Dimensions of Athletic Identity and their Associations with Drinking Behaviors among a National Sample of University Athletes in the United States.
Although prior studies have indicated athletic identity plays a role in alcohol use among college athletes, this research has largely drawn on a unidimensional conceptualization. Addressing this gap, the current study utilized a sample of 8,550 university athletes (Mage = 19.70 years, SD = 1.33, 50.8% men) from 203 U.S. post-secondary institutions to examine the associations between athletic identity dimensions (i.e., social identification, negative affectivity, and exclusivity) and alcohol use for athletes across gender, sport type, and division. The results indicated that negative affectivity and social identification were associated with higher levels of alcohol use, whereas exclusivity was associated with lower levels of alcohol use. Further, the association between dimensions of athletic identity and alcohol use varied across competitive level (i.e., Division I, II, and III). The findings implicate the need for (a) future research to approach athletic identity as a multidimensional concept when examining its association with alcohol use outcomes, and (b) post-secondary alcohol prevention professionals to integrate dimensions of athletic identity in alcohol prevention approaches.


Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis.
Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established. To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5). Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005). The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.


Comparison of Efficacy of Difluprednate 0.05% and Loteprednol Gel 0.5% After Cataract Surgery.
To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery. Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively. Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P>0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P<0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P>0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit. The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.


Consumption of sugars.
The mean percent of energy from total sugars minus lactose is 18% in the United States, according to data from the 1987-1988 US Department of Agriculture Nationwide Food Consumption Survey. When sugars intake is distributed among food pyramid groupings, the primary contributor is the "others" group (39%). The relationship between sugars intakes and micronutrients was age and sex dependent. Consumers of high amounts of sugars do not necessarily have poorer quality diets. In the European Union, the mean percent energy from all sugars is 15.2%. The top five sources of sugar contributed 68% of sugar intake but only 11% of fat intake (UK data). Although sugars intake varies among these major developed regions, the consistent inverse relation between fat and sugars intake and the scarcity of individuals achieving dietary guidelines raises serious questions regarding current dietary recommendations.


Protein-protein interactions in a crowded environment: an analysis via cross-docking simulations and evolutionary information.
Large-scale analyses of protein-protein interactions based on coarse-grain molecular docking simulations and binding site predictions resulting from evolutionary sequence analysis, are possible and realizable on hundreds of proteins with variate structures and interfaces. We demonstrated this on the 168 proteins of the Mintseris Benchmark 2.0. On the one hand, we evaluated the quality of the interaction signal and the contribution of docking information compared to evolutionary information showing that the combination of the two improves partner identification. On the other hand, since protein interactions usually occur in crowded environments with several competing partners, we realized a thorough analysis of the interactions of proteins with true partners but also with non-partners to evaluate whether proteins in the environment, competing with the true partner, affect its identification. We found three populations of proteins: strongly competing, never competing, and interacting with different levels of strength. Populations and levels of strength are numerically characterized and provide a signature for the behavior of a protein in the crowded environment. We showed that partner identification, to some extent, does not depend on the competing partners present in the environment, that certain biochemical classes of proteins are intrinsically easier to analyze than others, and that small proteins are not more promiscuous than large ones. Our approach brings to light that the knowledge of the binding site can be used to reduce the high computational cost of docking simulations with no consequence in the quality of the results, demonstrating the possibility to apply coarse-grain docking to datasets made of thousands of proteins. Comparison with all available large-scale analyses aimed to partner predictions is realized. We release the complete decoys set issued by coarse-grain docking simulations of both true and false interacting partners, and their evolutionary sequence analysis leading to binding site predictions. Download site: http://www.lgm.upmc.fr/CCDMintseris/


Physicochemical properties related to long-term phosphorus retention by drinking-water treatment residuals.
Drinking-water treatment residuals (WTRs) are nonhazardous materials that can be obtained free-of-charge from drinking-water treatment plants to reduce soluble phosphorus (P) concentrations in poorly P sorbing soils. Phosphorus sorption capacities of WTRs can vary 1-2 orders of magnitude, on the basis of short-term equilibration times (up to 7 d), but studies dealing with long-term (weeks to months) P retention by WTRs are lacking. Properties that most affect long-term P sorption capacities are pertinent to the efficacy of WTRs as amendments to stabilize P in soils. This research addressed the long-term (up to 80 d) P sorption/desorption characteristics and kinetics for seven WTRs, including the influence of specific surface area (SSA), porosity, and total C content on the overall magnitude of P sorption by seven WTRs. The data confirm a strong but variable affinity for P by WTRs. Aluminum-based WTRs tended to have higher P sorption capacity than Fe-based WTRs. Phosphorus sorption with time was biphasic in nature for most samples and best fit to a second-order rate model. The P sorption rate dependency was strongly correlated with a hysteretic P desorption, consistent with kinetic limitations on P desorption from micropores. Oxalate-extractable Al + Fe concentrations of the WTRs did not effectively explain long-term (80 d) P sorption capacities of the WTRs. Micropore (CO2-based) SSAs were greater than BET-N2 SSAs for most WTRs, except those with the lowest (<80 g kg(-1)) total C content. There was a significant negative linear correlation between the total C content and the CO2/N2 SSA ratio. The data suggest that C in WTRs increases microporosity, but reduces P sorption per unit pore volume or surface area. Hence, variability in C content confounds direct relations among SSA, porosity, and P sorption. Total C, N2-based SSA, and CO2-based SSAs explained 82% of the variability in the long-term P sorption capacities of the WTRs. Prediction of long-term P sorption capacities for different WTRs may be achieved by taking into account the three proposed variables.


[Emergency care and treatment costs of polytrauma patients].
Treatment costs of emergency therapy, surgery and intensive care were analysed in 20 randomly chosen, representative patients with severe multiple trauma (mean ISS 32 p). For an average stay of about 22.5 days on ICU, the total costs were DM 106924.36 (about 70,000 US $). DM 39,635.88 (= 37%) were the costs for physicians and nurses; DM 67,289.08 (= 63%) were needed for materials, X-rays, laboratory investigations, drugs and blood components. The whole treatment caused daily costs of DM 4752.22 or DM 3.30/min. The first emergency diagnostic procedures and emergency therapy take a mean time of 451.9 min from admission to the beginning of the ICU treatment and by itself already generates costs of about DM 12325.99. In Germany, a new way of compensation by a diagnosis-related group was introduced in 1996. These data suggest that treatment of severe multiple trauma is very expensive and trauma care could be economically harmful for smaller hospitals. We conclude that treatment of multiply injured patients (ISS > 16 p) should be compensated for by a special daily amount of about DM 5000 (about 3500 US $) for selected trauma centres.


The multifaceted nature of HIV latency.
Although antiretroviral therapies (ARTs) potently inhibit HIV replication, they do not eradicate the virus. HIV persists in cellular and anatomical reservoirs that show minimal decay during ART. A large number of studies conducted during the past 20 years have shown that HIV persists in a small pool of cells harboring integrated and replication-competent viral genomes. The majority of these cells do not produce viral particles and constitute what is referred to as the latent reservoir of HIV infection. Therefore, although HIV is not considered as a typical latent virus, it can establish a state of nonproductive infection under rare circumstances, particularly in memory CD4+ T cells, which represent the main barrier to HIV eradication. While it was originally thought that the pool of latently infected cells was largely composed of cells harboring transcriptionally silent genomes, recent evidence indicates that several blocks contribute to the nonproductive state of these cells. Here, we describe the virological and immunological factors that play a role in the establishment and persistence of the pool of latently infected cells and review the current approaches aimed at eliminating the latent HIV reservoir.


Prototype fabrication and preliminary in vitro testing of a shape memory endovascular thrombectomy device.
An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke-causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86 degrees C). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot-dissolving drugs.


Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients.
Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained >/=3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.


Simplifying complex PTSD: comment on Resick et al. (2012).
Although constructs related to complex posttraumatic stress disorder (CPTSD) have been discussed for many years, the field still lacks reliable and standardized definitions to guide research in this field. This comment responds to the article by Resick et al. (2012), who conclude that CPTSD lacks sufficient support to be recognized as a diagnosis. Even though there is no doubt that research is lacking, this comment argues that the key to progressing the field is introducing a standardized definition that will allow researchers to understand CPTSD in relation to other trauma-related disorders, identify key mechanisms driving the condition, and further treatment programs specifically for patients with CPTSD.


DESOXYCORTICOSTERONE ACETATE : THE POTENTIATION OF ITS ACTIVITY BY SODIUM CHLORIDE.
1. Desoxycorticosterone acetate (DCA) and NaCl, in the dosage employed in normal rats, caused renal and cardiac hypertrophy, characteristic changes in the renal tubular epithelium, atrophic changes in the subcapsular zone of the adrenal cortex, and serum electrolyte changes characterized by a rise in sodium and fall in potassium. 2. In rats rendered nephritic with a rabbit anti-rat-kidney serum, the same regimen caused similar changes. In addition, DCA given concurrently with NaCl greatly intensified the nephritic process and gave rise to striking arterial hypertension. 3. A diet, virtually sodium-free, administered to normal and nephritic rats receiving daily injections of DCA abolished or reduced to a minimum the effects of this steroid; i.e., a liberal ingestion of NaCl was essential for the potentiation of the action of DCA. 4. The addition of KCl to the drinking water of rats receiving DCA and NaCl tended to correct the depression of the level of potassium in the serum, but had no effect upon the hypertension in nephritic animals nor upon the anatomical lesions. 5. The mechanism by which the sodium ion potentiates the activity of DCA has not been established.


