Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006.
The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (>or=120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.


Measuring and modeling the bubble population produced by an underwater explosion.
Underwater explosions have been studied intensively in the United States since 1941 [e.g., R. H. Cole, Underwater Explosions (Princeton University Press, Princeton, NJ, 1945), pp. 3-13]. Research to date has primarily focused on the initial shock and subsequent pressure waves caused by the oscillations of the "gas-globe" resulting from charge detonation. These phenomena have relatively short timescales (typically less than 2 s). However, after the gas-globe rises through the water column and breaks the surface, there remains behind a cloud of bubbles and perhaps debris from the explosion container which has been markedly less studied. A recent experiment measured the spatial and temporal acoustic response of the bubble cloud resulting from a 13.6 kg PBXN-111 charge detonated at 15.2 m (50 ft) depth. A directional projector was used to propagate linear frequency-modulated (5-65 kHz) and 40 kHz tonal pulses through the bubble cloud. Two hydrophone arrays were positioned so as to measure the energy lost in propagating through the bubble cloud. Three methods have been utilized to invert measurements and estimate the bubble population. The bubble population estimates have been used to develop a model for the bubble population resulting from an underwater explosion.


Views on technology among people in need of health care at home.
The aim of this study was to describe how people in need of health care at home view technology. A qualitative approach was used based on qualitative interviews, followed by qualitative content analysis. District nurses (DNs) from 4 health care centres in Northern Sweden had access to different kinds of distance-spanning technology with mobile devices and who used it in their health care at home. Persons in whose home the technology was being used were asked to participate in an interview. The interviewed persons were selected consecutively. The results fall into 2 categories: (1) The well-known technology at hospital is new at home, (2) the new technology opens up possibilities but it also has limitations, with seven adherent subcategories. The participants viewed the technology at home as something good and as something that could open up possibilities. At the same time, they placed the use of the technology in the hands of the staff which indicates some degree of dissociation from the technology. The importance of personal meetings between patient and caregiver was very clearly stressed even when distance meetings could be performed and accepted. The participants expressed immense trust in the nursing staff and considered them responsible for the new technology at home.


Using tears as a non-invasive source for early detection of breast cancer.
The changing expression levels of ocular proteins in response to systemic disease has been well established in literature. In this study, we examined the ocular proteome to identify protein biomarkers with altered expression levels in women diagnosed with breast cancer. Tear samples were collected from 273 participants using Schirmer strip collection methods. Following protein elution, proteome wide trypsin digestion with Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used to identify potential protein biomarkers with altered expression levels in breast cancer patients. Selected biomarkers were further validated by enzyme linked immunosorbent assay (ELISA). A total of 102 individual tear samples (51 breast cancer, 51 control) were analyzed by LC-MS/MS which identified 301 proteins. Spectral intensities between the groups were compared and 14 significant proteins (p-value <0.05) were identified as potential biomarkers in breast cancer patients. Three biomarkers, S100A8 (p-value = 0.0069, 7.8-fold increase), S100A9 (p-value = 0.0048, 10.2-fold increase), and Galectin-3 binding protein (p-value = 0.01, 3.0-fold increase) with an increased expression in breast cancer patients were selected for validation using ELISA. Validation by ELISA was conducted using 171 individual tear samples (75 Breast Cancer and 96 Control). Similar to the observed LC-MS/MS results, S100A8 (p-value <0.0001) and S100A9 (p-value <0.0001) showed significantly higher expression in breast cancer patients. However, galectin-3 binding protein had increased expression in the control group. Our results provide further support for using tear proteins to detect non-ocular systemic diseases such as breast cancer. Our work provides crucial details to support the continued evaluation of tear samples in the screening and diagnosis of breast cancer and paves the way for future evaluation of the tear proteome for screening and diagnosis of systemic diseases.


Platelet-activating factor acetylhydrolase (PAF-AH).
Platelet-activating factor (PAF) is one of the most potent lipid messengers involved in a variety of physiological events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity, and its deacetylation induces loss of activity. The deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH). A series of biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Type I PAF-AH is a G-protein-like complex consisting of two catalytic subunits (alpha1 and alpha2) and a regulatory beta subunit. The beta subunit is a product of the LIS1 gene, mutations of which cause type I lissencephaly. Recent studies indicate that LIS1/beta is important in cellular functions such as induction of nuclear movement and control of microtubule organization. Although substantial evidence is accumulating supporting the idea that the catalytic subunits are also involved in microtubule function, it is still unknown what role PAF plays in the process and whether PAF is an endogenous substrate of this enzyme. Type II PAF-AH is a single polypeptide and shows significant sequence homology with plasma PAF-AH. Type II PAF-AH is myristoylated at the N-terminus and like other N-myristoylated proteins is distributed in both the cytosol and membranes. Plasma PAF-AH is also a single polypeptide and exists in association with plasma lipoproteins. Type II PAF-AH as well as plasma PAF-AH may play a role as a scavenger of oxidized phospholipids which are thought to be involved in diverse pathological processes, including disorganization of membrane structure and PAF-like proinflammatory action. In this review, we will focus on the structures and possible biological functions of intracellular PAF-AHs.


Looking for high-production and sustainable diets for lactating cows: A survey in Italy.
The aim of the present study was to evaluate, through a survey conducted on commercial farms, the global warming potential (GWP) of different lactating cow total mixed rations (TMR) and to identify the best dietary strategies to increase feed efficiency (FE) and reduce enteric CH4 emission. A total of 171 dairy herds were selected: data about dry matter intake (DMI), lactating cow TMR composition, and milk production and composition were provided by farmers. Diet GWP (kg of CO2 equivalents; CO2eq) was calculated as sum of GWP (kg of CO2eq) of each included ingredient, considering inputs needed at field level, feed processing, and transport. For soybean solvent meal, land use change was included in the assessment. Enteric methane production (g/d) was estimated [using the equation CH4 (g/d) = 2.54 + 19.14 × DMI] to calculate CH4 emission for kilograms of fat- and protein-corrected milk (FPCM). The data set was analyzed by generalized linear model and logistic analysis using SAS 9.4 (SAS Institute Inc., Cary, NC). The frequency distribution showed wide variation among farms for GWP (kg of CO2eq) of TMR: approximately 25% of the surveyed farms showed a diet GWP of 15 kg of CO2eq, 20% showed a GWP of 13 kg of CO2eq, and 16.7% showed a GWP of 17 kg of CO2eq. The variation among farms was due to the feedstuffs used. Among feedstuffs, soybean meal (SBM) had the highest correlation with the GWP of the TMR as shown by the following equation: TMR GWP (kg of CO2eq) = 2.49 × kg of SBM + 6.9 (R2 = 0.547). Moreover, diets with inclusion of SBM >15% of dry matter (DM) did not result in higher milk production than diets with a lower inclusion of SBM (≤15%). Average daily milk production of cows was 29.8 [standard deviation (SD) 4.83] kg with fat and protein contents of 3.86% (SD 0.22) and 3.40% (SD 0.14), respectively. The average DMI (kg/d) of lactating cows was 22.3 (SD 2.23). Logistic analysis demonstrated that corn silage ≤30% of diet DM was associated with higher FE. Almost 50% of farms had an average value of 15.0 g of CH4/kg of FPCM and about 30% of farms had an average of 12.5 g of CH4/kg of FPCM. The results demonstrated that lower enteric CH4 production was related to inclusion (% of diet DM) of ≤12% alfalfa hay and >30% corn silage. Diets with >34% neutral detergent fiber had higher CH4 production (>14.0 g/kg of FPCM) than those with lower neutral detergent fiber content. In contrast, lower enteric CH4 production (≤14.0 g/kg of FPCM) was related to diets characterized by net energy of lactation (NEL) >1.61 Mcal/kg and >4% ether extract. The variability in TMR GWP shows significant potential for reducing the GWP of a diet through choice and inclusion levels of ingredients (mainly SBM) and the possibility of decreasing methane enteric emission associated with milk production on a commercial scale.


Determinants and outcomes of acute pancreatitis in patients hospitalized for COVID-19: Early pandemic experience.
To examine the predictors and outcomes associated with the development of acute pancreatitis (AP) in patients hospitalized with Coronavirus Disease 2019 (COVID-19). This is an observational analysis of the 2020 National Inpatient Sample Database. The study includes adult patients who were admitted with a confirmed diagnosis of COVID-19 and stratifies them based on the presence or absence of AP during their hospitalization. Predictors of AP development between the two groups and differences in outcomes are examined. Multivariate logistic regression analysis using Stata/BE 17.0 is conducted, with adjustments made for age, sex, race, and Charlson Comorbidity Index (CCI). Statistical significance is determined at a p-value of <0.05. Significant factors associated with an increased risk of AP in COVID-19 patients include Hispanic ethnicity, higher Charlson Comorbidity Index (CCI) score, residence in states located in the southern region, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use. COVID-19 patients who developed AP were also found to be at higher risk of adverse outcomes, including mortality, acute coronary syndrome, acute kidney injury, sepsis, septic shock, in-hospital cardiac arrest, invasive mechanical ventilation, upper gastrointestinal bleeding, prolonged length of stay, and increased healthcare cost. In hospitalized patients with COVID-19, the presence of AP is associated with increased mortality and morbidity. Risk factors for developing AP in this population include Hispanic ethnicity, residence in the southern region, higher Charlson Comorbidity Index (CCI) score, history of chronic kidney disease, chronic liver disease, malnutrition, portal hypertension, and alcohol use.


