Genomic organization and molecular phylogenies of the beta (beta) keratin multigene family in the chicken (Gallus gallus) and zebra finch (Taeniopygia guttata): implications for feather evolution.
The epidermal appendages of reptiles and birds are constructed of beta (beta) keratins. The molecular phylogeny of these keratins is important to understanding the evolutionary origin of these appendages, especially feathers. Knowing that the crocodilian beta-keratin genes are closely related to those of birds, the published genomes of the chicken and zebra finch provide an opportunity not only to compare the genomic organization of their beta-keratins, but to study their molecular evolution in archosaurians. The subfamilies (claw, feather, feather-like, and scale) of beta-keratin genes are clustered in the same 5' to 3' order on microchromosome 25 in chicken and zebra finch, although the number of claw and feather genes differs between the species. Molecular phylogenies show that the monophyletic scale genes are the basal group within birds and that the monophyletic avian claw genes form the basal group to all feather and feather-like genes. Both species have a number of feather clades on microchromosome 27 that form monophyletic groups. An additional monophyletic cluster of feather genes exist on macrochromosome 2 for each species. Expression sequence tag analysis for the chicken demonstrates that all feather beta-keratin clades are expressed. Similarity in the overall genomic organization of beta-keratins in Galliformes and Passeriformes suggests similar organization in all Neognathae birds, and perhaps in the ancestral lineages leading to modern birds, such as the paravian Anchiornis huxleyi. Phylogenetic analyses demonstrate that evolution of archosaurian epidermal appendages in the lineage leading to birds was accompanied by duplication and divergence of an ancestral beta-keratin gene cluster. As morphological diversification of epidermal appendages occurred and the beta-keratin multigene family expanded, novel beta-keratin genes were selected for novel functions within appendages such as feathers.


In Their Own Words: Experiences of Caregivers of Adults With Cancer as Expressed on Social Media.
To explore caregivers' writings about their experiences caring for adult individuals with cancer on a social media health communication website. Journal entries (N = 392) were analyzed for 37 adult caregivers who were posting on behalf of 20 individuals with cancer. CaringBridge is a website used by patients and informal caregivers to communicate about acute and chronic disease. A retrospective descriptive study using qualitative content analysis of caregivers' journal entries from 2009 to 2015. Major categories identified in caregivers' online journals included patient health information, cancer awareness/advocacy, social support, caregiver burden, daily living, emotions (positive and negative), and spirituality. Nurses often recommend using social media as a communication strategy for patients with cancer and their caregivers. The findings from this study provide potential guidance nurses may wish to offer caregivers. For example, nurses may talk with caregivers about how and what to post regarding treatment decisions. In addition, nurses can provide support for caregivers struggling with when and how often to communicate on social media.


Diet as a moderator in the association of sedentary behaviors with inflammatory biomarkers among adolescents in the HELENA study.
To assess if a healthy diet might attenuate the positive sedentary-inflammation relation, whereas an unhealthy diet may increase the effect of sedentary behaviors on inflammatory biomarkers. In 618 adolescents (13-17 years) of the European HELENA study, data were available on body composition, a set of inflammation markers, and food intake assessed by a self-administered computerized 24 h dietary recall for 2 days. A 9-point Mediterranean diet score and an antioxidant-rich diet z-score were used as dietary indices and tested as moderators. A set of low-grade inflammatory characteristics was used as outcome: several cytokines in an inflammatory ratio (IL-6, IL-10, TNF-α, TGFβ-1), C-reactive protein, three cell-adhesion molecules (sVCAM-1, sICAM-1, sE-selectin), three cardiovascular risk markers (GGT, ALT, homocysteine) and three immune cell types (white blood cells, lymphocytes, CD3). Sedentary behaviors were self-reported and analyzed as total screen time. Multiple linear regression analyses tested moderation by diet in the sedentary behaviors-inflammation association adjusted for age, sex, country, adiposity (sum of six skinfolds), parental education, and socio-economic status. Both diet scores, Mediterranean and antioxidant-rich diet, were significant protective moderators in the effect of sedentary behaviors on alanine-transaminase enzyme (P = 0.014; P = 0.027), and on the pro/anti-inflammatory cytokine ratio (P = 0.001; P = 0.004), but not on other inflammatory parameters. A higher adherence to the Mediterranean diet or an antioxidant-rich diet may attenuate the onset of oxidative stress signs associated by sedentary behaviors, whereas a poor diet seems to increase inflammation.


Approaches to screening for intimate partner violence in health care settings: a randomized trial.
Screening for intimate partner violence (IPV) in health care settings has been recommended by some professional organizations, although there is limited information regarding the accuracy, acceptability, and completeness of different screening methods and instruments. To determine the optimal method for IPV screening in health care settings. Cluster randomized trial conducted from May 2004 to January 2005 at 2 each of emergency departments, family practices, and women's health clinics in Ontario, Canada. English-speaking women aged 18 to 64 years who were well enough to participate and could be seen individually were eligible. Of 2602 eligible women, 141 (5%) refused participation. Participants were randomized by clinic day or shift to 1 of 3 screening approaches: a face-to-face interview with a health care provider (physician or nurse), written self-completed questionnaire, and computer-based self-completed questionnaire. Two screening instruments-the Partner Violence Screen (PVS) and the Woman Abuse Screening Tool (WAST)-were administered and compared with the Composite Abuse Scale (CAS) as the criterion standard. The approaches were evaluated on prevalence, extent of missing data, and participant preference. Agreement between the screening instruments and the CAS was examined. The 12-month prevalence of IPV ranged from 4.1% to 17.7%, depending on screening method, instrument, and health care setting. Although no statistically significant main effects on prevalence were found for method or screening instrument, a significant interaction between method and instrument was found: prevalence was lower on the written WAST vs other combinations. The face-to-face approach was least preferred by participants. The WAST and the written format yielded significantly less missing data than the PVS and other methods. The PVS and WAST had similar sensitivities (49.2% and 47.0%, respectively) and specificities (93.7% and 95.6%, respectively). In screening for IPV, women preferred self-completed approaches over face-to-face questioning; computer-based screening did not increase prevalence; and written screens had fewest missing data. These are important considerations for both clinical and research efforts in IPV screening. clinicaltrials.gov Identifier: NCT00336297.


Radiation patterns from lens-coupled terahertz antennas.
We report on investigations of the angular distribution of the radiation emitted from a terahertz antenna system equipped with a truncated spherical silicon lens. The pattern is calculated by wide-angle interference principles and Huygens-Fresnel diffraction theory. Experimental determination of the radiation pattern is performed by spatially resolved terahertz time-domain spectroscopy. Good agreement between theory and experiment is obtained, and we find that the terahertz beam can be represented by a Gaussian beam emitted from a circular aperture equal to the diameter of the lens.


Helminth genomics: The implications for human health.
More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings.


Long-term protective effects of hepatitis A vaccines. A systematic review.
Data on duration and long-term protective effects of hepatitis A vaccines (HepA) have not been reviewed using a systematic approach. Our objective is to provide a comprehensive review of evidence on the duration of protection achieved by HepA, which is needed for revising existing vaccine policies. Limitations in data availability and implications for future research in this area are discussed. A systematic literature review was conducted including all studies published between 1997 and 2011 reporting on long-term protection of HepA. The outcomes considered were hepatitis A virus (HAV) infection and sero-protection measured by anti-HAV antibodies after follow-up times of over 5 years post-vaccination. 299 studies were identified from MEDLINE and 51 studies from EMBASE. 13 manuscripts met our inclusion criteria. The maximum observation times and reported persistence levels of sero-protective anti-HAV antibodies was 15 years for live attenuated HepA and 14 years for inactivated HepA. All data were from observational studies and showed that higher number of doses of live attenuated vaccine led to higher seropositivity and GMT, but dosage and schedule did not significantly impact the long-term protection following inactivated vaccine. Few comparisons were made between the two vaccine types indicating highest levels of antibody titers achieved by multiple doses of live attenuated vaccines 7 years post-vaccination. Available data indicate that both inactivated and live attenuated HepA are capable of providing protection up to 15 years as defined by currently accepted, conservative correlates of protection. Further investigations are needed to continue to monitor the long-term protection afforded by these vaccines. Standardized methods are required for vaccine-follow-up studies including assessment of co-variables potentially affecting long-term protection.


How does cognitive therapy prevent depressive relapse and why should attentional control (mindfulness) training help?
There is encouraging evidence that structured psychological treatments for depression, in particular cognitive therapy, can reduce subsequent relapse after the period of initial treatment has been completed. However, there is a continuing need for prophylactic psychological approaches that can be administered to recovered patients in euthymic mood. An information-processing analysis of depressive maintenance and relapse is used to define the requirements for effective prevention, and to propose mechanisms through which cognitive therapy achieves its prophylactic effects. This analysis suggests that similar effects can be achieved using techniques of stress-reduction based on the skills of attentional control taught in mindfulness meditation. An information-processing analysis is presented of mindfulness and mindlessness, and of their relevance to preventing depressive relapse. This analysis provides the basis for the development of Attentional Control Training, a new approach to preventing relapse that integrates features of cognitive therapy and mindfulness training and is applicable to recovered depressed patients.


