Normative values for the Bath Ankylosing Spondylitis Functional Index in the general population compared with ankylosing spondylitis patients in Morocco.
The Bath Ankylosing Spondylitis Functional Index (BASFI) has been commonly used in rheumatology to quantify functional disability in patients with ankylosing spondylitis (AS). Our aim was to evaluate the discriminating power of BASFI and determine the best cutoff score of this index in the general population compared with AS patients. A cross-sectional study that included 200 patients suffering from AS and 223 subjects from the general population matched for age and sex was carried-out. The discriminating power of the BASFI by strata of age was evaluated by the area under the Receiver Operating Characteristic curve and the best cutoff was determined by the Youden index. The mean age of the general population was 39 ± 12 years. 76.7% of them were male. The median BASFI of the healthy subjects and patients was 0.2 and 4.5 (P < 0.001) respectively. The best cutoff of BASFI was 1.5 with a sensitivity of 86% and a specificity of 90%. In the age group of 18-29 years, the best cutoff of the BASFI was 0.9 with a sensitivity of 93% and a specificity of 94%. In the age group of 30-50 years, the best cutoff of the BASFI was 1.5 with a sensitivity of 84% and a specificity of 88%. For those over 50 years of age, the best cutoff of the BASFI was 2.5 with a sensitivity of 84% and a specificity of 97%. This study suggests that the discriminating power of BASFI is considered good at any age. The best cutoff of this index increased as age increases as functional disability is associated in part with lifestyle choices and increases with age. The cutoff values of the BASFI that we have presented could be used as a reference benchmark for both clinical practice and research.


Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting: taking endometrial cancer trials into the translational era.
The second Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting was held on December 1, 2012, and included international multidisciplinary representatives of the 24 member groups. The aims were to review recent advances in molecular pathology of endometrial cancer, focusing on molecular-based therapy, and to identify key hypotheses and issues to be addressed through international collaborative clinical trials. Reviews and summaries of current knowledge were presented followed by parallel working group sessions for surgery, adjuvant and systemic therapy, and translational research. Plenary discussions were held to integrate translational and clinical issues, and a final discussion session to agree on key trial concepts. Proposals to take forward on the following trials were agreed: (1) lymphadenectomy to direct adjuvant treatment in women with high-risk endometrial cancer, including a sentinel node substudy; (2) conservative therapy for low-risk endometrial cancers in morbidly obese women with high surgical risks and for fertility-sparing treatment in premenopausal patients; (3) adjuvant therapy for women with early-stage carcinosarcoma. A proposal was made that a GCIG Early Phase Consortium be developed to serve as an international platform for rapid assessment of biomarkers.


Subsocial Cockroaches Nauphoeta cinerea Mate Indiscriminately with Kin Despite High Costs of Inbreeding.
Many animals have evolved strategies to reduce risks of inbreeding and its deleterious effects on the progeny. In social arthropods, such as the eusocial ants and bees, inbreeding avoidance is typically achieved by the dispersal of breeders from their native colony. However studies in presocial insects suggest that kin discrimination during mate choice may be a more common mechanism in socially simpler species with no reproductive division of labour. Here we examined this possibility in the subsocial cockroach Nauphoeta cinerea, a model species for research in sexual selection, where males establish dominance hierarchies to access females and control breeding territories. When given a binary choice between a sibling male and a non-sibling male that had the opportunity to establish a hierarchy prior to the tests, females mated preferentially with the dominant male, irrespective of kinship or body size. Despite the lack of kin discrimination during mate choice, inbred-mated females incurred significant fitness costs, producing 20% less offspring than outbred-mated females. We discuss how the social mating system of this territorial cockroach may naturally limit the probability of siblings to encounter and reproduce, without the need for evolving active inbreeding avoidance mechanisms, such as kin recognition.


Description of Verrucosispora qiuiae sp. nov., isolated from mangrove swamp sediment, and emended description of the genus Verrucosispora.
A Micromonospora-like strain, RtIII47(T), was isolated from a mangrove swamp in Sanya, Hainan Province, China. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the strain had a close association with the genus Verrucosispora and shared the highest sequence similarity with Verrucosispora lutea YIM 013(T) (98.0%). The strain also showed high 16S rRNA gene sequence similarities to Micromonospora olivasterospora DSM 43868(T) (97.9%), Plantactinospora mayteni YIM 61359(T) (97.9%), Salinispora tropica CNB-440(T) (97.8%), Micromonospora peucetia DSM 43363(T) (97.7%), Micromonospora auratinigra TT1-11(T) (97.7%), Verrucosispora sediminis CGMCC 4.3550(T) (97.6%) and Salinispora arenicola CNH-643(T) (97.5%). Phylogenetic analysis based on the gyrB gene sequence supported the conclusion that strain RtIII47(T) should be assigned to the genus Verrucosispora. DNA-DNA relatedness between strain RtIII47(T) and the most closely related type strain, V. lutea YIM 013(T), was less than 40%. Chemotaxonomic results confirmed the taxonomic position of the isolate in the genus Verrucosispora, and revealed differences at the species level in polar lipids, whole-cell sugars and DNA G+C content. A combination of physiological and biochemical tests also distinguished this strain from other Verrucosispora species. Based on genotypic and phenotypic observations, strain RtIII47(T) (=CGMCC 4.5826(T) =NBRC 106684(T)) is proposed as the type strain of a novel species, Verrucosispora qiuiae sp. nov. An emended description of the genus Verrucosispora is also provided.


Static, dynamic, integrated, and contextualized: a framework for understanding mental health service utilization among young adults.
Research has illuminated the problem of untreated mental illness among young adults, including evidence that young people who exit public care systems often discontinue mental health services in adulthood. The present study explored mental health service use experiences during the transition to adulthood among sixty young adults, ages 18-25, from a Midwestern U.S. state. In-depth semi-structured interviews were conducted. All participants had mood difficulties, and shared three childhood experiences: (a) mood disorder diagnosis; (b) use of public mental health services; and (c) experience with social service systems. Immersion and grounded theory coding techniques were applied to the interview data. Two major themes about mental health service use emerged from the findings, namely the changing nature of service use over time and characterizations of experiences associated with service use at a given point in time. Categories of explanatory constructs that emerged in the latter theme included perceived need, emotions, perceived efficacy of services, and social considerations, among others. Findings suggested a four-facet mid-level theory of service utilization, highlighting both the cross-sectional and time-variant character of service use and decision-making within context. Links between broader theoretical frameworks of service utilization and social psychological models of decision making were noted, and guidelines were presented for ten classes of variables that researchers interested in understanding service use by young adults should consider.


Friends' influence on adolescents' first sexual intercourse.
Social-psychological theories of health behavior suggest that adolescents' sexual behaviors are influenced by the sexual attitudes and behaviors of their friends. Data on 2,436 participants in the National Longitudinal Study of Adolescent Health (Add Health) who were sexually inexperienced at Wave 1 (1994-1995) were analyzed to examine whether friend-related variables predicted initiation of vaginal intercourse by Wave 2 (1996). Analyses also assessed whether predictive relationships varied by level of involvement with friends. Odds ratios were generated by logistic regression analysis. In the 9-18 months between Waves 1 and 2, 18% of participants initiated intercourse. In analyses controlling for gender, family structure and romantic relationships, the higher the proportion of a youth's friends who were sexually experienced, the greater the odds of sexual debut (odds ratio, 1.01); the odds also were elevated among youth who believed that they would gain their friends' respect by having sex (1.2). Relationships between friend variables and sexual initiation did not vary by level of involvement with friends. To maximize the likelihood of success, programs focused on delaying teenage sexual intercourse should address norms for sexual behavior among adolescents' close friends as well as the perceptions, skills and behaviors of individual youth.


Moderate to severe, but not mild, maternal anemia is associated with increased risk of small-for-gestational-age outcomes.
Anemia is highly prevalent globally, estimated at 40-50% in women of reproductive age. Prior studies have produced inconclusive evidence as to the association between maternal anemia and intrauterine growth restriction (IUGR). We conducted a systematic review of the literature containing associations between maternal anemia and small for gestational age (SGA) outcomes (as a proxy for IUGR). A meta-analysis was performed to pool associations, categorized by the hemoglobin cutoffs presented by the authors. We identified 12 studies reporting associations between maternal anemia and SGA. For the meta-analysis, there were 7 associations with a hemoglobin cutoff <110 g/L, 7 with a cutoff <100 g/L, and 5 with a cutoff <90 or <80 g/L. Although the <110- and <100-g/L categories showed no significant relationship with SGA, the <90- or <80-g/L category was associated with a 53% increase in risk of the newborn being SGA [pooled OR = 1.53 (95% CI: 1.24-1.87); P < 0.001]. Moderate to severe, but not mild, maternal anemia appears to have an association with SGA outcomes, but the findings must be viewed with caution due to the great heterogeneity of the studies. Further examination should be conducted using datasets with better standardized definitions and measurements of exposure and outcome.


International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.
This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.


