunction. In inactive lesions, increased expression of lactate-producing enzymes was observed in astrocytes, whereas lactate-catabolising enzymes were mainly detected in axons. Our results demonstrate that the expression of various enzymes involved in glucose metabolism is increased in both astrocytes and axons in active MS lesions. In inactive MS lesions, we provide evidence that astrocytes undergo a glycolytic shift resulting in enhanced astrocyte-axon lactate shuttling, which may be pivotal for the survival of demyelinated axons. In conclusion, we show that key enzymes involved in energy metabolism are differentially expressed in active and inactive MS lesions. Our findings imply that, in addition to reduced oxidative phosphorylation activity, other bioenergetic pathways are affected as well, which may contribute to ongoing axonal degeneration in MS.


A model for improving physician performance in developing countries: a three-year postgraduate training program in Laos.
The Faculty of Medical Sciences of the National University of Laos, in partnership with Health Frontiers, an American nonprofit organization, Case Western Reserve University of Cleveland, Ohio, and Khon Kaen University of Khon Kaen, Thailand, administer a postgraduate internal medicine training program for Lao physicians. Begun in 2001, the program admits six participants per year; participants complete clinical rotations in three hospitals in Vientiane, Laos, as well as one other clinical site. The goal of the program is to prepare a core group of local physicians to deliver healthcare, and train others according to an international standard of care. The program has two exceptional features. First, the vast majority of the training takes place in Laos. This avoids the "brain drain" that can occur when nationals of developing countries train abroad. In addition, because the training uses personnel, facilities, and technology available locally, graduates are better prepared to serve the needs of the Lao people. Second, the partnership is an all-volunteer model, committed to a long-term undertaking. American-trained specialists who live in Laos are available to work with the participants on a daily basis. Participants have a long period of time to acquire, reinforce, and be tested in new knowledge and benefit from learning from American colleagues who model an evidence-based approach to medical care, while still working in local conditions. As more Lao physicians receive this level of training, the program will become locally sustainable and help break a cycle of dependency on foreign expertise within the Lao health care sector. Preliminary results suggest that the program is succeeding, and could be replicated elsewhere.


Cognitive fatigue effects on physical performance: A systematic review and meta-analysis.
Recent research has examined the effect that undertaking a cognitively fatiguing task for ≤90 min has on subsequent physical performance. Cognitive fatigue is claimed to affect subsequent physical performance by inducing energy depletion in the brain, depletion of brain catecholamine neurotransmitters or changes in motivation. Observation of the psychophysiology and neurochemistry literature questions the ability of 90 min' cognitive activity to deplete energy or catecholamine resources. The purpose of this study, therefore, was to examine the evidence for cognitive fatigue having an effect on subsequent physical performance. A systematic, meta-analytic review was undertaken. We found a small but significant pooled effect size based on comparison between physical performance post-cognitive fatigue compared to post-control (g = -0.27, SE = -0.12, 95% CI -0.49 to -0.04, Z(10) = -2.283, p < 0.05). However, the results were not heterogenous (Q(10) = 2.789, p > 0.10, Τ2 < 0.001), suggesting that the pooled effect size does not amount to a real effect and differences are due to random error. No publication bias was evident (Kendall's τ = -0.07, p > 0.05). Thus, the results are somewhat contradictory. The pooled effect size shows a small but significant negative effect of cognitive fatigue, however tests of heterogeneity show that the results are due to random error. Future research should use neuroscientific tests to ensure that cognitive fatigue has been achieved.


Migration, Family Arrangement, and Children's Health in China.
With unprecedented migration taking place in China, millions of children are profoundly affected. Using a sample of 916 children (aged 5-18) of migrants and the life course perspective, this article examines the impact of parental migration on children's health. Results show that migration has a complex impact on children's health. Although migrating to cities itself does not benefit children, poor housing conditions in cities have a negative impact on their health. The timing of parental migration is important, as preschoolers migrating with parents and teenagers left behind by parents have significantly worse health than others. Migration also has a gendered effect, as teenage boys benefit from migrating to cities but suffer from being left behind when compared to teenage girls.


