An event-related potential study of response inhibition in ADHD with and without prenatal alcohol exposure.
The attention and cognitive problems seen in individuals with a history of prenatal alcohol exposure often resemble those associated with attention deficit hyperactivity disorder (ADHD), but few studies have directly assessed the unique influence of each on neurobehavioral outcomes. We recorded event-related potentials (ERPs) during a Go/No-go response inhibition task in young adults with prospectively obtained histories of prenatal alcohol exposure and childhood ADHD. Regardless of prenatal alcohol exposure, participants with childhood ADHD were less accurate at inhibiting responses. However, only the ADHD group without prenatal alcohol exposure showed a markedly diminished P3 difference between No-go and Go, which may reflect a more effortful strategy related to inhibitory control at the neural processing level. This finding supports a growing body of evidence suggesting that the manifestation of idiopathic ADHD symptoms may stem from a neurophysiologic process that is different from the ADHD symptomatology associated with prenatal alcohol exposure. Individuals who have been prenatally exposed to alcohol and present with ADHD symptomatology may represent a unique endophenotype of the disorder, which may require different treatment approaches from those found to be effective with idiopathic ADHD.


Adverse effects of psychosocial work factors on blood pressure: systematic review of studies on demand-control-support and effort-reward imbalance models.
A growing body of research has investigated the adverse effects of psychosocial work factors on blood pressure (BP) elevation. There is now a clear need for an up-to-date, critical synthesis of reliable findings on this topic. This systematic review aimed to evaluate the adverse effects of psychosocial work factors of both the demand-control-support (DCS) and effort-reward imbalance (ERI) models on BP among men and women, according to the methodological quality of the studies. To be eligible, studies had to: (i) evaluate at least one psychosocial work factor, (ii) evaluate BP or hypertension, (iii) comprise ≥100 workers, (iv) be written in English or French, and (v) be published in a peer-reviewed journal. A total of 74 studies were included. Of these, 64 examined the DCS model, and 12 looked at the ERI model, with 2 studies considering both models. Approximately half the studies observed a significant adverse effect of psychosocial work factors on BP. A more consistent effect was observed, however, among men than women. For job strain, a more consistent effect was also observed in studies of higher methodological quality, ie, studies using a prospective design and ambulatory BP measures. A more consistent adverse effect of psychosocial work factors was observed among men than women and in studies of higher methodological quality. These findings contribute to the current effort of primary prevention of cardiovascular disease by documenting the psychosocial etiology of elevated BP, a major cardiovascular risk factor.


Do minimum wage laws affect those who are not covered? Evidence from agricultural and non-agricultural workers.
Some employers are not obligated to pay at least minimum wages to all employees. U.S. farm employers comprise one of these groups. Employees of large farms and H-2A workers (lawfully admitted, nonimmigrant workers performing temporary or seasonal agricultural work) are protected by minimum wage legislation, while some migrant workers (often those paid piece rates) are exempt. U.S. agriculture also is characterized by a large percentage of unauthorized workers who may or may not earn above minimum wage. Following insights from dual labor market theory and from theories of the signaling capacity of the minimum wage, we compare labor market outcomes in the agricultural sector (where minimum wage coverage is limited) to low wage/skill non-agricultural sectors (where minimum wage coverage is more complete) nationally using data from the Current Population Survey. We then extend our analysis to a detailed state-level case study of agricultural workers in California using a representative survey of employed farm workers. Results suggest wage increases for covered workers that exceed those for uncovered workers, but insignificant differences in hours worked. This is the first study to our knowledge to examine the impacts of minimum wage coverage on agricultural workers relative to other workers for the U.S.


The future in craniofacial surgery: computer-assisted planning.
Advancements in computers, prototyping, and imaging, especially over the last 10 years, have permitted the adoption of three-dimensional imaging protocols in the health care field. In this article, the authors present an integrated simulation system for craniofacial surgical planning and treatment. Image fusion technology, which involves combining different imaging modalities, was utilized to create a realistic prototype and virtual image that can be manipulated in real time. The resultant data can then be shared over the Internet with distantly located practitioners.


Unraveling 14-3-3 proteins in C4 panicoids with emphasis on model plant Setaria italica reveals phosphorylation-dependent subcellular localization of RS splicing factor.
14-3-3 proteins are a large multigenic family of regulatory proteins ubiquitously found in eukaryotes. In plants, 14-3-3 proteins are reported to play significant role in both development and response to stress stimuli. Therefore, considering their importance, genome-wide analyses have been performed in many plants including Arabidopsis, rice and soybean. But, till date, no comprehensive investigation has been conducted in any C4 panicoid crops. In view of this, the present study was performed to identify 8, 5 and 26 potential 14-3-3 gene family members in foxtail millet (Si14-3-3), sorghum (Sb14-3-3) and maize (Zm14-3-3), respectively. In silico characterization revealed large variations in their gene structures; segmental and tandem duplications have played a major role in expansion of these genes in foxtail millet and maize. Gene ontology annotation showed the participation of 14-3-3 proteins in diverse biological processes and molecular functions, and in silico expression profiling indicated their higher expression in all the investigated tissues. Comparative mapping was performed to derive the orthologous relationships between 14-3-3 genes of foxtail millet and other Poaceae members, which showed a higher, as well as similar percentage of orthology among these crops. Expression profiling of Si14-3-3 genes during different time-points of abiotic stress and hormonal treatments showed a differential expression pattern of these genes, and sub-cellular localization studies revealed the site of action of Si14-3-3 proteins within the cells. Further downstream characterization indicated the interaction of Si14-3-3 with a nucleocytoplasmic shuttling phosphoprotein (SiRSZ21A) in a phosphorylation-dependent manner, and this demonstrates that Si14-3-3 might regulate the splicing events by binding with phosphorylated SiRSZ21A. Taken together, the present study is a comprehensive analysis of 14-3-3 gene family members in foxtail millet, sorghum and maize, which provides interesting information on their gene structure, protein domains, phylogenetic and evolutionary relationships, and expression patterns during abiotic stresses and hormonal treatments, which could be useful in choosing candidate members for further functional characterization. In addition, demonstration of interaction between Si14-3-3 and SiRSZ21A provides novel clues on the involvement of 14-3-3 proteins in the splicing events.


Gastrointestinal stromal tumors: A multicenter study of 1160 Turkish cases.
The aim of this multicenter study was to determine the histopathological features and immunohistochemical profiles of gastrointestinal stromal tumors diagnosed in Turkish patients. Twenty-eight participating centers registered their gastrointestinal stromal tumor cases on a nationwide database. The diagnosis of gastrointestinal stromal tumor relied upon hematoxylin & eosin features and the results of antibody panel including CD117, CD34, desmin, smooth muscle actin, S-100 protein, and Ki67. The database consisted of parameters including age, gender, location, and all other histopathological and immunohistochemical findings. Statistical analysis was performed using Pearson, Kruskal-Wallis, Mann-Whitney U, and Spearman tests. From all of the gastrointestinal stromal tumors in the database, 1160 cases with a male to female ratio of 1.22 and a mean age of 56.75 years were included in the study. The most common location was the stomach (45.0%), followed by the small intestine, omentum-peritoneum, large intestine, and esophagus (32.0%, 12.6%, 9.3%, 1.1%, respectively). The risk groups were distributed as: 6.1% very low, 21.7% low, 19.3% intermediate, and 53% high-risk cases. Many histopathologic findings were correlated with risk groups. CD117 was positive in 95.3% of gastrointestinal stromal tumors, whereas CD34 was positive in 74.9%, smooth muscle actin in 45.9%, desmin in 9.2%, and S-100 in 19.1.%. Though no significant relation was found between CD117 expression and tumor location, CD34, smooth muscle actin and Ki67 expressions significantly varied in different locations (p=0.001) and risk groups. The results of this multicenter study demonstrated that features other than tumor size and mitosis and immune markers other than CD117 and Ki67 included in the antibody panel seem to be useful as predictive risk factors.


Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease.
Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria.


Poverty: the double burden of malnutrition in mothers and the intergenerational impact.
Women are doubly vulnerable to malnutrition, because of their high nutritional requirements for pregnancy and lactation and also because of gender inequalities in poverty. Undernutrition and overnutrition coexist in developing countries undergoing rapid nutrition transition, and women are susceptible to this double burden of "dysnutrition," often cumulating stunting or micronutrient malnutrition with obesity or other nutrition-related chronic diseases. The purpose of the present paper is to describe the adverse impact of income and gender inequities on women's nutritional health, and the dramatic consequences, not only for women themselves, but for children, families, and societies. Improving women's resources, including health, nutrition, education, and decisional power, is critical for equity and for the health of children and adults of future generations, since poor fetal and infancy nutrition is another risk factor for chronic diseases, in particular abdominal obesity, type 2 diabetes, hypertension, and cardiovascular disease. Addressing malnutrition and nutrition-related chronic diseases simultaneously is a challenge facing developing countries, and examples of promising initiatives are provided. Focusing on women along the lifecycle, according to the continuum of care approach, is essential to achieving the Millennium Development Goals and to breaking the intergenerational cycle of poverty, malnutrition, and ill-health.


