Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma.
Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies. It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin. We investigated the association between the use of common systemic phototoxic drugs and development of CM. This study was a case-control study in a Dutch population-based cohort. The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands. The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004. Controls were sampled from the PHARMO population. Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti-inflammatory drugs (NSAIDs). A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM. The study population included 1,318 cases and 6,786 controls. Any phototoxic drug during the study period was dispensed for 46 % of the cases and 43 % of the controls (p = 0.012). The use of quinolones [odds ratio (OR) 1.33, 95 % confidence interval (CI) 1.01-1.76] and propionic acid derivative NSAIDs (OR 1.33, 95 % CI 1.14-1.54) had a positive association with CM. Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM. Even a short-term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM. Patient education to promote sun-protective behaviour is essential to avoid immediate adverse effects and possible long-term effects of phototoxic drugs.


[Surgery of superficial skin injuries (I of III). Nursing approach].
Among the procedures in minor surgery, to suture wounds is a technique which nursing professional frequently perform as part of their normal work load, especially those nurses who work in Primary Health Care Centers and Emergency Wards. This article in the first in a series of three articles which enables the reader to review his/her knowledge about how to repair superficial skin lesions. After citing the legal aspects, the authors shall review each step in this procedure. We will check to see if the indication for suture is correct, evaluating a wound adequately. Afterwards, we review the procedure to clean the wound and to apply an anti-tetanus prophylaxis. We will mention how to adequately select the technique, the suture material and the instrument to be used. We will show the manner to use to avoid complications derived from an inadequate technique and we will continue with the follow up procedure for cicatrisation after first treatment, which includes informing the patient and a precocious treatment of complications, assuring the patient's welfare and the defense of his/her rights at all times; all of which will make possible an intervention which guarantees quality and is satisfactory to both the patient and the nursing professional who employs it.


Reassessing optimal neural population codes with neurometric functions.
Cortical circuits perform the computations underlying rapid perceptual decisions within a few dozen milliseconds with each neuron emitting only a few spikes. Under these conditions, the theoretical analysis of neural population codes is challenging, as the most commonly used theoretical tool--Fisher information--can lead to erroneous conclusions about the optimality of different coding schemes. Here we revisit the effect of tuning function width and correlation structure on neural population codes based on ideal observer analysis in both a discrimination and a reconstruction task. We show that the optimal tuning function width and the optimal correlation structure in both paradigms strongly depend on the available decoding time in a very similar way. In contrast, population codes optimized for Fisher information do not depend on decoding time and are severely suboptimal when only few spikes are available. In addition, we use the neurometric functions of the ideal observer in the classification task to investigate the differential coding properties of these Fisher-optimal codes for fine and coarse discrimination. We find that the discrimination error for these codes does not decrease to zero with increasing population size, even in simple coarse discrimination tasks. Our results suggest that quite different population codes may be optimal for rapid decoding in cortical computations than those inferred from the optimization of Fisher information.


The effect of air abrasion with two new bonding agents on composite repair.
This study evaluated the shear bond strength of repairs made with a composite (Herculite/Kerr) when two different surface treatment methods and two new generation bond materials were used. The bonding surfaces were prepared by sanding with 500-grit aluminum oxide sandpaper or air abrading with 25-micron aluminum oxide. Treated resin surfaces were acid etched, washed for one minute and air dried. Before adding the composite Herculite, either Optibond Solo (Kerr), Solobond M (Voco) bonding agent or no bonding agent (control group) was applied. The specimens were evaluated for shear bond strength after thermocycling. Fracture surfaces of some samples were also evaluated with SEM. Light microscope and SEM examination of fractured repair surfaces indicated mostly cohesive failure within the air-abraded group. The results showed that surface treatment with air abrasion plus Optibond Solo application had the highest shear bond strength.


The Increasing Age of TBI Patients at a Single Level 1 Trauma Center and the Discordance Between GCS and CT Rotterdam Scores in the Elderly.
Introduction: Traumatic brain injury (TBI) is frequently encountered in geriatric patients, but there is a paucity of data describing TBI in the elderly. Here, we show the age of patients with TBI is increasing at our medical center and discuss the relationship between age and injury severity with patient outcomes. Methods: This is a retrospective analysis of 3,179 adult patients with TBI treated at the University of California, Davis Level 1 Trauma Center between 2009 and 2016. Age, Glasgow Coma Scale (GCS), and CT Rotterdam Scores were recorded. Age was analyzed as both a continuous and categorical variable (18-34, 35-50, 51-65, >65 years-old). Extended Glasgow Outcome Scale was obtained at 3 and 6 months and dichotomized into favorable and unfavorable outcomes. Multivariable general linear regression models, chi-square, logistic regression analyses and ANOVA were used for statistical analyses; a p < 0.05 was considered significant. Results: The mean age of patients was 52.2 ± 21.9 years with a male predominance (69%). There was a significant trend (p = 0.002) toward an increase in mean age each year, increasing by 4.4 years (p = 0.008) over the course of the analysis. Older patients had a higher mean GCS compared to younger patients with the same CT Rotterdam Score (p = 0.027), this becoming more pronounced with worse CT Rotterdam Scores. The >65 group had a 4-fold increased risk for unfavorable outcome when compared to the 18-34 group, this effect being most pronounced after mild TBI. Conclusions: The mean age of TBI patients is increasing at our trauma center. The largest disparity in outcomes across age was seen in patients with a mild GCS and low CT Rotterdam Scores, suggesting that these markers of injury severity may underestimate the severity of injury in the elderly population. This information highlights the need for clinical trials and validation of outcome markers in geriatric TBI.


Liquid chromatographic determination of hypoxanthine content in fish tissue.
A liquid chromatography (LC) method for determining the hypoxanthine content in fish tissues has been developed. Hypoxanthine is extracted with 0.6M perchloric acid, and determined by LC on a reverse phase microparticulate column with UV absorbance detection. The mobile phase is 0.01M potassium phosphate buffer (pH 4.5). The percent relative standard deviation for measurements by the recommended method was less than 7% with a detection limit of 10 ng. Recoveries of hypoxanthine added to various fish tissues were better than 90%. The operational errors, interferences, and recoveries for spiked samples have been investigated and compare favorably with an established xanthine oxidase enzyme method. The described LC method is simple, rapid, and specific for measuring hypoxanthine content in various fish tissues. Some post-mortem studies have indicated the method may also be used for the determination of adenosine monophosphate, inosine monophosphate, and inosine.


Alternatives to Meat and Dairy.
The increasing size and affluence of the global population have led to a rising demand for high-protein foods such as dairy and meat. Because it will be impossible to supply sufficient protein to everyone solely with dairy and meat, we need to transition at least part of our diets toward protein foods that are more sustainable to produce. The best way to convince consumers to make this transition is to offer products that easily fit into their current habits and diets by mimicking the original foods. This review focuses on methods of creating an internal microstructure close to that of the animal-based originals. One can directly employ plant products, use intermediates such as cell factories, or grow cultured meat by using nutrients of plant origin. We discuss methods of creating high-quality alternatives to meat and dairy foods, describe their relative merits, and provide an outlook toward the future.


Nurse practitioner certification: benefits and drawbacks.
This article discusses the history of certification process and distinguishes and analyzes past and present uses of the certification process. It explores changes in the regulatory process and the impact on nurse licensure and evaluates past, present, and future uses of certification related to advanced practice, credentialing, and the scope of nursing practice.


Supervised molecular dynamics (SuMD) as a helpful tool to depict GPCR-ligand recognition pathway in a nanosecond time scale.
Supervised MD (SuMD) is a computational method that allows the exploration of ligand-receptor recognition pathway investigations in a nanosecond (ns) time scale. It consists of the incorporation of a tabu-like supervision algorithm on the ligand-receptor approaching distance into a classic molecular dynamics (MD) simulation technique. In addition to speeding up the acquisition of the ligand-receptor trajectory, this implementation facilitates the characterization of multiple binding events (such as meta-binding, allosteric, and orthosteric sites) by taking advantage of the all-atom MD simulations accuracy of a GPCR-ligand complex embedded into explicit lipid-water environment.


