Optic neuritis: experience from a south Indian demyelinating disease registry.
Natural history of optic neuritis (OPN) has not been studied in India. To study consecutive patients with optic neuritis as the initial manifestation of the neurologic disease and with disease duration of 3 or more years registered in the Mangalore Demyelinating Disease Registry. The study included 59 patients with a primary diagnosis of optic neuritis (confirmed by either an ophthalmologist or a neurologist or both). All the patients were investigated and followed-up in the clinic. During the follow-up of the 59 patients, 29 (49%) patients developed multiple sclerosis (MS); 3 (5%) patients neuromyelitis optica (NMO); and 13 (22%) patients chronic relapsing inflammatory optic neuritis (CRION), while the remaining 14 (24%) did not either progress or relapse, monophasic OPN. An initial abnormal magnetic resonance imaging predicted conversion to MS in all 7 patients who had imaging at onset. Patients with NMO were left with significant residual visual loss distinguishing NMO from MS. In this large series of patients with CRION, nearly 50% of patients had deterioration in vision while steroids were being tapered. Long-term immunosuppression was essential for maintaining good visual outcome in both NMO and CRION. Optic neuritis in India appears similar to that in the West with nearly 50% developing MS in the long term.


Characterization of the cobaltochelatase CbiXL: evidence for a 4Fe-4S center housed within an MXCXXC motif.
CbiX is a cobaltochelatase required for the biosynthesis of vitamin B12 and is found in Archaea as a short form (CbiXS containing 120-145 amino acids) and in some bacteria as a longer version (CbiXL containing 300-350 amino acids). Purification of either recombinant Bacillus megaterium or Synechocystis CbiXL in Escherichia coli, which is facilitated by the presence of a naturally occurring histidine-rich region of the protein, results in the isolation of a dark brown protein solution. The UV/visible spectrum of the protein is consistent with the presence of a redox group, and the lack of definition within the spectrum is suggestive of a 4Fe-4S center. The presence of an iron-sulfur center was confirmed by EPR analysis of the proteins, which produces a pseudoaxial spectrum with g values at 2.04, 1.94, and 1.90. The EPR spectrum was absent at 70 K, an observation that is diagnostic of a 4Fe-4S center. Redox potentiometry coupled with optical spectroscopy allowed the midpoint potential of the redox center to be determined for the CbiXL from both B. megaterium and Synechocystis. Sequence analysis of CbiXL proteins reveals only two conserved cysteine residues within the CbiXL proteins, which are part of an MXCXXC motif. Mutagenesis of the two cysteines leads to loss of both the EPR spectrum and UV/visible spectral features of the Fe-S center in the protein, clearly indicating that these residues are involved in ligating the cofactor to the apoprotein possibly in a butterfly arrangement. The potential physiological role of the iron-sulfur center is discussed.


A challenge to the evidence behind noise guidelines for UK hospitals.
Teams assessing hospital noise against international guidelines regularly find that noise exceeds perceived safe levels in clinical settings. The care of sick people may be inherently noisy but recent efforts to tackle the problem propose a wider scope to identify sources and qualities of noise as well as more precision with noise recording. We sought to challenge the scientific evidence cited in the four major documents pertaining to hospital noise in the UK to clarify if evidence of harm from noise included in guidelines is available, contemporary and of high quality. Our team of hearing-health clinicians, acoustic scientists and acoustic engineers have conducted a narrative scoping review focused on critically appraising four of the most cited guidelines against which noise is measured in healthcare settings in the UK. There is a lack of high-quality evidence for commonly accepted consequences of noise cited in current guidelines. The current evidence base for noise guidelines in a healthcare setting is largely based on subjective heterogeneous and inconclusive research. Whilst reduced noise is not disputed as potentially beneficial for patient care, further hypothesis-driven research and interventions assessing the benefits or outcomes of any such intervention should be sought to produce high-quality evidence of relevance on the clinical coalface.


[Herbal supplement usage in cardiac patients].
Complementary and alternative medicine (CAM) has become more and more widespread around the world. CAM is a broad term that refers to all medical healthcare services, methods, and practices that are not part of standard medical care, as well as the accompanying theories and beliefs. The aim of the present study was to investigate the use of herbal medicinal products in cardiac patients, as well as the methods of administration of the products. This descriptive cross-sectional study included 199 patients aged over 18 years who were hospitalized in the Defne Hospital department of cardiology and volunteered to participate in a 20-item survey between April 2016 and June 2016. The study results indicated that 28.6% (n=57) of patients were using herbal products and 71.6% (n=142) said they did not. Only 14.03% (n=8) of those who used herbal products said they used them in consultation with their physician; 85.9% (n=49) had used herbal medicine without consulting their doctor. Of the participants with hypertension, 35.7% of them reported using herbal medicinal products. Of these, 22.5% of them were consuming lemon, 17.5% pomegranate syrup, and 17.5% green tea. Of the participants with cardiovascular diseases, 23.5% of them stated that they were taking herbal products. Of these, 25% were consuming green tea, 25% ginger, and 18.8% sage. Herbal medicinal supplements were used by a large portion of the cardiac patients in this study. Furthermore, most of the patients stated that they were using these products without informing their physician, a practice that can have unwanted consequences.


Factors affecting the diffusion of online end user literature searching.
The aim of this study was to identify factors that affect diffusion of usage of online end user literature searching. Fifteen factors clustered into three attribute sets (innovation attributes, organizational attributes, and marketing attributes) were measured to study their effect on the diffusion of online searching within institutions. A random sample of sixty-seven academic health sciences centers was selected and then 1,335 library and informatics staff members at those institutions were surveyed by mail with electronic mail follow-up. Multiple regression analysis was performed. The survey yielded a 41% response rate with electronic mail follow-up being particularly effective. Two dependent variables, internal diffusion (spread of diffusion) and infusion (depth of diffusion), were measured. There was little correlation between them, indicating they measured different things. Fifteen independent variables clustered into three attribute sets were measured. The innovation attributes set was significant for both internal diffusion and infusion. Significant individual variables were visibility for internal diffusion and image enhancement effects (negative relation) as well as visibility for infusion (depth of diffusion). Organizational attributes were also significant predictors for both dependent variables. No individual variables were significant for internal diffusion. Communication, management support (negative relation), rewards, and existence of champions were significant for infusion. Marketing attributes were not significant predictors. Successful diffusion of online end user literature searching is dependent on the visibility of the systems, communication among, rewards to, and peers of possible users who promote use (champions). Personal image enhancement effects have a negative relation to infusion, possibly because the use of intermediaries is still seen as the more luxurious way to have searches done. Management support also has a negative relation to infusion, perhaps indicating that depth of diffusion can increase despite top-level management actions.


Discovery of the β-barrel-type RNA methyltransferase responsible for N6-methylation of N6-threonylcarbamoyladenosine in tRNAs.
Methylation is a versatile reaction involved in the synthesis and modification of biologically active molecules, including RNAs. N(6)-methyl-threonylcarbamoyl adenosine (m(6)t(6)A) is a post-transcriptional modification found at position 37 of tRNAs from bacteria, insect, plants, and mammals. Here, we report that in Escherichia coli, yaeB (renamed as trmO) encodes a tRNA methyltransferase responsible for the N(6)-methyl group of m(6)t(6)A in tRNA(Thr) specific for ACY codons. TrmO has a unique single-sheeted β-barrel structure and does not belong to any known classes of methyltransferases. Recombinant TrmO employs S-adenosyl-L-methionine (AdoMet) as a methyl donor to methylate t(6)A to form m(6)t(6)A in tRNA(Thr). Therefore, TrmO/YaeB represents a novel category of AdoMet-dependent methyltransferase (Class VIII). In a ΔtrmO strain, m(6)t(6)A was converted to cyclic t(6)A (ct(6)A), suggesting that t(6)A is a common precursor for both m(6)t(6)A and ct(6)A. Furthermore, N(6)-methylation of t(6)A enhanced the attenuation activity of the thr operon, suggesting that TrmO ensures efficient decoding of ACY. We also identified a human homolog, TRMO, indicating that m(6)t(6)A plays a general role in fine-tuning of decoding in organisms from bacteria to mammals.


Missing focus on Human Factors - organizational and cognitive ergonomics - in the safety management for the petroleum industry.
More attention has recently been given to Human Factors in petroleum accident investigations. The Human Factors areas examined in this article are organizational, cognitive and physical ergonomics. A key question to be explored is as follows: To what degree are the petroleum industry and safety authorities in Norway focusing on these Human Factors areas from the design phase? To investigate this, we conducted an innovative exploratory study of the development of four control centres in Norwegian oil and gas industry in collaboration between users, management and Human Factors experts. We also performed a literature survey and discussion with the professional Human Factors network in Norway. We investigated the Human Factors focus, reasons for not considering Human Factors and consequences of missing Human Factors in safety management. The results revealed an immature focus and organization of Human Factors. Expertise on organizational ergonomics and cognitive ergonomics are missing from companies and safety authorities and are poorly prioritized during the development. The easy observable part of Human Factors (i.e. physical ergonomics) is often in focus. Poor focus on Human Factors in the design process creates demanding conditions for human operators and impact safety and resilience. There is lack of non-technical skills such as communication and decision-making. New technical equipment such as Closed Circuit Television is implemented without appropriate use of Human Factors standards. Human Factors expertise should be involved as early as possible in the responsible organizations. Verification and validation of Human Factors should be improved and performed from the start, by certified Human Factors experts in collaboration with the workforce. The authorities should check-back that the regulatory framework of Human Factors is communicated, understood and followed.