Leadership and innovation in nursing seen through a historical lens.
To explore nurses' archived accounts of Matron Muriel Powell's management and leadership style and the impact of this on the implementation and sustainability of innovation in the workplace. In popular discourse, the matron has become an emblem of leadership. Although the title disappeared in the UK in the late 1960s as part of the re-organization recommended by the Salmon Report, it re-appeared in 2002 in an attempt to improve care standards by reasserting a strong nursing presence and clinical leadership role. Secondary data analysis using qualitative thematic analysis. This paper draws on interview data held in the 'Nurses Voices' archive. The interview transcripts of 132 nurses who trained or worked at St George's hospital in 1920-1980 were analysed in depth between March 2011-January 2012 and themes were generated inductively by grouping together emergent codes in the data with similar meaning. Looking back, the nurses recalled strong memories of the leadership of Matron Powell. Her presence emerged as a significant influence throughout the interviews. Two resonant themes were identified: innovation and open communication. Through her visibility and direct access with patients and staff, Dame Muriel Powell showed what we would now call transformative leadership qualities. Her leadership created a culture of open communication and innovation that initiated change in the organization and the nursing workforce. Looking back and learning from historical figures can deepen understanding and provide pointers for the nurse leaders of today.


Two-photon and two-photon-assisted slow light.
We show that light pulses propagating in two-photon absorbing systems may present time delays like slow light produced via coherent population oscillations in one-photon interactions. Two regimes are numerically studied for a simplified two-level system: (a) a light pulse at frequency ω/2 undergoes two-photon absorption (TPA) and is delayed by the absorbing system (two-photon slow light) and (b) a light pulse at frequency ω is delayed in a system prepared by TPA of a light pulse at frequency ω/2 (two-photon-assisted slow light). The study carried out in solutions of dyes and dendrites shows significant delays, low distortion, and good transmission for easily reachable experimental conditions. The working principle can be applied to other media and can be used in telecommunications technology.


Comparison of the biologic activity of biosynthetic human insulin and natural pork insulin in juvenile-onset diabetic subjects assessed by the glucose controlled insulin infusion system.
To assess the biologic activity of biosynthetic human insulin (BHI) synthesized by Escherichia coli, six insulin-dependent juvenile-onset diabetic subjects were studied with BHI and natural pork insulin, by means of the glucose controlled insulin infusion system (GCIIS). First, after an overnight normalization of blood glucose levels, the 24-h insulin requirement was determined while the patients were consuming a diet of 30 kcal/kg. Then, the amount of glucose necessary to maintain normal blood glucose levels during a 5-h intravenous infusion of BHI and pork insulin, respectively, was assessed. Both studies demonstrate that in the insulin-dependent diabetic subject, BHI is at least as effective as natural pork insulin and may, therefore, be useful for the treatment of insulin-dependent diabetes mellitus.


The discovery of nitric oxide as the endogenous nitrovasodilator.
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.


Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements.
Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future.


[Depression 1. Clinical aspects and nurses' evaluation].
To review the recent advances made in evaluation and treatment procedures in cases of depression and their repercussions in nursing care. The growing efficiency of antidepressive medication, together with the importance given to community awareness of the upheavals which affect mental health, have modified the role nursing plays in evaluation of patients suffering depressive episodes. In this changing context, the therapeutic relationship between nurse and patient has developed into one of the pillars which sustain a correct and long-lasting stability in the depressed patient's state of mind. Primary source information on treatment methods by nurses handling depressed patients published from 1995 through 1999 and identified in the Medline data base. In a second article, these same authors will evaluate the intervention and the follow-up procedures carried out by nurses caring for patients suffering from depression.


Force-modulated reductive elimination from platinum(ii) diaryl complexes.
Coupled mechanical forces are known to drive a range of covalent chemical reactions, but the effect of mechanical force applied to a spectator ligand on transition metal reactivity is relatively unexplored. Here we quantify the rate of C(sp2)-C(sp2) reductive elimination from platinum(ii) diaryl complexes containing macrocyclic bis(phosphine) ligands as a function of mechanical force applied to these ligands. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand. We validated experimentally the computational finding for the most sensitive of the ligand designs, based on MeOBiphep, by coupling it to a macrocyclic force probe ligand. Consistent with the computations, compressive forces decreased the rate of reductive elimination whereas extension forces increased the rate relative to the strain-free MeOBiphep complex with a 3.4-fold change in rate over a ∼290 pN range of restoring forces. The calculated natural bite angle of the free macrocyclic ligand changes with force, but 31P NMR analysis and calculations strongly suggest no significant force-induced perturbation of ground state geometry within the first coordination sphere of the (P-P)PtAr2 complexes. Rather, the force/rate behavior observed across this range of forces is attributed to the coupling of force to the elongation of the O⋯O distance in the transition state for reductive elimination. The results suggest opportunities to experimentally map geometry changes associated with reactions in transition metal complexes and potential strategies for force-modulated catalysis.


Patterns of Pediatric Firearm-Related Ocular Trauma in the United States.
Gun violence represents a substantial public health issue, and firearm-related injuries rank second among the causes of injury-related deaths in children aged 0 to 17 years in the United States. Ocular trauma from firearm-related injuries can lead to devastating vision loss, but little is known to date about the specific demographics and characteristics of such injuries in children. To evaluate the epidemiologic pattern of pediatric firearm-related ocular injuries. This retrospective analysis used deidentified data from the National Trauma Data Bank, the largest national registry of hospitalized trauma cases in the United States. The firearm-related ocular injuries (n = 1972) of pediatric patients (defined as those younger than 21 years) hospitalized between January 1, 2008, and December 31, 2014, were analyzed. Statistical analyses were conducted from July 15, 2017, to June 15, 2019. Firearm-related ocular trauma. Pediatric patients with firearm-related ocular injuries were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes and external causes of injury codes. Patient demographics (age, sex, and race/ethnicity), type of ocular injury, injury intent, geographic location, length of hospital admission, health insurance status, disposition at discharge, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were collected. A total of 8715 firearm-related ocular injuries were identified. Of these injuries, 1972 (22.6%) occurred in pediatric patients, most of whom were male (1678 [85.1%]) and adolescents (1037 [52.6%]), with a mean (SD) age of 15.2 (5) years. Common locations of injury were home (761 [38.6%]) and street (490 [24.8%]). Mean (SD) hospital length of stay was 7.6 (12) days, ISS was 16 (13.1), and GCS score was 11 (5.1). The most common types of firearm-related ocular injuries were open wound of the eyeball (820 [41.6%]) and ocular adnexa (502 [25.5%]), orbital injuries or fractures (591 [30.0%]), and contusion of the eye or adnexa (417 [21.1%]). Patients aged 0 to 3 years had greater odds of unintentional injuries (odds ratio [OR], 4.41; 95% CI, 2.51-7.75; P < .001) and injuries occurring at home (OR, 5.39; 95% CI, 2.81-10.38; P < .001), and those aged 19 to 21 years had greater odds of assault injuries (OR, 2.17; 95% CI, 1.77-2.66; P < .001) and injuries occurring on the street (OR, 1.61; 95% CI, 1.3-1.98; P < .001). Black patients had the greatest odds of having injuries with assault intention (OR, 4.53; 95% CI, 3.68-5.59; P < .001), and white patients had the greatest likelihood for self-inflicted injury (OR, 7.1; 95% CI, 5.92-9.51; P < .001). Traumatic brain injury resulted mostly from self-inflicted trauma (OR, 5.99; 95% CI, 4.16-8.63; P < .001), as did visual pathway injuries (OR, 2.86; 95% CI, 1.95-4.20; P < .001). The inpatient mortality rate was 12.2%. This study found that pediatric firearm-related ocular injuries from 2008 through 2014 were predominantly sight-threatening and associated with traumatic brain injury. If the possible risk factors, including sex, age, race/ethnicity, and injury intention, can be confirmed for 2015 through 2019, these findings may be useful in developing strategies to prevent pediatric firearm-related ocular injuries.


Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of β-Cell Replacement.
The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.


[Methodological and regulatory features of clinical trials for behavioral and psychological symptoms in the course of dementia].
During the last few years there has been a growing awareness of behavioral and psychological symptoms of dementia (BPSD). These symptoms are usually classified in syndromes, which include psychosis, depression, agitation and sleep disturbances. BPSD have a major impact on the clinical course, prognosis and the quality of life of patients and caregivers. Moreover, BPSD considerably increase the social costs of dementia, since they often result in institutionalization. The therapy of BPSD was initially based on an empirical syndromic approach. However, in more recent years the efficacy and safety of treatments for these conditions have been tested in several controlled clinical trials. This paper addresses some of the methodological and regulatory issues that are relevant to the conducting of clinical trials for BPSD.


