Low lean tissue index and muscle strength combined with high fat tissue index are associated with cardiovascular disease-related hospitalisation in patients on haemodialysis.
The combined clinical impact of muscle mass, muscle function and adipose mass on hospitalisation events, especially those that have exact causes, such as cardiovascular diseases (CVDs), had been rarely studied in patients on haemodialysis (HD). This study aimed to determine the influence of lean tissue index (LTI), fat tissue index (FTI) and hand grip strength (HGS) on the risk of CVD-related hospitalisation in patients undergoing chronic HD. This multi-centre observational study enrolled a total of 2,041 clinically stable patients aged >18 years and who had undergone HD for at least three months at 17 HD units in 2019. The follow-up period was up to two years. LTI and FTI were assessed using a body composition monitoring machine, and HGS was measured by a CAMRY® dynamometer. Cox regression models were fit to estimate the associations of body composition and HGS with CVD-related hospitalisation risk. During a mean follow-up of 22.6 months, CVD-related hospitalisation occurred in 492 patients. Compared with the non-CVD group, patients with CVD-related hospitalisation were older; had lower diastolic blood pressure; were more likely to have a history of diabetes; had worse activity status scores and lower levels of LTI, HGS, serum uric acid and serum creatinine and had higher FTI levels, body mass index and extracellular water/ intracellular water ratio. In the Cox regression models, low LTI and high FTI were independently associated with CVD-related hospitalisation in both men and women. In men, low HGS was an independent risk factor for CVD-related hospitalisation. When patients were further stratified into four distinct groups according to the sex-specific median values of LTI and FTI, the combination of low LTI and high FTI was an independent risk factor for CVD-related hospitalization (hazard ratio =1.79 in men, 95% confidence interval 1.26-2.55; hazard ratio =2.48 in women, 95% confidence interval 1.66-3.71; reference: high LTI/low FTI group). Among patients on chronic HD, low LTI and high FTI were associated with CVD-related hospitalisation in men and women, whereas HGS was an independent risk factor for CVD-related hospitalisation in men but not in women. Combining low LTI and high FTI increased the association with hospitalisation risk and was an independent predictor of CVD-related hospitalisation.


Cardiorespiratory fitness levels and its correlates among adults with diabetes.
The purpose of this study is to report cardiorespiratory fitness levels among adults with diabetes and report differences by demographic (eg, body mass index) and behavioral (eg, physical activity) variables. Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were used in the analyses. Cardiorespiratory fitness was assessed using a non-exercise prediction equation and through a submaximal treadmill-based test using heart rate extrapolation. Participants completed a questionnaire to assess various demographic and behavior variables. Seventy eight participants met inclusion criteria and constituted the analyzed sample. The majority (55.1%) of participants were estimated as having low or moderate cardiorespiratory fitness. Results showed that for both methods normal weight individuals had greater cardiorespiratory fitness than obese individuals, and for the non-exercise prediction equation, participants who sat during the day and did not walk very much had lower cardiorespiratory fitness (mean = 26.1 mL/kg/min [95% CI: 18.9-33.4]) than those doing heavy work or carrying heavy loads (mean = 34.6 mL/kg/min [95% CI: 30.2-39.1]). These results suggest that obese and inactive adults with diabetes may be at an increased risk for morbidities and mortality associated with low cardiorespiratory fitness. Physical therapists are encouraged to apply evidence-based principles for exercise prescription and physical activity counseling to help patients with diabetes regulate their blood glucose control and improve cardiorespiratory fitness.


Imaging multiple conductance states in an alamethicin pore.
Alamethicin is the archetypal antimicrobial pore-forming peptide. Although the peptide has long been known to form pores of characteristic conductances in lipid membranes, the precise nature of these pores is not known. Simultaneous calcium-flux imaging and single-channel recording in a droplet interface bilayer allowed us to directly attribute multiple conductance states to a single point diffusing in the bilayer.


Advantages and limitations of experimental techniques used to measure cardiac energy metabolism.
The heart requires a constant supply of energy to sustain contractile function, which is supplied by hydrolysis of adenosine triphosphate derived primarily from the metabolism of fatty acids and carbohydrates. Understanding how production of adenosine triphosphate is regulated in the heart is critical to an understanding of how alterations in energy metabolism contribute to the severity of cardiac disease. A number of techniques can be used to measure energy metabolism in the heart. They include biochemical measurement of metabolites and enzymes of intermediary metabolism, measurement of arteriovenous differences in carbon substrate extraction by the heart, measurement of high-energy phosphates with 31P nuclear magnetic resonance, measurement of the rate of flux through the pathways of intermediary metabolism with 14C- and 3H-labeled carbon substrates, measurement of tricarboxylic acid cycle activity with 13C nuclear magnetic resonance, and measurement of glucose uptake and oxidative metabolism with positron emission tomography. Each of these techniques has advantages and limitations.


Biotic interaction strength and the intensity of selection.
Although the ecological and evolutionary impacts of species interactions have been the foci of much research, the relationship between the strength of species interactions and the intensity of selection has been investigated only rarely. I develop a simple model demonstrating how the opportunity for selection varies with interaction strength, and then use the relationship between the maximum value of the selection differential and the opportunity for selection (Arnold & Wade 1984) to evaluate how selection differentials vary in relation to species interaction strength. This model predicts an initial deceleration and then an accelerating increase in the intensity of selection with increasing strength of antagonistic interactions and with decreasing strength of mutualistic interactions. Empirical data from several studies provide support for this model. These results further support an evolutionary mechanism for some striking patterns of evolutionary diversification including the latitudinal species gradient, and should be relevant to studies of eco-evolutionary dynamics.


Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment.
Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC. Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed. Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually. Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8+ T cells and FOXP3+ Treg cells provides further theoretical basis and potential targets for GC immunotherapy.


The Tyranny of Hope.
Biomedical science is usually framed for the public in terms of its "promise." When a breakthrough results from scientific inquiry, that promise is translated into a hope for a cure. The "promise" of such advances in biomedical research can have a paradoxical effect. In the case of pediatric neuromuscular disease, rather than reducing suffering, the expectation of cure can be a burden-both physically and emotionally-for affected children and their families. If a family expects a cure, it is likely to do everything possible to help the child live as long as possible, in the hope that the child will eventually receive it. I am not arguing that the appropriate response to the paradox of promise is to impede scientific progress. What is needed, however, is a broader conception of hope-one that values hope for a good day, a good quality of life, good relationships, or even a good death-alongside the hope for a cure.


Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature.
Pseudomonas aeruginosa is a major cause of severe infections that lead to bacteremia and high patient mortality. P. aeruginosa has evolved numerous evasion and subversion mechanisms that work in concert to overcome immune recognition and effector functions in hospitalized and immunosuppressed individuals. Here, we have used multilaser spinning-disk intravital microscopy to monitor the blood-borne stage in a murine bacteremic model of P. aeruginosa infection. P. aeruginosa adhered avidly to lung vasculature, where patrolling neutrophils and other immune cells were virtually blind to the pathogen's presence. This cloaking phenomenon was attributed to expression of Psl exopolysaccharide. Although an anti-Psl mAb activated complement and enhanced neutrophil recognition of P. aeruginosa, neutrophil-mediated clearance of the pathogen was suboptimal owing to a second subversion mechanism, namely the type 3 secretion (T3S) injectisome. Indeed, T3S prevented phagosome acidification and resisted killing inside these compartments. Antibody-mediated inhibition of the T3S protein PcrV did not enhance bacterial phagocytosis but did enhance killing of the few bacteria ingested by neutrophils. A bispecific mAb targeting both Psl and PcrV enhanced neutrophil uptake of P. aeruginosa and also greatly increased inhibition of T3S function, allowing for phagosome acidification and bacterial killing. These data highlight the need to block multiple evasion and subversion mechanisms in tandem to kill P. aeruginosa.


The fucose-mannose ligand-ELISA in the diagnosis and prognosis of canine visceral leishmaniasis in Brazil.
The fucose-mannose ligand (FML)-ELISA assay showed a sensitivity of 100% and a specificity of 100% in diagnosis of canine visceral leishmaniasis (CVL) (kala-azar) in sera from naturally infected dogs from São Gonçalo do Amaranto, Rio Grande de Norte, Brazil. The overall prevalence of antibodies to Leishmania in the endemic area was 23% (79 of 343). Seroreactivity detected by a Leishmania chagasi immunofluorescent (IF) assay was much lower (2.9%) and similar to the percentage of dogs with kala-azar symptoms (2.6%). Twenty-one of 21 asymptomatic, FML-seropositive animals died of kala-azar in a period ranging from 0 to 6 months after diagnosis. The predictive value was 100% for the FML-ELISA, 43% for an L. mexicana ELISA, and 24% for the L. mexicana and L. chagasi IF assays, respectively. In experimentally infected dogs, all assays detected seropositivity between 90 and 120 days after infection. Since the current strategy for control of CVL is based on detection and destruction of infected dogs, the highly predictive, sensitive, and specific FML-ELISA represents a useful tool for field control of the disease.