Associations of Personality Traits and Emotional Intelligence: Comparing Individuals in Rehabilitation from Drug Misuse, Occasional Users and Non-Users.
Background: Personality traits and Emotional Intelligence abilities have gained a central place in the etiology of drug use, although understudied until recently. Objective: To examine the associations between personality traits and Emotional Intelligence in people that are in process of rehabilitation from drug misuse, to compare them with occasional users and non-users and to estimate the factors associated with the likelihood of drug misuse. Methods: 244 individuals (52.5% male) participated in the study. Sixty of them were suffering from drug misuse disorders, thirty-two were individuals that used drugs occasionally and 142 were non-users. Personality was assessed with the EPQ and Emotional Intelligence with the WEILS. Results: Results suggested that in drug misuse, emotional use and regulation are positively correlated with extraversion, and negatively correlated with neuroticism, whilst people that misuse drugs differ from occasional and non-users in emotional use and regulation, and in all personality traits except extraversion. Regression analyses proposed that a combination of sex, age, emotional regulation, and neuroticism contributes to the likelihood of a person abusing drugs, as opposed to occasional or no use. Conclusion: Our findings showcase that Emotional Intelligence and personality traits indeed play an important role in drug use, specifically when considering factors that protect from or drive towards misuse. Such results call for the implementation of preventive programs for occasional drug users and therapeutic interventions for people that misuse drugs, targeting the levels of neuroticism and enhancing the ability of regulating the negative emotions, to protect from drug misuse.


Role of wormwood (Artemisia absinthium) extract on oxidative stress in ameliorating lead induced haematotoxicity.
Effects of ROS generation have been postulated to be major contributors to lead-exposure related disease. The aim of the study was to investigate the effect of aqueous extract of wormwood (Artemisia absinthium) on oxidative stress in rats protractedly exposed to lead. Aqueous extract of wormwood plant was administered orally (200 mg x kg(-1) body weight). Plasma vitamin C, E and non-protein thiol concentrations, red blood cells (RBC) thiobarbituric acid reactive substances, reduced glutathione levels and haemolysis test were evaluated. In addition, RBC antioxidant enzymes activities such as superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase were also estimated. After 11-weeks, significant decreases of plasma vitamin C, E, non protein-thiol (NP-SH) and RBC-reduced glutathione levels were observed in Pb compared to control group (-32.9%, -57.1%, -53.1%, -33.9%, respectively); superoxide dismutase, glutathione peroxidase, uric aminolevulinic acid and haemolysis test significantly increased in Pb compared to control group (+64.3%, +40.3%, +145%, +44.3%, respectively). In our investigation, after 4-weeks of treatment all treated groups did not show any difference compared to the control group, except for glutathione peroxidase and RBC-superoxide dismutase activity (-15.7% and +16.4%, respectively). The findings of this study suggest that wormwood (Artemisia absinthium) extract restored the enzymes activities perturbed by exposure to lead, and had a protective role against lipid peroxidation.


Rope-producing strains of Bacillus spp. from wheat bread and strategy for their control by lactic acid bacteria.
Two types of white wheat bread (high- and low-type loaves) were investigated for rope spoilage. Thirty of the 56 breads tested developed rope spoilage within 5 days; the high-type loaves were affected by rope spoilage more than the low-type loaves. Sixty-one Bacillus strains were isolated from ropy breads and were characterized on the basis of their phenotypic and genotypic traits. All of the isolates were identified as Bacillus subtilis by biochemical tests, but molecular assays (randomly amplified polymorphic DNA PCR assay, denaturing gradient gel electrophoresis analysis, and sequencing of the V3 region of 16S ribosomal DNA) revealed greater Bacillus species variety in ropy breads. In fact, besides strains of B. subtilis, Bacillus licheniformis, Bacillus cereus, and isolates of Bacillus clausii and Bacillus firmus were also identified. All of the ropy Bacillus isolates exhibited amylase activity, whereas only 32.4% of these isolates were able to produce ropiness in bread slices after treatment at 96 degrees C for 10 min. Strains of lactic acid bacteria previously isolated from sourdough were first selected for antirope activity on bread slices and then used as starters for bread-making experiments. Prevention of growth of approximately 10(4) rope-producing B. subtilis G1 spores per cm(2) on bread slices for more than 15 days was observed when heat-treated cultures of Lactobacillus plantarum E5 and Leuconostoc mesenteroides A27 were added. Growth of B. subtilis G1 occurred after 7 days in breads started with Saccharomyces cerevisiae T22, L. plantarum E5, and L. mesenteroides A27.


Temperature-independent tilted fiber grating vibration sensor based on cladding-core recoupling.
A novel structure in which a short optical fiber stub containing a weakly tilted Bragg grating is spliced to another slightly offset fiber. The total power reflected from this structure is independent of temperature and occurs in two well-defined wavelength bands, only one of which reflects a different amount of power as the fiber stub bends or vibrates. The smart sensing structure presents an extremely high sensitivity for microbending, and its frequency response has been tested to higher than 2 kHz so far in temperature-immune vibration measurements via cost-effective power detection.


Molecular and Cellular Mechanisms of Action of Cannabidiol.
Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries for both recreational and medicinal purposes. CBD lacks the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) and has shown great therapeutic potential. CBD exerts a wide spectrum of effects at a molecular, cellular, and organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, and excitability, among others, modifying many physiological and pathophysiological processes. There is evidence that CBD may be effective in treating several human disorders, like anxiety, chronic pain, psychiatric pathologies, cardiovascular diseases, and even cancer. Multiple cellular and pre-clinical studies using animal models of disease and several human trials have shown that CBD has an overall safe profile. In this review article, we summarize the pharmacokinetics data, the putative mechanisms of action of CBD, and the physiological effects reported in pre-clinical studies to give a comprehensive list of the findings and major effects attributed to this compound.


[Changes in the activity of cyclic adenosine monophosphate metabolism enzymes in myocardial hypertrophy and after exposure to hyperbaric oxygenation].
Hypertrophy of myocardium, developed within 4 weeks after aorta stenosis, led to alteration in content of adrenaline in heart tissue as well as in some pathways of cAMP turnover: decrease in content of cAMP, an increase in the basal activity of adenylate cyclase, decrease in activation of the enzyme by adrenaline; activity of phosphodiesterase was not distinctly altered. Under conditions of hyperbaric oxygenation hypertrophy of myocardium became less distinct, content of cAMP was increased up to the normal value, the increased basal activity of adenylate cyclase was slightly decreased, whereas sensitivity of the enzyme to adrenaline did not reduce, content of adrenaline was increased.


Using e-health to enable culturally appropriate mental healthcare in rural areas.
The objective of this study was to review relevant research issues in the provision of culturally appropriate e-mental healthcare and make recommendations for expanding and prioritizing research efforts in this area. A workshop was convened by the Office of Rural Mental Health Research (ORMHR) at the National Institute of Mental Health (NIMH), the Center for Reducing Health Disparities at the University of California, Davis, the California Telemedicine and e-Health Center, and the California Endowment in December 2005, during which papers were presented concerning culture and e-mental health. Relevant literature was reviewed and research questions were developed. Major issues in the provision of culturally appropriate e-mental healthcare were defined, as were the barriers to the provision of such care in rural areas and interventions to overcome these barriers. Rural areas have increased barriers to culturally appropriate mental healthcare because of increased rates of poverty, increasingly large ethnic minority populations, and various degrees of geographical isolation and cultural factors specific to rural communities. Although culture and language are major barriers to receiving appropriate mental healthcare, including e-mental healthcare, they cannot be separated from other related influential variables, such as poverty and geography. Each of these critical issues must be taken into account when planning technologically enabled rural mental health services. This review describes one in a series of ORMHR/NIMH efforts aimed at stimulating research using culturally appropriate e-mental health strategies that address unique characteristics of various racial/ethnic groups, as well as rural and frontier populations.


The evolution of combinatorial gene regulation in fungi.
It is widely suspected that gene regulatory networks are highly plastic. The rapid turnover of transcription factor binding sites has been predicted on theoretical grounds and has been experimentally demonstrated in closely related species. We combined experimental approaches with comparative genomics to focus on the role of combinatorial control in the evolution of a large transcriptional circuit in the fungal lineage. Our study centers on Mcm1, a transcriptional regulator that, in combination with five cofactors, binds roughly 4% of the genes in Saccharomyces cerevisiae and regulates processes ranging from the cell-cycle to mating. In Kluyveromyces lactis and Candida albicans, two other hemiascomycetes, we find that the Mcm1 combinatorial circuits are substantially different. This massive rewiring of the Mcm1 circuitry has involved both substantial gain and loss of targets in ancient combinatorial circuits as well as the formation of new combinatorial interactions. We have dissected the gains and losses on the global level into subsets of functionally and temporally related changes. One particularly dramatic change is the acquisition of Mcm1 binding sites in close proximity to Rap1 binding sites at 70 ribosomal protein genes in the K. lactis lineage. Another intriguing and very recent gain occurs in the C. albicans lineage, where Mcm1 is found to bind in combination with the regulator Wor1 at many genes that function in processes associated with adaptation to the human host, including the white-opaque epigenetic switch. The large turnover of Mcm1 binding sites and the evolution of new Mcm1-cofactor interactions illuminate in sharp detail the rapid evolution of combinatorial transcription networks.


Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.
Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.


Nitro blue tetrazolium inhibits but does not mimic hypoxic vasoconstriction in isolated rabbit lungs.
It has been suggested that hypoxic pulmonary vasoconstriction (HPV) may mainly proceed via loss of normoxic vasodilation, forwarded by tonic O2-dependent formation of nitric oxide and superoxide (23). Both agents may stimulate guanylate cyclase, the latter via conversion to hydrogen peroxide and formation of compound I with catalase. We probed this hypothesis in perfused rabbit lungs, employing the superoxide scavengers superoxide dismutase (SOD), 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), and nitro blue tetrazolium (NBT) and the catalase inhibitor aminotriazole (AT). NBT turned out to be a potent dose-dependent inhibitor of HPV in a concentration range of 200 nM to 1 microM, and superimposable dose-inhibition curves were obtained when lung synthesis of nitric oxide and vasodilatory prostanoids was preblocked by NG-monomethyl-L-arginine (L-NMMA) and acetylsalicylic acid (ASA). The NBT effect was specific because no inhibition in the vasoconstrictor responses to the stable thromboxane analog U-46619 and angiotensin II was observed. In contrast, SOD and Tiron were ineffective. AT exerted nonspecific inhibition of the hypoxia- and chemical vasoconstrictor-induced pressor responses. When applied under normoxic conditions, however, NBT alone or coapplied with L-NMMA or ASA, both for blockage of parallel vasodilatory pathways, did not mimic the hypoxia-induced vasoconstrictor response. In conclusion, the present study supports an important role for superoxide in the basic mechanism of HPV, but it questions the concept that loss of tonic vasorelaxation via this pathway is the underlying event in rabbit lungs. The mechanisms relating O2 tension-dependent superoxide and hydrogen peroxide generation to the vasoconstrictor event occurring in HPV remain to be further elucidated.


Association between regional differences in muscle activation in one session of resistance exercise and in muscle hypertrophy after resistance training.
The purpose of this study was to examine if the regional difference in muscle hypertrophy after chronic resistance training is associated with muscle activation after one session of resistance exercise. Twelve men performed one session of resistance exercise of elbow extensors. Before and immediately after the exercise, transverse relaxation time (T2)-weighted magnetic resonance (MR) images of upper arm were recorded to evaluate the muscle activation along its length. In the MR images, T2 for the pixels within the triceps brachii muscle was quantified. The number of pixels with T2 greater than the threshold (mean + 1SD of T2 before the exercise) was expressed as the ratio to the number of pixels occupied by the muscle (%activated area). Another 12 subjects completed 12 weeks of training intervention (3 days per week), which consisted of the same program variables as used in the experiment for the T2 measurement. The cross-sectional areas of the triceps brachii before and after the training intervention were measured from MR images of upper arm. The %activated area of the triceps brachii induced by one session of the exercise was found to be significantly lower in the distal region than the middle and proximal regions. Similarly, the relative increase in muscle cross-sectional area after the 12 weeks of training intervention was significantly less in the distal region than the middle and proximal regions. The results suggest that the regional difference in muscle hypertrophy after chronic resistance training is attributable to the regional difference in muscle activation during the exercise.


[Development and validating an educational booklet for childbirth companions].
The article describes the steps in producing and validating an educational booklet for childbirth companions. Methodological study conducted in 2011 consisting of the following steps: situational assessment; establishing brochure content; content selection and referencing; drafting the text; design of illustrations; layout; consultation of specialists; consultation of target audience; amendments; proofreading; evaluation using the Flesch Reading Ease Formula. The topics portrayed the sequence of events involving support from gestation to the postpartum period. The concordance rate among companions was greater than or equal to 81.8% for the topics organisation, writing style, presentation and motives. The overall Content Validity Index of the booklet was 0.94. The booklet was classified as easy reading or very easy reading according to the results of the Flesch Reading Ease Formula. The presentation and content of the manual were validated for use with the target audience by the specialists and representatives of the target audience.


Overexpression of UBE2E2 in mouse pancreatic β-cells leads to glucose intolerance via reduction of the β-cell mass.
Genome-wide association studies have identified several gene polymorphisms, including UBE2E2, associated with type 2 diabetes. Although UBE2E2 is one of the ubiquitin-conjugating enzymes (E2s) involved in the process of ubiquitin modifications, the pathophysiological roles of UBE2E2 in metabolic dysfunction are not yet understood. Herein, we showed upregulated UBE2E2 expression in the islets of a mouse model of diet-induced obesity. The diabetes risk allele of UBE2E2 (rs13094957) in non-coding regions was associated with upregulation of the UBE2E2 mRNA in the human pancreas. While glucose-stimulated insulin secretion was intact in the isolated islets, pancreatic β-cells-specific Ube2e2-transgenic (TG) mice exhibited reduced insulin secretion and decreased β-cell mass. In the TG mice, suppressed proliferation of β-cells before the weaning period and under the high-fat-diet condition was accompanied by elevated gene expression levels of p21, resulting in decreased postnatal β-cell mass expansion and compensatory β-cell hyperplasia, respectively. In the TG islets, proteomic analysis identified enhanced formation of various types of polyubiquitin chains, accompanied by increased expression of Nedd4 E3 ubiquitin-protein ligase. Ubiquitination assays showed that UBE2E2 mediated the elongation of ubiquitin chains by Nedd4. The data suggest that UBE2E2-mediated ubiquitin modifications in the β-cells play an important role in regulating glucose homeostasis and β-cell mass.


Angiotensin II modulates CD40 expression in vascular smooth muscle cells.
The signalling pathway CD40/CD40L (CD40 ligand) plays an important role in atherosclerotic plaque formation and rupture. AngII (angiotensin II), which induces oxidative stress and inflammation, is also implicated in the progression of atherosclerosis. In the present study, we tested the hypothesis that AngII increases CD40/CD40L activity in vascular cells and that ROS (reactive oxygen species) are part of the signalling cascade that controls CD40/CD40L expression. Human CASMCs (coronary artery smooth muscle cells) in culture exposed to IL (interleukin)-1beta or TNF-alpha (tumour necrosis factor-alpha) had increased superoxide generation and enhanced CD40 expression, detected by EPR (electron paramagnetic resonance) and immunoblotting respectively. Both phenomena were abolished by previous incubation with membrane-permeant antioxidants or cell transfection with p22(phox)antisense. AngII (50-200 nmol/l) induced an early and sustained increase in CD40 mRNA and protein expression in CASMCs, which was blocked by treatment with antioxidants. Increased CD40 expression led to enhanced activity of the pathway, as AngII-treated cells stimulated with recombinant CD40L released higher amounts of IL-8 and had increased COX-2 (cyclo-oxygenase-2) expression. We conclude that AngII stimulation of vascular cells leads to a ROS-dependent increase in CD40/CD40L signalling pathway activity. This phenomenon may be an important mechanism modulating the arterial injury observed in atherosclerosis-related vasculopathy.


Acrokeratoelastoidosis treated with the erbium:YAG laser.
Acrokeratoelastoidosis is a rare skin disorder characterized by grouped, small, firm, translucent papules distributed on the margins of the hands and feet. We report a 21-year-old white patient with acrokeratoelastoidosis in whom Er:YAG laser surgery was carried out, resulting in a slight post-treatment improvement of the disease with slight flattening of the lesions. No clinical recurrence of the lesions developed during the 6 months of follow-up. We suggest that Er:YAG laser surgery of acrokeratoelastoidosis may be considered as a treatment option for this rare disease; however, patients should be informed of the limited clinical improvement obtained with this treatment.


Molecular analysis of mutations induced in human cells by N-ethyl-N-nitrosourea.
Mutational activation of cellular proto-oncogenes is an important event in the pathogenesis of chemically induced tumors. We have used the ori P-tk shuttle vector, pHET, to analyze the types of DNA sequence changes induced after treating mammalian cells with the carcinogen N-ethyl-N-nitrosourea (ENU). This shuttle vector contains the putative replication origin of the Epstein-Barr virus (EBV) and is stably maintained as a plasmid in EBV-transformed human lymphoblastoid cells. Populations of plasmid-bearing cells were treated with ENU, and plasmid DNA was isolated approximately 7-8 population doublings after treatment for analysis of mutations induced at the herpes simplex virus type 1 thymidine kinase (HSV-tk) target gene. After ENU treatment, frequencies of four of the six possible base substitution mutations significantly increased. Transition mutations were the most common sequence change: 48% of the 46 mutants sequenced were GC----AT transitions and 17% were AT----GC transitions. In addition, the number of AT----TA (20%) and AT----CG (9%) transversion mutations significantly increased after ENU treatment. Based on the comparison of mutations induced by ENU in human cells with the types of base pair changes previously reported for other alkylating agents, we propose that the O2-ethylthymine adduct may be a significant premutagenic lesion in mammalian cells, capable of resulting in AT base pair transversion mutations. Studies from other laboratories have demonstrated the importance of AT----TA transversion mutations in the activation of cellular proto-oncogenes by ENU.