An Automated System for Skeletal Maturity Assessment by Extreme Learning Machines.
Assessing skeletal age is a subjective and tedious examination process. Hence, automated assessment methods have been developed to replace manual evaluation in medical applications. In this study, a new fully automated method based on content-based image retrieval and using extreme learning machines (ELM) is designed and adapted to assess skeletal maturity. The main novelty of this approach is it overcomes the segmentation problem as suffered by existing systems. The estimation results of ELM models are compared with those of genetic programming (GP) and artificial neural networks (ANNs) models. The experimental results signify improvement in assessment accuracy over GP and ANN, while generalization capability is possible with the ELM approach. Moreover, the results are indicated that the ELM model developed can be used confidently in further work on formulating novel models of skeletal age assessment strategies. According to the experimental results, the new presented method has the capacity to learn many hundreds of times faster than traditional learning methods and it has sufficient overall performance in many aspects. It has conclusively been found that applying ELM is particularly promising as an alternative method for evaluating skeletal age.


Peptides in headlock--a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy.
Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a β-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once bound, the peptide is fastened by two nanobody side chains that clamp it in a headlock fashion. Exploiting this unusual binding mode, we generated a novel nanobody-derived capture and detection system. Matrix-coupled nanobody enables the fast and efficient isolation of epitope-tagged proteins from prokaryotic and eukaryotic expression systems. Additionally, the fluorescently labeled nanobody visualizes subcellular structures in different cellular compartments. The high-affinity-binding and modifiable peptide tag of this system renders it a versatile and robust tool to combine biochemical analysis with microscopic studies.


Risk factors for asthma-related healthcare use: longitudinal analysis using the NHI claims database in a Korean asthma cohort.
Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data. Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability. We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.


Red Flags for Maltese Adults with Congenital Heart Disease: Poorer Dental Care and Less Sports Participation Compared to Other European Patients-An APPROACH-IS Substudy.
Studies in recent years have explored lifestyle habits and health-risk behaviours in adult congenital heart disease (ACHD) patients when compared to controls. The aim of this study was to investigate differences in lifestyle habits between Maltese and other European ACHD patients. Data on alcohol consumption, cigarette smoking, substance misuse, dental care and physical activity collected in 2013-2015 during "Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study" (APPROACH-IS) were analysed. Responses from 119 Maltese participants were compared to those of 1616 participants from Belgium, France, Italy, Norway, Sweden, Switzerland and the Netherlands. Significantly fewer Maltese patients with simple (Maltese 84.1% vs. European 97.5%, p < 0.001) and moderately complex CHD (Maltese 83.6% vs. European 97.4%, p < 0.001) brushed their teeth daily. Only 67.2% of Maltese with moderately complex disease had dental reviews in the previous year compared to 80.3% of Europeans (p = 0.02). Maltese patients with simple (Maltese 31.8% vs. European 56.1%, p = 0.002) and moderately complex lesions (Maltese 30.0% vs. European 59.2%, p < 0.001) performed less regular sport activities. Comparison by country showed Maltese patients to have significantly poorer tooth brushing and sports participation than patients from any other participating country. Alcohol consumption, cigarette smoking and substance misuse were not significantly different. This study highlights lifestyle aspects that Maltese ACHD patients need to improve on, which might not be evident upon comparing patients to non-CHD controls. These findings should also caution researchers against considering behaviours among patients in one country as necessarily representative of patients on the larger scale.


The goal of locomotion: Separating the fundamental task from the mechanisms that accomplish it.
Human locomotion has been well described but is still not well understood. This is largely true because the observable aspects of locomotion-neuromuscular activity that generates forces and motions-relate to both the task solution and the problem being solved. Identifying the fundamental task achieved in locomotion makes it possible to critically evaluate the motor control strategy used to accomplish the task goal. We contend that the readily observed movements and activities of locomotion should be considered mechanism(s). Our proposal is that the fundamental task of walking and running is analogous to flight, and should be defined in terms of the interaction of the individual's mass with the medium in which it moves: a low-density fluid for flight, or the supporting substrate for legged locomotion. A rigorous definition of the fundamental task can help identify the constraints and opportunities that influence its solution and guide the selection of appropriate mechanisms to accomplish the task effectively. The results from robotics-based modeling studies have demonstrated how the interaction of the mass and substrate can be optimized, making the goal of movement a defined trajectory of the individual's mass. We assessed these concepts by evaluating the ground reaction forces generated by an optimization model that satisfies the task but uses none of the mechanisms that are available to the human leg. Then we compared this model to normal human walking. Although it is obvious that the specific task of locomotion changes with a variety of movement challenges, clearly identifying the fundamental task of locomotion puts all other features in an interpretable context.


Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course.
We describe an autopsied case of a Japanese woman with Gerstmann-Straeussler-Scheinker disease (GSS) presenting with a rapidly progressive clinical course. Disease onset occurred at the age of 54 with dementia and gait disturbance. Her clinical course progressively deteriorated until she reached a bedridden state with myoclonus 9 months after onset. Two months later, she reached the akinetic mutism state. Nasal tube feeding was introduced at this point and continued for several years. Electroencephalograms showed diffuse slowing without periodic sharp-wave complexes. Diffusion-weighted magnetic resonance imaging (MRI) showed widespread cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed a Pro to Leu point mutation at codon 102 with methionine homozygosity at codon 129. The patient died of respiratory failure after a total disease duration of 62 months. Neuropathologic examination revealed widespread spongiform change with numerous eosinophilic amyloid plaques (Kuru plaques) in the cerebral and cerebellar cortices by H & E staining. Diffuse myelin pallor with axon loss of the cerebral white matter, suggestive of panencephalopathic-type pathology was observed. Numerous PrP immunopositive plaques and diffuse synaptic-type PrP deposition were extensively observed, particularly in the cerebral and cerebellar cortices. Western blot analysis of proteinase Kresistant PrP showed a characteristic band pattern with a small molecular band of 6 kDa. The reason for the similarity in clinicopathologic findings between the present case and Creutzfeldt-Jakob disease is uncertain; however, the existence of an unknown disease-modifying factor is suspected.


Chemoenzymatic method for glycomics: Isolation, identification, and quantitation.
Over the past decade, considerable progress has been made with respect to the analytical methods for analysis of glycans from biological sources. Regardless of the specific methods that are used, glycan analysis includes isolation, identification, and quantitation. Derivatization is indispensable to increase their identification. Derivatization of glycans can be performed by permethylation or carbodiimide coupling/esterification. By introducing a fluorophore or chromophore at their reducing end, glycans can be separated by electrophoresis or chromatography. The fluorogenically labeled glycans can be quantitated using fluorescent detection. The recently developed approaches using solid-phase such as glycoprotein immobilization for glycan extraction and on-tissue glycan mass spectrometry imaging demonstrate advantages over methods performed in solution. Derivatization of sialic acids is favorably implemented on the solid support using carbodiimide coupling, and the released glycans can be further modified at the reducing end or permethylated for quantitative analysis. In this review, methods for glycan isolation, identification, and quantitation are discussed.


Complete genome sequence of Desulfurococcus mucosus type strain (O7/1).
Desulfurococcus mucosus Zillig and Stetter 1983 is the type species of the genus Desulfurococcus, which belongs to the crenarchaeal family Desulfurococcaceae. The species is of interest because of its position in the tree of life, its ability for sulfur respiration, and several biotechnologically relevant thermostable and thermoactive extracellular enzymes. This is the third completed genome sequence of a member of the genus Desulfurococcus and already the 8(th) sequence from a member the family Desulfurococcaceae. The 1,314,639 bp long genome with its 1,371 protein-coding and 50 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.


Self-starting of passively mode-locked lasers.
The self-starting condition of passively mode-locked lasers, including those locked by additive-pulse mode locking, is reexamined. A quantitative model is developed for a threshold intensity for self-starting based on the hypothesis that spurious reflections have to be overcome by coherent injection signals of sufficient amplitude.


Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes.
Caffeine biotransformation and four monooxygenase activities involving cytochrome P-450IA2, namely ethoxy- and methoxyresorufin O-dealkylases, phenacetin O-deethylase, and acetanilide 4-hydroxylation were studied in 25 human liver microsomes. All these activities were highly significantly intercorrelated (r greater than 0.72, p less than 0.001) and correlated with the level of immunoreactive P-450IA2 content (r greater than 0.65; p less than 0.001). P-450IA content was measured by immunoblotting with anti-rat P-450 beta-naphthoflavone-B, an antibody that detects only a single band corresponding to P-450IA2. The formation rate of two caffeine metabolites, namely paraxathine and theobromine, was correlated with the four monooxygenase activities measured and P-450IA2-specific content (r greater than 0.75). However, inhibition studies of caffeine metabolism by phenacetin, a specific substrate of P-450IA2, clearly indicated that only the N-3 demethylation of caffeine was supported by this enzyme. These in vitro data demonstrate that P-450IA2 is predominantly responsible for the major metabolic pathway of caffeine and that the formation of other demethylated metabolites is mediated, at least partly, by other P-450 enzymes.