Successful mucosal immunization of cotton rats in the presence of measles virus-specific antibodies depends on degree of attenuation of vaccine vector and virus dose.
After passive transfer of measles virus (MV)-specific antibodies, vaccine-induced seroconversion and subsequent protection is inhibited in cotton rats (Sigmodon hispidus). In this system, an attenuated, recombinant vesicular stomatitis virus expressing the MV haemagglutinin (VSV-H) was found previously to induce neutralizing antibodies and protection against MV challenge after intranasal (i.n.) immunization. Here it is demonstrated that, after i.n. immunization, VSV-H is found in both lung and brain tissue in the absence of clinical signs. Intratracheal inoculation, which does not lead to infection of the brain, proved that immunization via the lung mucosa is sufficient to protect. To reduce or eliminate infection of the brain after i.n. inoculation, stepwise-attenuated VSV-H mutants with truncated cytoplasmic tails of the G protein were tested in cotton rats. A mutant with 9 aa in the G cytoplasmic tail was found at much lower levels in the brain and was protective in the absence or presence of MV-specific antibodies. A more attenuated mutant containing only 1 aa in its tail was not found in brain tissue after inoculation, but it still induced protective antibody to measles in the absence of MV-specific antibody. However, its ability to induce MV-neutralizing antibodies in the presence of passively transferred MV-specific antibodies and its protective capacity was abolished unless higher-dose immunizations were used. This study demonstrates that a lower degree of attenuation is required to be able to immunize in the presence of MV-specific antibodies.


Differentiation of Legionella species by soluble protein patterns in polyacrylamide slab gels.
Water-soluble protein extracts were obtained from representative strains of eleven species of Legionella and examined by polyacrylamide slab gel electrophoresis (PAGE). The eleven species included: L. pneumophila (serogroups 1-9), L. micdadei, L. longbeachae (serogroups 1 and 2), L. gormanii, L. dumoffii, L. bozemanii, L. jordanis, L. oakridgensis, L. wadsworthii, L. feeleii and L. maceachernii. Species identification was verified by gas-liquid chromatography of the non-hydroxy, monohydroxy and dihydroxy fatty acids. Strains within each species shared common patterns of protein banding. Each species had a distinctive protein banding pattern. Results indicate that PAGE of water soluble protein extracts is a useful technique for identification of Legionella isolates.


Arrangement of peptidoglycan in the cell wall of Staphylococcus spp.
The arrangement of peptidoglycan in the cell wall of Staphylococcus was observed with the newly developed freeze-fracture technique, using n-octanol instead of water as the freezing medium. The replica of the trichloroacetic acid-extracted cell wall (TCA-wall) showed two areas. One of them has a concentric circular structure, a characteristic surface structure of the staphylococcal cell wall, and the other showed an irregular and rough surface. The chemical analysis of the wall revealed that the TCA-wall consisted of mostly peptidoglycan. By digesting the TCA-wall with lysozyme, the circular structures were greatly disturbed, and they disappeared after 60 min of treatment. From these observations it can be expected that the peptidoglycan is arranged in a concentric circular manner in the newly generated cell wall of Staphylococcus.


Immunization with Culex tarsalis mosquito salivary gland extract modulates West Nile virus infection and disease in mice.
Mosquito salivary proteins inoculated during blood feeding modulate the host immune response, which can contribute to the pathogenesis of viruses transmitted by mosquito bites. Previous studies with mosquito bite-naïve mice indicated that exposure to arthropod salivary proteins resulted in a shift toward a Th2-type immune response in flavivirus-susceptible mice but not flavivirus-resistant animals. In the study presented here, we tested the hypothesis that immunization with high doses of Culex tarsalis salivary gland extracts (SGE) with an adjuvant would prevent Th2 polarization after mosquito bite and enhance resistance to mosquito-transmitted West Nile virus (WNV). Our results indicate that mice immunized with Cx. tarsalis SGE produced increased levels of Th1-type cytokines (IFNγ and TNFα) after challenge with mosquito-transmitted WNV and exhibited both a delay in infection of the central nervous system (CNS) and significantly lower WNV brain titers compared to mock-immunized mice. Moreover, mortality was significantly reduced in the SGE-immunized mice, as none of these mice died, compared to mortality of 37.5% of mock-vaccinated mice by 8 days after infected mosquito bite. These results suggest that development of a mosquito salivary protein vaccine might be a strategy to control arthropod-borne viral pathogens such as WNV.


Nef-CD4 physical interaction sensed with the yeast two-hybrid system.
HIV-1 Nef protein has been known to induce downmodulation of CD4 receptor. In order to test whether the two proteins physically interact, the yeast two-hybrid system was exploited. A Saccharomyces cerevisiae strain carrying a GAL4-responsive lacZ fusion gene was cotransformed with plasmids in which the Nef and the CD4 cytoplasmic domain (CD4cd) coding sequences were fused to either the DNA binding (DB) or the activation (A) moiety of the GAL4 transcriptional activator. Both the DB-Nef + A-CD4cd and the DB-CD4cd + A-Nef combinations activated the reporter gene, weakly but specifically, as inferred by comparison with a number of controls. Reporter activation was similary observed when DB-Nef was cotransfected with the fusion A-CD4cd(aa 1-23). On the contrary, the combination DB-Nef + A-CD4cd(aa 24-40) was inactive. Also, mutating the CD4cd Leu20-Leu21 motif (known to be essential for both physiological and Nef-induced CD4 endocytosis) to Ala20-Ala21 abolished the GAL4 activity of DB-Nef + A-CD4cd. None of six DB-Nef derivatives in which Nef was partially deleted activated specifically the reporter when coexpressed with A-CD4cd. These findings suggest that CD4cd and Nef directly interact and that a largely complete Nef is required for the interaction. CD4cd aa 1-23 are sufficient for binding; in particular, the Leu20-Leu21 motif is essential. One can infer from these data that: (i) Nef-induced CD4 downmodulation involves a direct CD4-Nef contact and (ii) CD4cd Leu20-Leu21 is required in Nef-induced downmodulation, not simply as an endocytosis signal, but also as an essential component of the Nef-binding moiety.


Vaccine protection of rhesus macaques against simian immunodeficiency virus infection.
Rhesus macaques (Macaca mulatta) immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide (MDP), incomplete Freund's adjuvant (IFA), or aqueous suspension were challenged intravenously with 0.1 TCID50 of cell-free SIVmac. Whereas virus was readily recovered from the peripheral blood lymphocytes of 10 of 10 nonvaccinated controls following this challenge dose, virus was not recovered from the three animals that received the vaccine with MDP nor from one of two animals that received the vaccine with IFA and one of three animals that received the aqueous vaccine. The animals that were protected against challenge were those that had detectable SIV antibody response to the envelop, both the outer glycoprotein (gp120) and the truncated transmembrane glycoprotein (gp31). Protected monkeys tended to have higher titers of syncytial inhibition antibody prior to challenge. An anamnestic response after challenge was observed only in the vaccinated monkeys that became infected. Vaccinated animals that became challenge-infected tended to live longer than infected controls. These results confirm those at two other primate centers and indicate that killed whole SIV vaccines can protect against low challenge doses of SIV and prevent early death in those monkeys that do become infected. The mechanism of this protection remains undetermined. This finding adds optimism to the possibility of an eventual AIDS vaccine.


19.2% Efficient InP Heterojunction Solar Cell with Electron-Selective TiO2 Contact.
We demonstrate an InP heterojunction solar cell employing an ultrathin layer (∼10 nm) of amorphous TiO2 deposited at 120 °C by atomic layer deposition as the transparent electron-selective contact. The TiO2 film selectively extracts minority electrons from the conduction band of p-type InP while blocking the majority holes due to the large valence band offset, enabling a high maximum open-circuit voltage of 785 mV. A hydrogen plasma treatment of the InP surface drastically improves the long-wavelength response of the device, resulting in a high short-circuit current density of 30.5 mA/cm2 and a high power conversion efficiency of 19.2%.