Jaws of a large belemnite and an ammonite from the Aalenian (Middle Jurassic) of Switzerland.
Although belemnite rostra can be quite abundant in Jurassic and Cretaceous strata, the record of belemnite jaws was limited to a few specimens from Germany and Russia. Here, we describe and figure three cephalopod jaws from the Middle Jurassic Opalinus Clay of northern Switzerland. Although flattened, the carbonaceous fossils display enough morphological information to rule out an ammonoid, nautiloid or octobrachian origin of the two larger jaws. Their similarities to belemnite jaws from Germany and Russia conforms with our interpretation of these specimens as belemnite jaws. Based on their rather large size, we tentatively assign these two jaws to the megateuthidid Acrocoelites conoideus. The third jaw is a rather small upper jaw of an ammonoid. Since Leioceras opalinum is by far the most common ammonite in this unit in northern Switzerland, we tentatively suggest that the upper jaw belongs to this species.


Depression and ischemic heart disease mortality: evidence from the EPIC-Norfolk United Kingdom prospective cohort study.
The authors investigated the association between major depressive disorder, including its clinical course, and mortality from ischemic heart disease. This was a prospective cohort study of 8,261 men and 11,388 women 41-80 years of age who were free of clinical manifestations of heart disease and participated in the Norfolk, U.K., cohort of the European Prospective Investigation Into Cancer. The authors conducted a cross-sectional assessment of major depressive disorder during the period 1996-2000 and ascertained subsequent deaths from ischemic heart disease through linkage with data from the U.K. Office for National Statistics. As of July 31, 2006, 274 deaths from ischemic heart disease were recorded over a total follow-up of 162,974 person-years (the median follow-up period was 8.5 years). Participants who had major depression during the year preceding baseline assessment were 2.7 times more likely to die from ischemic heart disease over the follow-up period than those who did not, independently of age, sex, smoking, systolic blood pressure, cholesterol, physical activity, body mass index, diabetes, social class, heavy alcohol use, and antidepressant medication use. This association remained after exclusion of the first 6 years of follow-up data. Consideration of measures of major depression history (including recency of onset, recurrence, chronicity, and age at first onset) revealed recency of onset to be associated most strongly with ischemic heart disease mortality. Major depression was associated with an increased risk of ischemic heart disease mortality. The association was independent of established risk factors for ischemic heart disease and remained undiminished several years after the original assessment.


A novel and sensitive method for the detection of T cell stimulatory epitopes of alpha/beta- and gamma-gliadin.
It is now generally accepted that coeliac disease (CD) is caused by inflammatory T cell responses to gluten peptides bound to HLA-DQ2 or -DQ8 molecules. There is overwhelming evidence that CD patients can mount T cell responses to peptides found in both alpha-gliadin and gamma-gliadin molecules. Assays that would detect the presence or absence of such peptides in food would thus be accurate indicators of safety for consumption by CD patients. The development of a sensitive method to detect T cell stimulatory epitopes of alpha-gliadin and gamma-gliadin molecules in food products. Monoclonal antibodies (mAb) were raised against peptides encoding the T cell stimulatory epitopes of alpha-gliadin (amino acids (aa) 59-71) and aa gamma-gliadin (aa 142-153 and aa 147-159). These mAb competition assays were developed that quantitatively detect T cell stimulatory epitopes present on both intact proteins and peptides of sizes recognisable by CD4(+) T cells. With the mAb based competition assays, T cell epitopes were detected in pepsin/trypsin digests of wheat proteins and ethanol extracts of various food products, with detection levels lower than those reached with gluten specific T cells. Moreover, the presence of T cell stimulatory epitopes was also detected in preparations of barley, rye, and triticale, other cereals known to be toxic for CD patients. A new antibody based method has been developed, detecting the presence of T cell stimulatory gluten peptides. This can be used to further ensure the safety of food consumed by CD patients.


High energy, widely tunable Si-prism-array coupled terahertz-wave parametric oscillator with a deformed pump and optimal crystal location for angle tuning.
A high energy, widely tunable Si-prism-array coupled terahertz-wave parametric oscillator (TPO) has been demonstrated by using a deformed pump. The deformed pump is cut from a beam spot of 2 mm in diameter by a 1-mm-wide slit. In comparison with a small pump spot (1-mm diameter), the THz-wave coupling area for the deformed pump is increased without limitation to the low-frequency end of the tuning range. Besides, the crystal location is specially designed to eliminate the alteration of the output position of the pump during angle tuning, so the initially adjusted nearest pumped region to the THz-wave exit surface is maintained throughout the tuning range. The tuning range is 0.58-2.5 THz for the deformed pump, while its low frequency end is limited at approximately 1.2 THz for the undeformed pump with 2 mm diameter. The highest THz-wave output of 2 μJ, which is 2.25 times as large as that from the pump of 1 mm in diameter, is obtained at 1.15 THz under 38 mJ (300 MW/cm2) pumping. The energy conversion efficiency is 5.3×10-5.


Influence of survivin and Bcl-2 expression on the biological behavior of non-small cell lung cancer.
Survivin and Bcl-2 are generally considered to be inhibitors of apoptosis and are frequently overexpressed in several types of human cancers. However, their role in regulating the biological behavior of non-small cell lung carcinoma (NSCLC) remains controversial. We aimed to determine the expression of survivin and Bcl-2 and explore their correlation with clinicopathological features and prognosis. The expression of survivin and Bcl-2 proteins in 62 specimens of NSCLC tissues and 30 specimens of tumor adjacent tissues was detected using immunohistochemistry. The correlation between protein expression and clinicopathological features and prognosis was analyzed. The percentage of survivin-positive samples obtained from NSCLC tissues was 58.06% (36/62), which was significantly higher compared to that in normal lung tissues (10%, 3/30; P<0.05). Similarly, the percentage of Bcl-2-positive samples obtained from NSCLC tissues was statistically higher compared to that from normal lung tissues (51.61%, 32/62 vs. 6.67%, 2/30; P<0.05). Survivin expression was closely correlated with tumor differentiation, lymph node metastasis and TNM stage (P<0.05), while Bcl-2 expression was only associated with TNM stage (P<0.05). The expression of survivin was positively correlated with that of Bcl-2 (P<0.05). A five-year follow-up study revealed that the expression of survivin and Bcl-2 was negatively correlated with post-operative survival duration. Our findings suggest that survivin and Bcl-2 may act synergistically in the occurrence, development, invasion and metastasis of NSCLC, both of which are up-regulated in NSCLC tissues. The co-expression of survivin and Bcl-2, which is closely related to malignancy, may serve as a biomarker for predicting prognosis.


Antimicrobial activity and spectrum of LY146032, a lipopeptide antibiotic, including susceptibility testing recommendations.
LY146032, a new lipopeptide, was found to have a spectrum of gram-positive antimicrobial activity that includes activity against staphylococci (methicillin susceptible and resistant), beta-hemolytic Streptococcus spp., pneumococci, viridans group Streptococcus spp., anaerobic gram-positive cocci, Clostridium spp., and enterococci. The new lipopeptide was generally bactericidal and showed more rapid killing of Listeria spp. (MIC, 1 to 2 micrograms/ml) and staphylococci than either vancomycin or teicoplanin. The 30-micrograms disk was preferred to the 15-micrograms disk on the basis of the preliminary interpretive criteria for susceptibility which indicated zone diameters of greater than or equal to 16 mm for susceptible strains (MIC, less than or equal to 2.0 micrograms/ml) and greater than or equal to 12 mm for resistant strains (MIC, greater than or equal to 8.0 micrograms/ml). These criteria are valid pending the testing of additional gram-positive strains which have LY146032 MICs of greater than or equal to 8 micrograms/ml.


Feeling like the enemy: the emotion management and alienation of hospital doctors.
Globally, an epidemic of psychological distress, burnout, and workforce attrition signify an acute deterioration in hospital doctors' relationship with their work-intensified by COVID-19. This deterioration is more complicated than individual responses to workplace stress, as it is heavily regulated by social, professional, and organizational structures. Moving past burnout as a discrete "outcome," we draw on theories of emotion management and alienation to analyze the strategies through which hospital doctors continue to provide care in the face of resource-constraints and psychological strain. We used Mobile Instant Messaging Ethnography (MIME), a novel form of remote ethnography comprising a long-term exchange of digital messages to elicit "live" reflections on work-life experiences and feelings. The results delineate two primary emotion-management strategies-acquiescence and depersonalization-used by the hospital doctors to suppress negative feelings and emotions (e.g., anger, frustration, and guilt) stemming from the disconnect between professional norms of expertise and self-sacrifice, and organizational realities of impotence and self-preservation. Illustrating the continued relevant of alienation, extending its application to doctors who disconnect to survive, we show how the socio-cultural ideals of the medical profession (expertise and self-sacrifice) are experienced through the emotion-management and self-estrangement of hospital doctors. Practically, the deterioration of hospital doctors' relationship with work is a threat to health systems and organizations. The paper highlights the importance of understanding the social structures and disconnects that shape this deteriorating relationship and the broad futility of self-care interventions embedded in work contexts of unrealized professional ideals, organizational resource deficits and unhappy doctors, patients, and families.


On Extensions to Fisher's Linear Discriminant Function.
This correspondence describes extensions to Fisher's linear discriminant function which allow both differences in class means and covariances to be systematically included in a process for feature reduction. It is shown how the Fukunaga-Koontz transform can be combined with Fisher's method to allow a reduction of feature space from many dimensions to two. Performance is seen to be superior in general to the Foley-Sammon method. The technique is developed to show how a new radius vector (or pair of radius vectors) can be combined with Fisher's vector to produce a classifier with even more power of discrimination. Illustrations of the technique show that good discrimination can be obtained even if there is considerable overlap of classes in any one projection.