Tobacco Control Policies in Vietnam: Review on MPOWER Implementation Progress and Challenges.
In Vietnam, the WHO Framework Convention on Tobacco Control (WHO FCTC) took effect in March 2005 while MPOWER has been implemented since 2008. This paper describes the progress and challenges of implementation of the MPOWER package in Vietnam. We can report that, in term of monitoring, Vietnam is very active in the Global Tobacco Surveillance System, completing two rounds of the Global Adult Tobacco Survey (GATS) and three rounds of the Global Youth Tobacco Survey (GYTS). To protect people from tobacco smoke, Vietnam has issued and enforced a law requiring comprehensive smoking bans at workplaces and public places since 2013. Tobacco advertising and promotion are also prohibited with the exception of points of sale displays of tobacco products. Violations come in the form of promotion girls, corporate social responsibility activities from tobacco manufacturers and packages displayed by retail vendors. Vietnam is one of the 77 countries that require pictorial health warnings to be printed on cigarette packages to warn about the danger of tobacco and the warnings have been implemented effectively. Cigarette tax is 70% of factory price which is equal to less than 45% of retail price and much lower than the recommendation of WHO. However, Vietnam is one of the very few countries that require manufacturers and importers to make "compulsory contributions" at 1-2% of the factory price of cigarettes sold in Vietnam for the establishment of a Tobacco Control Fund (TCF). The TCF is being operated well. In 2015, 67 units of 63 provinces/cities, 22 ministries and political-social organizations and 6 hospitals received funding from TCF to implement a wide range of tobacco control activities. Cessation services have been starting with a a toll-free quit-line but need to be further strengthened. In conclusion, Vietnam has constantly put efforts into the tobacco control field with high commitment from the government, scientists and activists. Though several remarkable achievements have been gained, many challenges remain. To overcome those challenges, implementation strategies that take into account the contextual factors and social determinants of tobacco use in Vietnam are needed.


Quality control of fungus-specific glucosylceramide in Cryptococcus neoformans by endoglycoceramidase-related protein 1 (EGCrP1).
A fungus-specific glucosylceramide (GlcCer), which contains a unique sphingoid base possessing two double bonds and a methyl substitution, is essential for pathogenicity in fungi. Although the biosynthetic pathway of the GlcCer has been well elucidated, little is known about GlcCer catabolism because a GlcCer-degrading enzyme (glucocerebrosidase) has yet to be identified in fungi. We found a homologue of endoglycoceramidase tentatively designated endoglycoceramidase-related protein 1 (EGCrP1) in several fungal genomic databases. The recombinant EGCrP1 hydrolyzed GlcCer but not other glycosphingolipids, whereas endoglycoceramidase hydrolyzed oligosaccharide-linked glycosphingolipids but not GlcCer. Disruption of egcrp1 in Cryptococcus neoformans, a typical pathogenic fungus causing cryptococcosis, resulted in the accumulation of fungus-specific GlcCer and immature GlcCer that possess sphingoid bases without a methyl substitution concomitant with a dysfunction of polysaccharide capsule formation. These results indicated that EGCrP1 participates in the catabolism of GlcCer and especially functions to eliminate immature GlcCer in vivo that are generated as by-products due to the broad specificity of GlcCer synthase. We conclude that EGCrP1, a glucocerebrosidase identified for the first time in fungi, controls the quality of GlcCer by eliminating immature GlcCer incorrectly generated in C. neoformans, leading to accurate processing of fungus-specific GlcCer.


Thymus lanceolatus ethanolic extract protects human cells from t-BHP induced oxidative damage.
This study aimed to investigate the ethanolic extract of T. lanceolatus, a species native to north-western Algeria, traditionally used as herbal tea, seasoning and a preservative for meat and poultry. HPLC analysis showed the presence of fourteen bioactive compounds, among which rosmarinic acid is by far the most abundant one (15440.9 mg kg-1). Its biological activity on proliferation, viability and ROS protection was investigated towards K562, CaCo-2 and SH-SY5Y human cancer cell lines. Cell proliferation was inhibited in K562 and SH-SY5Y cells in the first 48 h at 500 μg mL-1 but slowly resumed after 72 h. A weak cytotoxic effect can be observed at 24, 48 and 72 hours: 12.8%, 14.9% and 24.2% reduction in K562 viability, and 11%, 15% and 12.7% in SH-SY5Y. No cytotoxicity was observed in CaCo-2 cells under the same experimental conditions. Even at the lowest concentrations (50 μg mL-1), the extract was efficiently able to protect human cells against t-BHP-induced oxidative damage. For instance, the highest concentration of the extract (100 μg mL-1) decreases ROS generation by about 30% in SH-SY5Y and 70% in CaCo-2 and K562 cells. The study confirms the very low cytotoxicity of the T. lanceolatus ethanolic extract and highlights its nutraceutical properties as an antioxidative and preservative agent and its possible use as an ingredient in functional foods.


Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation.
Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level.


Disruption of autophagy by the histone deacetylase inhibitor MGCD0103 and its therapeutic implication in B-cell chronic lymphocytic leukemia.
Evading apoptosis is a hallmark of B-cell chronic lymphocytic leukemia (CLL) cells and an obstacle to current chemotherapeutic approaches. Inhibiting histone deacetylase (HDAC) has emerged as a promising strategy to induce cell death in malignant cells. We have previously reported that the HDAC inhibitor MGCD0103 induces CLL cell death by activating the intrinsic pathway of apoptosis. Here, we show that MGCD0103 decreases the autophagic flux in primary CLL cells. Activation of the PI3K/AKT/mTOR pathway, together with the activation of caspases, and to a minor extent CAPN1, resulting in cleavage of autophagy components, were involved in MGCD0103-mediated inhibition of autophagy. In addition, MGCD0103 directly modulated the expression of critical autophagy genes at the transcriptional level that may contribute to autophagy impairment. Besides, we demonstrate that autophagy is a pro-survival mechanism in CLL whose disruption potentiates cell death induced by anticancer molecules including HDAC and cyclin-dependent kinase inhibitors. In particular, our data highlight the therapeutic potential of MGCD0103 as not only an inducer of apoptosis but also an autophagy suppressor in both combination regimens with molecules like flavopiridol, known to induce protective autophagy in CLL cells, or as an alternative to circumvent undesired immunomodulatory effects seen in the clinic with conventional autophagy inhibitors.


Proportion of illness acquired by foodborne transmission for nine enteric pathogens in Australia: an expert elicitation.
Estimates of the burden of illness acquired from food inform public health policy and prioritize interventions. A key component of such estimates is the proportion of illnesses that are acquired by foodborne transmission. In view of the shortage of requisite data, these proportions are commonly obtained through a process known as expert elicitation. We report findings from an elicitation process used to assess the importance of the foodborne transmission route for nine pathogens in Australia, circa 2010. Eleven experts were asked to estimate the proportion of illness acquired by five transmission routes: food, environmental, water, person, and zoonotic, together with a 90% certainty interval for foodborne transmission. Foodborne estimates and intervals from each expert were combined using both modified triangular and Program Evaluation and Review Technique (PERT) distributions, in @Risk version 6, to generate final distributions from which median estimates and 95% Credible Intervals (CrI) were calculated. Shiga toxin-producing Escherichia coli (STEC) was the only pathogen believed to have an important zoonotic transmission route, while norovirus, hepatitis A virus, non-STEC pathogenic E. coli, and Shigella spp. were all thought to be primarily spread from person to person. Foodborne transmission was the main route for Clostridium perfringens (98%, CrI: 84-100), Listeria monocytogenes (98%, CrI: 86-100), nontyphoidal Salmonella spp. (72%, CrI: 50-87), and Campylobacter spp. (77%, CrI: 60-90). Foodborne estimates using the modified triangular distribution had wider CrI than these calculated using the PERT distribution. Foodborne proportions for most pathogens in this study were the same or lower than those estimated circa 2000 in Australia, with the greatest decline for non-STEC pathogenic E. coli. Inclusion of certainty intervals from experts helps to quantify the precision of foodborne proportions. A decline in estimates of the foodborne proportion for common pathogens will influence final estimates of the burden of illness acquired from food.


alpha(2)-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats.
We examined the effect of alpha(2)-adrenoreceptor blockade in the nucleus of the solitary tract (NTS) on baroreflex responses elicited by electrical stimulation of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously hypertensive rats (SHR, n = 11) and normotensive Wistar-Kyoto rats (WKY, n = 11). ADN stimulation produced a frequency-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR, unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex control of MAP, RSNA, and HR and had a disproportionately greater influence on baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not significantly alter baroreflex function relative to control vehicle injections. These results suggest that baroreflex regulation of arterial pressure in SHR is highly dependent on NTS adrenergic mechanisms. The reflex regulation of sympathetic outflow to the kidney is less influenced by the altered alpha(2)-adrenoreceptor mechanisms in SHR.