Bayes-optimality motivated linear and multilayered perceptron-based dimensionality reduction.
Dimensionality reduction is the process of mapping high-dimension patterns to a lower dimension subspace. When done prior to classification, estimates obtained in the lower dimension subspace are more reliable. For some classifiers, there is also an improvement in performance due to the removal of the diluting effect of redundant information. A majority of the present approaches to dimensionality reduction are based on scatter matrices or other statistics of the data which do not directly correlate to classification accuracy. The optimality criteria of choice for the purposes of classification is the Bayes error. Usually however, Bayes error is difficult to express analytically. We propose an optimality criteria based on an approximation of the Bayes error and use it to formulate a linear and a nonlinear method of dimensionality reduction. The nonlinear method we propose, relies on using a multilayered perceptron which produces as output the lower dimensional representation. It thus differs from autoassociative like multilayered perceptrons which have been proposed and used for dimensionality reduction. Our results show that the nonlinear method is, as anticipated, superior to the linear method in that it can perform unfolding of a nonlinear manifold. In addition, the nonlinear method we propose provides substantially better lower dimension representation (for classification purposes) than Fisher's linear discriminant (FLD) and two other nonlinear methods of dimensionality reduction that are often used.


Gait analysis in adults with severe hip dysplasia before and after total hip arthroplasty.
Anatomical reconstruction of high riding hips by total hip arthroplasty (THA) and subtrochanteric shortening osteotomy aims to normalise gait pattern and improve functional hip scores. We present the medium-term clinical results of a group of patients with high riding dislocated hips in whom a cementless THA and subtrochanteric shortening osteotomy had been performed. We compared them with their preoperative status, with patients who had undergone a cementless THA for primary osteoarthritis, and also with a group of healthy gender and age-matched controls. Prospective computerized, three-dimensional gait analyses were performed in 8 female patients with uni-/ or bilateral severe developmental dysplasia of the hip (Group I). Gait analysis was performed preoperatively and at a mean of 12.5 months postoperatively. A group of 8 individuals who received cementless hip replacement for primary osteoarthritis (Group II), and a control group of 8 able-bodied individuals (Group III) were recruited for comparison. Patients in Group I improved and approached the values of Group II. However both were behind Group III. Limb length discrepancy was reduced from a mean of 4.3 cm (range, 1 - 8 cm) to a mean of 0.8 cm (range, 0 - 2 cm) at the latest follow-up. Pain was reliably relieved and activities of daily living were improved in patients with high riding developmental dysplasia of the hip, but they were still behind the normal population average. Nevertheless, the results can be as satisfactory as those in patients who undergo a THA for primary osteoarthritis.


The role of variability in evaluating ultra high dilution effects: considerations based on plant model experiments.
A series of experiments, performed on plant models with ultra high dilutions (UHD) of arsenic trioxide at 45th decimal potency has been reviewed with a particular focus on variability. The working variables considered are: the number of germinated seeds out of a fixed set of 33, the stem length of wheat seedlings and the number of necrotic lesions in tobacco leaf disks inoculated with tobacco mosaic virus (TMV). A thorough comparison between treatment and control group has been proposed, considering the two main sources of variability in each series of experiments: variability within and between experiments. In treated groups, a systematic decrease in variability between-experiments, as well as a general decrease, with very few exceptions, in variability within experiments has been observed with respect to control. Variability is traditionally considered as control parameter of model systems. Our hypothesis, based on experimental evidences, proposes a new role of variability as a target of UHD action. This hypothesis may help interpret unanswered questions that keep rising in basic and clinical research in homeopathy.


Planetary contamination I: the problem and the agreements.
The sterility requirements for landed spacecraft tentatively adopted in the COSPAR resolution of 1964 are so severe as to pose a major obstacle to planetary exploration. This by itself would not justify modification of the re quirements, since preservation of the biological integrity of Mars is essential for proper exploration of the planet. However, when the physical and biological assumptions underlying the COSPAR recommendations are com pared with actual conditions on Mars, as established by recent observations, it becomes apparent that the COSPAR as sumptions are unrealistic in important respects. Specifically, the belief that eolian erosion on Mars can effect the release of spores trapped in the interior of solids in periods of time that are short compared with the time scale of the unmanned space program is unsup ported by either observation or theory. On the contrary, the analysis suggests that rates of eolian erosion on Mars are very low. Similarly, present knowledge of the Martian environment opposes the view that terrestrial microorganisms would readily contaminate the planet. The combination of dryness, lack of oxygen, and high ultraviolet flux makes the surface of Mars peculiarly unsuit able for the multiplication of terrestrial organisms. Recent studies give little sup port to the proposal that significant areas of geothermal activity exist on Mars. These various findings suggest that the COSPAR-recommended constraints could be substantially relaxed without compromising to any significant degree the biological condition of Mars. In particular, a distinction needs to be made between microorganisms trapped in solids and those on exposed sur faces of landed spacecraft. Surface sterility is an unconditional require ment, in the sense that it is imposed by considerations unrelated to the nature of the Martian environment. Sterilization of the interior of solids to the extreme level recommended by COSPAR, however, is based on the as sumption that entrapped organisms con stitute a substantial hazard to the ecology of Mars. This assumption now seems unjustified, and the need for a high degree of interior sterility is doubt ful. Current spacecraft-sterilization pol icies should be revised accordingly.


Information transmission using non-poisson regular firing.
In many cortical areas, neural spike trains do not follow a Poisson process. In this study, we investigate a possible benefit of non-Poisson spiking for information transmission by studying the minimal rate fluctuation that can be detected by a Bayesian estimator. The idea is that an inhomogeneous Poisson process may make it difficult for downstream decoders to resolve subtle changes in rate fluctuation, but by using a more regular non-Poisson process, the nervous system can make rate fluctuations easier to detect. We evaluate the degree to which regular firing reduces the rate fluctuation detection threshold. We find that the threshold for detection is reduced in proportion to the coefficient of variation of interspike intervals.


[Case of solitary fibrous tumor of the pleura completely resected eleven years after detection].
A 65-year-old woman was referred to our hospital for investigation of increased opacity in the right lower lung field of the chest X-ray. Chest CT demonstrated a large tumor in the right thoracic cavity. A preoperative needle biopsy was performed. The microscopic appearance revealed many spindle cells. An immunohistochemical study was positive for CD34 and vimentin. Solitary fibrous tumor of the pleura was strongly suspected and the operation was performed. The tumor arose from the visceral pleura and was pedunculated. The resected specimen was positive for CD34 and vimentin. The tumor was diagnosed as solitary fibrous tumor of the pleura. Although this case was diagnosed 11 years after detection, the tumor was completely resected. Solitary fibrous tumors are usually cured with complete resection, but long-term clinical follow up is needed because of the possibility of recurrence and metastasis.


Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.
For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. None.


[Evidence-based interventions to prevent tobacco use among youth: a literature review].
This paper reviews the current knowledge of empirically validated interventions aimed at preventing tobacco use among children and adolescents. Given the increasing number of daily smokers among young people aged 17, there needs to be an emphasis on interventions aimed at promoting healthy behaviors. The study used a standard protocol to identify and review the literature and to classify the selected interventions. 22 interventions were found to have a positive impact on youth smoking. More than half of the interventions are aimed at the general population, while the other programs target vulnerable populations or young smokers. The study found that most of the interventions are aimed at adolescents, though some are aimed at children under 12 years of age. Around half of the interventions use several strategies, including actions in schools, parent involvement and/or community participation. Almost all individual-based programs are designed to promote the development of psychosocial skills. Effective mass media campaigns and national strategies to restrict access to tobacco are also presented. This study aims to contribute to the understanding of programs in other countries and to promote reflection on professional practice in France.


Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.
Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy. The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells. Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice. There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.


Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients.
Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables. Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis. Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer. The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.


Physiology and Endocrinology Symposium: heat shock proteins: potentially powerful markers for preimplantation embryonic development and fertility in livestock species.
For the mammalian embryo to successfully complete development, it must not only incur proper timing of internal machinery, but also protect itself from potentially harmful external stimuli. These stimuli, ranging from chemical to temperature flux, can result in defects in processes regulating gamete production and quality, as well as early embryonic development. To counterbalance these potential detriments, the mammalian cell has complex machinery consisting of heat shock factors and proteins that prevent protein misfolding and malfunction. Heat shock protein (HSP) genes have become a growing topic to understand the mechanisms of successful gamete formation and embryonic development, critical factors for livestock fertility. In addition, HSP have become a focus in understanding how external stimuli during the in vitro embryo production process may have a developmental impact. To further elucidate these mechanisms, it has become a necessity for more in-depth functional studies on HSP using technologies such as RNA interference and antibody use during embryo culture. Through these studies we can gain a more comprehensive perspective of HSP function and importance during early development. In addition, information from these studies may provide critical markers for improved fertility and development.


