Reduced sexual size dimorphism in a pipefish population where males do not prefer larger females.
Within a species' distribution, populations are often exposed to diverse environments and may thus experience different sources of both natural and sexual selection. These differences are likely to impact the balance between costs and benefits to individuals seeking reproduction, thus entailing evolutionary repercussions. Here, we look into an unusual population (Baltic Sea) of the broadnosed pipefish, Syngnathus typhle, where males do not seem to select females based on size and hypothesize that this pattern may derive from a reduction in direct benefits to the male. We further hypothesize that if larger females do not persistently secure a higher reproductive success, either through pre- or postcopulatory sexual selection, a decrease in sexual size dimorphism in the Baltic population should be apparent, especially when contrasted with a well-studied population, inhabiting similar latitudes (Swedish west coast), where males prefer larger females. We found that, in the Baltic population, variation in female quality is low. We were unable to find differences in abortion rates or protein concentration in oocytes produced by females of contrasting sizes. Direct benefits from mating with large partners seem, thus, reduced in the Baltic population. We also found no evidence of any postcopulatory mechanism that could favor larger mothers as embryo development was unrelated to female size. While female size can still be selected through intrasexual competition or fecundity selection, the pressure for large female body size seems to be lower in the Baltic. Accordingly, we found a noticeable decrease in sexual size dimorphism in the Baltic population. We conclude that, although far from negating the significance of other selective processes, sexual selection seems to have a decisive role in supporting pipefish sexual size asymmetries.


Protective Effects of Hydrogen-Rich Saline Against Lipopolysaccharide-Induced Alveolar Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis.
BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and α-smooth muscle actin (α-SMA). Transforming growth factor (TGF)-β1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. RESULTS Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-β1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of α-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of α-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. CONCLUSIONS Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.


The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors.
Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non-self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.


Report from the OMERACT Hand Osteoarthritis Working Group: Set of Core Domains and Preliminary Set of Instruments for Use in Clinical Trials and Observational Studies.
During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed. Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants. Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0. Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12.


miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2.
Cancer stemness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of stemness fate of cancer cells remain incompletely understood. Here, we show that miR-103/107 stimulate multiple stem-like features in colorectal cancer, including expression of stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these stemness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator of Wnt/β-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration of Wnt/β-catenin signaling and a sustained induction of Wnt responsive genes. In colorectal cancer patients, miR-103/107 expression correlates inversely with Axin2 expression and a signature of miR-103/107 high and Axin2 low expression profile correlates with poor prognosis. Together, our study identifies a novel function of miR-103/107 in promoting colorectal cancer stemness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.


Parallel direct laser writing in three dimensions with spatially dependent aberration correction.
We propose a hologram design process which aims at reducing aberrations in parallel three-dimensional direct laser writing applications. One principle of the approach is to minimise the diffractive power of holograms while retaining the degree of parallelisation. This reduces focal distortion caused by chromatic aberration. We address associated problems such as the zero diffraction order and aberrations induced by a potential refractive index mismatch between the immersion medium of the microscope objective and the fabrication substrate. Results from fabrication in diamond, fused silica and lithium niobate are presented.


Cell signalling in CNS and immune system in depression and during antidepressant treatment: focus on glial and natural killer cells.
CNS, endocrine and immune systems share the same molecules: neurotransmitters, cytokines and hormones to communicate within and among each other. Depression is associated with abnormalities in the noradrenergic, serotonergic and dopaminergic neurotransmitter systems and reductions in the level of their precursors and metabolic turnover. Most of these signalling molecules use trimeric G-proteins as a transduction system to transfer extracellular signal into cellular response. Altered levels or function of signalling proteins, especially alpha subunits of trimeric G-proteins, were found in post-mortem brain tissue and leukocytes of subject suffering from major depression. There is a considerable evidence that inflammatory response and immune system changes are the part of depression. Components of cellular immune system natural killer cells, important effectors of immune surveillance, are sensitive to stress response, and their functions are compromised in depressive subjects. Many lines of evidence also point to the loss of both neuronal and glial plasticity and neurotrophic factor support under chronic stress or in depression. There is an increasing knowledge of the role of astrocytic cells in neuroplastic processes and neurotransmitter metabolism. Alterations in the glial populations are observed in major depressive subjects. Antidepressant treatment is modulating glial signalization cascades, increasing production of neurotrophic molecules, supporting neuroplasticity processes, and also modulating functions of natural killers. At the level of membrane signalling, antidepressants show a direct influence upon G alpha subunit levels in both immune system and CNS. These findings support the view that antidepressants influence activity of natural killer and astrocytic populations, and this could be of importance in the depression etiopathogenesis and/or treatment.


Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains.
In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus-vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains.


Chronic left ventricular pacing preserves left ventricular function in children.
Chronic right ventricular (RV) pacing can induce structural and functional cardiac deterioration. Because animal studies showed a benefit of left ventricular (LV) over RV pacing, this study compared the effects of chronic RV and LV pacing in children. Retrospectively, echocardiographic data were evaluated from 18 healthy children (control subjects) and from children undergoing chronic epicardial RV pacing (7 RVP) or LV pacing (7 LVP). Assessment included LV end-diastolic wall thickness (LVEDWT) and end-systolic wall thickness (LVESWT) as well as LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD). The shortening fraction and eccentricity index (LV diameter/2xLV wall thickness) were calculated as measures of LV function and eccentricity, respectively. Duration of QRS and septal posterior wall motion delay (SPWMD) were used as measures of electrical and mechanical dyssynchrony, respectively. A p value less than 0.05 determined significance. As the findings showed, LVEDD, LVESD, LVEDWT, and LVESWT were not significantly different between the groups. The shortening fraction was significantly lower in the RVP (21.7%+/-6.0%) than in the LVP (32.2%+/-5.2%) or control (29.3%+/-4.3%) children. The systolic LV eccentricity index was significantly larger in the RVP (1.8+/-0.2) than in the LVP (1.4+/-0.1) or control (1.4+/-0.2) children. The SPWMD was significantly larger in the RVP (338+/-20 ms) than in the LVP (-16+/-14 ms) or control (-5+/-35 ms) group, whereas QRS duration was similarly longer in the RVP (157+/-10 ms) and LVP (158+/-22 ms) groups compared than in the control group (69+/-7 ms). The authors conclude that LV function in children is preserved by chronic pacing at the LV lateral wall.


p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells.
Pancreatic acinar cells acquire in vitro a pancreatic progenitor phenotype associated with activation of p53, growth arrest and senescence. A similar program is also activated in chronic pancreatitis. To assess the mechanisms involved in this process, we cultured pancreatic acinar cells from wild-type, p53(-/-), p16(-/-) and p21(-/-) mice. Cultures from p53(-/-) mice, but not those from p16(-/-) or p21(-/-) mice, display an enhanced proliferation and can be expanded continuously for more than 20 passages. p53(-/-) cells also display features of stemness such as enhanced sphere formation, increased expression of pancreatic multipotent progenitor markers (Ptf1a, Pdx1, Cpa1, c-myc, Sox9 and Hnf1b), and of the stemness regulators Bmi1 and Klf4. Upon subculture, p53(-/-) cells undergo an epithelial-mesenchymal transition (EMT) and express high levels of vimentin and of the transcriptional regulators Snai1, Snai2, Twist, Zeb1 and Zeb2. Genetic lineage tracing unequivocally demonstrates the epithelial origin of the cells with mesenchymal phenotype. These cells express the endodermal markers Hhex, Pdx1, Sox9, Hnf1b, Foxa2, Gata6 and Sox17, and the stem cell markers c-myc, Bmi1 and Klf4. Cultures from p53(+/-) mice display intermediate levels of the transcription factors involved in EMT but do not surpass the growth arrest. Our findings support the notion that p53 controls both growth and epithelial cell differentiation in the pancreas. These observations have important implications regarding the mechanisms through which p53 inactivation in tumors may be associated with aggressive biological behavior.