Switchable friction of stimulus-responsive hydrogels.
Poly(N-isopropylacrylamide) (pNIPAAm) gels are stimulus-responsive hydrogels that exhibit large reversible changes in their volume and surface physicochemical properties near the lower critical solution temperature (LCST) in response to external stimuli, such as a change in temperature or solvent composition. Here we report how different phase states, induced isothermally by changes in the solvent composition, affect the tribological properties of pNIPAAm hydrogels. Our measurements indicate that gels in a collapsed conformation (above the LCST) exhibit significantly more friction than swollen gels (below the LCST) at low shear rates. These differences arise from changes in the surface roughness, adhesive interactions, and chain entanglements of the gel surfaces associated with the phase transition. Importantly, we show that the changes in friction, triggered by an external stimulus, are reversible. These reversible and possibly tunable changes in friction may have a significant impact on the design of coatings for biosensors and for actuation devices based on stimulus-responsive hydrogels.


Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle.
Alopecia areata (AA) is an autoimmune hair loss disease caused by a cell-mediated immune attack of the lower portion of the cycling hair follicle. Feeding mice 3-7 times the recommended level of dietary vitamin A accelerated the progression of AA in the graft-induced C3H/HeJ mouse model of AA. In this study, we also found that dietary vitamin A, in a dose dependent manner, activated the hair follicle stem cells (SCs) to induce the development and growth phase of the hair cycle (anagen), which may have made the hair follicle more susceptible to autoimmune attack. Our purpose here is to determine the mechanism by which dietary vitamin A regulates the hair cycle. We found that vitamin A in a dose-dependent manner increased nuclear localized beta-catenin (CTNNB1; a marker of canonical wingless-type Mouse Mammary Tumor Virus integration site family (WNT) signaling) and levels of WNT7A within the hair follicle bulge in these C3H/HeJ mice. These findings suggest that feeding mice high levels of dietary vitamin A increases WNT signaling to activate hair follicle SCs.


Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies.
Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations. We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia. We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model. Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women. Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.


Human albumin administration in subarachnoid hemorrhage: results of an international survey.
Subarachnoid hemorrhage (SAH) is a devastating disease. Nimodipine is the only medical treatment shown to improve outcome of SAH patients. Human albumin (ALB) may exert neuroprotection in SAH. However, current usage of ALB in SAH is not known. We conducted an international survey of clinicians involved in the care of SAH patients to determine current practice of ALB administration in SAH. We constructed a 27-question survey. Our sampling frame consisted of neurointensivists, general intensivists, neurocritical care nurses, critical care pharmacists, and neurosurgeons. The survey was available from 11/15/2012 to 12/15/2012. We performed mostly descriptive statistical analysis. We obtained 362 responses from a diverse range of world regions. Most respondents were intensivist physicians (88 %), who worked in academic institutions (73.5 %) with a bed capacity >500 (64.1 %) and an established institutional management protocol for SAH patients (70.2 %). Most respondents (83.5 %) indicated that their institutions do not incorporate ALB in their protocol, but half of them (45.9 %) indicated using ALB outside it. ALB administration is influenced by several factors: geographic variation (more common among US respondents); institutions with a dedicated neuroICU; and availability of SAH management protocol. Most respondents (75 %) indicated that a clinical trial to test the efficacy of ALB in SAH is needed. In this survey we found that ALB administration in SAH patients is common and influenced by several factors. Majority of respondents support a randomized clinical trial to determine the safety and efficacy of ALB administration in SAH patients.


Hemoglobin switching in sheep and goats. V. Effect of erythropoietin concentration on in vitro erythroid colony growth and globin synthesis.
Erythroid colonies were generated in response to erythropoietin in plasma clot cultures of sheep and goat bone marrow cells. At low concentration erythropoietin only hemoglobin A (betaA globin) was synthesized in goat cultures, but at high concentrations 50% of the hemoglobin synthesized was hemoglobin C (betaC globin). This effect of erythropoietin on the expression of a specific beta globin gene was manifested only after 72 h in vitro and followed the development of erythroid colonies. Sheep colonies behaved differently from those of goat in that little or no betaC globin synthesis occurred even at high erythropoietin concentration. To investigate this difference, sheep marrow cells were fractionated by unit gravity sedimentation. The erythroid colony-forming cells sedimented more rapidly (3.5-6mm/h) than the hemoglobinized eththroid precursors (1-3.5 mm/h), suggesting that the colonies were formed from an early erythroid precursor, However, the colonies formed from the sheep marrow fractions synthesized only betaA globin even at concentrations of erythropoietin sufficient to stimulate betaC globin synthesis in goat colonies. Morphologically, the goat colonies were larger and more mature than those of the sheep. By 96 h in vitro three-fourths of the goat colonies contained enucleated red cells compared to only 3% of the sheep colonies. Thus, erythropoietin had an equivalent effect in stimulating erythroid colony growth from the marrow of both species although there were both biochemical and morphological differences between the colonies. Hemoglobin switching appeared to require exposure of an early precursor to high erythropoietin concentration, but the results with sheep marrow suggested that the rate of colony growth and cellular maturation might also be important.


"That's enough patients for everyone!": Local stakeholders' views on attracting patients into Barbados and Guatemala's emerging medical tourism sectors.
Medical tourism has attracted considerable interest within the Latin American and Caribbean (LAC) region. Governments in the region tout the economic potential of treating foreign patients while several new private hospitals primarily target international patients. This analysis explores the perspectives of a range of medical tourism sector stakeholders in two LAC countries, Guatemala and Barbados, which are beginning to develop their medical tourism sectors. These perspectives provide insights into how beliefs about international patients are shaping the expanding regional interest in medical tourism. Structured around the comparative case study methodology, semi-structured interviews were conducted with 50 medical tourism stakeholders in each of Guatemala and Barbados (n = 100). To capture a comprehensive range of perspectives, stakeholders were recruited to represent civil society (n = 5/country), health human resources (n = 15/country), public health care and tourism sectors (n = 15/country), and private health care and tourism sectors (n = 15/country). Interviews were transcribed verbatim, coded using a collaborative process of scheme development, and analyzed thematically following an iterative process of data review. Many Guatemalan stakeholders identified the Guatemalan-American diaspora as a significant source of existing international patients. Similarly, Barbadian participants identified their large recreational tourism sector as creating a ready source of foreign patients with existing ties to the country. While both Barbadian and Guatemalan medical tourism proponents share a common understanding that intra-regional patients are an existing supply of international patients that should be further developed, the dominant perception driving interest in medical tourism is the proximity of the American health care market. In the short term, this supplies a vision of a large number of Americans lacking adequate health insurance willing to travel for care, while in the long term, the Affordable Care Act is seen to be an enormous potential driver of future medical tourism as it is believed that private insurers will seek to control costs by outsourcing care to providers abroad. Each country has some comparative advantage in medical tourism. Assumptions about a large North American patient base, however, are not supported by reliable evidence. Pursuing this market could incur costs borne by patients in their public health systems.


Nicotine attenuates arachidonic acid-induced overexpression of nitric oxide synthase in cultured spinal cord neurons.
Primary spinal cord trauma can initiate a cascade of pathophysiologic events which markedly contribute to the expansion and amplification of the primary insult. The detailed mechanisms of these secondary neurochemical reactions are largely unknown; however, they involve membrane lipid derangements with the release of free fatty acids, in particular, arachidonic acid (AA). AA can induce several injury effects on spinal cord neurons. We hypothesize that upregulation of nitric oxide synthase (NOS) is among the most important mechanisms of arachidonic-acid-induced neuronal dysfunction and that nicotine can attenuate this effect. To study these hypotheses, spinal cord neurons were exposed to AA and/or nicotine, and several markers of neuronal nitric oxide synthase (nNOS) metabolism were measured. In addition, cotreatments with either inhibitors of nicotinic receptors or inhibitors of specific NOS isoforms were employed. Treatment with AA markedly increased activity of nNOS, as well as mRNA and protein levels of this enzyme. Changes in nNOS expression were accompanied by an increase in cellular cGMP and medium nitrite levels. Pretreatment with nicotine decreased AA-induced overexpression of nNOS and elevation of nitrite levels. In addition, it appeared that these nicotine effects could be partially modulated both by the alpha7 nicotinic receptors or by nonreceptor mechanisms. Alternatively, the observed changes could also be mediated by an alternate nicotinic receptor mechanism which is not blocked by alpha-bungarotoxin or mecamylamine. Results of the present study indicate that exposure to AA can lead to induction of nNOS in cultured spinal cord neurons. In addition, nicotine can exert a neuroprotective effect by attenuation of AA-induced upregulation of nNOS metabolism. These data may have therapeutic implications for the treatment of acute spinal cord trauma.