ACE2 and SCARF expression in human dorsal root ganglion nociceptors: implications for SARS-CoV-2 virus neurological effects.
SARS-CoV-2 has created a global crisis. COVID-19, the disease caused by the virus, is characterized by pneumonia, respiratory distress, and hypercoagulation and can be fatal. An early sign of infection is loss of smell, taste, and chemesthesis-loss of chemical sensation. Other neurological effects of the disease have been described, but not explained. It is now apparent that many of these neurological effects (for instance joint pain and headache) can persist for at least months after infection, suggesting a sensory neuronal involvement in persistent disease. We show that human dorsal root ganglion (DRG) neurons express the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 at the RNA and protein level. We also demonstrate that SARS-CoV-2 and coronavirus-associated factors and receptors are broadly expressed in human DRG at the lumbar and thoracic level as assessed by bulk RNA sequencing. ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs. Therefore, DRG sensory neurons are a potential target for SARS-CoV-2 invasion of the peripheral nervous system, and viral infection of human nociceptors may cause some of the persistent neurological effects seen in COVID-19.


Human plasma and urinary metabolic profiles of trimethylamine and trimethylamine N-oxide extrapolated using a simple physiologically based pharmacokinetic model.
Trimethylamine, a dietary- and medicinal carnitine-derived amine, is extensively metabolized by liver to non-malodorous trimethylamine N-oxide. Although trimethylamine and trimethylamine N-oxide under daily dietary consumption or carnitine treatment are generally regarded as nontoxic, they have been, and remain, of toxicological and clinical interest because of their potential association with atherosclerosis. The aim of the current study was to model the pharmacokinetics of trimethylamine after oral administration of trimethylamine in humans and compare the results with reported measured values. Adjusted biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human equivalents using known species allometric scaling factors. In vitro metabolic clearance data were obtained using rat and human liver microsomal preparations. Renal clearances in humans for trimethylamine and trimethylamine N-oxide were calculated with a clearance concept approach using reported 24-hr urinary excretion rates and assumed areas under plasma concentration curves. The resulting modeled plasma and urinary concentration curves by simple physiologically based pharmacokinetic models (or semi-physiological pharmacokinetic models) were consistent with reported concentrations. This study provides important information to help simulate human plasma levels of trimethylamine and trimethylamine N-oxide in trimethylamine loading tests and during treatment with prescribed medicinal l-carnitine, showing the similar range as that resulting from daily dietary foodstuff consumption along with little toxicological impacts. The present models could estimate relationship between plasma and urine concentrations of trimethylamine or trimethylamine N-oxide and the daily oral doses by both forward and reverse dosimetry from viewpoint of human risk assessment.


[Role of spectral filters for refraction dynamics in computer users].
The influence of the spectral-filter (SF) spectacles (when used for an extended time period--for 4 years), produced on the eye refraction of computer users, was studied. The persons in the main and control groups (mean age was, respectively, 49.46 +/- 2.27 and 46.0 +/- 3.28 years, and mean refraction was, respectively, -0.71 +/- 0.42 and -0.88 +/- 0.5 diopters) used the computers on the daily basis for as long as 4 hours during 4 years. A reliable weakening of refraction in its both variants (i.e. reduction of myopia by 0.16 +/- 0.06 diopters, and an increase of hypermetropia by 0.19 +/- 0.04 diopters) was registered in the main group in case of a prolonged use of the SF spectacles. As for the control group, a reliable increase of myopia by 0.25 +/- 0.06 diopters was noted in operators with myopia, and a reliable weakening of refraction (a growth in the level of hypermetropia) by 27 +/- 0.05 diopters was found in operators with hypermetropia and emmetropia. According to questionnaire results, 88.2% of computer operators, who used the SF spectacles, managed to preserve the initial improvement of comfort, while the comfort degree worsened in 11.8% of them.


Effect of manidipine as compared to atenolol on platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus.
This study was done to evaluate the effect of treatment with manidipine as compared with atenolol on thrombin-mediated platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus. After a 2-week washout placebo period, 60 elderly patients (aged 65-80 years) with isolated systolic hypertension (SBP > 140 mm Hg and DBP < 90 mm Hg) were randomly assigned to manidipine 10 mg or atenolol 50 mg 6-week treatment according to a double-blind, crossover design. Thirty patients had a concomitant well-controlled type 2 diabetes mellitus (HbA1c < or = 6.5%). At the end of the washout and of each treatment period, blood pressure (BP) (by mercury sphygmomanometer) and platelet aggregation (by Born-type aggregometer) were evaluated. Blood samples were collected using sodium citrate as anticoagulant, and platelet aggregation was induced by 2 different concentrations of ADP and collagen. Manidipine and atenolol produced a significant BP reduction in both diabetic and nondiabetic patients, with no difference between treatments. Despite the similar BP effect, in diabetic patients manidipine produced a significant reduction in platelet aggregation induced by both doses of either ADP or collagen. In nondiabetic hypertensives, manidipine inhibited platelet aggregation only at the highest doses of both inducers. The difference in the platelet inhibitory effect of manidipine between diabetic and nondiabetic subjects was statistically significant (P < 0.05) at both inducer concentrations. No changes in platelet aggregation were observed in the atenolol group. These data indicate that, unlike atenolol, manidipine inhibits platelet aggregation in elderly hypertensive patients, expecially in those with associated type II diabetes mellitus. The clinical impact of this positive effect in terms of prevention of cardiovascular complications in these high-risk patients remains to be clarified.


Physical activity on executive function in sedentary individuals: Systematic review and meta-analysis of randomized controlled trials.
Physical activity has been demonstrated to promote cognitive performance. However, the relationship between physical activity and executive function (EF) in sedentary individuals is not fully understood. This meta-analysis examined the impact of physical activity on EF in sedentary individuals and evaluated potential moderators of the relationship between physical activity and EF. In accordance with the PRISMA guidelines, the electronic databases MEDLINE, Embase, PsycINFO and Web of Science were searched. Included studies had to report sedentary individuals randomized to either a physical activity group or a control group. Subgroup analyses of EF sub-domains, exercise prescription and age were conducted alongside the overall meta-analysis. Thirteen RCT studies were included, with a total of 752 participants. Results showed a small to moderate beneficial effect of physical activity on EF (SMD = 0.24, 95% CI 0.08 to 0.40). In subgroup analysis by EF sub-domains, physical activity enhanced inhibitory control (SMD = 0.38, 95% CI 0.12 to 0.63) and working memory (SMD = 0.22, 95% CI -0.05 to 0.49), but not cognitive flexibility (SMD = 0.11, 95% CI -0.18 to 0.41). Interventions with an intervention length > 12 weeks improved overall EF (SMD = 0.26, 95% CI 0.06 to 0.46), but intervention length ≤ 12 weeks did not (SMD = 0.20, 95% CI -0.08 to 0.47). Interventions with session time ≥ 45 minutes improved overall EF (SMD = 0.47, 95% CI 0.22 to 0.77), but session time < 45 minutes did not (0.17, 95% CI -0.11 to 0.44). Physical activity improves EF for older adults (age ≥ 60 years) (SMD = 0.25, 95% CI 0.08 to 0.42), but not for younger individuals (age < 60 years) (SMD = 0.17, 95% CI -0.25 to 0.59). Overall, physical activity has a beneficial effect on EF in sedentary individuals, although the influence may be domain specific and influenced by exercise prescription and age. These findings have practical implications for those seeking to improve EF in sedentary individuals through physical activity.


