Infectious causes of posterior uveitis and panuveitis in Thailand.
To determine the infectious causes of posterior uveitis (PU) and panuveitis (panU) in Thailand. We investigated the infectious causes of uveitis involving the posterior segment of the eye by using real-time polymerase chain reaction (PCR) for cytomegalovirus (CMV), herpes simplex virus (HSV-1, HSV-2), varicella zoster virus and Toxoplasma gondii (T. gondii) DNA in intraocular samples of 80 human immunodeficiency virus (HIV)-negative patients. Additionally, in 61 patients, we performed Goldmann-Witmer coefficient (GWC) analysis for T. gondii. Twenty-four (30 %) patients with PU and/or panU had a positive PCR result. Overall, CMV was the most frequently identified organism. While CMV was the most common cause of uveitis in the patients on immunosuppressive medications for nonocular disorders, HSV was the most common cause of posterior and panuveitis in the patients not receiving such medication. In 38 PU patients, CMV was the most common detected pathogen. In 42 panU patients, CMV and HSV-2 were the most frequently identified pathogens. Out of 61 paired samples analyzed for T. gondii by GWC analysis, only 1 revealed a positive result. There was no difference in PCR results between aqueous humor and vitreous samples. CMV was the most frequently identified infectious organism in posterior and panuveitis of HIV-1-negative Thai patients. Aqueous humor and vitreous samples showed similar diagnostic values in PCR analysis.


Allogeneic stem cell transplant in myelodysplastic syndrome-factors impacting survival.
The primary aim of this study was to evaluate survival outcomes following allo-HCT in myelodysplastic syndrome (MDS), and the secondary aim was to study variables impacting survival. This analysis describes patient characteristics, treatment, and outcomes in 125 consecutive adult patients with MDS transplanted from 2005 to 2018. The median age was 61 years, and median follow-up in patients alive at last follow-up was 29 months. The 2-year OS and RFS were 39% (95%CI 30%-48%) and 35.3% (95% CI: 27%-44%), respectively. Transfusion dependence, high-risk cytogenetics, and high serum ferritin were independent risk factors for death. The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years were 23% and 41.6%, respectively. High serum ferritin was significantly associated with NRM. There was no association between the percentage of bone marrow blasts (either at diagnosis or at pretransplant evaluation), on relapse or survival. Induction chemotherapy did not offer any survival advantage in MDS RAEB-2 patients compared to cytoreduction with azacytidine alone. Our results highlight the importance of karyotype on survival after allo-HCT and identify serum ferritin and transfusion dependence as important surrogate markers of outcome. In addition, our results demonstrate the efficacy of azacytidine for pretransplant cytoreduction.


The effect of N-2-cyano-ethylamphetamine. HCl on total lipid contents of placenta and some material and fetal tissues of the rat.
Female rats received 1.25 mg/kg body weight of N-2-cyano-ethylamphetamine. HCl (Fenproporex chlorhydrate) by oral route, once daily from the 5th to the 21st day of pregnancy, and compared to untreated pregnant rats, showed an increased total lipid content in maternal blood and fetal hearts; liver and heart have had total lipids decrease, while in placenta and fetal livers they were not observed significant differences.


Air-pollution prediction in smart city, deep learning approach.
Over the past few decades, due to human activities, industrialization, and urbanization, air pollution has become a life-threatening factor in many countries around the world. Among air pollutants, Particulate Matter with a diameter of less than 2.5 μ m ( P M 2.5 ) is a serious health problem. It causes various illnesses such as respiratory tract and cardiovascular diseases. Hence, it is necessary to accurately predict the P M 2.5 concentrations in order to prevent the citizens from the dangerous impact of air pollution beforehand. The variation of P M 2.5 depends on a variety of factors, such as meteorology and the concentration of other pollutants in urban areas. In this paper, we implemented a deep learning solution to predict the hourly forecast of P M 2.5 concentration in Beijing, China, based on CNN-LSTM, with a spatial-temporal feature by combining historical data of pollutants, meteorological data, and P M 2.5 concentration in the adjacent stations. We examined the difference in performances among Deep learning algorithms such as LSTM, Bi-LSTM, GRU, Bi-GRU, CNN, and a hybrid CNN-LSTM model. Experimental results indicate that our method "hybrid CNN-LSTM multivariate" enables more accurate predictions than all the listed traditional models and performs better in predictive performance.


Public Health and Epidemiology Informatics: Recent Research Trends Moving toward Public Health Data Science.
To introduce and summarize current research in the field of Public Health and Epidemiology Informatics. PubMed searches of 2019 literature concerning public health and epidemiology informatics were conducted and the returned references were reviewed by the two section editors to select 14 candidate best papers. These papers were then peer-reviewed by external reviewers to allow the Editorial Committee a curated selection of the best papers. Among the 835 references retrieved from PubMed, two were finally selected as best papers. The first best paper leverages satellite images and deep learning to identify remote rural communities in low-income countries; the second paper describes the development of a worldwide human disease surveillance system based on near real-time news data from the GDELT project. Internet data and electronic health records are still widely used to detect and monitor disease activity. Identifying and targeting specific audiences for public health interventions is a growing subject of interest. The ever-increasing amount of data available offers endless opportunities to develop methods and tools that could assist public health surveillance and intervention belonging to the growing field of public health Data Science. The transition from proofs of concept to real world applications and adoption by health authorities remains a difficult leap to make.


Avoiding conflict of interest. How boards can withstand close scrutiny.
Recent corporate scandals have focused attention on both for-profit and not-for-profit boards. To avoid even the appearance of impropriety, boards need to be above reproach--starting with conflict of interest.


Is endothelial dysfunction of cerebral small vessel responsible for white matter lesions after chronic cerebral hypoperfusion in rats?
Cerebral white matter (WM) lesions contribute to cognitive impairment and motor dysfunction in the elderly. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important adhesion molecules that are upregulated during endothelial activation. Data from recent studies have suggested that ICAM-1 levels are related to progression of white matter hyperintensities (WMH) on MRI. In the present study, we hypothesized that ICAM-1 and VCAM-1 are involved in the endothelial dysfunction and the subsequent WM lesions after chronic cerebral hypoperfusion. Rats underwent bilateral common carotid artery ligation. They were divided into the lipoic acid group and the saline (vehicle) group. RT-PCR and double immunofluorescence for ICAM-1, VCAM-1, endothelial cells (staining positive for von Willebrand factor, vWF), reactive astrocytes (GFAP staining) and activated microglia/macrophages/(CD11b/c staining) were analyzed at baseline and at 1, 3, 7, 14 and 28 days after hypoperfusion. The severity of the WM lesions in the corpus callosum, internal capsule, and external capsule of both hemispheres was graded by luxol fast blue staining. RT-PCR and double immunofluorescence analysis of white matter from rats that had received lipoic acid (100mg/kg/day) for 28 days exhibited markedly reduced expression of ICAM-1 and VCAM-1 over endothelial cells compared with that of rats receiving saline. In the rats treated with lipoic acid, the WM lesions after chronic cerebral hypoperfusion were significantly less severe, and the number of reactive astrocytes and activated microglia/macrophages (CD11b/c staining) were also significantly lower as compared with the saline-treated rats. These findings indicate that endothelial dysfunction plays a critical role in overexpression of ICAM-1 and VCAM-1, glial cell activation and WM lesions after chronic cerebral hypoperfusion and suggest the potential value of lipoic acid as a therapeutic tool in cerebrovascular WM lesions. Our results also provide support for endothelial activation being involved in early pathogenesis of WM lesions and suggest that therapies that stabilize the endothelium may have a role in preventing WM lesions progression.


Sirtuin4 impacts mitochondrial homeostasis in pancreatic cancer cells by reducing the stability of AlkB homolog 1 via deacetylation of the HRD1-SEL1L complex.
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a poor prognosis. As a tumor inhibitor, the specific tumor suppressor mechanism of Sirtuin4(SIRT4) in PDAC remains elusive. In this study, SIRT4 was found to inhibit PDAC by impacting mitochondrial homeostasis. SIRT4 deacetylated lysine 547 of SEL1L and increased the protein level of an E3 ubiquitin ligase HRD1. As a central member of ER-associated protein degradation (ERAD), HRD1-SEL1L complex is recently reported to regulate the mitochondria, though the mechanism is not fully delineated. Here, we found the increase in SEL1L-HRD1 complex decreased the stability of a mitochondrial protein, ALKBH1. Downregulation of ALKBH1 subsequently blocked the transcription of mitochondrial DNA-coded genes, and resulted in mitochondrial damage. Lastly, a putative SIRT4 stimulator, Entinostat, was identified, which upregulated the expression of SIRT4 and effectively inhibited pancreatic cancer in vivo and in vitro.


The adult patient, informed consent and the emergency care setting.
How much information does a practitioner of emergency care give to an adult patient of sound mind in order for that patient to make a choice? This paper examines legal and professional perspectives and the challenges for the practitioner of emergency care in the process of information giving. Autonomy and human rights are significant themes in any health care context, and this paper argues that practitioners must discharge their duty of care, and facilitate an environment in which patients are informed despite the need for timely decisions about care and treatment.