Fit for the fight? Illnesses in the Norwegian team in the Vancouver Olympic Games.
The development of strategies to prevent illnesses before and during Olympic Games provides a basis for improved health and Olympic results. (1) To document the efficacy of a prevention programme on illness in a national Olympic team before and during the 2010 Vancouver Olympic Winter Games (OWG), (2) to compare the illness incidence in the Norwegian team with Norwegian incidence data during the Turin 2006 OWG and (3) to compare the illness incidence in the Norwegian team with illness rates of other nations in the Vancouver OWG. Information on prevention measures of illnesses in the Norwegian Olympic team was based on interviews with the Chief Medical Officer (CMO) and the Chief Nutrition and Sport Psychology Officers, and on a review of CMO reports before and after the 2010 OWG. The prevalence data on illness were obtained from the daily reports on injuries and illness to the International Olympic Committee. The illness rate was 5.1% (five of 99 athletes) compared with 17.3% (13 out of 75 athletes) in Turin (p=0.008). A total of four athletes missed one competition during the Vancouver Games owing to illness, compared with eight in Turin. The average illness rate for all nations in the Vancouver OWG was 7.2%. Conclusions Although no definite cause-and-effect link between the implementation of preventive measures and the prevalence of illness in the 2010 OWG could be established, the reduced illness rate compared with the 2006 OWG, and the low prevalence of illnesses compared with other nations in the Vancouver OWG suggest that the preparations were effective.


How I Do It: Temporarily Implanted Nitinol Device (iTind).
Benign prostatic hyperplasia is a common and progressive disease affecting aging men which has a significant impact on quality of life. The second-generation Temporarily Implanted Nitinol Device (iTind) is an FDA approved temporary prostatic urethral device which can be deployed using standard flexible cystoscopy without sedation or general anesthesia. The device is left in-situ for 5 to 7 days and is then entirely removed in the office, using an open-ended silicone catheter. Prospective, randomized data indicate that iTind has favorable functional and sexual patient outcomes. Readers will familiarize themselves with iTind, significant historical studies and the technique for deploying iTind using a flexible cystoscope in the office setting.


A filterless, visible-blind, narrow-band, and near-infrared photodetector with a gain.
In many applications of near-infrared (NIR) light detection, a band-pass filter is needed to exclude the noise caused by visible light. Here, we demonstrate a filterless, visible-blind, narrow-band NIR photodetector with a full-width at half-maximum of <50 nm for the response spectrum. These devices have a thick (>4 μm) nanocomposite absorbing layers made of polymer-fullerene:lead sulfide (PbS) quantum dots (QDs). The PbS QDs yield a photoconductive gain due to their hole-trapping effect, which effectively enhances both the responsivity and the visible rejection ratio of the external quantum efficiency by >10 fold compared to those without PbS QDs. Encouragingly, the inclusion of the PbS QDs does not increase the device noise. We directly measured a noise equivalent power (NEP) of 6.1 pW cm(-2) at 890 nm, and a large linear dynamic range (LDR) over 11 orders of magnitude. The highly sensitive visible-blind NIR narrow-band photodetectors may find applications in biomedical engineering.


IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma.
Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.


Detection of catechol using mixed Langmuir-Blodgett films of a phospholipid and phthalocyanines as voltammetric sensors.
The combination of metallic phthalocyanines (MPcs) and biomolecules has been explored in the literature either as mimetic systems to investigate molecular interactions or as supporting layers to immobilize biomolecules. Here, Langmuir-Blodgett (LB) films containing the phospholipid dimyristoyl phosphatidic acid (DMPA) mixed either with iron phthalocyanine (FePc) or with lutetium bisphthalocyanine (LuPc(2)) were applied as ITO modified-electrodes in the detection of catechol using cyclic voltammetry. The mixed Langmuir films of FePc + DMPA and LuPc(2) + DMPA displayed surface-pressure isotherms with no evidence of molecular-level interactions. The Fourier Transform Infrared (FTIR) spectra of the multilayer LB films confirmed the lack of interaction between the components. The DMPA and the FePc molecules were found to be oriented perpendicularly to the substrate, while LuPc(2) molecules were randomly organized. The phospholipid matrix induced a remarkable electrocatalytic effect on the phthalocyanines; as a result the mixed LB films deposited on ITO could be used to detect catechol with detection limits of 4.30 × 10(-7) and 3.34 × 10(-7) M for FePc + DMPA and LuPc(2) + DMPA, respectively. Results from kinetics experiments revealed that ion diffusion dominated the response of the modified electrodes. The sensitivity was comparable to that of other non-enzymatic sensors, which is sufficient to detect catechol in the food industry. The higher stability of the electrochemical response of the LB films and the ability to control the molecular architecture are promising for further studies with incorporation of biomolecules.