The EIIIA domain from astrocyte-derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination.
Central nervous system remyelination by oligodendrocyte progenitor cells (OPCs) ultimately fails in the majority of multiple sclerosis (MS) lesions. Remyelination benefits from transient expression of factors that promote migration and proliferation of OPCs, which may include fibronectin (Fn). Fn is present in demyelinated lesions in two major forms; plasma Fn (pFn), deposited following blood-brain barrier disruption, and cellular Fn, synthesized by resident glial cells and containing alternatively spliced domains EIIIA and EIIIB. Here, we investigated the distinctive roles that astrocyte-derived Fn (aFn) and pFn play in remyelination. We used an inducible Cre-lox recombination strategy to selectively remove pFn, aFn or both from mice, and examined the impact on remyelination of toxin-induced demyelinated lesions of spinal cord white matter. This approach revealed that astrocytes are a major source of Fn in demyelinated lesions. Furthermore, following aFn conditional knockout, the number of OPCs recruited to the demyelinated lesion decreased significantly, whereas OPC numbers were unaltered following pFn conditional knockout. However, remyelination completed normally following conditional knockout of aFn and pFn. Both the EIIIA and EIIIB domains of aFn were expressed following demyelination, and in vitro assays demonstrated that the EIIIA domain of aFn mediates proliferation of OPCs, but not migration. Therefore, although the EIIIA domain from aFn mediates OPC proliferation, aFn is not essential for successful remyelination. Since previous findings indicated that astrocyte-derived Fn aggregates in chronic MS lesions inhibit remyelination, aFn removal may benefit therapeutic strategies to promote remyelination in MS.


In vitro synergy of natamycin and voriconazole against clinical isolates of Fusarium, Candida, Aspergillus and Curvularia spp.
To determine the minimum inhibitory concentrations (MICs) of voriconazole and natamycin, alone and in combination, against the clinical isolates of Fungus and to evaluate the synergy between the drugs in an experimental in vitro study. In an experimental in vitro study, clinical isolates of Fusarium, Aspergillus, Candida and Curvularia spp were maintained on Sabouraud Dextrose Agar and used for the study. The MICs of natamycin and voriconazole, used alone and in combination, were evaluated by checkerboard microdilution technique based on the standard protocol proposed by the Clinical Laboratory Standards Institute. The interactions were assessed using the fractional inhibitory concentration (FIC) Index model. Tested with all the clinical isolates, the MICs ranged between 0.125 and 8 µg/mL both for natamycin and voriconazole. In descending order, maximum synergism (FIC ≤0.5) was observed in Candida spp (33.3%) followed by Curvularia spp and Fusarium spp (23.1%). Synergism was least for Aspergillus spp (22.2%). However, at 61.5% (8/13), maximum additive effect (>0.5-1) was observed in Aspergillus spp and minimum (33.3%, 2/6) in Candida spp. Indifference (FIC value >1 and≤4) was observed in 22.2% (2/9) of Aspergillus spp, 15.4% (2/13) of Fusarium spp, 33.3% (2/6) of Candida spp and 23.1% (3/13) of Curvularia spp. No cases of antagonism (FIC >4) were observed. Natamycin and voriconazole in combination demonstrated more effective antifungal activity than single-use in vitro treatment in all species tested, which implies that these combinations may be helpful in treating fungal keratitis. There was no antagonism between these two drugs.


Smoke and mirrors - does smoking cause discolouration of composite restorations?
Searches were carried out across PubMed, Embase, Scopus and Web of Science for studies published until 28th March 2022. In vitro studies assessing colour stability of resin-based composites (RBCs) exposed to conventional cigarette smoke (CS), tobacco heating systems (THS) or electronic nicotine delivery systems (ENDS) were considered. Included studies used a spectrophotometer or colorimeter for assessment of discolouration and measured discolouration using CIELAB or CIEDE2000 colour difference formulas. Literature not published in English was excluded. Data was extracted from thirteen studies which met the inclusion criteria. A data collection form was used to collate the extracted information on sample shape, sample diameter, sample thickness, time elapsed before smoke exposure, smoke exposure protocol, colour measurement device, sample finishing method, brushing simulation and whether exposure was to CS, THS or ENDS. All 13 included studies analysed CS, four studies analysed ENDS and two studies analysed THS. A high level of variability was identified between the studies in relation to smoke exposure protocol. CS caused the highest level of discolouration of RBCs. This systematic review of in vitro studies found CS caused irreversible RBC discolouration. ENDS and THS caused less colour change, which could be reversed with repolishing or bleaching procedures, although evidence was limited. Further research is required to consider the long-term effect of CS, ENDS and THS on discolouration of RBCs.


Association of vitamin D levels with incident depression among a general cardiovascular population.
Depression is associated with cardiovascular (CV) disease, and it has been hypothesized that vitamin (vit)D deficiency may be associated with depression and a contributing factor to excess CV events. Therefore, we evaluated whether there is an association between vitD and incident depression among a CV population. Patients (N = 7,358) > or =50 years of age, with a CV diagnosis (coronary artery disease, myocardial infarction, congestive heart failure, cerebrovascular accident, transient ischemic accident, atrial fibrillation, or peripheral vascular disease), no prior depression diagnosis, and a measured vitD level were studied. Vitamin D (ng/mL) was stratified into 4 categories: >50 (optimal [O] n = 367), 31 to 50 (normal [N] n = 2,264), 16 to 30 (low [L] n = 3,402), and > or =15 (very low [VL] n = 1,325). Depression was defined by International Classification of Diseases, Ninth Edition, codes: 296.2 to 296.36, 311. VitD categories were evaluated by Cox hazard regression with adjustment by standard CV risk factors. Age averaged 73.1 +/- 10.2 years, and 58.8% were female. When compared to O, VL, L, and N were associated with depression (adjusted: VL, hazard ratio [HR] 2.70 [1.35-5.40], P = .005; L, HR 2.15 [1.10-4.21], P = .03; N, HR 1.95 [0.99-3.87], P = .06). This association remained even after adjustment by parathyroid hormone levels. Parathyroid hormone was significantly associated with depression, however, became nonsignificant after adjustment by vitD. Winter (December-February) enhanced this association. Significant associations remained when stratifications were made by age (<65, > or =65), sex, and diabetes, although the associations among those age > or =65 and male sex were enhanced. Among a CV population > or =50 years with no history of depression, vitD levels were shown to be associated with incident depression after vitD draw. This study strengthens the hypothesis of the association between vitD and depression.


Structural basis for human monoglyceride lipase inhibition.
Monoglyceride lipase (MGL) is a serine hydrolase that hydrolyses 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. 2-AG is an endogenous ligand of cannabinoid receptors, involved in various physiological processes in the brain. We present here the first crystal structure of human MGL in its apo form and in complex with the covalent inhibitor SAR629. MGL shares the classic fold of the alpha/beta hydrolase family but depicts an unusually large hydrophobic occluded tunnel with a highly flexible lid at its entry and the catalytic triad buried at its end. Structures reveal the configuration of the catalytic triad and the shape and nature of the binding site of 2-AG. The bound structure of SAR629 highlights the key interactions for productive binding with MGL. The shape of the tunnel suggests a high druggability of the protein and provides an attractive template for drug discovery.


Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats.
To determine pharmacokinetics of troglitazone in healthy cats after i.v. and oral administration of a single dose of the drug. 5 healthy ovariohysterectomized adult cats. Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight i.v. and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography. Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 +/- 0.1 hours. Steady-state volume of distribution was 0.23 +/- 0.15 L/kg. After i.v. administration, clearance was 0.33 +/- 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%. The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans.


[Process of construction of the national research agenda on Human Resources in Health in Peru 2011 - 2014].
The National Health Authority of Peru, as part of the implementation of national priorities for health research in 2010 developed the process of building the national research agenda on health manpower (HM). In a scenario of technical challenges, national and international policy and under a nation-wide participatory approach with key stakeholders in the health system, training and aid HM linked to the subject, establishing a socially agreed agenda. Process consists of 3 phases: 1. National review of evidence and relevant information on RHUS, 2. Consultation with opinion leaders and subject experts, and 3. A collaborative space (national workshop) of deliberation, consensus and legitimacy of the agenda. Finally, we present the agenda consists of 30 research topics on health manpower, to be developed in the period 2011- 2014, and raises the challenges and prospects for implementation.


Lack of connexin 40 causes displacement of renin-producing cells from afferent arterioles to the extraglomerular mesangium.
In the adult kidney, renin-producing cells are typically located in the walls of afferent arterioles at the transition into the glomerular capillary network. The mechanisms that are responsible for restricting renin expression to the juxtaglomerular position are largely unknown. This study showed that in mice that lack connexin 40 (Cx40), the predominant connexin of renin-producing cells, renin-positive cells are absent in the vessel walls and instead are found in cells of the extraglomerular mesangium, glomerular tuft, and periglomerular interstitium. Blocking macula densa transport function by acute administration of loop diuretics strongly enhances renin secretion in vivo and in isolated perfused kidneys of wild-type mice. This effect of loop diuretics is markedly attenuated in vivo and even blunted in vitro in Cx40-deficient mice. Even after prolonged stimulation of renin secretion by severe sodium depletion, renin expression is not seen in juxtaglomerular cells or in cells of more proximal parts of the arterial vessel wall as occurs normally. Instead, renin remains restricted to the extra-/periglomerular interstitium in Cx40-deficient mice. In contrast to the striking displacement of renin-expressing cells in the adult kidney, renin expression in the vessels of the developing kidney was found to be normal. This is the first evidence to indicate that cell-to-cell communication via gap junctions is essential for the correct juxtaglomerular positioning and recruitment of renin-producing cells. Moreover, these findings support the notion that gap junctions are relevant for the macula densa signaling to renin-producing cells.