The osteogenic differentiation of human adipose-derived stem cells is regulated through the let-7i-3p/LEF1/β-catenin axis under cyclic strain.
The Wnt/β-catenin pathway is involved in the osteogenic differentiation of human adipose-derived stem cells (hASCs) under cyclic strain. Very little is known about the role of microRNAs in these events. Cells were obtained using enzyme digestion methods, and proliferation was detected using Cell Counting Kit 8. Cell cycles and immunophenotypes were detected by flow cytometry. The multilineage potential of hASCs was induced by induction media. Cyclic strain was applied to hASCs (0.5 Hz, 2 h/day, 6 days) to induce osteogenic differentiation and miRNA changes. Bioinformatic and dual-luciferase analyses confirmed lymphoid enhancer factor 1 (LEF1) as a potential target of let-7i-3p. The effect of let-7i-3p on LEF1 in hASCs transfected with a let-7i-3p mimic and inhibitor was analyzed by immunofluorescence. hASCs were transfected with a let-7i-3p mimic, inhibitor, or small interfering RNA (siRNA) against LEF1 and β-catenin. Quantitative real-time PCR (qPCR) and western blotting were performed to examine the osteogenic markers and Wnt/β-catenin pathway at the mRNA and protein levels, respectively. Immunofluorescence and western blotting were performed to confirm the activation of the Wnt/β-catenin pathway. Flow cytometry showed that 82.12% ± 5.83% of the cells were in G1 phase and 17.88% ± 2.59% of the cells were in S/G2 phase; hASCs were positive for CD29, CD90, and CD105. hASCs could have the potential for osteogenic, chondrogenic, and adipogenic differentiation. MicroRNA screening via microarray showed that let-7i-3p expression was decreased under cyclic strain. Bioinformatic and dual-luciferase analyses confirmed that LEF1 in the Wnt/β-catenin pathway was the target of let-7i-3p. Under cyclic strain, the osteogenic differentiation of hASCs was promoted by overexpression of LEF1and β-catenin and inhibited by overexpression of let-7i-3p. hASCs were transfected with let-7i-3p mimics and inhibitor. Gain- or loss-of-function analyses of let-7i-3p showed that the osteogenic differentiation of hASCs was promoted by decreased let-7i-3p expression and inhibited by increased let-7i-3p expression. Furthermore, high LEF1 expression inactivated the Wnt/β-catenin pathway in let-7i-3p-enhanced hASCs. In contrast, let-7i-3p inhibition activated the Wnt/β-catenin pathway. Let-7i-3p, acting as a negative regulator of the Wnt/β-catenin pathway by targeting LEF1, inhibits the osteogenic differentiation of hASCs under cyclic strain in vitro.


Developing a Hybrid Risk Assessment Tool for Familial Hypercholesterolemia: A Machine Learning Study of Chinese Arteriosclerotic Cardiovascular Disease Patients.
Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disorder with a high risk of premature arteriosclerotic cardiovascular disease (ASCVD). There are many alternative risk assessment tools, for example, DLCN, although their sensitivity and specificity vary among specific populations. We aimed to assess the risk discovery performance of a hybrid model consisting of existing FH risk assessment tools and machine learning (ML) methods, based on the Chinese patients with ASCVD. In total, 5,597 primary patients with ASCVD were assessed for FH risk using 11 tools. The three best performing tools were hybridized through a voting strategy. ML models were set according to hybrid results to create a hybrid FH risk assessment tool (HFHRAT). PDP and ICE were adopted to interpret black box features. After hybridizing the mDLCN, Taiwan criteria, and DLCN, the HFHRAT was taken as a stacking ensemble method (AUC_class[94.85 ± 0.47], AUC_prob[98.66 ± 0.27]). The interpretation of HFHRAT suggests that patients aged <75 years with LDL-c >4 mmol/L were more likely to be at risk of developing FH. The HFHRAT has provided a median of the three tools, which could reduce the false-negative rate associated with existing tools and prevent the development of atherosclerosis. The hybrid tool could satisfy the need for a risk assessment tool for specific populations.


Catheter drainage of symptomatic postoperative mediastinal effusion guided by computed tomography. A nonoperative approach.
Postoperative mediastinal effusion after cardiac operations is a common phenomenon and has a potential for serious complications, such as tamponade necessitating urgent drainage. Computed tomography of the chest provides excellent postoperative visualization of the mediastinum. Catheter insertion or paracentesis guided by computed tomography has been used to accomplish nonoperative drainage of symptomatic postoperative mediastinal effusion in six cases. This technique offers simplicity, safety, and cost effectiveness.


Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist.
The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. Model-independent pharmacokinetic analysis of the plasma concentration-time data showed that nalmefene was rapidly absorbed and had an elimination half-life that ranged from seven to 15 hours (mean, 10.7 hr). There was a good linear relationship (r = .97) between administered dose and total area under the curve at each dose level. Only about 4% of the dose was excreted in the urine as unchanged nalmefene, whereas up to 60% was excreted as a beta-glucuronidase/sulfatase hydrolysable conjugate(s) of nalmefene. In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.(ABSTRACT TRUNCATED AT 250 WORDS)


The mechanism of the effect of combination treatment with clomiphene and bromocriptine in patients with normoprolactinemic anovulation.
The combination treatment with bromocriptine and clomiphene citrate was applied to 11 normoprolactinemic anovulatory patients who did not respond to clomiphene citrate alone. This combination treatment restored ovulation in 8 of these patients (72.7%). Conception was observed in 2 patients (18.1%) out of 11. The patients who responded to combination treatment showed a significant increase in the serum level of estradiol in the preovulatory phase, of progesterone in the mid-luteal phase, and a significant decrease of serum prolactin. They also showed significant increase in the frequency of luteinizing hormone (LH) pulsatility on day 12 of the cycle from 1.38 +/- 0.86 to 3.75 +/- 0.83 pulses/4h. The 3 patients who did not respond to combination treatment showed no increase in the serum level of estradiol or progesterone, but showed increase in the frequency of LH pulsatility in spite of continuous anovulation. These results indicate that the combination treatment with bromocriptine and clomiphene citrate is effective for treatment of patients with normoprolactinemic anovulation who do not respond to clomiphene alone, and suggest that the mechanism of the effect of combination treatment is related to an increase in the frequency of LH pulsatility caused by bromocriptine, which in turn stimulates follicular maturation.


Characteristics of normal labour among different racial groups in Malaysia.
The characteristics of normal labour in 977 Malay, Chinese and Indian parturients were established from a retrospective study. Indian babies were found to be significantly smaller than Malay babies which were significantly smaller than Chinese babies (P less than 0-05, P less than 0-05). The mean duration of the first stage of labour taken from the time of admission to the labour ward was 3-4 hours in primiparae and 2-7 hours in multiparae. The mean durations of the second stage of labour were 23-7 minutes and 13-1 minutes respectively. Curves of mean dilatation of cervix and probit analysis at 80% revealed significant differences in the progress of normal labour in primiparae among the three racial groups. The Indian primiparae not only had a slower rate of cervical dilatation but seemed to reach the accelerated phase of dilatation later. No significant differences were noticed in the labours of multiparae.


Women in Urology Residency, 1978-2013: A Critical Look at Gender Representation in Our Specialty.
To evaluate changes over time in female representation among urology residents compared to those within other specialties. Urology match data were obtained from the American Urological Association from 1996 to 2015. Trends in match rates of male and female urology applicants were assessed. Data for gender representation among residencies were extracted from reports in the Journal of the American Medical Association from 1978 to 2013. We compared the annual percentage of women among urology residents vs residents of other specialties over time. Mean number of male vs female urology applicants per year was 285.0 ± 27.1 vs 76.5 ± 21.8 (P < .001). There was no statistically significant difference in the mean successful match rate of male vs female applicants (68.2% vs 66.6%, P = .36). From 1978 to 2013, the proportion of female residents across all specialties rose from 15.4% to 46.1%, whereas female residents in urology rose from 0.9% to 23.8%. Between 2009 and 2013, obstetrics and gynecology and orthopedics had the highest and lowest average proportion of women, respectively (80.7% and 13.5%). The largest growth occurred in urology among all other specialties (P < .001), with an 11-fold increase seen during the study period. Male and female applicants to urology residency have similar match rates. Although urology demonstrated the greatest fold-increase in proportion of women among all specialties during the study period, women have remained a minority among urology residents. Gender representation within urology is a reflection of many factors and demonstrates a need for further improvement.


Is the Acute: Chronic Workload Ratio (ACWR) Associated with Risk of Time-Loss Injury in Professional Team Sports? A Systematic Review of Methodology, Variables and Injury Risk in Practical Situations.
The acute: chronic workload ratio (ACWR) is an index of the acute workload relative to the cumulative chronic workloads. The monitoring of physical workloads using the ACWR has emerged and been hypothesized as a useful tool for coaches and athletes to optimize performance while aiming to reduce the risk of potentially preventable load-driven injuries. Our goal was to describe characteristics of the ACWR and investigate the association of the ACWR with the risk of time-loss injuries in adult elite team sport athletes. PubMed, EMBASE and grey literature databases; inception to May 2019. Longitudinal studies that assess the relationship of the ACWR and time-loss injury risk in adult professional or elite team sports. We summarized the population characteristics, workload metrics and ACWR calculation methods. For each workload metric, we plotted the risk estimates for the ACWR in isolation, or when combined with chronic workloads. Methodological quality was assessed using a modified version of the Downs and Black scale. Twenty studies comprising 2375 injuries from 1234 athletes (all males and mean age of 24 years) from different sports were included. Internal (65%) and external loads (70%) were collected in more than half of the studies and the session-rating of perceived exertion and total distance were the most commonly collected metrics. The ACWR was commonly calculated using the coupled method (95%), 1:4 weekly blocks (95%) and subsequent week injury lag (80%). There were 14 different binning methods with almost none of the studies using the same binning categories. The majority of studies suggest that athletes are at greater risk of sustaining a time-loss injury when the ACWR is higher relative to a lower or moderate ACWR. The heterogenous methodological approaches not only reflect the wide range of sports studied and the differing demands of these activities, but also limit the strength of recommendations. CRD42017067585.