Infant health production functions: what a difference the data make.
We examine the extent to which infant health production functions are sensitive to model specification and measurement error. We focus on the importance of typically unobserved but theoretically important variables (typically unobserved variables, TUVs), other non-standard covariates (NSCs), input reporting, and characterization of infant health. The TUVs represent wantedness, taste for risky behavior, and maternal health endowment. The NSCs include father characteristics. We estimate the effects of prenatal drug use, prenatal cigarette smoking, and first trimester prenatal care on birth weight, low birth weight, and a measure of abnormal infant health conditions. We compare estimates using self-reported inputs versus input measures that combine information from medical records and self-reports. We find that TUVs and NSCs are significantly associated with both inputs and outcomes, but that excluding them from infant health production functions does not appreciably affect the input estimates. However, using self-reported inputs leads to overestimated effects of inputs, particularly prenatal care, on outcomes, and using a direct measure of infant health does not always yield input estimates similar to those when using birth weight outcomes. The findings have implications for research, data collection, and public health policy.


Daxx, a novel Fas-binding protein that activates JNK and apoptosis.
The Fas cell surface receptor induces apoptosis upon receptor oligomerization. We have identified a novel signaling protein, termed Daxx, that binds specifically to the Fas death domain. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. A C-terminal portion of Daxx interacts with the Fas death domain, while a different region activates both JNK and apoptosis. The Fas-binding domain of Daxx is a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, while the FADD death domain partially inhibits death but not JNK activation. The Daxx apoptotic pathway is sensitive to both Bcl-2 and dominant-negative JNK pathway components and acts cooperatively with the FADD pathway. Thus, Daxx and FADD define two distinct apoptotic pathways downstream of Fas.


Overexpression of Functional SLC6A3 in Clear Cell Renal Cell Carcinoma.
Purpose: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer to discover novel clinical targets.Experimental Design: Using The Cancer Genome Atlas (TCGA) database, we investigated differences in membrane transporter expression in clear cell RCC (ccRCC) and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC. To investigate the functionality of SLC6A3, we used a [3H]-dopamine uptake assay on ccRCC cells. We further explored the effect of hypoxia-inducible factor (HIF) proteins on SLC6A3 expression by introducing siRNA in ccRCC cells and by hypoxic treatment of nonmalignant cells.Results: We show that ccRCC expresses very high transcript levels of SLC6A3 in contrast to normal kidney tissue and other tumor types, which do not express appreciable levels of this transporter. Importantly, we demonstrate that the elevated expression of SLC6A3 in ccRCC cells is associated with specific uptake of dopamine. By targeting the expression of HIF-1α and HIF-2α, we could show that SLC6A3 expression is primarily influenced by HIF-2α and that hypoxia can induce SLC6A3 expression in normal renal cells.Conclusions: We conclude that the dopamine transporter SLC6A3 constitutes a novel biomarker that is highly specific for ccRCC. We further postulate that the protein can be exploited for diagnostic or therapeutic purposes for detection or treatment of ccRCC. Clin Cancer Res; 23(8); 2105-15. ©2016 AACR.


Ehrlichia under our noses and no one notices.
Ehrlichia chaffeensis, an obligately intracellular bacterium, resides within a cytoplasmic vacuole in macrophages, establishes persistent infection in natural hosts such as white-tailed deer and canids, and is transmitted transstadially and during feeding by ticks, particularly Amblyomma americanum. Ehrlichial cell walls contain glycoproteins and a family of divergent 28 kDa proteins, but no peptidoglycan or lipopolysaccharide. The dense-cored ultrastructural form preferentially expresses certain glycoproteins, including a multiple repeat unit-containing adhesin. Ehrlichiae attach to L-selectin and E-selectin, inhibit phagolysosomal fusion, apoptosis, and JAK/STAT activation, and downregulate IL-12, IL-15, IL-18, TLR2 and 3, and CD14. Mouse models implicate overproduction of TNF-alpha by antigen-specific CD8 T lymphocytes in pathogenesis and strong type 1 CD4 and CD8 T lymphocyte responses, synergistic activities of IFN-gamma and TNF-alpha, and IgG2a antibodies in immunity. Human monocytotropic ehrlichiosis (HME) manifests as a flu-like illness that progresses in severity to resemble toxic shock-like syndrome, with meningoencephalitis or adult respiratory distress syndrome in some patients, and requires hospitalization in half. In immunocompromised patients, HME acts as an overwhelming opportunistic infection. In one family physician's practice, active surveillance for three years revealed an incidence of 1000 cases per million population. Diagnosis employs serology or polymerase chain reaction, which are not utilized sufficiently to establish the true impact of this emerging virus-like illness.


Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.
Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial. To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women. The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States. Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern. Invasive colorectal cancer incidence. A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention. In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up. ClinicalTrials.gov Identifier: NCT00000611.


Transillumination imaging for blood oxygen saturation estimation of skin lesions.
Detecting the early stages of melanoma can be greatly assisted by an accurate estimate of subsurface blood volume and blood oxygen saturation, indicative of angiogenesis. Visualization of this blood volume present beneath a skin lesion can be achieved through the transillumination of the skin. As the absorption of major chromophores in the skin is wavelength dependent, multispectral imaging can provide the needed information to separate out relative amounts of each chromophore. However, a critical challenge to this strategy is relating the pixel intensities observed in a given image to the wavelength-dependent total absorption existing at each spatial location. Consequently, in this paper, we develop an extension to Beer's law, estimated through a novel voxel-based, parallel processing Monte Carlo simulation of light propagation in skin which takes into account the specific geometry of our transillumination imaging apparatus. We then use this relation in a linear mixing model, solved using a multispectral image set, for chromophore separation and oxygen saturation estimation of an absorbing object located at a given depth within the medium. Validation is performed through the Monte Carlo simulation, as well as by imaging on a skin phantom. Results show that subsurface oxygen saturation can be reasonably estimated with good implications for the reconstruction of 3-D skin lesion volumes using transillumination toward early detection of malignancy.


Pigmented Bowen's disease of the genitalia masquerading as malignant melanoma.
Pigmented Bowen's disease is a rare subtype of in situ squamous cell carcinoma of the skin and mucosa, with a potential risk of invasion and metastasis. It is universally accepted that human papillomavirus (HPV) is the cause of genital Bowen's disease. Herein we report an unusual case of pigmented Bowen's disease of the genital area that clinically simulated malignant melanoma. Accurate diagnosis could only be established after histological examination. Polymerase chain reaction (PCR) analysis showed that the lesion harbored HPV 16 DNA. Although pigmented Bowen's disease is rare, it should be considered in the differential diagnosis of all pigmented lesions of the genitalia. This case report highlights the necessity of biopsy and histopathological examination for every suspicious cutaneous lesion.


Predictors of Acute Vertebrobasilar Vasospasm following Tumor Resection in the Foramen Magnum Region.
Cerebral vasospasm can occur after skull base tumor removal. Few studies concentrated on the posterior circulation vasospasm after tumor resection in the posterior fossa. We aimed to identify the risk factors associated with postoperative vertebrobasilar vasospasm after tumor resection in the foramen magnum. We retrospectively reviewed the data of 62 patients with tumors in the foramen magnum at our institution from January 2010 to January 2015. The demographic data, tumor features, surgical characteristics were collected. Vertebrobasilar vasospasm was evaluated by bedside transcranial Doppler before surgery and on postoperative day 1, 3, 7. Univariate and multivariate analyses were performed to determine the predictors of postoperative vasospasm in the posterior circulation. Vertebrobasilar vasospasm was detected in 28 (53.8%) of the 62 patients at a mean time of 3.5 days after surgery. There were 5 (8%) patients with severe vasospasm according to the grading criteria. Age, tumor type, tumor size, vertebral artery encasement, and surgical time were significantly related to vasospasm in the univariate analysis. Further multivariate analysis demonstrated that only age and vertebral artery encasement were independent risk factors predicting the occurrence of postoperative vertebrobasilar vasospasm. The incidence of acute vertebrobasilar vasospasm is not uncommon after foramen magnum tumor resection. Age and vertebral artery encasement are significantly correlated with postoperative vasospasm. Close monitoring of vasospasm should be given to patients with younger age and the presence of vertebral artery encasement on the preoperative imaging to facilitate early diagnosis and intervention.