Cleaner wrasse prefer client mucus: support for partner control mechanisms in cleaning interactions.
Recent studies on cleaning behaviour suggest that there are conflicts between cleaners and their clients over what cleaners eat. The diet of cleaners usually contains ectoparasites and some client tissue. It is unclear, however, whether cleaners prefer client tissue over ectoparasites or whether they include client tissue in their diet only when searching for parasites alone is not profitable. To distinguish between these two hypotheses, we trained cleaner fish Labroides dimidiatus to feed from plates and offered them client mucus from the parrotfish Chlorurus sordidus, parasitic monogenean flatworms, parasitic gnathiid isopods and boiled flour glue as a control. We found that cleaners ate more mucus and monogeneans than gnathiids, with gnathiids eaten slightly more often than the control substance. Because gnathiids are the most abundant ectoparasites, our results suggest a potential for conflict between cleaners and clients over what the cleaner should eat, and support studies emphasizing the importance of partner control in keeping cleaning interactions mutualistic.


Controlled delivery of SDF-1α and IGF-1: CXCR4(+) cell recruitment and functional skeletal muscle recovery.
Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1α) alone or in combination with insulin-like growth factor-I (SDF-1α/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1α will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1α alone (PEG-Fib/SDF-1α) or in combination with IGF-I (PEG-Fib/SDF-1α/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1α treatment, functional analysis showed no benefit from PEG-Fib/SDF-1α therapy, while dual delivery of PEG-Fib/SDF-1α/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1α-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient.


'It's like the bad guy in a movie who just doesn't die': a qualitative exploration of young people's adaptation to eczema and implications for self-care.
Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course. To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema. This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old. Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema. For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.


The effects of gender on the neural substrates of pitch memory.
Imaging studies have indicated that males and females differ anatomically in brain regions thought to underlie language functions. Functional studies have corroborated this difference by showing gender differences in terms of language processing with females relying on less lateralized processing strategies than males. Gender differences in musical functions might show similar differences in functional asymmetries, although no detailed study has been performed. The current study employed a pitch memory task while acquiring functional magnetic resonance images to investigate possible differences in hemispheric processing between males and females. Gender differences were found in the time course of activation (during the first four imaging time points after the end of the auditory stimulus-"perceptual phase"-and the subsequent three imaging time points after the end of the auditory stimulus-"memory phase") in both anterior and posterior perisylvian regions. Male subjects had greater lateralized activations (left > right) in anterior and posterior perisylvian regions during the "perceptual" as well as during the "memory" phase. There was a trend for males to have more cerebellar activation than females. Females showed more prominently posterior cingulate/retrosplenial cortex activation compared to males. Although activation patterns differed, there was no difference in the behavioral performance between both genders. These data indicate that similar to language studies, males rely more on left lateralized hemispheric processing even for basic pitch tasks.


* Biomimetic Versus Sintered Calcium Phosphates: The In Vitro Behavior of Osteoblasts and Mesenchymal Stem Cells.
The fabrication of calcium phosphates using biomimetic routes, namely, precipitation processes at body temperature, results in distinct features compared to conventional sintered calcium phosphate ceramics, such as a high specific surface area (SSA) and micro- or nanometric crystal size. The aim of this article is to analyze the effects of these parameters on cell response, focusing on two bone cell types: rat mesenchymal stem cells (rMSCs) and human osteoblastic cells (SaOS-2). Biomimetic calcium-deficient hydroxyapatite (CDHA) was obtained by a low temperature setting reaction, and α-tricalcium phosphate (α-TCP) and β-tricalcium phosphate were subsequently obtained by sintering CDHA either at 1400°C or 1100°C. Sintered stoichiometric hydroxyapatite (HA) was also prepared using ceramic routes. The materials were characterized in terms of SSA, skeletal density, porosity, and pore size distribution. SaOS-2 cells and rMSCs were seeded either directly on the surfaces of the materials or on glass coverslips subsequently placed on top of the materials to expose the cells to the CaP-induced ionic changes in the culture medium, while avoiding any topography-related effects. CDHA produced higher ionic fluctuations in both cell culture media than sintered ceramics, with a strong decrease of calcium and a release of phosphate. Indirect contact cell cultures revealed that both cell types were sensitive to these ionic modifications, resulting in a decrease in proliferation rate, more marked for CDHA, this effect being more pronounced for rMSCs. In direct contact cultures, good cell adhesion was found on all materials, but, while cells were able to proliferate on the sintered calcium phosphates, cell number was significantly reduced with time on biomimetic CDHA, which was associated to a higher percentage of apoptotic cells. Direct contact of the cells with biomimetic CDHA resulted also in a higher alkaline phosphatase activity for both cell types compared to sintered CaPs, indicating a promotion of the osteoblastic phenotype.


Diversity and characterization of culturable fungi from marine sediment collected from St. Helena Bay, South Africa.
Marine fungi are known to originate from a wide variety of habitats within the marine environment. Marine sediment represents one environmental niche, with most fungi occurring in these sediments being facultative marine fungi with terrestrial origins. It has not been proven whether these fungi merely survive the harsh environmental conditions presented by the ocean sediment, as opposed to playing an active role in this ecological niche. During this study, marine sediment was collected from St. Helena Bay, on the west coast of the Western Cape, South Africa. Using dilution, enrichment, and repetitive culturing techniques, 59 fungal isolates were obtained from marine sediments and identified to at least genus level using morphological and molecular methods. Moreover, a series of tests were performed to characterize the physical and physicochemical attributes of the isolates. Results showed that the isolates not only survived but also had the potential to grow in the natural conditions present in this environment. Extracellular cellulase was produced by the filamentous fungal isolates indicating their probable role in detrital decay processes and therefore the carbon cycle on the ocean bed. Also, denitrification patterns were observed when isolates were grown in liquid media amended with NaNO(2), NaNO(3), and (NH(4))SO(4), implicating that these fungi have the potential to play an active role in denitrification, co-denitrification, and ammonification phases of nitrogen cycles occurring in the marine sediments.


Integrated Analysis of Multiple Biomarkers from Circulating Tumor Cells Enabled by Exclusion-Based Analyte Isolation.
There is a critical clinical need for new predictive and pharmacodynamic biomarkers that evaluate pathway activity in patients treated with targeted therapies. A microscale platform known as VERSA (versatile exclusion-based rare sample analysis) was developed to integrate readouts across protein, mRNA, and DNA in circulating tumor cells (CTC) for a comprehensive analysis of the androgen receptor (AR) signaling pathway. Utilizing exclusion-based sample preparation principles, a handheld chip was developed to perform CTC capture, enumeration, quantification, and subcellular localization of proteins and extraction of mRNA and DNA. This technology was validated across integrated endpoints in cell lines and a cohort of patients with castrate-resistant prostate cancer (CRPC) treated with AR-targeted therapies and chemotherapies. The VERSA was validated in cell lines to analyze AR protein expression, nuclear localization, and gene expression targets. When applied to a cohort of patients, radiographic progression was predicted by the presence of multiple AR splice variants and activity in the canonical AR signaling pathway. AR protein expression and nuclear localization identified phenotypic heterogeneity. Next-generation sequencing with the FoundationOne panel detected copy number changes and point mutations. Longitudinal analysis of CTCs identified acquisition of multiple AR variants during targeted treatments and chemotherapy. Complex mechanisms of resistance to AR-targeted therapies, across RNA, DNA, and protein endpoints, exist in patients with CRPC and can be quantified in CTCs. Interrogation of the AR signaling pathway revealed distinct patterns relevant to tumor progression and can serve as pharmacodynamic biomarkers for targeted therapies. Clin Cancer Res; 1-11. ©2016 AACR.


Prevalence of and environmental factors associated with aerosolised Aspergillus spores at a zoological park.
Aspergillus is a significant pathogen in zoological species, although information on environmental variables influencing fungal prevalence in zoological settings are lacking. The objective of the study was to estimate the prevalence of and to identify environmental factors associated with aerosolised Aspergillus spores at a zoological park to advance the understanding of fungal exposure as a first step towards improved mitigation strategies for susceptible animals. Twenty-one locations were sampled for presence of Aspergillus species using the SAS Super 180 Microbial Air Sampler, while twenty-two environmental factors were evaluated every two weeks at SeaWorld of California during two 12-month periods. In each period, the frequency of investigated environmental factors was compared between samples classified as positive or negative for Aspergillus species using logistic regression. Prevalence of Aspergillus was higher (P<0.05) during the second 12-month period (110/525 or 21 per cent), compared with the first period (62/483 or 13 per cent). In both periods, positive Aspergillus samples were associated with indoor sites without high-efficiency particulate air (HEPA) filtration systems and other infection control measures (adjusted OR=4.33 and 5.19, P<0.01) or outdoor sites (adjusted OR=2.50 and3.79, P≤0.05), compared to indoor sites with HEPA filtration systems and other infection control measures, after controlling for season. Burden of airborne Aspergillus can be higher in indoor sites without HEPA filtration systems than in outdoor sites. The use of HEPA filtration systems and other infection control measures can mitigate the burden of Aspergillus. Risk-based surveillance systems that target indoor areas without HEPA filtration systems can be an efficient approach for early detection of high burden of Aspergillus at zoological parks.