Shame Mediates the Relationship Between Negative Trauma Attributions and Posttraumatic Stress Disorder (PTSD) Symptoms in a Trauma Exposed Sample.
Theoretical models of self-conscious emotions indicate that shame is elicited through internal, stable, and global causal attributions of the precipitating event. The current study aimed to investigate whether these negative attributions are related to trauma-related shame and PTSD symptom severity. A total of 658 participants aged 18 to 89 (M = 33.42; SD = 12.17) with a history of trauma exposure completed a range of self-report measures assessing trauma exposure, negative trauma-related attributions, shame, and PTSD symptoms. Higher levels of internal, stable, and global trauma-related attributions were significantly associated with shame and PTSD. Shame mediated the association between trauma-related attributions and PTSD symptom severity, even after controlling for the effects of number of trauma exposures, worst index trauma and depression. The present results suggest that negative attributions are a critical cognitive component related to shame and in turn, PTSD symptom severity. Future research should aim to replicate these findings in a clinical sample and extend these findings using prospective designs.


Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response.
Long-term immunity to Leishmania may require the continued presence of parasites, but previous attempts to create attenuated parasites that persist without causing disease have had limited success. Since Leishmania major mutants that lack lipophosphoglycan and other secreted phosphoglycans, termed lpg2-, persist indefinitely in infected mice without inducing any disease, we tested their ability to provide protection to virulent L. major challenge. In response to leishmanial Ag stimulation, cells from lpg2--infected mice produced minimal levels of IL-4 and IL-10, as well as very low levels of IFN-gamma. Nevertheless, when BALB/c mice infected with lpg2- parasites were challenged with virulent L. major they were protected from disease. Thus, these findings report on attenuated parasites that may be used to induce long-term protection against leishmaniasis and indicate that the immunity induced can be maintained in the absence of a strong Th1 response.


Difficult decisions: An interpretative phenomenological analysis study of healthcare professionals' perceptions of oxygen therapy in palliative care.
The role of oxygen therapy to palliate dyspnoea is controversial. Without a clear evidence base oxygen is commonly prescribed, sometimes to the detriment of patients. This use of oxygen appears to be an entrenched culture, the roots of which remain obscure. To explore healthcare professionals' perceptions of oxygen therapy in palliative care. Interpretative phenomenological analysis study utilising semi-structured interviews to explore beliefs and behaviours of healthcare professionals regarding palliative oxygen therapy. Data were recorded, transcribed and analysed using interpretative phenomenological analysis. A total of 34 healthcare professionals, including doctors, nurses, pharmacists and paramedics in the United Kingdom, who were involved in prescribing, or administering, oxygen therapy to palliate dyspnoea. Most healthcare professionals in this study were well informed about oxygen therapy; all recognised the role of oxygen in palliative care setting as important. The overarching theme of compassion identified sub-themes of 'comfort', 'do anything and everything' and 'family benefit'. However, the use of oxygen in the palliative care setting was not without its dilemmas, as additional sub-themes of 'controversy', 'doubt' and 'dependency' illustrated. Findings suggest that oxygen therapy in palliative care poses an on-going dilemma for healthcare professionals striving to provide optimum care. It seems patients and families often expect and welcome oxygen, but the perception of oxygen as a solution to dyspnoea can conflict with healthcare professionals' own doubt and experiences. There appears to be an emotional cost associated with this dilemma and the choices that need to be made.


'Just because we're younger doesn't mean our opinions should be any less valued': A qualitative study of youth perspectives on a Youth Advisory Council in a mental healthcare context.
Recognition of the importance of youth engagement in youth mental health and/or addiction (MHA) service design and delivery is increasing. Youth Advisory Councils embedded in MHA organizations represent one strategy that allows youth to be involved in MHA at the individual, organization and systemic levels. This level of involvement can facilitate positive outcomes for both the youth and the organization. As these councils become more common, it is important that organizations are prepared to partner with the participating youth. This study uses a descriptive qualitative approach to understand the motivations and expectations of youth with lived experience with MHA concerns who were beginning to work on a Youth Advisory Council in an MHA setting in the Greater Toronto Area. Semistructured interviews were conducted with each youth, ages 16-26, on the advisory council (N = 8) to understand their motivations, expectations and goals coming into the work. Interviews were transcribed verbatim and analysed using a reflexive thematic analysis. Analysis resulted in five overarching themes: providing opportunities for youth learning and growth, platforming youth, empowering youth, embracing youth leadership and promoting youth-driven change. The findings illustrate that these youth came into the Youth Advisory Council motivated to create positive change in the mental health system, take on leadership roles and had high expectations for organizational support. Our analyses provide insight for organizations planning and implementing Youth Advisory Councils in the MHA sector with the goal of best supporting youth in driving positive change across the system. Youth want to be provided authentic opportunities for their engagement to make a difference. MHA organizations must embrace youth leadership and move towards listening to youth experience and acting on youth recommendations to enhance service design and implementation to improve access and to better meet the needs of youth utilizing these services. This study incorporated service users, including youth ages 16-26 with lived experience of MHA concerns who served on the Youth Advisory Council at the Family Navigation Project, Sunnybrook. Youth Advisory Council members contributed to two relevant research activities: (1) youth reviewed the draft interview guide before data collection, and their feedback was prioritized in the final version and (2) youth contributed to knowledge translation through contributing to academic conference presentations.


Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder?
The authors' goal was to examine the relationship between subclinical depressive symptoms in adolescence and major depressive episodes in adulthood. An epidemiologic sample of 776 young people received psychiatric assessments in 1983, 1985, and 1992. Among adolescents not meeting criteria for major depression, the authors estimated the magnitude of the association between subclinical adolescent depressive symptoms and adult major depression. Symptoms of major depression in adolescence strongly predicted an adult episode of major depression: having depressive symptoms more than two-standard-deviations above the mean in number predicted a two-fold to three-fold greater risk for an adult major depressive episode. Symptoms of depression in adolescence strongly predict an episode of major depression in adulthood, even among adolescents without major depression.


Murine typhus in Cyprus: a 9-year survey.
Epidemiological and clinical data of 193 human cases of murine typhus in Cyprus were recorded and analysed during a 9-year period (2000-2008). The incidence rate was estimated at 24.5 cases/100,000 population/year. The incidence rate varied considerably between rural, urban and semi-urban areas, with residents in rural areas accounting for 79.3% of the total cases. Most (72.5%) of the cases occurred in late summer (July and August) and early autumn (September to October) with a peak in September. Well-established persistent endemic foci with clusters of cases were identified and characterised as 'high risk' areas. Presence of or contact with rats and fleas, presence of domestic/peridomestic animals and residence in rural areas, especially locations near the 'green line' (a narrow zone patrolled by UN forces that separates the northern and southern parts of the island), increased the possibility of murine typhus infection. The results of the current study enhance the belief that murine typhus is a serious public health problem in Cyprus.


Observations on the prevention of cleft palate in dogs by folic acid and potential relevance to humans.
Folic acid has been shown to prevent neural tube defects in humans, but its effects on other defects is unknown. In a consistent breeding programme of Boston terrier dogs started in 1974, folic acid supplementation (5 mg/day) was introduced in 1981. The frequency of cleft palate fell from 9/51 (17.6%) without folic acid to 8/191 (4.2%) after its introduction, giving a reduction of 76% (95% confidence limits 42%-90%, p = 0.003).


Immune responses to different patterns of exposure to ovalbumin in a mouse model of allergic rhinitis.
Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management.