The Role of Emotional Valence for the Processing of Facial and Verbal Stimuli-Positivity or Negativity Bias?
Emotional valence is predominately conveyed in social interactions by words and facial expressions. The existence of broad biases which favor more efficient processing of positive or negative emotions is still a controversial matter. While so far this question has been investigated separately for each modality, in this narrative review of the literature we focus on valence effects in processing both words and facial expressions. In order to identify the factors underlying positivity and negativity effects, and to uncover whether these effects depend on modality and age, we present and analyze three representative overviews of the literature concerning valence effects in word processing, face processing, and combinations of word and face processing. Our analysis of word processing studies points to a positivity bias or a balanced processing of positive and negative words, whereas the analysis of face processing studies showed the existence of separate positivity and negativity biases depending on the experimental paradigm. The mixed results seem to be a product of the different methods and types of stimuli being used. Interestingly, we found that children exhibit a clear positivity advantage for both word and face processing, indicating similar processing biases in both modalities. Over the course of development, the initial positivity advantage gradually disappears, and in some face processing studies even reverses into a negativity bias. We therefore conclude that there is a need for future research that systematically analyses the impact of age and modality on the emergence of these valence effects. Finally, we discuss possible explanations for the presence of the early positivity advantage and its subsequent decrease.


pH-sensing G protein-coupled orphan receptor GPR68 is expressed in human cartilage and correlates with degradation of extracellular matrix during OA progression.
Osteoarthritis (OA) is a debilitating joints disease affecting millions of people worldwide. As OA progresses, chondrocytes experience heightened catabolic activity, often accompanied by alterations in the extracellular environment's osmolarity and acidity. Nevertheless, the precise mechanism by which chondrocytes perceive and respond to acidic stress remains unknown. Recently, there has been growing interest in pH-sensing G protein-coupled receptors (GPCRs), such as GPR68, within musculoskeletal tissues. However, function of GPR68 in cartilage during OA progression remains unknown. This study aims to identify the role of GPR68 in regulation of catabolic gene expression utilizing an in vitro model that simulates catabolic processes in OA. We examined the expression of GPCR by analyzing high throughput RNA-Seq data in human cartilage isolated from healthy donors and OA patients. De-identified and discarded OA cartilage was obtained from joint arthroplasty and chondrocytes were prepared by enzymatic digestion. Chondrocytes were treated with GPR68 agonist, Ogerin and then stimulated IL1β and RNA isolation was performed using Trizol method. Reverse transcription was done using the cDNA synthesis kit and the expression of GPR68 and OA related catabolic genes was quantified using SYBR® green assays. The transcriptome analysis revealed that pH sensing GPCR were expressed in human cartilage with a notable increase in the expression of GPR68 in OA cartilage which suggest a potential role for GPR68 in the pathogenesis of OA. Immunohistochemical (IHC) and qPCR analyses in human cartilage representing various stages of OA indicated a progressive increase in GPR68 expression in cartilage associated with higher OA grades, underscoring a correlation between GPR68 expression and the severity of OA. Furthermore, IHC analysis of Gpr68 in murine cartilage subjected to surgically induced OA demonstrated elevated levels of GPR68 in knee cartilage and meniscus. Using IL1β stimulated in vitro model of OA catabolism, our qPCR analysis unveiled a time-dependent increase in GPR68 expression in response to IL1β stimulation, which correlates with the expression of matrix degrading proteases suggesting the role of GPR68 in chondrocytes catabolism and matrix degeneration. Using pharmacological activator of GPR68, our results further showed that GPR68 activation repressed the expression of MMPs in human chondrocytes. Our results demonstrated that GPR68 was robustly expressed in human cartilage and mice and its expression correlates with matrix degeneration and severity of OA progression in human and surgical model. GPR68 activation in human chondrocytes further repressed the expression of MMPs under OA pathological condition. These results identify GPR68 as a possible therapeutic target in the regulation of matrix degradation during OA.


Inhibition of rat heart ornithine decarboxylase by basic polypeptides.
Purified and partially purified ornithine decarboxylase (ODC) from rat heart was inhibited by basic polypeptides in vitro. Poly-L-arginine, the most effective, was inhibitory at a concentration as low as 0.1 microgram/ml; protamine and histone clearly inhibited ODC at concentrations higher than 2 micrograms/ml, but poly-L-lysine was less effective. The ability to inhibit ODC appeared to correlate with the arginine-residue content of basic polypeptides. The inhibition effect could be decreased by increasing substrate concentration and ionic strength.


Mechanisms through which reciprocal filial values protect wellbeing of Chinese adult-child caregivers in the US.
In this study, we explored the role of reciprocal filial values in protecting the wellbeing of Chinese adult-child caregivers in the US. Using survey data obtained from 137 Chinese adult-child caregivers living in seven US cities, we tested a latent variable model using structural equation modeling. In this model, informed by role theory, social exchange theory and stress-coping theory, reciprocal filial values affect caregiver wellbeing in the face of caregiver role strain, both directly and indirectly through protective effects of role rewards and coping. In the final model, reciprocal filial values had both direct and indirect protective effects on caregivers' wellbeing, offering evidence to address culturally sensitive issues in family caregivers with similar filial values.


Resting qualitative and quantitative myocardial contrast echocardiography to predict cardiac events in patients with acute myocardial infarction and percutaneous revascularization.
Successful restoration of patency of the infarct-related artery is important in management of acute ST-segment elevation myocardial infarction (STEMI); however, it does not necessarily translate into the restoration of perfusion at the tissue level. In this study, we evaluate the prognostic role of qualitative and quantitative myocardial contrast echocardiography (MCE) in predicting cardiac events (after adjustment for cardiovascular risk factors) in STEMI patients undergoing reperfusion. Bedside resting real-time MCE using continuous infusion of diluted contrast agent (Definity) was performed within a median of 21.4 h from revascularization in STEMI. Myocardial perfusion on qualitative MCE was graded 1 = homogenous; 2 = partial/patchy; and 3 = absent. Perfusion score index (PSI) was calculated by adding the perfusion score in all segments divided by the total number of evaluable segments. Quantitative perfusion parameters [A, dB; β, sec(-1); and Aβ] were analyzed using a 17-segment model. Patients were followed for cardiac events including death; nonfatal myocardial infarction (MI); hospitalization for cardiac symptoms; coronary revascularization; or heart failure. Thirty-seven reperfused STEMI patients with a mean age of 64 years (range, 40-86 years) were enrolled and followed for a median of 1.4 years. Cardiac events occurred in 22 patients. Patients with cardiac events had a higher perfusion score index (PSI), and lower A, β and Aβ parameters compared to patients without events [1.84 ± 0.36 vs 1.39 ± 0.17 for PSI, P < 0.001; 0.57 ± 0.24 vs 0.85 ± 0.30 for A, P = 0.03; 0.34 ± 0.15 vs. 0.53 ± 0.17 for β, P = 0.002; and 0.21 ± 0.12 vs. 0.49 ± 0.32, for Aβ, P = 0.003; respectively]. A PSI value of 1.58 provided an area under the curve (AUC) of 0.873, while β of 0.423 and Aβ of 0.323 provided an AUC of 0.858 and 0.842, respectively. PSI and Aβ were independent predictors of cardiac events with an adjusted hazard ratio of 3.41 (1.19-12.27); and 4.19 (1.3-19.09), respectively. No contrast-related side effects were reported. Evaluation of perfusion in reperfused STEMI patients by qualitative and quantitative MCE (myocardial blood flow, Aβ) provides independent prediction of cardiac events.


Formononetin alleviates hepatic steatosis by facilitating TFEB-mediated lysosome biogenesis and lipophagy.
Formononetin has been reported to ameliorate hyperlipidemia and obesity, but its effect and mechanism of action in anti-non-alcoholic fatty liver disease (NAFLD) remain unclear. Lipophagy is a critical protective mechanism during steatosis development that results in the decomposition of lipid droplets through autophagy and the prevention of cellular lipid accumulation. This study aimed to investigate the beneficial role of formononetin in treating NAFLD and explore the mechanism of lipophagy in formononetin anti-hepatic steatosis effects. Formononetin treatment significantly ameliorated hepatic steatosis in HFD mice. Consistently, formononetin also reduced FFAs-stimulated lipid accumulation in HepG2 cells and primary mouse hepatocytes. Further analysis revealed that steatosis increased LC3B-II, a marker of autophagy, but caused blockade of autophagic flux associated with a lack of lysosomes. Treatment with formononetin promoted lysosome biogenesis and autophagosome-lysosome fusion, relieving the blockade in autophagic flux and further induced lipophagy. Mechanistically, formononetin activated adenosine monophosphate activated protein kinase (AMPK) and promoted subsequent nuclear translocation of transcription factor EB (TFEB), a key regulator of lysosome biogenesis. TFEB inhibition markedly abolished formononetin-induced lysosome biogenesis, autophagosome-lysosome fusion and lipophagy and concomitantly alleviated lipid accumulation. Formononetin improved hepatic steatosis via TFEB-mediated lysosome biogenesis, which provides new evidence regarding formononetin's anti-NAFLD effects.


Evidence for efficient vertical transfer of maternal HIV-1 envelope-specific neutralizing antibodies but no association of such antibodies with reduced infant infection.
: Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. Antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breast-feeding transmission pairs, were compared. The envelope-binding titers were strongly correlated (r = 0.91, P < 0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, P < 0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and nontransmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.


Association of the CagA gene positive Helicobacter pylori and tissue levels of interleukin-17 and interleukin-8 in gastric ulcer patients.
It has been reported that CagA gene positive Helicobacter pylori (CagA+ H. pylon) induces severe gastric mucosal inflammation. On the other hand, Interleukin (IL)-17 is known to stimulate IL-8 release by the gastric epithelial cells which facilitates chemotaxis of neutrophils through an IL-8-dependent mechanism. The aim of the study is to determine the role of IL-17 and IL-8 in the development of gastritis and gastric ulcer in H. pylori infected patients. Mucosal biopsy samples were obtained from the ulcer site of gastric mucosa of 28 patients with gastric ulcer (GU), 27 with gastritis and 8 controls subjects without gastritis or ulcers. Infection with H. pylori of patients and controls was assessed by a rapid urease test, histological examination and culture. Measurement of the tissue levels of IL-17 and IL-8 were assayed by ELISA. H. pylori cagA gene was assessed by polymerase chain reaction (PCR). Out of the 28 patients with GU, 18 (64.2%) patients were positive for H. pylori infection, while 13 (48.1%) patients with gastritis and none of the controls were positive for H. pylori infection The CagA gene was detected in 12 (66.6%) in H. pylori GU patients, and 7 (53.8%) H. pylori positive gastritis. IL-17 was significantly higher in GU-CagA+ve H. pylori compared to GU-CagA- H. pylori (P <0.05), while IL-8 showed no significant difference between groups. The mean levels of IL-8 in gastritis-CagA+ H. pylori) was significantly higher compared to gastritis--CagA- H. pylori- (P <0.05). IL-17 showed significant association with the number of neutrophils in both GU and gastritis (r = 0.689, P < 0.05 & r = 0.618, P < 0.05). Also, IL-8 showed significant association with the number of neutrophils in both GU and gastritis n (r = 0.468, P < 0.05 & r = 0.727, P < 0.05). It is concluded that the Cag+ve H. pylori is associated with induction of mucosal injury. Also, IL-8 and IL-17 plays a role in the development of GU and gastritis especially in CagA+ H. pylori.