Interaction between orbital prefrontal and rhinal cortex is required for normal estimates of expected value.
Predicting and valuing potential rewards requires integrating sensory, associative, and contextual information with subjective reward preferences. Previous work has identified regions in the prefrontal cortex and medial temporal lobe believed to be important for each of these functions. For example, activity in the orbital prefrontal cortex (PFo) encodes the specific sensory properties of and preferences for rewards, while activity in the rhinal cortex (Rh) encodes stimulus-stimulus and stimulus-reward associations. Lesions of either structure impair the ability to use visual cues or the history of previous reinforcement to value expected rewards. These areas are linked via reciprocal connections, suggesting it might be their interaction that is critical for estimating expected value. To test this hypothesis, we interrupted direct, intra-hemispheric PFo-Rh interaction in monkeys by performing crossed unilateral ablations of these regions (functional disconnection). We asked whether this circuit is crucial primarily for cue-reward association or for estimating expected value per se, by testing these monkeys, as well as intact controls, on tasks in which expected value was either visually cued or had to be inferred from block-wise changes in reward size in uncued trials. Functional disconnection significantly affected performance in both tasks. Specifically, monkeys with functional disconnection showed less of a difference in error rates and reaction times across reward sizes, in some cases behaving as if they expected rewards to be of equal magnitude. These results support a model whereby information about rewards signaled in PFo is combined with associative and contextual information signaled within Rh to estimate expected value.


The structure-based expert model of the mental disorders--a validation study.
In an earlier study, our research group presented an alternative approach to measuring knowledge about mental disorders by constructing a structure-based expert model of the ICD-10 mental disorders. This article presents a validation of this expert model by measuring the emergence of such knowledge structures in psychotherapy students. The participants of a continuing education program in cognitive behavioral psychotherapy rated a selection of mental disorders based on their phenomenological similarity. The similarity judgments of each student were translated by nonmetric multidimensional scaling (NMDS) into a cognitive map. In a quasi-longitudinal section design, the maps of the students of the first to the fourth year of training were compared with each other and with an expert map (the expert model) of experienced therapists. The discrepancies of the trainee maps compared with each other and with the expert map significantly decreased with increasing training level. The convergence of the students' maps towards the expert model indicates that the structural knowledge about mental disorders of experienced therapists can also be found to be emerging in psychotherapy students. This finding supports the validity of the expert model and may reflect a general knowledge-structuring principle of the mental disorders. In spite of the statistical significance found, in view of the small number of participants in the third and fourth years of training, the results should be treated with caution and should be regarded as first indicators which need further confirmation.


Sources of health insurance and characteristics of the uninsured: analysis of the March 1999 Current Population Survey.
This Issue Brief provides summary data on the insured and uninsured populations in the nation and in each state. It discusses the characteristics most closely related to an individual's health insurance status. Based on EBRI estimates from the March 1999 Current Population Survey (CPS), it represents 1998 data--the most recent data available. In 1998, 194.7 million nonelderly Americans--81.6 percent--had some form of health insurance. More than 64 percent had it through an employment-based health plan; 6.5 percent purchased it on their own; and 14.3 percent were covered by a public program, mostly through Medicaid (10.4 percent). In 1998, 18.4 percent of the nonelderly population was uninsured (43.9 million people), compared with 14.8 percent in 1987. The percentage of uninsured Americans has generally been increasing since at least 1987, although the percentage uninsured in 1998 was not statistically different from the percentage uninsured in 1997 (18.3 percent). The increase in the uninsured prior to 1993 can be attributed to the erosion of employment-based health insurance. However, since 1993, the percentage of nonelderly Americans covered by an employment-based health plan has increased from 63.5 percent to 64.9 percent. The decline in public sources of health insurance would mostly explain the recent increase in the uninsured. For example, between 1994 and 1998 the percentage of nonelderly Americans covered by CHAMPUS/CHAMPVA declined from 3.8 percent to 2.9 percent, in large part due to downsizing in the military. Similarly, between 1993 and 1998, the percentage of nonelderly Americans covered by Medicaid declined from 12.7 percent to 10.4 percent as people left welfare. The increase in employment-based coverage since 1994 was due mainly to a higher likelihood that children were covered by an employment-based health plan. Between 1994 and 1998, the percentage of children covered by an employment-based health plan increased from 58.1 percent to 60.2 percent. For adults, it increased less than one percentage point, from 66.1 percent to 66.9 percent. Adults started to realize gains in employment-based health insurance between 1997 and 1998. Between 1994 and 1997, the percentage of working adults with employment-based health insurance coverage held steady at roughly 72.3 percent. During this period, health care cost inflation was essentially nonexistent. However, between 1997 and 1998, the percentage of working adults with employment-based health insurance increased from 72.2 percent to 72.8 percent, despite the apparent return of health care cost inflation in 1998. It is likely that the changing composition of the labor force accounted for some of the increase in employment-based coverage.


Structural and functional relationships in two families of beta-1,4-glycanases.
CenA and Cex are beta-1,4-glycanases produced by the cellulolytic bacterium Cellulomonas fimi. Both enzymes are composed of two domains and contain six Cys residues. Two disulfide bonds were assigned in both enzymes by peptide analysis of the isolated catalytic domains. A further disulfide bond was deduced in both cellulose-binding domains from the absence of free thiols under denaturing conditions. Corresponding Cys residues are conserved in eight of nine other known C. fimi-type cellulose-binding domains. CenA and Cex belong to families B and F, respectively, in the classification of beta-1,4-glucanases and beta-1,4-xylanases based on similarities in catalytic domain primary structure. Disulfide bonds in the CenA catalytic domain correspond to the two disulfide bonds in the catalytic domain of Trichoderma reesei cellobiohydrolase II (family B) which stabilize loops forming the active-site tunnel. Sequence alignment indicates the probable occurrence of disulfides at equivalent positions in the two other family B enzymes. Partial resequencing of the gene encoding Streptomyces KSM-9 beta-1,4-glucanase CasA (family B) revealed five errors in the original nucleotide sequence analysis. The corrected amino acid sequence contains an Asp residue corresponding to the proposed proton donor in hydrolysis catalysed by cellobiohydrolase II. Cys residues which form disulfide bonds in the Cex catalytic domain are conserved in XynZ of Clostridium thermocellum and Xyn of Cryptococcus albidus but not in the other eight known family F enzymes. Like other members of its family, Cex catalyses xylan hydrolysis. The catalytic efficiency (kcat/Km) for hydrolysis of the heterosidic bond of p-nitrophenyl-beta-D-xylobioside is 14,385 min-1.mM-1 at 25 degrees C; the corresponding kcat/Km for p-nitrophenyl-beta-D-cellobioside hydrolysis is 296 min-1.mM-1.


Expression of carbonic anhydrase III and skeletal muscle remodeling following selective denervation.
Carbonic anhydrase III (CAIII) is expressed selectively in type I (slow‑twitch) myofibers. To investigate the association between changes in the expression of CAIII and skeletal muscle structure following denervation, the present study stained adjacent sections of skeletal muscle for ATPase and immunohistochemically for CAIII. In addition, differences in the protein expression and phosphatase activity of CAIII were examined by western blot and phosphatase staining between rat soleus and extensol digitorum longus (EDL) muscles, which are composed of predominantly slow‑ and fast‑twitch fibers, respectively. Upon denervation, the EDL muscle showed more pronounced structural changes, compared with the soleus muscle. There was a transformation from fast to slow fibers, and a concomitant increase in fibers positive for CAIII. Following denervation, the protein expression of CAIII initially increased and then decreased in the soleus muscle, whereas the protein expression of CAIII in the EDL muscle increased gradually with time. In contrast to the protein changes, phosphatase activity in the soleus and EDL muscles decreased significantly following denervation. These results indicated that, following denervation, changes in the expression of CAIII were associated with myofiber remodeling. Specifically, the change in the expression of CAIII reflected the conversion to type I myofibers, suggesting the importance of CAIII in resistance to fatigue in skeletal muscle.


A case of histoid leprosy in a HIV infected person on HAART not responding to conventional MB-MDT.
A 46 year old male diagnosed case of Acquired Immune Deficiency Syndrome (AIDS) on Highly Active Anti Retroviral Therapy (HAART) presented with raised nodular skin lesions of two months duration which on skin biopsy was diagnosed as Histoid leprosy. Individual was put on standard Multi Bacillary Multi Drug Therapy (MB MDT) for two months has shown exacerbation of lesion and was later put on daily Rifampicin, Ofloxacin and Minocycline (ROM) for which he responded. Interesting feature is rarity of association of HIV with Histoid Leprosy where the patient did not respond to the conventional MB MDT and later responded to daily ROM.