Neural Mechanisms Underlying Cross-Modal Phonetic Encoding.
Audiovisual (AV) integration is essential for speech comprehension, especially in adverse listening situations. Divergent, but not mutually exclusive, theories have been proposed to explain the neural mechanisms underlying AV integration. One theory advocates that this process occurs via interactions between the auditory and visual cortices, as opposed to fusion of AV percepts in a multisensory integrator. Building upon this idea, we proposed that AV integration in spoken language reflects visually induced weighting of phonetic representations at the auditory cortex. EEG was recorded while male and female human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables /ba/ and /fa/, presented in Auditory-only, AV congruent or incongruent contexts. Subjects reported whether they heard /ba/ or /fa/. We hypothesized that vision alters phonetic encoding by dynamically weighting which phonetic representation in the auditory cortex is strengthened or weakened. That is, when subjects are presented with visual /fa/ and acoustic /ba/ and hear /fa/ (illusion-fa), the visual input strengthens the weighting of the phone /f/ representation. When subjects are presented with visual /ba/ and acoustic /fa/ and hear /ba/ (illusion-ba), the visual input weakens the weighting of the phone /f/ representation. Indeed, we found an enlarged N1 auditory evoked potential when subjects perceived illusion-ba, and a reduced N1 when they perceived illusion-fa, mirroring the N1 behavior for /ba/ and /fa/ in Auditory-only settings. These effects were especially pronounced in individuals with more robust illusory perception. These findings provide evidence that visual speech modifies phonetic encoding at the auditory cortex.SIGNIFICANCE STATEMENT The current study presents evidence that audiovisual integration in spoken language occurs when one modality (vision) acts on representations of a second modality (audition). Using the McGurk illusion, we show that visual context primes phonetic representations at the auditory cortex, altering the auditory percept, evidenced by changes in the N1 auditory evoked potential. This finding reinforces the theory that audiovisual integration occurs via visual networks influencing phonetic representations in the auditory cortex. We believe that this will lead to the generation of new hypotheses regarding cross-modal mapping, particularly whether it occurs via direct or indirect routes (e.g., via a multisensory mediator).


Prediction and analysis of beta-turns in proteins by support vector machine.
Tight turn has long been recognized as one of the three important features of proteins after the alpha-helix and beta-sheet. Tight turns play an important role in globular proteins from both the structural and functional points of view. More than 90% tight turns are beta-turns. Analysis and prediction of beta-turns in particular and tight turns in general are very useful for the design of new molecules such as drugs, pesticides, and antigens. In this paper, we introduce a support vector machine (SVM) approach to prediction and analysis of beta-turns. We have investigated two aspects of applying SVM to the prediction and analysis of beta-turns. First, we developed a new SVM method, called BTSVM, which predicts beta-turns of a protein from its sequence. The prediction results on the dataset of 426 non-homologous protein chains by sevenfold cross-validation technique showed that our method is superior to the other previous methods. Second, we analyzed how amino acid positions support (or prevent) the formation of beta-turns based on the "multivariable" classification model of a linear SVM. This model is more general than the other ones of previous statistical methods. Our analysis results are more comprehensive and easier to use than previously published analysis results.


Computer-based coding of free-text job descriptions to efficiently identify occupations in epidemiological studies.
Mapping job titles to standardised occupation classification (SOC) codes is an important step in identifying occupational risk factors in epidemiological studies. Because manual coding is time-consuming and has moderate reliability, we developed an algorithm called SOCcer (Standardized Occupation Coding for Computer-assisted Epidemiologic Research) to assign SOC-2010 codes based on free-text job description components. Job title and task-based classifiers were developed by comparing job descriptions to multiple sources linking job and task descriptions to SOC codes. An industry-based classifier was developed based on the SOC prevalence within an industry. These classifiers were used in a logistic model trained using 14 983 jobs with expert-assigned SOC codes to obtain empirical weights for an algorithm that scored each SOC/job description. We assigned the highest scoring SOC code to each job. SOCcer was validated in 2 occupational data sources by comparing SOC codes obtained from SOCcer to expert assigned SOC codes and lead exposure estimates obtained by linking SOC codes to a job-exposure matrix. For 11 991 case-control study jobs, SOCcer-assigned codes agreed with 44.5% and 76.3% of manually assigned codes at the 6-digit and 2-digit level, respectively. Agreement increased with the score, providing a mechanism to identify assignments needing review. Good agreement was observed between lead estimates based on SOCcer and manual SOC assignments (κ 0.6-0.8). Poorer performance was observed for inspection job descriptions, which included abbreviations and worksite-specific terminology. Although some manual coding will remain necessary, using SOCcer may improve the efficiency of incorporating occupation into large-scale epidemiological studies.


Involvement of the pyrilamine transporter, a putative organic cation transporter, in blood-brain barrier transport of oxycodone.
The purpose of this study was to characterize blood-brain barrier (BBB) transport of oxycodone, a cationic opioid agonist, via the pyrilamine transporter, a putative organic cation transporter, using conditionally immortalized rat brain capillary endothelial cells (TR-BBB13). Oxycodone and [3H]pyrilamine were both transported into TR-BBB13 cells in a temperature- and concentration-dependent manner with Km values of 89 and 28 microM, respectively. The initial uptake of oxycodone was significantly enhanced by preloading with pyrilamine and vice versa. Furthermore, mutual uptake inhibition by oxycodone and pyrilamine suggests that a common mechanism is involved in their transport. Transport of both substrates was inhibited by type II cations (quinidine, verapamil, and amantadine), but not by classic organic cation transporter (OCT) substrates and/or inhibitors (tetraethylammonium, 1-methyl-4-phenylpyridinium, and corticosterone), substrates of OCTN1 (ergothioneine) and OCTN2 (L-carnitine), or organic anions. The transport was inhibited by metabolic inhibitors (rotenone and sodium azide) but was insensitive to extracellular sodium and membrane potential for both substrates. Furthermore, the transport of both substrates was increased at alkaline extracellular pH and decreased in the presence of a protonophore (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone). Intracellular acidification induced with ammonium chloride enhanced the uptakes, suggesting that the transport is driven by an oppositely directed proton gradient. The brain uptake of oxycodone measured by in situ rat brain perfusion was increased in alkaline perfusate and was significantly inhibited by pyrilamine. These results suggest that blood-brain barrier transport of oxycodone is at least partly mediated by a common transporter with pyrilamine, and this transporter is an energy-dependent, proton-coupled antiporter.


Oligomers of Parkinson's Disease-Related α-Synuclein Mutants Have Similar Structures but Distinctive Membrane Permeabilization Properties.
Single-amino acid mutations in the human α-synuclein (αS) protein are related to early onset Parkinson's disease (PD). In addition to the well-known A30P, A53T, and E46K mutants, recently a number of new familial disease-related αS mutations have been discovered. How these mutations affect the putative physiological function of αS and the disease pathology is still unknown. Here we focus on the H50Q and G51D familial mutants and show that like wild-type αS, H50Q and G51D monomers bind to negatively charged membranes, form soluble partially folded oligomers with an aggregation number of ~30 monomers under specific conditions, and can aggregate into amyloid fibrils. We systematically studied the ability of these isolated oligomers to permeabilize membranes composed of anionic phospholipids (DOPG) and membranes mimicking the mitochondrial phospholipid composition (CL:POPE:POPC) using a calcein release assay. Small-angle X-ray scattering studies of isolated oligomers show that oligomers formed from wild-type αS and the A30P, E46K, H50Q, G51D, and A53T disease-related mutants are composed of a similar number of monomers. However, although the binding affinity of the monomeric protein and the aggregation number of the oligomers formed under our specific protocol are comparable for wild-type αS and H50Q and G51D αS, G51D oligomers cannot disrupt negatively charged and physiologically relevant model membranes. Replacement of the membrane-immersed glycine with a negatively charged aspartic acid at position 51 apparently abrogates membrane destabilization, whereas a mutation in the proximal but solvent-exposed part of the membrane-bound α-helix such as that found in the H50Q mutant has little effect on the bilayer disrupting properties of oligomers.


Using spontaneous photon emission to image lipid oxidation patterns in plant tissues.
Plants, like almost all living organisms, spontaneously emit photons of visible light. We used a highly sensitive, low-noise cooled charge coupled device camera to image spontaneous photon emission (autoluminescence) of plants. Oxidative stress and wounding induced a long-lasting enhancement of plant autoluminescence, the origin of which is investigated here. This long-lived phenomenon can be distinguished from the short-lived chlorophyll luminescence resulting from charge recombinations within the photosystems by pre-adapting the plant to darkness for about 2 h. Lipids in solvent were found to emit a persistent luminescence after oxidation in vitro, which exhibited the same time and temperature dependence as plant autoluminescence. Other biological molecules, such as DNA or proteins, either did not produce measurable light upon oxidation or they did produce a chemiluminescence that decayed rapidly, which excludes their significant contribution to the in vivo light emission signal. Selective manipulation of the lipid oxidation levels in Arabidopsis mutants affected in lipid hydroperoxide metabolism revealed a causal link between leaf autoluminescence and lipid oxidation. Addition of chlorophyll to oxidized lipids enhanced light emission. Both oxidized lipids and plants predominantly emit light at wavelengths higher than 600 nm; the emission spectrum of plant autoluminescence was shifted towards even higher wavelengths, a phenomenon ascribable to chlorophyll molecules acting as luminescence enhancers in vivo. Taken together, the presented results show that spontaneous photon emission imaged in plants mainly emanates from oxidized lipids. Imaging of this signal thus provides a simple and sensitive non-invasive method to selectively visualize and map patterns of lipid oxidation in plants.


PUFA ω-3 and ω-6 biomarkers and sleep: a pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE).
n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included α-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA + DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts, n = 18,791) was categorized as short (≤6 h), 7-8 h (reference), or long (≥9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles, the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.