A randomized, double-blind, placebo-controlled pilot study of Lactobacillus reuteri ATCC 55730 for the prevention of antibiotic-associated diarrhea in hospitalized adults.
The purpose of the study was to evaluate Lactobacillus reuteri for the prevention of antibiotic-associated diarrhea (AAD) in hospitalized adults. AAD is a problem in hospitalized adults, contributing to increased length of stay, cost, and mortality. Probiotics have been proposed as a way to prevent AAD. L. reuteri decreases acute infectious diarrhea in children; however, L. reuteri has never been evaluated for the prevention of AAD. In a randomized, double-blind, placebo-controlled pilot study, in-patients receiving antibiotics were given L. reuteri 1×10 colony-forming units twice daily or an identical placebo for 4 weeks. Stool frequency, consistency, and gastrointestinal symptoms were monitored during the 4-week treatment period and during a 2-week follow-up period. A total of 31 patients were enrolled. Eight patients were excluded in the data analysis because of length of study participation less than 14 days. Mean age was 51 ± 18 years; 63% were female and 37% male. Most frequent primary diagnosis was pneumonia (20%), followed by abscess (10%), chronic obstructive pulmonary disease (6.7%), and bronchitis (6.7%). Thirteen patients received L. reuteri and 10 received placebo. Patients treated with L. reuteri had a significantly lower frequency of diarrhea compared with placebo (50% in the placebo group vs. 7.7% in the probiotic group, P=0.02). There were no differences in the frequency or severity of gastrointestinal symptoms. In this placebo-controlled, pilot study, L. reuteri twice daily for 4 weeks significantly decreased AAD among hospitalized adults. L. reuteri was safe and well tolerated.


Screening for renal involvement in ANCA-associated vasculitis: room for improvement?
Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) requires prompt and aggressive immunosuppressive therapy. The aim of this study was to evaluate screening practice for renal involvement in AAV and its potential effect on renal outcomes. Between 2005 and 2015, ANCA-positive AAV patients in a teaching hospital in the Netherlands were retrospectively included. Complete screening for renal involvement was defined as: assessment of erythrocyturia, proteinuria and serum creatinine within two weeks of the diagnosis of AAV. Characteristics at presentation and at 12 months were compared between patients with and without complete screening. A total of 109 AAV patients (63% male) were identified with a mean age of 62 ±; 14 years. Complete screening for renal involvement was performed in 90 of the 109 patients (83%). Patients with incomplete screening had a lower serum creatinine (86 ±; 53 vs. 190 ±; 185 μmol/l, p < 0.001) and were more often diagnosed outside the renal department (100% vs. 78%, p = 0.02). Three patients with incomplete screening had a rise in serum creatinine of ≥ 30% at 12 months. Incomplete screening was not associated with the development of end-stage renal disease. Urine analysis of patients with renal biopsy-proven AAV (n = 31) showed erythrocyturia in 58% after one sample and in 94% after three samples. Screening for renal involvement in AAV was suboptimal, primarily in patients who presented outside the renal department. A higher sensitivity for erythrocyturia is achieved if urine analysis is repeated. Incomplete screening may lead to renal impairment if renal involvement is not treated appropriately.


Idiopathic chronic eosinophilic pneumonia in 7 horses.
Idiopathic chronic eosinophilic pneumonia of horses is incompletely described. To describe the physical examination, clinicopathologic, histopathologic, and radiographic features and response to corticosteroid treatment of idiopathic chronic eosinophilic pneumonia of horses. Seven horses with eosinophilic pneumonia. Retrospective, descriptive study. Anamnesis, clinical signs, and clinicopathologic and radiologic findings in 7 adult horses with histologically confirmed eosinophilic pneumonia were reviewed. The horses were examined for signs of chronic respiratory disease. The horses ranged in age from 8 to 20 years. Significant findings on physical examination included tachypnea and abnormal respiratory sounds. Thoracic radiography revealed severe diffuse interstitial patterns of increased pulmonary density in all horses. There was a predominance of eosinophils in bronchoalveolar lavage fluid (BALF), and 6 of 7 horses had peripheral blood eosinophilia. Lung biopsies revealed eosinophilic infiltrates in all horses. Dexamethasone was administered to 3 horses and resulted in short-term clinical improvement in all three. A diagnosis of idiopathic eosinophilic pneumonia should be considered in horses with a history of chronic pulmonary disease, diffuse interstitial pattern of increased pulmonary density on thoracic radiographs, and a predominance of eosinophils in BALF. Horses with this condition may show a temporary response to treatment with dexamethasone.


Highly immunogenic artificial complexes based on synthetic immunopotentiating polyions (artificial antigens and vaccines).
An interpretive review of the theoretical and experimental data on the immunogenetic concept that "there are no strong and weak antigens, there are high and low responder genotypes," developed and upheld by the authors is presented. To achieve phenotypic correction (finding ways of turning genetically low responder individuals into high responder ones) the authors have developed complex antigens--artificial macromolecular complexes containing both the required antigenic determinants and adjuvant structures. Synthetic nonnatural carbohydrates and heterochain polyions with controlled structure (PAA, PVP, polyconidine quarternary salts) were shown to act as immunopotentiators, substituting the helper signal of T-cells. The authors' data confirm this immunogenetic principle for developing highly immunogenic preparations, prototypes of future vaccines.


Penicillamine in multiple sclerosis. Therapeutic trial and design of uncontrolled pilot drug study.
Twenty-three patients with the chronic progressive or intermittent relapsing form of multiple sclerosis (MS) were treated with d-penicillamine over a period from 6 weeks to 12 months. Clinical effect was evaluated using Kurtzke's disability status scale with follow-up lasting from 7 weeks to 15 months. Fifteen patients remained unchanged, 7 became worse and 1 improved after the treatment. Administration of penicillamine to patients with MS resulted in an insignificant lowering of serum IgA, IgG and IgM levels. It is concluded that penicillamine neither prevented the occurrence of relapses nor slowed down the chronic progressive course of multiple sclerosis.


Nonpolar Resistive Switching in Ag@TiO2 Core-Shell Nanowires.
Nonpolar resistive switching (RS), a combination of bipolar and unipolar RS, is demonstrated for the first time in a single nanowire (NW) system. Exploiting Ag@TiO2 core-shell (CS) NWs synthesized by postgrowth shell formation, the switching mode is controlled by adjusting the current compliance effectively, tailoring the electrical polarity response. We demonstrate ON/OFF ratios of 105 and 107 for bipolar and unipolar modes, respectively. In the bipolar regime, retention times could be controlled up to 103 s, and in the unipolar mode, >106 s was recorded. We show how the unique dual-mode switching behavior is enabled by the defect-rich polycrystalline material structure of the TiO2 shell and the interaction between the Ag core and the Ag electrodes. These results provide a foundation for engineering nonpolar RS behaviors for memory storage and neuromorphic applications in CSNW structures.


[Case of cerebellar and spinal cord infarction presenting with acute brachial diplegia due to right vertebral artery occlusion].
A 73-year-old man was admitted for evaluation of sudden onset of dizziness, bilateral shoulder pain, and brachial diplegia. Neurological examination revealed severe bilateral weakness of the triceps brachii, wrist flexor, and wrist extensor muscles. There was no paresis of the lower limbs. His gait was ataxic. Pinprick and temperature sensations were diminished at the bilateral C6-C8 dermatomes. Vibration and position senses were intact. An MRI of the head revealed a right cerebellar infarction and occlusion of the right vertebral artery. An MRI of the cervical spine on T₂ weighted imaging (T₂WI) showed cord compression at the C3/4-C5/6 level secondary to spondylotic degeneration without any intramedullary signal changes of the cord. On the following day, however, high-signal lesions on T₂WI appeared in the C5-C6 spinal cord, suggesting cord infarction. Unilateral vertebral artery occlusion does not usually result in cervical cord infarction because of anastomosis of arteries. Because of the long-term mechanical compression in our case, it was likely that cervical cord ischemia was present before the onset of symptoms. On the basis of chronic cord compression, our case suggests that occlusion of a unilateral vertebral artery could cause cervical cord infarction.


Isokinetic strength testing in older women: a comparison of two systems.
National Institute of Aging; University of Wisconsin Graduate School. Isokinetic equipment is used for measuring muscular strength for both experimental and rehabilitative purposes. In this study two LIDO(R) isokinetic dynamometer systems, the LIDO-digital and the LIDO-active, were compared at 60, 180, 240, and 300 degrees /see for peak torque (PT) and average work output (WO) of knee flexion and extension. Twenty-five elderly women (age range = 65-86) were tested on both systems within seven days. The data were compared by using a repeated measures ANOVA followed by a Dunn-Bonferroni posthoc comparison (p </= .0125). Knee flexion PT was significantly different (p </= .0125) at all angular velocities tested. Knee extension PT was significantly different (p </= .0125) at all speeds except 180 degrees /sec. Knee flexion WO was significantly different (p </= .0125) at all angular velocities except 60 degrees /sec; whereas, knee extension WO was not significantly different. The data indicate that for healthy women over 65, these two systems are not totally comparable for knee extension and flexion. Therefore, in both clinical and experimental settings, caution should be taken when comparing results across systems or when comparing patients' results with norms established from data obtained on a different system. J Orthop Sports Phys Ther 1991;13(4):199-202.


