Breaking Out of the Lab: Measuring Real-Time Responses to Televised Political Content in Real-World Settings.
Real-time response (RTR) measurement is an important technique for analyzing human processing of electronic media stimuli. Although it has been demonstrated that RTR data are reliable and internally valid, some argue that they lack external validity. The reason for this is that RTR measurement is restricted to a laboratory environment due to its technical requirements. This paper introduces a smartphone app that 1) captures real-time responses using the dial technique and 2) provides a solution for one of the most important problems in RTR measurement, the (automatic) synchronization of RTR data. In addition, it explores the reliability and validity of mobile RTR measurement by comparing the real-time reactions of two samples of young and well-educated voters to the 2013 German televised debate. Whereas the first sample participated in a classical laboratory study, the second sample was equipped with our mobile RTR system and watched the debate at home. Results indicate that the mobile RTR system yields similar results to the lab-based RTR measurement, providing evidence that laboratory studies using RTR are externally valid. In particular, the argument that the artificial reception situation creates artificial results has to be questioned. In addition, we conclude that RTR measurement outside the lab is possible. Hence, mobile RTR opens the door for large-scale studies to better understand the processing and impact of electronic media content.


Keloids - the sebum hypothesis revisited.
The aetiology of the keloid scar has not been completely elucidated. Numerous hypotheses have been proposed in the past to explain the unusual characteristics of the keloid scar. While we do know that there is excessive and ongoing collagen-deposition, the exact triggering stimulus is a subject of conjecture. We present some of our photographic records of keloids and electron microscopic findings of keloid edges and reiterate the sebum hypothesis. We also attempt to explain the features of keloids in the light of the present knowledge of immunology and cell biology.


Postprandial coagulation factor VII activity: the effect of monounsaturated fatty acids.
The present study investigated the effect of monounsaturated fatty acids (MUFA) on postprandial coagulation factor VII activity. Fifteen healthy male volunteers consumed three meals containing equal amounts (40 g) of fat, but providing different proportions of MUFA (12, 17 and 24% energy) in random order. Fasting and postprandial blood samples were drawn every hour for 9 h. The magnitude of the postprandial triacylglycerolaemic response and the postprandial plasma non-esterified fatty acid (NEFA) concentrations were not significantly different following the three meals. Coagulation factor VII was activated during postprandial triacylglycerolaemia but the area under the curve of postprandial coagulation factor VII activity was not significantly different following the three meals. Regression analysis showed that fasting factor VII activity was the single most important factor affecting postprandial factor VII activity, irrespective of plasma lipid concentrations and meal fat composition. Peak postprandial factor VII activity was attained significantly earlier following the high-MUFA meal compared with the low-MUFA meal (6.33 (SD 2.16)h, 3.60 (SD 1.81)h respectively; P = 0.016). Regression analysis showed that meal MUFA content was the primary determinant of time to peak postprandial factor VII activity. Although the magnitude of postprandial coagulation factor VII activity was not affected by meal MUFA content, peak postprandial factor VII activity occurred earlier and fasting activity levels were quickly restored following the high-MUFA meal. A short-lived increase in factor VII activity may be more beneficial than a prolonged thrombotic response.


Factors predicting the efficacy of botulinum toxin-A treatment of the lower limb in children with cerebral palsy.
Botulinum toxin A is widely used for spasticity management in children with cerebral palsy, although outcomes are unpredictable. The aim of this study was to identify criteria for selecting patients most likely to benefit from botulinum toxin A treatment. Fifty-five subjects, aged 2.5 to 18 years, were recruited. The assessment covered measures of spasticity (Modified Ashworth Scale), function (using the Gross Motor Function Measure and the Physician's Rating Scale), selective motor control, static range of motion at the ankle with knee extended and flexed, range of motion of the knee flexors, central and peripheral vision, and cognitive ability. Outcomes at 3 months were compared with baseline values. All of the scales showed significant differences between pre- and postinjection values. Significantly increased Gross Motor Function Measure scores were found in children aged 48 months or under and in those able to walk with support. Greater improvements in selective motor control and Physician's Rating Scale were seen in those with a less severe pattern of paralysis, lower levels of impairment, the ability to walk (with or without support), normal visual acuity, and normal or borderline cognition. We identified factors that mark out patients as most likely to achieve functional gains: young age, hemiplegia or diplegia, slight to moderate disability, walking with support, normal or borderline cognition, and normal or borderline visual acuity.