Evaluation of Insulin Lispro Pharmacokinetics and Pharmacodynamics Over 10 Days of Continuous Insulin Infusion in People With Type 1 Diabetes.
We evaluated the effect of meloxicam on insulin lispro pharmacokinetics and glucose pharmacodynamics over 10 days of continuous subcutaneous insulin infusion (CSII) at one infusion site in people with type 1 diabetes (T1D). This phase 1, randomized, double-blind, single-center, two-way crossover study enrolled adults with T1D for ≥1 year on stable CSII for ≥3 months. Participants randomly received U100 insulin lispro and LY900027 (U100 insulin lispro + 0.25 mg/mL meloxicam). Primary end points were area under the insulin lispro curve from 0 to 5 hours (AUCIns.0-5h) after bolus administration prior to a mixed-meal tolerance test (MMTT) and maximum observed concentration of insulin lispro (CIns.max) on days 5, 7, and 10, versus day 3 (baseline). A total of 20 participants were randomized. Insulin absorption was accelerated for insulin lispro and LY900027 from days 1 to 7. The AUCIns.0-5h was significantly lower on day 10 versus day 3 for LY900027 (-19%) and insulin lispro (-14%); the AUCIns.0-5h did not differ significantly between treatments. The CIns.max increased with LY900027 and insulin lispro (by ~14%-23% and ~16%-51%) on days 5, 7, and 10 versus day 3. The CIns.max of LY900027 was ~14%-23% lower than insulin lispro CIns.max on days 7 and 10 (P ≤ .0805). Accelerated insulin absorption and a modest loss of total insulin exposure led to a loss of MMTT glycemic control at later time points. The pharmacokinetics of insulin changed over catheter wear time even when an anti-inflammatory agent was present. Postprandial glycemic control was adversely affected by the accelerated insulin absorption and decreased insulin exposure.


Combined auditory and articulatory training improves phonological deficit in children with dyslexia.
A group of 19 children with dyslexia aged 7 years 2 months to 10 years 9 months were selected from a clinical sample and tested using a large neuropsychological battery in order to specify the severity and subtype of dyslexia as well as the presence of comorbid conditions. Thereafter, they received a standardised training of 6 weeks of daily auditory exercises aimed at reinforcing explicit and implicit phonological awareness. Ten participants also received specific training of the sensory-motor aspects of articulatory production of individual phonemes during the first 3 weeks of auditory training, whereas the remaining received the same specific training during the last 3 weeks of auditory training. Repetition, phonological awareness, reading and spelling were assessed before the first session, between the two sessions and after the second session. Results confirm the overall efficiency of intensive phonological training, even with exclusively auditory material. The main outcome of this study is a significant improvement of phonology and non-word reading specifically during the periods where the two methods were associated, suggesting a significant contribution of articulatory training to the observed improvement. Finally performance to a motor tapping task proved to be one of the best predictors of training efficiency while comorbid co-ordination or attention deficit did not interfere. Results are interpreted with reference to current theories about mechanisms underlying dyslexia.


Quantitative analysis of the effect of near lens addition on accommodation and myopigenesis.
To develop a quantitative, objective, and scientific basis for understanding the effects of applying near bifocal additions (ADDs) on oculomotor control and myopia development. This is important because myopia is a major public health problem that affects 25% of the U.S. population and 75% or more in Asian countries. It is also associated with an increased risk for vision-threatening conditions, such as retinal breaks and detachments, as well as glaucoma. A comprehensive model of refractive error development was constructed based on a dual-interactive feedback model of accommodation and vergence, which represented the short-term dynamics pathway, with the addition of both genetic and environmental (defocus-induced axial growth) components in a long-term pathway. An alternating near- and far-viewing paradigm was simulated, with varying amounts of ADDs, to obtain a parametric relationship between the root mean square of accommodative error (AE) and the induced refractive error (IRE). The parametric relationship provided the crucial linkage between the long-term growth pathway and the conventional short-term dynamics pathway. ADD is the simulated lens placed before the eyes only during near viewing, whereas IRE is the simulated lens fixed before the eyes that represents the optical effect of slowly progressive refractive development caused by near work. A V-shaped functional relationship was found between AE and IRE. The left half of the curve is associated with hyperopic defocus and myopigenesis, whereas the right half is associated with myopic defocus and hyperogenesis. Introduction of an ADD shifts the V-shaped curve horizontally. Thus, an "optimal" ADD can be used to shift the minimum of the accommodative error curve to the zero IRE point, and thereby reduce or eliminate retinal defocus and its potential towards myopigenesis. On the other hand, sensitivity analysis of model parameters shows that increasing the accommodative convergence crosslink gain (AC) shifts the curve to the right and results in a tendency towards myopigenesis, which is consistent with clinical findings in progressive myopia. The model can be used to specify the precise ADD needed for an individual to retard or eliminate retinal defocus-induced myopic progression. If future experiments show that using the "optimal" ADD results in the greatest benefit (i.e., least myopia progression), there will be considerable worldwide public health benefit.


Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent.
Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size. Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted.


Effects of body weight support and pedal stance width on joint loading during pinnacle trainer exercise.
A pinnacle trainer is a stair climber that has a biplane exercise trajectory and an adjustable pedal stance width (PSW). A pinnacle trainer integrated with a body weight support (BWS) system can help overweight individuals or individuals with poor balance exercise safely by reducing excessive or improper joint loads, preventing training-related injuries. However, few studies have investigated the biomechanical features of the lower extremities during pinnacle trainer exercise with and without partial BWS for various PSWs. We aimed to investigate the effects of partial BWS and PSW on the joint loading of the lower extremities during stepping on a pinnacle trainer. Seventeen healthy adults exercised on the pinnacle trainer with or without BWS using various PSWs. The joint resultant forces and joint moments of the lower extremities were calculated according to the kinematic and kinetic data measured via a motion capture system and force transducers on the pedals, respectively. The joint resultant forces and joint moments of the lower extremities significantly decreased with increasing percentage of BWS. The internal knee adduction moment and internal hip abduction moment significantly increased with increasing PSW. For every kilogram of BWS, the joint loading of the lower extremities decreased by approximately 1% of the joint resultant forces of body weight during exercise with the pinnacle trainer. Exercise on the pinnacle trainer with partial BWS significantly reduced joint loading. Exercise with a wider pedal stance may be helpful for knee osteoarthritis rehabilitation as it produces greater internal hip abduction and internal knee adduction moments.


Brain state-dependence of electrically evoked potentials monitored with head-mounted electronics.
Inferring changes in brain connectivity is critical to studies of learning-related plasticity and stimulus-induced conditioning of neural circuits. In addition, monitoring spontaneous fluctuations in connectivity can provide insight into information processing during different brain states. Here, we quantified state-dependent connectivity changes throughout the 24-h sleep-wake cycle in freely behaving monkeys. A novel, head-mounted electronic device was used to electrically stimulate at one site and record evoked potentials at other sites. Electrically evoked potentials (EEPs) revealed the connectivity pattern between several cortical sites and the basal forebrain. We quantified state-dependent changes in the EEPs. Cortico-cortical EEP amplitude increased during slow-wave sleep, compared to wakefulness, while basal-cortical EEP amplitude decreased. The results demonstrate the utility of using portable electronics to document state-dependent connectivity changes in freely behaving primates.


Homozygous cystathionine beta-synthase deficiency, combined with factor V Leiden or thermolabile methylenetetrahydrofolate reductase in the risk of venous thrombosis.
Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine beta-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.


Arachidonic acid stimulates prostate cancer cell growth: critical role of 5-lipoxygenase.
Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-6 poly-unsaturated fatty acids, was found to be an effective stimulator of human prostate cancer cell growth in vitro at micromolar concentrations. Selective blockade of the different metabolic pathways of arachidonic acid (e.g. ibuprofen for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase specific inhibitors, AA861 and MK886, but not by others. Addition of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of prostate cancer cell growth similar to that of arachidonic acid, whereas the leukotrienes were ineffective. Moreover, the 5-series of eicosatetraenoids could reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed with arachidonic acid showed a dramatic increase in the production of 5-HETEs which is effectively blocked by MK886. These experimental observations suggest that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects on human prostate cancer cells.


Finite element prediction with experimental validation of damage distribution in single trabeculae during three-point bending tests.
There is growing evidence that information on trabecular microarchitecture can improve the assessment of fracture risk. One current strategy is to exploit finite element (FE) analysis applied to experimental data of mechanically loaded single trabecular bone tissue obtained from non-invasive imaging techniques for the investigation of the damage initiation and growth of bone tissue. FE analysis of this type of bone has mainly focused on linear and non-linear analysis to evaluate the bone's failure properties. However, there is a lack of experimentally validated FE damage models at trabecular bone tissue level allowing for the simulation of the progressive damage process (initiation and growth) till complete fracture. Such models are needed to perform enhanced prediction of the apparent failure mechanical properties needed to assess the fracture risk of bone organs. In the current study, we develop a FE model based on a continuum damage mechanics (CDM) approach to simulate the damage initiation and propagation of a single trabecula till complete facture in quasi-static regime. Three-point bending experiments were performed on single bovine trabeculae and compared to FE results. In order to validate the proposed FE mode, (i) the force displacement curve was compared to the experimental one and (ii) the damage distribution was correlated to the measured one obtained by digital image correlation based on stress whitening in bone, reported to be correlated to microdamage. A very good agreement was obtained between the FE and experimental results, indicating that the proposed damage investigation protocol based on FE analysis and testing is reliable to assess the damage behavior of bone tissue and that the current damage model is able to accurately simulate the damaging and fracturing process of single trabeculae under quasi static load.


