Retropharyngeal Blastomycosis Abscess Causing Osteomyelitis, Discitis, Cervical Deformity, and Cervical Epidural Abscess: A Case Report.
Blastomycosis infection is caused by the inhalation of the spores of the dimorphic Blastomyces sp.fungus. While more commonly a self-limited infection of the lungs, extrapulmonary manifestations arise from hematogenous or contiguous spread. Disseminated infection most often includes skin lesions and osteomyelitis; however, central nervous system (CNS) involvement is infrequently reported in the literature. Herein, we present a case of a retropharyngeal blastomycosis abscess leading to cervical spine osteonecrosis with retropulsion, deformity, and a spinal epidural abscess, and we discuss the relevant literature. The patient was successfully treated with cervical traction, followed by a combined anterior-posterior cervical approach, including abscess drainage, corpectomies, and instrumented fixation. Postoperatively, the patient completed 12 months of voriconazole and had near resolution of preoperative symptoms. Expediting neurosurgical intervention, such as the utilization of decompression, the clearance of infectious burden, and the correction of alignment, is critical for preventing downstream complications. Retropharyngeal blastomycosis abscesses are rare, and we report one of the rare instances of dissemination to and the degeneration of the cervical spine.


Deciding on a mixed-methods design in a doctoral study.
Research in social science, including nursing, can be broadly split into two main types, qualitative and quantitative. Each has strengths and weaknesses. In some studies both methods are employed. In all cases the method chosen should answer the question set, rather than simply reflect the preferences of the researcher. This article outlines how the authors, one of whom was studying for a doctorate in nursing (Al-Hamdan 2008), the other who was the supervisor, determined the most appropriate research method to use for the doctorate.


A Focus on Pharmacological Management of Catecholaminergic Polymorphic Ventricular Tachycardia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy characterized by adrenergic mediated ventricular arrhythmia. Untreated CPVT is a malignant syndrome with more than 50% of arrhythmic events and up to 25% of fatal or near-fatal cardiac events at 8 years follow-up. Prevention of sudden cardiac death starts with exclusion of competitive sports. Beta blockers (BB) are the cornerstone pharmacological therapy for the prevention of cardiac event in CPVT patients. Dose of BB should be highly tolerable, preferably nadolol. Efficiency of BB is undeniable but uncompleted. Therefore, on top of BB, one can propose the use of Calcium channel blockers or Class 1c antiarrythmic drugs. Indeed Flecainide allows reducing exercise- induced premature ventricular contraction and ventricular arrhythmia. Pharmacological management should be a stepwise approach with BB as the first line of choice. At each step of therapeutic changes, heart rhythm during exercise should be monitored by Holter monitoring and exercise testing. If the pharmacological management fails, left cardiac sympathetic denervation or implantation of cardioverter defibrillator should be considered.


Heavy metals and neurodevelopment of children in low and middle-income countries: A systematic review.
The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.


Subluxation of the shoulder in hemiplegia.
This is a study of 100 hemiplegic patients of whom 17 had downward subluxation of the shoulder joint. The mechanism of this complication is described and appropriate preventative treatment suggested.


[Study of the relevant factors of behavioral development among 30-month-old infants in rural area of Shaanxi Province].
Objective: To explore the relevant factors of behavioral development among 30-month-old infants in rural area, Shaanxi Province. Methods: The behavioral development among 977 infants aged 30-month-old was evaluated in Changwu and Binxian of Shaanxi province from July 2006 to August 2008. The inclusion criteria included single live birth between January 2004 and February 2006, mother had participated in a community-based intervention study named "Impact of multi-micronutrient supplementation during pregnancy on low birth weight and premature delivery" . Infants who had obvious deformity or other birth defects, infants who could not complete the questionnaire survey, physical examination were excluded from the study. The self-designed questionnaire was used to investigate the information of feeding patterns, disease status, physical development, and immunization status of the infants, and their behavioral development were assessed by Bayley scales of infant development (BSID). General Linear Model was used to adjust the possible confounding factors, and the analysis of variance was performed to explore the effects on the behavioral development among infants aged 30-month-old. Results: Among the infants in the study, the average age was (30.6±0.6) months old, the mean birth weight was (3 199.1±405.9)g. After adjusted the mothers' age of delivery, educational level and occupation of the parents, family ecnomic conditions and the number of children, infants whose mother exposed to toxic chemicals during pregnancy had lower score in activity (-0.179±0.961) and lower score in concentration (-0.177±1.099) compared with infants with unexposed mother (0.058±1.006, P=0.001; 0.057±0.960, P=0.003). Similarly, infants whose mother took drugs during pregnancy had lower score in persistent behaviors (-0.070±1.000) compared with infants whose mother did not(0.085±1.006, P=0.017). Compared with normal birth infants(0.043±0.981, P=0.007; 0.021±0.984, P=0.034), infants less than gestational age and low birth weight had lower score in concentration(-0.198±1.063 and-0.389±1.285, respectively). After adjusted the delivery gestational age of mothers, the months of infants, the mothers' age of delivery, educational level and occupation of the parents, family ecnomic conditions, the number of children, and the main orderlies of infants, the score of activity of infants suffered from diseases in early month age was-0.049±0.992, which was lower than those who did not(0.207±1.011, P=0.001). The infants with Rickets signs had lower score in motor coordination (-0.218±0.896) than normal infants (0.031±1.011, P=0.013). Infants whose mother with adequate micronutrient supplementation in pregnancy had higher score in concentration (0.066±0.966) than those whose mother with insufficient supplementation (-0.062±1.027, P=0.043). Furthermore, infants with fine protein added and minerals and vitamins added had higher score in activity and concentration compared with those insufficient, who scored 0.078±1.013 and 0.496±0.872 (-0.254±0.924, P<0.001; 0.001±0.997, P=0.033), respectively. Conclusion: Micronutrient supplementation during pregnancy and reasonable nutrition added during childhood could affect behavioral development among infants.


Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33.
The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5 q 33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. One 15-bp insertion/deletion in exon 4 of TIM 1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07--1.45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12--1.47]; P=.0003). SNPs in the 5' genomic region in ITK, which show moderate linkage disequilibrium with those in TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.


Tobacco use cessation counseling of parents.
Tobacco use and secondhand tobacco smoke exposure of children are a significant problem faced by pediatricians. This article reviews the recommendations of the 2008 update of the guideline Treating Tobacco Use and Dependence and their application in the pediatric setting. Every tobacco user seen in the clinical setting, including parents and other persons who are not patients, should be offered evidence-based treatment. At minimum, treatment consists of brief counseling and access to resources that support quit attempts. Pharmacotherapies should be offered to all tobacco users, except for pregnant women, adolescents, and other groups for which effectiveness of pharmacotherapies has not been shown. The five As (ask, advise, assess, assist, and arrange follow-up) continue to be recommended as the key points in counseling. Tobacco use is a chronic disease that develops early in life and affects many patients and families seen in the pediatric setting. Every tobacco user should be offered treatment, including parents and other family members, and the most effective treatment is a combination of counseling and pharmacotherapies.


Comparative characteristics of porous bioceramics for an osteogenic response in vitro and in vivo.
Porous calcium phosphate ceramics are used in orthopedic and craniofacial applications to treat bone loss, or in dental applications to replace missing teeth. The implantation of these materials, however, does not induce stem cell differentiation, so suitable additional materials such as porous calcium phosphate discs are needed to influence physicochemical responses or structural changes. Rabbit adipose-derived stem cells (ADSC) and mouse osteoblastic cells (MC3T3-E1) were evaluated in vitro by the MTT assay, semi-quantitative RT-PCR, and immunoblotting using cells cultured in medium supplemented with extracts from bioceramics, including calcium metaphosphate (CMP), hydroxyapatite (HA) and collagen-grafted HA (HA-col). In vivo evaluation of the bone forming capacity of these bioceramics in rat models using femur defects and intramuscular implants for 12 weeks was performed. Histological analysis showed that newly formed stromal-rich tissues were observed in all the implanted regions and that the implants showed positive immunoreaction against type I collagen and alkaline phosphatase (ALP). The intramuscular implant region, in particular, showed strong positive immunoreactivity for both type I collagen and ALP, which was further confirmed by mRNA expression and immunoblotting results, indicating that each bioceramic material enhanced osteogenesis stimulation. These results support our hypothesis that smart bioceramics can induce osteoconduction and osteoinduction in vivo, although mature bone formation, including lacunae, osteocytes, and mineralization, was not prominent until 12 weeks after implantation.


The potentiation of sinus arrhythmia by vasoactive intestinal polypeptide (VIP) in the anaesthetized dog.
Vasoactive intestinal polypeptide (VIP) is a neuropeptide released from the vagus, which in contrast to acetylcholine has a long-acting positive chronotropic effect on the heart. The aim of this study, in the anaesthetized dog, was to examine the effects of VIP and a VIP antagonist when injected into the sinus node artery of a vagally intact heart in sinus arrhythmia. The response was compared to that produced by noradrenaline (NAD) infusion and stimulation of the sympathetic nerves to the heart. Mean +/- S.D. of 30 R-R intervals was used to describe mean heart rate interval and heart rate variability. VIP, a VIP antagonist, NAD and sympathetic nerve stimulation all caused increases in heart rate without significant increases in blood pressure. However, only VIP caused an increase in heart rate variability; VIP antagonism and NAD caused a decrease and sympathetic nerve stimulation had no effect. These results suggest that VIP and acetylcholine when released from the vagus act synergistically to increase sinus arrhythmia.