Excess cost of care associated with sepsis in cancer patients: Results from a population-based case-control matched cohort.
Cancer patients are at significant risk of developing sepsis due to underlying malignancy and necessary treatments. Little is known about the economic burden of sepsis in this high-risk population. We estimate the short- and long-term healthcare costs of care of cancer patients with and without sepsis using individual-level linked-administrative data. We conducted a population-based matched cohort study of cancer patients aged ≥18, diagnosed between 2010 and 2017. Cases were identified if diagnosed with sepsis during the study period, and were matched 1:1 by age, sex, cancer type and other variables to controls without sepsis. Mean costs (2018 Canadian dollars) for patients with and without sepsis up to 5 years were estimated adjusted using survival probabilities at partitioned intervals. We estimated excess cost associated with sepsis presented as a cost difference between the two cohorts. Haematological and solid cancers were analysed separately. 77,483 cancer patients with sepsis were identified and matched. 64.3% of the cohort were aged ≥65, 46.3% female and 17.8% with haematological malignancies. Among solid tumour patients, the excess cost of care among patients who developed sepsis was $29,081 (95%CI, $28,404-$29,757) in the first year, rising to $60,714 (95%CI, $59,729-$61,698) over 5 years. This was higher for haematology patients; $46,154 (95%CI, $45,505-$46,804) in year 1, increasing to $75,931 (95%CI, $74,895-$76,968). Sepsis imposes substantial economic burden and can result in a doubling of cancer care costs, particularly during the first year of cancer diagnosis. These estimates are helpful in improving our understanding of burden of sepsis along the cancer pathway and to deploy targeted strategies to alleviate this burden.


Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers.
To examine the role of heritable factors in insulin-dependent diabetes mellitus (IDDM), we studied the incidence of IDDM in the offspring of patients with the disease who were identified by the medical records of the Joslin Diabetes Center from 1928 to 1939. We found 187 survivors who, after the diagnosis of IDDM, had produced 419 offspring for whom information about diabetes status was available. By the age of 20, 6.1 per cent of the offspring of the 88 men had diabetes; in contrast, only 1.3 per cent of the offspring of the 99 women had the disease by the age of 20 (P less than 0.05). Daughters and sons of the men with IDDM were affected equally (there were insufficient numbers of affected offspring of diabetic women to permit determination of whether the sexes were equally affected). We conclude that IDDM is transmitted less frequently to the offspring of diabetic women than to those of diabetic men. More study is required to determine whether this difference reflects a genetic mechanism or, instead, selective perinatal loss of the affected offspring of diabetic mothers.


Plasma and urinary luteinizing hormone levels in the diagnosis of endocrine disease.
The diagnostic value of measurements of plasma and urinary luteinizing hormone (LH) has been studied in 209 patients with endocrine disease. In 44 patients puberty was either delayed or had failed to occur. In those with chromosomal abnormalities the LH levels were often within the normal range, whereas those with a pituitary cause usually had low levels. In boys with delayed puberty plasma LH levels rose before physical changes occurred and had prognostic value. In patients with later gonadal failure, men with impotence or infertility, and women with secondary amenorrhoea LH assays proved of little value, although in one case a premature menopause was suspected and six patients with anorexia nervosa had low LH levels.Sixty patients with disorders of the hypothalamicpituitary area were studied. Levels of LH were measured and considered in relation to the other anterior pituitary hormones. Impairment of LH secretion was one of the first effects on hormone production of disease affecting this area, and this was, of course, most readily detected in postmenopausal women.The normal ranges of both plasma and urine LH are wide and there seems to be considerable day-to-day variation, especially of urinary output. Several samples should, therefore, be measured if therapeutic decisions are involved.


A principled approach to deriving approximate conditional sampling distributions in population genetics models with recombination.
The multilocus conditional sampling distribution (CSD) describes the probability that an additionally sampled DNA sequence is of a certain type, given that a collection of sequences has already been observed. The CSD has a wide range of applications in both computational biology and population genomics analysis, including phasing genotype data into haplotype data, imputing missing data, estimating recombination rates, inferring local ancestry in admixed populations, and importance sampling of coalescent genealogies. Unfortunately, the true CSD under the coalescent with recombination is not known, so approximations, formulated as hidden Markov models, have been proposed in the past. These approximations have led to a number of useful statistical tools, but it is important to recognize that they were not derived from, though were certainly motivated by, principles underlying the coalescent process. The goal of this article is to develop a principled approach to derive improved CSDs directly from the underlying population genetics model. Our approach is based on the diffusion process approximation and the resulting mathematical expressions admit intuitive genealogical interpretations, which we utilize to introduce further approximations and make our method scalable in the number of loci. The general algorithm presented here applies to an arbitrary number of loci and an arbitrary finite-alleles recurrent mutation model. Empirical results are provided to demonstrate that our new CSDs are in general substantially more accurate than previously proposed approximations.


The importance of Arabidopsis seed mutants in the elucidation of the molecular basis of Endosperm Balance Number in tuber-bearing Solanum species.
The Endosperm Balance Number (EBN) is an important concept for potato breeding and has evolutionary importance in tuber-bearing Solanum species. The EBN is part of the post-zygotic hybridization barriers in the group and represents a reproductive isolating mechanism. Few genes have been proposed to be involved in its genetic control; until now, however, neither specific genes nor its molecular basis have been well established. Histological observations of embryo and endosperm development in inter-EBN crosses in tuber-bearing Solanum revealed phenotypes similar to those recently described in Arabidopsis seed mutants. The common feature between them is that the endosperm nuclei become greatly enlarged and that embryos are arrested at the globular stage. The proteins encoded by the Arabidopsis TITAN genes are related to chromosome dynamics and cell division. Based on the sequence of titan mutants, genes in potato species related to cell cycle and microtubule assembly were isolated. In this article a perspective model is proposed to explore the utility of Arabidopsis mutants associated with cell cycle control as a tool to elucidate the molecular basis of EBN in potato. Further research focused on the expression pattern of these genes in intra- and inter-EBN crosses in potato species will be performed.


De-identifying an EHR database - anonymity, correctness and readability of the medical record.
Electronic health records (EHR) contain a large amount of structured data and free text. Exploring and sharing clinical data can improve healthcare and facilitate the development of medical software. However, revealing confidential information is against ethical principles and laws. We de-identified a Danish EHR database with 437,164 patients. The goal was to generate a version with real medical records, but related to artificial persons. We developed a de-identification algorithm that uses lists of named entities, simple language analysis, and special rules. Our algorithm consists of 3 steps: collect lists of identifiers from the database and external resources, define a replacement for each identifier, and replace identifiers in structured data and free text. Some patient records could not be safely de-identified, so the de-identified database has 323,122 patient records with an acceptable degree of anonymity, readability and correctness (F-measure of 95%). The algorithm has to be adjusted for each culture, language and database.


Women's experience of midwife-led counselling and its influence on childbirth fear: A qualitative study.
Women with childbirth fear have been offered counseling by experienced midwives in Sweden for decades without evidence for its effectiveness, in terms of decrease in childbirth fear. Women are usually satisfied with the counselling. However, there is a lack of qualitative data regarding women's views about counselling for childbirth fear. To explore women's experiences of midwife-led counselling for childbirth fear. A qualitative interview study using thematic analysis. Twenty-seven women assessed for childbirth fear who had received counselling during pregnancy at three different hospitals in Sweden were interviewed by telephone one to two years after birth. The overarching theme 'Midwife-led counselling brought positive feelings and improved confidence in birth' was identified. This consisted of four themes describing 'the importance of the midwife' and 'a mutual and strengthening dialogue' during pregnancy. 'Coping strategies and support enabled a positive birth' represent women's experiences during birth and 'being prepared for a future birth' were the women's thoughts of a future birth. In this qualitative study, women reported that midwife-led counselling improved their confidence for birth through information and knowledge. The women experienced a greater sense of calm and preparedness, which increased the tolerance for the uncertainty related to the birthing process. This, in turn, positively affected the birth experience. Combined with a feeling of safety, which was linked to the professional support during birth, the women felt empowered. The positive birth experience strengthened the self-confidence for a future birth and the childbirth fear was described as reduced or manageable.