Birefringence induced by irregular structure in photonic crystal fiber.
The unintentional birefringence induced by the irregular structure in photonic crystal fibers is analyzed numerically using the plane wave expansion method. The statistical correlations between the birefringence and the various irregularities are obtained. The birefringence is found to be largely dependent on the fiber design parameters as well as the degree of the irregularity. And the large pitch and the small air hole make the fiber less sensitive to the structural irregularity, which is successfully explained by the simple perturbation theory. The accuracy of our analyses is confirmed by the detailed investigation of computational errors. This study provides the essential information for the characterization and the design of low birefringence photonic crystal fibers.


Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro.
1. Concomitant application of the cholinergic agonist carbachol and nanomolar doses of kainate can elicit persistent gamma frequency oscillations in all layers of the mouse somatosensory cortex in vitro. Receptor pharmacology with bath-applied antagonists indicated that oscillatory network activity depended crucially on the participation of cholinergic muscarinic, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate and GABAA receptors. 2. The timing of action potentials and the occurrence of excitatory as well as inhibitory postsynaptic events was highly correlated with the phasic change of extracellularly recorded population activity. Firing probability was lowest during the peak negativity of IPSPs and gradually increased during their ensuing decay. In conjunction with the effect of a barbiturate to decrease the frequency of gamma oscillations, this suggests a crucial role of IPSPs in phasing the suprathreshold activity of principal neurons. 3. At nearby (< 1 mm) sites contained within any given cortical layer, oscillatory extra- and intracellular activity was highly synchronous with no apparent phase lag. However, interlaminar mapping experiments demonstrated a phase reversal of both extra- and intracellularly recorded activity near the lower border of thalamo-recipient layer 4, thus corroborating findings that have been obtained in vivo. 4. In conclusion, a modest increase of tonic excitatory drive in conjunction with the activation of cholinergic muscarinic receptors can elicit persistent gamma frequency network oscillations in the rodent somatosensory cortex. These findings (re)emphasize the role of the cholinergic ascending system in the cortical processing of sensory information.


Characterization and crystallization of mouse aldehyde oxidase 3: from mouse liver to Escherichia coli heterologous protein expression.
Aldehyde oxidase (AOX) is characterized by a broad substrate specificity, oxidizing aromatic azaheterocycles, such as N¹-methylnicotinamide and N-methylphthalazinium, or aldehydes, such as benzaldehyde, retinal, and vanillin. In the past decade, AOX has been recognized increasingly to play an important role in the metabolism of drugs through its complex cofactor content, tissue distribution, and substrate recognition. In humans, only one AOX gene (AOX1) is present, but in mouse and other mammals different AOX homologs were identified. The multiple AOX isoforms are expressed tissue-specifically in different organisms, and it is believed that they recognize distinct substrates and carry out different physiological tasks. AOX is a dimer with a molecular mass of approximately 300 kDa, and each subunit of the homodimeric enzyme contains four different cofactors: the molybdenum cofactor, two distinct [2Fe-2S] clusters, and one FAD. We purified the AOX homolog from mouse liver (mAOX3) and established a system for the heterologous expression of mAOX3 in Escherichia coli. The purified enzymes were compared. Both proteins show the same characteristics and catalytic properties, with the difference that the recombinant protein was expressed and purified in a 30% active form, whereas the native protein is 100% active. Spectroscopic characterization showed that FeSII is not assembled completely in mAOX3. In addition, both proteins were crystallized. The best crystals were from native mAOX3 and diffracted beyond 2.9 Å. The crystals belong to space group P1, and two dimers are present in the unit cell.


The Panama Aging Research Initiative Longitudinal Study.
The Panama Aging Research Initiative is a cohort study of 423 adults aged ≥65 years recruited from an outpatient geriatric department of Panama's largest public hospital, the Social Security Fund's Dr Arnulfo Arias Madrid Hospital Complex (Complejo Hospitalario Dr Arnulfo Arias Madrid de la Caja de Seguro Social). The study provides the first reports of modifiable and non-modifiable risk factors of cognitive impairment and dementia, as well as various health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and rates of comorbidity. The initial study, conducted September 2012-May 2016, included a clinical interview; physical assessments of body mass index and handgrip strength; and cognitive testing, plus non-fasting blood draws for measurements of genetic (Apolipoprotein E genotype) and blood-based biological markers. Information was collected regarding limitations in activities of daily living, symptoms of depression and fall incidents. A subsample of participants provided cerebrospinal fluid to measure proteins related to Alzheimer's disease; another subsample underwent ultrasonography and electroencephalography. This report describes the general study design and highlights lessons learned and future directions. In particular, drawing on lessons learned from this clinical research, a community-based prospective cohort study is currently under way among older adults in Panama to validate a blood-based biomarker profile for detecting mild cognitive impairment and Alzheimer's disease, as well as risk factors for cognitive decline. KEYWORDS: Dementia, biomarkers, Latin America, aging, cognition, chronic disease, Panama.


Characterization of the quasi-one-dimensional compounds δ-(EDT-TTF-CONMe2)2X, X=AsF6 and Br by vibrational spectroscopy and density functional theory calculations.
We have investigated the infrared spectra of the quarter-filled charge-ordered insulators δ-(EDT-TTF-CONMe2)2X (X= AsF6, Br) along all three crystallographic directions in the temperature range from 300 to 10 K. DFT-assisted normal mode analysis of the neutral and ionic EDT-TTF-CONMe2 molecule allows us to assign the experimentally observed intramolecular modes and to obtain relevant information on the charge ordering and intramolecular interactions. From frequencies of charge-sensitive vibrations we deduce that the charge-ordered state is already present at room temperature and does not change on cooling, in agreement with previous NMR measurements. The spectra taken along the stacking direction clearly show features of vibrational overtones excited due to the anharmonic electronic molecule potential caused by the large charge disproportionation between the molecular sites. The shift of certain vibrational modes indicates the onset of the structural transition below 200 K.


Cross-protective immune responses elicited by live attenuated influenza vaccines.
The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.


The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.
Elevated circulating levels of fibroblast growth factor 21 (FGF21) are associated with multiple cardiovascular disease (CVD) risk factors and incident events. Previous small cross-sectional studies, mainly in Chinese populations, have suggested FGF21 may play a role in the development of atrial fibrillation (AF). We therefore investigated the relationship of FGF21 levels with incident AF in participants free of clinically apparent CVD at baseline in a large, multi-ethnic cohort. A total of 5729 participants of four major ethnic groups (Caucasian, African American, Hispanic American, and Chinese American) from the Multi-Ethnic Study of Atherosclerosis (MESA), who were free of AF and had plasma FGF21 levels measured by ELISA at the baseline exam, were included in the analysis. Participants were followed up for incident AF over a median period of 12.9 years. Cox proportional hazards regression analysis was used. Among the 5729 participants, 778 participants developed incident AF. Participants with incident AF had significantly higher baseline FGF21 levels than those without incident AF (median = 166.0 and 142.8 pg/mL, p < 0.001). After adjusting for possible confounders, including demographic, socioeconomic and lifestyle factors, traditional CVD risk factors and circulating inflammatory markers, higher baseline FGF21 levels did not predict incident AF over the follow up period. There was no effect modification by sex or ethnicity. Baseline FGF21 levels were not associated with the development of AF in an ethnically diverse population followed long-term. Our findings do not support an important role of FGF21 in AF development.


Gray Matter Growth Is Accompanied by Increasing Blood Flow and Decreasing Apparent Diffusion Coefficient during Childhood.
Normal values of gray matter volume, cerebral blood flow, and water diffusion have not been established for healthy children. We sought to determine reference values for age-dependent changes of these parameters in healthy children. We retrospectively reviewed MR imaging data from 100 healthy children. Using an atlas-based approach, age-related normal values for regional CBF, apparent diffusion coefficient, and volume were determined for the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. All gray matter structures grew rapidly before the age of 10 years and then plateaued or slightly declined thereafter. The ADC of all structures decreased with age, with the most rapid changes occurring prior to the age of 5 years. With the exception of the globus pallidus, CBF increased rather linearly with age. Normal brain gray matter is characterized by rapid early volume growth and increasing CBF with concomitantly decreasing ADC. The extracted reference data that combine CBF and ADC parameters during brain growth may provide a useful resource when assessing pathologic changes in children.


The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA).
Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up.