Dexmedetomidine: a novel drug for the treatment of atrial and junctional tachyarrhythmias during the perioperative period for congenital cardiac surgery: a preliminary study.
Atrial and junctional tachyarrhythmias occur frequently during the perioperative period for congenital cardiac surgery and can be a cause of increased morbidity and mortality. These rhythm disturbances that may be well tolerated in a normal heart can cause significant hemodynamic instability in patients with congenital heart defects, particularly during the postcardiopulmonary bypass period. Management of these arrhythmias presents more of a challenge, since currently available antiarrhythmic drugs can be ineffective and poorly tolerated. In this study, we examined the possible effect of dexmedetomidine, a primarily sedative drug, on atrial and junctional tachyarrhythmias. Though some animal data have shown that it can prevent certain types of ventricular tachycardia, its therapeutic role during these types of arrhythmias has not been studied. This was a retrospective, nonrandomized, noncontrolled study. Fourteen patients admitted to the cardiac intensive care unit and who received dexmedetomidine for both, sedation/analgesia and for junctional ectopic tachycardia (JET), atrial ectopic tachycardia (AET), reentry type supraventricular tachycardia (Re-SVT), atrial flutter (AF) or junctional accelerated rhythm (JAR) were included. Dexmedetomidine was used as a primary drug or as a rescue if other antiarrhythmics had been used. Our primary end-points were (a) conversion to normal sinus rhythm (NSR) within 3 min for Re-SVT, and 2 h for all other arrhythmias or (b) heart rate (HR) reduction to improve hemodynamics; JET < or =170 bpm, AET > or =20%, AF < or =150 bpm and for JAR prevention of progression to JET. The mean age and weight were 2 +/- 3 mo and 4 +/- 1.5 kg, respectively. Most of the arrhythmias (79%) occurred during the postoperative period. Dexmedetomidine was used as a primary treatment in nine and as a rescue in five patients. Ten patients (71%) received an initial loading dose of 1.1 +/- 0.5 microg/kg. A continuous infusion, 0.9 +/- 0.3 microg x kg(-1) x h(-1) was administered in 12 patients. Thirteen patients' lungs were mechanically ventilated. Adverse effects were seen in four patients (28%). Three had hypotension that responded to fluid administration and one had a possible brief complete atrioventricular (AV) block. Nine of the 14 patients were transiently paced with atrial (seven) or AV sequential (two) pacing to improve AV synchrony. The primary outcome with rhythm and/or HR control was achieved in 13 patients (93%). JET rate decreased from 197 +/- 22 to 165 +/- 17 bpm within 67 +/- 75 min of dexmedetomidine administration. Five of these patients converted to NSR in 39 +/- 31 h and one remained in JAR. All four patients with Re-SVT had resolution of their tachyarrhythmia. Three converted to NSR and one to JAR. One patient with AET (220-270 bpm) responded well with decreasing HR to 120 bpm within 35 min and to NSR in 85 min. One patient with AF failed to respond. In two patients with JAR, neither progressed to JET and HR decreased from 158 +/- 11 to 129 +/- 1 bpm. This preliminary, observational report suggests that dexmedetomidine may have a potential therapeutic role in the acute phase of perioperative atrial and junctional tachyarrhythmias for either HR control or conversion to NSR.


Transgene delivery of plasmid DNA to smooth muscle cells and macrophages from a biostable polymer-coated stent.
Metallic stents coated with a polyurethane emulsion containing plasmid DNA were implanted in rabbit iliac arteries to evaluate transgene delivery and expression in the vessel wall. The expression of the plasmid-encoded marker genes, beta-galactosidase, luciferase and green fluorescence protein (GFP), were evaluated at 7 days after implantation. In all cases, plasmid transfer was confined to the vessel wall at the site of stent implantation, plasmid DNA was not observed in vessel segments immediately proximal or distal to the stent and dissemination of plasmid DNA to lung, liver or spleen was not observed. Expression of transgenes occurred only in vessel segments in contact with the stent and analysis of the GFP expression pattern revealed a high frequency of marker protein-positive cells occurring at or near the luminal surface. The extent of transgene expression was dependent upon the quantity of DNA loaded onto the stent and no signal was detected in vessel segments that received polymer-coated stents lacking plasmid DNA. Of significance, colocalization studies identified transgene expression not only in vascular smooth muscle cells but also in macrophages. Hence, polymer-coated stents provide a new capability for transgene delivery to immune cells that are believed to contribute to the development of in-stent restenosis.


Radiomics Features of the Spleen as Surrogates for CT-Based Lymphoma Diagnosis and Subtype Differentiation.
The spleen is often involved in malignant lymphoma, which manifests on CT as either splenomegaly or focal, hypodense lymphoma lesions. This study aimed to investigate the diagnostic value of radiomics features of the spleen in classifying malignant lymphoma against non-lymphoma as well as the determination of malignant lymphoma subtypes in the case of disease presence-in particular Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), and follicular lymphoma (FL). Spleen segmentations of 326 patients (139 female, median age 54.1 +/- 18.7 years) were generated and 1317 radiomics features per patient were extracted. For subtype classification, we created four different binary differentiation tasks and addressed them with a Random Forest classifier using 10-fold cross-validation. To detect the most relevant features, permutation importance was analyzed. Classifier results using all features were: malignant lymphoma vs. non-lymphoma AUC = 0.86 (p < 0.01); HL vs. NHL AUC = 0.75 (p < 0.01); DLBCL vs. other NHL AUC = 0.65 (p < 0.01); MCL vs. FL AUC = 0.67 (p < 0.01). Classifying malignant lymphoma vs. non-lymphoma was also possible using only shape features AUC = 0.77 (p < 0.01), with the most important feature being sphericity. Based on only shape features, a significant AUC could be achieved for all tasks, however, best results were achieved combining shape and textural features. This study demonstrates the value of splenic imaging and radiomic analysis in the diagnostic process in malignant lymphoma detection and subtype classification.


A symbiosis between cellular automata and dynamic weighted multigraph with application on virus spread modeling.
The pattern of coronavirus spread at different geographical scales verifies that travel or shipment by air, sea or road are potential to transmit viruses from one location to somewhere far away in a very short time. Simulation and analysis of such a situation requires the development of models that support long distance transmission of viruses. Cellular Automata (CA) are a family of spatiotemporal computational models frequently employed in analysis of biomedical systems. A CA consists of a topological combination of units called cells as well as a transition function that propagates the configuration of cells locally and step by step. In this paper, we first present some patterns that show the local interaction between CA cells is not sufficient for virus spread modeling, especially at large spatial scales. Then, we generalize the concept of CA by providing a symbiosis between the neighborhood relationship of cells and the transmission channels represented by a dynamic weighted multigraph. Furthermore, we characterize the capabilities of the proposed modeling tool in simulation of the virus spread, and estimating the risk control during the movement restrictions and related health protocols. Finally, we simulate the coronavirus outbreak in the five study areas including three states and two countries. Our experiments using the proposed model verify that the proposed model is capable of formulating different ways of virus transmission, including long-distance transmission, and supports high-precision simulation of the pandemic.


Lectin staining and Western blot data showing differential sialylation of nutrient-deprived cancer cells to sialic acid supplementation.
This report provides data that are specifically related to the differential sialylation of nutrient deprived breast cancer cells to sialic acid supplementation in support of the research article entitled, "Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation" [1]. Particularly, breast cancer cells, when supplemented with sialic acid under nutrient deprivation, display sialylated glycans at the cell surface, but non-malignant mammary cells show sialylated glycans intracellularly. The impact of sialic acid supplementation under nutrient deprivation was demonstrated by measuring levels of expression and sialylation of two markers, EGFR1 and MUC1. This Data in Brief article complements the main manuscript by providing detailed instructions and representative results for cell-level imaging and Western blot analyses of changes in sialylation during nutrient deprivation and sialic acid supplementation. These methods can be readily generalized for the study of many types of glycosylation and various glycoprotein markers through the appropriate selection of fluorescently-labeled lectins.


Enhanced results in mouse and human embryo culture using a modified human tubal fluid medium lacking glucose and phosphate.
Because various recent studies in both human and laboratory animals have indicated an influential role of glucose and phosphate in embryonic development, this study was initiated to assess the effect of culture medium lacking glucose and phosphate on human IVF. Initial studies with mouse zygotes indicated a significant improvement in embryonic development in both a F1 hybrid and a random-bred "two-cell block" strain, using a modified HTF medium which contained EDTA and glutamine (Gln) and also with a similar medium which lacked glucose and phosphate. Subsequently, a prospective randomized trial of human IVF has begun in which infertile patients are sequentially assigned to have IVF using one of three media. The three media are regular HTF, HTF containing EDTA and Gln (referred to as Basal HTF), and HTF with EDTA and Gln but devoid of glucose and phosphate ions (referred to as Basal XI HTF). Initial results indicate that Basal XI HTF medium, a modified form of HTF containing EDTA and glutamine but devoid of glucose and phosphate, greatly improves the in vitro development of mouse and human embryos over HTF and Basal HTF medium.


Activation/suppression of the immune response in vitro by antigen and dextran sulfate. 2. The role of T-cell subsets determined by cell separation and partition analysis.
Culture of spleen cells with dextran sulfate (DxS) and antigen at various different cell densities revealed a T-cell-dependent regulatory pathway not observed in conventional culture. This finding can be explained by the frequent presence in the cultures of a helper cell and the less frequent presence of a suppressor cell, both activated by antigen and DxS. The classic, radioresistant, antigen-specific, helper T cell was not regulated by this newly revealed pathway. The highly frequent, DxS-dependent helper T cell is Lyt-1+2-. The suppressive effect is mediated by a Lyt-1+2+ population consisting of helpers and latent suppressors that can be made active by DxS or Lyt-1+ cells. The specificity of the Lyt-1+ helper cells was not established, but the high frequency observed implies a nonspecific mechanism. The specificity of the suppressor effect was not determined by these experiments. This regulatory mechanism is similar to the phenomena exhibited by polyclonally activated T-cell populations.