Ambulatory blood pressure monitoring and structural changes in carotid arteries in normotensive workers occupationally exposed to lead.
Occupational exposure to lead may cause an increase in blood pressure. The aim of the study was to estimate the effect of occupational exposure to lead on selected parameters of ambulatory blood pressure monitoring (ABPM) and structural changes in carotid arteries. The study included 33 normotensive men occupationally exposed to lead and 39 unexposed men employed in administration of the foundry. All of the men underwent 24-hour ambulatory blood pressure monitoring and high-resolution B-mode ultrasonography to determine intima-media thickness (IMT). The group of men occupationally exposed to lead manifested significantly higher mean systolic blood pressure (MSBP), mean diastolic blood pressure (MDBP), mean blood pressure (MBP), pulse pressure (PP), variability of diastolic blood pressure (VDBP), and IMT than the unexposed group. The studied groups did not differ in mean values of variability of systolic blood pressure (VSBP). As compared to the unexposed group, in men exposed to lead, atherosclerotic plaques were significantly more common. In the group of persons exposed to lead the Pearson's correlation coefficient analysis revealed significant linear positive correlations between MSBP and IMT, between lead level and the number of atherosclerotic plaques, and between lead level and PP. Multivariate stepwise regression analysis demonstrated that higher lead level in blood and higher triglyceride concentration in blood represent independent risk factors of an increased pulse pressure in the group of individuals occupationally exposed to lead. Occupational exposure to lead can be associated with increased blood pressure and accelerated progression of atherosclerosis.


The social insurance systems in foreign countries and pricing of medical devices.
In this aging Japanese society, the demand for ensuring a healthy life and improving the quality of life is on the rise. The government declared "Health Japan 21" and dental health has been identified as one of the most important issues. At the same time, national medical care expenditure is increasing year by year. As such, efficiency in dentistry is required, and the quality, efficacy, and safety of medical devices have been standardized. As one of the steps toward introducing new medical devices and technology, this report contains a collection of data, research, and studies on the social insurance system and pricing of medical devices in foreign countries.


Landmarks help guide attention during visual search.
Using a novel visual search paradigm McCarley et al. (2003) concluded that the oculomotor system keeps a history of 3-4 previously attended objects. However, their displays were visually sparse, denying participants structural information which might be used during normal search. This might have underestimated memory capacity. To examine this possibility, we included landmarks in the same search paradigm. Previously examined items were re-examined less frequently when landmarks were present compared to when they were absent. Results indicate that objects in the environment that share no features with search items are used as external support to aid memory in guiding visual search.


Serum basic fibroblast growth factor levels in patients with ischemic heart disease.
Being a potent promoter of endothelial and smooth muscle cell proliferation, basic fibroblast growth factor (bFGF) is presumed to play a key role in coronary collateral development and atherogenesis. To characterize serum bFGF levels in patients with ischemic heart disease. The study population consisted of patients with angina (n=33) and after uncomplicated myocardial infarction (n=12). The number of significantly stenosed (> or = 50%) vessels and angiographic coronary collateral score were noted. Blood was drawn immediately prior to elective coronary angiography in study patients for bFGF levels. Twenty healthy, age-matched subjects served as control for serum bFGF. Serum bFGF levels were undetectable in all 20 control subjects, but were detectable in 15/33 (45%) patients with angina and 3/12 (25%) post-infarction patients, respectively (P=0.002). Serum bFGF levels were detectable in 13/23 (57%) patients with 0- or 1-vessel disease, as compared with 5/22 (23%) patients with 2- or 3-vessel disease (P<0.05). Detectable serum bFGF levels were not in correlation with coronary collateral score (P=1). Serum levels of bFGF are elevated in patients with ischemic heart disease, particularly in those with minimal coronary artery disease. We postulate that detectable serum bFGF levels reflect active atherogenesis rather than myocardial collateral development.


Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress.
Amyloid beta-peptide (A(beta)) is heavily deposited in the brains of Alzheimer's disease (AD) patients, and free radical oxidative stress, particularly of neuronal lipids and proteins, is extensive. Recent research suggests that these two observations may be linked by A(beta)-induced oxidative stress in AD brain. This review summarizes current knowledge on phospholipid peroxidation and protein oxidation in AD brain, one potential cause of this oxidative stress, and consequences of A(beta)-induced lipid peroxidation and protein oxidation in AD brain.


An overview of the pathogenesis of canine hip dysplasia.
Canine hip dysplasia (CHD) is an inherited, developmental condition that involves a lack of conformity between the femoral head and acetabulum and invariably leads to osteoarthritis. In this paper, the author briefly reviews what is known about the genetics of CHD, how joint laxity and growth rate are related to development of CHD, and the possibility that CHD is a systemic disease involving multiple joints, not just the hip joint.


Hypermagnesaemia, but Not Hypomagnesaemia, Is a Predictor of Inpatient Mortality in Critically Ill Children with Sepsis.
The effect of serum magnesium on the prognosis of children with sepsis in the pediatric intensive care unit (PICU) is unclear. This study was designed to assess the risk of inpatient mortality for children with sepsis in the PICU based on serum magnesium levels at admission. We collected patients' clinical information from the Pediatric Intensive Care database and then performed locally weighted scatterplot smoothing (LOWESS) analysis, Kaplan-Meier analysis, and multivariate logistic regression to determine the relationship between admission serum magnesium and inpatient mortality in children with sepsis. A total of 974 critically ill children with sepsis were included, with 246 patients in the hypomagnesemia group, 666 in the normal group, and 62 in the hypermagnesemia group. The chi-square test suggested that the hypermagnesemia group had higher in-hospital mortality than the normal group (14.5% vs. 2.4%, P < 0.001). Kaplan-Meier curves revealed that the 30-day overall survival rate was lower in the hypermagnesaemia group than in the normal group (P < 0.001). The multivariate logistic regression model revealed that hypermagnesaemia was a risk factor related to inpatient mortality (odds ratio 4.22, 95% CI 1.55-11.50), while hypomagnesaemia was not a significant factor for inpatient mortality (odds ratio 0.78, 95% CI 0.26-2.32). Hypermagnesaemia, but not hypomagnesaemia, is a predictor of inpatient mortality in critically ill children with sepsis.


Virus spread and initial pathological changes in the nervous system in genital herpes simplex virus type 2 infection in mice. A correlative immunohistochemical, light and electron microscopic study.
Mice were infected by the vaginal route with the MS strain of herpes simplex virus type 2 (HSV-2). Serial vaginal cultures were used to confirm infection and to select mice for this study. Two mice were killed by perfusion on days 2-6 post infection (p.i.) and lumbar and sacral cord with cauda were fixed and embedded for electron microscopy. Semithin Epon-sections were stained for viral antigen using a rabbit anti-HSV-2 antiserum and the Avidin-Biotin (ABC) method. Thin sections from antigen-positive blocks were examined by electron microscopy, and the number and types of infected cells detected by these two methods were compared. A good correlation was found between detection of infected cells by these methods. Infected cells included neurons of dorsal root ganglia and spinal cord, satellite cells of dorsal root ganglia, non-myelinating Schwann cells, astrocytes, oligodendrocytes and arachnoidal cells. Infected cells were first detected in the cauda on day 3 p.i. and in the spinal cord on day 5 p.i. The temporal and spatial distribution of infected cells was consistent with neural spread to and within the CNS. The pathological lesions showed a good correlation with the distribution and number of infected cells and are probably due to a direct virus effect. The similar sensitivity of the Epon-ABC method to electron microscopy in detecting infected cells indicates that this method may have useful applications in both experimental and diagnostic work.


Mycorrhizal colonization and grain Cd concentration of field-grown durum wheat in response to tillage, preceding crop and phosphorus fertilization.
A 3-year field trial was conducted to investigate the effect of agricultural management practices including tillage, preceding crop and phosphate fertilization on root colonization by arbuscular mycorrhizal (AM) fungi and grain cadmium (Cd) concentration of durum wheat (Triticum turgidum L.). The relationship between grain Cd and soil and plant variables was explored to determine the primary factors affecting grain Cd concentration. Mycorrhizal colonization of the roots was reduced by conventional tillage or when the preceding crop was canola (Brassica napus L.), compared to minimum tillage or when the preceding crop was flax (Linum usitatissimum L.). In contrast, grain Cd was not consistently affected by any treatment. Grain Cd was generally below the maximum permissible concentration (MPC) of 100 microg Cd kg(-1) proposed by WHO. Grain Cd varied substantially from year to year, and could be predicted with 70% of variance accounted for by using the model: grain Cd concentration = - 321.9 + 44.5x ln(grain yield) + 0.26x soil DTPA-Cd + 182.5x soil electrical conductivity (EC)- 0.98x grain Zn concentration. These common agricultural management practices had no effect on grain Cd concentration in durum wheat though they impacted mycorrhizal colonization of roots. Grain yield and to a lesser extent soil conditions of EC and DTPA-Cd and grain Zn influenced grain Cd, whereas mycorrhizal colonization levels did not.