A Contemporary Evaluation of Peyronie's Disease During Penile Prosthesis Placement: MOST, MUST, and More.
The use of penile implant for the treatment of both erectile dysfunction and Peyronie's disease has changed little in the last 40 years, primarily limited to modeling and plaque incision. In the current review, I explore the history of Peyronie's treatment at the time of penile prosthesis placement and explore new surgical options that help resolve several of the issues that were not treated with the traditional approaches. Advancements have been made in the area of graft material, lengthening procedures, and transcorporal techniques. The goal of these operations is not only to correct curvature, but also to restore length. Not surprisingly, the more complex and aggressive the attempt to correct the curvature, the more complications are possible. While modeling has a low rate of urethral injury, complex lengthening procedure with neurovascular bundle and urethral mobilization may lead to the dreaded complication of glans necrosis. Meanwhile, transcorporal techniques seem to offer a more modest improvement for length and curvature restoration with fewer risks than those seen in more aggressive lengthening procedures. The main limitation to the historical treatment of Peyronie's disease during penile prosthesis, modeling, and plaque incision is there is often no resolution to the penile length-as the maneuvers are made after the implant is already in place. Newer lengthening procedures are promising, however carry increased risks and complexity.


Inward versus reward: white matter pathways in extraversion.
The trait of extraversion is one of the longest-standing domains that captures the social dimension of personality and can potentially explain the covariation of a wide variety of behaviors. To date, there is a growing recognition that human behavior should be specified not only through the psychological mechanisms underlying each trait but also through their underlying neurobehavioral systems. While imaging studies have revealed important initial insights into the structural and functional neural correlates of extraversion, current knowledge about the relationships between extraversion and brain structures is still rather limited, especially with regard to the relationship between extraversion and white matter (WM). In this study, we aimed to investigate WM microstructure in extraversion in greater depth. Thirty-five healthy volunteers (21 women; mean age 35) underwent magnetic resonance imaging, as a part of a larger project aimed at investigating the longitudinal effect of motor training. WM integrity was assessed using the diffusion tensor imaging technique combining multiple diffusion tensor measures. Extraversion was assessed by the Eysenck Personality Questionnaire-Revised. Voxelwise correlation analyses between fractional anisotropy, axial diffusivities, and radial diffusivities maps and extraversion score showed decreased connectivity in the right inferior fronto-occipital fasciculus and forceps major among individuals who had high extraversion ratings. In conclusion, individual differences in extraversion may reflect differential organization of the WM tracts connecting frontal cortex, temporal, and occipital areas, which are related to socioemotional and control functions.


Acute compartment syndrome of the foot in a soccer player: a case report.
To present the diagnostic and clinical features including management of acute compartment syndrome (ACS) of the foot and to create a sense of emergency amongst clinicians of this rare and dangerous condition. A 28-year old male soccer player on acetylsalicylic acid (ASA) and verapamil presented with severe swelling, paresthesia, and pain in the left ankle after an acute grade three-inversion ankle sprain. A diagnosis of foot compartment syndrome was made. A fasciotomy was not performed and subsequent neurological sequelae occurred. We hypothesize that the edema caused by the ankle sprain was excessive due to the use of ASA and verapamil, resulting in increased compartmental pressure and neurological signs in the foot. Although rare, it is extremely important to be aware of the clinical features of ACS of the foot to obtain an appropriate diagnosis and manage this medical emergency promptly.


Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats.
Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb suspension. We have previously shown that protein synthesis is elevated in response to RE, but the effect on protein degradation, cell proliferation, or apoptosis was not investigated. We hypothesized that, in addition to affecting protein synthesis, RE inhibits processes that actively contribute to muscle atrophy during hindlimb suspension. Male rats were housed in regular cages (control), tail suspended for 2 wk (HS), or HS with RE every other day for 2 wk (HSRE). Although RE attenuated soleus muscle atrophy during HS, the observed fivefold elevation in apoptosis and the 53% decrease in cell proliferation observed with HS were unaffected by RE. Expression of genes encoding components of the ubiquitin-proteasome pathway of protein degradation were elevated with HS, including ubiquitin, MAFbx, Murf-1, Nedd4, and XIAP, and proteasome subunits C2 and C9. Total ubiquitinated protein was increased with HS, but proteasome activity was not different from control. RE selectively altered the expression of different components of this pathway: MAFbx, Murf-1, and ubiquitin mRNA abundance were downregulated, whereas C2 and C9 subunits remained elevated. Similarly, Nedd4 and XIAP continued to be upregulated, potentially accounting for the observed augmentation in total ubiquitinated protein with RE. Thus a different constellation of proteins is likely ubiquitinated with RE due to altered ubiquitin ligase composition. In summary, the flywheel-based resistance exercise paradigm used in this study is associated with the inhibition of some mechanisms associated with muscle atrophy, such as the increase in MAFbx and Murf-1, but not with others, such as proteasome subunit remodeling, apoptosis, and decreased proliferation, potentially accounting for the inability to completely restore muscle mass. Identifying specific exercise parameters that affect these latter processes may be useful in designing effective exercise strategies in the elderly or during spaceflight.


Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).
GOALS/OBJECTIVES: To review the scientific evidence on symptoms and specific complications that are associated with lung cancer, and the methods available to palliate those symptoms and complications. MEDLINE literature review (through March 2006) for all studies published in the English language, including case series and case reports, since 1966 using the following medical subject heading terms: bone metastases; brain metastases; cough; dyspnea; electrocautery; hemoptysis; interventional bronchoscopy; laser; pain management; pleural effusions; spinal cord metastases; superior vena cava syndrome; and tracheoesophageal fistula. Pulmonary symptoms that may require palliation in patients who have lung cancer include those caused by the primary cancer itself (dyspnea, wheezing, cough, hemoptysis, chest pain), or locoregional metastases within the thorax (superior vena cava syndrome, tracheoesophageal fistula, pleural effusions, ribs, and pleura). Respiratory symptoms can also result from complications of lung cancer treatment or from comorbid conditions. Constitutional symptoms are common and require attention and care. Symptoms referable to distant extrathoracic metastases to bone, brain, spinal cord, and liver pose additional problems that require a specific response for optimal symptom control. There are excellent scientific data regarding the management of many of these issues, with lesser evidence from case series or expert opinion on other aspects of providing palliative care for lung cancer patients. Palliation of symptoms and complications in lung cancer patients is possible, and physicians who provide such care must be knowledgeable about these issues.


Pathology of toxic death in mice following intravenous injection of Rickettsia tsutsugamushi strain gilliam: examination by light and scanning electron microscopy.
The pathologic manifestations of the toxic death elicited by the iv injection of mice with Rickettsia tsutsugamushi strain Gilliam were examined by light and scanning electron microscopic techniques to ascertain the cause of death. Light microscopic examinations of hematoxylin and eosin-stained sections of organs suggested the presence of fluid in the lungs; this was confirmed by an increase in the weight of the lungs of moribund mice. Scanning electron microscopy of blood cells demonstrated a marked crenation of erythrocytes from these mice. Death appears to be the result of shock brought on by vascular collapse secondary to plasma leakage.


Association between serum 25-hydroxyvitamin D concentration and severity of first-diagnosed bullous pemphigoid in older adults.
Higher vitamin D status has been associated with symptom improvement and decreased risk of various autoimmune disorders. Our objective was to determine whether higher serum 25-hydroxyvitamin D (25OHD) concentration correlated with less severe first-diagnosed bullous pemphigoid (BP) in older inpatients. This cross-sectional study was performed from November 2012 to February 2014 among 30 consecutive older inpatients (21 women; mean ± SD, 83 ± 7 years; all Caucasian) with a de novo diagnosis of active BP recruited in the Department of Dermatology of Angers University Hospital, France. The severity of BP was graded clinically on the basis of i) the number of bullae during the first three days of hospitalization (grade 0-4, worse), and ii) the extent of the lesions (grade 0-5, worse). Sixteen participants had ≤ 5 bullae at the time of diagnosis, 8 had 6-20 bullae, 3 had 20-50 bullae, and 3 had >50 bullae. The lesions were spread over 5 cutaneous areas in 5 participants (17%). The median 25OHD concentration was 23 [IQR, 16-42] nmol/L. Serum 25OHD concentration was inversely correlated with the bullae grade (ρ = - 0.38, p = 0.04) and the lesion extension grade (ρ = - 0.50, p = 0.005). Higher serum 25OHD concentration correlated with less severe BP prior to initiation of treatment among our sample of older inpatients. This result suggests that vitamin D may be involved in the pathophysiology of BP and could serve as prognostic biomarker of BP.


Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter.
Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3 beta-(4'-methylphenyl)- and 3 beta-(4'-chlorophenyl)tropane-2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3 beta-(4'-chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N- pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3 beta-(4'-iodophenyl)-tropane-2 beta-carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist.