Ten-year experience with extended criteria cardiac transplantation.
Extended criteria cardiac transplant (ECCT) programs expand the transplant pool by matching donors and recipients typically excluded from the transplant process because of age or comorbidity. There is a paucity of data examining long-term outcomes with this strategy. Between January 2000 and December 2009, adult patients undergoing isolated heart transplant were prospectively classified as ECCT based on prespecified criteria. Baseline characteristics and outcomes were compared between ECCT and standard criteria cardiac transplant recipients. Two Cox proportional hazards models were developed. The first to identify clinical variables contributing to survival between the 2 groups, and the second to determine the additional risk associated with assignment to ECCT. Among the 454 patients who underwent heart transplant, 84 (18.5%) were ECCT. Compared with the patients who underwent standard criteria cardiac transplant, ECCT patients were older (median, 66.6 years versus 53.2 years; P<0.001), with higher frequency of diabetes mellitus (46.4% versus 24.6%; P<0.001) and chronic kidney disease (median estimated glomerular filtration rate, 55 versus 61.6 mL/min; P=0.001). After adjustment for baseline characteristics, standard criteria cardiac transplant survival was higher than ECCT at 1 (89% versus 86%; P=0.18) and 5 (77% versus 66%; P=0.035) years. In a multivariate model that included listing criteria, creatinine (hazard ratio, 1.05 per 0.1 mg/dL; 95% confidence interval, 1.02-1.09; P=0.001) was a significant predictor of post-transplant mortality. ECCT is an acceptable alternative for advanced heart failure therapy in select patients. Age and renal dysfunction are important determinants of long-term survival and post-transplant morbidity.


DPPIV+ fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages.
Adult tissue-resident macrophages (RMs) are either maintained by blood monocytes or through self-renewal. While the presence of a nurturing niche is likely crucial to support the survival and function of self-renewing RMs, evidence regarding its nature is limited. Here, we identify fibro-adipogenic progenitors (FAPs) as the main source of colony-stimulating factor 1 (CSF1) in resting skeletal muscle. Using parabiosis in combination with FAP-deficient transgenic mice (PdgfrαCreERT2 × DTA) or mice lacking FAP-derived CSF1 (PdgfrαCreERT2 × Csf1flox/null), we show that local CSF1 from FAPs is required for the survival of both TIM4- monocyte-derived and TIM4+ self-renewing RMs in adult skeletal muscle. The spatial distribution and number of TIM4+ RMs coincide with those of dipeptidyl peptidase IV (DPPIV)+ FAPs, suggesting their role as CSF1-producing niche cells for self-renewing RMs. This finding identifies opportunities to precisely manipulate the function of self-renewing RMs in situ to further unravel their role in health and disease.


The role of somatostatin analogs in Cushing's disease.
Somatostatin (SRIF) has been proposed to be of therapeutic interest in the medical treatment of Cushing's disease. While in vitro data demonstrate the presence of SRIF-receptor subtype (sst) expression in corticotroph adenomas, the current clinically available SRIF-analog Octreotide, predominantly targeting sst(2), is ineffective in lowering ACTH levels in Cushing's disease and only appears to inhibit the release of ACTH in Nelson's syndrome. In the present review, current knowledge on the physiological role of SRIF in the regulation of ACTH secretion by the anterior pituitary gland, as well as by corticotroph tumor cells is summarized. In addition, the role of glucocorticoids in regulating sst-mediated inhibition of ACTH release by corticotroph adenoma cells is discussed. Recently, it was reported that the novel multiligand SRIF-analog SOM230 might have the potential to be of therapeutic interest for Cushing's disease. On the basis of the potent suppressive effects on ACTH release by SRIF-analogs with high binding affinity to sst(5) and the observation that sst(5) expression and action is relatively resistant to glucocorticoid treatment, including the recent observation that sst(5) is the predominant sst expressed in human corticotroph adenomas, it is hypothesized that sst(5) may be a new therapeutic target for the control of ACTH and cortisol hypersecretion in patients with pituitary dependent Cushing's disease.


Clinical leadership and rural and remote practice: A qualitative study.
To explore how clinical leadership is perceived by nurses in rural and remote areas of New South Wales, Australia. There are few empirical studies aimed at understanding clinical leadership from a rural and remote perspective. A qualitative approach, based on interpretive phenomenology, used thematic analysis of recorded and transcribed interviews. Ethical approval was secured, 56 interviews were undertaken, across 14 different rural and remote health facilities, with nurses across the spectrum of practice. Thematic analysis led to five themes and findings that support an understanding of clinical leadership from a rural and remote context. Clinical leaders were seen to considerably impact on the initiation of change and quality of care. They also faced barriers if the health facility was poorly staffed, lacked support and if the community were strongly co-dependent. In rural and remote areas, clinical leadership is evident to support change, innovation and care quality. Managers should be aware that staff shortages and challenges to staff retention or the initiation of change are affected by poor clinical leadership. This paper suggests that managers who facilitate clinical leadership are better able to support professional education and greater efficiencies in the delivery of quality health care.


Intracerebral infection with murine cytomegalovirus induces CXCL10 and is restricted by adoptive transfer of splenocytes.
The brain's intrinsic immune system consists of glial cells that produce cytokines and chemokines in response to stimulation with cytomegalovirus (CMV). The present experiments were undertaken to determine whether this intrinsic glial cell response alone is sufficient to control CMV infection of the central nervous system (CNS) or whether effector cells from the somatic immune system are also required. Following stereotactic, intracerebroventricular (icv), injection of murine cytomegalovirus (MCMV) into immunocompetent (C.B-17) mice, viral spread in the brain was limited to the cells of the ventricular walls and the infection was resolved by 10 days post infection (p.i.). In contrast, icv infection of immunodeficient (C.B-17 SCID/bg) mice resulted in viral spread from the ventricles throughout the brain parenchyma and these mice succumbed to lethal disease. Adoptive transfer of total splenocytes from major histocompatibility complex (MHC)-matched, MCMV-primed animals restricted intracerebral viral infection to the periventricular cells and reduced levels of reporter gene expression from the viral genome. Peripheral immune cell transfer also protected immunodeficient animals from lethal disease. Depletion of Thy 1.2(+) cells from MCMV-primed splenocytes abolished the protective effect of adoptive transfer. Viral expression was found to be fourfold greater in the brains of animals given Thy 1.2-depleted splenocytes than from those receiving total undepleted cells. As MCMV infection proceeded in the brains of immunodeficient mice, levels of the T-cell chemoattractants CXCL10 and CCL2 remained elevated, whereas CXCL10 levels waned in the brains of animals receiving transferred splenocytes. Taken together, these results demonstrate the ability of T lymphocytes to restrict intracerebral viral spread and indicate that intrinsic glial cell responses alone are insufficient to control MCMV brain infection.


Defragmenting care: testing an intervention to increase the effectiveness of interdisciplinary health care teams.
Few studies in the literature have examined the outcomes of health care interdisciplinary teams. Most existing studies have measured attributes of health care teams; however, none have implemented and examined outcomes of a team development intervention. This study was conducted to determine whether a development intervention used with an existing interdisciplinary team would reduce the length of stay for patients in an acute care setting. A quasi-experimental single-subject time series design was conducted with multiple measures of length of stay collected across baseline, intervention, and reversal phases of the study. Bronstein's Model for Interdisciplinary Collaboration provided the framework for this study. The components of this model were used to guide a team development intervention comprised of 4 consecutive weeks of classroom development sessions and 4 consecutive weeks of booster messaging. Length of stay (LOS) data were collected for each of the study phases to examine preintervention LOS and compare these data with LOS during the intervention and reversal phases. The results of this study revealed that the interdisciplinary team development intervention had no positive effect on the length of stay data. Baseline mean LOS across 12 baseline months was 4.83 days (SD=0.65) with monthly means ranging from 4.1 to 6.3 days. The mean LOS was 5.1 and 4.6 days for the intervention months of May and June and 6.0, 6.5, 5.7, and 5.4 days for the reversal months of July to October, respectively. All means in the intervention and reversal phases were higher than comparable months in the baseline phase. The pattern of the graphed trend was closely aligned with the seasonal variations seen during the baseline months. Although these results showed that the team development intervention provided for this interdisciplinary team had no positive effect on the LOS, there are many factors that may have influenced the results and may provide insights useful for future research. LOS may not be the outcome variable that reflects team effectiveness for this population. It is possible that the interdisciplinary team in this study had well-developed collaborative processes before the intervention. Physicians were not included in the team development intervention yet may be the discipline whose participation may have affected LOS.


Self-Powered Textile Triboelectric Pulse Sensor for Cardiovascular Monitoring.
Cardiovascular diseases have become a severe threat to human health. Fortunately, most of them can be effectively assessed and prevented through long-term monitoring of cardiovascular signals. Wearable medical sensors play an essential role in monitoring human physiological health, which are heading towards ultra-low power consumption, high sensitivity and stability. Furthermore, a comfortable wearable sensor also needs to be flexible and breathable. Here, a self-powered textile pulse sensor (STPS) based on triboelectric nanogenerator (TENG) is demonstrated for real-time monitoring of the radial artery pulse waveform. STPS can directly convert tiny pressure signals into electrical signals with excellent linearity (R2 = 0.996), low detection limit, and long-term stable performance (5×104 cycles). The flexible textile-based STPS can be conformally attached to the human body for continuously and stably recording physiological mechanical signals, which is expected to be utilized in the personalized cardiovascular pulse monitoring wearable devices in the Internet of Things era.


The effects of sexual selection on life-history traits: an experimental study on guppies.
Sexual selection is often prevented during captive breeding in order to maximize effective population size and retain genetic diversity. However, enforcing monogamy and thereby preventing sexual selection may affect population fitness either negatively by preventing the purging of deleterious mutations or positively by reducing sexual conflicts. To better understand the effect of sexual selection on the fitness of small populations, we compared components of female fitness and the expression of male secondary sexual characters in 19 experimental populations of guppies (Poecilia reticulata) maintained under polygamous or monogamous mating regimes over nine generations. In order to generate treatments that solely differed by their level of sexual selection, the middle-class neighbourhood breeding design was enforced in the monogamous populations, while in the polygamous populations, all females contributed similarly to the next generation with one male and one female offspring. This experimental design allowed potential sexual conflicts to increase in the polygamous populations because selection could not operate on adult-female traits. Clutch size and offspring survival showed a weak decline from generation to generation but did not differ among treatments. Offspring size, however, declined across generations, but more in monogamous than polygamous populations. By generation eight, orange- and black-spot areas were larger in males from the polygamous treatment, but these differences were not statistically significant. Overall, these results suggest that neither sexual conflict nor the purging of deleterious mutation had important effects on the fitness of our experimental populations. However, only few generations of enforced monogamy in a benign environment were sufficient to negatively affect offspring size, a trait potentially crucial for survival in the wild. Sexual selection may therefore, under certain circumstances, be beneficial over enforced monogamy during captive breeding.