Prevalence of video game use, cigarette smoking, and acceptability of a video game-based smoking cessation intervention among online adults.
Video games may serve as an ideal platform for developing and implementing technology-based contingency management (CM) interventions for smoking cessation as they can be used to address a number of barriers to the utilization of CM (e.g., replacing monetary rewards with virtual game-based rewards). However, little is known about the relationship between video game playing and cigarette smoking. The current study determined the prevalence of video game use, video game practices, and the acceptability of a video game-based CM intervention for smoking cessation among adult smokers and nonsmokers, including health care professionals. In an online survey, participants (N = 499) answered questions regarding their cigarette smoking and video game playing practices. Participants also reported if they believed a video game-based CM intervention could motivate smokers to quit and if they would recommend such an intervention. Nearly half of the participants surveyed reported smoking cigarettes, and among smokers, 74.5% reported playing video games. Video game playing was more prevalent in smokers than nonsmokers, and smokers reported playing more recently, for longer durations each week, and were more likely to play social games than nonsmokers. Most participants (63.7%), including those who worked as health care professionals, believed that a video game-based CM intervention would motivate smokers to quit and would recommend such an intervention to someone trying to quit (67.9%). Our findings suggest that delivering technology-based smoking cessation interventions via video games has the potential to reach substantial numbers of smokers and that most smokers, nonsmokers, and health care professionals endorsed this approach.


[Diagnostic significance of antinuclear antibodies].
In three patients, women of 17, 25 and 15 years, suffering from arthralgia and in whom the existence of antinuclear antibodies (ANA) was established, the diagnosis 'systemic lupus erythematosus' was made or considered. Upon reevaluation, the ANA results could not be confirmed. The conclusion was drawn that in patients, who lack one or more clinical signs of a connective tissue disease (CTD), no indication is present for determination of ANA. Literature data indicate that the positive predictive value of ANA for the presence of CTD is 5-10%. Conversely, a negative ANA result does not rule out that CTD is present (negative predictive value: 98.5-99.3%). In addition, the question is raised if a hospital laboratory, lacking experience or routine in ANA assays could reliably perform these assays.


Familial associations of lipids and lipoproteins in families of hypercholesterolemic probands.
We used the Princeton School Family Study hypercholesterolemic recall group to assess whether, and to what degree, the identification of hypercholesterolemic subjects could be improved through the phenomenon of familial lipid and lipoprotein aggregation. A second aim was to assess whether within-family lipid and lipoprotein correlations outlasted the period of shared family environment. Approximately twice as many (as expected) siblings and offspring of hypercholesterolemic probands had plasma total and low density lipoprotein cholesterol levels greater than the 90th and 75th percentiles respectively, emphasizing how identification of hypercholesterolemic subjects can be facilitated by use of the phenomenon of familial aggregation of plasma total and low density lipoprotein cholesterol. After exclusion of the hypercholesterolemic probands from calculations of within-family correlations, and use of natural log transformations for the probands' first-degree relatives' lipids as required, most father/pediatric offspring and mother/pediatric offspring correlations for lipids and lipoprotein cholesterols were significant, while most parent/adult offspring correlations were not significant. All pediatric sibling correlations for lipids and lipoprotein cholesterols were significant; most adult sibling correlations were not significant. The loss of significance and consistency in sibling and parent/offspring lipid and lipoprotein correlations in adults who no longer shared a common household environment points to environmental influences on total, high, and low density lipoprotein cholesterol in kindreds with a hypercholesterolemic proband.


Effect of moderate white wine consumption on serum IgA and plasma insulin under fasting conditions.
The present study aims to investigate the contribution of alcohol toxicity to the development of malnutrition by assessing the effect of consuming a moderate amount of white wine on plasma insulin and serum IgA under fasting conditions. A total of 5 non-alcoholic males aged between 19 and 22 years participated in the current investigation. The experimental procedure required participants to undergo a 6-hour fast before ingesting 4 standard units of alcohol (40 g) in the form of white wine over a 120-min period. The level of blood alcohol, plasma insulin and serum IgA was assessed at 30-min intervals across the 120-min experimental period. Consuming alcohol promotes a significant increase in serum IgA in the absence of any change in plasma insulin or ketone production in fasted individuals. White wine prior to a meal does not promote glucose metabolism and utilization and may increase the risk of developing a transient diabetic condition due to an alteration in energy metabolism.


Classifying orofacial pains: a new proposal of taxonomy based on ontology.
We propose a new taxonomy model based on ontological principles for disorders that manifest themselves through the symptom of persistent orofacial pain and are commonly seen in clinical practice and difficult to manage. Consensus meeting of eight experts from various geographic areas representing different perspectives (orofacial pain, headache, oral medicine and ontology) as an initial step towards improving the taxonomy. Ontological principles were introduced, reviewed and applied during the consensus building process. Diagnostic criteria for persistent dento-alveolar pain disorder (PDAP) were formulated as an example to be used to model the taxonomical structure of all orofacial pain conditions. These criteria have the advantage of being (i) anatomically defined, (ii) in accordance with other classification systems for the provision of clinical care, (iii) descriptive and succinct, (iv) easy to adapt for applications in varying settings, (v) scalable and (vi) transferable for the description of pain disorders in other orofacial regions of interest. Limitations are that the criteria introduce new terminology, do not have widespread acceptance and have yet to be tested. These results were presented to the greater conference membership and were unanimously accepted. Consensus for the diagnostic criteria of PDAP was established within this working group. This is an initial first step towards developing a coherent taxonomy for orofacial pain disorders, which is needed to improve clinical research and care.


Eternal Sunshine of the Spotless Machine: Protecting Privacy with Ephemeral Channels.
Modern systems keep long memories. As we show in this paper, an adversary who gains access to a Linux system, even one that implements secure deallocation, can recover the contents of applications' windows, audio buffers, and data remaining in device drivers-long after the applications have terminated. We design and implement Lacuna, a system that allows users to run programs in "private sessions." After the session is over, all memories of its execution are erased. The key abstraction in Lacuna is an ephemeral channel, which allows the protected program to talk to peripheral devices while making it possible to delete the memories of this communication from the host. Lacuna can run unmodified applications that use graphics, sound, USB input devices, and the network, with only 20 percentage points of additional CPU utilization.


Impact of metabolic disorders on the structural, functional, and immunological integrity of the blood-brain barrier: Therapeutic avenues.
Mounting evidence has linked the metabolic disease to neurovascular disorders and cognitive decline. Using a murine model of a high-fat high-sugar diet mimicking obesity-induced type 2 diabetes mellitus (T2DM) in humans, we show that pro-inflammatory mediators and altered immune responses damage the blood-brain barrier (BBB) structure, triggering a proinflammatory metabolic phenotype. We find that disruption to tight junctions and basal lamina due to loss of control in the production of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) causes BBB impairment. Together the disruption to the structural and functional integrity of the BBB results in enhanced transmigration of leukocytes across the BBB that could contribute to an initiation of a neuroinflammatory response through activation of microglia. Using a humanized in vitro model of the BBB and T2DM patient post-mortem brains, we show the translatable applicability of our results. We find a leaky BBB phenotype in T2DM patients can be attributed to a loss of junctional proteins through changes in inflammatory mediators and MMP/TIMP levels, resulting in increased leukocyte extravasation into the brain parenchyma. We further investigated therapeutic avenues to reduce and restore the BBB damage caused by HFHS-feeding. Pharmacological treatment with recombinant annexin A1 (hrANXA1) or reversion from a high-fat high-sugar diet to a control chow diet (dietary intervention), attenuated T2DM development, reduced inflammation, and restored BBB integrity in the animals. Given the rising incidence of diabetes worldwide, understanding metabolic-disease-associated brain microvessel damage is vital and the proposed therapeutic avenues could help alleviate the burden of these diseases.


Surgeon-specific performance reports in general surgery: an observational study of initial implementation and adoption.
As national quality initiatives are increasing requirements for individual physician data, our department of surgery initiated a surgeon-specific reporting (SSR) program to assess the value of personal knowledge on individual performance quality. We sought to evaluate the use of SSR as a tool to enable surgeons to assess and improve their clinical performance, and to identify barriers to use of their reports. Qualitative research design involving semistructured interviews of surgeons who received performance reports derived from National Surgical Quality Improvement Program (NSQIP), Surgical Care Improvement Project (SCIP), and the Centers for Medicare and Medicaid Services (CMS) core measures and hospital administrative data. Transcripts were analyzed by the constant comparative method. Twenty-four of 39 surgeons (61.5%) who received their SSRs agreed to be interviewed and 23 were interviewed. About half (11 of 23) demonstrated comprehension of the data validity, accuracy, or complexity. Of these, 6 took steps to validate data or improve performance. Most respondents believed SSR would lead to performance improvement through knowledge of personal outcomes and peer comparison; however, they perceived SSR had limitations, such as small sample size and potential coding errors, and could lead to unintended consequences, such as inaccurate interpretation by others and surgeons' aversion to selecting high-risk patients. Respondents also suggested logistical improvements to reporting methods, such as report format and definitions of metrics. Surgeon-specific reporting has the potential to empower surgeons to improve their practice; however, more surgeons need efficient guidelines to understand the metrics. Our findings can be used to guide development of more SSR programs. Whether SSR programs lead to improvements in surgical outcomes is a matter for future research.