A new series of aryl sulfamate derivatives: Design, synthesis, and biological evaluation.
Steroid sulfatase (STS) has recently emerged as a drug target for management of hormone-dependent malignancies. In the present study, a new series of twenty-one aryl amido-linked sulfamate derivatives 1a-u was designed and synthesized, based upon a cyclohexyl lead compound. All members were evaluated as STS inhibitors in a cell-free assay. Adamantyl derivatives 1h and 1p-r were the most active with more than 90% inhibition at 10 µM concentration and, for those with the greatest inhibitory activity, IC50 values were determined. These compounds exhibited STS inhibition within the range of ca 25-110 nM. Amongst them, compound 1q possessing a o-chlorobenzene sulfamate moiety exhibited the most potent STS inhibitory activity with an IC50 of 26 nM. Furthermore, to assure capability to pass through the cell lipid bilayer, compounds with low IC50 values were tested against STS activity in JEG-3 whole-cell assays. Consequently, 1h and 1q demonstrated IC50 values of ca 14 and 150 nM, respectively. Thus, compound 1h is 31 times more potent than the corresponding cyclohexyl lead (IC50 value = 421 nM in a JEG-3 whole-cell assay). Furthermore, the most potent STS inhibitors (1h and 1p-r) were evaluated for their antiproliferative activity against the estrogen-dependent breast cancer cell line T-47D. They showed promising activity with single digit micromolar IC50 values (ca 1-6 µM) and their potency against T-47D cells was comparable to that against STS enzyme. In conclusion, this new class of adamantyl-containing aryl sulfamate inhibitor has potential for further development against hormone-dependent tumours.


Number of conspecifics and reproduction in the invasive plant Eschscholzia californica (Papaveraceae): is there a pollinator-mediated Allee effect?
The component Allee effect has been defined as 'a positive relationship between any measure of individual fitness and the number or density of conspecifics'. Larger plant populations or large patches have shown a higher pollinator visitation rate, which may give rise to an Allee effect in reproduction of the plants. We experimentally tested the effect of number of conspecifics on reproduction and pollinator visitation in Eschscholzia californica Cham., an invasive plant in Chile. We then built patches with two, eight and 16 flowering individuals of E. californica (11 replicates per treatment) in an area characterised by dominance of the study species. We found that E. californica exhibits a component Allee effect, as the number of individuals of this species has a positive effect on individual seed set. However, individual fruit production was not affected by the number of plants examined. Pollinator visitation rate was also independent of the number of plants, so this factor would not explain the Allee effect. This rate was positively correlated with the total number of flowers in the patches. We also found that the number of plants did not affect the seed mass or proportion of germinated seeds in the patches. Higher pollen availability in patches with 16 plants and pollination by wind could explain the Allee effect. The component Allee effect identified could lead to a weak demographic Allee effect that might reduce the rate of spread of E. californica. Knowledge of this would be useful for management of this invasive plant in Chile.


Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.
Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).


Early precut is as efficient as pancreatic stent in preventing post-ERCP pancreatitis in high-risk subjects - A randomized study.
The most common adverse event of endoscopic retrograde cholangiopancreatography is pancreatitis. Precut sphincterotomy has been regarded as a risk factor. Some authors have stated that early precut may actually reduce post-ERCP pancreatitis risk. However, early precut as a preventive measure has not been compared to other preventive measures, such as pancreatic duct stent placement. To compare the efficacy of early precut sphincterotomy versus pancreatic duct stent placement in high-risk subjects undergoing endoscopic retrograde cholangiopancreatography for the prevention of post-endoscopic cholangiopancreatography. This was a single-blinded, randomized trial that took place in two tertiary referral centers in Buenos Aires, from November 2011 to December 2013. ERCP subjects presented at least one of the following risk factors: female sex, age less than 40 years, clinical suspicion of sphincter of Oddi dysfunction, previous pancreatitis, and/or common bile duct diameter of less than 8 mm. Only those who presented a difficult biliary cannulation were randomized into two groups: those who received early precut sphincterotomy and those in whom persistency of biliary cannulation was intended, with subsequent pancreatic duct stent placement after cholangiography was achieved. The incidence of post-ERCP pancreatitis, as well as other adverse events incidence, was compared. Overall, 101 patients were enrolled, 51 in the pancreatic duct stent group and 50 in the early precut group. Pancreatitis rate was similar in both groups (3.92% vs 4%, p NS). In all cases, pancreatitis was classified as mild. There were no deaths registered. Early precut was associated with an incidence of adverse events similar to pancreatic duct stent placement.


Identification of dematiaceous fungi and their role in human disease.
Phaeohyphomycosis is the disease caused by the dematiaceous hyphomycetes or those fungi that are darkly pigmented because of the presence of melanin in their cell wall. Infections with these fungi may remain localized at the site of traumatic inoculation or within the sinuses or may become disseminated. As these fungi pose a significant problem to both the clinician who must treat the patient and the laboratorian faced with identification of the organism, a selection of representative organisms was presented at the meeting entitled "Focus on Fungus Infections." These fungi often infect patients who are not overtly immunocompromised and therefore may be encountered in a wide variety of cases.


[TISSUE-ENGINEERED SUBSTITUTION URETHROPLASTY BASED ON DECELLULARIZED VASCULAR MATRIX AND AUTOLOGOUS CELLS OF THE BUCCAL MUCOSA: THE FIRST EXPERIENCE].
Urethral strictures and anomalies remain a challenging urological problem. Reconstructive plastic surgery has been shown to be the most effective way to treat them. There are two main types of urethroplasty: anastomosis (anastomotic urethroplasty) and expansion of the urethral lumen using of flaps and grafts (substitution urethroplasty). Currently the ideal material for substitution urethroplasty does not exist. Tissue engineering of the urethra seems to be one of the most promising approaches to address this problem. Various tissues-engineering techniques were proposed for substitution urethroplasty. In this study, tissue-engineering design was based on the decellularized cadaveric arterial wall. The study results demonstrated the feasibility of creating stable tissue-engineered structures with autologous cultured epithelial cells of the buccal mucosa and decellularized matrix from human cadaveric arterial wall (DMCAW). There was a complete engraftment of tissue-engineering design based on DMCAW and buccal mucosa cells, used for substitution urethroplasty in a patient with the bulbar urethral stricture. Postoperatively (within 4 months after surgery) no complications and/or adverse events were observed. However, in the late postoperative period (12 months) there was recurrence of urethral stricture in the middle of the tissue-engineering design and the native urethra that warranted another surgery. Tissue-engineering design based on DMCAW and autologous buccal mucosa is safe as a material for substitution urethroplasty. Further research is required to ascertain the effectiveness of the method.


Assembly of the otoconia complex to the macular sensory epithelium of the vestibule.
In the inner ear, specificity of stimulus perception is achieved by associating the sensory epithelia of the three mechanoreceptor organs, the utricle/saccule, cristae, and cochlea, with distinct types of acellular matrices. Only the utricle and saccule have an extremely dense matrix, the otoconial complex, which overlies the sensory epithelium (macula) and provides inertial mass to generate shearing forces essential for the mechanoreceptors to sense gravity and linear acceleration. Such sensation is necessary for spatial orientation and balance. The importance of otoconia is clearly demonstrated by the impact of balance disorders upon the elderly population that involve otoconia degeneration, as well as by canalithiasis and cupulolithiasis, in which otoconia are dislocated. This underscores the need to understand how otoconia are formed and maintained and how to prevent their degeneration. To date, a number of otoconia-related proteins have been identified mostly in mice and bony fish. Although most of these proteins are also present in other structures of the inner ear, a distinct collection of proteins in the macula plus the unique ionic microenvironment of the endolymph near its epithelium likely contribute to the site-specific calcification of otoconia. Based on the current literature and ongoing research, this mini-review postulates a working model of how the otoconia complex is assembled specifically above the macular sensory epithelium of the vestibule. The central hypothesis of this model is that proteins are critical in sequestering calcium for crystallization in the calcium-poor endolymph. The review also sets forth some issues that need to be resolved in the future.


[Nutrition and health--toxic substances in food].
With respect to food, the most important factors causing adverse health effects are: an unbalanced diet, resulting in obesity or vitamin deficiencies, overconsumption of alcohol or fat, the presence of microbial contamination and the presence of natural toxins. Two additional factors, the presence of environmental contaminants and products formed on heating food, may also be of importance. It is generally assumed that, when combined, food-related factors contribute to around 35% of overall cancer incidence. The most important groups of health-threatening compounds to be found in the food chain include natural toxins, such as those produced by plants (phytotoxins), fungi (mycotoxins), marine algae (phycotoxins) and by bacteria, and toxins present in animals for human consumption, especially fish. A second important group of toxic compounds in food consists of environmental contaminants, including heavy metals and persistent organic pollutants, such as dioxins and polychlorinated biphenyls, all of which may unintentionally end up in the food chain. A third group of toxins present in food are those substances produced when food is heated, and include polycyclic aromatic hydrocarbons, heterocyclic amines and acrylamide.