Purification and characterization of 6-phosphogluconate dehydrogenase from the wing-polymorphic cricket, Gryllus firmus, and assessment of causes of morph-differences in enzyme activity.
Considerable information exists on the physiological correlates of life history adaptation, while molecular data on this topic are rapidly accumulating. However, much less is known about the enzymological basis of life history adaptation in outbred populations. In the present study, we compared developmental profiles of fat body specific activity, kinetic constants of homogeneously purified and unpurified enzyme, and fat body enzyme concentration of the pentose-shunt enzyme, 6-phosphogluconate dehydrogenase (6PGDH, E.C.126.96.36.199) between the dispersing [long-winged, LW(f)] and flightless [short-winged, SW] genotypes of the cricket Gryllus firmus. Neither kcat nor the Michaelis constant for 6-phosphogluconate differed between 6PGDH from LW(f) versus SW morphs for either homogeneously purified or unpurified enzyme. Purified enzyme from the LW(f) morph exhibited reduced KM for NADP(+), but this was not observed for multiple KM(NADP+) estimates for unpurified enzyme. A polyclonal antibody was generated against 6PGDH which was used to develop a chemiluminescence assay to quantify 6PGDH concentration in fat body homogenates. Elevated enzyme concentration accounted for all of the elevated 6PGDH specific activity in the LW(f) morph during the juvenile and adult stages. Finally, activity of another pentose-shunt enzyme, glucose-6-phosphate dehydrogenase, strongly covaried with 6PGDH activity suggesting that variation in 6PGDH activity gives rise to variation in pentose shunt flux. This is one of the first life-history studies and one of the few studies of intraspecific enzyme adaptation to identify the relative importance of evolutionary change in enzyme concentration vs. kinetic constants to adaptive variation in enzyme activity in an outbred population.


Adaptation of cerebral circulation to brain arteriovenous malformations increases feeding artery pressure and decreases regional hypotension.
To determine how the adaptation of extranidal cerebral vessels affects feeding artery pressure, draining vein pressure, and regional hypotension due to the presence of brain arteriovenous malformations (BAVMs). BAVMs cause high flows in feeding arteries and draining veins and can induce profound hypotension in the neighboring vasculature. Despite the large difference in flow, endothelial shear stress (tau) observed in vessels ipsilateral to the BAVM is similar to tau in vessels contralateral to the BAVM, suggesting that the conductance vessels successfully adapt to keep tau constant. However, because BAVMs are discovered only after they are well developed, the natural history of the adaptation process in extranidal vessels is unknown. Currently, no way exists to determine experimentally the effects of adaptation of extranidal vessels in human patients. Therefore, a mathematical model of the cerebral vasculature is used to study adaptation in response to BAVMs. By comparing pressures and flows calculated before and after adaptation, the effect of adaptation of the conductance vessels on regional hemodynamics can be evaluated. Structural adaptation of the extranidal circulation seems not only to reset tau, but also to ameliorate regional hypotension induced by BAVMs. However, this compensatory mechanism also increases feeding artery pressure and thus may increase the risk of hemorrhagic stroke.


Risk factors for L. monocytogenes contamination of dairy products in Switzerland, 1990-1999.
Our purpose was to identify the main hazards associated with the spread of Listeria monocytogenes in dairy products in Switzerland and to determine the changes in predominant serotypes of the isolates, using databases on dairy-processing and environments from the Swiss Dairy Research Station during the years 1990-1999. Overall, of 76,271 samples collected, 3722 (4.9%) were positive for the presence of L. monocytogenes. Cheese-ripening facilities had the highest proportion of positive samples (7.6%), followed by small-scale local dairies (4.4%). By sample type, the highest proportion of positive samples (9.5%) was observed in water samples used for cheese-washing, followed by cheese-surface swabs (5.0%). During the 10-year period, no positive samples were obtained from cream, ice cream, milk powder, yogurt, or fresh cheese. Of 3722 L. monocytogenes isolates, 1328 (35.7%) were serologically typeable. Serotypes 1/2a, 1/2b, and 4b accounted for 92.7% of the 1328 isolates. Until 1995, the most-prevalent serotype was 1/2b (annual proportional prevalence 39.3-72.2%)--whereas since 1996, 1/2a was the most prevalent (34.7-54.7%). During 1996-1999, serotype 1/2a increased by 88%, compared to the average of 1990-1995. In the final random-effect multivariable logistic model, the strongest predictor of a positive culture was samples from cheese-ripening plant (OR=1.54; 95% CI: 1.14, 2.08) and the second-strongest predictor was samples collected by someone who was employed by the plant (OR=1.48; 1.29, 1.71). Hard and semi-hard cheeses were more likely to be associated with serotype 1/2b and soft cheeses with serotype 1/2a.


Pharmacokinetics and pharmacodynamics of intravenously administered anesthetic drugs: concepts and lessons for drug development.
The drugs used in the clinical practice of anesthesiology, specifically the intravenously administered compounds that create the hypnotic aspect (unconsciousness) and the analgesic aspect (opiates) of an anesthetic, provide important insights into principles that can be applied to drug development in general. Additionally, research involving these drugs and their therapeutic applications has advanced some of the fundamental principles of pharmacokinetic (PK) and pharmacodynamic (PD) modeling. This article reviews several examples of anesthetic drugs used in clinical pharmacology and points out how they provide insights into methods of applying these modeling concepts to modern drug development in general.


Effect of calcium restriction on renal excretion of oxalate and the probability of stones in the various pathophysiological groups with calcium stones.
To evaluate the adequacy of simple calcium restriction for patients with idiopathic calcium stones the effect of 5 days of calcium restriction without oxalate restriction on renal excretion of calcium and oxalate, and the corresponding probability of stones were assessed in 50 controls and 48 patients. Renal excretion of calcium decreased and that of oxalate increased significantly in all groups but the importance of the changes was critically dependent upon the underlying pathophysiological condition. The probability of stones decreased only in patients with absorptive hypercalciuria type II owing to the usual excessive calcium intake and increased in those with absorptive hypercalciuria type I and renal hypercalciuria, which are associated with true hyperabsorption of calcium and represent the 2 forms of idiopathic hypercalciuria. We believe that simple calcium restriction is beneficial for patients with idiopathic calculi only when the hypercalciuria is caused by exaggerated intake of calcium, since it increases the probability of stones in patients with idiopathic hypercalciuria. Calcium restriction always is associated with an increase in oxalate excretion, suggesting that simultaneous oxalate restriction should be added in all cases to decrease the probability of stones.


Serum lipid and lipoprotein abnormalities in major clinical entities of renal disease.
More than half of the patients with glomerulonephritis, nephrotic syndrome and renovascular hypertension showed obviously abnormal profiles of serum lipoproteins (Lps). The abnormal profiles returned to normal or near-normal when the disease was ameliorated or corrected surgically. A unique Lp profile (broad midband pattern, BMP) was observed in approximately 89% of uremic patients on hemodialysis therapy. The results of the current investigations indicated that the BMP could probably be formed by the accumulation of catabolic remnants of VLDL.


Cognitive and contextual influences in determination of latent fingerprint suitability for identification judgments.
We examined forensic fingerprint examiners' suitability determinations of latent fingerprints comparing situations in which the latent is assessed solo (in isolation) versus situations in which it is presented alongside a comparison (matching or non-matching) exemplar print. The presence of a non-matching comparison exemplar led examiners to be more inclined to draw the conclusion that the latent was suitable for comparison compared to when the latent was presented solo. This effect persisted even when the latent presented was highly unsuitable for comparison. The presence of a matching comparison exemplar led examiners to be less likely to decide that the latent was suitable and more likely to decide the latent was questionable compared to solo analysis. This effect persisted even when the latent presented was highly suitable, suggesting a strong main effect. Knowledge of another examiner's previous determination that the latent was unsuitable was found to increase the likelihood that the examiner would conclude that the latent was unsuitable. However, knowledge of a previous "suitable" determination by another examiner did not increase the likelihood of a "suitable" conclusion by examiners. The finding that effects were weaker, although not entirely removed, in those with IAI certification suggests that training may be an appropriate route for reducing the effect of contextual influence and bias in suitability determinations. It was also shown that latent prints that were previously classed as "unsuitable" in a non-biasing context, continued to be judged to be "unsuitable" in a strongly biasing context (a major case in which a previous examiner was purported to have made an Individualization).


Heterogeneous Fenton degradation of persistent organic pollutants using natural chalcopyrite: effect of water matrix and catalytic mechanism.
Natural chalcopyrite was evaluated as heterogeneous Fenton catalyst. Catalytic performance was evaluated considering different systems, catalyst dosage, H2O2 concentration, and reaction temperature, and increasing the parameters favors rhodamine B degradation. Effect of aqueous matrix was systematically examined, involving solution pH, anions, cations, dissolved organic matter, and initial pollutant concentration. The degradation performance is slightly influenced by these parameters. Rhodamine B removal is 96.5% within 120 min, the rate constant ranges from 0.0086 min-1 to 0.0415 min-1 depending on temperature, and the activation energy is 79 kJ/mol. Effective degradation of different persistent organic pollutants including methylene blue, malachite green, sodium butyl xanthate, tetracycline, and p-nitrophenol is verified by UV-vis spectra. Natural chalcopyrite was characterized by advanced techniques including scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Reactions between chalcopyrite and H2O2 cause copper leaching and iron oxidation. Quenching experiments and electron paramagnetic resonance reveal the dominant role of hydroxyl radical in catalytic process. The catalytic mechanism induced by surface iron and leached copper derived from chalcopyrite is proposed.