Prolonged survival in an aged Labrador retriever with a metastatic insulinoma.
This case report highlights an unusually prolonged, asymptomatic, disease-free interval in an aged male Labrador retriever that underwent partial pancreatectomy for a functionally active pancreatic insulinoma with histologically confirmed hepatic metastasis. The patient developed pancreatitis and nonseptic suppurative peritonitis 24 hr after surgical resection of the insulinoma and was managed medically until discharge. Three mo after surgery, the dog was diagnosed with exocrine pancreatic insufficiency (EPI) that was effectively managed with parenteral pancreatic enzymes. Due to normal glucose levels 3 mo postsurgically, liver samples from the initial surgery were resubmitted for immunohistochemistry. Results confirmed insulinoma metastasis with insulin expression. Ten mo postsurgically, the blood glucose was normal and serum insulin levels were slightly above the upper reference limit. The first hypoglycemic episode was documented 23 mo postoperatively, which was effectively managed with prednisone. The cause for the prolonged disease remission and survival was unknown, but was possibly a result of pancreatitis and peritonitis, partial spontaneous regression of metastatic lesions, or idiopathic. Despite life-threatening postoperative complications, this patient enjoyed a profoundly longer than expected survival. This case highlights the importance of removing the primary tumor (insulinoma) despite the presence of metastatic disease.


Stress specifically deteriorates working memory in peripheral neuropathic pain and fibromyalgia.
This study aimed to explore the influence of chronic stress, measured through hair cortisol, on executive functions in individuals with chronic pain. We expected that there would be significant differences in chronic stress and executive functioning between pain patients and healthy controls, as well as between primary and secondary pain classifications. We also hypothesized that hair cortisol concentration was predictive of worse performance on tests of executive functions, controlling for objective and subjective covariates. For this study, 122 participants provided a hair sample (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 58 matched healthy controls). Eighty-four of these participants also completed highly detailed testing of executive functions (n = 40 with fibromyalgia; n = 24 with peripheral neuropathic pain; n = 20 healthy controls). To assess differences in stress levels and executive functions, t-tests were used to compare patients with controls as well as fibromyalgia with peripheral neuropathic pain. Then, univariate regressions were used to explore associations between stress and executive functioning in both chronic pain classifications. Any significant univariate associations were carried over to hierarchical multivariate regression models. We found that patients with chronic pain had significantly higher cortisol levels than healthy controls, but all groups showed similar executive functioning. Hierarchical multiple regression analyses disclosed that in a model controlling for age, sex and pain medication usage, hair cortisol levels explained 8% of the variance in spatial working memory strategy in individuals with chronic pain. The overall model explained 24% of the variance in spatial working memory. In a second model using imputed data, including both objective and subjectively reported covariates, hair cortisol levels explained 9% of the variance, and the full model 31% of the variance in spatial working memory performance. Higher levels of cortisol indicated worse performance. In this study, an applied measure of chronic stress, namely hair cortisol, explained a substantial part of the variance on a spatial working memory task. The current results have important implications for understanding and treating cognitive impairments in chronic pain.


Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma.
In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.


The Association Between Chronic Ankle Instability and Neuromuscular Performance in Pre-Recruitment Infantry Soldiers.
Ankle instability can include various impairments, including perceived instability (PI), mechanical instability (MI), and recurrent sprains (RS), alone or combined. To examine the prevalence of eight ankle impairment subgroups and their effect on neuromuscular performance in pre-recruitment combat soldiers. Cross-sectional study. Military Infantry basic training base. A total of 364 pre-recruitment males combat soldiers (aged 18-21). The participants were assessed for PI (via the Cumberland Ankle Instability Tool), MI (using the Anterior Drawer Test and Medial Talar Tilt Test ), and RS (based on history) in their dominant and non-dominant legs; injuries were combined into eight subgroups: (A) PI; (B) RS; (C) PI+RS; (D) MI; (E) PI+MI; (F) MI+RS; (G) PI+MI+RS; and (H) none. Participants were screened for neuromuscular performance (proprioceptive ability, hopping agility, triceps surae muscle strength, and dynamic postural balance) during the first week of military basic training. For the dominant and non-dominant leg, RS were reported by 18.4% and 20.5% of the participants, respectively; PI was reported by 27.8% and 29.2%; and MI was seen in 9.9% and 8.8% of the participants, respectively. One-Way ANOVA showed significant differences in the mean proprioceptive ability scores (assessed using the Active Movement Extent Discrimination Apparatus) of all subgroups with impairments in both the dominant and non-dominant leg [F=6.943, η2=.081, p<.001; and, F=7.871, η2=.091, p<.001, respectively]. Finally, significant differences were found in the mean muscle strength of subgroups with impairments in the non-dominant leg [F=4.884, η2=.056, p=.001]. A high prevalence of ankle impairments were identified among the participants, who exhibited reduced abilities in most neuromuscular assessments compared to those without impairments. Moreover, participants with one impairment (either PI, RS, or MI) exhibited different neuromuscular performance deficits than those with more than one impairment.


Dietary supplementation with rutin has pro-/anti-inflammatory effects in the liver of juvenile GIFT tilapia, Oreochromis niloticus.
Dietary supplementation with rutin may have some pharmacological qualities including anti-inflammatory effects. Kupffer cell activation resulted in increased transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities in juvenile freshwater tilapia, Oreochromis niloticus, in response to 0.1 or 0.3 g/kg dietary supplementation of rutin. Results showed that hepatic IgM, anti-inflammatory-cytokines, and pro-inflammatory cytokines were significantly decreased in groups treated with high doses of rutin. Hepatic IgM and anti-inflammatory cytokines (IL-10 and IFN-γ) transcripts were significantly decreased, whereas the transcripts of the pro-inflammatory cytokines, TNFα and IL-1β were significantly decreased, whereas IL-8 was significantly increased. The number of Kupffer cells in rutin-treated groups was significantly decreased, and scanning electron micrographs showed that rutin enriched the number of gut microvilli and secretion pits. With the phenomena of cell apoptosis occurred in the rutin groups, the present study demonstrated that optimum levels of rutin may be beneficial but excessive level may cause liver impairment, which may be absorbed by the gut and then transported to the liver.


Effect of fit adjustment on CEREC CAD-CAM veneers.
To measure and compare the adaptation of CEREC CAD-CAM porcelain veneers with and without fit adjustment. Two groups of porcelain veneers were fabricated using the CEREC CAD-CAM technique for standardized preparations on 10 artificial teeth. Mesial preparation contacts were broken, but distal contacts remained intact. One group was adjusted using a disclosing spray to improve fit, another group made for the same teeth was not adjusted before cementation. The veneers were cemented in a standardized manner to their teeth. The veneers and their attached cement were retrieved, embedded in epoxy resin and sectioned twice to produce eight sections. Each section was measured at three defined points from the external surface inwards. Three-way ANOVA disclosed that fit adjustment was relatively ineffective (P approximately 0.05), but that measurement section location, measurement point location and their interaction significantly affected fit (P < 0.05). Restoration of the broken proximal contact, or simulated diastema closure did not compromise fit. Incisal margins ranked worst for fit. Surface measurement point locations ranked worse than internal points. The fit of these CEREC CAD-CAM veneers was not substantially different from previously published fit values for conventional porcelain veneers.


Allosteric interactions in sipunculid and brachiopod hemerythrins.
Chemical and spectroscopic consequences of allosteric interactions for ligand binding to sipunculid (Phascolopsis gouldii) and brachiopod (Lingula reevii) hemerythrins (Hrs) have been investigated. Possible allosteric effectors for homotropic effects in sipunculid Hrs have been examined, but only reduction in ligand affinity is observed without cooperativity. In contrast to sipunculid Hr, L. reevii Hr binds O2 cooperatively in the pH range 7-8 and exhibits a Bohr effect. Spectroscopic comparisons of the sipunculid and brachiopod Hrs show no significant differences in the active site structures; therefore, modulation of oxygen affinity is attributable to effects linking the site to quaternary structural changes in the octamer. Oxygen equilibria can be fit with a conformational model incorporating a minimum of three states, tensed (T), relaxed (R), and an R-T hybrid. Resonance Raman spectra of L. reevii oxyHr show a shift in the peroxo stretching frequency when the pH is lowered from pH 7.7 (predominantly R oxyHr) to pH 6.3 (a mixture of R, T, and R-T hybrid), but P. gouldii Hr does not have a frequency shift under the same conditions. In contrast to hemoglobins, ligand binding to the deoxy and met forms is noncooperative for brachiopod (and sipunculid) Hrs. It is thus suggested that conformational changes in the protein are linked to the oxidation state change that accompanies oxygenation of the coupled binuclear iron site (deoxy [FeIIFeII]----oxy [FeIIIFeIII]). The total allosteric energy expended in oxygenation is about 1.4 kcal/mol, and such a shift is possible in the relaxed-tense conversion with relatively limited constraints of the iron coordination environment via the protein quaternary structure. The mechanism of cooperativity in the binuclear copper oxygen carrier hemocyanin is discussed in light of these results.


The association between recipient alcohol dependency and long-term graft and recipient survival.
The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.