[Urogenital and anal papillomavirus infections].
Recently virologists and clinicians have focused attention on infections with human papillomaviruses (HPV). This is due to the ubiquity, the increasing frequency and the possible association of these viruses with the development of squamous cell carcinomas of the skin and of the mucous membranes of the respiratory, gastrointestinal, genitourinary and anorectal tracts. HPV represent a very heterogeneous group of DNA tumor viruses. By means of molecular-biological techniques, more than 40 HPV types have been recognized. In the urogenital and anal tract, papillomaviruses have been associated with venereal warts (condylomata acuminata), which have been known and recognized as a sexually transmitted disease since the Romans. Furthermore, an association has been made recently between HPV and nonpapillomatous, sometimes macular lesions: flat condylomata of the uterine cervix and of the vagina, flat condylomatous lesions and pigmented papules. The latter are localized at the mucocutaneous borders and at the skin of the lower genital tract and of the perianal and crural region. Like epidermodysplasia verruciformis, only some virus types (HPV 16, HPV 18) are regularly found in malignant, invasive squamous cell carcinomas of the genital tract, whereas others (HPV 6, HPV 11, HPV 2, HPV 10, HPV 31) are associated preferentially with benign papillomas and dysplasias. In view of the different possible oncogenic potential of the individual genotypes, early determination of the virus type probably has not only diagnostic but also prognostic value. As HPV 16 DNA is regularly present in bowenoid papulosis (flat condylomatous lesions and pigmented papules of the male genital tract), a natural reservoir has been found from which these viruses could be transmitted to the sexual partner. Knowledge of the HPV-associated clinical pictures is therefore the prerequisite for diagnosis and treatment of both the patient and his sexual partner. Clinical observation, cytology and virus typing from genital smears of both partners represent preventive methods that may contribute to the early detection of genital cancer.


Molecular Pathology of Skin Melanoma: Epidemiology, Differential Diagnostics, Prognosis and Therapy Prediction.
Similar to other malignancies, TCGA network efforts identified the detailed genomic picture of skin melanoma, laying down the basis of molecular classification. On the other hand, genome-wide association studies discovered the genetic background of the hereditary melanomas and the susceptibility genes. These genetic studies helped to fine-tune the differential diagnostics of malignant melanocytic lesions, using either FISH tests or the myPath gene expression signature. Although the original genomic studies on skin melanoma were mostly based on primary tumors, data started to accumulate on the genetic diversity of the progressing disease. The prognostication of skin melanoma is still based on staging but can be completed with gene expression analysis (DecisionDx). Meanwhile, this genetic knowledge base of skin melanoma did not turn to the expected wide array of target therapies, except the BRAF inhibitors. The major breakthrough of melanoma therapy was the introduction of immune checkpoint inhibitors, which showed outstanding efficacy in skin melanoma, probably due to their high immunogenicity. Unfortunately, beyond BRAF, KIT mutations and tumor mutation burden, no clinically validated predictive markers exist in melanoma, although several promising biomarkers have been described, such as the expression of immune-related genes or mutations in the IFN-signaling pathway. After the initial success of either target or immunotherapies, sooner or later, relapses occur in the majority of patients, due to various induced genetic alterations, the diagnosis of which could be developed to novel predictive genetic markers.


Cerebellar damage diminishes long-latency responses to multijoint perturbations.
Damage to the cerebellum can cause significant problems in the coordination of voluntary arm movements. One prominent idea is that incoordination stems from an inability to predictively account for the complex mechanical interactions between the arm's several joints. Motivated by growing evidence that corrective feedback control shares important capabilities and neural substrates with feedforward control, we asked whether cerebellar damage impacts feedback stabilization of the multijoint arm appropriate for the arm's intersegmental dynamics. Specifically, we tested whether cerebellar dysfunction impacts the ability of posterior deltoid to incorporate elbow motion in its long-latency response (R2 = 45-75 ms and R3 = 75-100 ms after perturbation) to an unexpected torque perturbation. Healthy and cerebellar-damaged subjects were exposed to a selected pattern of shoulder-elbow displacements to probe the response pattern from this shoulder extensor muscle. The healthy elderly subjects expressed a long-latency response linked to both shoulder and elbow motion, including an increase/decrease in shoulder extensor activity with elbow flexion/extension. Critically, cerebellar-damaged subjects displayed the normal pattern of activity in the R3 period indicating an intact ability to rapidly integrate multijoint motion appropriate to the arm's intersegmental dynamics. However, cerebellar-damaged subjects had a lower magnitude of activity that was specific to the long-latency period (both R2 and R3) and a slightly delayed onset of multijoint sensitivity. Taken together, our results suggest that the basic motor pattern of the long-latency response is housed outside the cerebellum and is scaled by processes within the cerebellum.


Label-Free Time-Gated Luminescent Detection Method for the Nucleotides with Varying Phosphate Content.
A new label-free molecular probe for luminescent nucleotide detection in neutral aqueous solution is presented. Phosphate-containing molecules, such as nucleotides possess vital role in cell metabolism, energy economy, and various signaling processes. Thus, the monitoring of nucleotide concentration and nucleotide related enzymatic reactions is of high importance. Two component lanthanide complex formed from Tb(III) ion carrier and light harvesting antenna, readily distinguishes nucleotides containing different number of phosphates and enable direct detection of enzymatic reactions converting nucleotide triphosphate (NTP) to nucleotide di/monophosphate or the opposite. Developed sensor enables the detection of enzymatic activity with a low nanomolar sensitivity, as highlighted with K-Ras and apyrase enzymes in their hydrolysis assays performed in a high throughput screening compatible 384-well plate format.


Regional reduction in intestinal neuroendocrine cell populations in enterocolitis complicating Hirschsprung's disease.
Enterocolitis (EC) remains the most serious complication of Hirschsprung's disease (HD). The aetiology of EC is uncertain. Ischemic and bacterial causes, and recently rotavirus infection, have been suggested to explain the occurrence of EC. The gut has an abundance of neuroendocrine (NE) cells which modulate gut function by endocrine, paracrine, or neurocrine routes. We studied NE cell populations in the bowel from 16 patients with HD (six of whom had clinical evidence of EC) and rectal tissue from 6 controls. Immunohistochemical studies were carried out using monoclonal and polyclonal antibodies against chromogranin A, synaptophysin (general markers of NE cells), 5-Hydroxytryptamine (5-HT), somatostatin, peptide YY (PYY), and glucagon/glicentin (neuropeptides). The six patients who had clinical evidence of EC prior to defunctioning colostomy showed histological evidence of EC in the defunctioned bowel. Using immunocytochemistry and serial tissue sectioning it was found that the number of NE cells in the aganglionic segment of colon in patients with HD was significantly (P < .05) increased compared with the numbers in the ganglionic segment. However, in the ganglionic colon, there was a significant (P < .05) reduction in NE cells in EC patients compared with non-EC patients. These results were seen both with the generic endocrine cell marker chromogranin A, which stains virtually all endocrine cells, and with specific markers for 5-HT, PYY, and glucagon/glicentin, which identify distinct subpopulations of endocrine cells. These differences may be partially responsible for previous conflicting reports of NE cell distribution in HD.(ABSTRACT TRUNCATED AT 250 WORDS)


Smoking and peripheral vascular disease. Epidemiology and podiatric perspective.
Virtually no attention has been given in public education efforts to the potentially devastating effects of smoking on the lower extremities. An analysis of the epidemiologic studies that have been done by the Office of the Surgeon General and other clinical investigators has been presented, leading to the conclusion that cigarette smoking is the single most powerful risk factor for peripheral vascular disease. In the care of patients with peripheral vascular disease, the podiatric physician has an opportunity to be a participant in efforts to solve one of the nation's major public health problems.


An evaluation of fruit and vegetable consumption and cigarette smoking among youth.
Research across the past 4 decades has supported a cross-sectional association between adult cigarette smoking and lower fruit and vegetable consumption (FVC), and emerging research suggests higher FVC may predict cessation. Among youth, findings are limited to a few cross-sectional studies with somewhat mixed results. Here we evaluated the FVC-smoking association among youth both cross-sectionally and longitudinally. We analyzed data from a subsample of the National Longitudinal Survey of Youth 1979: Child and Young Adult. The subsample included adolescents aged 14-18 years at baseline in the year 2004. Multivariable cross-sectional analyses assessed whether baseline FVC was associated with smoking frequency among ever-smokers (n = 578). Longitudinally, the study assessed whether baseline FVC predicted smoking progression among baseline never-smokers who tried a cigarette by 4-year follow-up (n = 388). Multivariable regression models adjusted for age, gender, race/ethnicity, parental education, and health behavior orientation. Cross-sectionally, youth who consumed fruit ≥2 times per day were 53% less likely (RR = 0.47; p < .05) than those who typically did not consume fruit to be in a higher smoking frequency category. Longitudinally, the fruit consumption and smoking association was not significant (RR = 0.61; p = .282). There were no significant associations observed between vegetable consumption and smoking. Fruit consumption, but not vegetable consumption, was inversely associated with smoking frequency cross-sectionally but not longitudinally. Further research is needed to provide information on the consistency of the FVC-smoking relationship among youth and may help to elucidate possible explanatory mechanisms.