[Hereditary angioedema due to C1-inhibitor deficiency, a national disease management programme].
Hereditary angioedema (HAE) is a rare, painful, disabling and potentially fatal disease, where early diagnosis and effective treatment are critical. These Austrian guidelines for the diagnosis and management of HAE provide instructions and advice on the state of the art management of HAE in Austria in contrast to global guidelines, where the situation of all countries worldwide must be taken into account. Our goal is to help Austrian physicians to consider HAE as a differential diagnosis with corresponding symptoms, to make rational decisions for the diagnosis and management of HAE with C1-inhibitor deficiency (type 1 or type 2). The guidelines provide information on common and important clinical symptoms, diagnostic methods, treatment modalities, available HAE-specific medications in Austria and last but not least to motivate physicians to refer patients to HAE centers for confirmation of the diagnosis and adequate treatment decisions.


A Review of Neuroimaging in Rare Neurodegenerative Diseases.
Due to the variety of clinical symptoms that occur in rare neurodegenerative diseases and difficulties in the correct diagnosis, there is a need to learn their characteristic imaging findings by using conventional MRI. That knowledge helps to determine the appropriate differential diagnosis and avoid misdiagnosis. The aim of this review is to present the typical neuroimaging signs of the selected neurodegenerative disorders and to create a practical approach to imaging findings useful in everyday clinical practice. Images: Images of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), Creutzfeldt-Jakob disease (CJD), Wilson's disease (WD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are provided to visualize and distinguish the typical features of those diseases and therefore to assist neurologists and neuroradiologists in decision-making process. It is important to know the characteristic MRI features of rare neurodegenerative diseases and to use them in everyday clinical practice. MRI is a valuable tool when considering the initial diagnosis because it is proven to be very useful in the differentiation of more advanced stages of the rare neurodegenerative diseases but also from other neurodegenerative disorders.


Dementia and aphasia in motor neuron disease: an underrecognised association?
To determine the prevalence and nature of global cognitive dysfunction and language deficits in an unselected population based cohort of patients with motor neuron disease (MND). A battery of neuropsychological and language tests was administered to patients presenting consecutively over a 3 year period to a regional neurology service with a new diagnosis of sporadic motor neuron disease. The 18 patients could be divided on the basis of their performance into three groups: Three patients were demented and had impaired language function (group 1); two non-demented patients had an aphasic syndrome characterised by word finding difficulties and anomia (group 2). Major cognitive deficits were therefore found in five of the 18 patients (28%). The remaining 13 performed normally on the test battery apart from decreased verbal fluency (group 3). The prevalence of cognitive impairment in MND in this population based study of an unselected cohort was higher than has been previously reported. Language deficits, especially anomia, may be relatively frequent in the MND population. Aphasia in MND may be masked by dysarthria and missed if not specifically examined.


Expression profiles of androgen independent bone metastatic prostate cancer cells indicate up-regulation of the putative serine-threonine kinase GS3955.
We established gene expression profiles by gene array analysis in the LNCaP model of human prostate cancer progression and evaluated genes differentially expressed in the androgen independent and bone metastatic C4-2 cell line compared to the androgen dependent and nonmetastatic parental LNCaP cell line. Gene expression profiles were generated using Atlas cDNA arrays (Clontech, Palo Alto, California), comprising 1,176 genes. Intrinsic expression of the novel serine/threonine kinase GS3955 in LNCaP, C4-2 and PC-3 prostate cancer cells, and expression when stimulated with growth factors, was monitored by real-time reverse transcriptase-polymerase chain reaction. Furthermore, expression in human tumor specimens was evaluated. Cellular localization of GS3955 protein was analyzed by expressing it as a fusion with green fluorescent protein. Comparable numbers of genes were up-regulated and down-regulated in C4-2 compared to LNCaP. The novel serine/threonine kinase GS3955 was markedly up-regulated (greater than 40-fold) in C4-2, differentially regulated in LNCaP and C4-2 by insulin-like growth factor-1, and variably expressed in human prostate tumor specimens. Moreover, GS3955 was shown to localize in the cell cytoplasm and nucleus. Differential expression and mitogenic regulation of the serine/threonine kinase GS3955 in LNCaP and C4-2 suggest its functional involvement in the development of androgen independence and/or metastatic potential. GS3955 is also expressed in human prostate cancer specimens and further analysis may provide insights into the biology of prostate cancer progression.


A randomized trial of telephone counseling with adult moist snuff users.
To evaluate telephone counseling for moist snuff use. We recruited 221 adult males using snuff and randomized them into a telephone-counseling intervention or a quit-manual comparison group. Subjects were contacted by mail at 3 and 6 months to complete a 4-page follow-up questionnaire. A significantly higher proportion of subjects randomized to the intervention quit tobacco at each time point compared to the comparison group. With appropriate staff training, moist snuff and other types of nonsmoked tobacco should be added to the state-funded smoking cessation quit lines started in recent years.


Electrochemical Synthesis of Bismuth Particles: Tuning Particle Shape through Substrate Type within a Narrow Potential Window.
Bismuth (Bi) electrodeposition was studied on Si/Ti/Au, FTO-, and ITO-coated glasses from acidic nitrate solutions with and without gluconate within a narrow potential window (ΔE = 80 mV). This potential range was sufficient to observe a change in particle shape, from polyhedrons (including hexagons) to dendrites, the trend being slightly different depending on substrate activity. In all cases, though, the formation of dendrites was favoured as the applied potential was made more negative. Bi particles were more uniformly distributed over the substrate when sodium gluconate was added to the electrolyte. X-ray diffraction analyses of dendrites grown at -0.28 V indicated that they exhibit the rhombohedral phase of Bi and are predominantly oriented along the (003) plane. This orientation is exacerbated at the lowest applied potential (-0.20 V vs. Ag|AgCl) on glass/ITO substrate, for which completed and truncated hexagons are observed from the top view scanning electron microscopy images.


Encoder-X: Solving Unknown Coefficients Automatically in Polynomial Fitting by Using an Autoencoder.
Modeling, prediction, and recognition tasks depend on the proper representation of the objective curves and surfaces. Polynomial functions have been proved to be a powerful tool for representing curves and surfaces. Until now, various methods have been used for polynomial fitting. With a recent boom in neural networks, researchers have attempted to solve polynomial fitting by using this end-to-end model, which has a powerful fitting ability. However, the current neural network-based methods are poor in stability and slow in convergence speed. In this article, we develop a novel neural network-based method, called Encoder-X, for polynomial fitting, which can solve not only the explicit polynomial fitting but also the implicit polynomial fitting. The method regards polynomial coefficients as the feature value of raw data in a polynomial space expression and therefore polynomial fitting can be achieved by a special autoencoder. The entire model consists of an encoder defined by a neural network and a decoder defined by a polynomial mathematical expression. We input sampling points into an encoder to obtain polynomial coefficients and then input them into a decoder to output the predicted function value. The error between the predicted function value and the true function value can update parameters in the encoder. The results prove that this method is better than the compared methods in terms of stability, convergence, and accuracy. In addition, Encoder-X can be used for solving other mathematical modeling tasks.


Effect of once daily and twice daily sustained release theophylline formulations on daytime variation of bronchial hyperresponsiveness in asthmatic patients.
Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the prototype theophylline given twice a day. The aim of this study was to compare the effects on bronchial responsiveness to methacholine of an ultrasustained release theophylline formulation (Diffumal-24, Malesci, Florence, Italy) administered once a day, a sustained release theophylline formulation (Theo-Dur, Recordati, Milan, Italy) administered twice a day, and placebo. The study was performed in 12 adult patients with asthma using a randomised, double blind, three phase, cross-over design. Each phase lasted seven days and was followed or preceded by at least three days of theophylline washout. Diffumal-24 was administered once a day at 20.00 hours whereas Theo-Dur was given twice a day at 08.00 hours and 20.00 hours. In each patient the total daily dose of theophylline was the same during both phases. The dose of the two active preparations was titrated to individual needs before the beginning of the study and then given in divided or once daily doses. At 08.00, 14.00, and 20.00 hours on day 7 of each phase serum theophylline concentrations were measured and spirometric tests (FEV1) and bronchial challenge with methacholine were also performed. When the administration of Diffumal-24 was compared with that of Theo-Dur, a higher serum theophylline concentration of the former was seen in the morning whereas at 20.00 hours the reverse was true. Compared with placebo, at 08.00 hours Diffumal-24 improved FEV1 whereas Theo-Dur did not (difference between treatments 0.29 1, 95% CI 0.12 to 0.45). At 08.00 hours Diffumal-24 decreased bronchial sensitivity to methacholine, expressed as a natural logarithm of PD20, to a greater extent than Theo-Dur (difference between treatments 0.54 log units, 95% CI 0.016 to 1.08). The morning advantage observed with Diffumal-24 administration was not associated with a deterioration in the state of the airway during the daytime, the protective activity against methacholine during the 12 hours of the monitoring period being constant. Furthermore there was no difference in the mean FEV1 between the two treatments at 14.00 and 20.00 hours. In adults with stable bronchial asthma treatment with a single dose of Diffumal-24 administered in the evening improved airflow obstruction and reduced bronchial hyperresponsiveness.