Regions in the transit peptide of SSU essential for transport into chloroplasts.
Deletion mutations, 3-19 amino acids in size, were introduced into the transit peptide (57 amino acids) of a small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase from pea. Transport of the authentic small subunit precursor (pSSU) and of the mutant pSSUs by isolated chloroplasts of pea was examined. We show that the transit peptide contains two different, separated functional regions. A deletion mutation in the central region of the transit peptide, a region purported to be important for function, barely affected transport. Changes in the amino-terminal region of the transit peptide appeared normal. A deletion mutation at the carboxy-terminus of the transit peptide interfered with both transport and processing. From the aberrant processing we suggest that pSSU is matured in more than one step, and that the maturation signal is located within the carboxy-terminal 16 amino acids. The methionine residue at the evolutionarily conserved cleavage site (cysteine-methionine) between the transit peptide and the mature protein is not essential processing.


Kitamycin C, a new antimycin-type antibiotic from Streptomyces antibioticus strain 200-09.
An actinomycete strain 200-09, isolated from a soil sample collected from the coast of Hawaii, USA, was identified as Streptomyces antibioticus on the basis of its morphological, physiological and biochemical characteristics as well as 16S rDNA analysis. A new antimycin-type antibiotic, kitamycin C (1), together with kitamycin A (2), kitamycin B (3), urauchmycin B (4), deisovaleryblastomycin (5) was isolated from a cultured broth of strain 200-09. The structure of the new compound was determined by spectroscopic data, including HR-ESI-MS and NMR. All the compounds exhibited antifungal activities against Candida albicans with MIC of about 25.0 μg mL-1.


Z-score of weight for age of infants with atopic dermatitis and cow's milk allergy fed with a rice-hydrolysate formula during the first two years of life.
Recently, rice-based formulas have been widely used in hypoallergenic diets, but data on nutritional values are scarce. To evaluate the growth of infants fed with a rice-based hydrolysate formula, compared to those infants fed with a soy formula or an extensively hydrolysed casein formula, in the first 2 y of life. A total of 88 infants were enrolled between March 2002 and March 2004. Fifty-eight infants with atopic dermatitis (AD) and cow's milk allergy (CMA), confirmed by open challenge, were enrolled as study group: 15 were fed with a rice-based hydrolysate formula (RHF), 17 with a soy-based formula (SF) and 26 with an extensively hydrolysed casein formula (eHCF). Thirty infants with AD without cow's milk allergy were recruited as a control group (CG) and fed with a free diet. Weight was recorded on enrolment and at 3-monthly intervals in the first year of life, and at 6-monthly intervals in the second year. Infants were weighed naked, before feeding, by means of an electronic integrating scale. The z-scores of weight for age were calculated. One-way analysis of variance and Student's t-test were used for statistical comparison. Significance was set at p<0.05. No significant differences between the RHF, SF and eHCF groups were observed for the z-score of weight for age during the first 2 y of life, but a significantly lower difference was seen in the RHF group compared to the control group in the intervals 9 mo-1 y (p=0.025) and 1-1.5 y (p=0.020) of age. In contrast, the SF and eHCF groups were comparable to the control group, but the eHCF group was significantly lower (p=0) in the first trimester of life. Even if our findings show no significant difference between RHF and control, low weight observed in infants fed with RHF raises doubts about the nutritional adequacy of rice-hydrolysate formulas.


Faster escalation from first drink to first intoxication as a risk factor for binge and high-intensity drinking among adolescents.
Age of first drink is a key risk factor for adolescent high-risk alcohol use. The current study examined whether speed of escalation from first drink to first intoxication is an additional risk factor, and whether these two factors are associated with binge and high-intensity drinking among adolescents. Data collected in 2005-2017 from a nationally-representative sample of 11,100 U.S. 12th grade students participating in the Monitoring the Future study were coded to indicate grade of first drink, grade of first intoxication, and speed of escalation from first drink to first intoxication. Logistic regression models estimated bivariate and multivariable odds of past 2-week binge (5+ drinks in a row) and high-intensity (10+ drinks in a row) drinking in 12th grade. Of those who reported intoxication by 12th grade, almost 60% reported first drunkenness in the same grade in which they first drank. The likelihoods of 12th grade binge and high-intensity drinking were significantly associated with both grade of first drink and speed of escalation to intoxication. Past two-week high-intensity drinking prevalence was 17.4% among those with immediate (same-grade) escalation from first drink to first intoxication; 15.8% among those with a 1-grade delay, and 12.6% among those with a 2+ grade delay to intoxication. The majority of students escalate quickly from having their first drink to being intoxicated for the first time. Both earlier age of first drink and a faster escalation from first drink to first intoxication are important indicators of binge and high-intensity drinking risk among adolescents.


Early-Age Properties of Concrete Based on Numerical Hydration Modelling: A Parametric Analysis.
The early-age performances of cement-based mixtures are governed by cement hydration reactions. As a matter of fact, the heat generated during the setting and hardening phases due to the hydration processes increases the temperatures within the concrete elements while it starts developing its mechanical properties. These thermal stresses can cause the premature cracking of the cementitious matrix and undermine the long-term durability of the whole concrete element, especially in the case of massive structures where the dissipation of generated heat is more difficult. It is worth highlighting that the kinetics of cement hydration is mainly governed by the mixture composition; on the other hand, the heat generated during the setting and hardening is also influenced by the geometry of the element and/or its curing conditions. In this context, this study presents a numerical procedure intended to simulate the hydration reactions, and hence scrutinize the development of concrete properties at the early-age. Specifically, considering the variation of several factors, such as concrete strength class, element size and curing conditions, a comprehensive parametric analysis is presented herein, leading to the proposal of a simplified approach for both predicting the time evolution of the concrete mechanical performances at the early-age and mitigating the risk of premature cracking.


Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient.
Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed.


Reworking professional nursing identity.
In spite of professional socialization through nursing education programs, new graduates experience stress as they become working professionals. This grounded theory study explores experienced nurses' perceptions of how they became professional. The central problem for nurses was dissonance between expectations and experiences; they addressed this through an iterative, three-stage process of reworking professional identity. The stages of this process are assuming adequacy, realizing practice, and developing a reputation. Iterations of this process occur as new discrepancies are noticed, enhanced awareness dawns, practice changes, learning is undertaken, or experienced nurses become relative novices in another work area. Nurses move through stages more quickly and at different levels with each iteration. Three contextual factors influence the process: expectation; perception of the status accorded by others to nursing; and supportiveness by acceptance, assistance, and advocacy from others in the workplace. These findings expand knowledge about professional socialization and how nurses themselves understand developing professional identity.


Quantitative evaluation of retention of surgical skills learned in simulation.
While initial results suggest that simulation does promote learning, there is a dearth of studies that define the extent to which skills learned through simulation are retained. Residents skills were measured upon completion of an initial simulation training (baseline scores) and then every month for 6 months. Analysis was also performed to identify the number of iterations of practice required to regain baseline scores. While skill scores did not deteriorate from baseline after the first 3 months (p = 0.61, p = 0.44, p = 0.2, respectively), all scores (except time elapsed) reflected significant deterioration from the fourth month onward (p < 0.05, p < 0.032, p < 0.02). However the number of practice sessions required to regain baseline scores was significantly less than that required to achieve the baseline skill set (p < 0.0003). Skills learned through simulation show significant deterioration over long periods of time, suggesting that periodic retraining of skills may be necessary to maintain surgical proficiency.


Bowman's layer transplantation: evidence to date.
Surgical management of keratoconus (KC) has undergone a paradigm shift in the last two decades and component corneal transplantation technique of deep anterior lamellar keratoplasty has established itself as a modality of choice for management of advanced cases of KC. Every now and then, new minimalist modalities are being innovated for the management of KC. On the same lines, a new technique, Bowman's layer transplantation, for surgical management of moderate to advanced KC has been reported in recent years. The procedure has shown to be beneficial in reducing ectasia in advanced KC with minimal intraoperative and postoperative complications. In this review, we intend to describe available information and literature with reference to this new surgical technique - Bowman's layer transplantation.


Ecological analyses of the intestinal helminth communities of the wolf, Canis lupus, in Spain.
This work describes the ecological characteristics of the intestinal helminth communities of 50 wolves (Canis lupus L.) from Spain. The species found were classified into three groups according to prevalence, intensity and intestinal distribution. Taenia hydatigena Pallas, 1766 and Uncinaria stenocephala (Railliet, 1884) are the core species of the community. Taenia multiceps (Leske, 1780) is a secondary species. The rest of the species, Alaria alata (Goeze, 1782), Taenia serialis (Gervais, 1847). Taenia pisiformis (Bloch, 1780), Dipylidium caninum (Linnaeus, 1758), Mesocestoides sp. aff. litteratus, Toxocara canis (Werner, 1782), Toxascaris leonina (von Linstow, 1902), Ancylostoma caninum (Ercolani, 1859) and Trichuris vulpis (Froelich, 1789), behave as satellite species. The linear intestinal distribution of all helminth species was analysed. The location of most species can be considered predictable, especially for core and secondary species. The analysis of interspecific relationships between infracommunities shows that negative associations are more numerous than positive associations. The role of A. caninum in the community is compared with that of U. stenocephala.