A pilot study of postoperative pain felt after two implant surgery techniques: a randomized blinded prospective clinical study.
To evaluate postoperative pain after successful implant surgery and compare pain experienced using conventional flap and flapless techniques. Between January 2007 and September 2012, consecutive patients with bilateral partially edentulous maxillae or mandibles were included in the study. Patients were randomly allocated to receive implants with an atraumatic flapless procedure or with a conventional flap procedure in a split-mouth design in a two-stage surgery. This randomized blinded prospective clinical study considered each patient as one unit. The data were analyzed using the Mann-Whitney and chi-square tests. One hundred eight implants were placed in 19 patients. Radiographic and clinical examination showed that all implants were successful. Postoperative pain was significantly more intense after surgery with the conventional flap technique than after surgery with the atraumatic flapless technique. Likewise, the inflammatory response was more intense with the flap technique. Postoperative pain depends on the surgical technique used and is less intense with a flapless technique.


Reconsidering contact precautions for endemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.
Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing. To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals. A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE. Hospital epidemiologists and infection prevention experts. No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE. Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.


Synthesis of metal-fluoride nanoparticles supported on thermally reduced graphite oxide.
Metal-fluoride nanoparticles, (MF x -NPs) with M = Fe, Co, Pr, Eu, supported on different types of thermally reduced graphite oxide (TRGO) were obtained by microwave-assisted thermal decomposition of transition-metal amidinates, (M{MeC[N(iPr)]2} n ) or [M(AMD) n ] with M = Fe(II), Co(II), Pr(III), and tris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium, Eu(dpm)3, in the presence of TRGO in the ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIm][BF4]). The crystalline phases of the metal fluorides synthesized in [BMIm][BF4] were identified by powder X-ray diffraction (PXRD) to be MF2 for M = Fe, Co and MF3 for M = Eu, Pr. The diameters and size distributions of MF x @TRGO were from (6 ± 2) to (102 ± 41) nm. Energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) were used for further characterization of the MF x -NPs. Electrochemical investigations of the FeF2-NPs@TRGO as cathode material for lithium-ion batteries were evaluated by galvanostatic charge/discharge profiles. The results indicate that the FeF2-NPs@TRGO as cathode material can present a specific capacity of 500 mAh/g at a current density of 50 mA/g, including a significant interfacial charge storage contribution. The obtained nanomaterials show a good rate capacity as well (220 mAh/g and 130 mAh/g) at a current density of 200 and 500 mA/g, respectively.


Single-gene influences on brain and behavior.
As traditional behavioral genetics analysis merges with neurogenetics, the field of neurobehavioral genetics, focusing on single-gene effects, comes into being. New biotechnology has greatly accelerated gene discovery and the study of gene function in relation to brain and behavior. More than 7,000 genes in mice and 10,000 in humans have now been documented, and extensive information about the genetics of several species is readily available on the World Wide Web. Based on knowledge of the DNA sequence of a gene, a targeted mutation with the capacity to disable it can be created. These knockouts--also called null mutants--are employed in the study of a wide range of phenotypes, including learning and memory, appetite and obesity, and circadian rhythms. The era of examining single-gene effects from a reductionistic perspective is waning, and research with interacting arrays of genes in various environmental contexts is demonstrating a need for systems-oriented theory.


Dissecting total genetic variance into additive and dominance components of purebred and crossbred pig traits.
The partition of the total genetic variance into its additive and non-additive components can differ from trait to trait, and between purebred and crossbred populations. A quantification of these genetic variance components will determine the extent to which it would be of interest to account for dominance in genomic evaluations or to establish mate allocation strategies along different populations and traits. This study aims at assessing the contribution of the additive and dominance genomic variances to the phenotype expression of several purebred Piétrain and crossbred (Piétrain × Large White) pig performances. A total of 636 purebred and 720 crossbred male piglets were phenotyped for 22 traits that can be classified into six groups of traits: growth rate and feed efficiency, carcass composition, meat quality, behaviour, boar taint and puberty. Additive and dominance variances estimated in univariate genotypic models, including additive and dominance genotypic effects, and a genomic inbreeding covariate allowed to retrieve the additive and dominance single nucleotide polymorphism variances for purebred and crossbred performances. These estimated variances were used, together with the allelic frequencies of the parental populations, to obtain additive and dominance variances in terms of genetic breeding values and dominance deviations. Estimates of the Piétrain and Large White allelic contributions to the crossbred variance were of about the same magnitude in all the traits. Estimates of additive genetic variances were similar regardless of the inclusion of dominance. Some traits showed relevant amount of dominance genetic variance with respect to phenotypic variance in both populations (i.e. growth rate 8%, feed conversion ratio 9% to 12%, backfat thickness 14% to 12%, purebreds-crossbreds). Other traits showed higher amount in crossbreds (i.e. ham cut 8% to 13%, loin 7% to 16%, pH semimembranosus 13% to 18%, pH longissimus dorsi 9% to 14%, androstenone 5% to 13% and estradiol 6% to 11%, purebreds-crossbreds). It was not encountered a clear common pattern of dominance expression between groups of analysed traits and between populations. These estimates give initial hints regarding which traits could benefit from accounting for dominance for example to improve genomic estimated breeding value accuracy in genetic evaluations or to boost the total genetic value of progeny by means of assortative mating.


Classroom-based cognitive behaviour therapy (FRIENDS): a cluster randomised controlled trial to Prevent Anxiety in Children through Education in Schools (PACES).
Anxiety in children is common, impairs everyday functioning, and increases the risk of severe mental health disorders in adulthood. We investigated the effect of a classroom-based cognitive behaviour therapy prevention programme (FRIENDS) on anxiety symptoms in children. Preventing Anxiety in Children though Education in Schools (PACES) is a three-group parallel cluster randomised controlled trial. Interventions were given between September, 2011, and July, 2012, with schools as the unit of allocation and individual participants as the unit of analysis. We enrolled state-funded junior schools in southwest England. We sent information to all eligible schools (state-funded junior schools in southwest England) inviting them to enrol in the study. School year groups were assigned by computer-generated randomisation (1:1:1) to receive either school-led FRIENDS (led by teacher or school staff member), health-led FRIENDS (led by two trained health facilitators), or usual school provision. Children were not masked to treatment allocation. The allocated programme was given to all students (aged 9-10 years) in the school year (ie, universal delivery) as part of the school curriculum as nine, 60 min weekly sessions. Outcomes were collected by self-completed questionnaire administered by researchers masked to allocation. Primary outcome was symptoms of anxiety and low mood at 12 months assessed by the Revised Child Anxiety and Depression Scale (RCADS 30). Analyses were intention to treat and accounted for the clustered nature of the design. The study is registered, number ISRCTN23563048. 45 schools were enrolled: 14 (n=497 children) were randomly assigned to school-led FRIENDS, 14 (n=509) to health-led FRIENDS, and 12 (n=442) to usual school provision. 1257 (92%) children completed 12 month assessments (449 in health-led FRIENDS, 436 in school-led FRIENDS, and 372 in usual school provision). We recorded a difference at 12 months in adjusted mean child-reported RCADS scores for health-led versus school-led FRIENDS (19·49 [SD 14·81] vs 22·86 [15·24]; adjusted difference -3·91, 95% CI -6·48 to -1·35; p=0·0004) and health-led FRIENDS versus usual school provision (19·49 [14·81] vs 22·48 [15·74]; -2·66, -5·22 to -0·09; p=0·043). We noted no differences in parent or teacher ratings. Training teachers to deliver mental health programmes was not as effective as delivery by health professionals. Universally delivered anxiety prevention programmes can be effective when used in schools. However, programme effectiveness varies depending on who delivers them. National Institute for Health Research Public Health Research Programme.