Factors influencing route choice by avian migrants: a dynamic programming model of Pacific brant migration.
We used stochastic dynamic programming to investigate a spectacular migration strategy in the black brant Branta bernicla nigricans, a species of goose. Black brant migration is well suited for theoretical analysis since there are a number of existing strategies that easily can be compared. In early autumn, almost the entire population of the black brant gathers at Izembek Lagoon on the Alaska Peninsula to stage and refuel before the southward migration. There are at least three distinct strategies, with most geese making a spectacular direct migration more than 5000km across the Gulf of Alaska to their wintering grounds in southern Baja California or mainland Mexico. This is a potentially dangerous strategy since foraging is not possible during the overseas passage. Some individuals instead use shorter flights to make a detour along the coast, a longer route that all individuals use for northwards migration in spring. Since flight costs accelerate with increasing body mass, migration by short flights is energetically cheaper than long-distance flights. A small but increasing part of the population has recently begun to winter at Izembek. We investigated this migration under two different suppositions using a dynamic state variable model. First, if the geese are free to make a strategic choice, under what assumptions should they prefer direct migration and under what assumptions should they prefer detour migration/winter residency? Second, provided that the dominating direct migration strategy is optimal, what conditions will force the geese to go for detour migration/winter residency? In the second case the geese may try to follow an optimal direct migration strategy, but stochastic events may force them to choose a suboptimal policy. We also simulated possible effects of global warming. The model suggests that the fuel level at arrival in Izembek and fuel gain rates are key factors and that tail winds must have been reliable in the past, otherwise direct migration could not have evolved. It also suggests that a change to milder winters may promote an unexpectedly abrupt change from long-distance to short-distance migration or winter residency. Finally, it produced a number of predictions that might be testable in the field.


Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.
Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.


Adherence to physical activity guidelines and functional fitness of elderly women, using objective measurement.
Physical activity is an important factor in maintaining the health and functional fitness of elderly people. The aim of the study was to determine the number of senior women meeting the physical activity guidelines, and their level of functional fitness in comparison to women who are not sufficiently physically active. The study involved 61 women, aged 60-75. Physical activity was monitored on seven consecutive days of the week, using a triaxial accelerometer ActiGraph GT3X. Results of the assessment of physical activity were verified against the Global Recommendations of Physical Activity for Health. The Senior Fitness Test (Fullerton Test) was used to evaluate functional fitness. In the studied group, 36.1% achieved the recommended level of physical activity. All those examined mainly undertook physical activity of low intensity. Vigorous physical activity during the week was noted in only 6 seniors. Women who met the recommendations of physical activity achieved significantly better results in test trials, e.g. Chair Stands, Up and Go, Six Minute Step Test. Adherence to physical activity guidelines was associated with better functional fitness of older women. However, less than half of the examined seniors met the Global Recommendations on Physical Activity for Health.


Incidence of surgical site infection following adult spinal deformity surgery: an analysis of patient risk.
Surgical site infection (SSI) following spinal surgery is a frequent complication and results in higher morbidity, mortality and healthcare costs. Patients undergoing surgery for spinal deformity (scoliosis/kyphosis) have longer surgeries, involving more spinal levels and larger blood losses than typical spinal procedures. Previous research has identified risk factors for SSI in spinal surgery, but few studies have looked at adult deformity surgeries. We retrospectively performed a large case cohort analysis of all adult patients who underwent surgery for kyphosis or scoliosis, between June 1996 and December 2005, by our adult spine division in an academic institution to asses the incidence and identify risk factors for SSI. We reviewed the electronic patient records of 830 adult patients. SSI was classified as deep or superficial to the fascia. 46 (5.5%) patients were found to have a SSI with 29 patients (3.5%) having deep infections. Obesity was found to be an independent risk factor for all SSI and superficial SSI (P = 0.014 and P = 0.013). As well, a history of prior SSI was also found to be a risk factor for SSI (P = 0.041). Patient obesity and history of prior SSI lead to increased risk of infection. Since obesity was related to an increased risk of both superficial and deep SSI, counseling and treatment for obesity should be considered before elective deformity surgery.


Field Distribution of Wheat Stripe Rust Latent Infection Using Real-Time PCR.
Stripe rust of wheat, caused by Puccinia striiformis f. tritici, is of worldwide significance. Quantification of latent infection level is critical to estimate the potential for disease epidemics. In this study, field distribution of latent infection and the corresponding observed disease were studied in two growing seasons from 2009 to 2011 in Gangu, Gansu Province and Shangzhuang, Beijing, China. A previously developed real-time polymerase chain reaction (PCR) assay was applied to obtain the molecular disease index (MDX) to quantify the level of latent infection. At 1 to 3 weeks after leaf sampling, the observed disease indices (DX) were assessed in the corresponding experimental sites. The computer software SURFER showed that the spatial distribution patterns of MDX had a linear relationship with DX in field plots with P = 0.01. The aggregation levels of MDX correlated with those of DX in the fields. The disease foci which were correctly detected for latent infections with the real-time PCR for the Gangu and Shangzhuang field plots were 71.4 and 85.7%, respectively. The triadimefon fungicide treatment focused on the detected latent infection foci reduced both the initial inoculum and disease development, resulting in an average reduction in disease area in the field plots of 73 to 81%.


Differentiation of neural-crest-derived intermediate pluripotent progenitors into committed periodontal populations involves unique molecular signature changes, cohort shifts, and epigenetic modifications.
Intermediate progenitor populations play a crucial role in the regional specification and differentiation of the cranial neural crest. On the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, we have defined key factors involved in the differentiation of dental follicle (DF) intermediate progenitors into periodontal lineages, including alveolar bone (AB) osteoblasts, cementoblasts, and periodontal ligament (PDL) cells. When comparing differentially expressed genes, PDL cells most closely resembled DF progenitors, followed by AB osteoblasts and cementoblasts as the most distant population. According to gene ontology analyses, extracellular matrix-adhesion proteins were substantially increased in PDL cells, osteogenesis factors were elevated in AB osteoblasts, and gene expression levels were lower in cementoblasts, especially in the cytokine group. Unique signature proteins included interleukin 6, paired-like homeodomain transcription factor 2, thrombospondin 2, and glial cell line-derived neurotrophic factor for DF progenitors; asporin and prostaglandin-H2 D-isomerase for AB osteoblasts; and keratin 18, Netrin 4, Jagged 1, and Dickkopf1 for cementoblasts, as verified by western blot analysis. Secreted frizzled-related protein 1 was preferentially expressed in PDL cells, whereas matrix Gla-protein, bone sialoprotein, and insulin-like growth factor binding protein 5 were higher in AB osteoblasts than in cementoblasts. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Together, our data indicate that in addition to changes in signature gene expression, unique shifts in gene cohort expression levels, epigenetic modifications, and changes in cell morphology contribute to the individuation of tissue populations from a common neural-crest-derived ancestor.


Rust Fungi Forming Aecia on Berberis spp. in Sweden.
Barberry (Berberis spp.) hosts the aecial stage of several rust species, including Puccinia graminis, which causes stem rust on grasses and cereals. The aecial stage of this pathogen has received less attention because it is not as economically important compared with the uredinial and telial stages. The main objective of this study was to identify and describe the rust species that were found on Berberis spp. collected in different parts of Sweden. A morphological study, including spore measurements and aecia descriptions, was conducted, as well as DNA sequence analyses (using the internal transcribed spacer region and the EF1-α gene). Based on spore and aecia morphology as well as the genetic analyses, three different taxa could be distinguished on barberry: P. graminis f. sp. avenae, P. graminis f. sp. tritci/secalis, and P. arrhenatheri. The genetic analysis revealed little or no differentiation between P. graminis f. sp. tritici and P. graminis f. sp. secalis and, thus, this group of samples was denominated P. graminis f. sp. tritici/secalis. Aecial morphology may be used to differentiate between different taxa. In particular, examination of aecial cross-sections may be used to distinguish between P. graminis f. sp. avenae and P. graminis f. sp. tritici/secalis. A clear differentiation in the mode of growth on barberry was also found; P. arrhenatheri always appeared systemic whereas P. graminis always appeared localized.


A new use for an old Holter monitor: an ambulatory cough meter.
Cough is commonly used as an outcome measure in clinical studies, although the subjective reporting of cough is unreliable when compared to objective measures. We describe an inexpensive new ambulatory cough meter that is based on a disused Holter monitor. The cough meter consists of a Holter monitor and a cough processor, designed on a computer to select the most appropriate filters. The cough meter was then validated against the overnight tape recorder on 21 occasions in 18 children (aged 6-15 yrs). The agreement between the cough meter and the tape recorder was good (mean difference of -0.3 coughs x h(-1); limits of agreement -2.2 to 1.7 coughs x h(-1)). We conclude that our newly described ambulatory cough meter provides a valid and inexpensive method of objectively monitoring cough for up to 24 h.


Profiling relative clause constructions in children with specific language impairment.
This study highlights the importance of error analysis in providing a comprehensive profile of an individual's grammatical ability with regard to relative clause (RC) constructions. The aim was to identify error patterns in the production of RCs by English-speaking, school-aged children with specific language impairment (SLI) and to relate them to their level of competence with these structures. Children with SLI (mean age = 6;10, n = 32) and two control groups - a typically developing group matched for age (mean age = 6;11, n = 32) and a younger typically developing group (mean age = 4;9, n = 20), repeated sentences containing RCs that represented a range of syntactic roles. Data are presented on three distinct error patterns - the provision of simple sentences, obligatory relativizer omission and RC conversions. Each is related to the level of competence on RCs that each child has achieved.