Rhythmic pineal-hypophyseal-adrenal intermodulations ex vivo.
To assess circadian and circaseptan rhythmic intermodulation, female mice, kept on regimens of 12 hr light (L) alternating with 12 hr of darkness (D) (LD 12:12) were sampled for 1-13 days at six circadian stages. Pineals were removed and homogenized with 0.9% NaCl. Adenohypophyses were bisected and incubated in Krebs-Ringer buffer (KRb) and/or with 10(-7) M melatonin (Mt). Adrenals were bisected and incubated with KRb, with 10(-7) M Mt, with 0.05 IU of ACTH 1-17 (Sy; Hoechst, Italy), or with Sy + 0.025 ml of the aqueous pineal homogenate (APH). ACTH and prolactin (PRL) in adenohypophysis incubation fluid were determined by radioimmunoassay (RIA), and corticosterone in adrenal incubation fluid was determined by RIA or by a fluorometric method. By this chronobiologic approach, time series were collected systematically in the search for predictable variability. Once these series reveal an algorithmically formulatable pattern, with a waveform validated by inferential statistical means, they are graded in terms of complexity as alpha, beta, gamma, and delta rhythms. Spontaneously (alpha-) rhythmic along the 24-h scale is the corticosterone produced by bisected adrenal glands incubated with KRb only, and the Mt content of the APH, in keeping with earlier work. Reactively (beta-) rhythmic is the response, again along the 24-hr scale, of the adrenal to Sy or Mt and the response of the anterior pituitary to Mt at different circadian times. Modulatory (gamma and delta) rhythms characterize the Mt effect on the (beta-rhythmic) adrenal stimulation by Sy. Chronomodulations thus emerge as more or less complete sequences of a decrease, no effect and/or increase; or, rather, as an attenuation, no effect and/or amplification by the pineal, of the pituitary effect upon the adrenal. Linear least-squares rhythmometry, mostly single cosinors, describes and quantifies circadian (alpha, beta, and gamma) and infradian (delta) rhythms in the original series and in the differences in responses [beta - alpha] and [gamma - beta] (P less than 0.001 in each case). These spontaneous alpha, response beta, modulatory gamma, and frequency-divided delta rhythms reveal a collateral neuroendocrine hierarchy, characterized by the pineal feedsideward phenomenon, as a feature of interactions recurring with circadian and infradian frequencies.


RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4.
Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain-containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17-positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4-treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.


Relationship between negative symptoms and plasma levels of insulin-like growth factor 1 in first-episode schizophrenia and bipolar disorder patients.
Previous studies have suggested that insulin-like growth factor-1 (IGF-1) is altered in schizophrenia. The objective of this study was to investigate whether plasma IGF-1 levels were altered at the onset of psychiatric disorders such as schizophrenia or bipolar disorder. We focused at the first psychotic episode (FPE) and during 1-year follow-up. We also studied if IGF-1 levels were related to clinical symptoms. 50 patients and 43 healthy controls matched by age, gender and educational level were selected from the Basque Country catchment area in Spain. Plasma IGF-1 levels were measured at FPE and 1 month, 6 months and one year later. Patient symptoms were assessed at the same disease stages using the Positive and Negative Symptoms Scale (PANSS), the Global Assessment of Functioning (GAF), the Hamilton Depression Rating Scale (HDRS21) and the Young Mania Rating Scale (YMRS). A statistically significant increase in the plasma levels of IGF-1 was found in the whole cohort of patients one month after FPE compared to matched controls (219.84 ng/ml vs 164.15 ng/ml; p=0.014), as well as in schizophrenia patients alone at that stage (237.60 ng/ml vs 171.60 ng/ml; p=0.039). In turn, negative symptoms in both groups of patients were positively correlated with IGF-1 levels both at FPE (β=0.521; p<0.001) and after 1 year (β=0.659; p=0.001), being patients diagnosed with schizophrenia the main contributors to this relationship. These results indicate that there is a significant change in the plasma levels of IGF-1 at the initial stages of schizophrenia but not in bipolar disorder, and suggest that IGF-1 could have role in the pathophysiology of negative symptoms.


Effect of a nighttime magnetic field exposure on sleep patterns in young women.
Since poor sleep quality is associated with multiple health problems, it is important to understand factors that may affect sleep patterns. The purpose of this study was to determine the effect of a continuous, 60-Hz, nighttime magnetic field exposure on sleep outcomes in young women sleeping at home. The study was a randomized crossover trial, comparing intervention (0.5-1.0 micro T above ambient levels) with ambient magnetic field levels, during two 5-night measurement periods. Subjects lived in the Seattle, Washington, area and were 20-40 years of age, had regular menstrual cycles, were not taking oral contraceptives, and had not breastfed or been pregnant during the previous year. The study was conducted between March and September of 2001. Sleep outcomes were measured via actigraphy. The range of magnetic field exposure was 0.001-0.50 micro T during the ambient period and 0.41-1.21 micro T during the intervention period. Sleep outcomes were not significantly different between the intervention and the ambient measurement periods. The intervention magnetic field had no effect on sleep patterns, suggesting that this exposure may not be an important factor in predicting sleep of young women who sleep at home.


The aetiology of acute viral hepatitis among some Egyptian youth.
Sero-diagnosis for HA, B, C & D were determined among acute hepatitis in 99 male military recruits, admitted to MOH Fever Hospital. Their ages ranged from 18-25 years. The results showed that hepatitis A was 1%, hepatitis B was 52%, acute hepatitis on HBsAg carrier was 3%, and hepatitis C was 8%. Among acute B 3% had anti-delta antibody. Anti-HCV was found in 2/5 of cases with acute hepatitis in HBsAg carriers, 4/21 of cases with past exposure of HBV and in 2/18 of cases negative for HBV.


Structural transitions accompanying the activation of peptide binding to the endoplasmic reticulum Hsp90 chaperone GRP94.
GRP94, the endoplasmic reticulum Hsp90 paralog, binds a diverse array of peptides, a subset of which are suitable for assembly onto nascent MHC class I molecules. At present, the mechanism, site, and regulation of peptide binding to GRP94 are unknown. Using VSV8, the immunodominant peptide epitope of the vesicular stomatitis virus, and native, purified GRP94, we have investigated GRP94-peptide complex formation. The formation of stable GRP94-VSV8 complexes was slow; competition studies demonstrated that peptide binding to GRP94 was specific. VSV8 binding to GRP94 was stimulated 2-fold or 4-fold, respectively, following chemical denaturation/renaturation or transient heat shock. The activation of GRP94-peptide binding occurred coincident with a stable, tertiary conformational change, as identified by tryptophan fluorescence and proteolysis studies. Analysis of GRP94 secondary structure by circular dichroism spectroscopy indicated an identical alpha-helical content for the native, chemically denatured/renatured, and heat-shocked forms of GRP94. Through use of the environment-sensitive fluorophores acrylodan and Nile Red, it was observed that the activation of peptide binding was accompanied by enhanced peptide and solvent accessibility to a hydrophobic binding site(s). Peptide binding to native or activated GRP94 was identical in the presence or absence of ATP or ADP. These results are discussed with respect to a model in which peptide binding to GRP94 occurs within a hydrophobic binding pocket whose accessibility is conformationally regulated in an adenine nucleotide-independent manner.


Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug for the Treatment of Osteoporosis.
A dual-action bone-targeting prodrug has been designed, synthesized, and evaluated for in vitro and in vivo metabolic stability, in vivo tissue distribution, and rates of release of the active constituents after binding to bones through the use of differentially double-labeled derivatives. The conjugate (general structure 7) embodies the merger of a very potent and proven anabolic selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic acid, a potent inhibitor of bone resorption, optimally linked through a differentially hydrolyzable linker unit, N-4-carboxymethylphenyl-methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg-PABA). Optimized conjugate 16 was designed so that esterase activity will liberate 5 and cathepsin K cleavage of the Leu-Arg-PABA element will liberate alendronic acid. Studies with doubly radiolabeled 16 provide a proof-of-concept for the use of a cathepsin K cleavable peptide-linked conjugate for targeting of bisphosphonate prodrugs to bone and slow release liberation of the active constituents in vivo. Such conjugates are potential therapies for the treatment of bone disorders such as osteoporosis.


[Hidradenitis suppurativa--treatment with myocutaneous island flap or the traditional method].
Inflammations of the apocrine sweat glands are characterized by painful, nodose and often superficially phlogistic infiltrates with a tendency towards abscess-formation and fistulation. These foci of inflammation are situated particularly in the armpit as well as the anal and genital region. The failure of conservative therapy--e.g., application of antibacterial ointments, red light, short-wave therapy or irradiation--is followed by a surgical intervention which involves excising the abscess cavity and leaving the wound open for secondary closure by granulation. The resultant scar is an impairment both functionally and cosmetically, particularly in the axilla; and, in many cases, a new focus of inflammation eventually develops in the immediate vicinity. For multiple occurrence of sudoriparous abscesses in the axilla with undermining of the surrounding cutaneous soft tissue mantle and fistulation, we therefore suggest the following therapeutic concept as an alternative to conventional methods: radical removal of the focus of inflammation far into the healthy tissue with concomitant excision of all sweat glands in the affected area and coverage of the resultant defect with a partial myocutaneous island flap from the latissimus dorsi muscle.