No evidence of nanodiamonds in Younger-Dryas sediments to support an impact event.
The causes of the late Pleistocene megafaunal extinctions in North America, disappearance of Clovis paleoindian lithic technology, and abrupt Younger-Dryas (YD) climate reversal of the last deglacial warming in the Northern Hemisphere remain an enigma. A controversial hypothesis proposes that one or more cometary airbursts/impacts barraged North America ≈12,900 cal yr B.P. and caused these events. Most evidence supporting this hypothesis has been discredited except for reports of nanodiamonds (including the rare hexagonal polytype) in Bølling-Ållerod-YD-boundary sediments. The hexagonal polytype of diamond, lonsdaleite, is of particular interest because it is often associated with shock pressures related to impacts where it has been found to occur naturally. Unfortunately, previous reports of YD-boundary nanodiamonds have left many unanswered questions regarding the nature and occurrence of the nanodiamonds. Therefore, we examined carbon-rich materials isolated from sediments dated 15,818 cal yr B.P. to present (including the Bølling-Allerod-YD boundary). No nanodiamonds were found in our study. Instead, graphene- and graphene/graphane-oxide aggregates are ubiquitous in all specimens examined. We demonstrate that previous studies misidentified graphene/graphane-oxide aggregates as hexagonal diamond and likely misidentified graphene as cubic diamond. Our results cast doubt upon one of the last widely discussed pieces of evidence supporting the YD impact hypothesis.


RETRACTED - Risk factors for mild behavioral impairment in non-demented geriatrics: a population-based survey in Taiwan.
To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics. Population-based, cross-sectional survey. Taiwan Alzheimer Disease Association (TADA) Database. Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013. Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models. In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 - 0.12). Low body weight (OR 2.01, 95% CI 1.21-3.33), low-to-medium education (OR 1.40, 95%CI 1.06-1.85; OR 2.32, 95% CI 1.67-3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25-1.95), hyperlipidemia (OR 1.29, 95% CI 1.00-1.67), cancer (OR 2.05, 95% CI 1.37-3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76-1.32). Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.


Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130).
In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)-positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation. Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1-positive subgroup). These were also assessed in the Japanese subpopulation. There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1-positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25-0.90). In the PD-L1-positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, <0.01-0.35). Safety results in the Japanese subgroup were consistent with those in the overall population. The Japanese subgroup had a lower incidence of adverse events leading to treatment withdrawal than the overall population. More patients in the atezo + nab-P arm had neutrophil count decreases and stomatitis than patients in the plac + nab-P arm. Atezo + nab-P efficacy in Japanese patients was consistent with the overall IMpassion130 population. No new safety signals were observed, and tolerability was consistent with that of the overall population.


Location and distribution of a receptor for the 987P pilus of Escherichia coli in small intestines.
Frozen sections of rabbit or pig small intestines were stained with fluorescein-labeled antibody specific for the 987P receptor isolated from adult rabbit small intestines. The 987P receptor was present along the entire villous surface and in goblet cells in adult rabbits, but only in goblet cells in infant rabbits. In adult rabbits, the receptor was distributed equally in the jejunum and the ileum. Material antigenically similar to the rabbit 987P receptor was demonstrated in goblet cells in neonatal piglet ileum.


Physiology and pathology of somatostatin in the mammalian retina: a current view.
In the retina, peptidergic signalling participates in multiple circuits of visual information processing. The neuropeptide somatostatin (SRIF) is localised to amacrine cells and, in some instances, in a subset of ganglion cells. The variegated expression patterns of SRIF receptors (sst(1)-sst(5)) and the variety of signalling mechanisms activated by retinal SRIF suggest that this peptide may exert multiple actions on retinal neurons and on retinal physiology, although our current understanding reflects a rather complicated picture. SRIF, mostly through sst(2), may act as a positive factor in the retina by regulating retinal homeostasis and protecting neurons against damage. In this respect, SRIF analogues seem to constitute a promising therapeutic arsenal to cure different retinal diseases, as for instance, ischemic and diabetic retinopathies. However, further investigations are needed not only to fully understand the functional role of the SRIF system in the retina but also to exploit new chemical space for drug-like molecules.


A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study.
Six hundred eighty assessable patients with measureable stage III M1, non-small-cell lung cancer (NSCLC) were randomized to one of five treatment arms including cisplatin, etoposide (VP-16) +/- methylglyoxal bisguanylhydrazone (MGBG; PVp, PVpM); cisplatin, vinblastine (PVe); or PVe alternating with vinblastine, mitomycin (PVeMi); or fluorouracil, vincristine, mitomycin/cyclophosphamide, doxorubicin, cisplatin (FOMi/CAP). The overall response rate was 20% with 3% complete responses and 17% partial remissions. The duration of these responses was not statistically different by treatment regimen and varied from 2.7 months to 5.0 months. The overall median survival for all patients was 5.3 months and is not different by treatment. Toxicity was greater in PVpM. The similarity of results for response, duration of response, and survival does not establish the superiority of any of these platinum-based regimens for standard clinical usage.


Xylella fastidiosa: a model for analyzing agricultural biosecurity.
The threat to national security posed by the hostile release of human pathogens has been extensively documented. However, conclusions regarding the menace that plant pests and pathogens pose to the national economy and food supply are less developed. Here we present a risk analysis for the arrival and spread of foreign plant pathogens into the U.S. agricultural system. Xylella fastidiosa Citrus Variegated Chlorosis strain, an exotic plant pathogenic bacterium listed as a regulated biological agent under the Agricultural Bioterrorism Protection Act of 2002, serves as a model to evaluate the threat that plant diseases pose to crops and agriculture-dependent industries. We assess the nation's capacity to detect, contain, and manage newly introduced plant pathogens, exposing areas that need improvement and limitations of the system. This analysis provides a framework for understanding the risk that exotic plant diseases pose to U.S. agricultural biosecurity and a reference to continue preparing for the possible arrival of these threats.


Blood pressure control assessed by home, ambulatory and conventional blood pressure measurements in the Japanese general population: the Ohasama study.
To assess blood pressure control in the Japanese population, we analyzed previously obtained measurements of conventional, home and ambulatory blood pressures in 1,174 subjects aged > or =40 in a Japanese community. On the basis of conventional blood pressure values and the use of antihypertensive medication, participants were classified as normotensive, untreated hypertensive and treated hypertensive subjects. When 140/90, 135/85 and 135/85 mmHg were used as the hypertension criteria for conventional, home and ambulatory blood pressure measurements, respectively, all three blood pressure values were higher in untreated and treated hypertensive subjects than in normotensive subjects. Among the treated hypertensive subjects, approximately half were classified as hypertensive not only by conventional blood pressure, but also by home or ambulatory measurements. Approximately 10% of the subjects defined as normotensive by conventional blood pressure measurement were classified as hypertensive by home or ambulatory measurements, whereas 60% of the untreated hypertensive subjects as defined by conventional blood pressure measurement had normal home or ambulatory blood pressure values. Therefore, we concluded that 1) the poor blood pressure control in treated hypertensive subjects was attributable not only to the white coat effect but also to inadequate control of blood pressure; and 2) a certain percentage of subjects were misclassified as hypertensive or normotensive by conventional blood pressure measurement.


Effect of one-lung ventilation on oxygen delivery in anesthetized dogs with an open thoracic cavity.
To evaluate effects of one-lung ventilation on oxygen delivery in anesthetized dogs with an open thoracic cavity. 8 clinically normal adult Walker Hound dogs. Each dog was anesthetized and subjected to one-lung ventilation during a period when it had an open thoracic cavity. A Swan-Ganz catheter was used to measure hemodynamic variables and obtain mixed-venous blood samples. A catheter was inserted in the dorsal pedal artery to measure arterial pressure and obtain arterial blood samples. Oxygen delivery index was calculated and used to assess effects of one-lung ventilation on cardiopulmonary function. Effects on hemodynamic and pulmonary variables were analyzed. One-lung ventilation caused significant decreases in PaO2, arterial oxygen saturation (SaO2), mixed-venous oxygen saturation, and arterial oxygen content (CaO2). One-lung ventilation caused significant increases in PaCO2, physiologic dead space, and alveolar-arterial oxygen difference. Changes in SaO2, CaO2, and PaCO2, although significantly different, were not considered to be of clinical importance. One-lung ventilation induced a significant increase in pulmonary arterial wedge pressure, mean pulmonary artery pressure, and shunt fraction. One-lung ventilation did not have a significant effect on cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, and oxygen delivery index. One-lung ventilation affected gas exchange and hemodynamic function, although oxygen delivery in clinically normal dogs was not affected during a period with an open thoracic cavity. One-lung ventilation can be used safely in healthy dogs with an open thoracic cavity during surgery.


Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide.
Medical therapy is essential in the management of patients with Cushing's syndrome (CS) when curative surgery has failed, surgery is not feasible, when awaiting radiation effect, and in recurrent cases of CS. Steroidogenesis inhibitors have a rapid onset of action and are effective in reducing hypercortisolism, however, adverse effects, including adrenal insufficiency require very close patient monitoring. Osilodrostat is the only steroidogenesis inhibitor to have been assessed in prospective randomized controlled trials and approved for Cushing's disease (CD) by the US Food and Drug Administration and for CS by the European Medical Agency (EMA). Osilodrostat has been shown to be highly effective at maintaining normal urinary free cortisol in patients with CD. Drugs such as metyrapone, ketoconazole (both EMA approved), and etomidate lack prospective evaluation(s). There is, however, considerable clinical experience and retrospective data that show a very wide efficacy range in treating patients with CS. In the absence of head-to-head comparative clinical trials, therapy choice is determined by the specific clinical setting, risk of adverse events, cost, availability, and other factors. In this review practical points to help clinicians who are managing patients with CS being treated with steroidogenesis inhibitors are presented.


A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese.
Although many large-scale genome-wide association studies (GWASs) have been performed, only a few studies have successfully identified replicable, large-impact hypertension loci; even fewer studies have been done on Chinese subjects. Young-onset hypertension (YOH) is considered to be a more promising target disorder to investigate than late-onset hypertension because of its stronger genetic component. To map YOH genetic variants, we performed a 3-stage study combining 1st-stage multilocus GWASs, 2nd-stage gene expression analysis, and 3rd-stage multilocus confirmatory study. In the 1st stage, Illumina550K data from 400 case-control pairs were used, and 22 genes flanked by 14 single nucleotide polymorphism (SNP) septets (P values adjusted for false discovery rate (pFDR) < 3.16×10(-7)) were identified. In the 2nd stage, differential gene expression analysis was carried out for these genes, and 5 genes were selected (pFDR < 0.05). In the 3rd stage, we re-examined the finding with an independent set of 592 case-control pairs and with the joint samples (n = 992 case-control pairs). A total of 6 SNP septets flanking C1orf135, GSN, LARS, and ACTN4 remained significant in all 3 stages. Among them, the same septet flanking ACTN4 was also associated with blood pressure traits in the Hong Kong Hypertension Study (HKHS) and in the Wellcome Trust Case-Control Consortium Hypertension Study (WTCCCHS). LARS was detected in the HKHS, but not in the WTCCCHS. GSN may be specific to Taiwanese individuals because it was not found by either the HKHS or the WTCCCHS. Our study identified 4 previously unknown YOH loci in Han Chinese. Identification of these genes enriches the hypertension susceptibility gene list, thereby shedding light on the etiology of hypertension in Han Chinese.


Early Atrial Fibrillation During Acute Myocardial Infarction May Not Be an Indication for Long-Term Anticoagulation.
Patients with new-onset of atrial fibrillation (NOAF) during acute myocardial infarction (AMI) currently receive long-term oral anticoagulation. The risk for stroke of "early" versus "late" onset of atrial fibrillation (AF) has not been elucidated. Consecutively, AMI patients admitted to a tertiary medical center were analyzed. We excluded patients with preexisting AF, AMI onset ≥24 hours prior to admission, significant valvular disease, fever >38.5°C, in-hospital death, or coronary artery bypass graft. Atrial fibrillation was verified by electrocardiography and medical records. Overall 7061 patients were included, 1.4% developed "early-paroxysmal AF (PAF)" that resolved within 24 hours of admission and 2.5% had "late-AF" beyond the first 24 hours. Median follow-up was ≈6 years. Primary end points included ischemic stroke and all-cause mortality. Stroke rates were higher only in patients with late-AF versus no-AF but not in the early-PAF: 10.6% versus 4.2%, 5.3%, respectively (P < .001). Death rates were higher in patients with late-AF and early-PAF versus no-AF: 55.3%, 43.2%, and 29.2%, respectively (P < .001). Congestive heart failure, hypertension, age ≥75, diabetes mellitus, a stroke or transient ischemic attack, vascular disease, age 65-74, female (CHA2DS2-VASc) score underestimated stroke risk in the late-AF group. In conclusion, the study generates the hypothesis that patients with early-PAF may not have a high stroke risk questioning the indication for long-term anticoagulation.


The colR4 and colR15 beta-tubulin mutations in Chlamydomonas reinhardtii confer altered sensitivities to microtubule inhibitors and herbicides by enhancing microtubule stability.
The colR4 and colR15 beta 2-tubulin missense mutations for lysine-350 in Chlamydomonas reinhardtii (Lee and Huang, 1990) were originally isolated by selection for resistance to the growth inhibitory effects of colchicine. The colR4 and colR15 mutants have been found to be cross resistant to vinblastine and several classes of antimitotic herbicides, including the dinitroanilines (oryzalin, trifluralin, profluralin, and ethafluralin); the phosphoric amide amiprophos methyl; and the dimethyl propynl benzamide pronamide. Like colchicine and vinblastine, the antimitotic effects of these plant-specific herbicides have been associated with the depolymerization of microtubules. In contrast to their resistance to microtubule-depolymerizing drugs, the mutants have an increased sensitivity to taxol, a drug which enhances the polymerization and stability of microtubules. This pattern of altered sensitivity to different microtubule inhibitors was found to cosegregate and corevert with the beta-tubulin mutations providing the first genetic evidence that the in vivo herbicidal effects of the dinitroanilines, amiprophos methyl, and pronamide are related to microtubule function. Although wild-type like in their growth characteristics, the colR4 and colR15 mutants were found to have an altered pattern of microtubules containing acetylated alpha-tubulin, a posttranslational modification that has been associated with stable subsets of microtubules found in a variety of cells. Microtubules in the interphase cytoplasm and those of the intranuclear spindle of mitotic cells, which in wild-type Chlamydomonas cells do not contain acetylated alpha-tubulin, were found to be acetylated in the mutants. These data taken together suggest that the colR4 and colR15 missense mutations increase the stability of the microtubules into which the mutant beta-tubulins are incorporated and that the altered drug sensitivities of the mutants are a consequence of this enhanced microtubule stability.


Assessment and Implications of Right Ventricular Afterload in Tetralogy of Fallot.
Patients with tetralogy of Fallot (TOF) have abnormal right ventricular (RV) afterload because of residual or recurrent outflow tract obstruction, often with abnormal pulmonary artery (PA) vascular function. The purpose of this study was to determine if RV afterload was independently associated with death and/or heart transplant in patients with TOF. This is a retrospective study of TOF patients that underwent cardiac catheterization for clinical indications at Mayo clinic between 1990 and 2015. Invasively measured RV systolic pressure (RVSP) was used to define RV afterload. To explore clinical utility for echocardiographic estimates of invasive data, correlations between invasive and Doppler-derived indices of RV afterload were examined. Among 266 patients with TOF (age 35 ± 14 years, TOF-pulmonary atresia 117 [44%]), RVSP was 72 ± 28 mm Hg, PA systolic pressure 45 ± 19 mm Hg, mean PA pressure 27 ± 10 mm Hg, pulmonary vascular resistance 4.2 ± 3.1 WU, and PA wedge pressure 14 ± 5 mm Hg. Over a mean follow up of 12.9 years, there were 35 deaths and 4 heart transplants. Invasively measured RVSP (hazard ratio 1.25, 95% confidence interval 1.12 to 1.37; p <0.001) and TOF-pulmonary atresia (hazard ratio 1.18, 95% confidence interval 1.08 to 1.41; p = 0.023) were independent risk factors for death and/or transplant. Doppler-derived RVSP was well-correlated with invasive RVSP (r = 0.92, p <0.001), and was also independently associated with the combined end point. RVSP, a composite measure of RV afterload, is independently prognostic in patients with TOF, and can be reliably assessed using Doppler echocardiography. Further study is required to test whether interventions to reduce RVSP can improve outcomes in patients with TOF.


[Translated article] SCIWORA in children. A rare clinical entity: Ambispective study.
SCIWORA has a low incidence but a high functional repercussion. The aim of the present study was to characterize the epidemiology of this clinical-radiological condition and evaluate functional outcome with a mean of 10-years follow-up. Observational, longitudinal ambispective cohort study. Thirteen SCIWORA patients were admitted in the study period. Demographics, mechanism of injury, spinal cord MRI findings, neurological level of injury, time to SCI, neurological status (AIS) at admission/discharge/5 years, spinal cord independence measure (SCIM III) scale at admission and discharge, hospital length of stay and mean follow-up were recorded. On October 2022 patients were re-evaluated using NDI, Oswestry, and SV-QLI/SCI. Median age was 4 years. The study population for this investigation was mostly men (77%). 54% of level of injury correspond to cervical spine. AIS at admission was A (31%) and C (31%). Neurological level of injury was C2 (22%) and T10 (15%). Motor vehicle-related injury was the most prevalent mechanism of injury (77%), SCIM III scale at admission and discharge: 28.5/42, hospital length of stay was 115 days. The NDI was 11.6, Oswestry: 15.3 and SV-QLI/SCI: 17. Seventy-seven percent of SCIWORA patients was detected under 8 years-old. At 1 year follow-up after discharge 31% patients were AIS grade D and with 5 years follow-up the percentage remain constant. No statistically significant differences in the mechanism of injury and MRI findings (P=0.872), age and MRI spinal cord findings (P=0.149) were found in SCIWORA patients.