Renal response to atrial peptides is reduced in experimental nephrosis.
The aim of this study was to evaluate the renal response to atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) in control rats and in rats with experimental nephrotic syndrome (NS). NS was obtained by a single intravenous injection of adriamycin (7.5 mg/kg). Bolus injection of AE from normal or NS rats resulted in marked increase of diuresis and natriuresis in bioassay control rats (AE from normal rats, urine flow rate, 14.87 +/- 2.94 to 186.18 +/- 55.86 microliters/min; Na excretion, 0.68 +/- 0.26 to 21.80 +/- 5.45 mu eq/min; AE from NS, urine flow rate, 13.49 +/- 4.30 to 167.14 +/- 51.44 microliters/min; Na excretion, 0.98 +/- 0.57 to 20.71 +/- 9.76 mu eq/min). In contrast, blunted diuretic (from 11.26 +/- 3.05 to 65.20 +/- 27.30 microliters/min) and natriuretic (from 0.58 +/- 0.15 to 4.52 +/- 1.59 mu eq/min) effect was observed when AE were injected in rats with NS. Injection of the vehicle in which AE were dissolved or ventricular extracts did not increase urinary flow rate or Na excretion in both control and NS animals. Bolus injection of synthetic ANF (Arg-101-Tyr-126) induced marked diuretic and natriuretic response in control but not in NS rats. Similar results were obtained when AE were infused by constant infusion in control or in NS bioassay rats. AE given by constant infusion induced comparable increase in glomerular filtration rate (GFR) over basal values both in control and NS animals (controls, 39%; NS rats, 40%).(ABSTRACT TRUNCATED AT 250 WORDS)


Curtailment: a method to reduce the length of self-report questionnaires while maintaining diagnostic accuracy.
Minimizing the respondent burden and maximizing the classification accuracy of tests is essential for efficacious screening for common mental health disorders. In previous studies, curtailment of tests has been shown to reduce average test length considerably, without loss of accuracy. In the current study, we simulate Deterministic (DC) and Stochastic (SC) Curtailment for three self-report questionnaires for common mental health disorders, to study the potential gains in efficiency that can be obtained in screening for these disorders. The curtailment algorithms were applied in an existing dataset of item scores of 502 help-seeking participants. Results indicate that DC reduces test length by up to 37%, and SC reduces test length by up to 46%, with only very slight decreases in diagnostic accuracy. Compared to an item response theory based adaptive test with similar test length, SC provided better diagnostic accuracy. Consequently, curtailment may be useful in improving the efficiency of mental health self-report questionnaires.


Drinking from the firehose of experience.
Computational concepts from robotics and computer vision hold great promise to account for major aspects of the phenomenon of consciousness, including philosophically problematical aspects such as the vividness of qualia, the first-person character of conscious experience, and the property of intentionality. We present a dynamical systems model describing human or robotic agents and their interaction with the environment. In order to cope with the enormous information content of the sensory stream, this model includes trackers for selected coherent spatio-temporal portions of the sensory input stream, and a self-constructed plausible coherent narrative describing the recent history of the agent's sensorimotor interaction with the world. We describe how an agent can autonomously learn its own intentionality by constructing computational models of hypothetical entities in the external world. These models explain regularities in the sensorimotor interaction, and serve as referents for the agent's symbolic knowledge representation. The high information content of the sensory stream allows the agent to continually evaluate these hypothesized models, refuting those that make poor predictions. The high information content of the sensory input stream also accounts for the vividness and uniqueness of subjective experience. We then evaluate our account against 11 features of consciousness "that any philosophical-scientific theory should hope to explain", according to the philosopher and prominent AI critic John Searle. The essential features of consciousness can, in principle, be implemented on a robot with sufficient computational power and a sufficiently rich sensorimotor system, embodied and embedded in its environment.


Early osteoarthritis of the knee.
There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.


Observation of the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on recurrent implantation failure of kidney deficiency and blood stasis.
To observe the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on the patients with recurrent implantation failure (RIF) of kidney deficiency and blood stasis undergoing frozen embryo transfer of the conventional hormone replacement therapy cycle. Sixty RIF of kidney deficiency and blood stasis patients who planned for frozen embryo transfer were randomly divided into a combined treatment group (30 cases) and a western medication group (30 cases). In the western medication group, the conventional hormone replacement therapy was performed for endometrial preparation during transfer cycle. On the basis of treatment as the western medication group, in the combined treatment group, Tongyuan needling combined with jingyu herb-separated moxibustion was adopted. Regarding tongyuan needling, the acupoint prescription for Tongdu Tiaoshen (promoting the governor vessel and regulating the spirit, e.g. Dazhui [GV 14], Ganshu [BL 18], Shenshu [BL 23] and back-shu points) and that for Yinqi Guiguan (conducting qi back to the primary, e.g. Zhongwan [CV 12], Qihai [CV 6], Guanyuan [CV 4] and front-mu points) were selected. Acupuncture was delivered at these two prescriptions alternatively each time. After acupuncture, the herb-separated moxibustion (in which, the herbal powder was prepared with the modified Yangjing Zhongyu decoction for cultivating the kidney essence and promoting pregnancy) was operated at Shenque (CV 8). This combined therapy was delivered once every two days, 3 sessions a week till the day of embryo transfer. The pregnancy outcomes (positive rate of human chorionic gonadotropin [β-HCG] and clinical pregnancy rate) were compared between the two groups, as well as the TCM syndrome score, serum estradiol (E2) and progesterone (P) levels, endometrial thickness and type, endometrial blood flow index (pulsatility index [PI], resistance index [RI]) before and after treatment. After treatment, the clinical pregnancy rate of the combined treatment group was 40.0% (12/30), higher than that of the western medication group (16.7%, 5/30, P<0.05); and the difference in the positive rate of β-HCG was not significant statistically between the two groups (P>0.05). After treatment, the serum levels of E2 and P were elevated (P<0.05), the endometrial thickness was thickened (P<0.05); the scores of TCM syndrome, and the levels of PI and RI were reduced (P<0.05) when compared with those before treatment in the two groups. The proportion of type A endometrium increased compared with that before treatment in the combined treatment group (P<0.05). Except the levels of E2 and P, the above indexes in the combined treatment group were superior to the western medication group (P<0.05). On the basis of frozen embryo transfer of conventional hormone replacement cycle, the intervention of Tongyuan needling combined with jingyu herb-separated moxibustion can effectively relieve the clinical symptoms, increase the endometrial blood flow and its thickness, and improve the endometrial receptivity, thereby ameliorate pregnancy outcomes in RIF patients of kidney deficiency and blood stasis.


Low tuberculosis case detection in Gokwe North and South, Zimbabwe in 2006.
Case detection is an important component of tuberculosis control programmes. It helps identify sources of infection, treat them, and thus break the chain of infection. To determine the reasons of low tuberculosis case detection in Gokwe Districts, Zimbabwe. A descriptive cross sectional study was conducted. We used interviewer administered questionnaire for nurses and patients, checklists, key informant interviews. Thirty-eight nurses, forty-two patients and seven key informants were interviewed and 1254 entries in tuberculosis register were reviewed. Nurses correctly defined pulmonary tuberculosis, listed signs and symptoms, preventive measures and methods of tuberculosis diagnosis. Exit interviews showed 9/42 (21%) of patients presenting with cough were asked to submit sputa for examination and asked about household contacts with tuberculosis. About 27% of patients who were sputum positive in the laboratory register were not recorded in the district tuberculosis register. This contributed to the high proportion of early defaulters among tuberculosis suspects. Low tuberculosis case detection was because nurses were not routinely requesting for sputum for examination in patients presenting with a cough or history of previous treatment for cough. Nurses should routinely request for sputum for examination in patients presenting with a cough or history of recent treatment for cough.


Effects of interferon-γ knockdown on vaccine-induced immunity against Marek's disease in chickens.
Interferon (IFN)-γ has been shown to be associated with immunity to Marek's disease virus (MDV). The overall objective of this study was to investigate the causal relationship between IFN-γ and vaccine-conferred immunity against MDV in chickens. To this end, 3 small interfering RNAs (siRNAs) targeting chicken IFN-γ, which had previously been shown to reduce IFN-γ expression in vitro, and a control siRNA were selected to generate recombinant avian adeno-associated virus (rAAAV) expressing short-hairpin small interfering RNAs (shRNAs). An MDV challenge trial was then conducted: chickens were vaccinated with herpesvirus of turkey (HVT), administered the rAAAV expressing shRNA, and then challenged with MDV. Tumors were observed in 4 out of 10 birds that were vaccinated with HVT and challenged but did not receive any rAAAV, 5 out of 9 birds that were administered the rAAAV containing IFN-γ shRNA, and 2 out of 10 birds that were administered a control enhanced green fluorescent protein siRNA. There was no significant difference in MDV genome load in the feather follicle epithelium of the birds that were cotreated with the vaccine and the rAAAV compared with the vaccinated MDV-infected birds. These results suggest that AAAV-based vectors can be used for the delivery of shRNA into chicken cells. However, administration of the rAAAV expressing shRNA targeting chicken IFN-γ did not seem to fully abrogate vaccine-induced protection.


Mapping Selection within Drosophila melanogaster Embryo's Anatomy.
We present a survey of selection across Drosophila melanogaster embryonic anatomy. Our approach integrates genomic variation, spatial gene expression patterns, and development with the aim of mapping adaptation over the entire embryo's anatomy. Our adaptation map is based on analyzing spatial gene expression information for 5,969 genes (from text-based annotations of in situ hybridization data directly from the BDGP database, Tomancak et al. 2007) and the polymorphism and divergence in these genes (from the project DGRP, Mackay et al. 2012).The proportion of nonsynonymous substitutions that are adaptive, neutral, or slightly deleterious are estimated for the set of genes expressed in each embryonic anatomical structure using the distribution of fitness effects-alpha method (Eyre-Walker and Keightley 2009). This method is a robust derivative of the McDonald and Kreitman test (McDonald and Kreitman 1991). We also explore whether different anatomical structures differ in the phylogenetic age, codon usage, or expression bias of the genes they express and whether genes expressed in many anatomical structures show more adaptive substitutions than other genes.We found that: 1) most of the digestive system and ectoderm-derived structures are under selective constraint, 2) the germ line and some specific mesoderm-derived structures show high rates of adaptive substitution, and 3) the genes that are expressed in a small number of anatomical structures show higher expression bias, lower phylogenetic ages, and less constraint.