A new technique to assess insulin sensitivity in humans: the rapid insulin sensitivity test (RIST).
The objective of this study was to develop a Rapid Insulin Sensitivity Test (RIST) in humans, a test already used in animal studies. Insulin sensitivity was assessed using a rapid modified euglycemic clamp, the RIST. In this test, glucose disposition was determined after an intravenous (i.v.) bolus (50mU/kg bw administered over 30 seconds) of insulin, before and after feeding a standardized test meal, in healthy male subjects (aged 27.8 +/- 2.4 years, BMI 23.5 +/- 1.2 kg/m2). The RIST uses as the index of insulin sensitivity, the total amount of glucose required to be infused to maintain euglycemia during insulin action following an i.v. bolus of insulin. During the RIST, glucose levels are determined at 2-min intervals in order to clamp the glycemia at baseline values. Following a 24 hr fasting period, the RIST index was 225.6 +/- 25.1 mg glucose/kg bw. The volunteers were then fed a standardized test meal, a new stable glucose level was obtained 100 min after the meal, and a second RIST was performed. The glucose requirement (RIST index) increased to 647.9 +/- 73.5 mg glucose/kg bw following the standardized test meal (n = 5, p < 0.001). This report describes a new technique to evaluate insulin sensitivity in healthy humans. The RIST is a powerful research tool to assess the glucose utilization action of an insulin bolus in fasted and fed states both evaluated in the same day.


Relationship between Spinopelvic Parameters and Hip Function in Patients with Femoroacetabular Impingement at Diagnosis: A Cross-Sectional Study.
The aim of this study was to determine correlation between the spinopelvic parameters in sitting and standing positions (sacral slope [SS], lumbar lordosis [LL], spinopelvic tilt [SPT], pelvic incidence [PI], and pelvic femoral angle [PFA]), with hip function assessed using the modified Harris hip scores (mHHs) in patients with symptomatic femoroacetabular impingement (FAI) at diagnosis. A retrospective study of 52 patients diagnosed with symptomatic FAI was conducted. Evaluation of the spinopelvic complex in terms of SS, LL, SPT, PI and PFA was performed using lateral radiographs of the pelvis and lumbosacral spine in standing and sitting positions. Assessment of hip function at diagnosis was performed using the mHHs. Calculation of spinopelvic mobility was based on the difference (Δ) between measurements performed in standing and sitting position. The median time of pain evolution was 11 months (interquartile range [IQR], 5-24 months) with a median mHHs of 66.0 points (IQR, 46.0-73.0) at diagnosis. The mean change of LL, SS, SPT, and PFA was 20.9±11.2°, 14.2±8.6°, 15.5±9.0°, and 70.7±9.5°, respectively. No statistically significant correlation was observed between spinopelvic parameters and the mHHs (P>0.05). Radiological parameters of the spinopelvic complex did not show correlation with hip function at the time of diagnosis in patients with symptomatic FAI. Conduct of further studies will be required in the effort to understand the effect of the spinopelvic complex and its compensatory mechanics, primarily between the hip and spine, in patients with FAI before and after hip arthroscopy.


Percutaneous cannulated screw fixation of sacral fractures and sacroiliac joint disruptions with CT-controlled guidewires performed by interventionalists: single center experience in treating posterior pelvic instability.
The purpose of our study was to evaluate minimally invasive sacroiliac screw fixation for treatment of posterior pelvic instability with the help of CT controlled guidewires, assess its accuracy, safety and effectiveness, and discuss potential pitfalls. 100 guidewires and hollow titan screws were inserted in 38 patients (49.6±19.5 years) suffering from 35 sacral fractures and/or 16 sacroiliac joint disruptions due to 33 (poly-)traumatic, 2 osteoporotic and 1 post-infectious conditions. The guidewire and screw positions were analyzed in multiplanar reconstructions. The mean minimal distance between guidewire and adjacent neural foramina was 4.5±2.01mm, with a distinctly higher precision in S1 than S2. Eight guidewires showed cortical contacts, resulting in a total of 2% mismatched screws with subsequent wall violation. The fracture gaps were reduced from 3.6±0.53mm to 1.2±0.54mm. During follow-up 3 cases of minor iatrogenic sacral impaction (<5mm) due to the bolting and 2 cases of screw loosening were observed. Interventional time was 84.0min with a mean of 2.63 screws per patient whilst acquiring a mean of 93.7 interventional CT-images (DLP 336.7mGycm). The treatment of posterior pelvic instability with a guidewire-based screw insertion technique under CT-imaging results in a very high accuracy and efficacy with a low complication rate. Careful attention should be drawn to radiation levels.


In situ effects of restorative materials on dental biofilm and enamel demineralisation.
Since secondary caries is one of the main reasons for replacing restorations, this study assessed the effects of different restorative materials on the microbiological composition of dental biofilm and on enamel demineralisation around the restoration. A randomized, double-blind, split-mouth in situ design was conducted in one phase of 14 days, during which, 20 volunteers wore palatal devices containing five human dental enamel slabs. Each slab was randomly restored with one of the following materials: Filtek-Z-250/Single Bond, control group (composite resin), Permite (amalgam), Fuji II (encapsulated resin-modified glass ionomer), Vitremer (resin-modified glass ionomer) and Ketac Molar (conventional glass ionomer). The volunteers used fluoride dentifrice, 3x/day and a 20% sucrose solution was dripped onto the slabs 8x/day. The biofilm formed on the slabs was analyzed to determine the counts of total streptococci, mutans streptococci and lactobacilli. Enamel demineralisation was determined by cross-sectional microhardness (CSMH) at 20 and 70 microm from the margin of the restoration. Kruskal-Wallis and analysis of variance, followed by least mean squares (LMS) test, were used to evaluate microbiota and CSMH among the groups. The significance level used was 5%. No statistically significant differences were found in the cariogenic microbiota grown on the slabs. At a 20-mum distance, only Fuji II statistically differed from the other groups, showing the lowest demineralisation. At 70 microm, Fuji II significantly inhibited demineralisation when compared to Permite, Filtek-Z-250 and Ketac Molar. In the context of fluoride dentifrice and under the cariogenic exposure conditions of this study, only the encapsulated resin-modified glass ionomer material provided additional protection against secondary caries.


Evolution of hybrid interventions for congenital heart disease.
Surgical and transcatheter interventions have seen a tremendous evolution in last three decades. Hybrid technology combines the achievements of both disciplines to bring substantial hemodynamic benefit to patients with congenital heart disease (CHD) in a minimally invasive manner. This collaboration between surgeons and interventionalists will continue to grow as the technology evolves to meet the demands of CHD patients, potentially avoiding cardiopulmonary bypass and vascular access complications as well as optimizing immediate technical outcomes with exit angiography. Areas covered: This review covers application of such technology to initial palliation of infants with hypoplastic left heart syndrome, ventricular septal defect closure, pulmonary atresia with intact ventricular septum, pulmonary valve replacement, intra-operative pulmonary artery stenting and vascular cut-down in small neonates. Expert commentary: Careful planning and investment in infrastructure is necessary to optimize outcomes, however patients can benefit tremendously from integration of this approach into clinical practice.


A quantitative structural and morphometric analysis of the Purkinje network and the Purkinje-myocardial junctions in pig hearts.
The morpho-functional properties of the distal section of the cardiac Purkinje network (PN) and the Purkinje-myocardial junctions (PMJs) are fundamental to understanding the sequence of electrical activation in the heart. The overall structure of the system has already been described, and several computational models have been developed to gain insight into its involvement in cardiac arrhythmias or its interaction with implantable devices, such as pacemakers. However, anatomical descriptions of the PN in the literature have not enabled enough improvements in the accuracy of anatomical-based electrophysiological simulations of the PN in 3D hearts models. In this work, we study the global distribution and morphological properties of the PN, with special emphasis on the cellular and architectural characterization of its intramural branching structure, mesh-like sub-endocardial network, and the PMJs in adult pig hearts by both histopathological and morphometric evaluation. We have defined three main patterns of PMJ: contact through cell bodies, contact through cell prolongations either thick or piliform, and contact through transitional cells. Moreover, from hundreds of micrographs, we quantified the density of PMJs and provided data for the basal/medial/apical regions, anterior/posterior/septal/lateral regions and myocardial/sub-endocardial distribution. Morphometric variables, such as Purkinje cell density and thickness of the bundles, were also analyzed. After combining the results of these parameters, a different septoanterior distribution in the Purkinje cell density was observed towards the cardiac apex, which is associated with a progressive thinning of the conduction bundles and the posterolateral ascension of intramyocardial terminal scattered fibers. The study of the PMJs revealed a decreasing trend towards the base that may anatomically explain the early apical activation. The anterolateral region contains the greatest number of contacts, followed by the anterior and septal regions. This supports the hypothesis that thin distal Purkinje bundles create a junction-rich network that may be responsible for the quick apical depolarization. The PN then ascends laterally and spreads through the anterior and medial walls up to the base. We have established the first morphometric study of the Purkinje system, and provided quantitative and objective data that facilitate its incorporation into the development of models beyond gross and variable pathological descriptions, and which, after further studies, could be useful in the characterization of pathological processes or therapeutic procedures.