A sensitive membrane-targeted biosensor for monitoring changes in intracellular chloride in neuronal processes.
Regulation of chloride gradients is a major mechanism by which excitability is regulated in neurons. Disruption of these gradients is implicated in various diseases, including cystic fibrosis, neuropathic pain and epilepsy. Relatively few studies have addressed chloride regulation in neuronal processes because probes capable of detecting changes in small compartments over a physiological range are limited. In this study, a palmitoylation sequence was added to a variant of the yellow fluorescent protein previously described as a sensitive chloride indicator (YFPQS) to target the protein to the plasma membrane (mbYFPQS) of cultured midbrain neurons. The reporter partitions to the cytoplasmic face of the cellular membranes, including the plasma membrane throughout the neurons and fluorescence is stable over 30-40 min of repeated excitation showing less than 10% decrease in mbYFPQS fluorescence compared to baseline. The mbYFPQS has similar chloride sensitivity (k(50) = 41 mM) but has a shifted pKa compared to the unpalmitoylated YFPQS variant (cytYFPQS) that remains in the cytoplasm when expressed in midbrain neurons. Changes in mbYFPQS fluorescence were induced by the GABA(A) agonist muscimol and were similar in the soma and processes of the midbrain neurons. Amphetamine also increased mbYFPQS fluorescence in a subpopulation of cultured midbrain neurons that was reversed by the selective dopamine transporter (DAT) inhibitor, GBR12909, indicating that mbYFPQS is sensitive enough to detect endogenous DAT activity in midbrain dopamine (DA) neurons. The mbYFPQS biosensor is a sensitive tool to study modulation of intracellular chloride levels in neuronal processes and is particularly advantageous for simultaneous whole-cell patch clamp and live-cell imaging experiments.


Uncovering the evolutionary origin of plant molecular processes: comparison of Coleochaete (Coleochaetales) and Spirogyra (Zygnematales) transcriptomes.
The large and diverse land plant lineage is nested within a clade of fresh water green algae, the charophytes. Collection of genome-scale data for land plants and other organisms over the past decade has invigorated the field of evolutionary biology. One of the core questions in the field asks: how did a colonization event by a green algae over 450 mya lead to one of the most successful lineages on the tree of life? This question can best be answered using the comparative method, the first step of which is to gather genome-scale data across closely related lineages to land plants. Before sequencing an entire genome it is useful to first gather transcriptome data: it is less expensive, it targets the protein coding regions of the genome, and provides support for gene models for future genome sequencing. We built Expressed Sequence Tag (EST) libraries for two charophyte species, Coleochaete orbicularis (Coleochaetales) and Spirogyra pratensis (Zygnematales). We used both Sanger sequencing and next generation 454 sequencing to cover as much of the transcriptome as possible. Our sequencing effort for Spirogyra pratensis yielded 9,984 5' Sanger reads plus 598,460 GS FLX Standard 454 sequences; Coleochaete orbicularis yielded 4,992 5' Sanger reads plus 673,811 GS FLX Titanium 454 sequences. After clustering S. pratensis yielded 12,000 unique transcripts, or unigenes, and C. orbicularis yielded 19,000. Both transcriptomes were very plant-like, i.e. most of the transcripts were more similar to streptophytes (land plants + charophyte green algae) than to other green algae in the sister group chlorophytes. BLAST results of several land plant genes hypothesized to be important in early land plant evolution resulted in high quality hits in both transcriptomes revealing putative orthologs ripe for follow-up studies. Two main conclusions were drawn from this study. One illustrates the utility of next generation sequencing for transcriptome studies: larger scale data collection at a lower cost enabled us to cover a considerable portion of the transcriptome for both species. And, two, that the charophyte green algal transcriptoms are remarkably plant-like, which gives them the unique capacity to be major players for future evolutionary genomic studies addressing origin of land plant questions.


ERCC1 as a biological marker guiding management in malignant pleural mesothelioma.
To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). ERCC1 was identified as poor prognostic factor in patients with MPM.


Evolutionary aspects of human exercise--born to run purposefully.
This article is intended to raise awareness of the adaptive value of endurance exercise (particularly running) in the evolutionary history of humans, and the implications of the genetic disposition to exercise for the aging populations of modern technology-driven societies. The genome of Homo sapiens has evolved to support the svelte phenotype of an endurance runner, setting him/her apart from all other primates. The cellular and molecular mechanisms underlying the competitive advantages conferred by exercise capacity in youth can also provide a survival benefit beyond the reproductive period. These mechanisms include up-regulation of genes encoding proteins involved in protecting cells against oxidative stress, disposing of damaged proteins and organelles, and enhancing bioenergetics. Particularly fascinating are the signaling mechanisms by which endurance running changes the structure and functional capabilities of the brain and, conversely, the mechanisms by which the brain integrates metabolic, cardiovascular and behavioral responses to exercise. As an emerging example, I highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of the effects of exercise on the brain, and BDNF's critical role in regulating metabolic and cardiovascular responses to endurance running. A better understanding of such 'healthspan-extending' actions of endurance exercise may lead to new approaches for improving quality of life as we advance in the coming decades and centuries.


Serum ferritin concentration and recurrence of colorectal adenoma.
Both body iron stores and dietary iron intake have been reported to increase risk of colorectal neoplasms. We assessed whether serum ferritin concentration was associated with recurrence of colorectal adenomas among 733 individuals with baseline determinations of ferritin as part of a multicenter clinical trial of antioxidant supplements for adenoma prevention. All study participants had at least one adenoma removed within 3 months before enrollment, and 269 of them developed one or more adenomas between follow-up colonoscopies conducted 1 and 4 years after enrollment. Baseline serum ferritin concentrations were analyzed both as a log-transformed continuous variable and as a categorical variable, defined as whether iron stores were nonreplete and low (ferritin < or =30 microg/liter), nonreplete and borderline (31-70 microg/liter), replete and adequate (71-160 microg/liter), or replete and high (>160 microg/liter). Analyses were based on multiple logistic regression models, including age, sex, study center, energy, alcohol, fiber, folate, and total fat intake, number of months between colonoscopic examinations, smoking status, and aspirin use. Overall, there was no statistically significant linear association between log ferritin concentration and adenoma recurrence (P = 0.33). Risk of adenoma recurrence was modestly increased among participants with ferritin concentrations >70 microg/liter relative to those with lower ferritin (odds ratio, 1.39; 95% confidence interval, 0.96-2.02). This result seemed more pronounced among women than men. Dietary intake of iron and red meat was inversely associated with adenoma recurrence among participants with replete iron stores but not consistently associated among those with nonreplete stores. Our findings suggest that any role of iron stores and dietary iron in influencing risk of colorectal adenoma recurrence is likely complex.


[Multidisciplinary protocol for the treatment of epidermoid carcinoma of the esophagus: experience from 1985 to 1989].
A phase II study activated in 1985 for the multidisciplinary treatment of squamous cell carcinoma of the esophagus is described. The treatment program included simultaneous neoadjuvant continuous infusion chemotherapy with cisplatinum and 5-fluorouracil, preoperative radiotherapy (46 Gy in 5 weeks) and delayed programmed surgery (or radical irradiation in selected cases). Twenty-one patients with tumor stages I (6), II (10), III (5) entered in the study and 20 patients completed the treatment program. Severe toxicity observed was: esophagitis 100%, bone marrow aplasia 30%, severe weight loss 52%. One patient developed a tracheo-esophageal fistula at the end of radiotherapy. Clinical objective tumor response rate was 85%. Pathologic complete tumor response rate was 47%. Median follow-up of the entire group is 11 months (range 2 + to 49 + months). Ten patients have been alive for more than 12 months; six are still alive without any evidence of disease (from 12 + to 49 + months). It is concluded that the protocol described is feasible, with treatment related severe but reversible toxicities, and able to induce a high rate of tumor response and long term survivors in patients with initial locally advanced tumor stages.