Influence of cement type and thickness on polyfiber post adhesion.
To evaluate the effect of two different post space diameters and related resin cement film thicknesses on the bond strength of a polyfiber post. A total of 48 premolars were randomly divided into two according to the post space diameter: 1.1 mm and 1.5 mm. Then each group was divided into three sub-groups according to luting cement used: RelyX U100, Panavia F2.0/ED primer, Clearfil SA cement. Spirapost was then luted into the canal using luting cements. Two slices were obtained from each root specimen. Push-out tests were performed. Data was analyzed with Kruskal-Wallis and Connover post-hoc and Mann-Whitney U-test (P < 0.05). Push-out bond strength was found to vary significantly according to type of adhesive system and post space diameter size (P < 0.05). The self-adhesive resin cement RelyX U100 had significantly higher bond strengths compared with the other adhesive system (P < 0.05). The self-etch adhesive system (Panavia F2.0) showed significantly lower bond strengths compared with the other systems (P < 0.05). There was a significant interaction between the luting systems and post space diameter (P < 0.05). The increases in post space diameter significantly reduced the bond strength of Spirapost to root dentine for both groups.


[Dyspepsia in general practice].
110 patients who presented dyspeptic complaints to their general practitioner were interviewed using a questionnaire. Most patients had a long history of dyspeptic symptoms. 36 had been treated before for a peptic ulcer. Only 12 patients had a history of dyspepsia lasting less than three months. It is difficult to distinguish between organic and non-organic dyspepsia from the symptoms, and long-standing symptoms at any rate should be investigated further. The effect of medical treatment varies. Many patients have to live with their discomfort.


Modulation of CD8+ T Cell Responses by Radiotherapy-Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors.
Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest in the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials to evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are currently undergoing. In this review, we summarize the current status of knowledge regarding the changes in CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biological mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.


The Use of Geographic Information Systems for Spatial Ecological Risk Assessments: An Example from the Athabasca Oil Sands Area in Canada.
There is an acknowledged need in ecotoxicology for methods that integrate spatial analyses in risk assessment. This has resulted in the emergence of landscape ecotoxicology, a subdiscipline of ecotoxicology. However, landscape ecotoxicology has yet to become common practice in risk assessment due to the underdevelopment of techniques and a lack of standardized methods. In the present study, we demonstrate how geographic information systems (GISs) can serve as a standardized platform to integrate data, assess spatial patterns of ecotoxicological data for multiple species, and assess relationships between chemical mixture exposures and effects on biota for landscape ecotoxicological risks assessment. We use data collected under the Joint Oil Sands Monitoring Program in the Athabasca Oil Sands Region in Alberta, Canada. This dataset is composed of concentrations of contaminants including metals and polycyclic aromatic compounds, and health endpoints measured in 1100 biological samples, including tree swallows, amphibians, gull and tern eggs, plants, and mammals. We present 3 examples using a GIS as a platform and geospatial analysis to: 1) integrate data and assess spatial patterns of contaminant exposure in the region, 2) assess spatial patterns of exposures to complex mixtures, and 3) examine patterns of exposures and responses across the landscape. We summarize the methods used in the present study into a workflow for ease of use. The GIS methods allow researchers to identify hot spots of contamination, use georeferenced monitoring data to derive quantitative exposure-response relationships, and assess complex exposures with more realism. Environ Toxicol Chem 2019;38:2797-2810. © 2019 SETAC.


[A systematic review about the scientific production with focus on the relation between health and environment].
The discussion on points linked to the interface between the environment and health has turned into a very important subject of interest nowadays. Thus, this article aims to show a survey of the national and international scientific production about this subject, in an attempt to identify the most frequent themes of this production. The data were collected during the months of March and April of 2005, from two homepages where scientific publications are available on the web, from which, 603 publications were used as analysis material, by means of categorization. The data showed that there is a very significant number of countries with scientific production on this area, being the most frequent the USA and Russia, whose most relevant theme area is related to risk evaluation. Brazil appears as the third most frequent country in terms of production and most of its work is directed to the study of vectors (transmitters) of infecting-contagious diseases. About the other countries, there is a diversification of lines of investigation. In general, it is perceived that the production of knowledge of this area still occurs in a very isolated and fragmented way, with little importance to the diversity of factors involved in the environmental questions, as well as with little space to interdisciplinary and inter sectorial work, so important in the analysis of the interface health-environment.


Suitability of air sampling locations downstream of bends and static mixing elements.
The revised standard for sampling effluent air from stacks and ducts of the nuclear industry places limits on the non-uniformity of velocity and contaminant profiles at the sampling location; namely, the coefficients of variation must not exceed 20% over an area that encompasses at least the center 2/3 of the cross sectional area. Tests were conducted to characterize the degree of mixing at downstream locations as affected by several types of flow disturbances, including 90 degree elbows and commercial static mixing devices. Flow straighteners were incorporated into the ducting upstream of the mixer to be tested to simulate the dampening of flow turbulence that might occur because of upstream HEPA filters. The coefficients of variation of velocity and tracer gas concentration measured in a straight tube at a distance of 3 diameters downstream from a 90 degree elbow were 17% and 69%, respectively. The mixing is impacted by the upstream flow turbulence. Without a flow straightener, the tracer gas concentration coefficient of variation was reduced to 33% at the 3-diameter location. The use of static mixing elements can greatly enhance the mixing process. A ring placed just downstream of a 90 degree elbow, which blocks the outer 56% of the cross sectional area, results in a coefficient of variation of 19% for tracer gas concentration at the 3-diameter location. Pressure loss across the elbow with the ring is about nine times that of the basic elbow. One of the commercially available static mixers provides coefficients of variation that are less than 10% for both velocity and tracer gas concentration at 4 diameters downstream from the mixer with a pressure loss that is only about 3.5 times as large as that of a 90 degree elbow.


Cancer risk with alemtuzumab following kidney transplantation.
Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.


Effective interventions for depressive symptoms among caregivers of people with dementia: A systematic review and meta-analysis.
Caring for a family member with dementia puts caregivers at risk for depressive symptoms. Yet, interventions with promising effects on caregiver depressive symptoms are not well documented. This review aimed to examine the quality and effectiveness of interventions to reduce depressive symptoms reported by caregivers of people with dementia. A systematic review and meta-analysis of nonpharmacological intervention trials was conducted. The electronic databases searched included MEDLINE, CINAHL, and PsycINFO to find randomized controlled trials published between 2007 and 2017. A total of 31 randomized controlled trials were included in the meta-analysis. Cognitive-behavioral therapy (838 participants) showed a large, significant effect (standardized mean difference = -0.905; 95% CI = (-1.622, -0.187); p = 0.013) and mindfulness interventions (186 participants) showed moderate, significant effects (standardized mean difference = -0.578; 95% CI = (-0.881, -0.275); p < 0.001) on decreasing caregiver depressive symptoms, while psychoeducational interventions demonstrated small but significant effects (standardized mean difference = -0.244; 95% CI = (-0.395, -0.092); p = 0.002). Emotional support, cognitive rehabilitation, and multicomponent interventions showed less than small or nonsignificant effects related to depressive symptoms among caregivers. Cognitive-behavioral therapy interventions, which focus on diminishing negative thoughts and increasing positive activities, can effectively decrease depressive symptoms for caregivers of individuals with dementia. Future research is recommended to assess the long-term effectiveness of cognitive-behavioral therapy in this population.


A model for investigating the systemic effects of adrenaline in dental local anaesthetic solutions in patients under surgical stress.
A model has been developed which permits the investigation of the systemic effects of adrenaline injected during dental local anesthesia. The model employs patients undergoing the removal of third molars under general anaesthesia. This design allows the study of the effects of exogenous adrenaline administration in clinical doses in patients experiencing surgical stress. In the present investigation the influence of the intra-oral injection of 50 micrograms adrenaline contained in lignocaine local anaesthetic solution on haemodynamic and biochemical responses was established by comparing the effects of inferior alveolar block injections of 4 ml 2% lignocaine and 4 ml 2% lignocaine with 1:80,000 adrenaline in 20 patients having third molars removed with a standardised general anaesthetic regime. No significant changes in haemodynamic responses between treatments were apparent, however significant changes occurred between treatments in blood glucose and plasma potassium levels.