Thiorhodococcus mannitoliphagus sp. nov., a purple sulfur bacterium from the White Sea.
A novel purple sulfur bacterium, strain WS(T), was isolated from a microbial mat from an estuary of the White Sea. Individual cells are coccoid shaped, motile by flagella and do not contain gas vesicles. The mean cell diameter is 1.85 mum (range 1.5-2.0 mum). Cell suspensions exhibit a purple-violet colour. They contain bacteriochlorophyll a and carotenoids of the rhodopinal series as photosynthetic pigments. The novel bacterium is an anoxygenic photoautotroph, using sulfide, thiosulfate, sulfite and elemental sulfur as electron donors for photosynthesis and is capable of photoassimilating several organic carbon sources in the presence of carbonate and a reduced sulfur source (sulfide and/or thiosulfate). Sulfur globules, formed during oxidation of sulfide, are stored transiently inside the cells. Optimal salinity and pH for growth are at 0.5-2.0 % NaCl and pH 7.0-7.5. The DNA base composition of strain WS(T) is 61.8 mol% G+C. 16S rRNA gene sequence analysis showed that the new isolate belongs to the genus Thiorhodococcus, with Thiorhodococcus minor CE2203(T) as the nearest relative (sequence similarity of 97.3 %). Several distinct differences from described species necessitate the description of a novel species. Thiorhodococcus mannitoliphagus sp. nov. is the proposed name, with strain WS(T) (=ATCC BAA-1228(T)=VKM B-2393(T)) as the type strain.


Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL.
Mild hypothermia is considered to have a protective effect during ischemic neuronal cell death. The present study provides experimental evidence for this beneficial role of mild hypothermia using reversible middle cerebral artery occlusion (MCAo) in a Sprague-Dawley (SD) rat model. MCAo was induced in rats for 1 h followed by reperfusion at different periods. Hematoxylin-eosin (HE) staining in normothermic (NT) 37 degrees C and hypothermic (HT) 33 degrees C groups of rats confirmed cerebral infarcts. The mean per cent infarct area was significantly reduced in the HT group of rats. Immunohistochemical analysis was done using anti-Fas and caspase-3 antibodies. The immunohistochemical expression of Fas and caspase-3 was demonstrable as early as 5 h after reperfusion, but the expression pattern maximized at 24 h after reperfusion. The expression of Fas and caspase-3 proteins showed a clear decrease in the HT group over the NT group. In situ detection of DNA fragmentation was done using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method (TUNEL). TUNEL-positive cells were first observed at 5h after reperfusion and progressively increased by 24h. A higher number of TUNEL-positive cells was found in the NT group, but they were significantly decreased in the HT group. Further, DNA fragmentation was confirmed by size fractionation in agarose gel. These findings demonstrate a positive relation between the expression of Fas, caspase-3 and TUNEL-positive cells.


Glenoid Bone Loss in Traumatic Glenohumeral Instability in the Adolescent Population.
Glenoid bone loss can affect the outcome and treatment for posttraumatic recurrent anterior glenohumeral instability. Clinical presentation in the adolescent age group with shoulder instability and glenoid bone loss is largely unknown. On the basis of this information, we believe there will be a high incidence of glenoid bone loss in adolescent patients with recurrent glenohumeral instability. We hypothesize that high-impact injuries, sports injuries, and reductions requiring sedation will be factors associated with glenoid bone loss. We performed a retrospective cross-sectional cohort study reviewing consecutive adolescent patients (n=114) with recurrent traumatic glenohumeral instability between 2004 and 2012. Chart analysis included demographic, presenting, and radiographic data. Glenoid bone loss was interpreted from plain radiographs, computed tomography (2D and/or 3D), magnetic resonance imaging, and/or arthroscopy. We compared possible risk factors between subjects with and without glenoid bone defects using the χ test or 2 sample t tests. Glenoid bone loss was seen in 55 patients (48.2%) with 15 of these patients (27%) having critical bone loss. Forty-five percent of appreciated glenoid bone loss was not visualized on plain radiographs. The average age was 15.1 years (range, 6.5 to 18.1) with male to female ratio 3.7:1. Male sex, older age, and taller stature were all statistically associated with glenoid bone loss (P=0.02, 0.01, and 0.02, respectively). Primary dislocations that occurred during sports were more likely to have glenoid bone loss (55.9% vs. 78.2%, P=0.01). The presence of an apprehension sign on physical examination was positively correlated with bone loss (P=0.008). The presence of glenoid bone loss in primary traumatic glenohumeral instability in the adolescent population is high, however, not as high as previously reported. Factors associated with glenoid bone loss include male sex, older age, taller stature, sports injuries, and the presence of apprehension on physical examination. This study establishes patients who may be at high risk for glenoid bone loss based on mechanism of injury and physical examination findings. This prognostic study is a level II retrospective study.


Conduct disorder and antisocial personality disorder in persons with severe psychiatric and substance use disorders.
Conduct disorder (CD) and antisocial personality disorder (ASPD) are established risk factors for substance use disorders in both the general population and among persons with schizophrenia and other severe mental illnesses. Among clients with substance use disorders in the general population, CD and ASPD are associated with more severe problems and criminal justice involvement, but little research has examined their correlates in clients with dual disorders. To address this question, we compared the demographic, substance abuse, clinical, homelessness, sexual risk, and criminal justice characteristics of 178 dual disorder clients living in 2 urban areas between 4 groups: No CD/ASPD, CD Only, Adult ASPD Only, and Full ASPD. Clients in the Adult ASPD Only group tended to have the most severe drug abuse severity, the most extensive homelessness, and the most lifetime sexual partners, followed by the Full ASPD group, compared with the other 2 groups. However, clients with Full ASPD had the most criminal justice involvement, especially with respect to violent charges and convictions. The results suggest that a late-onset ASPD subtype may develop in clients with severe mental illness secondary to substance abuse, but that much criminal behavior in clients with dual disorders may be due to the early onset of the full ASPD syndrome in this population and not the effects of substance use disorders.


A comparison of two behavioral measures of psychomotor activation following intravenous amphetamine or cocaine: dose- and sensitization-dependent changes.
This paper presents data concerning the dose-effect relationships of intravenously administered amphetamine and cocaine on two widely used measures of psychomotor activation: locomotor crossover activity in neurologically intact rats, and rotational behavior in rats with a unilateral 6-hydroxydopamine lesion. There were marked differences in dose-effect relationships, both as a function of drug and of behavioral measure. Amphetamine produced a linear increase in rotational behavior over a wide range of doses (the highest effective dose was 76.8 times the lowest), but a linear increase in locomotor crossover activity over only a narrow dose range (the highest effective dose was only four times the lowest). In contrast, for cocaine, the dose-effect relationships for the two behaviors were very similar, but for both behaviors the effective dose range was quite narrow, the highest effective dose being only between two and four times the lowest. The data highlight the advantages and disadvantages of these measures as indices of the psychomotor activating effects of psychostimulant drugs.


Classification and characterization of multimodal nanoparticle size distributions by size-exclusion chromatography.
Size-exclusion chromatography (SEC) is a well-known, versatile and scalable technique for the separation of molecules according to their hydrodynamic size in solution as well as for the determination of molecular weight distributions of polymers. In this paper we demonstrate and generalize the applicability of SEC to the classification and characterization of multimodal distributions of nanoparticles over a broad size range. After calibration with gold standards from 5 nm to 80 nm, the calibration curve is used to determine the particle size distributions (PSDs) of the standards which are in agreement with comprehensive nanoparticle size analysis by analytical ultracentrifugation. Universal calibration curves independent of the core material and surface functionality can be constructed if the pore diameter of the stationary phase exceeds the particle diameter by a factor of 2-3. Mixtures of gold standards are separated by SEC and evaluated in terms of peak resolution and size-dependent separation curves depending on how well the individual peaks are resolved. Baseline separation of a multimodal mixture is observed and its PSD is determined. Mixtures can be fractionated into coarse and fine fractions with nm precision at different switching times of the fraction collector. Our study demonstrates the strength of SEC to classify multimodal PSDs as well as to accurately determine size distributions of complex nanoparticle dispersions over a broad size range.


Determination of the level of DNA modification with cisplatin by catalytic hydrogen evolution at mercury-based electrodes.
Electrochemical methods proved useful as simple and inexpensive tools for the analysis of natural as well as chemically modified nucleic acids. In particular, covalently attached metal-containing groups usually render the DNA well-pronounced electrochemical activity related to redox processes of the metal moieties, which can in some cases be coupled to catalytic hydrogen evolution at mercury or some types of amalgam electrodes. In this paper we used voltammetry at the mercury-based electrodes for the monitoring of DNA modification with cis-diamminedichloroplatinum (cisplatin), a representative of metallodrugs used in the treatment of various types of cancer or being developed for such purpose. In cyclic voltammetry at the mercury electrode, the cisplatin-modified DNA yielded catalytic currents the intensity of which reflected DNA modification extent. In square-wave voltammetry, during anodic polarization after prereduction of the cisplatinated DNA, a well-developed, symmetrical signal (peak P) was obtained. Intensity of the peak P linearly responded to the extent of DNA modification at levels relevant for biochemical studies (rb = 0.01-0.10, where rb is the number of platinum atoms bound per DNA nucleotide). We demonstrate a correlation between the peak P intensity and a loss of sequence-specific DNA binding by tumor suppressor protein p53, as well as blockage of DNA digestion by a restriction endonuclease Msp I (both caused by the DNA cisplatination). Application of the electrochemical technique in studies of DNA reactivity with various anticancer platinum compounds, as well as for an easy determination of the extent of DNA platination in studies of its biochemical effects, is discussed.