Dual time point imaging fluorine-18 flourodeoxyglucose positron emission tomography for evaluation of large loco-regional recurrences of breast cancer treated with electrochemotherapy.
Electrochemotherapy is a local anticancer treatment very efficient for treatment of small cutaneous metastases. The method is now being investigated for large cutaneous recurrences of breast cancer that are often confluent masses of malignant tumour with various degrees of inflammation. To this end 18-Flourine-Flourodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) could be a method for response evaluation. However, a standard FDG-PET/CT scan cannot differentiate inflammatory tissue from malignant tissue. Dual point time imaging (DTPI) FDG-PET has the potential of doing so. The purpose of this study was to investigate if DTPI FDG-PET/CT could assess response to electrochemotherapy and to assess the optimal timing of imaging. Within a phase II clinical trial 11 patients with cutaneous recurrences had FDG-PET/CT scans at three time points: 60 min, 120 min and 180 min after FDG injection. The scans were performed before and 3 weeks after electrochemotherapy. A significant reduction in maximum standard uptake value at 60 min post injection was seen after treatment. Furthermore a change in the FDG uptake pattern was observed; from increasing uptake in up to 180 min post injection before treatment to stabilization of FDG uptake at 120 min post injection after treatment. The change in FDG uptake pattern over time lead to change of response in three target lesions; two lesions changed from stable metabolic disease to partial metabolic response and one lesion changed from partial metabolic response to stable metabolic disease. To ensure detection of the change in uptake pattern, scanning 60 and 180 min post injection seems optimal. The present study shows that FDG-PET/CT 60 and 180 min after tracer injection is a promising tool for response evaluation of cutaneous recurrences of breast cancer treated with electrochemotherapy.


A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility.
Insulin resistance is necessary but not sufficient for the development of type 2 diabetes. Diabetes results when pancreatic beta-cells fail to compensate for insulin resistance by increasing insulin production through an expansion of beta-cell mass or increased insulin secretion. Communication between insulin target tissues and beta-cells may initiate this compensatory response. Correlated changes in gene expression between tissues can provide evidence for such intercellular communication. We profiled gene expression in six tissues of mice from an obesity-induced diabetes-resistant and a diabetes-susceptible strain before and after the onset of diabetes. We studied the correlation structure of mRNA abundance and identified 105 co-expression gene modules. We provide an interactive gene network model showing the correlation structure between the expression modules within and among the six tissues. This resource also provides a searchable database of gene expression profiles for all genes in six tissues in lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 wk of age. A cell cycle regulatory module in islets predicts diabetes susceptibility. The module predicts islet replication; we found a strong correlation between (2)H(2)O incorporation into islet DNA in vivo and the expression pattern of the cell cycle module. This pattern is highly correlated with that of several individual genes in insulin target tissues, including Igf2, which has been shown to promote beta-cell proliferation, suggesting that these genes may provide a link between insulin resistance and beta-cell proliferation.


Spectral and electro-optic response of UV-written waveguides in LiNbO3 single crystals.
An experimental study of the spectral and electro-optic response of direct UV-written waveguides in LiNbO3 is reported. The waveguides were written using c.w. laser radiation at 275, 300.3, 302, and 305 nm wavelengths with various writing powers (35-60 mW) and scan speeds (0.1-1.0 mm/sec). Spectral analysis was used to determine the multimode and single mode wavelength regions and, the cut-off point of the fabricated waveguides. Electro-optic characterization of these waveguides reveals that the electro-optic coefficient (r33) decreases for longer writing wavelengths, with a maximum of 31 pm/V for 275 nm and, is reduced to 14 pm/V for waveguides written with 305 nm.


Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I.
Insulin-like growth factor binding proteins (IGFBPs) have been shown to serve as carrier proteins for the insulin-like growth factors (IGFs) and to modulate their biologic effects. Since extracellular matrix (ECM) has been shown to be a reservoir for IGF-I and IGF-II, we examined the ECM of cultured human fetal fibroblasts and found that IGFBP-5 was incorporated intact into ECM, while mostly inert proteolytic fragments were found in the medium. In contrast, two other forms of IGFBP that are secreted by these cells were either present in ECM in minimal amounts (IGFBP-3) or not detected (IGFBP-4). Likewise, when purified IGFBPs were incubated with ECM, IGFBP-5 bound preferentially. IGFBP-5 was found to bind to types III and IV collagen, laminin, and fibronectin. Increasing salt concentrations inhibited the binding of IGFBP-5 to ECM and accelerated the release of IGFBP-5 from ECM, suggesting an ionic basis for this interaction. ECM-associated IGFBP-5 had a sevenfold decrease in affinity for IGF-I compared to IGFBP-5 in solution. Furthermore, when IGFBP-5 was present in cell culture substrata, it potentiated the growth stimulatory effects of IGF-I on fibroblasts. When IGFBP-5 was present only in the medium, it was degraded to a 22-kD fragment and had no effect on IGF-I-stimulated growth. We conclude that IGFBP-5 is present in fibroblast ECM, where it is protected from degradation and can potentiate the biologic actions of IGF-I. These findings provide a molecular explanation for the association of the IGF's with the extracellular matrix, and suggest that the binding of the IGF's to matrix, via IGFBP-5, may be important in mediating the cellular growth response to these growth factors.


Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes.
Taking advantage of a sporozoite challenge model established to evaluate the efficacy of new malaria vaccine candidates, we have explored the kinetics of systemic cytokine responses during the prepatent period of Plasmodium falciparum infection in 18 unvaccinated, previously malaria-naive subjects, using a highly sensitive, bead-based multiplex assay, and relate these data to peripheral parasite densities as measured by quantitative real-time PCR. These data are complemented with the analysis of cytokine production measured in vitro from whole blood or PBMC, stimulated with P. falciparum-infected RBC. We found considerable qualitative and quantitative interindividual variability in the innate responses, with subjects falling into three groups according to the strength of their inflammatory response. One group secreted moderate levels of IFN-gamma and IL-10, but no detectable IL-12p70. A second group produced detectable levels of circulating IL-12p70 and developed very high levels of IFN-gamma and IL-10. The third group failed to up-regulate any significant proinflammatory responses, but showed the highest levels of TGF-beta. Proinflammatory responses were associated with more rapid control of parasite growth but only at the cost of developing clinical symptoms, suggesting that the initial innate response may have far-reaching consequences on disease outcome. Furthermore, the in vitro observations on cytokine kinetics presented here, suggest that intact schizont-stage infected RBC can trigger innate responses before rupture of the infected RBC.


A clinical trial of Integra Template for diabetic foot ulcer treatment.
Individuals with diabetes mellitus are at an increased risk of developing a diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs. The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized, controlled, parallel group clinical trial conducted under an Investigational Device Exemption. Thirty-two sites enrolled and randomized 307 subjects with at least one DFU. Consented patients were entered into the 14-day run-in phase where they were treated with the standard of care (0.9% sodium chloride gel) plus a secondary dressing and an offloading/protective device. Patients with less than 30% reepithelialization of the study ulcer after the run-in phase were randomized into the treatment phase. The subjects were randomized to the control treatment group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n = 154). The treatment phase was 16 weeks or until confirmation of complete wound closure (100% reepithelialization of the wound surface), whichever occurred first. Following the treatment phase, all subjects were followed for 12 weeks. Complete DFU closure during the treatment phase was significantly greater with IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks. The median time to complete DFU closure was 43 days for IDRT subjects and 78 days for control subjects in wounds that healed. The rate of wound size reduction was 7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p = 0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to complete wound closure, increased the rate of wound closure, improved components of quality of life and had less adverse events compared with the standard of care treatment. IDRT could greatly enhance the treatment of nonhealing DFUs.


A statistical primer on subgroup analyses.
Resources for clinical research are limited. With increasing demand for patient-centred care, which is growing into an integral component of modern medicine, studying outcomes of patients with specific clinical characteristics is becoming increasingly important. Given the high cost of clinical trials and the time it takes to complete an investigation, it has become compulsory for investigators to assess not only treatment effects between the main randomized groups but also to try to identify clinically relevant subgroups that may particularly benefit from specific treatments. Publications of subgroup analyses turned out to be prevalent, and more importantly, these findings play a significant role in strategic planning and decision-making processes. Therefore, raising awareness among clinicians about the concepts and values of subgroup analysis is an aspect of improving patient outcomes. In this statistical primer, we give a broad introduction to the topic of subgroup analysis in scientific research. We furthermore discuss the concept of subgroup analysis; the motivation for assessing subgroups; the types of subgroup analyses and the paradigm of hypothesis-generating research; the proper statistical methods for the examination of subgroup effects; and the optimal approach for interpretation of results. Finally, this review establishes the comprehensive users' guide for analysing and reporting subgroup studies on a point-by-point basis, using real-world examples that may help readers to gain experience to pursue their own subgroup analyses or interpret those of others.