Allergenicity and antigenicity of fenugreek (Trigonella foenum-graecum) proteins in foods.
Fenugreek is an ingredient in Indian-style spiced foods. Reports of adverse reactions reflect a trend toward a more international cuisine. Fenugreek allergy has not been systematically investigated so far. Study the allergenicity and antigenicity of fenugreek proteins using patient sera and a newly developed polyclonal antifenugreek antibody. Allergenic fenugreek proteins were identified by immunoblotting, using sera from 29 patients with specific IgE to peanut and other legumes. In addition, 2 patients were evaluated by skin prick test and open food challenge with native fenugreek powder. Spiced and flavored food products were analyzed for fenugreek by semiquantitative IgE and IgG immunoblotting. High levels of specific IgE to both peanut and fenugreek were seen in most sera. Fenugreek sensitization is believed to be a consequence of cross-reactivity in patients with peanut allergy. Primary fenugreek allergy was suspected in only 1 case. The fenugreek dose eliciting objective symptoms was about 2 mg in the open food challenge. Major fenugreek allergens were identified at 50, 52, and 74 kd and peanut proteins at 22, 36, and 40 kd. A specific polyclonal antifenugreek antibody was found suitable for food analysis. In a food survey, about 1/3 of the fenugreek-containing products were labeled correctly. Fenugreek seed powder, an ingredient in spiced foods, contains several potential allergens. There is evidence for a high rate of cross-reactivity to peanut.


Renal Cell Carcinoma: Delayed Metachronous Metastases to Parotid and Cerebellum.
The purpose of this report is to describe a rare case of delayed metachronous isolated metastases of renal cell carcinoma (RCC) to the parotid gland and the cerebellum. The metastases occurred more than a decade after treatment of the primary tumor without any other systemic involvement. In addition, the potential differential diagnosis of the parotid mass based on presentation and imaging is discussed. An 83-year-old man presented for evaluation and treatment of a rapidly growing mass at the right parotid region. He had a history of RCC resection 10 years before this presentation and had no evidence of persistent disease at the primary site. The diagnosis of metastatic RCC was made after fine-needle aspiration biopsy examination of the mass. The patient underwent superficial parotidectomy for resection of the tumor. Approximately 1.5 years later, he complained of loss of balance. Further investigation disclosed a cerebellar mass that at biopsy examination was found to represent RCC. He underwent stereotactic ablation of the mass. He currently remains free of disease at the primary site and the parotid and without further known brain metastases. This report presents the 29th case of a solitary parotid mass consistent with metastatic RCC 10 years after successful treatment of the primary RCC. Approximately 1.5 years later, the patient presented with new-onset loss of balance. Further investigation disclosed a mass to the cerebellum consistent with metastatic RCC. This case is unique because the brain involvement occurred extremely late, 11.5 years after successful treatment of primary RCC and 1.5 years after resection of a metastatic RCC to the parotid, and without any evidence of other metastases. Late distant metastases of RCC are not uncommon and patients require life surveillance follow-up, but such late presentation of metachronous metastases without systemic disease progression is unique. The patterns of metastases of RCC are not clearly defined and this diagnosis should be considered, especially in patients with relevant history.


Cost-effectiveness of inhaled corticosteroids for chronic obstructive pulmonary disease according to disease severity.
Inhaled corticosteroids reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), but their cost-effectiveness is not known. We used a Markov model to determine, from a societal perspective, the cost-effectiveness of four treatment strategies involving inhaled corticosteroids: no use regardless of COPD severity; use in all disease stages; use in patients with stage 2 or 3 disease (forced expiratory volume in 1 second [FEV(1)] <50% of predicted); and use in patients with stage 3 disease (FEV(1) <35% of predicted). Data from the literature were used to estimate mortality, exacerbation, and disease progression rates, as well as the costs associated with care and quality-adjusted life-years (QALYs), according to disease stage and use or nonuse of inhaled corticosteroids. A time horizon of 3 years was used. Use of inhaled corticosteroids in patients with stage 2 or 3 disease was associated with a cost of 17,000 dollars per QALY gained. In stage 3 patients, use resulted in a cost of 11,100 dollars per QALY gained. Providing inhaled corticosteroids to all COPD patients was associated with a less favorable cost-effectiveness ratio. Results were robust to various assumptions in a Monte Carlo simulation. In patients with COPD, use of inhaled corticosteroids in those with stage 2 or 3 disease for 3 years results in improved quality-adjusted life expectancy at a cost that is similar to that of other therapies commonly used in clinical practice.


The core episodic simulation network dissociates as a function of subjective experience and objective content.
Episodic simulation - the mental construction of a possible future event - has been consistently associated with enhanced activity in a set of neural regions referred to as the core network. In the current functional neuroimaging study, we assessed whether members of the core network are differentially associated with the subjective experience of future events (i.e., vividness) versus the objective content comprising those events (i.e., the amount of episodic details). During scanning, participants imagined future events in response to object cues. On each trial, participants rated the subjective vividness associated with each future event. Participants completed a post-scan interview where they viewed each object cue from the scanner and verbally reported whatever they had thought about. For imagined events, we quantified the number of episodic or internal details in accordance with the Autobiographical Interview (i.e., who, what, when, and where details of each central event). To test whether core network regions are differentially associated with subjective experience or objective episodic content, imagined future events were sorted as a function of their rated vividness or the amount of episodic detail. Univariate analyses revealed that some regions of the core network were uniquely sensitive to the vividness of imagined future events, including the hippocampus (i.e., high > low vividness), whereas other regions, such as the lateral parietal cortex, were sensitive to the amount of episodic detail in the event (i.e., high > low episodic details). The present results indicate that members of the core network support distinct episodic simulation-related processes.


Rare case of atypical epitelioid hemangioma of penis initially misdiagnosed as Peyronie's disease: report with clinical, radiologic, and immunohistochemical analysis.
We report a rare case of atypical epithelioid hemangioma of the penis in a 42-year-old man with a painful penile dorsal nodule, first misdiagnosed on simple penile ultrasonography as Peyronie's disease. Even though the patient underwent treatment, the lesion improved and a penile echo-color Doppler scan showed abundant vascularization. After local excision, the pathologic diagnosis was atypical epithelioid hemangioma (central epithelioid cells bordered by immature vessels), with immunohistochemical positivity for CD31 and CD34 and negativity for epithelial membrane antigen. At 12 months after surgery, the patient was free of disease. Penile echo-color Doppler ultrasonography is essential to perform a differential diagnosis between Peyronie's disease from other penile nodular diseases.


[HAIR STRAIGHTENING - NOT STRAIGHTFORWARD].
The rising popularity of hair straightening in younger ages has become a medical issue, since glycolic acid and formaldehyde may be present, even in "formaldehyde-free" labeled products. Formaldehyde - a colorless material, evaporates during the hair straightening procedure, inhaled and absorbed into the blood stream causing oxidative stress and cytotoxic damage to the proximal tubule cells leading to acute kidney injury (AKI). Glycolic acid is processed to glyoxylate and eventually to oxalate, whose deposition may also cause AKI. We present three cases of female teenagers with AKI, recently after a hair straightening procedures. All patients had features of tubular damage and kidney biopsies in the first 2 cases showed acute tubular necrosis (ATN), one with oxalate deposition and the other with unidentified depositions. Two cases required acute dialysis, and shortly after commencing it, kidney function rapidly improved. We believe that in the presented cases, the prompt dialysis cleared a nephrotoxic ingredient, allowing improvement of renal function, therefore preventing long-standing and maybe, even permanent damage. This case presentation highlights the danger of hair straightening products in pediatric populations aiming to increase its index of suspicion among adult and pediatric nephrologists.


Medicare Diabetes Prevention: Enrollment Short Of Projections.
After years of research, Medicare agreed to pay for diabetes prevention programming, but few beneficiaries and providers have enrolled.


Repurposing miconazole and tamoxifen for the treatment of Mycobacterium abscessus complex infections through in silico chemogenomics approach.
Drug repositioning is an alternative to overcome the complexity of the drug discovery and approval procedures for the treatment of Mycobacterium abscessus Complex (MABSC) infections that are increasing globally due to the emergency of antimicrobial resistance mechanisms. Here, an in silico chemogenomics approach was performed to compare the sequences from 4942 M. abscessus subsp. abscessus (M. abscessus) proteins with 5258 or 3473 therapeutic targets registered in the DrugBank or Therapeutic Target Database, respectively. This comparison identified 446 drugs or drug candidates whose targets were homologous to M. abscessus proteins. These identified drugs were considered potential inhibitors of MABSC (anti-MABSC activity). Further screening and inspection resulted in the selection of ezetimibe, furosemide, itraconazole, miconazole (MCZ), tamoxifen (TAM), and thiabendazole (THI) for experimental validation. Among them, MCZ and TAM showed minimum inhibitory concentrations (MIC) of 32 and 24 µg mL-1 against M. abscessus, respectively. For M. bolletii and M. massiliense strains, MCZ and TAM showed MICs of 16 and 24 µg mL-1, in this order. Subsequently, the antibacterial activity of MCZ was confirmed in vivo, indicating its potential to reduce the bacterial load in the lungs of infected mice. These results show that MCZ and TAM can serve as molecular scaffolds for the prospective hit-2-lead optimization of new analogs with greater potency, selectivity, and permeability.


A 3D-geometric model for the deformation of a transversally loaded muscle.
Very recent measurements provided data on the ratio between the change in length of the active fibres and the lifting height of a mass compressing the muscle belly transversally to the direction of fibre contraction. In this study, we present additional data of the change in the third (unloaded) muscle dimension, extracted from the same contraction experiments. Using this data set for validation, we verify whether body models of two different geometries, cylindrical or ellipsoidal, can explain the three-dimensional deformation of a contracting muscle, when volume constancy is required as a constraint. Presetting the contractile length change and using this constraint, an additional equation is needed for model predictions. To that, we minimise the sum of the squared and weighted circumference length changes. With a specific set of the three penalty weights, it turns out that the ellipsoid model can explain the three-dimensional deformation. The set of penalty weights can also be interpreted as an anisotropic stiffness distribution of the connective tissue of the muscle belly. In various loading situations, our ellipsoidal model may help to predict the corresponding deformation scenarios or to calculate the stiffness distribution from measured load and deformation data.