Community proteomics of a natural microbial biofilm.
Using genomic and mass spectrometry–based proteomic methods, we evaluated gene expression, identified key activities, and examined partitioning of metabolic functions in a natural acid mine drainage (AMD) microbial biofilm community. We detected 2033 proteins from the five most abundant species in the biofilm, including 48% of the predicted proteins from the dominant biofilm organism, Leptospirillum group II. Proteins involved in protein refolding and response to oxidative stress appeared to be highly expressed, which suggests that damage to biomolecules is a key challenge for survival. We validated and estimated the relative abundance and cellular localization of 357 unique and 215 conserved novel proteins and determined that one abundant novel protein is a cytochrome central to iron oxidation and AMD formation.


Effects of solarization and ammonium amendments on plant-parasitic nematodes.
The effects of soil solarization and ammonium bicarbonate or ammonium sulfate against plant-parasitic nematodes on yellow squash (Cucurbita pepo) and on vinca (Catharanthus roseus) were evaluated at two sites. Solarization for 3 weeks in the spring suppressed population levels of Belonolaimus longicaudatus, Criconemella spp., and Dolichodorus heterocephalus throughout the growing season on both crops at both sites. Levels of Meloidogyne incognita were suppressed initially, but population densities increased by the end of the crop in several cases. In one site, numbers of Paratrichodorus minor resurged following solarization to levels that were greater than those present in unsolarized control plots. The effect of solarization was not enhanced by combination with ammonium amendments, but, in one site, application of ammonium bicarbonate or ammonium sulfate resulted in lower numbers of B. longicaudatus than in the unamended control. Additional research and improved efficacy of candidate amendments are required before they can be successfully integrated with solarization for nematode management. Efficacy of solarization against plant-parasitic nematodes was achieved despite a relatively short (3 weeks) solarization period.


Internet-Based Interventions for Adults With Hearing Loss, Tinnitus, and Vestibular Disorders: A Systematic Review and Meta-Analysis.
Internet-based interventions have been developed to improve access to audiovestibular health care. This review aimed to identify outcomes of Internet interventions for adults with hearing loss, tinnitus, and vestibular disorders. Electronic databases and manual searches were performed to identify studies meeting eligibility for inclusion. Fifteen studies (1,811 participants) met the inclusion criteria, with nine studies targeting tinnitus distress, five considering hearing loss, and one for vestibular difficulties. Only the tinnitus and hearing loss Internet intervention studies were eligible for data synthesis. Internet-based interventions for hearing loss were diverse. Overall, they showed no significant effects, although a statistically significant moderate effect (d = 0.59) was found after removing the study with the highest risk of bias (as a result of high attrition). Most Internet-based interventions for tinnitus provided cognitive behavioural therapy. They yielded statistically significant mean effect sizes for reducing tinnitus distress compared with both inactive (d = 0.59) and active controls (d = 0.32). Significant effects were also present for the secondary outcomes of anxiety, depression, insomnia, and quality of life (combined effect d = 0.28). Only Internet-based interventions for tinnitus evaluated the 1-year postintervention effects indicated that results were maintained long term (d = 0.45). Scientific study quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach and found to vary from very low to moderate. This review indicates the potential of Internet interventions for tinnitus to provide evidence-based accessible care. There is a need for additional high-quality evidence before conclusive results can be established regarding the effects of audiovestibular Internet interventions.


Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion.
Colony stimulating factor-1 (CSF-1) regulates macrophage morphology and motility, as well as mononuclear phagocytic cell proliferation and differentiation. The CSF-1 receptor (CSF-1R) transduces these pleiotropic signals through autophosphorylation of eight intracellular tyrosine residues. We have used a novel bone-marrow-derived macrophage cell line system to examine specific signaling pathways activated by tyrosine-phosphorylated CSF-1R in macrophages. Screening of macrophages expressing a single species of CSF-1R with individual tyrosine-to-phenylalanine residue mutations revealed striking morphological alterations upon mutation of Y721. M⁻/⁻.Y721F cells were apolar and ruffled poorly in response to CSF-1. Y721-P-mediated CSF-1R signaling regulated adhesion and actin polymerization to control macrophage spreading and motility. Moreover, the reduced motility of M⁻/⁻.Y721F macrophages was associated with their reduced capacity to enhance carcinoma cell invasion. Y721 phosphorylation mediated the direct association of the p85 subunit of phosphoinositide 3-kinase (PI3K) with the CSF-1R, but not that of phospholipase C (PLC) γ2, and induced polarized PtdIns(3,4,5)P₃ production at the putative leading edge, implicating PI3K as a major regulator of CSF-1-induced macrophage motility. The Y721-P-motif-based motility signaling was at least partially independent of both Akt and increased Rac and Cdc42 activation but mediated the rapid and transient association of an unidentified ~170 kDa phosphorylated protein with either Rac-GTP or Cdc42-GTP. These studies identify CSF-1R-Y721-P-PI3K signaling as a major pathway in CSF-1-regulated macrophage motility and provide a starting point for the discovery of the immediate downstream signaling events.


Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways.
It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients. Forty-five moderate asthmatics were administered sulforaphane (100 μmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption. Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly. These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.


The when and how of the gynaecological examination: a survey among Norwegian general practitioners.
Introduction: Little is known about the indications general practitioners (GPs) perceive as relevant for performing gynaecological examinations (GEs), how GPs master the GE and associated procedures, and how they handle the sensitive nature of GEs. Methods: In 2015, 70 medical students at the University of Bergen distributed a questionnaire to all 175 GPs in the practices they visited. The questions covered practical routines related to GEs, insertion of intrauterine device, frequency of GEs in different clinical settings and use of assisting personnel. Statistical analyses included chi-square tests and multiple logistic regressions adjusting for age, gender, specialization and localization. Results: Ninety male and 61 female GPs (87% of invited GPs) responded to the questionnaire. A minority (8%) usually had other staff present during GEs. Compared with female colleagues, male GPs performed bimanual palpation significantly less often in connection with routine Pap smear (AOR 0.3 (95% CI 0.1-0.6)). Twenty-eight percent of the GPs stated that they often/always omitted the GE if the patient was anxious about GE and 35% when the patient asked for referral to a gynaecologist. Omission was more frequent among male GPs. When the GP decided to refer to a gynaecologist based on the patient's symptoms, more male than female GPs omitted GE (AOR 2.5 (95% CI 1.1-5.4)). Conclusion: Male gender of the GP may be associated with barriers to medical evaluation of pelvic symptoms in women, potentially leading to substandard care. Possibly, however, male GPs' reluctance to perform the GE may also limit unnecessary bimanual palpation in asymptomatic women.


Prospective matched study on comparison of volumetric-modulated arc therapy and intensity-modulated radiotherapy for nasopharyngeal carcinoma: dosimetry, delivery efficiency and outcomes.
Background: The purpose of this study is to assess the feasibility of volumetric-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients by comparing the physical dosimetry, delivery efficiency and clinical outcomes with intensity-modulated radiotherapy (IMRT). Methods: A prospective matched study was performed for patients with newly diagnosed NPC who underwent VMAT or IMRT. The patients in two groups were equally matched in terms of gender, age, tumor stage and chemotherapy. The target coverage, homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV), organs at risk (OARs) sparing, average treatment time and clinical outcomes were analyzed. Results: From June 2013 to August 2015, a total of 80 patients were enrolled in this study, with 40 patients in each group. The coverage of PTV was similar for both groups. D2 was observed slight difference only in early stage disease (T1-2) (VMAT vs. IMRT, 7494±109 cGy vs. 7564±92 cGy; p=0.06). The HI of VMAT group was better than that of IMRT group (p=0.001), whereas CI was slightly worse (p=0.061). The maximum doses received by the brain stem, spinal cord, and optic nerve of VMAT were higher than those of IMRT (p<0.05). But the irradiation volumes in healthy tissue were generally lower for VMAT group, with significant differences in V20, V25 and V45 (p<0.05). With regard to the delivery efficiency compared with IMRT (1160 ± 204s), a 69% reduction in treatment time was achieved by VMAT (363 ± 162s). Both groups had 5 cases of nasopharyngeal residual lesions after radiotherapy. The 2-year estimated local relapse-free survival, regional relapse-free survival and locoregional relapse-free survival, distant metastasis-free survival, disease-free survival and overall survival were similar between two groups, with the corresponding rates of 100%, 97.4%, 97.4%, 90.0%, 90.0% and 92.4% in VMAT group, and 100%, 100%, 100%, 95.0%, 95.0% and 97.5% in IMRT group, respectively. Conclusions: Both VMAT and IMRT can meet the clinical requirements for the treatment of NPC. The short-term tumor regression rates and 2-year survival rates with the two techniques are comparable. The faster treatment time benefits of VMAT will enable more patients to receive precision radiotherapy.


Electrohypersensitivity: state-of-the-art of a functional impairment.
Recently, a new category of persons, claiming to suffer from exposure to electromagnetic fields, has been described in the literature. In Sweden, electrohypersensitivity (EHS) is an officially fully recognized functional impairment (i.e., it is not regarded as a disease). Survey studies show that somewhere between 230,000-290,000 Swedish men and women report a variety of symptoms when being in contact with electromagnetic field (EMF) sources. The aim of our studies has been to investigate possible alterations, in the cellular and neuronal systems of these person' skin. As controls, age- and sex-matched persons, without any subjective or clinical symptoms or dermatological history, served. Immunohistochemistry using antisera to the previously characterized marker substances of interest has been utilized. In summary, it is evident from our preliminary data that various alterations are present in the electrohypersensitive person' skin. In view of recent epidemiological studies, pointing to a correlation between long-term exposure from power-frequent magnetic fields or microwaves and cancer, our data ought to be taken seriously and further analyzed.