Seasonal changes in juvenile hormone titers and rates of biosynthesis in honey bees.
Honey bee colonies can respond to changing environmental conditions by showing plasticity in age related division of labor, and these responses are associated with changes in juvenile hormone. The shift from nest tasks to foraging has been especially well characterized; foraging is associated with high juvenile hormone titers and high rates of juvenile hormone biosynthesis, and can be induced prematurely in young bees by juvenile hormone treatment or by a shortage of foragers. However, very few studies have been conducted that study plasticity in division of labor under naturally occurring changes in the environment. To gain further insight into how the environment and juvenile hormone influence foraging behavior, we measured juvenile hormone titers and rates of biosynthesis in workers during times of the year when colony activity in temperature climates is reduced: late fall, winter, and early spring. Juvenile hormone titers and rates of biosynthesis decreased in foragers in the fall as foraging diminished and bees became less active. This demonstration of a natural drop in juvenile hormone confirms and extends previous findings when bees were experimentally induced to revert from foraging to within-hive tasks. In addition, endocrine changes in foragers in the fall are part of a larger seasonally related phenomenon in which juvenile hormone levels in younger, pre-foraging bees also decline in the fall and then increase the following spring as colony activity increases. The seasonal decline in juvenile hormone in foragers was mimicked in summer by placing a honey bee colony in a cold room for 8 days. This suggests that seasonal changes in juvenile hormone are not related to photoperiod changes, but rather to changes in temperature and/or colony social structure that in turn influence endocrine and behavioral development. We also found that active foragers in the late winter and early spring had lower juvenile hormone levels than active foragers in late spring. In light of recent findings of a possible link between juvenile hormone and neuroanatomical plasticity in the bee brain, these results suggest that bees can forage with low juvenile hormone, after previous exposure to some threshold level of juvenile hormone leads to changes in brain structure.


Laparotomy closure techniques: Do surgeons follow the latest guidelines? Results of a questionnaire.
Incisional hernias after laparotomy are associated with significant morbidity and increased costs. Recent research on prevention of incisional hernia formation suggests that a laparotomy closure technique using a slowly absorbable monofilament suture with small fascial steps and bites in a continuous, single layer with a suture length to wound length (SL/WL) ratio of at least 4:1 is effective in lowering morbidity. Little is known about application of this evidence in daily practice. Therefore, a survey was performed among Dutch surgeons. All members of the Dutch Surgical Society were invited to participate in a 24-question online survey on techniques and materials used for abdominal wall closure after midline laparotomy. Subgroup analysis was performed based on surgical subspecialty, type of hospital and experience. Response rate was 26% (402 respondents), representing 97% of all Dutch surgical departments. More than 90% of participants closed the abdominal wall in a single mass layer, using a slowly absorbable monofilament running suture The SL/WL ratio of >4:1 is practiced by only 35% of participants and preferred suture size was variable among participants. Risk factors for incisional hernia development were generally identified correctly but more than half of the participants were unaware of the incidence and time of occurrence of incisional hernia. Subgroup analysis found that gastrointestinal and oncologic surgeons preferred smaller diameter sutures and higher suture-length to wound-length ratios. Trauma, vascular and pediatric surgeons had lower estimates of incidence of incisional hernia than other subspecialties. Surgeons employed in academic hospitals were more likely to use small fascial steps and smaller suture sizes than their colleagues in non-academic hospitals. Correct estimates of incisional hernia incidence decreased when surgeons perform less than 10 laparotomies annually. Implementation of the latest evidence regarding closure techniques of the abdominal wall is not widespread. Only 35% of surgeons close the abdominal fascia using a suture length to wound length ratio of 4:1, which is recommended based on the latest evidence. Surgical trainees, gastrointestinal and oncological surgeons are most familiar with the recommended technique and use it in their daily practice. Efforts should be directed at improving spreading of this technique.


Sry induces cell proliferation in the mouse gonad.
Sry is the only gene on the Y chromosome that is required for testis formation in mammals. One of the earliest morphological changes that occurs as a result of Sry expression is a size increase of the rudimentary XY gonad relative to the XX gonad. Using 5'-bromo-2'-deoxyuridine (BrdU) incorporation to label dividing cells, we found that the size increase corresponds with a dramatic increase in somatic cell proliferation in XY gonads, which is not detected in XX gonads. This male-specific proliferation was observed initially in the cells of the coelomic epithelium and occurred in two distinct stages. During the first stage, proliferation in the XY gonad was observed largely in SF1-positive cells and contributed to the Sertoli cell population. During the second stage, proliferation was observed in SF1-negative cells at and below the coelomic epithelium and did not give rise to Sertoli cells. Both stages of proliferation were dependent on Sry and independent of any other genetic differences between male and female gonads, such as X chromosome dosage or other genes on the Y chromosome. The increase in cell proliferation began less than 24 hours after the onset of Sry expression, before the establishment of male-specific gene expression patterns, and before the appearance of any other known male-specific morphological changes in the XY gonad. Therefore, an increase in cell proliferation in the male coelomic epithelium is the earliest identified effect of Sry expression.


Body composition in Chinese subjects: relationship with age and disease.
Body composition measurement by dual energy absorptiometry was carried out in 160 men (age 45-87 years) and 407 women (age 20-88 years) consisting of volunteers and 25 men and 14 women with chronic obstructive airways disease (COAD) not receiving steroids from a hospital respiratory clinic. The objectives of this study were to provide normal reference values for adult Chinese including the elderly; to examine the effect of age and COAD on body composition; and to compare the use of body mass index (BMI) as a measure of obesity or malnutrition compared with body composition measurements. Values for body composition were different when compared with studies in the Caucasian population. In both sexes, height and lean mass decreased in a linear fashion with aging. In men, total body water increased till the 55-65 age group and then decreased. In women, total body water and bone mineral content also decreased with aging in a linear fashion. Changes in weight, BMI, fat mass and percentage fat with aging were also present in women and followed a quadratic trend. BMI was not a sensitive index of obesity or undernutrition, having approximately only 50-60% sensitivity in detecting high percentage fat or low standardised lean mass values. COAD was associated with low BMI only. Body composition measurements changes with aging, and should be used instead of BMI as a better indication of obesity or undernutrition. Reference values derived from the appropriate ethnic group should be used.


Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis.
The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA.


Comprehensive analysis of tumor microenvironment cytokines in Waldenstrom macroglobulinemia identifies CCL5 as a novel modulator of IL-6 activity.
Although proinflammatory and chemotactic cytokines can profoundly affect the tumor microenvironment, and many of them have been shown to have therapeutic efficacy in preclinical models, the role of these molecules in Waldenström macroglobulinemia (WM) remains poorly understood. In this study, simultaneous analysis of WM patient sera and bone marrow biopsies identified a set of dysregulated cytokines including CCL5, G-CSF, and soluble IL-2 receptor, that were significantly elevated in WM patients whereas IL-8 and EGF levels were significantly lower in these patients compared with healthy controls. Interestingly, CCL5 levels positively correlated with features of disease aggressiveness such as elevated IgM levels and bone marrow involvement. Functional analysis of tumor microenvironment revealed a functional correlation between CCL5 levels and IL-6 levels, a proinflammatory cytokine with an important role in normal and malignant B-cell biology. Furthermore, CCL5 stimulated IL-6 secretion in WM stromal cells resulting in increased IgM secretion by WM malignant cells via the JAK/STAT signaling pathway. Thus, together these results define a novel signaling network in the WM tumor microenvironment controlling IgM secretion and suggest CCL5 as a potential target for the treatment of this disease.


Academic Achievement and Risk Factors for Adolescents with Attention-Deficit Hyperactivity Disorder in Middle School and Early High School.
Examine academic achievement of students with attention-deficit hyperactivity disorder (ADHD) during the early high school period and identify potentially modifiable risk factors for low achievement. Data were collected through surveys (adolescent, parent, and teacher) and direct assessment of Australian adolescents (12-15 yr; n = 130) with ADHD in early high school (i.e., US middle and high school grades). Academic achievement outcomes were measured by linking to individual performance on the National Assessment Program-Literacy and Numeracy (NAPLAN) tests, direct assessment of reading and math, and teacher report of academic competence. Linear regression models examined associations between adolescent, parent/family, and school factors and NAPLAN domain scores. Students with ADHD had lower NAPLAN scores on all domains and fewer met minimum academic standards in comparison with state benchmarks. The poorest results were for persuasive writing. Poor achievement was associated with lower intelligence quotient across all academic domains. Adolescent inattention, bullying, poor family management, male sex, and attending a low socioeconomic status school were associated with lower achievement on specific domains. Students with ADHD are at increased academic risk during the middle school and early high school period. In addition to academic support, interventions targeting modifiable factors including inattention, bullying, and poor family management may improve academic achievement across this critical period.