Effect of 2,4-dihydroxybenzophenone (BP1) on early life-stage development of the marine copepod Acartia tonsa at different temperatures and salinities.
Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and sunscreen products and can enter the aquatic environment. Therefore, we investigated the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the marine calanoid copepod Acartia tonsa in an early life-stage development study. Since developmental endpoints depend on environmental conditions, a preceding study of A. tonsa development was performed at three temperatures, four salinities, four light:dark regimes, six food densities, and four culture densities. Times elapsed until 50% of the population had reached a copepodite stage (DT(½) ) at the different conditions were calculated. The DT(½) values decreased from 296 h at 15°C to 89 h at 25°C and were also affected by salinity (126 h at 15‰ and 167 h at 30‰), whereas the light:dark regime and culture density influenced development only to a minor extent. BP1 was found acutely toxic at 2.6 mg/L (48-h median lethal concentration [LC50]). The toxicity of BP1 on early life-stage development was studied in combinations of three temperatures (15, 20, 25°C) and three salinities (15, 20, 25‰) using five toxicant concentrations between 0.051 and 2 mg/L in each scenario. Concentrations causing 10 and 50% inhibition of development (EC10 and EC50) were determined. Acartia tonsa was most resistant towards BP1 at 20°C where an EC50 of 1.1 mg/L was found, whereas EC50 values were significantly lower at 15°C (0.49 mg/L) and 25°C (0.77 mg/L), respectively. The EC50 also decreased with increasing salinity. Our results demonstrate that environmental conditions do influence toxicity test results; thus, they need to be considered carefully when developing test protocols as well as for environmental risk assessments of chemicals.


Inferring social status and rich club effects in enterprise communication networks.
Social status, defined as the relative rank or position that an individual holds in a social hierarchy, is known to be among the most important motivating forces in social behaviors. In this paper, we consider the notion of status from the perspective of a position or title held by a person in an enterprise. We study the intersection of social status and social networks in an enterprise. We study whether enterprise communication logs can help reveal how social interactions and individual status manifest themselves in social networks. To that end, we use two enterprise datasets with three communication channels--voice call, short message, and email--to demonstrate the social-behavioral differences among individuals with different status. We have several interesting findings and based on these findings we also develop a model to predict social status. On the individual level, high-status individuals are more likely to be spanned as structural holes by linking to people in parts of the enterprise networks that are otherwise not well connected to one another. On the community level, the principle of homophily, social balance and clique theory generally indicate a "rich club" maintained by high-status individuals, in the sense that this community is much more connected, balanced and dense. Our model can predict social status of individuals with 93% accuracy.


Calmodulin mediates Ca2+-dependent modulation of M-type K+ channels.
To quantify the modulation of KCNQ2/3 current by [Ca2+]i and to test if calmodulin (CaM) mediates this action, simultaneous whole-cell recording and Ca2+ imaging was performed on CHO cells expressing KCNQ2/3 channels, either alone, or together with wild-type (wt) CaM, or dominant-negative (DN) CaM. We varied [Ca2+]i from <10 to >400 nM with ionomycin (5 microM) added to either a 2 mM Ca2+, or EGTA-buffered Ca2+-free, solution. Coexpression of wt CaM made KCNQ2/3 currents highly sensitive to [Ca2+]i (IC50 70 +/- 20 nM, max inhibition 73%, n = 10). However, coexpression of DN CaM rendered KCNQ2/3 currents largely [Ca2+]i insensitive (max inhibition 8 +/- 3%, n = 10). In cells without cotransfected CaM, the Ca2+ sensitivity was variable but generally weak. [Ca2+]i modulation of M current in superior cervical ganglion (SCG) neurons followed the same pattern as in CHO cells expressed with KCNQ2/3 and wt CaM, suggesting that endogenous M current is also highly sensitive to [Ca2+]i. Coimmunoprecipitations showed binding of CaM to KCNQ2-5 that was similar in the presence of 5 mM Ca2+ or 5 mM EGTA. Gel-shift analyses suggested Ca2+-dependent CaM binding to an "IQ-like" motif present in the carboxy terminus of KCNQ2-5. We tested whether bradykinin modulation of M current in SCG neurons uses CaM. Wt or DN CaM was exogenously expressed in SCG cells using pseudovirions or the biolistic "gene gun." Using both methods, expression of both wt CaM and DN CaM strongly reduced bradykinin inhibition of M current, but for all groups muscarinic inhibition was unaffected. Cells expressed with wt CaM had strongly reduced tonic current amplitudes as well. We observed similar [Ca2+]i rises by bradykinin in all the groups of cells, indicating that CaM did not affect Ca2+ release from stores. We conclude that M-type currents are highly sensitive to [Ca2+]i and that calmodulin acts as their Ca2+ sensor.


Inflammatory potential of the diet and risk of breast cancer in the European Investigation into Cancer and Nutrition (EPIC) study.
The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01-1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04-1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01-1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.


Helper-independent mink cell focus-inducing strains of Friend murine type-C virus: potential relationship to the origin of replication-defective spleen focus-forming virus.
Recent studies have indicated that both the replication-defective spleen focus-forming virus (SFFV) in the Friend virus complex and the helper-independent mink cell focus-inducing (MCF) viruses derived from AKR-murine leukemia virus (MuLV) are env gene recombinants between ecotropic virus and xenotropic virus. In an attempt to isolate additional env gene recombinants between Friend murine leukemia virus (F-MuLV) and xenotropic virus, we have inoculated cloned ecotropic F-MuLV into newborn NIH Swiss mice and analyzed MuLV released from preleukemic and leukemic spleens of infected mice. Two helper-independent MCF strains of F-MuLV have been isolated. Like the previously described AKR-MCF viruses, the Friend MCF viruses are env gene recombinants between an ecotropic virus (F-MuLV) and a mouse xenotropic virus, as shown by host range, interference pattern, and tryptic peptide analysis of the gp70s of these MuLV. Furthermore, RNA from the Friend MCF viruses hybridizes completely to cDNAsffv, a nucleic acid probe which detects that portion of SFFV which was not derived from P-MuLV. The ability to isolate replicating MCF viruses derived from F-MuLV FURTHER strengthens the parallels between the Friend erythroleukemia system and the AKR thymic leukemia system. Finally, the potential relationship of helper-independent env gene recombinants between F-MuLV and xenotropic virus to be highly leukemogenic SFFV is discussed.


Novel immunomodulatory properties of berbamine through selective down-regulation of STAT4 and action of IFN-gamma in experimental autoimmune encephalomyelitis.
Berbamine (BM) is an herbal compound derived from Berberis vulgaris L commonly used in traditional Chinese medicine. In this study, we show that BM has potent anti-inflammatory properties through novel regulatory mechanisms, leading to reduced encephalitogenic T cell responses and amelioration of experimental autoimmune encephalomyelitis (EAE). The treatment effect of BM was attributable to its selective inhibitory effect on the production and action of IFN-gamma in CD4(+) T cells, which was mediated through altered STAT4 expression in T cells. BM was found to up-regulate SLIM, a ubiquitin E3 ligase for STAT4, and promote STAT4 degradation, resulting in markedly decreased IFN-gamma production in CD4(+) T cells in EAE mice. Regulation of IFN-gamma by BM had profound anti-inflammatory actions through its effect on both CD4(+) T cells and APCs. BM-treated APCs exhibited reduced stimulatory function as a result of altered expression of PD-L1, CD80, and CD86 in treated mice. The treatment effect of BM in EAE was directly related to its action on IFN-gamma, and was abolished in IFN-gamma knockout mice. The study also confirmed that BM was able to inhibit NFAT translocation through effecting calcium mobilization in lymphocytes. However, this effect was not directly responsible for the treatment efficacy of BM in EAE. The study has important implications in our approaches to evaluating the utility of natural compounds in drug discovery and to probing the role of cytokine network in the development of autoimmune conditions.


Non-coding RNAs in Alzheimer's disease.
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common dementia among the elderly. Accumulating research indicates that noncoding RNAs (ncRNAs), especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are increasingly being implicated in AD. MiRNAs are conserved small ncRNAs that control gene expression post-transcriptionally while lncRNAs function in many ways. Recent profiling research in human or mouse models suggests that miRNAs are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-β (Aβ) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of miRNAs varies in blood, and cerebral spinal fluid may indicate alterations in AD. Together with brain-specific miRNAs, these miRNAs could be potential AD biomarkers. All the above may provide the basis for new approaches for AD. Here, we review current findings regarding ncRNA research in human and mouse models to provide a strong basis for future study aiming at promising contributions of ncRNA in AD.


Functional compensation in partially denervated muscles.
In patients with various types of chronic motor denervation, the numbers of surviving motor units have been compared with the twitch tensions developed by the same muscle (extensor digitorum brevis). It was found that functional compensation in partially denervated muscles was often marked; in most patients abnormally small twitches occurred only when fewer than 10% of motor axons remained. The factors responsible for this compensation are considered. The twitch speeds of partially denervated muscles differed markedly, even among patients with the same disorder; there was evidence to suggest that the twitches of some motor units might become slower than those found in normal muscles.