Patients fifty years and older attending two sexually transmitted disease clinics in Baltimore, Maryland.
Many individuals remain sexually active into their eighth decade. Surveillance data suggest that rates of sexually transmitted infections in older patients are increasing. We compared demographics, risk behaviors, and predictors of acute infections in patients 50 years and older versus younger patients attending sexually transmitted disease clinics in Baltimore, Maryland. This was a retrospective study from a large electronic database of visits to two urban sexually transmitted disease clinics between 2005 and 2010. Proportions were compared using the Chi square test. Logistic regression was used to assess predictors of acute sexually transmitted infections in older versus younger groups. It was found that patients over 50 were more likely than younger patients to report never using condoms (32.6% [CI 0.31-0.34] versus 24.1% [CI 0.23-0.25]). The overall prevalence of acute sexually transmitted infections was 18.1% (CI 0.17-0.19) in older and 25.8% (CI 0.25-0.27) in younger patients. Older women were more likely to be diagnosed with trichomoniasis (21.5% [CI 18.6-24.5] versus 13.1% [CI 11.5-14.8]). Black race was predictive of having an acute sexually transmitted infections in younger men (OR 2.2 [CI 1.47-3.35]) and women (OR 2.7 [CI 1.34-5.30]) but not in older men (OR 1.2 [CI 0.79-1.73]) or women (OR 1.2 [CI 0.43-3.15]). Older age was associated with a decreased risk of acute STI diagnosis in younger men and older women only, while having had sex for money or drugs in the past month was predictive only in younger women. Reporting symptoms and increasing numbers of sexual partners in the last six months was predictive of acute sexually transmitted infection diagnosis in all age groups. Older patients seeking care at sexually transmitted disease clinics engage in important risk behaviors. Race, a factor predictive of acute sexually transmitted infections in younger patients is not a significant predictor of sexually transmitted infections in older persons.


Aflatoxicosis in nine dogs after exposure to contaminated commercial dog food.
The purpose of this study was to characterize light and electron microscopic findings from 9 dogs that had consumed aflatoxin-contaminated commercial dog food from recalled batches. Four dogs died and 5 were euthanized after signs of liver failure. Analysis of feed and liver samples confirmed exposure to aflatoxin. Of the 9 dogs, 8 had classic signs of liver failure, and 1 had signs of liver failure. Enlarged, pale yellow livers were seen macroscopically at necropsy in the dogs with subacute hepatopathy, and cirrhosis was noted in the dog with chronic hepatopathy. Histopathologic findings included hepatic lipidosis, portal fibroplasia, and biliary hyperplasia, which supported a diagnosis of subacute toxic hepatopathy in the 8 symptomatic animals. Marked lobular atrophy, bridging portal fibrosis, and regenerative hepatocellular nodules characterized the dog with chronic hepatopathy. Electron microscopy revealed marked hepatocellular lipid vacuolation and early fibroplasia in the dogs with acute hepatopathy and marked fibrosis and regeneration in the dog with chronic hepatopathy. Analysis of feed for aflatoxin consistently revealed high levels of aflatoxin B1 (range of 223-579 ppb), and hepatic tissue contained elevated levels of aflatoxin B1 metabolite M1 (0.6-4.4 ppb). Although dogs are not commonly affected by aflatoxicosis, they are highly susceptible and can present with classic signs of acute or chronic hepatopathy. Characteristic gross, histologic, and electron microscopic changes help pathologists determine a presumptive toxic insult. Detecting aflatoxins or their metabolites in feed or liver specimens can help confirm the diagnosis of aflatoxicosis.


Mineralogical variables that control the antibacterial effectiveness of a natural clay deposit.
As antibiotic-resistant bacterial strains emerge and pose increased global health risks, new antibacterial agents are needed as alternatives to conventional antimicrobials. Naturally occurring antibacterial clays have been identified which are effective in killing antibiotic-resistant bacteria. This study examines a hydrothermally formed antibacterial clay deposit near Crater Lake, OR (USA). Our hypothesis is that antibacterial clays buffer pH and Eh conditions to dissolve unstable mineral phases containing transition metals (primarily Fe(2+)), while smectite interlayers serve as reservoirs for time release of bactericidal components. Model pathogens (Escherichia coli ATCC 25922 and Staphylococcus epidermidis ATCC 14990) were incubated with clays from different alteration zones of the hydrothermal deposit. In vitro antibacterial susceptibility testing showed that reduced mineral zones were bactericidal, while more oxidized zones had variable antibacterial effect. TEM images showed no indication of cell lysis. Cytoplasmic condensation and cell wall accumulations of <100 nm particles were seen within both bacterial populations. Electron energy loss analysis indicates precipitation of intracellular Fe(3+)-oxide nanoparticles (<10 nm) in E. coli after 24 h. Clay minerals and pyrite buffer aqueous solutions to pH 2.5-3.1, Eh > 630 mV and contain elevated level (mM) of soluble Fe (Fe(2+) and Fe(3+)) and Al(3+). Our interpretation is that rapid uptake of Fe(2+) impairs bacterial metabolism by flooding the cell with excess Fe(2+) and overwhelming iron storage proteins. As the intracellular Fe(2+) oxidizes, it produces reactive oxygen species that damage biomolecules and precipitates Fe-oxides. The ability of antibacterial clays to buffer pH and Eh in chronic non-healing wounds to conditions of healthy skin appears key to their healing potential and viability as an alternative to conventional antibiotics.


Studying mechanosensitive ion channels using liposomes.
Mechanosensitive (MS) ion channels are the primary molecular transducers of mechanical force into electrical and/or chemical intracellular signals in living cells. They have been implicated in innumerable mechanosensory physiological processes including touch and pain sensation, hearing, blood pressure control, micturition, cell volume regulation, tissue growth, or cellular turgor control. Much of what we know about the basic physical principles underlying the conversion of mechanical force acting upon membranes of living cells into conformational changes of MS channels comes from studies of MS channels reconstituted into artificial liposomes. Using bacterial MS channels as a model, we have shown by reconstituting these channels into liposomes that there is a close relationship between the physico-chemical properties of the lipid bilayer and structural dynamics bringing about the function of these channels.


A new sono-electrochemical method for enhanced detoxification of hydrophilic chloroorganic pollutants in water.
A new method for detoxification of hydrophilic chloroorganic pollutants in effluent water was developed, using a combination of ultrasound waves, electrochemistry and Fenton's reagent. The advantages of the method are exemplified using two target compounds: the common herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and its derivative 2,4-dichlorophenol (2,4-DCP). The high degradation power of this process is due to the large production of oxidizing hydroxyl radicals and high mass transfer due to sonication. Application of this sono-electrochemical Fenton process (SEF) treatment (at 20 kHz) with quite a small current density, accomplished almost 50% oxidation of 2,4-D solution (300 ppm, 1.2 mM) in just 60 s. Similar treatments ran for 600 s resulted in practically full degradation of the herbicide; sizable oxidation of 2,4-DCP also occurs. The main intermediate compounds produced in the SEF process were identified. Their kinetic profile was measured and a chemical reaction scheme was suggested. The efficiency of the SEF process is tentatively much higher than the reference degradation methods and the time required for full degradation is considerably shorter. The SEF process maintains high performance up to concentrations which are higher than reference methods. The optimum concentration of Fe2+ ions required for this process was found to be of about 2 mM, which is lower than that in reference techniques. These findings indicate that SEF process may be an effective method for detoxification of environmental water.


A mutant dec-1 transgene induces dominant female sterility in Drosophila melanogaster.
The Drosophila dec-1 gene produces three proproteins required for female fertility and eggshell assembly. The three proproteins are distinguished by their C termini. Fc106, the most abundant proprotein, is cleaved within the vitelline membrane to three mature derivatives in a developmentally regulated manner. To define sequences within fc106 that are critical for its function, we created wild-type and mutant versions of an fc106 cDNA transgene. The functional consequences of the mutations were assessed in dec-14, a female-sterile splicing mutant that does not produce the fc106 isoform. The fertility of dec-14 females was restored by the introduction of either a wild-type transgene or a transgene bearing a C-terminal deletion that included fc106-specific sequences. Surprisingly, the removal of internal coding sequences created an aberrant DEC-1 proprotein that induced female sterility when introduced into wild-type flies. Dominant female sterility was not associated with larger deletions that included the fc106 N terminus, suggesting that abnormal juxtaposition of N- and C-terminal sequences in the aberrant proprotein interfered with endogenous DEC-1 proteins. Changes in the fractionation behavior of the endogenous fc106 C-terminal derivative, s60, and morphological changes in the endochorion in response to expression of the aberrant proprotein support this interpretation.


Extraskeletal effects of vitamin D: potential impact on WV disease morbidity and mortality.
Vitamin D is an essential nutrient and a secosteroid hormone that regulates many physiologic processes beyond calcium and bone homeostasis. These "extraskeletal" effects are impacted by the circulating levels of the storage form of vitamin D, 25-hydroxyvitamin D3. Levels of vitamin D can be detected after completing a simple 25(OH)D blood test. Vitamin D deficiency (< 30 ng/mL) is associated with a higher risk of many chronic diseases including, but not limited to, fourteen types of cancers, type 1 and 2 diabetes mellitus, obesity, cardiovascular disease, hypertension, stroke, and asthma. This article explores the association between vitamin D deficiency and the burden of chronic diseases in West Virginia.