The mediating role of parenting in the associations between household chaos and children's representations of family dysfunction.
Children's drawings are thought to reflect their mental representations of self and their interpersonal relations within families. Household chaos is believed to disrupt key proximal processes related to optimal development. The present study examines the mediating role of parenting behaviors in the relations between two measures of household chaos, instability and disorganization, and how they may be evidenced in children's representations of family dysfunction as derived from their drawings. The sample (N = 962) is from a longitudinal study of rural poverty exploring the ways in which child, family, and contextual factors shape development over time. Findings reveal that, after controlling for numerous factors including child and primary caregiver covariates, there were significant indirect effects from cumulative family disorganization, but not cumulative family instability, on children's representation of family dysfunction through parenting behaviors. Results suggest that the proximal effects of daily disorganization outweigh the effects of periodic instability overtime.


Molecules and morphology reveal overlooked populations of two presumed extinct Australian sea snakes (Aipysurus: Hydrophiinae).
The critically endangered leaf-scaled (Aipysurus foliosquamaI) and short-nosed (A. apraefrontalis) sea snakes are currently recognised only from Ashmore and Hibernia reefs ~600km off the northwest Australian coast. Steep population declines in both species were documented over 15 years and neither has been sighted on dedicated surveys of Ashmore and Hibernia since 2001. We examine specimens of these species that were collected from coastal northwest Australian habitats up until 2010 (A.foliosquama) and 2012 (A. apraefrontalis) and were either overlooked or treated as vagrants in conservation assessments. Morphological variation and mitochondrial sequence data confirm the assignment of these coastal specimens to A. foliosquama (Barrow Island, and offshore from Port Hedland) and A.apraefrontalis (Exmouth Gulf, and offshore from Roebourne and Broome). Collection dates, and molecular and morphological variation between coastal and offshore specimens, suggest that the coastal specimens are not vagrants as previously suspected, but instead represent separate breeding populations. The newly recognised populations present another chance for leaf-scaled and short-nosed sea snakes, but coastal habitats in northwest Australia are widely threatened by infrastructure developments and sea snakes are presently omitted from environmental impact assessments for industry. Further studies are urgently needed to assess these species' remaining distributions, population structure, and extent of occurrence in protected areas.


The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer's disease.
This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFα. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFα response from the oral epithelium. Prolonged exposure to high levels of circulating TNFα compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease.


The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study.
It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post-intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol (8.7+/-3.3% versus 2.8+/-0.7%) and HS (10.0+/-2.3% versus 3.5+/-0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7+/-2.4%) compared with its control (2.5+/-0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3+/-2.5%) and HS (5.8+/-1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol.


Bis-Metal Complexes of Doubly N-Confused Dioxohexaphyrins as Potential Near-Infrared-II Photoacoustic Dyes.
We investigated the detailed photophysical properties of a series of bis-metal (Zn and Cu) dioxohexaphyrin complexes as potential second near-infrared (NIR-II)-light responsive dyes. A cisoid-configured 28π-electron-conjugated dioxohexaphyrin analogue (c-3a) containing two peculiar "confused pyrrole" moieties in the framework is identified as a reduced isomer derivative of a transoid 26π-dioxohexaphyrin (t-2a). The symmetry-altered structure of c-3a affords a heteroleptic inner environment within the NNNN/NNOO donor core, which imparts its highly flexible electronic features and nonplanar geometry. The macrocycle c-3a can be transformed into the corresponding 26π-electron congener (c-2a) having a coplanar rectangular structure by unique solvent-mediated redox reactivity. Furthermore, upon metal complexation, saddle-distorted bis-metal complexes (c-M2-2a) were formed as the 26π-conjugated structural isomer of the trans-dioxohexaphyrin species (i.e., t-M2-2a). These isoelectronic dioxohexaphyrins demonstrate precise geometry-dependent photophysical properties. Broad tailing NIR-II absorption, weak emissive character, and rapid-decay of the S1 state are observed for c-Zn2-2a. In contrast, the coplanar t-M2-2a exhibits efficient photoacoustic response upon laser excitation with NIR-II light (λ > 1000 nm). To the best of our knowledge, this is the first example of an expanded porphyrin-based photoacoustic contrast agent responsive to NIR-II light.


Effect of bioconcentration and trophic transfer on realized exposure to oxazepam in 2 predators, the dragonfly larvae (Aeshna grandis) and the Eurasian perch (Perca fluviatilis).
Psychoactive substances are used worldwide and constitute one of the most common groups of pharmaceutical contaminants in surface waters. Although these pharmaceuticals are designed to be efficiently eliminated from the human body, very little is known about their trophic-transfer potential in aquatic wildlife. Therefore, the goal of the present study was to quantify and compare uptake of an anxiolytic (oxazepam) from water (bioconcentration) and via the consumption of contaminated diet (trophic transfer) in 2 common freshwater predators: Eurasian perch (Perca fluviatilis) and the dragonfly larvae Aeshna grandis. Bioconcentration and trophic transfer of oxazepam were found in both predator species. However, higher bioconcentrations were observed for perch (bioconcentration factor [BCF], 3.7) than for dragonfly larvae (BCF, 0.5). Perch also retained more oxazepam from consumed prey (41%) than dragonfly larvae (10%), whereas the relative contribution via prey consumption was 14% and 42% for perch and dragonflies, respectively. In addition, bioconcentration was negatively correlated with perch weight, indicating that exposure levels in natural contaminated environments differ between individuals of different size or between different developmental stages. Hence, trophic transfer of pharmaceuticals may indeed occur, and estimates of environmental exposures that do not consider intake via food or size-dependent bioconcentration may therefore lead to wrongful estimations of realized exposure levels in natural contaminated ecosystems.


Phase imaging of cells by simultaneous dual-wavelength reflection digital holography.
We present a phase-imaging technique to quantitatively study the three-dimensional structure of cells. The method, based on the simultaneous dual-wavelength digital holography, allows for higher axial range at which the unambiguous phase imaging can be performed. The technique is capable of nanometer axial resolution. The noise level, which increases as a result of using two wavelengths, is then reduced to the level of a single wavelength. The method compares favorably to software unwrapping, as the technique does not produce non-existent phase steps. Curvature mismatch between the reference and object beams is numerically compensated. The 3D images of SKOV-3 ovarian cancer cells are presented.


Bone healing dynamics at buccal peri-implant sites.
It is common belief that immediate implant placement into extraction sites may act to preserve the alveolar process. The objective of this study was to evaluate healing dynamics at buccal peri-implant sites in relation to the dimensions of the alveolar ridge. Bilateral, critical-size, supraalveolar, peri-implant defects were created in 12 male Hound Labrador mongrel dogs following surgical horizontal cut-down of the alveolar ridge. Each jaw quadrant received three 10-mm titanium implants placed 5 mm into extraction sites of the third and fourth premolar teeth leaving 5 mm in a supraalveolar position. The mucoperiosteal flaps were advanced, adapted, and sutured for primary intention healing. Bone fluorescent markers were administered at weeks 3 and 4 postsurgery, and pre-euthanasia. Incandescent, polarized, and fluorescent light microscopies were used to assess the width of the buccal wall of the alveolar ridge and local bone remodeling over the 8-week healing interval. There was a significant association between the width of the buccal alveolar ridge and extent of bone resorption evaluated by incandescent and fluorescent light microscopy. A non-linear association was observed between the buccal ridge width and resorption of the alveolar ridge. A 2-mm threshold was established to account for this non-linearity. The strength of this association was two times greater in specimens with a buccal ridge width <2 mm compared with a wider ridge (beta=1.62 vs. 0.80) observed by fluorescent light microscopy. Accordingly, mean buccal resorption was significantly greater when the ridge width was <2 mm. Fluorescent light microscopy consistently showed greater buccal resorption compared with incandescent light microscopy (P<0.05). Agreement between the examination techniques was low (concordance correlation coefficient=0.49), especially for higher values of buccal resorption. When implants are placed into extraction sites, proximity to the buccal alveolar crest appears a major consideration. The observations herein suggest that the width of the buccal alveolar ridge should be at least 2 mm to maintain the alveolar bone level. These observations likely have general implications for implant placement using most surgical protocols.