Robot-assisted partial nephrectomy: evolution and recent advances.
Robot-assisted partial nephrectomy (RAPN) is emerging as a viable complement to traditional laparoscopic and open partial nephrectomy. As a relatively new technique, the techniques and technologies employed during RAPN continue to evolve. In the present article, we provide an overview of the evolution of robot-assisted renal surgery, and highlight the recent advances that have helped to bring RAPN to the fore. The learning curve for RAPN appears to be slight, and technical proficiency may be quickly achieved, even for those with limited laparoscopic experience. Recent advances include improvements in ergonomics of the robotic system itself, as well as the introduction of sliding-clip renorrhaphy, early unclamping techniques, and off-clamp techniques. Early-to-intermediate outcomes are very promising, demonstrating short warm ischemic times, and a low rate of complication and recurrence. Disadvantages to the approach include substantial cost, as well as increased reliance upon the assistant to perform critical maneuvers. Robot-assisted partial nephrectomy appears to be a safe and efficacious technique for the surgical management of localized renal malignancy. Recent developments have focused upon reducing ischemic insult, as well as decreasing reliance upon the assistant.


Reaction mechanism of the Me3AuPMe3-H2 plasma-enhanced ALD process.
The reaction mechanism of the recently reported Me3AuPMe3-H2 plasma gold ALD process was investigated using in situ characterization techniques in a pump-type ALD system. In situ RAIRS and in vacuo XPS measurements confirm that the CH3 and PMe3 ligands remain on the gold surface after chemisorption of the precursor, causing self-limiting adsorption. Remaining surface groups are removed by the H2 plasma in the form of CH4 and likely as PHxMey groups, allowing chemisorption of new precursor molecules during the next exposure. The decomposition behaviour of the Me3AuPMe3 precursor on a Au surface is also presented and linked to the stability of the precursor ligands that govern the self-limiting growth during ALD. Desorption of the CH3 ligands occurs at all substrate temperatures during evacuation to high vacuum, occurring faster at higher temperatures. The PMe3 ligand is found to be less stable on a gold surface at higher substrate temperatures and is accompanied by an increase in precusor decomposition on a gold surface, indicating that the temperature dependent stability of the precursor ligands is an important factor to ensure self-limiting precursor adsorption during ALD. Remarkably, precursor decomposition does not occur on a SiO2 surface, in situ transmission absorption infrared experiments indicate that nucleation on a SiO2 surface occurs on Si-OH groups. Finally, we comment on the use of different co-reactants during PE-ALD of Au and we report on different PE-ALD growth with the reported O2 plasma and H2O process in pump-type versus flow-type ALD systems.


[Hypertension consensus in The Netherlands].
It is known that mild hypertension is a common disorder and there is increasing evidence that it is possible to decrease the incidence of cardiovascular damage by antihypertensive treatment. Stimulated by the controversy on the identification and treatment of patients with mild hypertension, a Dutch hypertension consensus meeting was held on March 16th 1990. Consensus was reached that the decision to treat should be taken on the basis of both the blood pressure level and the individual risk profile, including hypercholesterolaemia, history of smoking, diabetes, or a family history of cardiovascular disease. Subjects at risk should be identified by selective case finding (persons with known additional risk factors) and screening restricted to men aged 55 to 65 years. All patients should be started on non-pharmacological treatment by decreasing sodium intake, and where necessary reducing body weight and alcohol consumption, and stopping smoking. If antihypertensive drugs are to be given, diuretics, beta-blockers, ACE-inhibitors, and (or) calcium antagonists are the drugs of choice.


Extreme mortality in nineteenth-century Africa: the case of Liberian immigrants.
Several studies have examined the mortality of immigrants from Europe to Africa in the nineteenth century. This paper examines the level of mortality in Liberia of Africans who emigrated there from the United States. A life table is estimated from data collected by the American Colonization Society from 1820 to 1843. The analysis reflects the mortality experience of a population that is transplanted from one disease environment to another, more exacting, disease environment. The results of this analysis show that these Liberian immigrants experienced the highest mortality rates in accurately recorded human history.


Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.
Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state-of-the-art High-resolution CT (HRCT). Brain death was caused by surgical decapitation. To maintain mean aortic pressure > 60 mmHg, pigs were treated with forced electrolyte solution infusion (GI; n = 6) or the pharmacological therapy (GII; n = 11). GIII (n = 11) were non-decapitated controls. Lung function was investigated with blood gases and lung morphology with HRCT. GI pigs became circulatory instable 4-6 h after brain death in spite of forced fluid infusion, five pigs showed moderate to severe pulmonary edema on HRCT and median final PaO2 /FiO2 was 29 kPa (Q1; Q3; range 26; 40; 17-76). GII and GIII were circulatory stable (mean aortic pressure > 80 mmHg) and median final PaO2 /FiO2 after 24 h was 72 kPa (Q1; Q3; range 64; 76; 53-91) (GII) and 66 kPa (55; 78; 43-90) (GIII). On HRCT, only two pigs in GII had mild pulmonary edema and none in GIII. More than 50% of HRCT exams revealed unexpected lung disease even in spite of PaO2 /FiO2 > 40 kPa. Pharmacological therapy but not forced fluid infusion prevented circulatory collapse and extensive HRCT verified pulmonary edema after acute brain death. HRCT was useful to evaluate lung morphology and revealed substantial occult parenchymal changes justifying efforts toward a more intense use of HRCT in the pre-transplant evaluation.


The new ABCs of AV block. A revised classification to remove the mental block from recognizing AV block.
This revised classification system is designed to etch the indicators of a block into your memory. You only have to remember that the degree is the number of atrial beats getting through to the ventricles (all, some or none) and the type is where the block occurs (AV node or septum). Once you learn this system, simply practice interpreting block rhythms (see "AV Block Case Studies," p. 33). This revised block classification brings bundle branch blocks into the fold, so to speak, allowing you to focus on the block's anatomical location (see Figure 14, left). It also reinforces the fact that whenever we use the word block, we're talking about AV block. So how do you put it all together to use this new classification system? Use your usual rhythm strip analysis of rate, rhythm, P, PR, QRS, ST, T, U and summary to do the following: 1. Note any PR or QRS abnormalities. 2. Count the number of atrial and ventricular beats in a six-second ECG strip. If the ratio is 1-to-1 and the PR and QRS are normal, then there's no block present. If the ratio is 1-to-1, the PR is prolonged and the QRS is narrow, it's a first-degree, type 1 block. If the ratio is 1-to-1, the PR is normal and the QRS is wide, it's a first-degree, type 2 block. If the ratio is greater than 1-to-1 (such as 2-to-1, 3-to-1, etc.), but some of the beats are conducted, it's a some (second-degree) block. If the PR prolongs and the QRS is narrow on the conducted beats, it's considered a second-degree, type 1 block (Mobitz 1 or Wenckebach). If the PR is normal and the QRS is wide on the conducted beats, it's a second-degree, type 2 block (Mobitz 2). If none of the beats appear conducted (the PR interval is completely variable), it's a none (third-degree) block. If the QRS complex is at a normal width, then it's probably a third-degree, type 1 block. And if the QRS complex is wide, it's a third-degree, type 2 block. As with anything in medicine, no system is perfect. However, through using this revised classification of AV block--based on the heart's anatomy--you can permanently retain the features of the various AV blocks in your memory. Now that you're feeling more comfortable with block rhythms, examine Figure 15. This is a patient in sinus tachycardia who has received adenosine. Notice how the patient goes from sinus tachycardia to first-degree, type 1 to second-degree, type 1 to second-degree, type 2 and back again. It's a very rare strip that you can use to test your ability--and the ability of your crews--to interpret block rhythms.


Search for global-minimum geometries of medium-sized germanium clusters. II. Motif-based low-lying clusters Ge21-Ge29.
We performed a constrained search for the geometries of low-lying neutral germanium clusters Ge(N) in the size range of 21 < or = N < or = 29. The basin-hopping global optimization method is employed for the search. The potential-energy surface is computed based on the plane-wave pseudopotential density functional theory. A new series of low-lying clusters is found on the basis of several generic structural motifs identified previously for silicon clusters [S. Yoo and X. C. Zeng, J. Chem. Phys. 124, 054304 (2006)] as well as for smaller-sized germanium clusters [S. Bulusu et al., J. Chem. Phys. 122, 164305 (2005)]. Among the generic motifs examined, we found that two motifs stand out in producing most low-lying clusters, namely, the six/nine motif, a puckered-hexagonal-ring Ge6 unit attached to a tricapped trigonal prism Ge9, and the six/ten motif, a puckered-hexagonal-ring Ge6 unit attached to a bicapped antiprism Ge10. The low-lying clusters obtained are all prolate in shape and their energies are appreciably lower than the near-spherical low-energy clusters. This result is consistent with the ion-mobility measurement in that medium-sized germanium clusters detected are all prolate in shape until the size N approximately 65.