Proliferation and apoptosis of hippocampal granule cells require local oestrogen synthesis.
Ovarian oestrogens have been demonstrated to influence neurogenesis in the dentate gyrus. As considerable amounts of oestrogens are synthesized in hippocampal neurones, we focused on the role of hippocampus-derived estradiol on proliferation and apoptosis of granule cells in vitro. We used hippocampal dispersion cultures, which allowed for cultivation of the cells under steroid- and serum-free conditions and monitoring of oestrogen synthesis. To address the influence of hippocampus-derived estradiol on neurogenesis, we inhibited oestrogen synthesis by treatment of hippocampal cell cultures with letrozole, a specific aromatase inhibitor. Alternatively, we used siRNA against steroidogenic acute regulatory protein (StAR). The number of proliferative cells decreased whereas the number of apoptotic cells increased dose-dependently, in response to reduced estradiol release into the medium after treatment with letrozole. This also held true for siRNA against StAR transfected cell cultures. Application of estradiol to the medium had no effect on proliferation and apoptosis whereas the anti-proliferative and pro-apoptotic effects of StAR knock-down and letrozole treatment were restored by treatment of the cultures with estradiol. Our findings suggest that neurogenesis and apoptosis in the hippocampus require a defined range of estradiol concentrations that is physiologically provided by hippocampal cells but not by gonads.


Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial.
An association between ocular adnexal MALT lymphoma (OAL) and Chlamydia psittaci (Cp) infection has been proposed, and recent reports suggest that doxycycline treatment causes tumor regression in patients with Cp-related OAL. The effectiveness of doxycycline treatment in Cp-negative OAL has not been tested. In a prospective trial, 27 OAL patients (15 newly diagnosed and 12 having experienced relapse) were given a 3-week course of doxycycline therapy. Objective lymphoma response was assessed by computerized tomography scans or magnetic resonance imaging at 1, 3, and 6 months after the conclusion of therapy and every 6 months during follow-up. Cp infection in patients was determined by touchdown enzyme time-release polymerase chain reaction (TETR-PCR). Statistical tests were two-sided. Eleven patients were Cp DNA-positive and 16 were Cp DNA negative. Doxycycline was well tolerated. At a median follow-up of 14 months, lymphoma regression was complete in six patients, and a partial response (> or = 50% reduction of all measurable lesions) was observed in seven patients (overall response rate [complete and partial responses] = 48%). Lymphoma regression was observed in both Cp DNA-positive patients (seven of 11 experienced regression) and Cp DNA-negative patients (six of 16 experienced regression) (64% versus 38%; P = .25, Fisher's exact test). The three patients with regional lymphadenopathies and three of the five patients with bilateral disease achieved objective response. In relapsed patients, response was observed both in previously irradiated and nonirradiated patients. The 2-year failure-free survival rate among the doxycycline-treated patients was 66% (95% confidence interval = 54 to 78), and 20 of the 27 patients were progression free. Doxycycline is a fast, safe, and active therapy for Cp DNA-positive OAL that was effective even in patients with multiple failures involving previously irradiated areas or regional lymphadenopathies. The responses observed in PCR-negative OAL may suggest a need for development of more sensitive methods for Cp detection and investigation of the potential role of other doxycycline-sensitive bacteria.


Crystal structure of tRNA m1G9 methyltransferase Trm10: insight into the catalytic mechanism and recognition of tRNA substrate.
Transfer RNA (tRNA) methylation is necessary for the proper biological function of tRNA. The N(1) methylation of guanine at Position 9 (m(1)G9) of tRNA, which is widely identified in eukaryotes and archaea, was found to be catalyzed by the Trm10 family of methyltransferases (MTases). Here, we report the first crystal structures of the tRNA MTase spTrm10 from Schizosaccharomyces pombe in the presence and absence of its methyl donor product S-adenosyl-homocysteine (SAH) and its ortholog scTrm10 from Saccharomyces cerevisiae in complex with SAH. Our crystal structures indicated that the MTase domain (the catalytic domain) of the Trm10 family displays a typical SpoU-TrmD (SPOUT) fold. Furthermore, small angle X-ray scattering analysis reveals that Trm10 behaves as a monomer in solution, whereas other members of the SPOUT superfamily all function as homodimers. We also performed tRNA MTase assays and isothermal titration calorimetry experiments to investigate the catalytic mechanism of Trm10 in vitro. In combination with mutational analysis and electrophoretic mobility shift assays, our results provide insights into the substrate tRNA recognition mechanism of Trm10 family MTases.


Fire in the Plio-Pleistocene: the functions of hominin fire use, and the mechanistic, developmental and evolutionary consequences.
Fire is a powerful natural force that can change landscapes extremely quickly. Hominins have harnessed this resource for their own purposes, with mechanistic and developmental physiological consequences. In addition, the use of fire has niche constructive effects, altering selective environments for genetic and cultural evolution. We review the record for hominin fire use in the Plio-Pleistocene, before considering the various functions for its use, and the resultant mechanistic and developmental consequences. We also adopt the niche construction framework to consider how the use of fire can modify selective environments, and thus have evolutionary consequences at genetic and cultural levels. The light that fire produces may influence photoperiodicity and alter hormonally-controlled bodily rhythms. Fire used for cooking could have extended the range of foods hominins were able to consume, and reduced digestion costs. This may have contributed to the expansion of the hominin brain and facial anatomy, influenced by a higher quality cooked diet. Fire may also have allowed dispersal into northern areas with much cooler climates than the hominin African origin, posing novel problems that affected diet and social behaviour.


The Sbi protein is a multifunctional immune evasion factor of Staphylococcus aureus.
The second immunoglobulin-binding protein (Sbi) of Staphylococcus aureus has two N-terminal domains that bind the Fc region of IgG in a fashion similar to that of protein A and two domains that can bind to the complement protein C3 and promote its futile consumption in the fluid phase. It has been proposed that Sbi helps bacteria to avoid innate immune defenses. By comparing a mutant defective in Sbi with mutants defective in protein A, clumping factor A, iron-regulated surface determinant H, and capsular polysaccharide, it was shown that Sbi is indeed an immune evasion factor that promotes bacterial survival in whole human blood and the avoidance of neutrophil-mediated opsonophagocytosis. Sbi is present in the culture supernatant and is also associated with the cell envelope. S. aureus strains that expressed truncates of Sbi lacking N-terminal domains D1 and D2 (D1D2) or D3 and D4 (D3D4) or a C-terminal truncate that was no longer retained in the cell envelope were analyzed. Both the secreted and envelope-associated forms of Sbi contributed to immune evasion. The IgG-binding domains contributed only when Sbi was attached to the cell, while only the secreted C3-binding domains were biologically active.


Modeling Somatic Mutations Associated With Neurodevelopmental Disorders in Human Brain Organoids.
Neurodevelopmental disorders (NDDs) are a collection of diseases with early life onset that often present with developmental delay, cognitive deficits, and behavioral conditions. In some cases, severe outcomes such as brain malformations and intractable epilepsy can occur. The mutations underlying NDDs may be inherited or de novo, can be gain- or loss-of-function, and can affect one or more genes. Recent evidence indicates that brain somatic mutations contribute to several NDDs, in particular malformations of cortical development. While advances in sequencing technologies have enabled the detection of these somatic mutations, the mechanisms by which they alter brain development and function are not well understood due to limited model systems that recapitulate these events. Human brain organoids have emerged as powerful models to study the early developmental events of the human brain. Brain organoids capture the developmental progression of the human brain and contain human-enriched progenitor cell types. Advances in human stem cell and genome engineering provide an opportunity to model NDD-associated somatic mutations in brain organoids. These organoids can be tracked throughout development to understand the impact of somatic mutations on early human brain development and function. In this review, we discuss recent evidence that somatic mutations occur in the developing human brain, that they can lead to NDDs, and discuss how they could be modeled using human brain organoids.


Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection.
In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM. To review the evidence for and estimate the effect on neonatal mortality due to pre-term birth complications or infection, of administration of antibiotics to women with pPROM, in low and middle-income countries. We performed a systematic review to update a Cochrane review. Standardized abstraction forms were used. The quality of the evidence provided by individual studies and overall was assessed using an adapted GRADE approach. Eighteen RCTs met our inclusion criteria. Most were from high-income countries and provide strong evidence that antibiotics for pPROM reduce the risk of respiratory distress syndrome [risk ratio (RR) = 0.88; confidence interval (CI) 0.80, 0.97], and early onset postnatal infection (RR = 0.61; CI 0.48, 0.77). The data are consistent with a reduction in neonatal mortality (RR = 0.90; CI 0.72, 1.12). Antibiotics for pPROM reduce complications due to pre-term delivery and post-natal infection in high-income settings. There is moderate quality evidence that, in low-income settings, where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of those due to infection.