Efficiency statistics at all times: Carnot limit at finite power.
We derive the statistics of the efficiency under the assumption that thermodynamic fluxes fluctuate with normal law, parametrizing it in terms of time, macroscopic efficiency, and a coupling parameter ζ. It has a peculiar behavior: no moments, one sub-, and one super-Carnot maxima corresponding to reverse operating regimes (engine or pump), the most probable efficiency decreasing in time. The limit ζ→0 where the Carnot bound can be saturated gives rise to two extreme situations, one where the machine works at its macroscopic efficiency, with Carnot limit corresponding to no entropy production, and one where for a transient time scaling like 1/ζ microscopic fluctuations are enhanced in such a way that the most probable efficiency approaches the Carnot limit at finite entropy production.


Implementation of a screen and treat program for child posttraumatic stress disorder in a school setting after a school suicide.
To provide effective treatments for childhood posttraumatic stress disorder (PTSD) children with PTSD must first be identified. The authors implemented a "screen and treat" program following a widely witnessed school suicide. Three months after the suicide, exposed students received the Child Trauma Symptom Questionnaire at school. Parents received the questionnaire to rate their children's PTSD symptoms. Children with scores > or =5 received follow-up interviews and those diagnosed with PTSD were referred for treatment. Ninety-six percent of exposed students were screened, 14% screened positive, and 6% had PTSD. Child and parent agreement was generally poor. All children with PTSD were successfully referred to treatment. Screen and treat programs using existing clinical instruments are efficient and acceptable for use in school settings following trauma.


Allosteric discrimination at the NADH/ADP regulatory site of glutamate dehydrogenase.
Glutamate dehydrogenase (GDH) is a target for treating insulin-related disorders, such as hyperinsulinism hyperammonemia syndrome. Modeling native ligand binding has shown promise in designing GDH inhibitors and activators. Our computational investigation of the nicotinamide adenine diphosphate hydride (NADH)/adenosine diphosphate (ADP) site presented in this paper provides insight into the opposite allosteric effects induced at a single site of binding inhibitor NADH versus activator ADP to GDH. The computed binding free-energy difference between NADH and ADP using thermodynamic integration is -0.3 kcal/mol, which is within the -0.275 and -1.7 kcal/mol experimental binding free-energy difference range. Our simulations show an interesting model of ADP with dissimilar binding conformations at each NADH/ADP site in the GDH trimer, which explains the poorly understood strong binding but weak activation shown in experimental studies. In contrast, NADH showed similar inhibitory binding conformations at each NADH/ADP site. The structural analysis of the important residues in the NADH/ADP binding site presented in this paper may provide potential targets for mutation studies for allosteric drug design.


An eccentric rod-like linear connection of two heterocycles: synthesis of pyridine trans-tetrafluoro-λ6-sulfanyl triazoles.
The trans-tetrafluoro-λ6-sulfane (SF4) group has been utilized as a unique three-dimensional building block for the linear connection of two independent N-heterocycles, pyridines and triazoles. The linearly connected heterocyclic compounds were synthesized by thermal Huisgen 1,3-dipolar cycloaddition between previously unknown pyridine SF4-alkynes and readily available azides, providing a series of rod-like SF4-connected N-heterocycles in good to excellent yields. X-ray crystallographic analysis of the target products revealed the trans-geometry of the SF4 group, which linearly connects two independent N-heterocycles. This research will open the field of chemistry of SF4-connected heterocyclic compounds.


Managing resources in NHS dentistry: the views of decision-makers in primary care organisations.
To investigate priority setting and decision-making in primary care organisations and to determine how resources are managed in order to meet the oral health needs of local populations. This is a qualitative study. The purposive sample comprised twelve dental public health consultants and six senior finance representatives from contrasting care systems across the United Kingdom. Participants completed a written information sheet followed by a recorded semi-structured telephone interview. Conversations were professionally transcribed verbatim and analysed independently by two investigators using the constant comparative method. The emergent themes focused upon: the role of participants in decision-making; professional relationships; managing change; information needs; and identifying and managing priorities. There was wide interpretation with respect to participants' roles and perceived information needs for decision-making and commissioning. A unifying factor was the importance placed by participants upon trust and the influence of individuals on the success of relationships forged between primary care organisations and general dental practitioners. To facilitate decision-making in primary care organisations, commissioners and managers could engage further with practitioners and incorporate them into commissioning and resource allocation processes. Greater clarity is required regarding the role of dental public health consultants within primary care organisations and commissioning decisions.


Complex analysis of the p53 tumor suppressor in lung carcinoma.
Lung cancer is the leading cause of cancer-related deaths worldwide. The p53 tumor suppressor is a transcription factor controlling expression of its target genes in response to various stress stimuli. Mutations of the TP53 gene occur very frequently in lung carcinomas and they play an important role in both oncogenic transformation of lung epithelial cells and lung carcinoma progression. We determined the TP53 status in 42 samples of squamous cell lung carcinoma (SQCC) and 56 samples of lung adenocarcinoma (AC) by the functional analysis FASAY and its variant called split assay. Altogether, we detected 64 TP53 mutations in 63 patients and analyzed them by cDNA and gDNA sequencing. The TP53 mutations were found in 76.2% (32/42) of SQCC cases, and 55.4% (31/56) of ACs. Immunoblotting revealed the p53 protein accumulation in 18 samples (42.9%) among SQCC cases and 19 samples (33.9%) among AC cases. Using fluorescence in situ hybridization we detected loss of the TP53-specific 17p13.3 locus in 23 from 41 analyzed SQCC samples (56.1%) and in 20 from 54 analyzed AC samples (37.0%). We did not find any statistically significant differences in overall and disease-free survival in relation to TP53 status.


Decreased hepatic copper levels. A possible chemical marker for the pathogenesis of aortic aneurysms in man.
The spontaneously aneurysm-prone Blotchy mouse has a mutation on the X chromosome resulting in low hepatic copper levels; and copper is an essential cofactor for lysyl oxidase, which catalyzes reactions leading to the cross-linking of collagen and elastin. Population characteristics and family histories of patients with aneurysms suggest that aneurysmal disease may also be sex linked in man. Hepatic copper levels were determined in 13 patients who died with abdominal aortic aneurysms and in 13 control patients selected on the criterion of severe atherosclerotic occlusive disease of the abdominal aorta. Excluding two patients with severe liver disease, the tissue copper level in the patients with aneurysms was only 26% of the control level. The results suggest that additional studies of the biologic markers for aneurysm formation in the Blotchy mouse should be carried out prospectively in human subjects.


Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
We sought to explore the relationship between a Tcap gene (TCAP) abnormality and cardiomyopathy. Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc. The TCAP was analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays-yeast two-hybrid and glutathion S-transferase pull-down competition-were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q. Two TCAP mutations, T137I and R153H, were found in patients with HCM, and another TCAP mutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1. These observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components.


Downregulation of ADAMTS18 May Serve as a Poor Prognostic Biomarker for Cervical Cancer Patients.
ADAMTS18 is a member of ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family proteins which have been found to play important roles in cancer progression and metastasis in different cancer types. The present study aims at evaluating the prognostic significance of ADAMTS18 in cervical cancer. The expression levels of ADAMTS18 was evaluated by real-time PCR in normal (N=28) and cervical cancer tissues from patients at different stages as well as in tumor tissues from 35 cervical cancer patients with primary cancer and 29 patients with metastasis. The correlation between serum ADAMTS18 expression levels and clinicopathologic features or overall survival of cervical cancer patients was analyzed. ADAMTS18 expression levels were significantly decreased in cervical cancer tissues compared with normal tissues and it decreased gradually from early stage to late stage. Low expression of ADAMTS18 was positively associated with high tumor stage (P=0.0239), positive lymph node metastasis (P=0.0388), and distant metastasis (P=0.0004). Tissue levels of ADAMTS18 in patients with primary cancer were significantly lower compared with those with metastasis. Moreover, patients with low ADAMTS18 expression levels had shorter overall survival (P=0.0119) or disease-free survival (P=0.0033). Multivariate analysis demonstrated that ADAMTS18 was an independent prognostic factor for cervical cancer. Our study suggests that ADAMTS18 is downregulated in cervical cancer and ADAMTS18 may serve as a potential prognostic biomarker for cervical cancer.