Treatment of bleeding complications in patients on anticoagulant therapy.
Anticoagulant therapy is often refrained from out of fear of hemorrhagic complications. The most frequent type of major bleeding is gastrointestinal, but intracranial hemorrhage has the worst prognosis. Management of these complications in patients on anticoagulants should follow the same routines as for nonanticoagulated patients, as described here with the previously mentioned bleeds as examples. In addition, for life-threatening or massive hemorrhages, reversal of the anticoagulant effect is also crucial. Adequate reversal requires information on which anticoagulant the patient has taken and when the last dose was ingested. Laboratory data can be of some help, but not for all anticoagulants in the emergency setting. This is reviewed here for the different types of anticoagulants: vitamin K antagonists, heparins, fondaparinux, thrombin inhibitors and factor Xa inhibitors. Specific antidotes for the latter are becoming available, but supportive care and nonspecific support for hemostasis with antifibrinolytic agents or prothrombin complex concentrates, which are widely available, should be kept in mind.


[Effect of TCM treatment for purging fire, removing toxic substance, relieving stagnation and eliminating phlegm on cytoplasmic free calcium and intercellular adhesion molecule-1 in rats with intracerebral hemorrhage].
To study the effects and possible mechanisms of TCM treatment for purging fire, removing toxic substance, relieving stagnation and eliminating phlegm on cytoplasmic free calcium ([Ca2+]i) and intercellular adhesion molecule-1 (ICAM-1) in rats with intracerebral hemorrhage (ICH). Adult SD rats were randomly divided into six groups: the normal group, the operated group, the model group, the Naoqing Decoction (NQD) low- and high-dose groups, and the Qingkailing Injection (QKL) group. ICH model was induced by injecting collagenase into right caudate nucleus, level of [Ca2+]i was determined by fluorescent tracing assay, and the expression of ICAM-1 was determined using immunohistochemical technique. High- and low-dose of NQD and QKL could significantly antagonize the collagenase injection induced increase of [Ca2+]i (P < 0.01), inhibit the expression of ICAM-1 and shorten its sustainable time. NQD plays a role in protecting neuron by inhibiting calcium overload, regulating cytokines network, and inhibiting inflammatory reaction through postponing the release of cytokines and inflammatory mediators.


Extracellular signal-regulated kinase involvement in human astrocyte migration.
Glial scar formation occurs after virtually any injury to the brain. The migration of astrocytes into regions of brain injury underlies the formation of the glial scar. The exact role of the glial scar has yet to be elucidated, although it is likely to impair brain recovery. Understanding astrocyte migration is fundamental to understanding the formation of the glial scar. We have used human astrocytes (NT2A cells), derived from human NT2/D1 precursor cells to study astrocyte migration using an in vitro scratch wound model. Time-lapse microscopy and bromodeoxyuridine labeling revealed that the astrocytes migrated rather than proliferated across the scratch. Time course immunocytochemical studies showed that scratching human astrocytes induced the activation (phosphorylation) of ERK 1/2 at 10 min after scratch. The MEK 1/2 inhibitor U0126 inhibited both the ERK 1/2 phosphorylation and the migration of the astrocytes across the wound after scratch. Thus, the migration of human astrocytes after injury is partly initiated by activation of the MEK-ERK signalling pathway.


The Western Denmark Cardiac Computed Tomography Registry: a review and validation study.
As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. We examined the content, data quality, and research potential of the WDHR-CCTR. We retrieved 2008-2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%-100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%). WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research.


Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples.
Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.


Men's preferences for women's body odours are not associated with human leucocyte antigen.
Body odours reportedly portray information about an individual's genotype at the major histocompatibility complex (MHC, called human leucocyte antigen, HLA, in humans). While there is strong experimental support for MHC-associated mating behaviour in animals, the situation in humans is more complex. A lot of effort has been spent on testing HLA-associated odour preferences of women. To date, only very few studies have looked at HLA-linked olfactory preferences in men and these studies have revealed inconsistent results. Here, we investigate men's HLA-associated preferences for women's body odours. Importantly, and in contrast to previous studies, these odours were gathered at peak fertility (i.e. just before ovulation) when any HLA-associated odour preferences should be strongest. We scrutinized whether men's preference for women's body odours is influenced by (i) the number of shared HLA alleles between men and women, (ii) HLA heterozygosity, and (iii) the frequency of rare HLA alleles. We found that men could readily differentiate between odours they found attractive and odours they found less attractive, but that these preferences were not associated with HLA. Specifically, men did not prefer odours from women who are HLA dissimilar, HLA heterozygous, or who have rare HLA alleles. Together, these findings suggest that HLA has no effect on men's odour preferences.


Full-scale investigation of ferrous dosing in sewers and a wastewater treatment plant for multiple benefits.
This study demonstrates the full scale application of iron dosing in a metropolitan wastewater treatment plant (WWTP) and the upstream sewer system for multiple benefits. Two different dosing locations, i.e., the WWTP inlet works (Trial-1) and upstream sewer network (Trial-2) were tested in this study. Both dosing trials achieved multiple benefits such as sulfide control, phosphate removal and improved sludge dewaterability. During Trial-1, a sulfide reduction of >90% was achieved at high dosing rates (>19 kgFe ML-1) of ferrous chloride in the inlet works and in Trial-2 the in-sewer ferrous dosing had significant gas phase hydrogen sulfide (H2S) concentration reduction in the sewer network. The ferrous dosing enhanced the phosphate removal in the bioreactor up to 76% and 53 ± 2% during Trial-1 & 2, respectively. The iron ending up in the anaerobic sludge digester reduced the biogas H2S concentration by up to 36% and 45%, respectively. The dewaterability of the digested sludge was improved, with relative increases of 9.7% and 9.8%, respectively. The presence of primary clarifier showed limited impact on the downstream availability of iron for achieving the afore-mentioned multiple benefits. The iron dosing enhanced the total chemical oxygen demand removal in the primary clarifier reaching up to 49% at the high dose rates during Trial-1 and 42 ± 1% during Trial-2. This study demonstrated that multiple benefits could be achieved independent of the iron dosing location (i.e., at the WWTP inlet or in the network). Further, iron dosing at both locations enhances primary settling, beneficial for bioenergy recovery from wastewater.


Methodologies and approaches for the analysis of cell-nanoparticle interactions.
How to study nanoparticle-cell interactions is the key question that puzzles researchers in the fields of nanomedicine as well as in nanotoxicology. In nanotoxicology, the amount of nanoparticles internalized by the cells or bound to the external surfaces of cells determines the toxic profile of those particles. In medical applications, cellular uptake and binding of medically effective nanoparticles decides their efficacy. Despite the importance of understanding the extent and mode of nanoparticle-cell interactions, these processes are underinvestigated, mainly due to the lack of suitable user-friendly methodologies. Here we discuss the advantages and limitations of currently available (and most advanced) microscopic, spectroscopic, and other bioanalytical methods that could be used to assess cell-nanoparticle interactions either qualitatively or quantitatively. Special emphasis is given to the methods that enable analysis and identification of nanoparticles at single-cell level, and allow intracellular localization and speciation analysis of nanoparticles. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.


Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles.
A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results.


Epigenetic drugs as new therapy for tumor necrosis factor-α-compromised bone healing.
Impaired bone regeneration by excess inflammation leads to failure of bone healing. Current therapies display limited benefits making new treatments imperative. Our recent discoveries of the anti-inflammatory characteristics of bromodomain and extra terminal domain (BET) inhibitors, N-methylpyrrolidone (NMP) and N,N-Dimethylacetamide (DMA), implicate possible therapeutic use of epigenetic drugs in inflammation-impaired bone healing. Here, we investigated the effects of NMP and DMA on osteogenesis in vitro and ex vivo under the influence of TNFα, a key cytokine responsible for impaired fracture healing. NMP and DMA pre-treatment recovered TNFα-inhibited expression of essential osteoblastic genes, Alp, Runx2, and Osterix as well as mineralization in multipotent stem cells, but not in pre-osteoblasts and calvarial osteoblasts. The mechanism of action involves the recovery of TNFα-suppressed BMP-induced Smad signaling and the reduction of TNFα-triggered ERK pathway. In addition, ERK inhibitor treatment diminished the effect of TNFα on osteogenesis, which reinforces the role of ERK pathway in the adverse effect of TNFα. Furthermore, endochondral ossification was analyzed in an ex vivo bone culture model. TNFα largely abrogated BMP-promoted growth of mineralized bone while pre-treatment of NMP and DMA prevented the deleterious effect of TNFα. Taken together, these data shed light on developing low- affinity epigenetic drugs as new therapies for inflammation-compromised bone healing.