Interferometric scattering microscopy (iSCAT): new frontiers in ultrafast and ultrasensitive optical microscopy.
Optical microscopes have for centuries been our window to the microscopic world. The advent of single-molecule optics over the past few decades has ushered in a new era in optical imaging, partly because it has enabled the observation of motion and more recently structure on the nanoscopic scale through the development of super-resolution techniques. The large majority of these studies have relied on the efficient detection of fluorescence as the basis of single-molecule sensitivity. Despite the many advantages of using single emitters as light sources, the intensity and duration of their emission impose fundamental limits on the imaging speed and precision for tracking studies. Here, we discuss the potential of a novel imaging technique based on interferometric scattering (iSCAT) that pushes both the sensitivity and time resolution far beyond what is currently achievable by single-emitter-based approaches. We present recent results that demonstrate single-molecule sensitivity and imaging speeds on the microsecond timescale.


Changes in brain architecture are consistent with altered fear processing in domestic rabbits.
The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.


The MRI findings of meniscal root tear of the medial meniscus: emphasis on coronal, sagittal and axial images.
The purpose of this study was to evaluate the accuracy of the characteristic magnetic resonance imaging (MRI) findings of medial meniscal root tear in the coronal, sagittal and axial planes. Thirty arthroscopically diagnosed patients who had undergone preoperative knee MRI were included in this study. They were compared to 30 age-matched patients with medial meniscus tears without root tears. The findings used for imaging analysis were as follows: the radial tear on the meniscal root of the medial meniscus in the axial plane, the presence of the truncation sign in the coronal plane and the ghost meniscus sign in the sagittal plane. Meniscal extrusion in the coronal plane was also evaluated. All the MRI findings of both groups were statistically analyzed. All the findings were more frequently found in the root tear group than those in the control group (P < 0.05). The sensitivity, specificity, positive predictive value and negative predictive value of finding a radial tear in the axial plane were 93.3, 100, 100 and 93.8%, respectively. In the coronal plane, rates for the presence of the truncation sign were 90, 100, 100 and 90.9%, respectively. In the sagittal plane, rates for the presence of the ghost meniscus sign were 96.7, 96.7, 96.7 and 96.7%, respectively. The rates for the meniscus extrusion in the coronal plane were 63.3, 90, 86.4 and 71.1%, respectively. The findings of medial meniscal root tear were characteristic as compared with the control group. Radial tear in the axial plane also showed similar diagnostic accuracy as that seen in the other planes. The characteristic findings provide high diagnostic accuracy, and axial plane is helpful to detect medial meniscal root tear. Diagnostic study, Level III.


Problems in setting up an executing large-scale psychiatric epidemiological studies.
This paper focuses on problems that can be encountered in conceptualizing, executing and writing up large-scale psychiatric epidemiological studies. It makes no attempt to cover fundamental issues of design and analysis, rather it centers on problems associated with projects of considerable size. In the conceptual area, it discusses the prerequisites to be considered before deciding to launch such a study. It notes the administrative and scientific uses of epidemiological studies and considers the strengths and weaknesses of large-scale studies to address those concerns. Issues in carrying out such studies are discussed including decisions about study design, sampling method and instrumentation. All are dependent on the central purpose of the study but trade-offs between feasibility and scientific rigor are always present. Data collection and analysis problems highlighted in large-scale studies are examined. They include the difficulty, in the former, of adequately motivating and supervising field personnel and, in the latter, of dealing with problems that accompany missing data and complicated sampling strategies. Potential problems in data access and use and writing up the results are seen as arising from the presence of a large investigative team with diverse interests. Lastly, the comparative worth of these studies is considered.


Evidence of climate-driven selection on tree traits and trait plasticity across the climatic range of a riparian foundation species.
Selection on quantitative traits by heterogeneous climatic conditions can lead to substantial trait variation across a species range. In the context of rapidly changing environments, however, it is equally important to understand selection on trait plasticity. To evaluate the role of selection in driving divergences in traits and their associated plasticities within a widespread species, we compared molecular and quantitative trait variation in Populus fremontii (Fremont cottonwood), a foundation riparian distributed throughout Arizona. Using SNP data and genotypes from 16 populations reciprocally planted in three common gardens, we first performed QST -FST analyses to detect selection on traits and trait plasticity. We then explored the environmental drivers of selection using trait-climate and plasticity-climate regressions. Three major findings emerged: (1) There was significant genetic variation in traits expressed in each of the common gardens and in the phenotypic plasticity of traits across gardens, both of which were heritable. (2) Based on QST -FST comparisons, there was evidence of selection in all traits measured; however, this result varied from no effect in one garden to highly significant in another, indicating that detection of past selection is environmentally dependent. We also found strong evidence of divergent selection on plasticity across environments for two traits. (3) Traits and/or their plasticity were often correlated with population source climate (R2 up to .77 and .66, respectively). These results suggest that steep climate gradients across the Southwest have played a major role in shaping the evolution of divergent phenotypic responses in populations and genotypes now experiencing climate change.


A mouse model of Townes-Brocks syndrome expressing a truncated mutant Sall1 protein is protected from acute kidney injury.
It has been postulated that developmental pathways are reutilized during repair and regeneration after injury, but functional analysis of many genes required for kidney formation has not been performed in the adult organ. Mutations in SALL1 cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the kidney and urinary tract, both of which lead to childhood kidney failure. Sall1 is a transcriptional regulator that is expressed in renal progenitor cells and developing nephrons in the embryo. However, its role in the adult kidney has not been investigated. Using a mouse model of TBS (Sall1TBS), we investigated the role of Sall1 in response to acute kidney injury. Our studies revealed that Sall1 is expressed in terminally differentiated renal epithelia, including the S3 segment of the proximal tubule, in the mature kidney. Sall1TBS mice exhibited significant protection from ischemia-reperfusion injury and aristolochic acid-induced nephrotoxicity. This protection from acute injury is seen despite the presence of slowly progressive chronic kidney disease in Sall1TBS mice. Mice containing null alleles of Sall1 are not protected from acute kidney injury, indicating that expression of a truncated mutant protein from the Sall1TBS allele, while causative of congenital anomalies, protects the adult kidney from injury. Our studies further revealed that basal levels of the preconditioning factor heme oxygenase-1 are elevated in Sall1TBS kidneys, suggesting a mechanism for the relative resistance to injury in this model. Together, these studies establish a functional role for Sall1 in the response of the adult kidney to acute injury.


Consumption of vegetables and fruits and risk of ovarian carcinoma.
To the authors' knowledge, only a few prospective studies to date have investigated the correlation between vegetable and fruit consumption and the risk of ovarian carcinoma and their results have been inconclusive. Vegetable and fruit intake was assessed in relation to ovarian carcinoma, among 62,573 postmenopausal women participating in The Netherlands Cohort Study on Diet and Cancer. Women reported on dietary habits and on other risk factors for cancer in a self-administered questionnaire in 1986. Follow-up of cancer was implemented by annual record linkage with The Netherlands Cancer Registry and a pathology register. After 11.3 years of follow-up, data regarding 252 incident invasive epithelial ovarian carcinoma cases and of 2216 subcohort members were available for case-cohort analyses. Multivariable-adjusted rate ratios (RR) of ovarian carcinoma for women in the highest compared with the lowest quintile of intake (RR(Q5 vs. Q1)) were 0.98 (95% confidence interval [95% CI], 0.61-1.58) for total vegetables and 1.11 (95% CI, 0.70-1.78) for total fruit. The RR(Q5 vs. Q1) values of ovarian carcinoma with intake of cooked vegetables, raw vegetables, brassicas, legumes, cooked leafy vegetables, and raw leafy vegetables were 1.35 (95% CI, 0.83-2.21), 0.75 (95% CI, 0.48-1.18), 1.42 (95% CI, 0.88-2.29), 0.93 (95% CI, 0.60-1.44), 1.05 (95% CI, 0.66-1.67), and 1.23 (95% CI, 0.75-2.02), respectively. With the exception of raw endive (multivariable-adjusted RR, 0.24; 95% CI, 0.07-0.78), none of the individual vegetable or fruit items showed a statistically significant association with ovarian carcinoma. The results of the current study did not support a significant association between vegetable or fruit consumption and ovarian carcinoma risk in a cohort of postmenopausal women.


Focused differential glycan analysis with the platform antibody-assisted lectin profiling for glycan-related biomarker verification.
Protein glycosylation is a critical subject attracting increasing attention in the field of proteomics as it is expected to play a key role in the investigation of histological and diagnostic biomarkers. In this context, an enormous number of glycoproteins have now been nominated as disease-related biomarkers. However, there is no appropriate strategy in the current proteome platform to qualify such marker candidate molecules, which relates their specific expression to particular diseases. Here, we present a new practical system for focused differential glycan analysis in terms of antibody-assisted lectin profiling (ALP). In the developed procedure, (i) a target protein is enriched from clinic samples (e.g. tissue extracts, cell supernatants, or sera) by immunoprecipitation with a specific antibody recognizing a core protein moiety; (ii) the target glycoprotein is quantified by immunoblotting using the same antibody used in (i); and (iii) glycosylation difference is analyzed by means of antibody-overlay lectin microarray, an application technique of an emerging glycan profiling microarray. As model glycoproteins having either N-linked or O-linked glycans, prostate-specific antigen or podoplanin, respectively, were subjected to systematic ALP analysis. As a result, specific signals corresponding to the target glycoprotein glycans were obtained at a sub-picomole level with the aid of specific antibodies, whereby disease-specific or tissue-specific glycosylation changes could be observed in a rapid, reproducible, and high-throughput manner. Thus, the established system should provide a powerful pipeline in support of on-going efforts in glyco-biomarker discovery.


cAMP-activated chloride channels in a CFTR-transfected pancreatic adenocarcinoma-derived cell line, pANS6.
Pancreatic adenocarcinoma cell lines rarely express the CFTR gene, despite the high levels of CFTR protein that are present in primary pancreatic duct cells. We have attempted to generate a non-CF pancreatic adenocarcinoma cell line that stably produces high levels of CFTR mRNA and protein by transfecting a vector containing the CFTR cDNA, driven by a strong mammalian promoter, into the poorly differentiated pancreatic adenocarcinoma cell line, Panc-1. The pANS6 pancreatic duct cell line expresses substantial levels of CFTR mRNA, but little CFTR protein. Despite this we were able to detect low conductance chloride channels in 40% of patches, stimulated with cAMP, that have similar biophysical properties to CFTR.