Use of vascular access ports with intrathoracic drains for treatment of pleural effusion in three dogs.
3 dogs (9 to 12 years old) were evaluated because of recurrent pleural effusion that was refractory to treatment of the underlying cause. Dogs were evaluated because of cough, dyspnea, tachypnea, or lethargy or a combination of these clinical signs. Radiography, ultrasonography, or thoracocentesis were used to confirm the presence of pleural fluid in each dog. A neoplastic cause of pleural effusion was confirmed in 2 dogs. In 1 dog, fasciitis of the mediastinum and the left parietal pleura was diagnosed, with no evidence of neoplasia. Each dog was anesthestized, and thoracotomy was performed with manual perforation of the mediastinum. Permanent, subcutaneously placed vascular access ports were attached to intrathoracic, Jackson-Pratt drain tubing for repeated drainage of pleural fluid. Drains were used successfully in the 3 dogs for periods of 6 weeks, 11 weeks, and > 3 years. Findings suggest that subcutaneous vascular access ports attached to intrathoracic drain tubing may be an effective way to remove recurrent pleural effusion in dogs.


Sperm ultrastructure of the hydrothermal vent octopod Vulcanoctopus hydrothermalis.
Sperm ultrastructure of the deep-sea hydrothermal vent octopod Vulcanoctopus hydrothermalis has been carried out by transmission electron microscopy. Spermatozoa of this species have the shortest head observed so far in octopodids. The acrosome possesses a helix with six gyres. The rod-shaped nucleus is short and wide in relation with other octopodids. Noteworthy features along the nucleus are the regularly disposed dense bands of cytoplasm, which have not been observed before in octopodids. The nuclear fossa is very short and wavy. Mitochondrial sheath has 10 elongated mitochondria running parallel to the axoneme-coarse fibers complex. Sperm morphology of V. hydrothermalis resembles that of Enteroctopus dofleini, suggesting a close phylogenetic relationship.


Barrier versus oral contraceptive use: a study of female college students.
Although they provide birth control and are easier to use, oral contraceptives (OCPs) are not the preferred approach to preventing sexually transmitted disease (STD). Do the knowledge, attitudes, and experiences of oral contraceptive users place them at greater risk for STDs than those who employ barrier methods? This study examined differences between sexually active female college students (ie, those who reported ever having had vaginal intercourse) who used OCPs and those who employed barrier methods of contraception at the time of their most recent intercourse. The authors analyzed HIV- and other STD-related knowledge, attitudes, and behaviors from three consecutive annual health surveys of young women about to begin their first year of college. Findings showed barrier and OCP users to be comparable in knowledge about the effectiveness of various contraceptive methods in protecting them against STDs, perceived personal susceptibility to HIV, and experiences with alcohol before sexual intercourse. Oral contraceptive users, compared with those in the group who used barrier methods, reported a greater number of recent partners (p less than .03) and greater perceived vulnerability to STDs (p less than .03). Student healthcare providers must develop creative educational strategies to encourage simultaneous use of both oral contraceptives and barrier methods to protect students against STDs and pregnancy.


Motor and emotional behaviours elicited by electrical stimulation of the human cingulate cortex.
The cingulate cortex is a mosaic of different anatomical fields, whose functional characterization is still a matter of debate. In humans, one method that may provide useful insights on the role of the different cingulate regions, and to tackle the issue of the functional differences between its anterior, middle and posterior subsectors, is intracortical electrical stimulation. While previous reports showed that a variety of integrated behaviours could be elicited by stimulating the midcingulate cortex, little is known about the effects of the electrical stimulation of anterior and posterior cingulate regions. Moreover, the internal arrangement of different behaviours within the midcingulate cortex is still unknown. In the present study, we extended previous stimulation studies by retrospectively analysing all the clinical manifestations induced by intracerebral high frequency electrical stimulation (50 Hz, pulse width: 1 ms, 5 s, current intensity: average intensity of 2.7 ± 0.7 mA, biphasic) of the entire cingulate cortex in a cohort of 329 drug-resistant epileptic patients (1789 stimulation sites) undergoing stereo-electroencephalography for a presurgical evaluation. The large number of patients, on one hand, and the accurate multimodal image-based localization of stereo-electroencephalography electrodes, on the other hand, allowed us to assign specific functional properties to modern anatomical subdivisions of the cingulate cortex. Behavioural or subjective responses were elicited from the 32.3% of all cingulate sites, mainly located in the pregenual and midcingulate regions. We found clear functional differences between the pregenual part of the cingulate cortex, hosting the majority of emotional, interoceptive and autonomic responses, and the anterior midcingulate sector, controlling the majority of all complex motor behaviours. Particularly interesting was the 'actotopic' organization of the anterior midcingulate sector, arranged along the ventro-dorsal axis: (i) whole-body behaviours directed to the extra-personal space, such as getting-up impulses, were elicited ventrally, close to the corpus callosum; (ii) hand actions in the peripersonal space were evoked by the stimulation of the intermediate position; and (iii) body-directed actions were induced by the stimulation of the dorsal branch of the cingulate sulcus. The caudal part of the midcingulate cortex and the posterior cingulate cortex were, in contrast, poorly excitable, and mainly devoted to sensory modalities. In particular, the caudal part of the midcingulate cortex hosted the majority of vestibular responses, while posterior cingulate cortex was the principal recipient of visual effects. We will discuss our data in the light of current controversies on the role of the cingulate cortex in cognition and emotion.


Endoscopic ultrasound-guided vascular interventions: Current insights and emerging techniques.
Endoscopic ultrasound (EUS) is one of the significant breakthroughs in the field of advanced endoscopy. In the last two decades, EUS has evolved from a diagnostic tool to a real-time therapeutic modality. The luminal gastrointestinal (GI) tract provides a unique opportunity to access multiple vascular structures, especially in the mediastinum and abdomen, thus permitting a variety of EUS-guided vascular interventions. The addition of the doppler and contrast-enhanced capability to EUS has further helped provide real-time visualization of blood flow in vessels through the GI tract. EUS-guided vascular interventions rely on standard endoscopic accessories and interventional tools such as fine-needle aspiration needles and fine-needle biopsy. EUS allows the visualization of various structures in real-time by differentiating tissue densities and vascularity, thus, avoiding radiation exposure. EUS-guided techniques also allow real-time microscopic examination after target biopsy. Furthermore, many necessary interventions can be done during the same procedure after diagnosis. This article provides an overview of EUS-guided vascular interventions such as variceal, non-variceal bleeding interventions, EUSguided portal vein (PV) access with the formation of an intrahepatic portosystemic shunt, and techniques related to diagnosis of GI malignancies. Furthermore, we discuss current insights and future outlook of therapeutic modalities like PV embolization, PV sampling, angiography, drug administration, and portal pressure measurement.


Novel methodology to obtain salient biomechanical characteristics of insole materials.
Viscoelastic inserts are commonly used as artificial shock absorbers to prevent neuropathic foot ulcerations by decreasing pressure on the sole of the foot. Unfortunately, there is little scientific information available to guide physicians in the selection of appropriate insole materials. Therefore, a novel methodology was developed to form a rational platform for biomechanical characterizations of insole material durability, which consisted of in vivo gait analysis and in vitro bioengineering measurements. Results show significant differences in the compressive stiffness of the tested insoles and the rate of change over time in both compressive stiffness and peak pressures measured. Good correlations were found between pressure-time integral and Young's modulus (r2 = 0.93), and total energy applied and Young's modulus (r2 = 0.87).


Complex carbohydrates reduce the frequency of antagonistic interactions among bacteria degrading cellulose and xylan.
Bacterial competition for resources is common in nature but positive interactions among bacteria are also evident. We speculate that the structural complexity of substrate might play a role in mediating bacterial interactions. We tested the hypothesis that the frequency of antagonistic interactions among lignocellulolytic bacteria is reduced when complex polysaccharide is the main carbon source compared to when a simple sugar such as glucose is available. Results using all possible pairwise interactions among 35 bacteria isolated from salt marsh detritus showed that the frequency of antagonistic interactions was significantly lower on carboxymethyl cellulose (CMC)-xylan medium (7.8%) than on glucose medium (15.5%). The two interaction networks were also different in their structures. Although 75 antagonistic interactions occurred on both media, there were 115 that occurred only on glucose and 20 only on CMC-xylan, indicating that some antagonistic interactions were substrate specific. We also found that the frequency of antagonism differed among phylogenetic groups. Gammaproteobacteria and Bacillus sp. were the most antagonistic and they tended to antagonize Bacteroidetes and Actinobacteria, the most susceptible groups. Results from the study suggest that substrate complexity affects how bacteria interact and that bacterial interactions in a community are dynamic as nutrient conditions change.


Community screening for mental illness: a validity study of the General Health Questionnaire.
The 60-item GHQ was validated in a community population by comparison with the CIS. The GHQ failed to identify nearly half of the psychiatric 'cases' in this population. Those missed were similar to those detected except for greater chronicity of illness and more frequent social and interpersonal problems. The GHQ appears to be unsuitable as a screening instrument for mental illness in the community and the possible reasons are discussed. Principal components and analysis resulted in a 15-item GHQ factor which, when used with Likert scoring, resulted in considerable improvement and failed to identify only 4 per cent of 'cases'. It is suggested that this may prove a more satisfactory screening instrument.