Strategies for development of Dengue virus inhibitors.
Antiviral drug discovery is becoming increasingly important due to the global threat of viral disease pandemics. Many members of the genus Flavivirus are significant human pathogens, among which dengue virus (DENV) alone poses a public health threat to 2.5 billion worldwide, leading to 50-100 million human infections each year. Neither vaccine nor effective therapeutics is currently available for DENV. Development of a DENV vaccine has been challenging, because of the need to simultaneously immunize and induce a long-lasting protection against all four serotypes of DENV; an incompletely immunized individual may be sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The challenges associated with vaccine development have underscored the importance of development of antiviral therapies for DENV and other flaviviruses. Here we review the strategies to identify inhibitors for DENV therapy. Both viral and host proteins essential for viral replication cycle are potential targets for antiviral development. Inhibitors could be identified by multiple approaches, including enzyme-based screening, viral replication-based screening, structure-based rational design, virtual screening, and fragment-based screening. The strategies discussed in this report should be applicable to antiviral development of other viruses.


Candida Empyema Thoracis at Two Academic Medical Centers: New Insights Into Treatment and Outcomes.
Candida empyema thoracis (pleural empyema) is an uncommon manifestation of invasive candidiasis, for which optimal treatment is unknown. This is a retrospective study of patients with Candida empyema at 2 academic medical centers from September 2006 through December 2015. We identified 81 patients with Candida empyema (median age, 62 years; 68% men). Sixty-five percent of patients underwent surgery or an invasive intervention of the thorax or abdomen within the preceding 90 days. Candida empyema originated from intrathoracic (51%) or intra-abdominal sources (20%), spontaneous esophageal rupture (12%), pleural space manipulation (9%), and pneumonia (6%). Eighty-four percent and 41% of patients were intensive care unit residents and in septic shock, respectively, within 3 days of diagnosis. Causative species were Candida albicans (65%), Candida glabrata (26%), Candida parapsilosis (11%), Candida tropicalis (4%), Candida krusei (2%), and Candida dubliniensis (1%). Bacteria were recovered from empyemas in 51% of patients. Concurrent candidemia was diagnosed in only 2% of patients. Management included pleural drainage and antifungal treatment in 98% and 85% of patients, respectively. Mortality at 100 days was 27%, and it was highest for cases stemming from esophageal rupture (67%). Spontaneous esophageal rupture and echinocandin rather than fluconazole treatment were independent risk factors for death at 100 days (P = .003 and .04, respectively); receipt of antifungal therapy was an independent predictor of survival (P = .046). Candida empyema mortality rates were lower than reported previously. Optimal management included pleural drainage and fluconazole treatment. Superiority of fluconazole over echinocandins against Candida empyema needs to be confirmed in future studies.


[24-hour ECG monitoring in young patients with ischemic heart disease].
The paper presents the results of the study into the diagnostic potentialities of 24-hour ECG monitoring in young patients. The monitoring is a sensitive and informative technique for the diagnosis of coronary heart disease in young patients, allowing the signs of coronary insufficiency to be revealed in 91.4% of the patients with verified coronary heart disease. The young patients were demonstrated to have ischemia accompanied by ST-segment elevation, presumably of vasospastic genesis.


Posttraumatic stress disorder among earthquake survivors of the Wenchuan area (Sichuan, China).
On May 12, 2008, an earthquake with a power of 8.0 M on the Richter scale occurred in the Wenchuan County of Sichuan Province in southwest China, which was unprecedented in magnitude and aftermath. Approximately 70,000 people were killed and nearly 20,000 went missing. The earthquake caused a wide number of mental and physical health outcomes among survivors, and posttraumatic stress disorder (PTSD) was one of the most commonly studied. We conducted a systematic overview to assess research achievements about PTSD in the past 6 years after the Wenchuan earthquake, including symptoms and risk factors about PTSD among Wenchuan earthquake survivors, as well as research developments in genetics, molecular biology, and treatment of PTSD. The large body of research conducted after the Wenchuan earthquake suggests that the burden of PTSD among persons with high exposure was substantial. Adolescents and adults were among the most studied populations with high prevalence rates. Phytotherapy with Chinese herbs as well as acupuncture were rarely studied as of yet, although published data indicated promising therapy effects. Genome-wide microarray technologies are widely used in experimental mice and rat models to study PTSD mechanisms as well as in patients suffering from PTSD and other psychosomatic disorders to search for novel biomarkers and to monitor the effectiveness of treatment interventions. Using genomic and transcriptomic technologies, our future research will focus on the efficacy and safety of Chinese medicine to find potential interventions and effective treatments of PTSD.


Higher-order sequences of vocal mimicry performed by male Albert's lyrebirds are socially transmitted and enhance acoustic contrast.
Most studies of acoustic communication focus on short units of vocalization such as songs, yet these units are often hierarchically organized into higher-order sequences and, outside human language, little is known about the drivers of sequence structure. Here, we investigate the organization, transmission and function of vocal sequences sung by male Albert's lyrebirds (Menura alberti), a species renowned for vocal imitations of other species. We quantified the organization of mimetic units into sequences, and examined the extent to which these sequences are repeated within and between individuals and shared among populations. We found that individual males organized their mimetic units into stereotyped sequences. Sequence structures were shared within and to a lesser extent among populations, implying that sequences were socially transmitted. Across the entire species range, mimetic units were sung with immediate variety and a high acoustic contrast between consecutive units, suggesting that sequence structure is a means to enhance receiver perceptions of repertoire complexity. Our results provide evidence that higher-order sequences of vocalizations can be socially transmitted, and that the order of vocal units can be functionally significant. We conclude that, to fully understand vocal behaviours, we must study both the individual vocal units and their higher-order temporal organization.


Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway.
In this investigation, a potentially novel signaling pathway in gentamicin-induced acute kidney injury-worsened by overexpression of proximal tubular enzyme, myo-inositol oxygenase (MIOX)-was elucidated. WT, MIOX-transgenic (MIOX-Tg), and MIOX-KO mice were used. Gentamicin was administered to induce tubular injury. MIOX-Tg mice had severe tubular lesions associated with increased serum creatinine and proteinuria. Lesions were relatively mild, with no rise in serum creatinine and no albuminuria in MIOX-KO mice. Transfection of HK-2 cells with MIOX-pcDNA led to increased gentamicin-induced reactive oxygen species (ROS). Marked increase of ROS-mediated lipid hydroperoxidation was noted in MIOX-Tg mice, as assessed by 4-HNE staining. This was associated with increased expression of arachidonate 12-lipoxygenase (ALOX-12) and generation of 12-hydroxyeicosatetraenoic acid (12-HETE). In addition, notable monocyte/macrophage influx, upregulation of NF-κB and inflammatory cytokines, and apoptosis was observed in MIOX-Tg mice. Treatment of cells with ALOX-12 siRNA abolished gentamicin-mediated induction of cytokines and 12-HETE generation. HETE-12 treatment promoted this effect, along with upregulation of various signaling kinases and activation of GPCR31. Similarly, treatment of cells or mice with the ALOX-12 inhibitor ML355 attenuated inflammatory response, kinase signaling cascade, and albuminuria. Collectively, these studies highlight a potentially novel mechanism (i.e., the ROS/ALOX-12/12-HETE/GPR31 signaling axis) relevant to gentamicin-induced nephrotoxicity modulated by MIOX.


The intergenic region of the maize defensin-like protein genes Def1 and Def2 functions as an embryo-specific asymmetric bidirectional promoter.
Bidirectional promoters are identified in diverse organisms with widely varied genome sizes, including bacteria, yeast, mammals, and plants. However, little research has been done on any individual endogenous bidirectional promoter from plants. Here, we describe a promoter positioned in the intergenic region of two defensin-like protein genes, Def1 and Def2 in maize (Zea mays). We examined the expression profiles of Def1 and Def2 in 14 maize tissues by qRT-PCR, and the results showed that this gene pair was expressed abundantly and specifically in seeds. When fused to either green fluorescent protein (GFP) or β-glucuronidase (GUS) reporter genes, P ZmBD1 , P ZmDef1 , and P ZmDef2 were active and reproduced the expression patterns of both Def1 and Def2 genes in transformed immature maize embryos, as well as in developing seeds of transgenic maize. Comparative analysis revealed that PZmBD1 shared most of the expression characteristics of the two polar promoters, but displayed more stringent embryo specificity, delayed expression initiation, and asymmetric promoter activity. Moreover, a truncated promoter study revealed that the core promoters only exhibit basic bidirectional activity, while interacting with necessary cis-elements, which leads to polarity and different strengths. The sophisticated interaction or counteraction between the core promoter and cis-elements may potentially regulate bidirectional promoters.


Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence "transmission blocking" assay.
Current anti-malarial drugs have been selected on the basis of their activity against the symptom-causing asexual blood stage of the parasite. Which of these drugs also target gametocytes, in the sexual stage responsible for disease transmission, remains unknown. Blocking transmission is one of the main strategies in the eradication agenda and requires the identification of new molecules that are active against gametocytes. However, to date, the main limitation for measuring the effect of molecules against mature gametocytes on a large scale is the lack of a standardized and reliable method. Here we provide an efficient method to produce and purify mature gametocytes in vitro. Based on this new procedure, we developed a robust, affordable, and sensitive ATP bioluminescence-based assay. We then assessed the activity of 17 gold-standard anti-malarial drugs on Plasmodium late stage gametocytes. Difficulties in producing large amounts of gametocytes have limited progress in the development of malaria transmission blocking assays. We improved the method established by Ifediba and Vanderberg to obtain viable, mature gametocytes en masse, whatever the strain used. We designed an assay to determine the activity of antimalarial drugs based on the intracellular ATP content of purified stage IV-V gametocytes after 48 h of drug exposure in 96/384-well microplates. Measurements of drug activity on asexual stages and cytotoxicity on HepG2 cells were also obtained to estimate the specificity of the active drugs. The work described here represents another significant step towards determination of the activity of new molecules on mature gametocytes of any strain with an automated assay suitable for medium/high-throughput screening. Considering that the biology of the forms involved in the sexual and asexual stages is very different, a screen of our 2 million-compound library may allow us to discover novel anti-malarial drugs to target gametocyte-specific metabolic pathways.


Functional insights from the structure of the multifunctional C345C domain of C5 of complement.
The complement protein C5 initiates assembly of the membrane attack complex. This remarkable process results in lysis of target cells and is fundamental to mammalian defense against infection. The 150-amino acid residue domain at the C terminus of C5 (C5-C345C) is pivotal to C5 function. It interacts with enzymes that convert C5 to C5b, the first step in the assembly of the membrane attack complex; it also binds to the membrane attack complex components C6 and C7 with high affinity. Here a recombinant version of this C5-C345C domain is shown to adopt the oligosaccharide/oligonucleotide binding fold, with two helices packed against a five-stranded beta-barrel. The structure is compared with those from the netrin-like module family that have a similar fold. Residues critical to the interaction with C5-convertase cluster on a mobile, hydrophobic inter-strand loop that protrudes from the open face of the beta-barrel. The opposite, helix-dominated face of C5-C345C carries a pair of exposed hydrophobic side chains adjacent to a striking negatively charged patch, consistent with affinity for positively charged factor I modules in C6 and C7. Modeling of homologous domains from complement proteins C3 and C4, which do not participate in membrane attack complex assembly, suggests that this provisionally identified C6/C7-interacting face is indeed specific to C5.


The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification.
Human UDP-glucuronosyltransferase (UGT) exists as a superfamily of 22 proteins, which are divided into 5 families and 6 subfamilies on the basis of sequence identity. Members of the UGT1A and 2B subfamilies play a key role in terminating the biological actions and enhancing the renal elimination of non-polar (lipophilic) drugs from all therapeutic classes. These enzymes primarily catalyse the covalent linkage of glucuronic acid, derived from the cofactor UDP-glucuronic acid, to a substrate with a suitable acceptor functional group. This process is referred to as glucuronidation. While the liver is the major detoxification organ, and as such contains the greatest abundance and diversity of UGTs, these enzymes also exhibit significant, but variable extra-hepatic expression. This review discusses recent advances in the understanding of the functional roles of UGT, their regulation and tissue expression, and clinical significant factors (ontogeny, interactions and polymorphisms) that affect glucuronidation activity in humans.


Associations between traumatic events and suicidal behavior in South Africa.
Research conducted predominantly in the developed world suggests that there is an association between trauma exposure and suicidal behavior. However, there are limited data available investigating whether specific traumas are uniquely predictive of suicidal behavior or the extent to which traumatic events predict the progression from suicide ideation to plans and attempts. A national survey was conducted with 4351 adult South Africans between 2002 and 2004 as part of the World Health Organization World Mental Health Surveys. Data on trauma exposure and subsequent suicidal behavior were collected. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and lifetime suicidal behavior. A range of traumatic events are associated with lifetime suicide ideation and attempt; however, after controlling for all traumatic events in a multivariate model, only sexual violence (odds ratio = 4.7; confidence interval, 2.3 to 9.4) and having witnessed violence (odds ratio = 1.8; confidence interval, 1.1 to 2.9) remained significant predictors of lifetime suicide attempts. The disaggregation of the associations between traumatic events and suicide attempts indicates that they are largely caused by traumatic events predicting suicide ideation rather than by the progression from suicide ideation to attempt. This article highlights the importance of traumatic life events in the occurrence of suicidal thoughts and behaviors and provides important information about the nature of this association. Future research is needed to better understand how and why such experiences increase the risk of suicidal outcomes.


Preliminary study on mouse interleukin-21 application in tumor gene therapy.
Interleukin-21 (IL-21) is a recently characterized T cell-derived cytokine with a significant homology to IL-2, IL-4 and IL-15. To determine whether IL-21 has broad immunoregulatory activity and can stimulate durable antitumour responses, we constructed mouse IL-21 (mIL-21) recombinant plasmid and evaluated its antitumor efficacy. Mouse IL-21 cDNA was amplified from Con A-activated mouse T cells by RT-PCR. Recombinant pcDNA3.1/mIL-21 was constructed and transfected into Sp2/0 cells. Mouse IL-21 expression was analyzed by Western blotting and its activities were detected by 3H-TdR incorporation and MTT assay. The recombinant pcDNA3.1/mIL-21 was injected s.c. into tumor lump. Tumor size, weight, the activities of CTLs, NK cells and LAK cells and serum IFN-gamma level were measured for evaluating mIL-21 mediated antitumor responses. The results indicated that mIL-21 was correctly expressed in Sp2/0 cells and it can improve the proliferation of T cells and B cells, and enhance NK cytotoxic activity in vitro. The activities of CTL and NK cells, and serum IFN-gamma level were significantly improved, furthermore the tumor growth was obviously suppressed in pcDNA3.1/mIL-21 treated mice. However, the LAK activity did not alter significantly. Taken together, this study suggests that the injection with recombinant plasmid containing mIL-21 is a potential approach for tumor gene therapy.


Stimulation of electro-oxidation catalysis by bulk-structural transformation in intermetallic ZrPt₃ nanoparticles.
Although compositional tuning of metal nanoparticles (NPs) has been extensively investigated, possible control of the catalytic performance through bulk-structure tuning is surprisingly overlooked. Here we report that the bulk structure of intermetallic ZrPt3 NPs can be engineered by controlled annealing and their catalytic performance is significantly enhanced as the result of bulk-structural transformation. Chemical reduction of organometallic precursors yielded the desired ZrPt3 NPs with a cubic FCC-type structure (c-ZrPt3 NPs). The c-ZrPt3 NPs were then transformed to a different phase of ZrPt3 with a hexagonal structure (h-ZrPt3 NPs) by annealing at temperatures between 900 and 1000 °C. The h-ZrPt3 NPs exhibited higher catalytic activity and long-term stability than either the c-ZrPt3 NPs or commercial Pt/C NPs toward the electro-oxidation of ethanol. Theoretical calculations have elucidated that the enhanced activity of the h-ZrPt3 NPs is attributed to the increased surface energy, whereas the stability of the catalyst is retained by the lowered bulk-free-energy.


Chocolate equals stop. Chocolate-specific inhibition training reduces chocolate intake and go associations with chocolate.
Earlier research has demonstrated that food-specific inhibition training wherein food cues are repeatedly and consistently mapped onto stop signals decreases food intake and bodyweight. The mechanisms underlying these training effects, however, remain unclear. It has been suggested that consistently pairing stimuli with stop signals induces automatic stop associations with those stimuli, thereby facilitating automatic, bottom-up inhibition. This study examined this hypothesis with respect to food-inhibition training. Participants performed a training that consistently paired chocolate with no go cues (chocolate/no-go) or with go cues (chocolate/go). Following training, we measured automatic associations between chocolate and stop versus go, as well as food intake and desire to eat. As expected, food that was consistently mapped onto stopping was indeed more associated with stopping versus going afterwards. In replication of previous results, participants in the no-go condition also showed less desire to eat and reduced food intake relative to the go condition. Together these findings support the idea that food-specific inhibition training prompts the development of automatic inhibition associations, which subsequently facilitate inhibitory control over unwanted food-related urges.


An approach to the patient with skin disease.
We practise an integrated approach to the management of skin diseases, leprosy and sexually transmitted diseases because the latter diseases are still stigmatized and patients are unwilling to attend clinics so labelled. When approached by a patient with skin disease it is advisable to see the patient promptly, because any further delay encourages the use of assorted remedies which may lead to undesirable complications, physically, emotionally and financially. Since there is no health insurance scheme, it is also prudent to manage the patient as much as possible without admission to hospital and with minimal laboratory investigations, to save cost, so that the patient still has sufficient money to buy the required drugs. Family health workers treat patients at the primary health care (PHC) level. At this level, patients are managed by the use of specially prepared standing orders (SO), where checklists and flow charts are grouped by problems or complaints, to facilitate usage by an individual with minimal training in morphology. The SO presents, so far as is possible, the best treatment available for each condition, but which cannot be misused by the primary health care personnel. Before discussing the management of individual diseases, it is important for the reader to appreciate the milieu in which we practise which determines our approach to the patient with skin disease. Some of its features will be highlighted before the management of individual disorders is discussed.