Double trouble: Nonsuicidal self-injury and its relationship to suicidal ideation and number of past suicide attempts in clinical adolescents.
Death by suicide is one of the leading causes of mortality among adolescents, and nonsuicidal self-injury (NSSI) is one of the strongest predictors of suicide attempts (SAs). The underlying bases for this relationship are unknown. We derived two hypotheses from the Interpersonal Psychological Theory of Suicide (IPTS): unmet interpersonal needs would explain NSSI's association with suicidal ideation (SI) and increased capability for suicide would explain NSSI's relationship with SA. Adolescents hospitalized on a psychiatric inpatient unit (N = 289) provided measures of current SI, number of past SAs, unmet interpersonal needs (perceived burdensomeness and thwarted belongingness), capability for suicide (fearlessness about death [FAD] and pain tolerance), depressive symptoms, and number of NSSI methods utilized. Depressive symptoms, but not unmet interpersonal needs, explained NSSI's association with SI. FAD and SI, but not depressive symptoms or pain tolerance, accounted for NSSI's relationship with SA. FAD was associated with SA, but it did not fully account for NSSI's relationship with SA. This study utilized a cross-sectional design and retrospective, self-report measures. Our study provides partial support for the role of the IPTS variables in NSSI's relationship with SA in adolescents. The finding that depressive symptoms and not unmet interpersonal needs explained NSSI's relationship with SI contradicts the IPTS. However, in those with SI, FAD was linearly associated with SA, which is consistent with the IPTS. Future studies are needed to clarify the persistent basis for NSSI's relationship with SA beyond FAD and SI.


The Neuroprotective Properties, Functions, and Roles of Cannabis sativa in Selected Diseases Related to the Nervous System.
Cannabis and its extracts are now being explored due to their huge health benefits. Although, the effect they elicit, whether on humans or rodents, may vary based on the age of the animal/subject and or the time in which the extract is administered. However, several debates exist concerning the various medical applications of these compounds. Nonetheless, their applicability as therapeutics should not be clouded based on their perceived negative biological actions. Articles from reliable databases such as Science Direct, PubMed, Google Scholar, Scopus, and Ovid were searched. Specific search methods were employed using multiple keywords: ''Medicinal Cannabis; endocannabinoid system; cannabinoids receptors; cannabinoids and cognition; brain disorders; neurodegenerative diseases''. For the inclusion/exclusion criteria, only relevant articles related to medicinal Cannabis and its various compounds were considered. The current review highlights the role, effects, and involvement of Cannabis, cannabinoids, and endocannabinoids in preventing selected neurodegenerative diseases and possible amelioration of cognitive impairments. Furthermore, it also focuses on Cannabis utilization in many disease conditions such as Alzheimer's and Parkinson's disease among others. In conclusion, the usage of Cannabis should be further explored as accumulating evidence suggests that it could be effective and somewhat safe, especially when adhered to the recommended dosage. Furthermore, in-depth studies should be conducted in order to unravel the specific mechanism underpinning the involvement of cannabinoids at the cellular level and their therapeutic applications.


[In vitro antibacterial activity of a new cephalosporin: cefpirome (HR 810). Comparison with ceftriaxone, cefotaxime, latamoxef and ceftazidime].
In vitro activity of a new cephalosporin, cefpirome (HR 810) was tested using an agar dilution procedure against 393 hospital bacterial isolates. Results were compared to those obtained with ceftriaxone, cefotaxime, latamoxef and ceftazidime. Cefpirome was the most active drug against oxacillin-susceptible staphylococci and the only drug with activity against streptococci D (MIC 90%: 7 mg/l). Against Enterobacteriaceae strains with varying degrees of resistance to cephalosporins, results varied across species: activity of cefpirome was greater than that of the four other drugs for E. cloacae and C. freundii, similar to that of ceftriaxone for E. coli, S. marcescens, P. morganii and Salmonella sp., inferior to that of latamoxef for P. stuartii. However, against all Enterobacteriaceae strains as a whole, cefpirome proved the most active of the five agents tested (99.1% of strains inhibited by 4 mg/l) as a result of its greater activity against strains with resistance to second generation cephalosporins or cefotaxime. Cefpirome in a concentration of 4 mg/l inhibited 50% of tested P. aeruginosa strains (MIC 90%; 13 mg/l) and was inferior only to ceftazidime (MIC 90%: 4 mg/l). However, cefpirome exhibited no activity against A. calcoaceticus and L. monocytogenes.


Development and evaluation of microporous osmotic tablets of diltiazem hydrochloride.
Microporous osmotic tablet of diltiazem hydrochloride was developed for colon targeting. These prepared microporous osmotic pump tablet did not require laser drilling to deliver the drug to the specific site of action. The tablets were prepared by wet granulation method. The prepared tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan coating process. The incorporation of sodium lauryl sulfate (SLS), a leachable pore-forming agent, could form in situ delivery pores while coming in contact with gastrointestinal medium. The effect of formulation variables was studied by changing the amounts of sodium alginate and NaCMC in the tablet core, osmogen, and that of pore-forming agent (SLS) used in the semipermeable coating. As the amount of hydrophilic polymers increased, drug release rate prolonged. It was found that drug release was increased as the concentration of osmogen and pore-former was increased. Fourier transform infrared spectroscopy and Differential scanning calorimetry results showed that there was no interaction between drug and polymers. Scanning electron microscopic studies showed the formation of pores after predetermined time of coming in contact with dissolution medium. The formation of pores was dependent on the amount of pore former used in the semipermeable membrane. in vitro results showed acid-resistant, timed release at an almost zero order up to 24 hours. The developed osmotic tablets could be effectively used for prolonged delivery of Diltiazem HCl.


Withholding and withdrawing treatment for cost-effectiveness reasons: Are they ethically on par?
In healthcare priority settings, early access to treatment before reimbursement decisions gives rise to problems of whether negative decisions for cost-effectiveness reasons should result in withdrawing treatment, already accessed by patients. Among professionals there seems to be a strong attitude to distinguish between withdrawing and withholding treatment, viewing the former as ethically worse. In this article the distinction between withdrawing and withholding treatment for reasons of cost effectiveness is explored by analysing the doing/allowing distinction, different theories of justice, consequentialist and virtue perspectives. The authors do not find any strong reasons for an intrinsic difference, but do find some reasons for a consequentialist difference, given present attitudes. However, overall, such a difference does not, all things considered, provide a convincing reason against withdrawal, given the greater consequentialist gain of using cost-effective treatment. As a result, patients should be properly informed when given early access to treatment, that such treatment can be later withdrawn following a negative reimbursement decision.


Rainbow Trout Red Blood Cells Exposed to Viral Hemorrhagic Septicemia Virus Up-Regulate Antigen-Processing Mechanisms and MHC I&II, CD86, and CD83 Antigen-presenting Cell Markers.
Nucleated teleost red blood cells (RBCs) are known to express molecules from the major histocompatibility complex and peptide-generating processes such as autophagy and proteasomes, but the role of RBCs in antigen presentation of viruses have not been studied yet. In this study, RBCs exposed ex vivo to viral hemorrhagic septicemia virus (VHSV) were evaluated by means of transcriptomic and proteomic approaches. Genes and proteins related to antigen presentation molecules, proteasome degradation, and autophagy were up-regulated. VHSV induced accumulation of ubiquitinated proteins in ex vivo VHSV-exposed RBCs and showed at the same time a decrease of proteasome activity. Furthermore, induction of autophagy was detected by evaluating LC3 protein levels. Sequestosome-1/p62 underwent degradation early after VHSV exposure, and it may be a link between ubiquitination and autophagy activation. Inhibition of autophagosome degradation with niclosamide resulted in intracellular detection of N protein of VHSV (NVHSV) and p62 accumulation. In addition, antigen presentation cell markers, such as major histocompatibility complex (MHC) class I & II, CD83, and CD86, increased at the transcriptional and translational level in rainbow trout RBCs exposed to VHSV. In summary, we show that nucleated rainbow trout RBCs can degrade VHSV while displaying an antigen-presenting cell (APC)-like profile.


Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.
Mammalian sterile 20-like kinase 1 (Mst1) is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE) and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.


Differential Scanning Calorimetry (DSC): a tool to study the thermal behavior of lipid bilayers and liposomal stability.
Thermodynamical techniques are applied for determining the thermal stress of medicinal compounds of the excipients as well as their interactions during the formulation process. The physicochemical properties and the stability of the medicinal products could be measured as a function of temperature or time using thermal analysis. Differential Scanning Calorimetry (DSC) is a suitable thermal analysis technique for determining the purity, the polymorphic forms and the melting point of a sample in the Pharmaceutical Industry. It is also considered as a tool to study the thermal behavior of lipid bilayers and of lipidic drug delivery systems, like liposomes by measuring thermodynamic parameters (i.e. DeltaH and Tm), which affect the stability of the liposomal suspension under given storage conditions.


Tobacco use and nicotine dependence among conflict-affected men in the Republic of Georgia.
There is very little evidence globally on tobacco use and nicotine dependence among civilian populations affected by armed conflict, despite key vulnerability factors related to elevated mental disorders and socio-economic stressors. The study aim was to describe patterns of smoking and nicotine dependence among conflict-affected civilian men in the Republic of Georgia and associations with mental disorders. A cross-sectional household survey using multistage random sampling was conducted in late 2011 among conflict-affected populations in Georgia. Respondents included in this paper were 1,248 men aged ≥18 years who were internally displaced persons (IDPs) and former IDPs who had returned in their home areas. Outcomes of current tobacco use, heavy use (≥20 cigarettes per day), and nicotine dependence (using the Fagerström Test for Nicotine Dependence) were used. PTSD, depression, anxiety and hazardous alcohol use were also measured, along with exposure to traumatic events and a range of demographic and socio-economic characteristics. Of 1,248 men, 592 (47.4%) smoked and 70.9% of current smokers were heavy smokers. The mean nicotine dependence score was 5.0 and the proportion with high nicotine dependence (≥6) was 41.4%. In multivariate regression analyses, nicotine dependence was significantly associated with PTSD (β 0.74) and depression (β 0.85), along with older age (except 65+ years), and being a returnee (compared to IDPs). The study reveals very high levels of heavy smoking and nicotine dependence among conflict-affected persons in Georgia. The associations between nicotine dependence, PTSD and depression suggest interventions could yield synergistic benefits.