Population Vectors Can Provide Near Optimal Integration of Information.
Much attention has been paid to the question of how Bayesian integration of information could be implemented by a simple neural mechanism. We show that population vectors based on point-process inputs combine evidence in a form that closely resembles Bayesian inference, with each input spike carrying information about the tuning of the input neuron. We also show that population vectors can combine information relatively accurately in the presence of noisy synaptic encoding of tuning curves.


Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer.
To investigate human epidermal growth factor receptor 2 (HER2)-phosphatidylinositol 3-kinase (PI3K)-v-Akt murine thymoma viral oncogene homolog signaling pathway. We analyzed 231 formalin-fixed, paraffin-embedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment. The patients' age, sex, tumor location, depth of invasion, pathological type, lymph node metastasis, and pathological stage were determined by a review of the medical records. Expression of HER2 was analyzed by immunohistochemistry (IHC) using the HercepTest(TM) kit. Standard criteria for HER2 positivity (0, 1+, 2+, and 3+) were used. Tumors that scored 3+ were considered HER2-positive. Expression of phospho Akt (pAkt) was also analyzed by IHC. Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more. PI3K, catalytic, alpha polypeptide (PIK3CA) mutations in exons 1, 9 and 20 were analyzed by pyrosequencing. Epstein-Barr virus (EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA (EBER) with an EBER-RNA probe. Microsatellite instability (MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26. HER2 expression levels of 0, 1+, 2+ and 3+ were found in 167 (72%), 32 (14%), 12 (5%) and 20 (8.7%) samples, respectively. HER2 overexpression (IHC 3+) significantly correlated with intestinal histological type (15/20 vs 98 /205, P = 0.05). PIK3CA mutations were present in 20 cases (8.7%) and significantly correlated with MSI (10/20 vs 9/211, P < 0.01). The mutation frequency was high (21%) in T4 cancers and very low (6%) in T2 cancers. Mutations in exons 1, 9 and 20 were detected in 5 (2%), 9 (4%) and 7 (3%) cases, respectively. Two new types of PIK3CA mutation, R88Q and R108H, were found in exon1. All PIK3CA mutations were heterozygous missense single-base substitutions, the most common being H1047R (6/20, 30%) in exon20. Eighteen cancers (8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type (13/18 vs 93/198, P = 0.04). There were 7 cases of lymphoepithelioma-like carcinomas (LELC) and 6 of those cases were EBV-positive (percent/EBV: 6/18, 33%; percent/all LELC: 6/7, 86%). pAkt expression was positive in 119 (53%) cases but showed no correlation with clinicopathological characteristics. pAkt expression was significantly correlated with HER2 overexpression (16/20 vs 103/211, P < 0.01) but not with PIK3CA mutations (12/20 vs 107/211, P = 0.37) or EBV infection (8/18 vs 103/211, P = 0.69). The frequency of pAkt expression was higher in cancers with exon20 mutations (100%) than in those with exon1 (40%) or exon9 (56%) mutations. One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection. However, no cases showed both PIK3CA mutations and HER2 overexpression. One EBV-positive cancer with PIK3CA mutation (H1047R) was MSI-positive. Three of these 4 cases were positive for pAkt expression. In survival analysis, pAkt expression significantly correlated with a poor prognosis (hazard ratio 1.75; 95%CI: 1.12-2.80, P = 0.02). HER2 expression, PIK3CA mutations and EBV infection in gastric cancer were characterized. pAkt expression significantly correlates with HER2 expression and with a poor prognosis.


Glycomic and glycotranscriptomic profiling of mucin-type O-glycans in planarian Schmidtea mediterranea.
O-Glycans on cell surfaces play important roles in cell-cell, cell-matrix and receptor-ligand interaction. Therefore, glycan-based interactions are important for tissue regeneration and homeostasis. Free-living flatworm Schmidtea mediterranea, because of its robust regenerative potential, is of great interest in the field of stem cell biology and tissue regeneration. Nevertheless, information on the composition and structure of O-glycans in planaria is unknown. Using mass spectrometry and in silico approaches, we characterized the glycome and the related transcriptome of mucin-type O-glycans of planarian S. mediterranea. Mucin-type O-glycans were composed of multiple isomeric, methylated, and unusually extended mono- and disubstituted O-N-acetylgalactosamine structures. Extensions made of hexoses and 3-O-methyl hexoses were the glycoforms observed. From glycotranscriptomic analysis, 60 genes belonging to five distinct enzyme classes were identified to be involved in mucin-type O-glycan biosynthesis. These genes shared homology with those in other invertebrate systems. Although a majority of the genes involved in mucin-type O-glycan biosynthesis were highly expressed during organogenesis and in differentiated cells, a few select genes in each enzyme class were specifically enriched during early embryogenesis. Our results indicate a unique temporal and spatial role for mucin-type O-glycans during embryogenesis and organogenesis and in adulthood. In summary, this is the first report on O-glycans in planaria. This study expands the structural and biosynthetic possibilities in cellular glycosylation in the invertebrate glycome and provides a framework towards understanding the biological role of mucin-type O-glycans in tissue regeneration using planarians.


Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach.
Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. Calcium binding induces conformational transitions in calmodulin that make it specifically active to particular target proteins. The precise mechanisms underlying calcium binding to calmodulin are still, however, quite poorly understood. In this study, we adopt a structural systems biology approach and develop a mathematical model to investigate various types of cooperative calcium-calmodulin interactions. We compare the predictions of our analysis with physiological dose-response curves taken from the literature, in order to provide a quantitative comparison of the effects of different mechanisms of cooperativity on calcium-calmodulin interactions. The results of our analysis reduce the gap between current understanding of intracellular calmodulin function at the structural level and physiological calcium-dependent calmodulin target activation experiments. Our model predicts that the specificity and selectivity of CaM target regulation is likely to be due to the following factors: variations in the target-specific Ca2+ dissociation and cooperatively effected dissociation constants, and variations in the number of Ca2+ ions required to bind CaM for target activation.


Single molecule characterization of the interactions between amyloid-β peptides and the membranes of hippocampal cells.
Oligomers of the 40 and 42 residue amyloid-β peptides (Aβ40 and Aβ42) have been implicated in the neuronal damage and impaired cognitive function associated with Alzheimer's disease. However, little is known about the specific mechanisms by which these misfolded species induce such detrimental effects on cells. In this work, we use single-molecule imaging techniques to examine the initial interactions between Aβ monomers and oligomers and the membranes of live cells. This highly sensitive method enables the visualization of individual Aβ species on the cell surface and characterization of their oligomerization state, all at biologically relevant, nanomolar concentrations. The results indicate that oligomers preferentially interact with cell membranes, relative to monomers and that the oligomers become immobilized on the cell surface. Additionally, we observe that the interaction of Aβ species with the cell membrane is inhibited by the presence of ATP-independent molecular chaperones. This study demonstrates the power of this methodology for characterizing the interactions between protein aggregates and the membranes of live neuronal cells at physiologically relevant concentrations and opens the door to quantitative studies of the cellular responses to potentially pathogenic oligomers.


Dissection of the molecular basis of pp60(v-src) induced gating of connexin 43 gap junction channels.
Suppression of gap-junctional communication by various protein kinases, growth factors, and oncogenes frequently correlates with enhanced mitogenesis. The oncogene v-src appears to cause acute closure of gap junction channels. Tyr265 in the COOH-terminal tail of connexin 43 (Cx43) has been implicated as a potential target of v-src, although v-src action has also been associated with changes in serine phosphorylation. We have investigated the mechanism of this acute regulation through mutagenesis of Cx43 expressed in Xenopus laevis oocyte pairs. Truncations of the COOH-terminal domain led to an almost complete loss of response of Cx43 to v-src, but this was restored by coexpression of the independent COOH-terminal polypeptide. This suggests a ball and chain gating mechanism, similar to the mechanism proposed for pH gating of Cx43, and K+ channel inactivation. Surprisingly, we found that v-src mediated gating of Cx43 did not require the tyrosine site, but did seem to depend on the presence of two potential SH3 binding domains and the mitogen-activated protein (MAP) kinase phosphorylation sites within them. Further point mutagenesis and pharmacological studies in normal rat kidney (NRK) cells implicated MAP kinase in the gating response to v-src, while the stable binding of v-src to Cx43 (in part mediated by SH3 domains) did not correlate with its ability to mediate channel closure. This suggests a common link between closure of gap junctions by v-src and other mitogens, such as EGF and lysophosphatidic acid (LPA).


Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double-Blind, Placebo-Controlled Study.
The global prevalence of stress is increasing. Stress adversely affects cognitive ability, sleep quality, and overall psychological well-being. Ashwagandha (Withania somnifera (L.) Dunal), an essential medicine in Ayurveda, is reportedly beneficial in reducing stress and improving memory. This double-blind, randomized, placebo-controlled clinical study evaluated the effect of Ashwagandha root extract sustained-release capsule 300 mg (Prolanza™; hereafter Ashwagandha SR) on cognitive functions, stress levels, sleep quality, overall well-being, and safety in stressed subjects. Subjects (130 healthy cognitively sound adults [20-55 years, body mass index:18-29 kg/m2]) having a Perceived Stress Scale (PSS) score of 14-24 were randomized to receive either Ashwagandha SR or placebo. Subjects took one capsule of Ashwagandha SR or placebo daily for 90 consecutive days. This study was registered on Clinical Trials Registry-India (CTRI) on 13/11/2019 [number: CTRI/2019/11/021990]. The primary endpoint was the change in cognitive function as measured by CANTAB from baseline to the end of the study period (90 ± 7 days). The secondary outcomes included the change in PSS-10 score, serum cortisol level (9-11 am), the OHQ score, the PSQI, and serum BDNF levels. Only 125 completed the study and were evaluated. The Cambridge Neuropsychological Test Automated Battery (CANTAB) reported significantly improved recall memory, and the total error rate in recalling patterns significantly decreased at visit 4 in the Ashwagandha SR group vs. the placebo group (first attempt memory score:12.9 ± 6.7 vs. 10.1 ± 6.3; total errors:17.5 ± 23.3 vs. 27.7 ± 23.6). At visit 4, lower PSS-10 score (13.0 ± 5.0 vs. 18.7 ± 4.6; p < .0001), serum cortisol levels (p=0.0443), and Pittsburgh Sleep Quality Index (PSQI) score (p < .0001) but higher Oxford Happiness Questionnaire (OHQ) scores (p < .0001) were seen in Ashwagandha SR vs. the placebo group, suggesting significantly lower stress levels and significantly better psychological well-being and sleep quality in the former. No adverse events were reported. This is the first clinical study assessing Ashwagandha SR for its safety and efficacy. Treatment with one Ashwagandha SR capsule once daily for 90 days improved memory and focus, psychological well-being, and sleep quality, reduced stress levels, and was safe and well-tolerated.


Paternal long-term exercise programs offspring for low energy expenditure and increased risk for obesity in mice.
Obesity has more than doubled in children and tripled in adolescents in the past 30 yr. The association between metabolic disorders in offspring of obese mothers with diabetes has long been known; however, a growing body of research indicates that fathers play a significant role through presently unknown mechanisms. Recent observations have shown that changes in paternal diet may result in transgenerational inheritance of the insulin-resistant phenotype. Although diet-induced epigenetic reprogramming via paternal lineage has recently received much attention in the literature, the effect of paternal physical activity on offspring metabolism has not been adequately addressed. In the current study, we investigated the effects of long-term voluntary wheel-running in C57BL/6J male mice on their offspring's predisposition to insulin resistance. Our observations revealed that fathers subjected to wheel-running for 12 wk produced offspring that were more susceptible to the adverse effects of a high-fat diet, manifested in increased body weight and adiposity, impaired glucose tolerance, and elevated insulin levels. Long-term paternal exercise also altered expression of several metabolic genes, including Ogt, Oga, Pdk4, H19, Glut4, and Ptpn1, in offspring skeletal muscle. Finally, prolonged exercise affected gene methylation patterns and micro-RNA content in the sperm of fathers, providing a potential mechanism for the transgenerational inheritance. These findings suggest that paternal exercise produces offspring with a thrifty phenotype, potentially via miRNA-induced modification of sperm.


Multitrait-Multimethod Analysis of the Strengths and Difficulties Questionnaire in Young Asian American Children.
The Strengths and Difficulties Questionnaire (SDQ) is a widely used psychopathology screening tool that measures children's emotional symptoms, peer problems, conduct problems, hyperactivity/inattention, and prosocial behavior. Previous psychometric studies of the SDQ focused primarily on older children in Western cultures and suffered from several methodological limitations. This study examined the reliability, factor structure, convergent, and discriminant validity of the SDQ by focusing on young Asian American children and using more rigorous methods. The five-factor structure of the SDQ was confirmed by confirmatory factor analysis. The ω coefficients indicated adequate reliability for all subscales except parent-rated peer problems and conduct problems. The correlated trait-correlated method minus one multitrait-multimethod model provided evidence for convergent validity and discriminant validity of all subscales except for conduct problems relative to hyperactivity/inattention. This study provided new evidence for the psychometric properties of the SDQ in young children and cultural suitability of the SDQ for Asian Americans.


A longitudinal examination of the influence of maturation on physical self-perceptions and the relationship with physical activity in early adolescent girls.
This longitudinal study investigated the influence of maturation on physical self-perceptions and the relationship with physical activity in early adolescent girls (N=150; mean age=12.79+/-0.31). Physical characteristics were measured and participants completed the Physical Activity Questionnaire for Children, the Children and Youth Physical Self-Perception Profile and the Pubertal Development Scale on two occasions 12 months apart. The results demonstrated a decrease in overall physical activity levels over 12 months which was not influenced by maturational status or physical characteristics. Additional analysis indicated that physical self-perceptions partially accounted for the explained variance in physical activity change, with physical condition being an important individual predictor of physical activity. Further analysis indicated that body mass was an important individual predictor of changes in perceptions of body attractiveness and physical self-worth. At this age maturation has a limited influence on the physical activity behaviours of early adolescent girls and although the variance in physical activity was partly accounted for by physical self-perceptions, this was a relatively small contribution and other factors related to this drop in physical activity need to be considered longitudinally.


Vaccines for cytomegalovirus.
Cytomegalovirus (CMV) is a leading cause of congenital infection worldwide and therefore is recognized as an important target for vaccine development. Data from natural infections and work done with animal models, including models of congenital infection, provide the rationale for their development. CMV vaccine evaluations were begun in the mid-1970's with an attenuated live virus vaccine, Towne, but this vaccine has not consistently provided protection. Most recently, data from a trial with a subunit glycoprotein B (gB) vaccine administered with the adjuvant MF59 became available. This trial, conducted in post-partum women, demonstrated that the vaccine decreased CMV infections, increasing optimism that a protective CMV vaccine could be developed. Other approaches for CMV that have entered clinical trials include replicons, DNA vaccines, prime boost strategies, and chimeric live viruses. The replicon vaccine included gB and the T cell targets phosphoprotein (pp)65 and Immediate Early (IE)1 while the DNA vaccine was given with a new adjuvant and included gB and pp65. The optimal composition for a CMV vaccine remains to be defined but trials continue with the gB vaccine and others.


Long-term effect of gene therapy on Leber's congenital amaurosis.
Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).


Characterization of organic matter in beef feedyard manure by ultraviolet-visible and fourier transform infrared spectroscopies.
Manure from beef cattle feedyards is a valuable source of nutrients and assists with maintaining soil quality. However, humification and decomposition processes occurring during feedyard manure's on-farm life cycle influence the forms, concentrations, and availability of carbon (C) and nutrients such as nitrogen (N) and phosphorus (P). Improved understanding of manure organic matter (OM) chemistry will provide better estimates of potential fertilizer value of manure from different feedyard sources (e.g., manure accumulated in pens, stockpiled manure after pen scraping) and in settling basin and retention pond sediments. This will also assist with identifying factors related to nutrient loss and environmental degradation via volatilization of ammonia and nitrous oxide and nitrate leaching. We used Fourier-transform infrared (FTIR) and ultraviolet-visible (UV-vis) spectroscopies to characterize structural and functional properties of OM and water-extractable OM (WEOM) from different sources (surface manure, manure pack, settling basin, retention pond) on a typical commercial beef feedyard in the Texas Panhandle. Results showed that as beef manure completes its on-farm life cycle, concentrations of dissolved organic C and N decrease up to 98 and 95%, respectively. The UV-vis analysis of WEOM indicated large differences in molecular weight, lignin content, and proportion of humified OM between manures from different sources. The FTIR spectra of OM and WEOM indicate preferential decomposition of fats, lipids, and proteins over aromatic polysaccharides such as lignin. Further work is warranted to evaluate how application of feedyard manure from different sources influences soil metabolic functioning and fertility.


Pelagic and benthic communities of the Antarctic ecosystem of Potter Cove: Genomics and ecological implications.
Molecular technologies are more frequently applied in Antarctic ecosystem research and the growing amount of sequence-based information available in databases adds a new dimension to understanding the response of Antarctic organisms and communities to environmental change. We apply molecular techniques, including fingerprinting, and amplicon and metagenome sequencing, to understand biodiversity and phylogeography to resolve adaptive processes in an Antarctic coastal ecosystem from microbial to macrobenthic organisms and communities. Interpretation of the molecular data is not only achieved by their combination with classical methods (pigment analyses or microscopy), but furthermore by combining molecular with environmental data (e.g., sediment characteristics, biogeochemistry or oceanography) in space and over time. The studies form part of a long-term ecosystem investigation in Potter Cove on King-George Island, Antarctica, in which we follow the effects of rapid retreat of the local glacier on the cove ecosystem. We formulate and encourage new approaches to integrate molecular tools into Antarctic ecosystem research, environmental conservation actions, and polar ocean observatories.