[Mycoplasma genitalium--a new challenge in sexually transmitted diseases].
Although Mycoplasma genitalium was described 20 years ago, the knowledge concerning it is still limited. The publications in the area are surprisingly few in number, especially considering that the pathogen is rather common and has been connected with a number of different urogenital diseases. The PCR technique has made it possible to perform investigations on a large scale, which might elucidate the pathogenic role of M. genitalium in the urogenital tract. However, it seems well established that M. genitalium causes non-gonococcal urethritis (NGU). The mycoplasma behaves almost identically to Chlamydia trachomatis with respect to routes of infection and inflammatory response, but no further relationship between the two organisms seems obvious. M. genitalium is believed to produce urethritis with almost the same frequency as C. trachomatis. In the female genital tract, M. genitalium is strongly incriminated as a primary cause of cervicitis, endometritis and salpingitis, the latter complicated by tubal damage. The role of the organisms in epididymitis, prostatitis and neonatal infections is unclear. In the case of urethritis and upper genital tract infections in the female, it is recommended to test for M. genitalium using molecular biological assays and in the event of a positive result institute antimicrobial therapy.


A unified sensor architecture for isothermal detection of double-stranded DNA, oligonucleotides, and small molecules.
Pathogen detection is an important problem in many areas of medicine and agriculture, which can involve genomic or transcriptomic signatures or small-molecule metabolites. We report a unified, DNA-based sensor architecture capable of isothermal detection of double-stranded DNA targets, single-stranded oligonucleotides, and small molecules. Each sensor contains independent target detection and reporter modules, enabling rapid design. We detected gene variants on plasmids by using a straightforward isothermal denaturation protocol. The sensors were highly specific, even with a randomized DNA background. We achieved a limit of detection of ∼15 pM for single-stranded targets and ∼5 nM for targets on denatured plasmids. By incorporating a blocked aptamer sequence, we also detected small molecules using the same sensor architecture. This work provides a starting point for multiplexed detection of multi-strain pathogens, and disease states caused by genetic variants (e.g., sickle cell anemia).


Craniopharyngioma: a pathologic, clinical, and surgical review.
Craniopharyngioma is a rare and mostly benign epithelial tumor of the sellar and suprasellar region. Two principal patterns of craniopharyngioma are recognized: papillary and adamantinomatous. Papillary craniopharyngiomas are encountered in adults and may lack the cystic spaces filled with "motor oil" as well as the palisading peripheral rows of epithelial cells, keratinization, or calcification typical of pediatric adamantinomatous craniopharyngioma. Secondary to their anatomic location, craniopharyngiomas may present with endocrinologic dysfunction and visual disturbances. Differential diagnosis includes Rathke's cleft cyst, pituitary adenoma, dermoid/epidermoid cysts, and other rare sellar/suprasellar lesions as pituicytomas. Many controversies exist concerning the preferred surgical approach for these tumors. Endoscopic endonasal surgery is no longer reserved only for sellar or small cystic suprasellar lesions. Prechiasmatic/preinfundibular lesions are effectively removed using an endonasal transtuberculum/transplanum approach; subchiasmatic/transinfundibular tumors require the addition of a transellar approach with inferior pituitary transposition; and retrochiasmatic/retroinfundibular lesions are better accessed performing an endonasal superior pituitary transposition. Compared with well-established trancranial approaches (pterional, subfrontal, presigmoid), endoscopic endonasal surgery combines the virtues of the caudocranial and midline approaches, allowing for appropriate infrachiasmatic exposure without the need for manipulation of surrounding neurovascular structures to access the tumor. This anatomic advantage, combined with high-definition wide-angle visualization, exquisite endonasal microsurgical techniques, and devoted instrumentation facilitates a high rate of endocrine function preservation and visual improvement, while concurrently achieving comparable resections. Endoscopic skull base reconstruction with the vascularized nasoseptal flap has dramatically reduced the incidence of cerebrospinal fluid leak, consolidating endoscopic endonasal surgery as an effective and safe alternative for the treatment of these challenging tumors.


Psychometric properties of the Assessment of Positive Occupation 15 final version in individuals with mental illness.
This study was to test the reliability and validity of the Assessment of Positive Occupational 15 (APO-15) for individuals experiencing mental illness. A sample of 408 people experiencing mental illness living in communities or admitted to hospitalized was recruited. The sample has completed demographic information, the Assessment of Positive Occupation 15 (APO-15), the Japanese version of the Self-identified Stage of Recovery Part-B (SISR-B), the Japanese version of the Recovery Assessment Scale (RAS), the General Health Questionnaire 12 (GHQ-12). APO-15 is a measure of how engaged one is in occupations that promote well-being. The final version of the APO-15 was developed by assessing the validity and reliability by mainly using confirmatory factor analysis (CFA), item response theory (IRT). This study indicated satisfactory the validity and reliability of APO-15 in a group of individuals experiencing mental illness. CFA showed acceptable values for all indices of fit, namely comparative fit index (CFI), Tucker-Lewis index (TLI) (i.e., greater than .90), and the value of root mean square error of approximation (RMSEA) was .087, which was acceptable. The IRT showed satisfactory responses for the item slope parameter (α) and item difficulty parameter (β) in APO-15. APO-15 was demonstrated good psychometric properties in measuring involvement in the occupation to promote well-being in individuals experiencing mental illness. In conclusion, the APO-15 is an important tool to enable occupational therapists to assess clients who are not engaged in well-being promoting occupations and thus enable them to participate in such occupations.


Treatment of hypertension at the university medical clinic.
The treatment of high blood pressure at the general medical clinic of a traditionally oriented university hospital was found to be unsatisfactory for most patients. Charts of all hypertensive patients (diastolic blood pressure, greater than or equal to 105 mm Hg) who made their first clinic visit in 1964 or 1971 were reviewed. Half of all patients were lost to follow-up within the first year, and blood pressure control was achieved by only one third of the patients. New information contained in the Veterans Administration study reports (1967 and 1970) had no effect on workup, compliance, or blood pressure decline. Furthermore, no significant relationship was found between blood pressure reduction and medical process, therapeutic regimens, or patient compliance. These data suggest that, in contrast to experience obtained in programs specifically designed for long-term management of this chronic disease, the present-day general medical clinic cannot satisfy the needs of most hypertensive patients.


[Scintigraphy with indium 111-labeled polynuclears: correlation with the extensiveness and activity of cryptogenetic enterocolitis].
We have studied prospectively the usefulness of indium 111 granulocytes scanning in patients with Crohn's disease and ulcerative colitis. Abdominal scans were performed 1 h, 3 h and 20 h after the injection of a pure autologous granulocyte preparation containing 3.7-5.5 MBq of radioindium. The extent of bowel involvement, evaluated on the 3-hour scan, was compared to the X-rays and endoscopic findings. The disease activity was assessed by the intensity of intestinal radionuclide uptake (IRU), the fecal indium 111 measurement (FIM) after a 4-day fecal collection, the decrease of the hepatic and splenic uptake (DHSU). It was compared to clinical and biological data as CDAI, sedimentation rate, albumin and alpha-2-globulin levels. Thirty-three examinations were performed in 26 patients, 16 with Crohn's disease and 10 with ulcerative colitis. The correlation of disease location between indium scan and other diagnosis procedures was good in 81 p. 100 of cases. CDAI was significantly correlated with radionuclide indexes: IRU, FIM, DHSU. FIM was not significantly different between mild and moderates diseases (respectively 1.5 +/- 1.0 p. 100 and 3.6 +/- 3.2 p. 100), but was different between moderate and moderately severe diseases (respectively 3.6 +/- 3.2 p. 100 and 23.6 +/- 16.7 p. 100, p less than 0.001). DHSU was significantly different between mild and moderate diseases (respectively 10.9 +/- 7.2 p. 100 and 22.5 +/- 10.7 p. 100, p less than 0.05) and between moderate and moderately severe diseases (respectively 22.7 +/- 10.7 and 42.4 +/- 7.3 p. 100, p less than 0.001). The radionuclide activity indexes were significantly correlated between themselves.(ABSTRACT TRUNCATED AT 250 WORDS)


Anti-inflammatory medication adherence and cost and utilization of asthma care in a commercially insured population.
The authors hypothesized that adherence to anti-inflammatory treatment could reduce overall cost of asthma care, as higher spending on drugs would be offset by reductions in hospital and emergency care. A retrospective observational study using 2 years of claims data for 41,234 commercially insured asthmatics on monotherapy with either leukotriene inhibitors (LI) or inhaled corticosteriods (ICS). Patients were grouped into adherence quartiles based on the percentage of days per year they had prescriptions filled (medication possession ratio). The relationship between adherence and four outcomes was examined: ( 1 ) emergency department (ED) visits, ( 2 ) hospitalizations, ( 3 ) nondrug net payments for asthma care, ( 4 ) total net payments for asthma care (including drug costs). Multivariate and logistic regression models adjusting for demographics, comorbidities, and measures of past asthma utilization were used. Adherence rates were low with a median medication possession ratio of 39% for LI and 15% for ICS. Both ED and hospital use was negatively associated with adherence to LI. Patients in the lowest quartile experienced 80 (95% confidence interval (CI) = 62-102) ED visits and 34 (95% CI = 22-52) admissions per 1000 patient-years compared to 36 (95% CI = 27-49) ED visits and 13 (95% CI = 8-22) admissions in the highest quartile. In contrast, ED visits and hospital admissions did not differ significantly between adherence groups for ICS. Total payments for asthma care increased significantly with higher adherence for both LI and ICS patients. Comparing the lowest and highest adherence quartile, payments per person per month increased significantly from $65.11 (95% CI = $57.02-$73.20) to $147.46 (95% CI = $139.48-$155.44) for patients on LI and from $38.71 (95% CI = $29.52-$47.90) to 93.13 (95% CI = $83.70-$102.56) for patients on ICS. The only subgroup, for which overall asthma payments did not increase with better adherence, were patients with past ED visit or hospital admission on LI. In this observational study, treatment with LI, but not with ICS, appears to improve disease control, as evidenced by the reduction in the incidence of ED visits and hospitalizations in patients on LI. Savings generated by this reduction in high-cost events don't offset the increased payments for drugs in more adherence patients, except for selected high-risk patients.