Anxiety, mood, and substance use disorders in adult men and women with and without attention-deficit/hyperactivity disorder: A substantive and methodological overview.
Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n > 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n = 550,748; no ADHD n = 14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for ADs, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.


Analysis of acenocoumarin and its amino and acetamido metabolites in body fluids by high-performance liquid chromatography.
Acenocoumarin and its acetamido metabolite, after extraction at pH 4.4, were analysed by isocratic reversed-phase high-performance liquid chromatography using aqueous acetonitrile (pH 4.90) as eluent. Warfarin was used as internal standard. The amino metabolite, after back-extraction into 0.5 N HCl, was derivatized by diazotization and heat treatment. The resulting product was analysed by the same reversed-phase system. The sensitivity of the method for acenocoumarin and its amino metabolite was in the range of 20 ng/ml. To achieve this sensitivity for the analysis of the acetamido compound, the acetonitrile content of the eluent had to be lowered. The assay was applied to the analysis of plasma samples of patients under acenocoumarin therapy. The disposition of the amino compound in rats was investigated.


MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis.
Translation inhibition is a major but poorly understood mode of action of microRNAs (miRNAs) in plants and animals. In particular, the subcellular location where this process takes place is unknown. Here, we show that the translation inhibition, but not the mRNA cleavage activity, of Arabidopsis miRNAs requires ALTERED MERISTEM PROGRAM1 (AMP1). AMP1 encodes an integral membrane protein associated with endoplasmic reticulum (ER) and ARGONAUTE1, the miRNA effector and a peripheral ER membrane protein. Large differences in polysome association of miRNA target RNAs are found between wild-type and the amp1 mutant for membrane-bound, but not total, polysomes. This, together with AMP1-independent recruitment of miRNA target transcripts to membrane fractions, shows that miRNAs inhibit the translation of target RNAs on the ER. This study demonstrates that translation inhibition is an important activity of plant miRNAs, reveals the subcellular location of this activity, and uncovers a previously unknown function of the ER.


Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.
Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.


α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.
A series of α-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an α-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with Ki(CAP)=0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor.


Enkephalin binding systems in human plasma. III: Comparative protection of different peptides.
We have investigated the hydrolysis and protection from hydrolysis of several peptides by plasma enzymes and by the plasma components previously described as inhibitors of enkephalins' hydrolysis. The results shown indicate that all the peptides actually hydrolyzed are also partially protected from hydrolysis by the enkephalin-protecting substances. Protection is fairly uniform for all the peptides tested, but considerably higher in the case of leu- and met-enkephalin, suggesting a partial specificity of the protecting substances towards opioid peptides.


Management of Hypertension in Primary Care Safety-Net Clinics in the United States: A Comparison of Community Health Centers and Private Physicians' Offices.
To examine adherence to guideline-concordant hypertension treatment practices at community health centers (CHCs) compared with private physicians' offices. National Ambulatory Medical Care Survey from 2006 to 2010. We examined four guideline-concordant treatment practices: initiation of a new medication for uncontrolled hypertension, use of fixed-dose combination drugs for patients on multiple antihypertensive medications, use of thiazide diuretics among patients with uncontrolled hypertension on ≥3 antihypertensive medications, and use of aldosterone antagonist for resistant hypertension, comparing use at CHC with private physicians' offices overall and by payer group. We identified visits of nonpregnant adults with hypertension at CHCs and private physicians' offices. Medicaid patients at CHCs were as likely as privately insured individuals to receive a new medication for uncontrolled hypertension (AOR 1.0, 95 percent CI: 0.6-1.9), whereas Medicaid patients at private physicians' offices were less likely to receive a new medication (AOR 0.3, 95 percent CI: 0.1-0.6). Use of fixed-dose combination drugs was lower at CHCs (AOR 0.6, 95 percent CI: 0.4-0.9). Thiazide use for patients was similar in both settings (AOR 0.8, 95 percent CI: 0.4-1.7). Use of aldosterone antagonists was too rare (2.1 percent at CHCs and 1.5 percent at private clinics) to allow for statistically reliable comparisons. Increasing physician use of fixed-dose combination drugs may be particularly helpful in improving hypertension control at CHCs where there are higher rates of uncontrolled hypertension.


Implantation and Extraction of Penetrating Electrode Arrays in Minipig Retinas.
This work was motivated by the goals of demonstrating methods to fabricate and implant large numbers of penetrating arrays into the retina and the feasibility of extraction. Arrays of inactive, three-dimensional (3D) SU-8 structures were microfabricated onto 13-µm polyimide substrates. Standard vitreoretinal surgical techniques were used with an ab externo approach for subretinal implantation of arrays in 12 mini-pigs. In the first three surgeries, different post-geometries were explored, while a preferred design (128-µm tall, 30-µm diameter, 200-µm spacing) was used for the remaining nine implantations. Two arrays were extracted. Funduscopy, optical coherence tomography (OCT) and immunohistochemistry of the retinae were performed. The unoperated eyes and tissue far from implantation served as controls. A thirteenth pig was implanted with a planar array. Ten implant surgeries had no significant complication, and two arrays were successfully extracted. One retinal tear occurred after implantation due to too long posts in an early surgery. In "successful" cases, OCT showed close apposition of the arrays to the retina and integration of the posts, the tops of which were positioned at the junction of the inner plexiform and ganglion cells, without significant gliosis. These results provide a proof-of-concept that relatively large numbers of 3D posts can be implanted into, and extracted from, the retina of mini-pigs. Our surgical numbers were relatively small, especially for the extractions, and our conclusions must be viewed with that limitation. Our methods are applicable for human surgeries. This study provides results of implantation and extraction of relatively large numbers of 3D posts from the retina of minipig eyes. If similar technology were used in humans, a 3D array of this type should lower perceptual thresholds, provide safer long-term stimulation, and perhaps provide better perceptual outcomes.


Can inpatient multidisciplinary rehabilitation improve health-related quality of life in MS patients on the long term - The Danish MS Hospitals Rehabilitation Study.
Inpatient multidisciplinary rehabilitation (MDR) can improve health-related quality of life (HRQoL) in multiple sclerosis (MS) patients. However, the evidence of a long-term benefit is limited. To investigate the long-term effectiveness of inpatient MDR on HRQoL in MS patients. We conducted a randomized controlled partial crossover trial with 427 MS patients. Statistical significant long-term improvements in HRQoL were found in three of the six outcome measures at 12-month follow-up. Three in four suggested minimal clinically important differences (MCIDs) were unmet. These results indicate that the administration of inpatient MDR may lead to long-lasting improvements in HRQoL in MS patients.


Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex.
To assess intellectual outcomes in a clinic-based population of patients with tuberous sclerosis complex (TSC) who also have a history of infantile spasms (IS) and to identify clinical risk factors for mental retardation in these patients. This is a retrospective study of 50 patients with TSC and IS seen consecutively at the Massachusetts General Hospital Tuberous Sclerosis Comprehensive Clinic from December 2001 to October 2003. Data were obtained by chart review and by interview with patients' parents. Thirty-two (64%) of 50 patients with TSC with IS were found to have mental retardation (IQ or developmental quotient < 70). Three clinical variables showed an association with mental retardation: increased duration of IS from clinical onset to cessation (odds ratio [OR] per 1-month interval 1.09, 95% CI: 1.03 to 1.15, p = 0.004), increased time from treatment initiation until IS cessation (OR 1.07, 95% CI: 1.01 to 1.14, p = 0.020), and poor control of other seizures after IS (OR 17.76, 95% CI: 3.47 to 129.1, p = 0.00004). The following variables did not show an association with intellectual outcome: gender, initial seizure type, age at IS onset, or time from IS onset to treatment initiation. In patients with tuberous sclerosis complex who also have a history of infantile spasms (IS), the rate of mental retardation may be lower than previously reported. The risk of mental retardation increases significantly with prolonged duration of IS, prolonged time from treatment initiation until the cessation of IS, and poor control of subsequent seizures after IS.


High prevalence of abdominal aortic aneurysm in men with peripheral vascular disease: screening by ultrasonography.
A study was carried out to see if an ultrasonic examination of the abdominal aorta was indicated in every patient who attended an outpatient clinic with peripheral vascular disease (PVD). One hundred consecutive patients were studied and compared with a control group. The incidence of abdominal aortic aneurysm (AAA) in the control group was 2 per cent. In the study group, the male patients had an incidence of 20 per cent of aneurysm and ectasia, while the female patients had an incidence of 12 per cent. Of all the abnormal aortas found by ultrasound, only 31 per cent were palpable clinically. Two aneurysms that required operation were found, while the remainder are to be followed by regular ultrasound assessment. Further studies are necessary to conclude if screening of a high risk group, such as patients with PVD, is worthwhile.