Pseudohypoparathyroidism with basal ganglia calcification: A case report of rare cause of reversible parkinsonism.
Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection. The son of the patient was also examined and was diagnosed as pseudohypoparathyroidism, who had ever complained of the history of epilepsy. The clinical manifestations of parkinsonism of the patient was reevaluated after the supplement of serum calcium according to the diagnosis. The brain computed tomography revealed the basal ganglia calcification of the patient, accompanying by serum hypocalcemia and hyperphosphatemia. Loss of function mutation also confirmed the diagnosis. Five days after the therapy targeting at correction of serum hypocalcemia, the patient improved greatly in dyskinesia. This study reported a patient presenting as acute reversible parkinsonism, who was finally diagnosed as pseudohypoparathyroidism. It indicated us that secondary parkinsonism should be carefully differentiated for its dramatic treatment effect. And the family history of seizures might be an indicator for the consideration of pseudohypoparathyroidism.


Fabrication and characterization of indium fluoride multimode fused fiber couplers for the mid-infrared.
Results of the fabrication and characterization of optical fiber couplers made of multimode step-index fluoroindate (InF3) fibers are presented. The fabrication setup was customized for this type of glass with a constant source of controlled nitrogen flow heated to a target temperature with an accuracy ±1°C. Combined with a novel fast fusion approach and with excellent control of the viscosity throughout the process, the clean gas flow and well-controlled temperature enable the fabrication of fused fiber couplers absent of any noticeable crystallization. A coupling ratio of 45/55 was achieved, with an excess loss of 0.35 dB, at 1.7 µm. To the best of our knowledge, this represents the first low excess loss (<1 dB), multimode, InF3 fiber couplers.


Sexual Arousal in Obsessive-Compulsive Disorder With and Without Contamination/Washing Symptoms: A Moderating Role of Disgust Sensitivity.
Different findings would indicate that obsessive-compulsive disorder (OCD), a common psychiatric condition, might significantly impair intimate relationships and sexual well-being. The aim of the present study was to ascertain whether OCD outpatients with contamination/washing symptoms experience a lower sexual arousal than those experiencing other symptoms. In addition, we explored whether a higher disgust propensity/sensitivity might moderate the relation between contamination/washing symptoms and impaired sexual arousal. A total of 72 outpatients (27 with contamination/washing symptoms and 45 with other obsessive-compulsive symptoms) were selected for this study and assessed by a battery of specific rating scales. The results highlighted how OCD patients with contamination/washing symptoms and higher disgust sensitivity showed an increased propensity to inhibition due to threat of sexual performance failure and consequences. It may be speculated that the disgust sensitivity may be a mechanism involved in the impairment of this well-being domain. In conclusion, these findings suggest that the sexual wellbeing should be evaluated during routine clinical evaluation of OCD patients.


Adherence to guidelines on red blood cell transfusions in women having post-partum haemorrhage.
Transfusion of blood products occurs frequently as part of the treatment of post-partum haemorrhage, but since it is both expensive and has potentially severe complications, prescription of blood products should be restricted. The aim of this study was to examine if restrictive red blood cell transfusion (RBC-T) practice for obstetric patients was in line with national Danish guidelines. A retrospective quality assurance study was conducted at Rigshospitalet, Denmark. The study counted the participation of the Department of Anaesthesiology and Surgery, the Juliane Marie Centre, the Danish Blood Bank and the Department of Obstetrics. Patients were identified via the patient database of the Danish Blood Bank in 2015-2017, and patient files were read. Out of 16,698 delivering women, 196 (1.2%) received one or more RBC-T from 2015 to 2017. A total of 133 women (67.9%) received more than one RBC-T and the median was two. The most common reason for RBC-T was a "low haemoglobin level (Hb) + anaemic symptoms" (37.0%). A total of 20.3% of all RBC-Ts were prescribed based simply on a low Hb. The most common symptom of anaemia was dizziness. The majority of RBC-Ts for obstetric patients were conducted in line with the guidelines. However, 6.0% of RBC-Ts were registered to be in discrepancy with the guidelines and 20.3% of RBC-Ts were prescribed on the "low Hb" criterium solely. It is possible, though, that the 20.3% is overestimated due to insufficient descriptions of indications for RBC-T in patient files. none. The study was approved by the management at Rigshospitalet.


Stroke survivors' experiences of occupation in hospital-based stroke rehabilitation: a qualitative exploration.
Purpose: Studies highlighting the time spent in self-isolating and inactive activities during stroke rehabilitation have led to the introduction of group programs and environmental enrichment to improve activity levels. A less explored perspective is to understand how the introduced changes align with the occupational needs of the stroke survivors. Therefore, the aim of this study was to explore stroke survivors experiences of engagement in occupations during stroke rehabilitation.Methods: A descriptive phenomenological approach with semi-structured interviews explored stroke survivors experiences.Results: Eight participants (five male and three female, mean age 72 years) described their experiences with two themes emerging: (1) "I'm here for that reason:" which highlighted therapy as an occupation which participants wanted to perform and (2) "Celebration of quiet moments:" exploring the value of rest and recreation.Conclusion: This study provides a preliminary understanding of how stroke survivors experience occupational engagement during rehabilitation. There was an apparent shift in priorities with therapy considered the most important occupation and a strong need expressed for rest and relaxation to be factored into people's days. It appears the increasing activity levels may not always align with people's occupations and that due consideration of this malalignment may further enhance engagement and outcomes.Implications for rehabilitationDuring hospital-based stroke rehabilitation, stroke survivors prioritized the occupations of therapy, rest, and recreation.People with stroke are motivated to participate when the activities within and outside of, therapy align with their pre-stroke life and occupations.A daily stroke rehabilitation program should be balanced with opportunities for rest to support recovery time from therapy and possible consolidation of learning.


Celiac disease, pregnancy, small for gestational age: role of extravillous trophoblast.
It is questionable whether development of the intrauterine growth retardation or small for gestational age (SGA) children is related directly to inflammation associated with celiac disease. Localization and the amount of gliadin, Fas-L, as well as the incidence of apoptosis in 32-term placentas, was analyzed immunohistochemically and with in situ hybridization in a blinded fashion; these were correlated with the weight of their newborns. Extravillous trophoblasts (EVTs) from the noncompliant women were overloaded with gliadin; there was a moderate amount or no gliadin present in the controls. The weight of newborns was lower if extravillous trophoblasts were loaded with gliadin (-2.24SD) (p = 0.004). Increased apoptosis of EVT in placentas of noncompliant women was consistent with abundant expression of Fas-L in those cells and was linked to the low birth weight of newborns. Exposure to gliadin alters extravillous trophoblast dynamics by causing an increase in apoptotic shedding. In genetically predisposed individuals, gliadin affects fetal part of the placenta causing children to be small for their age. A gluten-free diet during pregnancy prevents SGA children and, thus, the fetal origin of serious adult diseases.


[Revision ossiculoplasty: anatomical and functional results].
To analyse the anatomical and functional results after second-look ossiculoplasty using Titanium (TI) and Hydroxyapatite (HA) prosthesis and to study the prognostic factors for good functional results. Forty nine patients (19 men and 30 women) with an average age of 36 years were included in this study. The patients presented with anatomical and/or functional failures after a first ossiculoplasty and had a second-look intervention. The status of the first prosthesis and also the anatomical status of the middle ear and the remaining ossicular chain were described intra operatively. The functional and anatomical results were assessed 2 months after the second ossiculoplasty and during the most recent out patient clinic. Postoperative air conduction gain (ACG) and air bone gap (ABG) were calculated in average values using four frequencies: 0.5, 1, 2 and 4 kHz. The variables used in statistical analysis were the following: Tympanic membrane and preoperative middle ear status, the type of prosthesis (partial or total) and its material (TI and HA). The average time to second-look operation was 18 months. The postoperative ABG did not show any significant statistic improvement and in several patients auditory function deteriorated in the operated ear The predictive factors for good functional results were: The integrity of the tympanic membrane, chronic otitis media without cholesteatoma, total prosthesis and HA prosthesis. If three of these factors were present, the postoperative ABG would always be less than 20 dB. When selecting patients for second look ossibuloplasty it is important to understand the predictive facctors for good results. This will allow a full discussion of options, risks and morbidity with the patient.


Testing the Assessment of New Radiation Oncology Technology and Treatments framework using the evaluation of post-prostatectomy radiotherapy techniques.
We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.


Current and Future Role of the Gastroenterologist in GI Cancer Management.
With advances in technology, advances in the understanding of biology of cancer, and the advent of improved and novel therapies, the role of the gastroenterologist has been modified greatly over the past 2 decades, and continues to be shaped by the knowledge, skill, and opportunity to capitalize on the unique position that gastroenterologists hold in the patient care continuum. The gastroenterologist is evolving from a "pure" diagnostician to an endoscopic surgeon, a geneticist, a nutritionist, an immunologist and chemotherapist, and palliative care physician.