Healthcare-associated infections in home healthcare: an extensive assessment, 2019.
IntroductionThe number of patients and clinical conditions treated in home healthcare (HHC) is increasing. Care in home settings presents many challenges, including healthcare-associated infections (HAI). Currently, in Belgium, data and guidelines on the topic are lacking.AimTo develop a definition of HAI in HHC and investigate associated risk factors and recommendations for infection prevention and control (IPC).MethodsThe study included three components: a scoping literature review, in-depth interviews with individuals involved in HHC and a two-round Delphi survey to reach consensus among key informants on the previous steps' results.ResultsThe literature review included 47 publications. We conducted 21 in-depth interviews. The Delphi survey's two rounds had 21 and 23 participants, respectively. No standard definition was broadly accepted or known. Evidence on associated risk factors was impacted by methodological limitations and recommendations were inconsistent. Agreement was reached on defining HAI in HHC as any infection specifically linked with providing care that develops in a patient receiving HHC from a professional healthcare worker and occurs ≥ 48 hours after starting HHC. Risk factors were hand hygiene, untrained patients and caregivers, patients' hygiene and presence and management of invasive devices. Agreed recommendations were to adapt and standardise existing IPC guidelines to HHC and to perform a national point prevalence study to measure the burden of HAI in HHC.ConclusionsThis study offers an overview of available evidence and field knowledge of HAI in HHC. It provides a framework for a prevalence study, future monitoring policies and guidelines on IPC in Belgium.


Evidence for a Causal Dissociation of the McGurk Effect and Congruent Audiovisual Speech Perception via TMS.
Congruent visual speech improves speech perception accuracy, particularly in noisy environments. Conversely, mismatched visual speech can alter what is heard, leading to an illusory percept known as the McGurk effect. This illusion has been widely used to study audiovisual speech integration, illustrating that auditory and visual cues are combined in the brain to generate a single coherent percept. While prior transcranial magnetic stimulation (TMS) and neuroimaging studies have identified the left posterior superior temporal sulcus (pSTS) as a causal region involved in the generation of the McGurk effect, it remains unclear whether this region is critical only for this illusion or also for the more general benefits of congruent visual speech (e.g., increased accuracy and faster reaction times). Indeed, recent correlative research suggests that the benefits of congruent visual speech and the McGurk effect reflect largely independent mechanisms. To better understand how these different features of audiovisual integration are causally generated by the left pSTS, we used single-pulse TMS to temporarily impair processing while subjects were presented with either incongruent (McGurk) or congruent audiovisual combinations. Consistent with past research, we observed that TMS to the left pSTS significantly reduced the strength of the McGurk effect. Importantly, however, left pSTS stimulation did not affect the positive benefits of congruent audiovisual speech (increased accuracy and faster reaction times), demonstrating a causal dissociation between the two processes. Our results are consistent with models proposing that the pSTS is but one of multiple critical areas supporting audiovisual speech interactions. Moreover, these data add to a growing body of evidence suggesting that the McGurk effect is an imperfect surrogate measure for more general and ecologically valid audiovisual speech behaviors.


Vocational rehabilitation services in workers' compensation programs: evaluating research model effectiveness.
Vocational rehabilitation programs are a strategy used by many, employers to manage workers' compensation costs and the consequence of injuries for their workers. Soaring costs for employers and public entities associated with workers' compensation programs and vocational rehabilitation services indicate that additional research is needed--a need further demonstrated by the serious financial, social and psychological costs that workplace disability exacts from workers.


Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant Enterococcus spp.
We conducted a retrospective study on the impact of the empiric use of linezolid on mortality in vancomycin-resistant Enterococcus spp (VRE)-colonized hematology and hematopoietic stem cell transplantation (HSCT) patients. VRE-colonized inpatients for whom complete data were available (n=100) were divided into two groups: those who received empiric linezolid in the course of fever refractory to broad-spectrum antibiotics, replacing the glycopeptide utilized for the previous 48 h, and those who did not (control group). All patients were followed until hospital discharge or death. The impact of linezolid and risk factors for all-cause mortality were evaluated; variables with p<0.10 were analyzed in a multivariate model. A Kaplan-Meier survival analysis was done to compare survival among febrile patients colonized by VRE who received empiric linezolid with patients who did not receive linezolid. Patients empirically prescribed linezolid were generally younger (median age 33 vs. 44 years; p=0.008) and more likely to be recipients of an allogeneic HSCT (24 (68.6%) vs. 24 (36.9%); p=0.009) than patients who did not receive the drug. Fourteen (21.5%) VRE bloodstream infections were diagnosed, all in patients who did not receive empiric linezolid (p=0.002). In-hospital mortality was comparable in empiric linezolid and non-linezolid users (19 (54.3%) vs. 27 (41.5%), respectively; p=0.293). The Kaplan-Meier survival analysis showed no significant difference in survival comparing the group that received linezolid to the group that did not (p=0.72). Graft-versus-host disease (GVHD; odds ratio (OR) 5.90, 95% confidence interval (CI) 1.46-23.79; p=0.012) and persistence of neutropenia (OR 6.93, 95% CI 1.72-27.94; p=0.0065) were independent predictors of all-cause in-hospital death in HSCT patients, and persistence of neutropenia in non-HSCT patients (OR 8.12, 95% CI 1.22-53.8; p=0.030). The empiric use of linezolid in VRE-colonized hematology patients had no impact on mortality, which appeared rather to be associated with the persistence of neutropenia in general and GVHD in the HSCT group.


Crop Wild Relatives as Germplasm Resource for Cultivar Improvement in Mint (Mentha L.).
Mentha is a strongly scented herb of the Lamiaceae (formerly Labiatae) and includes about 30 species and hybrid species that are distributed or introduced throughout the globe. These fragrant plants have been selected throughout millennia for use by humans as herbs, spices, and pharmaceutical needs. The distilling of essential oils from mint began in Japan and England but has become a significant industrial product for the US, China, India, and other countries. The US Department of Agriculture (USDA), Agricultural Research Service, National Clonal Germplasm Repository (NCGR) maintains a mint genebank in Corvallis, Oregon. This facility preserves and distributes about 450 clones representing 34 taxa, hybrid species, advanced breeder selections, and F1 hybrids. Mint crop wild relatives are included in this unique resource. The majority of mint accessions and hybrids in this collection were initially donated in the 1970s by the A.M. Todd Company, located in Kalamazoo, Michigan. Other representatives of diverse mint taxa and crop wild relatives have since been obtained from collaborators in Australia, New Zealand, Europe, and Vietnam. These mints have been evaluated for cytology, oil components, verticillium wilt resistance, and key morphological characters. Pressed voucher specimens have been prepared for morphological identity verification. An initial set of microsatellite markers has been developed to determine clonal identity and assess genetic diversity. Plant breeders at private and public institutions are using molecular analysis to determine identity and diversity of the USDA mint collection. Evaluation and characterization includes essential oil content, disease resistance, male sterility, and other traits for potential breeding use. These accessions can be a source for parental genes for enhancement efforts to produce hybrids, or for breeding new cultivars for agricultural production. Propagules of Mentha are available for distribution to international researchers as stem cuttings, rhizome cuttings, or seed, which can be requested through the GRIN-Global database of the US National Plant Germplasm System, subject to international treaty and quarantine regulations.


Knockout of the neurokinin-1 receptor reduces cholangiocyte proliferation in bile duct-ligated mice.
In bile duct-ligated (BDL) rats, cholangiocyte proliferation is regulated by neuroendocrine factors such as α-calcitonin gene-related peptide (α-CGRP). There is no evidence that the sensory neuropeptide substance P (SP) regulates cholangiocyte hyperplasia. Wild-type (WT, (+/+)) and NK-1 receptor (NK-1R) knockout (NK-1R(-/-)) mice underwent sham or BDL for 1 wk. Then we evaluated 1) NK-1R expression, transaminases, and bilirubin serum levels; 2) necrosis, hepatocyte apoptosis and steatosis, and the number of cholangiocytes positive by CK-19 and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling in liver sections; 3) mRNA expression for collagen 1α and α-smooth muscle (α-SMA) actin in total liver samples; and 4) PCNA expression and PKA phosphorylation in cholangiocytes. In cholangiocyte lines, we determined the effects of SP on cAMP and D-myo-inositol 1,4,5-trisphosphate levels, proliferation, and PKA phosphorylation. Cholangiocytes express NK-1R with expression being upregulated following BDL. In normal NK-1R(-/-) mice, there was higher hepatocyte apoptosis and scattered hepatocyte steatosis compared with controls. In NK-1R (-)/(-) BDL mice, there was a decrease in serum transaminases and bilirubin levels and the number of CK-19-positive cholangiocytes and enhanced biliary apoptosis compared with controls. In total liver samples, the expression of collagen 1α and α-SMA increased in BDL compared with normal mice and decreased in BDL NK-1R(-/-) compared with BDL mice. In cholangiocytes from BDL NK-1R (-)/(-) mice there was decreased PCNA expression and PKA phosphorylation. In vitro, SP increased cAMP levels, proliferation, and PKA phosphorylation of cholangiocytes. Targeting of NK-1R may be important in the inhibition of biliary hyperplasia in cholangiopathies.