Experimental and theoretical investigations of cyclometalated ruthenium(ii) complex containing CCC-pincer and anti-inflammatory drugs as ligands: synthesis, characterization, inhibition of cyclooxygenase and in vitro cytotoxicity activities in various cancer cell lines.
The new cyclometalated ruthenium(ii) complex, [Ru(CCC-Nap)(Ibu)(PTA)] was designed and synthesized using ibuprofen (Ibu), 1,3,5-triaza-7-phosphaadamantane (PTA) and CCC-pincer containing naproxen moiety (CCC-Nap) as ligands. The compounds were fully characterized by elemental analysis, FT-IR, multinuclear (1H, 13C, and 31P) NMR spectroscopy, and electrospray ionization mass spectrometry. The cytotoxicity of the newly synthesized Ru(ii) complex was found to be low, and the complex was about twice as active as cisplatin with IC50 values in the range of 0.9-1.32 μM for both MCF-7 and MDA-MB-231 cell lines. Cyclooxygenase (COX) inhibition studies revealed that the Ru(ii) complex displayed strong interactions with COX-2, about 16 and 5 times more than free Ibu and CCC-Nap ligands, respectively. The Ru(ii) complex improved the production of reactive oxygen species (ROS) by 10.7 fold compared to the control (H2O2 as a positive control) in MCF-7 cells. Quantum chemical calculations gave more insights into the geometry and electronic properties of the novel Ru(ii) complex, while molecular docking provided theoretical information on the interactions of Ru(ii) complex with human cyclooxygenase-2 (COX-2) and the results were compared with those of the interactions of the free ligands with COX-2.


Lessons learned while starting multi-institutional genetics research in diverse populations: A report from the Clinical Sequencing Evidence-Generating Research (CSER) consortium.
Increasing diversity in clinical trial participation is necessary to improve health outcomes and requires addressing existing social, structural, and geographic barriers. The Clinical Sequencing Evidence-Generating Research Consortium (CSER) included six research projects to enroll historically underrepresented/underserved (UR/US) populations in clinical genomics research. Delays and project re-designs emerged shortly after work began. Understanding common experiences of these projects may inform future trial implementation. Semi-structured interviews with six CSER principal investigators and seven project managers were performed. An interview guide included questions of research/clinical infrastructure, logistics across sites, language, communication, and allocation of grant-related resources. Interviews were recorded, transcribed verbatim; transcripts were analyzed using inductive coding, thematic analysis and consensus building. All projects collaborating with new clinical sub-sites to recruit UR/US populations. Refining trial logistics continued long after enrollment for all projects. Themes of challenges included: sub-site customization for workflow and genetics support, conflicting input from participant advisory groups and approval bodies, developing research personnel, complex data management structures, and external changes (e.g. subcontractors ending contracts) that required redesign. Themes of beneficial lessons included: domains with prior experience were easier, develop project champions at each sub-site, structure communication within the research team, and simplify research design when possible. The operational aspects of expanding clinical research into novel sub-sites are significant and require investment of time and resources. The themes arising from these interviews suggest priority areas for more quantitative analyses in the future including multi-institutional approval policies and processes, data management structures, and incremental research complexity.


Differences between fixed day shift workers and rotating shift workers in gastrointestinal problems: a systematic review and meta-analysis.
This study comprised a review and compilation of literature to gain an in-depth understanding of the impact of rotating shift work on gastrointestinal health. PubMed, CINAHL, and the Cochrane Library were searched for studies published between January 1, 1985, and June 30, 2020. Fixed day shifts were defined as work shifts that began between 7:00 and 9:00 in the morning. Shifts beginning at any other time were classified as rotating shifts. A meta-analysis was performed using Comprehensive Meta-Analysis Software (CMA) version 3. In the end, 16 studies were included in the meta-analysis. An odds ratio (OR) of 1.56 (95% confidence interval (CI): 1.24-1.95), indicating that gastrointestinal problems are more common in rotating shift workers than in fixed day shift workers. Four gastrointestinal problems, namely, irritable bowel syndrome, constipation, indigestion, and peptic ulcers, were then analyzed separately. Significant differences between rotating shift workers and fixed day shift workers were found only for indigestion and peptic ulcers. For indigestion, the OR was 1.72 (95% CI: 1.28-2.30). For peptic ulcers, the OR was 1.66 (95% CI: 1.19-2.30). Thus, research indicates that rotating shift work may increase the risk of gastrointestinal problems, particularly indigestion and peptic ulcers.


Postural control system influences intrinsic alerting state.
Numerous studies using dual-task paradigms (postural and cognitive) have shown that postural control requires cognitive resources. However, the influence of postural control on attention components has never been directly addressed. Using the attention network test (ANT), which assesses specifically each of the 3 components of attention-alertness, orientation, and executive control-within a single paradigm, we investigated the effect of postural balance demand on these 3 components. Forty-two participants completed the ANT in 3 postural conditions: (a) supine, a very stable position; (b) sitting on a chair, an intermediate position; and (c) standing with feet lined up heel to toe, a very instable position known as the Romberg position. Our results revealed that the difficulty of postural control does modulate alerting in such a way that it improves with the level of instability of the position. Regarding the orienting and executive control components of attention, performance was not different when participants were standing upright or seated, whereas in the supine position, performance dropped. The strong and specific interaction between postural control and the alerting system suggests that these mechanisms may share parts of the underlying neural circuits. We discuss the possible implication of the locus coeruleus, known to be involved in both postural balance and alerting. Also, our findings concerning orienting and executive control systems suggest that supine posture could have a specific effect on cognitive activities. These effects are discussed in terms of particularities resulting from the supine position.


A qualitative investigation into the impact of hemophagocytic lymphohistiocytosis on children and their caregivers.
Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare and life-threatening disorder, which usually occurs during infancy or early childhood and is characterized by abnormal activation of the immune system. However, the burden of pHLH on children and their families has not been previously evaluated. This qualitative study investigated the impact of pHLH and its treatment on the physical, emotional, and social well-being of patients and caregivers in the USA and UK using interviews to provide a comprehensive insight from the perspective of the caregivers and young survivors. Twenty-one caregivers were enrolled (median [range] age, 41.1 [26-58] years) and represented 20 patients, four from the UK and 16 from the USA. At enrollment, 17 of the 20 patients were alive with a median [range] age of 12.75 [5-31] years at a mean [range] of 7.8 [0.6-11.6] years after diagnosis. In addition, four adult survivors (median [range] age, 23.3 [21-30] years) were also enrolled (total participants n = 25). From noticing initial symptoms to receiving a diagnosis, caregivers reported a mean (range) of 25.9 (0-258) months. pHLH and its treatment had a substantial and long-lasting impact on patients and caregivers, affecting their physical, emotional and social well-being, family relationships, friendships, and ability to work and study. Many of the experiences reported were negative, even after curative treatment, and some participants experienced long-lasting physical and emotional issues. The most noticeable impact of pHLH for patients was on their physical well-being, whereas for caregivers it was emotional well-being. Across all participants there was a sense of isolation due to the illness and its treatment, particularly regarding the patient being immunocompromised and the fear of infection. Areas having a major impact and considered in need of improvement included: delays in diagnosis, lack of patient-specific information on pHLH and a lack of support and understanding about the condition. pHLH placed a substantial burden on patients and caregivers, which for some were long-lasting. This was compounded by the lack of awareness and understanding of pHLH by healthcare professionals, and a lack of accessible information for those affected by pHLH.


New biomaterials and methods for craniofacial bone defect: chondroid bone grafts in maxillary alveolar clefts.
The purpose of this study was to evaluate autogenous osteogenic marrow within chondroid bone grafts in simulated alveolar defects of mice in order to determine the ability of the graft material to effectively close the cleft from an osseous standpoint and to observe the effect of the grafting procedure. Critical-sized defects were made in the premaxillary bones of male mice using a surgical trephine and a low-speed dental engine as a model of the maxillary alveolar cleft for testing bone-inductive agents. Premaxillary trephine defects were not repaired by fibrous tissue or bone formation 30 days after operation. This nonhealing bony wound of the premaxilla in mice may be useful as a model for studying the effect of bone-inductive agents on the healing of alveolar clefts. Distraction osteogenesis is a recently advanced principle of bone lengthening in which a long bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. The osteotomy site was surrounded by an external callus consisting of hyaline cartilage. The callus contained a lot of chondroid bone. The transplant bone within chondroid bone was characterized by bone formation and remodeling 30 days after transplantation. Throughout the experiment, our findings demonstrated, for the first time, that the transplant bone that contains chondroid bone may be used clinically in relation to craniofacial bone defects to improve the treatment of bone grafts.