Accuracy of liver and spleen stiffness on magnetic resonance elastography for detecting portal hypertension: a systematic review and meta-analysis.
The purpose of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of liver and spleen stiffness on magnetic resonance elastography (MRE) for detecting clinically significant portal hypertension. A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Grey Literature through to 15 August 2019 was performed. Original articles with >10 patients evaluating liver and/or spleen stiffness on MRE using a reference standard of portal hypertension defined as intractable ascites, esophageal varices, encephalopathy and/or death were included in analysis. Patient, clinical, MRI, and diagnostic performance was independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. Fourteen studies were included with 12 studies evaluating liver stiffness and eight studies evaluating spleen stiffness. The pooled and weighted sensitivity, specificity, and area under the curve (AUC) values for liver stiffness on MRE were 83% [95% confidence interval (CI) 72-90%], 80% (95% CI 70-88%), and 88% (95% CI 85-91%), respectively. The pooled and weighted sensitivity, specificity, and AUC values for spleen stiffness on MRE were 79% (95% CI 61-90%), 90% (95% CI 80-95%), and 92% (95% CI 89-94%), respectively. The liver and spleen stiffness sensitivity and specificity values were comparable when evaluating for esophageal varices only at of 80% (95% CI 66-89%) and 76% (95% CI 62-86%) for liver stiffness, and 75% (95% CI 52-90%) and 89% (95% CI 70-96%) for spleen stiffness. Liver and spleen stiffness on MRE can serve as a supplemental noninvasive assessment tools for detecting clinically significant portal hypertension. Spleen stiffness may be more specific and accurate than liver stiffness for detecting portal hypertension.


Surgical pathology for the oncology patient in the age of standardization: of margins, micrometastasis, and molecular markers.
From initial diagnosis through definitive treatment, pathologic evaluation plays a central role in the care of patients with cancer. All patient management is dependent on the correct tissue diagnosis. For surgically resected malignancies, the pathologic stage is widely recognized as the most accurate predictor of survival, and it typically determines the appropriateness of adjuvant treatment as well. Numerous additional pathologic factors have been shown by multivariate analyses to have prognostic significance that is independent of stage, and these may help to further substratify tumors, individualize treatment, and more accurately predict outcome. On a larger scale, pathologic data are essential for epidemiologic and clinical research and is the common language of cancer worldwide. Despite its overriding importance, however, current pathologic analysis is fraught with variations in methodology, interpretation of findings, terminology, reporting norms, and statistical approaches that compromise its utility, both to the individual patient and to the progress of cancer medicine and research. In the last 5 years, increasing attention has been focused on the negative impact of variation in pathology practices on patient care and medical progress at all levels including institutional, regional, national, and international. This problem is within the immediate ability of the pathology profession to correct, and the author's prediction for oncologic pathology over the next 5 years is that standardization based on best practices will become, itself, the standard.


Knowledge of AIDS and HIV risk-related sexual behavior among Nigerian naval personnel.
The epidemic of HIV continues to grow in Nigeria. Personnel in the military are at increased risk of HIV infection. Although HIV-risk related sexual behavior of Nigerian police officers has been studied, little is known about the sexual behavior of their counterparts in the Navy. This study describes knowledge of AIDS, and HIV-risk sexual behavior of naval personnel in Lagos Nigeria. Four hundred and eighty personnel of the Nigerian Navy completed a 70-item questionnaire in 2002. Group discussion and in-depth interviews of four key informants were also conducted to gain insights into the context of risky sexual behaviors and suggestions for feasible HIV primary prevention interventions. The mean age of the respondents was 34 years. Although the overall mean AIDS knowledge score was 7.1 of 10 points, 52.1% of respondents believed that a cure for AIDS was available in Nigeria and that one can get HIV by sharing personal items with an infected person (25.3%). The majority (88.1%) had had lifetime multiple partners ranging from 1-40 with a mean of 5.1; 32.5% of male respondents had had sexual contact with a female sex worker, 19.9% did so during the six months preceding the survey. Forty-one percent of those with sexual contact with a female sex worker did not use a condom during the most recent sexual encounter with these women. Naval personnel who have been transferred abroad reported significantly more risky sexual behaviors than others. Group discussants and key informants believed that sex with multiple partners is a tradition that has persisted in the navy even in the era of AIDS because of the belief that AIDS affects only foreigners, that use of traditional medicine provides protection against HIV infection, and influence of alcohol. Many naval personnel report participating in high-risk sexual behavior which may increase their risk of acquiring and spreading HIV. Naval personnel live and interact freely with civilian population and are potential bridging group for disseminating HIV into the larger population. Interventions including sustained educational program, promotion of condoms, changes in transfer policies are recommended to address this problem.


Reduction by oral propranolol treatment of left ventricular hypertrophy secondary to pressure-overload in the rat.
1. Studies on cardiac myocyte cell cultures have postulated a role for alpha 1-adrenoceptors and mechanical stretch in the induction of cellular changes thought to be important in compensatory cardiac hypertrophy. However, in vivo work suggests that beta-adrenoceptors are important and the present study was designed to analyse the effect of propranolol on the cardiac hypertrophy caused by a pressure-overload in a way that takes account of the effects of propranolol on the work load itself. 2. The compensatory cardiac hypertrophy that develops in response to experimental coarctation of the aorta was studied in the rat. Pressure gradients and total cardiac work load (expressed as rate x pressure product) were assessed, and the relationship between increasing cardiac work load and the resulting left ventricular hypertrophy was established in a control group and compared with left ventricular hypertrophy in a group treated with a high dose of oral propranolol (80 mg kg-1 body weight). 3. In the rats with mean pressure gradients over the coarctation in the range of 15-31 mmHg, the animals on control diet showed a 38% increase in left ventricular weight/body weight ratio (LV ratio) and a 30% increase in heart weight/body weight ratio (heart ratio), whereas rats given high dose oral propranolol-treatment showed increases of only 13% and 9%, respectively. 4. In a second series of rats with a wider range of pressure gradients, the regression lines of LV ratio versus mean pressure gradient, and of LV ratio versus cardiac work, were different in the two groups with a slope that was only half as steep in the propranolol-treated rats as in the controls. Thus, for the same increment in cardiac work load, the degree of compensatory cardiac hypertrophy in propranolol-treated rats was half that observed in controls. 5. The reduction in compensatory cardiac hypertrophy was not associated with an increase in incidence of congestive heart failure and the propranolol-treated rats were able to sustain equally high (or higher) degrees of pressure over-load as controls did. 6. It is concluded that propranolol treatment approximately halves the compensatory cardiac hypertrophy occurring in response to a left ventricular pressure over-load by a mechanism independent of its effect on cardiac work load. This finding provides further support for the view that noradrenaline released from sympathetic nerve terminals in the heart exerts a trophic effect on cardiac myocytes, and that the sympathetic nervous system may be the final common pathway in many forms of compensatory cardiac hypertrophy. In contrast to in vitro models, this effect appears to be largely mediated via beta-adrenoceptors in the intact animal.


Cross Talk between Viruses and Insect Cells Cytoskeleton.
Viruses are excellent manipulators of host cellular machinery, behavior, and life cycle, with the host cell cytoskeleton being a primordial viral target. Viruses infecting insects generally enter host cells through clathrin-mediated endocytosis or membrane fusion mechanisms followed by transport of the viral particles to the corresponding replication sites. After viral replication, the viral progeny egresses toward adjacent cells and reaches the different target tissues. Throughout all these steps, actin and tubulin re-arrangements are driven by viruses. The mechanisms used by viruses to manipulate the insect host cytoskeleton are well documented in the case of alphabaculoviruses infecting Lepidoptera hosts and plant viruses infecting Hemiptera vectors, but they are not well studied in case of other insect-virus systems such as arboviruses-mosquito vectors. Here, we summarize the available knowledge on how viruses manipulate the insect host cell cytoskeleton, and we emphasize the primordial role of cytoskeleton components in insect virus motility and the need to expand the study of this interaction.


Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis.
The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis.