Effect of a selected Lactobacillus spp.-based probiotic on Salmonella enterica serovar enteritidis-infected broiler chicks.
The effect of a Lactobacillus spp.-based probiotic (FM-B11) on Salmonella enterica serovar Enteritidis (SE) recovery was evaluated in liquid (Expt. 1) and lyophilized (Expt. 2) forms in two separate experiments with two trials each. For each trial, 80 broiler chicks were randomly allocated into two treatments: control and probiotic culture. All chicks were challenged with SE (approximately 10(4) colony-forming units [cfu]) upon arrival at our laboratory. In both experiments, probiotic culture was administered in the drinking water for 3 consecutive days at a final concentration of approximately 10(6) cfu/ml, beginning 1 hr after SE challenge. Cecal tonsils were aseptically removed at 24 and 72 hr postchallenge, followed by enrichment and plating on xylose lactose deoxycholate (XLD) agar for the presence or absence of Salmonella-typical colonies. In Expt. 1, a significant reduction (P < 0.05) in SE-positive samples was observed in both trials at 24 and 72 hr postchallenge. Additionally, in Expt. 2, the lyophilized probiotic decreased (P < 0.05) SE recovery at both 24 and 72 hr postchallenge compared with the control group in trial 1. In trial 2, SE evaluation was performed only at 72 hr after challenge and fewer (P < 0.001) treated samples were positive for SE. Results showed that application of either liquid or lyophilized probiotic culture in the drinking water for 3 consecutive days can help to reduce SE recovery from young birds, although further research is needed to elucidate the mechanism of this response.


Epidemiology of oral health conditions in older people.
The main conditions of interest when considering the epidemiology of oral diseases among older people are tooth loss, dental caries, periodontitis, dry mouth and oral pre-cancer/cancer, along with oral-health-related quality of life (OHRQoL). This article presents an overview of what is known about the epidemiology of each of the main conditions of interest among older populations.


An approach for acute disruption of large arteries in patients with advanced cervical cancer: endoluminal balloon occlusion technique.
To test the feasibility of an intraluminal balloon occlusion technique for the control of sudden arterial disruption from cervical branches in patients with advanced malignancy. A sudden disruption of large cervical arteries is a devastating complication of advanced cervical malignancy and local infection. Three patients with this complication underwent endoluminal balloon occlusion before surgical management. A double-lumen balloon catheter was introduced from the femoral artery to the bleeding point. Angiographic examination of the intracranial cross-filling could be performed by the injection of contrast medium from the opposite carotid artery, and consciousness levels could be directly confirmed under unilateral carotid occlusion. Resection of the carotid or innominate artery was safely performed in all the patients. No neurologic complications occurred. Bleeding did not recur during follow-up (range 5-32 months). This experience, although limited, suggests that surgical intervention to control cervical arterial bleeding with intraluminal balloon occlusion prevents excessive bleeding, decreases the risk of damage to the central nervous system, and improves the outcome in these critically ill patients.


Royal Society of Chemistry--sixth international symposium on applied bioinorganic chemistry.
This was the sixth in a series of symposia that began in Beijing, China in 1986. Approximately 100 chemists, environmental and biomedical scientists from 25 countries attended the meeting and presented some 80 papers on topics ranging from cancer chemotherapy to the production of paper. About half the papers presented could be broadly described as having medical implications, and of these, approximately half related directly to the use of platinum and the potential uses of other metals, such as palladium and the lanthanides, as anticancer agents. Many of these papers provided valuable insights into mechanisms of action and offered pointers for future research, but only rarely did they point to potential new drugs that might find early exploitation in clinical medicine. Two of the more exciting clinical developments were the introduction of the insulin-mimetic bis(maltolato)oxovanadium(IV) (KP-102; Kinetek Pharmaceuticals Inc/University of British Columbia) into clinical trials in the UK for the treatment of Type II diabetes, and the increasing importance of the orally active agent 3-hydroxy-pyridin-4-one-deferiprone (Apotex Inc/Cipla Ltd), in the treatment of iron overload in thalassemia.


Vascular effects of Siberian ginseng (Eleutherococcus senticosus): endothelium-dependent NO- and EDHF-mediated relaxation depending on vessel size.
Siberian ginseng (SG) has been widely and historically consumed as a health food product for the improvement of self well-being, but whether vascular relaxation may contribute to such a therapeutic health effect has not been studied. We therefore investigated the vasorelaxant effect of the aqueous extract of the roots of SG (Eleutherococcus senticosus Maxim) using several in vitro vascular rings prepared from dog carotid artery, rat aorta and rat mesenteric artery. SG extract (0.04-0.8 mg/ml) caused concentration-dependent relaxation in dog carotid arterial rings pre-contracted with 100 microM phenylephrine (PE), and the relaxation was primarily endothelium-dependent. Treatment with 100 microM L-NOARG (a nitric oxide synthase inhibitor) either prevented or totally reverted SG-induced relaxation, suggesting that the endothelium-dependent relaxation was mediated by NO. Similar endothelium-dependent vascular relaxant responses were also obtained with rat aortic and mesenteric arterial rings, except that it occurred over a relatively higher concentration range of SG (0.5-2.0 mg/ml). When tested in the presence of 300 microM L-NAME, the vasorelaxant effect of SG was inhibited totally in rat aorta but only partially in rat mesenteric artery. The relaxation to SG that was insensitive to L-NAME in rat mesenteric arterial rings was eliminated when the rings (both proximal and distal ends) were pre-treated with a combination of 300 microM L-NAME and 15 mM KCl indicating the involvement of endothelium-derived hyperpolarizing factor (EDHF). This vasorelaxant response of the SG extract was inhibited partially by atropine (1 microM), completely by TEA (5 mM), but not by indomethacin (1 microM) or propranolol (10 microM). SG up to 2 mg/ml had no effect on KCl-induced contraction in any of the vascular rings studied. When compared with carbachol-induced (CCh) relaxation, SG resembles CCh in that the sensitivity to L-NAME inhibition is dependent on vascular size, i.e. aorta >proximal end of mesenteric artery >distal end of mesenteric artery. However, SG exhibited different potencies to relaxation while CCh showed similar potency (EC(50) of about 0.2 microM) in all three vascular segments. In conclusion, we have demonstrated that the vascular effect of SG is endothelium-dependent and mediated by NO and/or EDHF depending on the vessel size. Other vasorelaxation pathways, such as inhibition of K(+)-channels and activation of muscarinic receptors, may also be involved.


Effectiveness of delivering integrated COPD care at public healthcare facilities: a cluster randomised trial in Pakistan.
In Pakistan chronic obstructive pulmonary disease (COPD) prevalence is 2.1% in adults aged >40 years. Despite being a health policy focus, integrated COPD care has remained neglected, with wide variation in practice. To assess whether enhanced care at public health facilities resulted in better control of COPD, treatment adherence, and smoking cessation. A two-arm cluster randomised controlled trial was undertaken in 30 public health facilities (23 primary and 7 secondary), across three districts of Punjab, between October 2014-December 2016. Both arms had enhanced diagnosis and patient recording processes. Intervention facilities also had clinical care guides; drugs for COPD; patient education flipcharts; associated staff training; and mobile phone follow-up. Facilities were randomised in a 1:1 ratio (sealed envelope independent lottery method), and 159 intervention and 154 control patients were recruited. The eligibility criteria were as follows: diagnosed with COPD, aged ≥18 years, and living in the catchment area. The primary outcome was change in BODE (Body mass index, airway Obstruction, Dyspnoea, Exercise capacity) index score from baseline to final follow-up visit. Staff and patients were not blinded. Six-month primary outcomes were available for 147/159 (92.5%) intervention and 141/154 (91.6%) control participants (all clusters). The primary outcome results cluster-level analysis were as follows: mean intervention outcome = -1.67 (95% confidence intervals [CI] = -2.18 to -1.16); mean control outcome = -0.66 (95% CI = -1.09 to -0.22); and covariate-adjusted mean intervention-control difference = -0.96 (95% CI = -1.49 to -0.44; P = 0.001). The findings of this trial and a separate process evaluation study support the scaling of this integrated COPD care package at primary and secondary level public health facilities in Pakistan and similar settings.