Human papillomavirus in anal squamous cell carcinoma: an angel rather than a devil?
Anal cancer is a rare disease with an increasing incidence worldwide but, unfortunately, even today the scientific community still has a limited knowledge and limited options of treatment. More than 50% of patients with anal cancer presenting at diagnosis with locoregional disease have good chances of cure with chemoradiotherapy (CT-RT). However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in more than 80% of anal cancers and while multiple etiologic connections between HPV infection and anal cancer have already been well elucidated, its prognostic and/or predictive role is currently under investigation, especially among immunocompetent patients affected by this disease. In a single-institutional set, we have retrospectively analysed clinical data of 50 consecutive cases homogeneously treated with CT-RT for stage I-III anal squamous cell carcinoma. We found that HPV-positive anal cancers had a statistically significant improved five-year disease-free survival (DFS) compared to HPV-negative group. These findings could be explained by an increased chemo/radiosensitivity of HPV-positive tumours. Further efforts should be directed towards a better understanding of HPV-related oncogenesis and towards designing novel tailored strategies for the management of this disease both in terms of prevention and treatment.


Human Papillomavirus and Epidermal Growth Factor Receptor in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma: Correlation With Dynamic Contrast-Enhanced MRI Parameters.
The objective of this study was to investigate differences in dynamic contrast-enhanced MRI (DCE-MRI) parameters on the basis of the status of human papillomavirus (HPV) and epidermal growth factor receptor (EGFR) biomarkers in patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx by use of histogram analysis. A total of 22 consecutive patients with oral cavity and oropharyngeal SCC underwent DCE-MRI before receiving treatment. DCE parameter maps of the volume transfer constant (K(trans)), the flux rate constant (kep), and the extravascular extracellular volume fraction (ve) were obtained. The histogram parameters were calculated using the entire enhancing tumor volume and were compared between the patient subgroups on the basis of HPV and EGFR biomarker statuses. The cumulative histogram parameters of K(trans) and kep showed lower values in the HPV-negative and EFGR-overexpression group than in the HPV-positive EGFR-negative group. These differences were statistically significant for the mean (p = 0.009), 25th, 50th, and 75th percentile values of K(trans) and for the 25th percentile value of kep when correlated with HPV status in addition to the mean K(trans) value (p = 0.047) and kep value (p = 0.004) when correlated with EGFR status. No statistically significant difference in ve was found on the basis of HPV and EGFR status. DCE-MRI is useful for the assessment of the tumor microenvironment associated with HPV and EGFR biomarkers before treatment of patients with oral cavity and oropharyngeal SCC.


Suicidal thoughts and behaviors among college students and same-aged peers: results from the World Health Organization World Mental Health Surveys.
The primary aims are to (1) obtain representative prevalence estimates of suicidal thoughts and behaviors (STB) among college students worldwide and (2) investigate whether STB is related to matriculation to and attrition from college. Data from the WHO World Mental Health Surveys were analyzed, which include face-to-face interviews with 5750 young adults aged 18-22 spanning 21 countries (weighted mean response rate = 71.4%). Standardized STB prevalence estimates were calculated for four well-defined groups of same-aged peers: college students, college attriters (i.e., dropouts), secondary school graduates who never entered college, and secondary school non-graduates. Logistic regression assessed the association between STB and college entrance as well as attrition from college. Twelve-month STB in college students was 1.9%, a rate significantly lower than same-aged peers not in college (3.4%; OR 0.5; p < 0.01). Lifetime prevalence of STB with onset prior to age 18 among college entrants (i.e., college students or attriters) was 7.2%, a rate significantly lower than among non-college attenders (i.e., secondary school graduates or non-graduates; 8.2%; OR 0.7; p = 0.03). Pre-matriculation onset STB (but not post-matriculation onset STB) increased the odds of college attrition (OR 1.7; p < 0.01). STB with onset prior to age 18 is associated with reduced likelihood of college entrance as well as greater attrition from college. Future prospective research should investigate the causality of these associations and determine whether targeting onset and persistence of childhood-adolescent onset STB leads to improved educational attainment.


Superhydrophobic ZnO networks with high water adhesion.
ZnO structures were deposited using a simple chemical bath deposition technique onto interdigitated electrodes fabricated by a conventional photolithography method on SiO2/Si substrates. The X-ray diffraction studies show that the ZnO samples have a hexagonal wurtzite crystalline structure. The scanning electron microscopy observations prove that the substrates are uniformly covered by ZnO networks formed by monodisperse rods. The ZnO rod average diameter and length were tuned by controlling reactants' concentration and reaction time. Optical spectroscopy measurements demonstrate that all the samples display bandgap values and emission bands typical for ZnO. The electrical measurements reveal percolating networks which are highly sensitive when the samples are exposed to ammonia vapors, a variation in their resistance with the exposure time being evidenced. Other important characteristics are that the ZnO rod networks exhibit superhydrophobicity, with water contact angles exceeding 150° and a high water droplet adhesion. Reproducible, easily scalable, and low-cost chemical bath deposition and photolithography techniques could provide a facile approach to fabricate such ZnO networks and devices based on them for a wide range of applications where multifunctionality, i.e., sensing and superhydrophobicity, properties are required. 81.07.-b; 81.05.Dz; 68.08.Bc.


Periodic electroencephalogram discharges in a case of Lafora body disease: An unusual finding.
Lafora body disease (LBD) is a form of progressive myoclonic epilepsy, characterized by seizures, myoclonic jerks, cognitive decline, ataxia, and intracellular polyglucosan inclusion bodies (Lafora bodies) in the neurons, heart, skeletal muscle, liver, and sweat gland duct cells. Electroencephalogram (EEG) findings in LBD may include multiple spikes and wave discharges, photosensitivity, multifocal epileptiform discharges, and progressive slowing in background activity. Periodicity in epileptiform discharges has not been frequently depicted in LBD. We herein report an unusual case of LBD who showed generalized periodic epileptiform discharges in EEG.


The Laterally Closed Tunnel for the Treatment of Deep Isolated Mandibular Recessions: Surgical Technique and a Report of 24 Cases.
Predictable coverage of deep isolated mandibular gingival recessions is one of the most challenging endeavors in plastic-esthetic periodontal surgery, and limited data is available in the literature. The aim of this paper is to present the rationale, the step-by-step procedure, and the results obtained in a series of 24 patients treated by means of a novel surgical technique (the laterally closed tunnel [LCT]) specifically designed for deep isolated mandibular recessions. A total of 24 healthy patients (21 women and 3 men, mean age 25.75 ± 7.12 years) exhibiting one single deep mandibular Miller Class I (n = 4), II (n = 10), or III (n = 10) gingival recession ≥ 4 mm were consecutively treated with LCT in conjunction with an enamel matrix derivative (EMD) and palatal subepithelial connective tissue graft (SCTG). The following clinical parameters were assessed at baseline and 12 months postoperatively: probing depth (PD), clinical attachment level (CAL), complete root coverage (CRC), mean root coverage (MRC), recession depth (RD), and keratinized tissue width (KTW). The primary outcome variable was CRC. The postoperative morbidity was low, and no complications, such as bleeding, infections/abscesses, or loss of SCTG, occurred. At 12 months, CRC was obtained in 17 of the 24 defects (70.83%), while in the remaining 7 defects RC amounted to 80% to 90% (in 6 cases) and 79% (in 1 case). Of the 17 defects exhibiting CRC, 12 were central incisors and 5 were canines. With respect to defect type, CRC was found in 3 of the 4 Miller Class I, 8 of the 10 Class II, and in 6 of the 10 Class III defects. Mean RD changed from 5.14 ± 1.26 mm at baseline to 0.2 ± 0.37 mm at 12 months, while MRC amounted to 4.94 ± 1.19 mm, representing 96.11% (P < .0001). Mean KTW increased from 1.41 ± 1.00 mm at baseline to 4.14 ± 1.67 mm (P < .0001) at 12 months, yielding a KTW gain of 2.75 ± 1.52 (P < .0001). No statistically significant changes in mean PD occurred following root coverage surgery (1.8 ± 0.2 mm at baseline and 2.1 ± 0.3 mm at 12 months). The present results suggest that the LCT is a valuable approach for the treatment of deep isolated mandibular Miller Class I, II, and III gingival recessions.