Differential gene regulation by V(IV) and V (V) ions in the branchial sac, intestine, and blood cells of a vanadium-rich ascidian, Ciona intestinalis.
Ascidians are hyperaccumulators that have been studied in detail. Proteins and genes involved in the accumulation process have been identified, but regulation of gene expression related to vanadium accumulation remains unknown. To gain insights into the regulation of gene expression by vanadium in a genome-wide manner, we performed a comprehensive study on the effect of excess vanadium ions on a vanadium-rich ascidian, Ciona intestinalis, using a microarray. RT-PCR and enzyme activity assay were performed from the perspective of redox and accumulation of metal ions in each tissue. Glutathione metabolism-related proteins were significantly up-regulated by V(IV) treatment. Several genes involved in the transport of vanadium and protons, such as Nramp and V-ATPase, were significantly up-regulated by V(IV) treatment. We observed significant up-regulation of glutathione synthesis and degradation pathways in the intestine and branchial sac. In blood cells, expression of Ci-Vanabin4, glutathione reductase activity, glutathione levels, and vanadium concentration increased after V(IV) treatment. V(IV) treatment induced significant changes related to vanadium exclusion, seclusion, and redox pathways in the intestine and branchial sac. It also induced an enhancement of the vanadium reduction and accumulation cascade in blood cells. These differential responses in each tissue in the presence of excess vanadium ions suggest that vanadium accumulation and reduction may have regulatory functions. This is the first report on the gene regulation by the treatment of vanadium-rich ascidians with excess vanadium ions. It provided much information for the mechanism of regulation of gene expression related to vanadium accumulation.


[Prevalence of hepatitis B virus markers within household contacts in the State of Amazonas].
The aim of our investigation was to evaluate, with a prevalence study, the modes of transmission of Hepatitis B virus (HBV), within infected subjects and their household contacts in the State of Amazon, western Brazilian Amazon. We studied 97 index cases and 258 household contacts. Out of the 258 household contacts of HBV, 51.6% had serological markers of a past infection, 12.0% signs of active infection, suggesting that the virus circulates within household members. The high prevalence among siblings (23.6%) demonstrates the importance of personal contact in the transmission of this virus. Another indirect indicator of intra-familial transmission was the high prevalence of HBV markers within contacts of a fulminant hepatitis. The vertical transmission of HBV in our region may or may not occur, but if it does it as a rare event. Our results demonstrate the importance of the presence of HBV, and demand other investigations to clarify the inter-familial transmission of these viruses in our region.


Hand and wrist fractures in occupational medicine.
Hand fractures are so common in the workplace that a wide variety of physicians see and treat these injuries on a daily basis. This article is designed to assist in their primary diagnosis and care, as well as to recommend when it is best to arrange treatment by a hand specialist.


NCCN outcomes research database: data collection via the Internet.
Since 1997, the National Comprehensive Cancer Network (NCCN) outcomes database has successfully collected and reported patterns of care and outcomes data in the oncology setting. Breast cancer was the first cancer site chosen for this outcomes study, with non-Hodgkin's lymphoma targeted as the next site. Quarterly reports of the data are compiled and distributed to all participating centers. The results for each institution are given to the Principal Investigator at the respective institution. At present, the NCCN database contains more than 100,000 records of longitudinal data on more than 5,000 women with breast cancer. Extending data collection to the community setting is a goal.


Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2.
Anastrozole is a widely prescribed aromatase inhibitor for the therapy of estrogen receptor positive (ER+) breast cancer. We performed a genome-wide association study (GWAS) for plasma anastrozole concentrations in 687 postmenopausal women with ER+ breast cancer. The top single-nucleotide polymorphism (SNP) signal mapped across SLC38A7 (rs11648166, P = 2.3E-08), which we showed to encode an anastrozole influx transporter. The second most significant signal (rs28845026, P = 5.4E-08) mapped near ALPPL2 and displayed epistasis with the SLC38A7 signal. Both of these SNPs were cis expression quantitative trait loci (eQTL)s for these genes, and patients homozygous for variant genotypes for both SNPs had the highest drug concentrations, the highest SLC38A7 expression, and the lowest ALPPL2 expression. In summary, our GWAS identified a novel gene encoding an anastrozole transporter, SLC38A7, as well as epistatic interaction between SNPs in that gene and SNPs near ALPPL2 that influenced both the expression of the transporter and anastrozole plasma concentrations.


Microscopic and molecular characterization of ovarian follicle atresia in Rhodnius prolixus Stahl under immune challenge.
In this work we characterized the degenerative process of ovarian follicles of the bug Rhodnius prolixus challenged with the non-entomopathogenic fungus Aspergillus niger. An injection of A. niger conidia directly into the hemocoel of adult R. prolixus females at the onset of vitellogenesis caused no effect on host lifespan but elicited a net reduction in egg batch size. Direct inspection of ovaries from the mycosed insects revealed that fungal challenge led to atresia of the vitellogenic follicles. Light microscopy and DAPI staining showed follicle shrinkage, ooplasm alteration and disorganization of the monolayer of follicle cells in the atretic follicles. Transmission electron microscopy of thin sections of follicle epithelium also showed nuclei with condensed chromatin, electron dense mitochondria and large autophagic vacuoles. Occurrence of apoptosis of follicle cells in these follicles was visualized by TUNEL labeling. Resorption of the yolk involved an increase in protease activities (aspartyl and cysteinyl proteases) which were associated with precocious acidification of yolk granules and degradation of yolk protein content. The role of follicle atresia in nonspecific host-pathogen associations and the origin of protease activity that led to yolk resorption are discussed.


Iron Causes Lipid Oxidation and Inhibits Proteasome Function in Multiple Myeloma Cells: A Proof of Concept for Novel Combination Therapies.
Adaptation to import iron for proliferation makes cancer cells potentially sensitive to iron toxicity. Iron loading impairs multiple myeloma (MM) cell proliferation and increases the efficacy of the proteasome inhibitor bortezomib. Here, we defined the mechanisms of iron toxicity in MM.1S, U266, H929, and OPM-2 MM cell lines, and validated this strategy in preclinical studies using Vk*MYC mice as MM model. High-dose ferric ammonium citrate triggered cell death in all cell lines tested, increasing malondialdehyde levels, the by-product of lipid peroxidation and index of ferroptosis. In addition, iron exposure caused dose-dependent accumulation of polyubiquitinated proteins in highly iron-sensitive MM.1S and H929 cells, suggesting that proteasome workload contributes to iron sensitivity. Accordingly, high iron concentrations inhibited the proteasomal chymotrypsin-like activity of 26S particles and of MM cellular extracts in vitro. In all MM cells, bortezomib-iron combination induced persistent lipid damage, exacerbated bortezomib-induced polyubiquitinated proteins accumulation, and triggered cell death more efficiently than individual treatments. In Vk*MYC mice, addition of iron dextran or ferric carboxymaltose to the bortezomib-melphalan-prednisone (VMP) regimen increased the therapeutic response and prolonged remission without causing evident toxicity. We conclude that iron loading interferes both with redox and protein homeostasis, a property that can be exploited to design novel combination strategies including iron supplementation, to increase the efficacy of current MM therapies.


Is ergothioneine a 'longevity vitamin' limited in the American diet?
There is mounting evidence for the potential for the natural dietary antioxidant and anti-inflammatory amino acid l-Ergothioneine (ERGO) to prevent or mitigate chronic diseases of aging. This has led to the suggestion that it could be considered a 'longevity vitamin.' ERGO is produced in nature only by certain fungi and a few other microbes. Mushrooms are, by far, the leading dietary source of ERGO, but it is found in small amounts throughout the food chain, most likely due to soil-borne fungi passing it on to plants. Because some common agricultural practices can disrupt beneficial fungus-plant root relationships, ERGO levels in foods grown under those conditions could be compromised. Thus, research is needed to further analyse the role agricultural practices play in the availability of ERGO in the human diet and its potential to improve our long-term health.


Accumulation of beta ig-h3 gene product in corneas with granular dystrophy.
We isolated and identified the major protein present in corneas with granular dystrophy (GCD). We compared Coomassie-blue-stained protein bands obtained on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) from the extracts of corneas with GCD, corneas with other disorders, and normal human corneal tissue. After SDS-PAGE and transfer to a polyvinylidene difluoride membrane, bands of interest were analyzed by amino acid sequencing and by Western blotting. Corneas with GCD were also examined immunohistochemically. On SDS-PAGE a 63-kd band just below albumin was present in extracts of all corneas. The albumin/63-kd ratio was normally approximately 3:1, suggesting that the protein is a dominant constituent of the cornea. This band was much more plentiful than normal in corneas with GCD. Amino-terminal sequence analysis of the protein revealed a Gly-Pro-Ala-Lys-Ser-Pro-Tyr-Gln-Leu-Val-Leu-Gln-His-Ser-Arg sequence indistinguishable from an amino-terminal protein sequence deduced from a cDNA clone designated beta ig-h3, and it as well as the abnormal accumulations in GCD cross-reacted with beta ig-h3 antiserum. The presence of excessive beta ig-h3 in human corneas with GCD together with reported mutations in the beta ig-h3 gene in GCD suggests that the mutated gene product is a fundamental constituent of the characteristic corneal accumulations in GCD.


Effect of polymeric substrate on sludge settleability.
The study aims to evaluate the role of a polymeric substrate (starch) on sludge settleability. Despite being an important COD component of the wastewater, the relationship between polymeric substrates and bulking sludge has been hardly studied. The polymers are hydrolysed at a rate smaller than the consumption rate of monomers. This means that the soluble substrate resulting from hydrolysis is likely to be present at growth rate limiting concentrations. According to the kinetic selection theory this leads to bulking sludge. However, a recently postulated theory suggests that, strong diffusion limited micro-gradients of substrate concentration inside flocs lead to bulking sludge, and not a low substrate concentration as such. If the polymeric COD is first incorporated in the sludge floc and afterwards hydrolysed in the sludge floc then there is essentially no substrate gradient inside the biological flocs. The experiments showed that conditions leading to bulking sludge with monomers (glucose) did not lead to bulking when starch was used. A bulking sludge event was even cured just by substituting the monomer with starch. These results are clearly in line with a diffusion gradient--based theory for bulking sludge. Nevertheless, flocs growing on starch are more open, fluffy and porous than flocs formed on maltose or glucose, most likely because the starch needs to be hydrolysed at the surface of the micro-colonies forming the flocculated sludge. Some additional observations on occurrence of filamentous bacteria in oxygen diffusion limited systems are also discussed in this manuscript.