Health and health-related quality of life: differences between men and women who seek gastric bypass surgery.
The aim of this study was to examine the differences between male and female bariatric surgery candidates with respect to health-related quality of life (HRQOL), health, sociodemographic variables, and interactions among these variables in a bariatric surgery practice in the United States. Women seek bariatric surgery 5 times more often than men. Research on gender differences in HRQOL is limited, and the results are conflicting. A total of 794 surgery candidates (mean age 42.2 y; body mass index 46.9 kg/m2; 84.8% women) completed both a weight-related (Impact of Weight on Quality of Life-Lite questionnaire) and a generic (Medical Outcomes Study Short-Form-36) measure of HRQOL. Health was evaluated by questionnaire and clinical interviews. Compared to men, women reported reduced HRQOL on 3 of the 5 scales assessing obesity-specific HRQOL and also the physical aspects of general HRQOL. Women also had double the rate of depression (48.5% versus 22.5%), and men had double the rate of sleep apnea (80.3% versus 40.2%). Women were younger, less obese, and were less likely to be married. No gender differences were found in the association between HRQOL and co-morbidities. However, an increasing number of co-morbidities was associated with decreasing physical and mental HRQOL. Additionally, depression was associated with decreased mental HRQOL, and coronary heart disease was associated with decreased physical HRQOL. Women's reduced HRQOL, particularly in self-esteem, sexual life, and physical functioning, and their greater rates of depression, might play a role in their decision to seek bariatric surgery. Although we could not determine causality, this study is a first step toward understanding why women seek surgery 5 times more often than men.


The preclinical sheep model of high tibial osteotomy relating basic science to the clinics: standards, techniques and pitfalls.
To develop a preclinical large animal model of high tibial osteotomy to study the effect of axial alignment on the lower extremity on specific issues of the knee joint, such as in articular cartilage repair, development of osteoarthritis and meniscal lesions. Preoperative planning, surgical procedure and postoperative care known from humans were adapted to develop a HTO model in the adult sheep. Thirty-five healthy, skeletally mature, female Merino sheep between 2 and 4 years of age underwent a HTO of their right tibia in a medial open-wedge technique inducing a normal (group 1) and an excessive valgus alignment (group 2) and a closed-wedge technique (group 3) inducing a varus alignment with the aim of elucidating the effect of limb alignment on cartilage repair in vivo. Animals were followed up for 6 months. Solid bone healing and maintenance of correction are most likely if the following surgical principles are respected: (1) medial and longitudinal approach to the proximal tibia; (2) biplanar osteotomy to increase initial rotatory stability regardless of the direction of correction; (3) small, narrow but long implant with locking screws; (4) posterior plate placement to avoid slope changes; (5) use of bicortical screws to account for the brittle bone of the tibial head and to avoid tibial head displacement. Although successful high tibial osteotomy in sheep is complex, the sheep may--because of its similarities with humans--serve as an elegant model to induce axial malalignment in a clinically relevant environment, and osteotomy healing under challenging mechanical conditions.


Comparing the fermentation performance of Escherichia coli KO11, Saccharomyces cerevisiae 424A(LNH-ST) and Zymomonas mobilis AX101 for cellulosic ethanol production.
Fermentations using Escherichia coli KO11, Saccharomyces cerevisiae 424A(LNH-ST), and Zymomonas mobilis AX101 are compared side-by-side on corn steep liquor (CSL) media and the water extract and enzymatic hydrolysate from ammonia fiber expansion (AFEX)-pretreated corn stover. The three ethanologens are able produce ethanol from a CSL-supplemented co-fermentation at a metabolic yield, final concentration and rate greater than 0.42 g/g consumed sugars, 40 g/L and 0.7 g/L/h (0-48 h), respectively. Xylose-only fermentation of the tested ethanologenic bacteria are five to eight times faster than 424A(LNH-ST) in the CSL fermentation.All tested strains grow and co-ferment sugars at 15% w/v solids loading equivalent of ammonia fiber explosion (AFEX)-pretreated corn stover water extract. However, both KO11 and 424A(LNH-ST) exhibit higher growth robustness than AX101. In 18% w/w solids loading lignocellulosic hydrolysate from AFEX pretreatment, complete glucose fermentations can be achieved at a rate greater than 0.77 g/L/h. In contrast to results from fermentation in CSL, S. cerevisiae 424A(LNH-ST) consumed xylose at the greatest extent and rate in the hydrolysate compared to the bacteria tested. Our results confirm that glucose fermentations among the tested strains are effective even at high solids loading (18% by weight). However, xylose consumption in the lignocellulosic hydrolysate is the major bottleneck affecting overall yield, titer or rate of the process. In comparison, Saccharomyces cerevisiae 424A(LNH-ST) is the most relevant strains for industrial production for its ability to ferment both glucose and xylose from undetoxified and unsupplemented hydrolysate from AFEX-pretreated corn stover at high yield.


Postoperative pain facilitates nonthermoregulatory tremor.
Spontaneous tremor is relatively common in normothermic patients after operation and has been attributed to many causes. The hypothesis that nonthermoregulatory shivering-like tremor is facilitated by postoperative pain was tested. In addition, the effects of intravenous lidocaine on nonthermoregulatory tremor were evaluated. Patients undergoing knee surgery were anesthetized with 2 microg/kg intravenous fentanyl and 0.2 mg/kg etomidate. Anesthesia was maintained with 1.7 +/- 0.8% (mean +/- SD) isoflurane. Intraoperative forced-air heating maintained normothermia The initial 44 patients were randomly allocated to receive an intra-articular injection of 20 ml saline (n = 23) or lidocaine, 1.5% (n = 21). The subsequent 30 patients were randomly allocated to receive an intravenous bolus of 250 microg/kg lidocaine followed by an infusion of 13 microg x kg(-1) x h(-1) lidocaine or an equivalent volume of saline when shivering was observed. Patient-controlled analgesia was provided for all patients: 3.5 mg piritramide, with a lockout interval of 5 min, for an unlimited total dose. Shivering was graded by a blinded investigator using a four-point scale. Pain was assessed by a 100-mm visual analog scale (0 = no pain and 100 = worst pain). The arteriovenous shunt status was evaluated with forearm-minus-fingertip skin-temperature gradients. Morphometric characteristics and hemodynamic responses were similar in the four groups. Core and mean skin temperature remained constant or increased slightly compared with preoperative values, and postoperative skin-temperature gradients were negative (indicating vasodilation) in nearly all patients. After intra-articular injection of saline, pain scores for the first postoperative hour averaged 46 +/- 32 mm (mean +/- SD), and 10 of the 23 (43%) patients shivered. In contrast, the pain scores of patients who received intra-articular lidocaine were significantly reduced to 5 +/- 9 mm and shivering was absent in this group (P < 0.05). In the second portion of the study, neither intravenous lidocaine nor saline reduced the magnitude or duration of nonthermoregulatory tremor or the patients' pain scores. Intra-articular, but not intravenous, lidocaine reduced surgical pain and prevented nonthermoregulatory shivering. Therefore, these data indicate that postoperative pain facilitates nonthermoregulatory shivering.


Validation of sobriety tests for the marine environment.
The objective of this project was to develop sobriety tests that can be administered in the seated position to assist water patrol officers in detecting alcohol-related impairment in boaters. Four seated sobriety tests were administered to 330 boaters to determine the tests' usefulness in classifying boaters as having blood alcohol concentrations (BACs) below the illegal limit (BAC<.08%) or above the illegal limit (BAC ≥ .08%). Data were obtained by a team of four marine officers and two civilian observers on Lake of the Ozarks in central Missouri. The overall correct percentages, sensitivity, and specificity of the tests were consistent with what is typically reported in literature on the roadside sobriety tests. The tests' reliability was also consistent with what is typically reported in literature on the roadside sobriety tests. Thus, the four tests may assist marine officers with assessments of alcohol-related impairment in boaters.


Treatment and secondary prevention of venous thromboembolism in cancer.
Patients with cancer who develop venous thromboembolism (VTE) are at elevated risk for recurrent thrombotic events, even during anticoagulant therapy. The clinical picture is further complicated because these patients are also at increased risk of bleeding while on anticoagulants. In general, there are four key goals of treatment for VTE: preventing fatal pulmonary embolism (PE); reducing short-term morbidities associated with acute leg or lung thrombus; preventing recurrent VTE; and preventing the long-term sequelae of VTE (e.g., post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension). A fifth goal - minimising the risk for bleeding while on anticoagulation - is particularly warranted in patients with cancer. Traditionally, pharmacological treatment of VTE has two phases, with the transition between phases marked by a switch from a rapid-acting, parenterally administered anticoagulant (such as unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux) to an oral vitamin K antagonist (e.g., warfarin). Recent clinical trials of established agents and the advent of new pharmacological options are changing this paradigm. Low-molecular-weight heparin continued for 6 months is more effective than warfarin in the secondary prevention of VTE in cancer patients without increasing the risk of bleeding and is now the preferred treatment option. Given the impact of VTE on short-term and long-term outcomes in patients with cancer, a group of health-care providers based in the United Kingdom gathered in London in 2009 to discuss recent data on cancer-associated thrombosis and to evaluate how these recommendations can be integrated or translated into UK clinical practice. This article, which is the third of four articles covering key topics in cancer thrombosis, focuses on treatment and secondary prevention of VTE in cancer patients.


Tomographic reconstruction of three-dimensional refractive index fields by use of a regularized phase-tracking technique and a polynomial approximation method.
We present a complete data-processing procedure for quantitative reconstruction of three-dimensional (3D) refractive index fields from limited multidirectional interferometric data. The proposed procedure includes two parts: (1) extraction of the projection data from limited multidirectional interferograms by a regularized phase-tracking technique and wavefront fitting and (2) reconstruction of the 3D refractive index fields by a modified polynomial approximation method. It has been shown that the procedure gives a satisfactory solution to the reconstruction issue in interferometric tomography, from the initial projection data extraction to the final image reconstruction. Computer simulation and experimental results are both presented.