An emerging role for IQGAP1 in regulating protein traffic.
IQGAP1, an effector of CDC42p GTPase, is a widely conserved, multifunctional protein that bundles F-actin through its N-terminus and binds microtubules through its C-terminus to modulate the cell architecture. It has emerged as a potential oncogene associated with diverse human cancers. Therefore, IQGAP1 has been heavily investigated; regardless, its precise cellular function remains unclear. Work from yeast suggests that IQGAP1 plays an important role in directed cell growth, which is a conserved feature crucial to morphogenesis, division axis, and body plan determination. New evidence suggests a conserved role for IQGAP1 in protein synthesis and membrane traffic, which may help to explain the diversity of its cellular functions. Membrane traffic mediates infections by intracellular pathogens and a range of degenerative human diseases arise from dysfunctions in intracellular traffic; thus, elucidating the mechanisms of cellular traffic will be important in order to understand the basis of a wide range of inherited and acquired human diseases. Recent evidence suggests that IQGAP1 plays its role in cell growth through regulating the conserved mTOR pathway. The mTOR signaling cascade has been implicated in membrane traffic and is activated in nearly all human cancers, but clinical response to the mTOR-specific inhibitor rapamycin has been disappointing. Thus, understanding the regulators of this pathway will be crucial in order to identify predictors of rapamycin sensitivity. In this review, I discuss emerging evidence that supports a potential role of IQGAP1 in regulating membrane traffic via regulating the mTOR pathway.


Beyond core knowledge: Natural geometry.
For many centuries, philosophers and scientists have pondered the origins and nature of human intuitions about the properties of points, lines, and figures on the Euclidean plane, with most hypothesizing that a system of Euclidean concepts either is innate or is assembled by general learning processes. Recent research from cognitive and developmental psychology, cognitive anthropology, animal cognition, and cognitive neuroscience suggests a different view. Knowledge of geometry may be founded on at least two distinct, evolutionarily ancient, core cognitive systems for representing the shapes of large-scale, navigable surface layouts and of small-scale, movable forms and objects. Each of these systems applies to some but not all perceptible arrays and captures some but not all of the three fundamental Euclidean relationships of distance (or length), angle, and direction (or sense). Like natural number (Carey, 2009), Euclidean geometry may be constructed through the productive combination of representations from these core systems, through the use of uniquely human symbolic systems.


Theoretical analysis of the evolution of immune memory.
The ability of an immune system to remember pathogens improves the chance of the host to survive a second exposure to the same pathogen. This immunological memory has evolved in response to the pathogen environment of the hosts. In vertebrates, the memory of previous infection is physiologically accomplished by the development of memory T and B cells. Many questions concerning the generation and maintenance of immunological memory are still debated. Is there a limit to how many memory cells a host can generate and maintain? If there is a limit, how should new cells be incorporated into a filled memory compartment? And how many different pathogens should the immune system remember? In this study, we examine how memory traits evolve as a response to different pathogen environments using an individual-based model. We find that even without a cost related to the maintenance of a memory pool, the positive effect of bigger memory pool sizes saturates. The optimal diversity of a limited memory pool is determined by the probability of re-infection, rather than by the prevalence of a pathogen in the environment, or the frequency of exposure. Relating immune memory traits to the pathogen environment of the hosts, our population biological framework sheds light on the evolutionary determinants of immune memory.


Automated syndromic surveillance for the 2002 Winter Olympics.
The 2002 Olympic Winter Games were held in Utah from February 8 to March 16, 2002. Following the terrorist attacks on September 11, 2001, and the anthrax release in October 2001, the need for bioterrorism surveillance during the Games was paramount. A team of informaticists and public health specialists from Utah and Pittsburgh implemented the Real-time Outbreak and Disease Surveillance (RODS) system in Utah for the Games in just seven weeks. The strategies and challenges of implementing such a system in such a short time are discussed. The motivation and cooperation inspired by the 2002 Olympic Winter Games were a powerful driver in overcoming the organizational issues. Over 114,000 acute care encounters were monitored between February 8 and March 31, 2002. No outbreaks of public health significance were detected. The system was implemented successfully and operational for the 2002 Olympic Winter Games and remains operational today.


Urinary tract infection attributed to Escherichia coli isolated from participants attending an unorganized gathering.
Participants in an unorganized gathering are potential hosts of diseases, bringing diseases from around the world to be introduced to a large at-risk population. Therefore, we investigated the gene repertoire in 29 Escherichia coli strains linked to urinary tract infection isolated from patients transferred to the hospital after attending an unorganized gathering in Cairo. Virulence and resistance determinants, phenotypic antibiotic resistance, biofilm formation, their serotypes and phylogenetic relationships were analyzed. The 29 tested serovars were phenotypically virulent, with the prevalence of group B2, and resistant to tetracycline, naldixic acid, ampicillin, trimethoprim, neomycin, oxytetracycline and erythromycin encoding the iss virulent gene. A One Health approach is a must to monitor and control E. coli urinary tract infections.


[Morphological evidence of the presence of a bacillus in cell cultures of the synovial membrane from rheumatoid arthritis patients].
34 synovial membranes (SM) from 24 rheumatoid arthritis (RA) patients, and two from osteoarthrosis cases as controls, were studied by culturing the cells on elongated coverslips and Giemsa staining them. 33/34 RA-SM, a 97%, disclosed the presence of a rod-shaped bacterium and its cell wall-deficient forms (CWDB), all adhering to the cells. An external contamination as the organism origin, was ruled out. From one of the RA-SM, a Gram (-), nonfermentative bacillus was isolated, which up to now remains unidentified. This bacillus, when reinoculated onto human embryonic fibroblasts, reproduces the images shown in the rest of the RA-SM. The possibility of this bacillus being the etiological agent of RA is discussed.


Unravelling the Antibacterial Activity of Terminalia sericea Root Bark through a Metabolomic Approach.
Terminalia sericea Burch. ex. DC. (Combretaceae) is a popular remedy for the treatment of infectious diseases. It is widely prescribed by traditional healers and sold at informal markets and may be a good candidate for commercialisation. For this to be realised, a thorough phytochemical and bioactivity profile is required to identify constituents that may be associated with the antibacterial activity and hence the quality of raw materials and consumer products. The aim of this study was to explore the phytochemistry and identify the antibacterial constituents of T. sericea root bark, using a metabolomic approach. The chemical profiles and antibacterial activities of 42 root bark samples collected from three districts in the Limpopo Province, South Africa, were evaluated. Dichloromethane:methanol (1:1) extracts were analysed using ultraperformance liquid chromatography (UPLC)-mass spectrometry (MS), and chemometric models were constructed from the aligned data. The extracts were tested against Bacillus cereus (ATCC 11778), Staphylococcus epidermidis (ATCC 12223), Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 8739), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (ATCC 27853), Shigella sonnei (ATCC 9292) and Salmonella typhimurium (ATCC 14028), using the minimum inhibition microdilution assay. Nine compounds; sericic acid, sericoside, resveratrol-3-O-β-rutinoside, ellagic acid, flavogallonic acid dilactone, methyl-flavogallonate, quercetin-3-(2''-galloylrhamnoside), resveratrol-3-(6''-galloyl)-O-β-d-glucopyranoside and arjunetin, were isolated from the root bark. All the compounds, with the exception of sericic acid, sericoside and resveratrol-3-O-β-rutinoside, were isolated for the first time from the root bark of T. sericea. Chemometric analysis revealed clustering that was not population specific, and the presence of three groupings within the samples, characterised by sericic acid, sericoside and an unidentified compound (m/z 682/4.66 min), respectively. The crude extracts from different populations displayed varied antibacterial activities against S. typhimurium (minimum inhibitory concentrations (MICs) 0.25-1.0 mg/mL), but similar activity towards Bacillus cereus (1.0 mg/mL). Several compounds present in the root bark were highly active towards all or most of the pathogens tested, but this activity was not reflected by the chemical profiles of extracts prepared from the individual samples. Among the pure compounds tested, only flavogallonic acid dilactone and methyl-flavogallonate exhibited broad-spectrum activity. A biochemometric analysis indicated that there was no consistent association between the levels of phytochemicals and the activity of the active or non-active extracts. Although it was deduced that the major constituents of T. sericea root bark contributed to the chemotypic variation, further investigation of the interactions of compounds present in the root bark may provide antibacterial efficacies not evident when examining compounds singularly. The data reported herein will provide information that is fundamentally important for the development of quality control protocols.


Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway.
Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis). This study investigated how the stress hormone corticosterone (CORT) affects neuronal cells. The first aim is to test whether administration of CORT to hippocampal and amygdaloid cell lines induces different changes in the 5-HT receptor subtypes. The second goal is to determine whether stress induced morphological changes in these two cell lines were involved in the 5-HT receptor subtypes expression. We now show that 5-HT(7) receptor mRNA levels were significantly upregulated in HT-22 cells, but downregulated in AR-5 cells by exposure to a physiologically relevant level of CORT (50 μM) for 24 h, which was later confirmed by primary hippocampal and amygdaloid neuron cultures. Additionally, pretreatment of cells with 5-HT(7) antagonist SB-269970 or agonist LP-44 reversed CORT induced cell lesion in a dose-dependent manner. Moreover, CORT induced different changes in neurite length, number of neurites and soma size in HT-22 and AR-5 cells were also reversed by pretreatment with either SB-269970 or LP-44. The different effects of 5-HT(7) receptors on cell lines were observed in two members of the Rho family small GTPase expression: the Cdc-42 and RhoA. These observed results support the hypothesis that 5-HT may differentially modulate neuronal morphology in the hippocampus and amygdala depending on the expression levels of the 5-HT receptor subtypes during stress hormone insults.