[Analysis of distribution characteristics and drug resistance of 2748 strains of pathogens isolated from burn patients].
To provide epidemiological data of the distribution characteristics and drug resistance of the pathogens isolated from burn patients in recent years for guiding rational use of antibiotics in clinic. Totally 2748 strains of pathogens were isolated from 1977 specimens (blood, catheter, wound excretion, etc.) collected from 478 patients hospitalized in Institute of Burn Research of Southwest Hospital from March 2003 to June 2011. After being identified by API strips, drug resistance of the 2748 isolated pathogens to 55 commonly-used antibiotics including gentamicin, tobramycin, piperacillin, amikacin, etc. was tested by K-B paper disk diffusion method. The WHONET 5.3 software was used to analyze the following subjects: the distribution of the pathogens with different types and different sources each year, the changes in drug-resistant rates of Gram negative bacilli, Gram positive cocci, and fungi to several antibiotics, and the changes in sensitive rates of Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), Acinetobacter baumannii (AB), Candida albicans (CA) to several antibiotics. Among 2748 strains of pathogens, 1879 strains of Gram negative bacilli accounted for 68.38%, 628 strains of Gram positive cocci accounted for 22.85%, and 241 strains of fungi accounted for 8.77%. The isolation rate of strains from wound excretion ranked the first (1022 strains accounted for 37.19%), followed by those from respiratory tract (995 strains accounted for 36.21%) and blood (421 strains accounted for 15.32%). Strains isolated from other types of specimens were rare. Isolation rate of PA ranked the first (996 strains accounted for 36.24%), followed by SA (495 strains accounted for 18.01%) and AB (395 strains accounted for 14.37%). Isolation rate of AB showed a trend of increase year by year, but that of SA presented the opposite trend. Isolation rate of PA was quite stable. There were 484 strains of methicillin resistant SA among Staphylococci, accounting for 17.61%. Resistant rates of PA and AB to polymyxin B and polymyxin E were below 30.00%, and those of PA and AB to other antibiotics, such as the third generation cephalosporins, β-lactams, aminoglycosides, and quinolones, were from 57.91% to 100.00%. Resistant rate of AB to minocycline was 39.68%. From 2004 to 2011, sensitive rate of PA to quinolone antibiotics showed an increasing trend year by year, but that of AB to minocycline, netilmicin, imipenem, meropenem, tobramycin, and cefoperazone/sulbactam presented the opposite trend. Resistant rates of Enterococcus faecalis, Enterococcus faecium, and SA to teicoplanin and linezolid were less than 10.00%. Resistant rate of SA, Staphylococcus epidermidis and Enterococcus faecium to vancomycin was 0. Resistant rates of SA to quinupristin/dalfopristin, minocycline, fusidic acid, and compound sulfamethoxazole were low, respectively 0.82%, 9.35%, 2.21%, and 31.85%. Sensitive rates of SA to erythromycin, clindamycin, compound sulfamethoxazole, tetracycline, and minocycline showed an increasing trend year by year. Both infection rate and resistant rate of fungi were low. The resistant rates of CA to 5 kinds of antibiotics were less than 15.00%. The sensitive rate of CA to 5-flucytosine declined slightly, and those of CA to the other 4 antibiotics showed an increasing trend year by year. The three dominant pathogens that cause infection in burn patients hospitalized in Institute of Burn Research of Southwest Hospital in recent years are PA, SA, and AB in order. PA and AB are outstandingly multidrug-resistant among the isolated strains. AB might replace PA as the main pathogenic bacterium that cause the death of burn patients with infection.


Analysis of ganciclovir-resistant human herpesvirus 6B clinical isolates using quenching probe PCR methodology.
Quenching probe PCR (QP-PCR) analysis was used to determine the frequency of ganciclovir (GCV) resistance among clinical isolates of human herpesvirus 6B (HHV-6B) obtained from patients with primary viral infection and viral reactivation. Forty-two HHV-6B clinical isolates were repeatedly recovered from 15 hematopoietic stem cell transplant (HSCT) recipients, and 20 isolates were recovered from 20 exanthem subitum (ES) patients. Of the 15 HSCT recipients, 9 received GCV during the observation period; however, none of the ES patients were treated with GCV. Two established laboratory strains, Z29 and HST, were used as standards in this study. Regions 1 and 2 of the U69 gene of all of the clinical isolates demonstrated the same melting temperature as regions 1 and 2 of the Z29 strain. For region 3, the melting temperatures of all clinical isolates fell between the melting temperature of the plasmid containing the A462D single nucleotide polymorphism (SNP) and the melting temperature of the Z29 strain, and the melting temperatures profiles of all clinical isolates were similar to the melting temperature profile of the Japanese HST strain. As expected, none of the 20 clinical isolates recovered from the ES patients and the 14 isolates recovered from the HSCT recipients who did not receive GCV treatment carried the six known SNPs associated with GCV resistance. Interestingly, these six SNPs were not detected in the 28 clinical isolates recovered from the 9 HSCT recipients who received GCV. Additional sequence analysis of the U69 gene from the 15 representative isolates from the 15 HSCT recipients identified other SNPs. These SNPs were identical to those identified in the HST strain. Therefore, the rate of emergence of GCV-resistant HHV-6B strains appears to be relatively low, even in HSCT recipients treated with GCV.


The chicken or the egg: mitochondrial dysfunction as a cause or consequence of toxicity in Huntington's disease.
Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington's disease, Alzheimer's disease, and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell. The effects of these various parameters are difficult to quantify and not fully understood, but clearly have an impact on interpreting the bioenergetics of MT or their failure in disease states. A major goal of the review is to discuss issues and coalesce detailed information into a reference table to help in assessing mitochondrial dysfunction as a cause or consequence of Huntington's disease.


One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.
A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO3) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO3 was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO3 nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.


Working Pasteur's Quadrant: harnessing science and action for community change.
Community psychology in general and the field of prevention in particular has unquestioningly accepted the assumption that the research process should proceed in a linear fashion from a search for basic knowledge to application in the community context. This ignores the compelling insight offered by Stokes (1997) that the drive for new knowledge and the pursuit of application can be combined in a single effort. If research in community psychology pursues the drive for application without an equal commitment to the development of knowledge about underlying community processes of social cooperation and change, it will become a field less capable of innovative and enduring contributions to community well-being and effectiveness Opportunities abound in community psychology for the simultaneous pursuit of new knowledge and more effective practice. We offer the example of a community leadership development program to promote collective efficacy as a case in point.


Gradual PACS adoption.
For more than a decade, radiology professionals have hoped that picture archiving and communications systems (PACS) would improve efficiency and reduce costs. However, pioneer PACS systems were extremely expensive, and they didn't always meet their users' needs. Recent changes mean that PACS are more accessible. Advances in technology have resulted in decreased costs and increased computer power, and many radiologists recognize that they must consider new tools, such as teleradiology, to compete. There are roughly five classes of digital image systems used by radiologists: modality clusters, on-call review and teleradiology, remote primary diagnosis, mini-PACS and PACS. Even though hospitals seem to view PACS as inevitable, the challenge is to manage PACS implementation economically. One answer is to install PACS incrementally. Once teleradiology and mini-PACS are in place, they can be used as the building blocks of full-fledged PACS. Because PACS have a broad impact on healthcare facilities, careful planning is needed. Design your system to support future, as well as current, applications. Another important planning step is to set goals for improved efficiency and cost reduction.


Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.
Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.


[Facial aging. The evolution of the soft tissues].
Ageing of the face is one of the most apparent. Face varies in shape and aspect. The reasons of these modifications are various: skin ageing, lost of teeth, changes in facial skeleton and modifications of the whole facial soft tissues. Soft tissues evolution in mentalis and anterior nasal spin regions was studied on a 206, 21 to 101 years old subjects population. It was shown that in both men and women samples the soft tissues thickness increase in the mentalis region and decrease in that of anterior nasal spin.


Antidepressant use in pregnancy.
Depression during pregnancy can affect up to 20% of all women and may be treated effectively with antidepressants. Currently, information on > 20,000 women exposed to antidepressants with pregnancy outcomes is available in the literature. However, there is a continuing fear of physicians prescribing and women taking these drugs during pregnancy, probably due to many of the studies reporting conflicting outcomes and subsequently, the dissemination of these results. The authors searched the literature using Medline, Embase and Reprotox followed by a manual search of retrieved articles and reviews of the topic. The authors then selected key publications in this field which they considered relevant to the subsequent discussion of this topic. In this review, the authors evaluate the safety of different classes of antidepressants and find no convincing evidence of an increased risk for any adverse outcomes in an appreciable fashion. The authors note that even in studies documenting a potential for harm, the risk is marginal with rarely an odds ratio above 2. Therefore, it is important that each woman discusses the risks/benefits of treatment with her healthcare provider to allow an informed decision to be made based on scientific evidence.