Exploiting development to evaluate auditory encoding of amplitude modulation.
During development, detection for many percepts matures gradually. This provides a natural system in which to investigate the neural mechanisms underlying performance differences: those aspects of neural activity that mature in conjunction with behavioral performance are more likely to subserve detection. In principle, the limitations on performance could be attributable to either immature sensory encoding mechanisms or an immature decoding of an already-mature sensory representation. To evaluate these alternatives in awake gerbil auditory cortex, we measured neural detection of sinusoidally amplitude-modulated (sAM) stimuli, for which behavioral detection thresholds display a prolonged maturation. A comparison of single-unit responses in juveniles and adults revealed that encoding of static tones was adult like in juveniles, but responses to sAM depth were immature. Since perceptual performance may reflect the activity of an animal's most sensitive neurons, we analyzed the d prime curves of single neurons and found an equivalent percentage with highly sensitive thresholds in juvenile and adult animals. In contrast, perceptual performance may reflect the pooling of information from neurons with a range of sensitivities. We evaluated a pooling model that assumes convergence of a population of inputs at a downstream target neuron and found poorer sAM detection thresholds for juveniles. Thus, if sAM detection is based on the most sensitive neurons, then immature behavioral performance is best explained by an immature decoding mechanism. However, if sAM detection is based on a population response, then immature detection thresholds are more likely caused by an inadequate sensory representation.


COVID-19 and animals: What do we know?
Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.


Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia.
Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa.


In vitro effect of naftidrofuryl oxalate on cerebral mitochondria impaired by microsphere-induced embolism in rats.
The present study was designed to determine whether naftidrofuryl oxalate (Naftidrofuryl) may exert a beneficial effect on the cerebral mitochondria after microsphere-induced embolism assessed under in vitro conditions. For this purpose, 600 microspheres (48 microns in diameter) were injected into the right carotid canal of rats, which induced an irreversible embolism in the right cerebrum. Three days after the operation, the cerebral mitochondria were isolated and their oxidative phosphorylation ability and succinate dehydrogenase activity were determined. Two types of mitochondria were obtained after cerebral embolism: one was mitochondria which revealed a marked decline in the oxidative phosphorylation activity when measured in the presence of glutamate or succinate as a substrate (severely injured mitochondria), and the other, those which revealed a decrease in the activity in the presence of succinate and an appreciable increase in the activity in the presence of glutamate (mildly injured mitochondria). Naftidrofuryl at the concentration of 3 microM elicited slight but significant restoration of the oxidative phosphorylation ability of the mildly injured mitochondria isolated from rats after the cerebral embolism, but not of the severely injured mitochondria. The succinate dehydrogenase activity of the brain mitochondria isolated from rats 3 days after the cerebral embolism was significantly decreased. Exposure of these mitochondria to 0.1 to 1 microM Naftidrofuryl significantly restored the succinate dehydrogenase activity. The results suggest that Naftidrofuryl is capable of exerting a beneficial effect in vitro on the brain mitochondria activity impaired by the cerebral embolism, particularly on the activity of mildly injured mitochondria.


Early Earth and the rise of complex life.
The history of life on Earth progressed in parallel with the evolving oxygen state of the atmosphere and oceans, but the details of that relationship remain poorly known and debated. There is, however, general agreement that the first appreciable and persistent accumulation of oxygen in the oceans and atmosphere occurred around 2.3 to 2.4 billion years ago. Following this Great Oxidation Event, biospheric oxygen remained at relatively stable intermediate levels for more than a billion years. Much current research focuses on the transition from the intermediate conditions of this middle chapter in Earth history to the more oxygenated periods that followed - often emphasizing whether increasing and perhaps episodic oxygenation drove fundamental steps in the evolution of complex life and, if so, when. These relationships among early organisms and their environments are the thematic threads that stitch together the papers in this collection. Expert authors bring a mix of methods and opinions to their leading-edge reviews of the earliest proliferation and ecological impacts of eukaryotic life, the subsequent emergence and ecological divergence of animals, and the corresponding causes and consequences of environmental change.


Genomics assisted ancestry deconvolution in grape.
The genus Vitis (the grapevine) is a group of highly diverse, diploid woody perennial vines consisting of approximately 60 species from across the northern hemisphere. It is the world's most valuable horticultural crop with ~8 million hectares planted, most of which is processed into wine. To gain insights into the use of wild Vitis species during the past century of interspecific grape breeding and to provide a foundation for marker-assisted breeding programmes, we present a principal components analysis (PCA) based ancestry estimation method to calculate admixture proportions of hybrid grapes in the United States Department of Agriculture grape germplasm collection using genome-wide polymorphism data. We find that grape breeders have backcrossed to both the domesticated V. vinifera and wild Vitis species and that reasonably accurate genome-wide ancestry estimation can be performed on interspecific Vitis hybrids using a panel of fewer than 50 ancestry informative markers (AIMs). We compare measures of ancestry informativeness used in selecting SNP panels for two-way admixture estimation, and verify the accuracy of our method on simulated populations of admixed offspring. Our method of ancestry deconvolution provides a first step towards selection at the seed or seedling stage for desirable admixture profiles, which will facilitate marker-assisted breeding that aims to introgress traits from wild Vitis species while retaining the desirable characteristics of elite V. vinifera cultivars.


SLIT3 deficiency attenuates pressure overload-induced cardiac fibrosis and remodeling.
In pulmonary hypertension and certain forms of congenital heart disease, ventricular pressure overload manifests at birth and is an obligate hemodynamic abnormality that stimulates myocardial fibrosis, which leads to ventricular dysfunction and poor clinical outcomes. Thus, an attractive strategy is to attenuate the myocardial fibrosis to help preserve ventricular function. Here, by analyzing RNA-sequencing databases and comparing the transcript and protein levels of fibrillar collagen in WT and global-knockout mice, we found that slit guidance ligand 3 (SLIT3) was present predominantly in fibrillar collagen-producing cells and that SLIT3 deficiency attenuated collagen production in the heart and other nonneuronal tissues. We then performed transverse aortic constriction or pulmonary artery banding to induce left and right ventricular pressure overload, respectively, in WT and knockout mice. We discovered that SLIT3 deficiency abrogated fibrotic and hypertrophic changes and promoted long-term ventricular function and overall survival in both left and right ventricular pressure overload. Furthermore, we found that SLIT3 stimulated fibroblast activity and fibrillar collagen production, which coincided with the transcription and nuclear localization of the mechanotransducer yes-associated protein 1. These results indicate that SLIT3 is important for regulating fibroblast activity and fibrillar collagen synthesis in an autocrine manner, making it a potential therapeutic target for fibrotic diseases, especially myocardial fibrosis and adverse remodeling induced by persistent afterload elevation.


The production and perception of long calls by cotton-top tamarins (Saguinus oedipus): acoustic analyses and playback experiments.
The authors' goal was to provide a better understanding of the relationship between vocal production and perception in nonhuman primate communication. To this end, the authors examined the cotton-top tamarin's (Saguinus oedipus) combination long call (CLC). In Part 1 of this study, the authors carried out a series of acoustic analyses designed to determine the kind of information potentially encoded in the tamarin's CLC. Using factorial analyses of variance and multiple discriminant analyses, the authors explored whether the CLC encodes 3 types of identity information: individual, sex, and social group. Results revealed that exemplars could be reliably assigned to these 3 functional classes on the basis of a suite of spectrotemporal features. In Part 2 of this study, the authors used a series of habituation-dishabituation playback experiments to test whether tamarins attend to the encoded information about individual identity. The authors 1st tested for individual discrimination when tamarins were habituated to a series of calls from 1 tamarin and then played back a test call from a novel tamarin; both opposite- and same-sex pairings were tested. Results showed that tamarins dishabituated when caller identity changed but transferred habituation when caller identity was held constant and a new exemplar was played (control condition). Follow-up playback experiments revealed an asymmetry between the authors' acoustic analyses of individual identity and the tamarins' capacity to discriminate among vocal signatures; whereas all colony members have distinctive vocal signatures, we found that not all tamarins were equally discriminable based on the habituation-dishabituation paradigm.


Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men with pedophilia.
Previous studies have suggested that abnormalities in plasma phospholipid fatty acids may play a role in aggressive behavior. Recently, it was suggested that a dysfunctional serotonergic turnover in the brain may be involved in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids (PUFA) may cause alterations in the serotonergic system that may be related to pedophilia and aggression. This study examines the serum phospholipid n-3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen healthy volunteers participated in this study. In pedophilia there was a significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3 fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower DHA in pedophiles is related to more impulsiveness and lower agreeableness (trust, altruism, straightforwardness, compliance) and conscientiousness (self-discipline). The results of this study suggest that a depletion of the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in particular, of DHA may take part in the pathophysiology of pedophilia. One hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the serotonergic turnover, which are related to impulse discontrol and aggression-hostility, behaviors which are associated with pedophilia.


A social chemosignaling function for human handshaking.
Social chemosignaling is a part of human behavior, but how chemosignals transfer from one individual to another is unknown. In turn, humans greet each other with handshakes, but the functional antecedents of this behavior remain unclear. To ask whether handshakes are used to sample conspecific social chemosignals, we covertly filmed 271 subjects within a structured greeting event either with or without a handshake. We found that humans often sniff their own hands, and selectively increase this behavior after handshake. After handshakes within gender, subjects increased sniffing of their own right shaking hand by more than 100%. In contrast, after handshakes across gender, subjects increased sniffing of their own left non-shaking hand by more than 100%. Tainting participants with unnoticed odors significantly altered the effects, thus verifying their olfactory nature. Thus, handshaking may functionally serve active yet subliminal social chemosignaling, which likely plays a large role in ongoing human behavior.


Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice.
Tubular cell apoptosis is involved in ischemic renal failure, but the underlying mechanism is unclear. Bid, a proapoptotic Bcl-2 family protein, may regulate the intrinsic as well as the extrinsic pathway of apoptosis. In vivo, Bid is most abundantly expressed in the kidneys. However, the role played by Bid in renal pathophysiology is unknown. Our recent work demonstrated Bid activation during renal ischemia-reperfusion. The current study has determined the role of Bid in ischemic renal injury and renal failure using Bid-deficient mice. In wild-type C57BL/6 mice, Bid was proteolytically processed into active forms during renal ischemia-reperfusion, which subsequently targeted mitochondria. This was accompanied by the development of tissue damage and severe renal failure, showing serum creatinine of 3.0 mg/dl after 48 h of reperfusion. The same ischemic insult induced acute renal failure in Bid-deficient mice, which was nonetheless less severe than the wild-type, showing 1.3 mg/dl serum creatinine. In addition, Bid deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3 activation during 48 h of reperfusion. Compared with wild-type, animal death following renal ischemia was delayed in Bid-deficient mice. Collectively, the results suggest a role for Bid in ischemic renal injury and renal failure.


Retrospective review of rapid pediatric brain MR imaging at an academic institution including practice trends and factors affecting scan times.
In an effort to reduce radiation exposure in children requiring regular follow up for shunted hydrocephalus, our institution implemented a rapid brain MR imaging protocol. The purpose of this study was to review an academic practice experience with pediatric rapid brain MR imaging without patient sedation in the evaluation of hydrocephalus and a limited group of other conditions. We retrospectively analyzed limited-sequence, rapid brain MR imaging scans performed in nonsedated patients younger than 14 years between April 2009 and December 2011. So-called failed examinations were determined by consensus of 2 authors as insufficiently diagnostic for evaluation of ventricular size. CT and MR imaging quarterly volumes for hydrocephalus-related indications were determined from 2005-2012. Multivariable logistic regression analysis was performed to elucidate factors potentially affecting scan durations including examination indication and patient age, sex, inpatient status, and clinical conditions. A total of 398 examinations were performed on 168 patients (103 boys, 65 girls; median age, 13 months). None were deemed to be failed examinations. Median scan duration was 4.43 minutes (interquartile range, 4.42 minutes-5.88 minutes; SD, 2.42 minutes). Examination indication of altered mental status was the only factor associated with increased scan duration (+1.77 minutes; P = .0021). Hydrocephalus-related imaging volumes approximately doubled in the 7 years reviewed, but rapid MR imaging introduced in 2009 is quickly replacing CT scanning for these indications, accounting for nearly 7 of every 8 examinations at the end of the study period. In every case of initial work-up and follow-up, rapid brain MR imaging effectively evaluated ventricular size and/or intracranial fluid and represents a viable alternative to CT scanning, irrespective of a child's age or clinical condition. For this indication and patient group, MR imaging is now the predominant imaging method in our practice.


Implementing an e-Assessment of Professional Practice.
The ability to accurately document undergraduate student nurses' development while in the clinical area is a requirement of the Nursing and Midwifery Council. Owing to a number of strategic and pragmatic drivers, the Faculty of Health Sciences at the University of Southampton has developed and implemented an e-Assessment of Professional Practice (eAoPP). This platform enables the student, mentor and academic staff to access the portfolio from any internet enabled device and has been rolled out in phases over 2 years to more than 5000 students and mentors. The key factors underpinning the success of the project are presented along with an audit and preliminary analysis of support service activity provided during the roll out to 380 students in January 2015 across Hampshire and the Isle of Wight. Plans for future development, including employability and roll out to other student groups are discussed.


Oral herbal supplement containing magnesium sulfate improve metabolic control and insulin resistance in non-diabetic overweight patients: A randomized double blind clinical trial.
Background: Magnesium deficiency plays a key role in obesity and decreases insulin sensitivity. In our previous study, significant evidence was provided for the contribution of oral Mg supplement that could improve insulin sensitivity and body weight in animal trials. The purpose of the present study was to investigate the effects of an herbal supplement containing 300 mg magnesium sulfate on lipid profile, as well as insulin resistance and secretion in overweight patients. Methods: Seventy overweight non-diabetic volunteers with Body Mass Index (BMI) >28 kg/m2 were included in a randomized double blind placebo-controlled clinical trial (ethic number HUMS REC.1394.57) and registered in Iranian Registry of Clinical Trials (IRCT2012110124756N2 with registration number 24756). They received either placebo or an herbal supplement capsule containing 300 mg magnesium sulfate (MgSO4) for 6 months on a daily basis. Metabolic control, lipid profile and magnesium status were determined at baseline and every three months. Student t-test, repeated measure ANOVA and ANCOVA were used to compare the groups. Results: There was no significant difference between groups before intervention, but daily Mg supplement for 6 months significantly improved fasting insulin level (6.71±0.11 to 6.27±0.3 three months after Mg therapy, p<0.01 vs. 6.41±0.11 in control group (5.83±0.063) six months after Mg therapy, p< 0.0001), HOMA-IR (1.52±0.03 )in control group to 1.36±0.03 after three months Mg therapy, p<0.05 vs 1.37±0.05 in control group to 1.22±0.02 six months after Mg therapy, p< 0.05), high density lipoprotein cholesterol (HDL) (43.57±0.82 in control group to 43.91±1.92 three months after Mg therapy, p<0.001vs 43.57±0.82 in control group to 46±0.88 six months after Mg therapy, <0.01), triglyceride (TG) (163.17±6.1 in control group to 141.2±5.84 six months after g therapy, p<0.05) and low density lipoprotein cholesterol (LDL) (112.62±3.41 in control group to 104.42±2.35 six months after Mg therapy, p<0.05). Conclusion: Oral herbal supplement containing MgSO4 (300 mg/day) could improve plasma insulin level, lipid profile, and insulin resistance in non-diabetic overweight volunteers.