Molecular Mechanisms of Crude Oil Developmental Toxicity in Fish.
With major oil spills in Korea, the United States, and China in the past decade, there has been a dramatic increase in the number of studies characterizing the developmental toxicity of crude oil and its associated polycyclic aromatic compounds (PACs). The use of model fish species with associated tools for genetic manipulation, combined with high throughput genomics techniques in nonmodel fish species, has led to significant advances in understanding the cellular and molecular bases of functional and morphological defects arising from embryonic exposure to crude oil. Following from the identification of the developing heart as the primary target of crude oil developmental toxicity, studies on individual PACs have revealed a diversity of cardiotoxic mechanisms. For some PACs that are strong agonists of the aryl hydrocarbon receptor (AHR), defects in heart development arise in an AHR-dependent manner, which has been shown for potent organochlorine agonists, such as dioxins. However, crude oil contains a much larger fraction of compounds that have been found to interfere directly with cardiomyocyte physiology in an AHR-independent manner. By comparing the cellular and molecular responses to AHR-independent and AHR-dependent toxicity, this review focuses on new insights into heart-specific pathways underlying both acute and secondary adverse outcomes to crude oil exposure during fish development.


Serum immunoreactivity of cancer/testis antigen OY-TES-1 and its tissues expression in glioma.
OY-TES-1 is a member of the cancer/testis antigen family that is expressed in healthy testis tissue and certain types of cancerous tissue. The present study aimed to analyze the expression pattern of OY-TES-1 and serum anti-OY-TES-1 antibody concentration in patients with glioma. OY-TES-1 mRNA was detected in 28/36 (78%) of glioma cases using conventional reverse transcription polymerase chain reaction (RT-PCR) analysis. RT-quantitative-PCR revealed that OY-TES-1 was expressed at a higher level in glioma tissues compared with normal adult tissues (with the exception of testis tissue). Anti-OY-TES-1 antibodies were present in the serum of 5/36 (14%) of patients with glioma, but absent in all the serum samples from 107 healthy donors. Immunohistochemical analysis demonstrated that OY-TES-1 protein was expressed in all glioma tissues from patients with anti-OY-TES-1 antibody seropositivity. These results suggest that OY-TES-1 is a novel candidate for glioma immunotherapy.


Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that has transitioned from a debilitating disease to a chronic, controllable disease. This has been possible due to the introduction of new treatment strategies like "treat-to-target," in which the clinician treats the patient aggressively enough to reach low disease activity or remission, and the introduction of new therapeutic agents, such as biological therapies, which can lead to the prevention of damage by early diagnosis and initiation of treatment. Attention is now being directed toward identifying the optimal treatment for each patient, one that will be the most efficient and have the least number of side effects. Much work has been done to find serologic and synovial biomarkers of response to various RA treatments. Proteomics, genomics and, in the past few years, metabolomics, have all been used in the quest of identifying these biomarkers. Blood-based liquid biopsies provide a minimally invasive alternative to synovial biopsies to identify cellular and molecular signatures that can be used to longitudinally monitor response and allow for personalized medicine approach. Liquid biopsies are comprised of cell-free DNA, immune circulating cells, and extracellular vesicles, and are being increasingly and successfully used in the field of oncology for diagnosis, progression, prognosis, and prediction of response to treatment. Recently, researchers have also begun investigating the usefulness of liquid biopsies in the field of rheumatology; in this review, we will focus on the potential of liquid biopsy blood samples as biomarkers of response to treatment in patients with RA.


Major depressive disorder in adolescents exposed to a friend's suicide.
To evaluate whether the risk of DSM-III major depressive disorder (MDD) is uniform across the 6 months after adolescent exposure to a friend's suicide, and to examine potential moderating or mediating processes that may influence the risk of new-onset MDD. One-month incidence rates of MDD were compared between 129 adolescents who were exposed to a friend's suicide between December 1988 and March 1991 and 145 similar-aged, unexposed community controls participating in the Youth Exposed to Suicide study. Clinical, family, and social factors that antedated the exposure were examined as predictors of new-onset MDD within 1 month of the suicide. Exposed adolescents had a markedly increased risk of developing new-onset MDD that was restricted to a narrow period of time, within 1 month after exposure. In contrast, there were no differences in the incidence of MDD between the groups in months 2 to 6. Past history of alcohol abuse increased the risk of exposure to suicide, which subsequently increased the risk of new-onset MDD within 1 month of exposure. Exposed youths who had both a family history of MDD and feelings of accountability for the death were at considerably increased risk of new-onset MDD. For adolescents exposed to a friend's suicide, events surrounding the death interact with family history of MDD to greatly increase the risk for new-onset MDD.


An audiometric study of the effects of paraspinal stimulation on hearing acuity in human subjects - understanding the Harvey Lillard phenomenon.
The founder of chiropractic, Daniel David Palmer, constructed a model of causation of disease based on his seminal experience with a patient, Harvey Lillard, who lost his hearing at the instant of injuring his upper back, but had his hearing restored suddenly 17 years later after receiving spinal manipulation. Palmer's model of disease causation, that of displaced vertebrae impinging on spinal nerves and thereby disrupting the innervation of dependent organs, was in fact incongruent with what was known at the time about human neuroanatomy and neurophysiology. The current study proposes and tests an alternative hypothesis: that increased afferent input from paraspinal muscles attenuates the central transmission of auditory information. Between September 13 and November 13, 2013, forty healthy young adults were recruited and randomly divided into two cohorts: one receiving successive trials of sham TENS, and the second receiving sham and then authentic TENS. During the administration of sham and authentic TENS to the upper thoracic spine, hearing acuity was measured to determine perception thresholds at the frequencies normally tested clinically. In the first cohort, there were no differences in perception thresholds in the first and second trials of sham TENS, speaking to the reliability of the testing process. In the second cohort, there were no significant differences in perception thresholds during sham and authentic TENS. Within the constraints of the current study design, including demographic characteristics and TENS parameters, there was no evidence that innocuous afferent input to upper thoracic paraspinal muscles modulated thresholds of audibility.


Spatial decoupling of facilitation and competition at the origin of gapped vegetation patterns.
Spatially periodic vegetation patterns, forming gaps, bands, labyrinths, or spots, are characteristic of arid and semiarid landscapes. Self-organization models can explain this variety of structures within a unified conceptual framework. All these models are based on the interplay of positive and negative effects of plants on soil water, but they can be divided according to whether they assume the interactions to be mediated by water redistribution through runoff/diffusion or by plants' organs. We carried out a multi-proxy approach of the processes operating in a gapped pattern in southwest Niger dominated by a shrub species. Soil moisture within the root layer was monitored in time and space over one month of the rainy season. Soil water recharge displayed no spatial variation with respect to vegetation cover, but the stock half-life under cover was twice that of bare areas. A kernel of facilitation by the aboveground parts of shrubs was parameterized, and soil water half-life was significantly correlated to the cumulated facilitative effects of shrubs. The kernel range was found to be smaller than the canopy radius (81%). This effect of plants on soil water dynamics, probably through a reduction of evaporation by shading, is shown to be a better explanatory variable than potentially relevant soil and topography parameters. The root systems of five individuals of Combretum micranthum G. Don were excavated. Root density data were used as a proxy to parameterize a kernel function of interplant competition. The range of this kernel was larger than the canopy radius (125%). The facilitation-to-competition range ratio, reflecting the above-to-belowground ratio of plant lateral extent, was smaller than 1 (0.64), a result supporting models assuming that patterning may emerge from an adaptation of plant morphology to aridity and shallow soils by means of an extended lateral root system. Moreover, observed soil water gradients had directions opposite to those assumed by alternative mathematical models based on underground water diffusion. This study contributes to the growing awareness that combined facilitative and competitive plant interactions can induce landscape-scale patterns and shape the two-way feedback loops between environment and vegetation.


Factors associated with poor prognosis in patients with atrial fibrillation: An emergency department perspective the EMERG-AF study.
We sought to identify the factors associated with a worse prognosis in Emergency Department (ED) patients with atrial fibrillation (AF), crucial information to guide management decisions. This is a secondary analysis of a prospective, multicenter, observational cohort of consecutive AF patients attended in 62 EDs in Spain. Clinical variables were collected on enrollment. Follow-up was performed at 30 days and one year. The primary composite outcome was all-cause mortality, major bleeding and/or stroke at one year. Secondary outcomes were each of these components considered separately, plus one-year cardiovascular mortality and the composite outcome at 30 days. We analyzed 1107 patients. The primary outcome occurred in 209 patients (18.9%), one-year all-cause mortality in 151 (13.6%), major bleeding in 47 (4.2%), and stroke in 31 (2.8%). Disability (HR 2.064, 95% CI 1.478-2.882), previous known AF (HR 1.829, 95% CI 1.096-3.051), long duration of the AF episode (HR 1.849, 95% CI 1.052-3.252) and renal failure (HR 2.073, 95% CI 1.433-2.999) were independently associated with the primary outcome, whereas anticoagulation at discharge was inversely associated (HR 0.576, 95% CI 0.415-0.801). Disability was associated with mortality, cardiovascular mortality, and the composite at 30 days, and renal failure with mortality and major bleeding. Comorbidities like renal failure, long AF duration and disability were related to adverse outcomes and should be decisive to guide management decisions in ED patients with AF. Anticoagulation had a positive impact on prognosis and should be the mainstay of therapy in AF patients attended in ED.