Differences in health status and health behaviour among young Swiss adults between 1993 and 2003.
Very few studies specifically have examined the health status of 20-year-olds. The purpose of the present study is to examine the changes in health status and behaviour among young Swiss adults between 1993 and 2003. The present study used data from the Swiss Federal Surveys of Adolescents, conducted in 1993 and 2003 among 20-year-olds in Switzerland. The study sample included military recruits and a representative community cohort. More than 20,000 subjects participated in each survey. Young adults in 2003 reported fewer traffic- and sports-related accidents, but more work-related and other accidents versus young adults in 1993. A greater percentage of men were overweight or obese in 2003. Also in 2003, a greater percentage of males and females regularly used alcohol, cigarettes and cannabis. In particular, the number that smoked cigarettes daily increased by almost 30% and daily cannabis users increased more than two-fold. Young adults reported higher rates of inter-personal violence and theft in 2003. Compared to 1993, in 2003 young adults were more likely to report a sense of coherence; they also had fewer thoughts of suicide, but a greater sense that life is meaningless. Our study provides the first Swiss data comparing the health status of 20-year-olds a decade apart. The findings suggest a significant increase in substance use. Health prevention efforts among young adults ages 18-24 should focus on substance use. In addition, developing strategies to decrease interpersonal violence, delinquent behaviour, and obesity should be a major public health priority.


Biportal endoscopic discectomy for high-grade migrated lumbar disc herniation.
Although endoscopic procedures for lumbar disc herniation have improved greatly and offer many advantages, the indications are limited mostly to nonmigrated or low-grade migrated disc herniation. Endoscopic application in migrated disc herniation cases is still challenging and technically demanding. The goal in this study was to determine the feasibility of biportal endoscopic discectomy for removal of high-grade migrated disc herniation. A retrospective review was performed in 262 patients who had undergone biportal endoscopic discectomy after the diagnosis of lumbar herniated disc. According to preoperative MRI findings, disc herniation was classified into 5 zones based on the direction and distance from the disc space. Patients were divided into 2 groups-a high-grade migration group and a low-grade migration group. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified Macnab criteria, and those outcomes and operation time were compared between the 2 groups. There were 10 patients with "high-grade up," 8 with "low-grade up," 98 with disc-level, 102 with "low-grade down," and 44 with "high-grade down" herniation, thereby yielding 54 patients in the high-grade group and 208 in the low-grade group. Demographic data for the 2 groups showed no significant difference. There was no significant difference between the 2 groups in ODI, VAS, and modified Macnab criteria. Operation time between the 2 groups was not significantly different (60.74 vs 65.63 minutes, p > 0.05). Biportal endoscopic discectomy can be effective for high-grade migrated lumbar disc herniation with no prolonged operation time and satisfactory clinical outcomes.


Cytotoxicity of Portuguese propolis: the proximity of the in vitro doses for tumor and normal cell lines.
With a complex chemical composition rich in phenolic compounds, propolis (resinous substance collected by Apis mellifera from various tree buds) exhibits a broad spectrum of biological activities. Recently, in vitro and in vivo data suggest that propolis has anticancer properties, but is the cytoxicity of propolis specific for tumor cells? To answer this question, the cytotoxicity of phenolic extracts from Portuguese propolis of different origins was evaluated using human tumor cell lines (MCF7-breast adenocarcinoma, NCI-H460-non-small cell lung carcinoma, HCT15-colon carcinoma, HeLa-cervical carcinoma, and HepG2-hepatocellular carcinoma), and non-tumor primary cells (PLP2). The studied propolis presented high cytotoxic potential for human tumor cell lines, mostly for HCT15. Nevertheless, excluding HCT15 cell line, the extracts at the GI50 obtained for tumor cell lines showed, in general, cytotoxicity for normal cells (PLP2). Propolis phenolic extracts comprise phytochemicals that should be further studied for their bioactive properties against human colon carcinoma. In the other cases, the proximity of the in vitro cytotoxic doses for tumor and normal cell lines should be confirmed by in vivo tests and may highlight the need for selection of specific compounds within the propolis extract.


Cheilitis glandularis progressing to squamous cell carcinoma in an hiv-infected patient: case report.
Cheilitis glandularis (CG), is a rare inflammatory minor salivary gland disease affecting the lower lip. The hallmarks of which include progressive enlargement and eversion of the lower labial mucosa resulting in the obliteration of the mucosal-vermillion interface. A case is presented of a 47-year-old HIV-infected woman who initially manifested clinical features of CG with a typical histopathology picture of a non-specific sialadenitis while a second biopsy performed six months later revealed well differentiated squamous cell carcinoma (SCC). She is symptom free one year following excision and radiotherapy treatment.


Motor imagery during action observation enhances automatic imitation in children with and without developmental coordination disorder.
Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by uncoordinated movement relative to age. While action observation (AO) and motor imagery (MI) can both independently enhance movement skills in children, we report the first study to assess the effects of combined action observation and motor imagery (AO + MI) on automatic imitation in children aged 7-12 years both with DCD (n = 12) and without DCD (n = 12). On each trial, participants planned to execute an instructed rhythmical action (face washing or paint brushing). Before responding, participants observed a rhythmical distractor showing the same or a different action with a subtle speed manipulation across trials (fast vs. slow). Automatic imitation was quantified as an imitation bias in subsequent response cycle times. Across blocks of trials, participants engaged in AO, MI, or combined AO + MI during the distractor phase or intentionally imitated the distractor speeds. Although there were no between groups differences, combined AO + MI instructions produced a significantly greater imitation bias (115%) than both AO (109%) and MI (109%), with intentional imitation yielding the strongest effects overall (128%). Within groups analyses revealed a significant bias for AO and MI in both groups. Combined AO + MI effects were significantly greater than AO in typically developing children and were greater than both AO and MI in children with DCD. These results demonstrate a clear capacity for different forms of motor simulation in children both with and without DCD. Moreover, combined AO + MI instructions represent an advantageous method for training movements in children with different motor abilities compared with separate AO and MI instructions.


Emotional intelligence in orthopedic surgery residents.
Emotional intelligence (EI) is the ability to understand and manage emotions in oneself and others. It was originally popularized in the business literature as a key attribute for success that was distinct from cognitive intelligence. Increasing focus is being placed on EI in medicine to improve clinical and academic performance. Despite the proposed benefits, to our knowledge, there have been no previous studies on the role of EI in orthopedic surgery. We evaluated baseline data on EI in a cohort of orthopedic surgery residents. We asked all orthopedic surgery residents at a single institution to complete an electronic version of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We used completed questionnaires to calculate total EI scores and 4 branch scores. Data were analyzed according to a priori cutoff values to determine the proportion of residents who were considered competent on the test. Data were also analyzed for possible associations with age, sex, race and level of training. Thirty-nine residents (100%) completed the MSCEIT. The mean total EI score was 86 (maximum score 145). Only 4 (10%) respondents demonstrated competence in EI. Junior residents (p = 0.026), Caucasian residents (p = 0.009) and those younger than 30 years (p = 0.008) had significantly higher EI scores. Our findings suggest that orthopedic residents score low on EI based on the MSCEIT. Optimizing resident competency in noncognitive skills may be enhanced by dedicated EI education, training and testing.


Session Availability as a Result of Prior Injury Impacts the Risk of Subsequent Non-contact Lower Limb Injury in Elite Male Australian Footballers.
Prior injury is a commonly identified risk factor for subsequent injury. However, a binary approach to classifying prior injury (i.e., yes/no) is commonly implemented and may constrain scientific findings, as it is possible that variations in the amount of time lost due to an injury will impact subsequent injury risk to differing degrees. Accordingly, this study investigated whether session availability, a surrogate marker of prior injury, influenced the risk of subsequent non-contact lower limb injury in Australian footballers. Data were collected from 62 male elite Australian footballers throughout the 2015, 2016, and 2017 Australian Football League seasons. Each athlete's participation status (i.e., full or missed/modified) and any injuries that occurred during training sessions/matches were recorded. As the focus of the current study was prior injury, any training sessions/matches that were missed due to reasons other than an injury (e.g., load management, illness and personal reasons) were removed from the data prior to all analyses. For every Monday during the in-season periods, session availability (%) in the prior 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84 days was determined as the number of training sessions/matches fully completed (injury free) relative to the number of training sessions/matches possible in each window. Each variable was modeled using logistic regression to determine its impact on subsequent injury risk. Throughout the study period, 173 non-contact lower limb injuries that resulted in at least one missed/modified training session or match during the in-season periods occurred. Greater availability in the prior 7 days increased injury probabilities by up to 4.4%. The impact of session availability on subsequent injury risk diminished with expanding windows (i.e., availability in the prior 14 days through to the prior 84 days). Lesser availability in the prior 84 days increased injury probabilities by up to 14.1%, only when coupled with greater availability in the prior 7 days. Session availability may provide an informative marker of the impact of prior injury on subsequent injury risk and can be used by coaches and clinicians to guide the progression of training, particularly for athletes that are returning from long periods of injury.