The levels of nitric oxide in beta-thalassemia minor.
The aim of this study was to investigate the relationship between NO (nitric oxide) and beta-thalassemia minor. A total of 60 patients with beta-thalassemia minor (30 M, 30 F) were included in the study. The control group consisted of 60 healthy subjects (30 M, 30 F). Plasma nitrite/nitrate levels were measured using the Griess reaction method and analyzed by spectrophotometry at 545 nm. Plasma direct nitrite, total nitrite and nitrate levels were 7.561±6.19, 42.548±7.37 and 34.84±6.24 in beta-thalassemia minor patients versus 36.9±19.8, 85.9±35.3 and 48.61±17.35 Ìmol/dl in controls, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in beta-thalassemia minor patients compared with the control group (p<0.001). These findings confirm that plasma NO levels in beta-thalassemia minor patients are decreased at the time of diagnosis. This may be helpful in assessing the prognosis and follow-up evaluation of patients with beta-thalassemia minor.


Biotransformation of tribenoside into benzoic acid in man.
In an experiment on three healthy volunteers, plasma levels of tribenoside and the elimination of benzoic acid in plasma and urine were followed up during a 7-day period of daily oral medication with tribenoside. Plasma levels of tribenoside, and plasma and urine concentrations of free and total benzoic acid were determined quantitatively. The concentrations of alpha- and beta-tribenosides found in the plasma were very low and did not increase during treatment. Total benzoic acid in the plasma remained at almost the same level during treatment as that observed before treatment. Biotransformation of tribenoside therefore does not appear to result in any significant change in the plasma concentrations of free or total benzoic acid. The average daily excretion of total benzoic acid in the urine of the 3 subjects was greater during treatment than before. The average increases in total benzoic excretion in the 3 subjects correspond to 23.5, 11.9, and 23.7% of the theoretical amount that would be produced by the metabolic oxidation of the 3 benzyl groups. This study demonstrates that tribenoside does not accumulate in plasma. Around 20% of the administered dose is metabolized to benzoic acid, which is almost entirely present in the body as hippuric acid. Hippuric acid is excreted at such a rate that it does not accumulate in plasma and does not exceed the normal concentration range.


P53 and beta-catenin activity during estrogen treatment of osteoblasts.
This study was undertaken to examine the relationship between the tumor suppressor gene p53 and the nuclear signaling protein beta-catenin during bone differentiation. Cross talk between p53 and beta-catenin pathways has been demonstrated and is important during tumorigenesis and DNA damage, where deregulation of beta catenin activates p53. In this study, we used estrogen treatment of osteoblasts as a paradigm to study the relationship between the two proteins during osteoblast differentiation. We exposed osteoblast-like ROS17/2.8 cells to 17-beta estradiol (E2), in a short term assay, and studied the cellular distribution and expression of beta-catenin. We found beta-catenin to be up regulated several fold following E2 treatment. Levels of p53 and its functional activity mirrored the quantitative changes seen in beta-catenin. Alkaline phosphatase, an early marker of osteoblast differentiation, was increased in a manner similar to beta-catenin and p53. In order to determine if there was a direct relationship between alkaline phosphatase expression and beta-catenin, we used two different approaches. In the first approach, treatment with LiCl, which is known to activate beta-catenin, caused a several fold increase in alkaline phosphatase activity. In the second approach, transient transfection of wild type beta-catenin into osteoblasts increased alkaline phosphatase activity two fold over basal levels, showing that beta catenin expression can directly affect alkaline phosphatase expression. However increase in beta catenin activity was not associated with an increase in its signaling activity through TCF/LEF mediated transcription. Immunofluorescence analyses of p53 and beta-catenin localization showed that E2 first caused an increase in cytosolic beta-catenin followed by the accumulation of beta-catenin in the nucleus. Nuclear p53 localization was detected in several cells. Expression of p53 was accompanied by distribution of beta-catenin to the cytoplasm and cell borders. A sub population of cells staining strongly for both proteins appeared to be apoptotic. These results suggest that interactions between p53 and beta-catenin signaling pathways may play a key role in osteoblast differentiation and maintenance of tissue homeostasis.


Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases.
Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. Tumor infiltrating lymphocytes (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1-132). In 6 patients no lethal progression was noted, while 3 died of disease. In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed gains of chromosomes 7 and 17. Warthin-like PRCC is a potentially aggressive tumor since a lethal outcome was recorded in 3/9 cases.


Comparative in vitro antimicrobial activity of carumonam (Ro 17-2301) and its influence on the activity of other antibiotics.
The antimicrobial activity of carumonam (Ro 17-2301) was compared with that of 20 antibiotics against 338 clinical isolates. Carumonam did not possess activity against gram-positive cocci, MIC90 of carumonam were less than or equal to 0.5 mg/l for Enterobacteriaceae, except for Citrobacter (less than or equal to 8 mg/l) and less than or equal to 32 mg/l for nonfermenters. It was slightly more active than aztreonam against gentamicin-resistant bacilli (MIC90 less than or equal to 64 vs greater than or equal to 256). Combinations of carumonam with antibiotics with activity against gram-positive microorganisms were indifferent.


Race categorization and face recognition stages in the processing of laterally displayed unknown faces.
Bruyer and Dussart (1985) have recently shown that the "race effect", i.e. the difficulty in recognizing faces issuing from an ethnic group different from that of the subject, is limited to the right visual field. They suspected familiarization to be responsible for this asymmetry. In Exp. I, we tested this hypothesis by repeating the experiment of Bruyer and Dussart with a greater number of trials. A sample of 16 subjects were given the task of recognizing black and white faces laterally displayed for 180 msec. No laterality effect appeared, and the race effect was observed to an equal degree in each hemifield at all stages of the experimental session. It could thus be that various kinds of familiarization must be distinguished. In Exp. II, with 16 new subjects, the black and white faces were mixed so that the subjects had first to perform racial categorization, then a recognition. This time, an advantage of the left field appeared, the race effect was larger in the right than in the left field, and the race effect decreased with familiarization in the left field only. Two complementary experiments with 24 and 16 subjects showed that this phenomenon was not explainable by laterality effects in the early racial decision operation, but well by a lateralized effect of tasks requirements.


Percutaneous aortic valve replacement: valvuloplasty studies in vitro.
Valvuloplasty of the aortic valve is currently used in selected patients for severe calcified aortic valve disease, but clinical effectiveness is low and complication rate remains high. In this study, the total particle load after valvuloplasty and the embolization risk of calcific debris into the coronary arteries was analyzed in an in vitro model. Three highly calcified human aortic leaflets have been sutured into a porcine annulus (N = 9). Both coronary arteries were separated and each was anastomized to a silicon line, which was drained off into a measuring beaker. Then valvuloplasty was performed (Thyshak II, 20 mm, 1.5 atm). After removal of the balloon, 100ml of sodium chloride solution irrigated the ascending aorta. After passing through the separated coronary arteries, the solution was filtered (filter size 0.45 μm), dried, and the total amount of particles was analyzed microscopically. Nine experiments were analyzed. After valvuloplasty, all hearts showed a median of 18 particles larger than 1mm in the coronary arteries (range 0-307). The amount of particles smaller than 1mm was 6574 (median, range 2207-14200). In five cases, coronary arteries were completely occluded by bulky particles. This study demonstrated a large amount of calcific particles after valvuloplasty with a consequently high risk for coronary embolic events in case of highly calcified aortic valves. In times of valvuloplasty rediscovering as part of transcatheter valve implantation, the risk of embolization should be taken into consideration and filtering techniques have to be developed.


Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study.
Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days. Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients. A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001). This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high.


Temperature variability in the day-night cycle is associated with further intracranial pressure during therapeutic hypothermia.
To assess whether circadian patterns of temperature correlate with further values of intracranial pressure (ICP) in severe brain injury treated with hypothermia. We retrospectively analyzed temperature values in subarachnoid hemorrhage patients treated with hypothermia by endovascular cooling. The circadian patterns of temperature were correlated with the mean ICP across the following day (ICP24). We analyzed data from 17 days of monitoring of three subarachnoid hemorrhage patients that underwent aneurysm coiling, sedation and hypothermia due to refractory intracranial hypertension and/or cerebral vasospasm. ICP24 ranged from 11.5 ± 3.1 to 24.2 ± 6.2 mmHg. The ratio between the coefficient of variation of temperature during the nocturnal period (18:00-6:00) and the preceding diurnal period (6:00-18:00) [temperature variability (TV)] ranged from 0.274 to 1.97. Regression analysis showed that TV correlated with ICP24 (Pearson correlation = -0.861, adjusted R square = 0.725, p < 0.001), and that ICP24 = 6 (4-TV) mmHg or, for 80% prediction interval, [Formula: see text] mmHg. The results indicate that the occurrence of ICP24 higher than 20 mmHg is unlikely after a day with TV ≥1.0. TV correlates with further ICP during hypothermia regardless the strict range that temperature is maintained. Further studies with larger series could clarify whether intracranial hypertension in severe brain injury can be predicted by analysis of oscillation patterns of autonomic parameters across a period of 24 h or its harmonics.


Panton-Valentine leukocidin-producing Staphylococcal aureus: report of four siblings.
Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus results in leukocyte destruction and tissue necrosis (Pediatric Dermatology 2007;24:401). It can be associated with a spectrum of clinical manifestations that range from localized staphylococcal skin infections to sometimes severe necrotizing pneumonia (Clin Infect Dis 1999;29:1128). We report a case of four siblings, three brothers whose atopic dermatitis was complicated by cutaneous lesions and furunculosis, while their 21-month-old sister had a fatal PVL positive staphylococcal pneumonia.