Crossover in structure and dynamics of a primary alcohol induced by hydrogen-bonds dilution.
Primary alcohols show a prominent Debye process in the dielectric relaxation located at a timescale longer than the main structural relaxation. Böhmer and co-workers studied dilution effects of the hydrogen bonding network of n-butanol (BuOH) with n-bromobutane (BuBr) to better understand the origin of this process. Interestingly, this work has evidenced a crossover in Debye relaxation time (τD) for a critical concentration in BuBr xc = 0.5. By using molecular dynamics simulations and NMR experiments we propose here to explore further dilution effects on the dipolar and translational dynamics. Moreover, we discuss the relation between structural and dynamical properties in the context of a detailed study of the microstructure and the H-bond network. The overall results are consistent with the existence of a topological change in the liquid structure occurring at about xc = 0.5 from a hypernetted percolating network to independent nanodomains of n-butanol molecules embedded in the n-bromobutane phase.


[Treatment of human alveolar echinococcosis with flubendazole. Clinical, morphological and immunological study].
Flubendazole has been given at a daily dosage of 50 mg/kg for 16 months (extremes 10 and 24 months) to 10 patients with hepatic alveolar echinococcosis. Clinical, morphological and immunological evaluations have been performed every 2 months during the treatment, and in 6 patients after discontinuation of the drug for 24 months. Jaundice persisted or occurred in 7 patients; infectious complications were observed in 4 patients; portal hypertension appeared in 5 patients; metastatic spread was suspected in 2 patients. Subjective improvement and weight gain were reported by 6 patients during the first 4 months of treatment. Severe complications occurring during the period of FZ therapy or within 2 months after withdrawal of the drug led to surgery in 6 patients, and death occurred in 3 cases. These observations demonstrate the inefficacy of FZ in this series of 10 patients with alveolar echinococcosis, possibly related to the extremely poor bioavailability of FZ. Higher plasma concentrations obtained with mebendazole and albendazole could explain the better efficacy of these two drugs despite their similar chemical structures and experimental toxicity upon larval cestodes.


Current perspectives on immunology and psychiatry.
We selectively review recent research findings in the field of psychoimmunology which test the hypotheses that immunological dysfunction may be aetiologically related to mental illnesses such as schizophrenia, and that certain morbid affective states such as depression and other forms of psychosocial distress may be the cause of immunosuppression and through this mechanism affect the outcome of illnesses such as cancer. Our examination of research implicating immunological or infective mechanisms in the aetiology of schizophrenia indicates that most studies have been unable to control for major methodological difficulties but the compatibility of these theories with the dopamine hypothesis suggests that further research attention is warranted. More clearly, there is growing evidence demonstrating a link between depression, other states of psychological distress and immunosuppression, but the clinical significance of these findings remains uncertain. The complex relationship between stress and the outcome of illnesses such as cancer is discussed and the possible implications of these findings for clinical psychiatry are suggested.


Veterinary Student Confidence after Practicing with a New Surgical Training Model for Feline Ovariohysterectomy.
Lack of confidence and self-efficacy are the main causes of negative emotions experienced by veterinary students when performing surgery. A surgical training model (STM) was developed to test the hypothesis that practical training on an STM before performing live surgery would enhance the students' confidence. In addition, low-cost and easily accessible materials were used for the construction. In the STM, neodymium magnets that were detached if too much traction was applied were used to ensure careful tissue handling during ligation of the ovarian pedicles and cervix. A pilot study was performed to evaluate veterinary undergraduate students' confidence when using the STM before performing their first live feline ovariohysterectomy (OHE) as lead surgeon. The results showed that the students rated their confidence level higher after performing feline OHE if they had practiced with the STM before surgery. Voluntary written comments revealed that live surgery as a learning situation could have a very negative emotional impact on some students.


Low-dose amiodarone for patients with advanced heart failure who are intolerant of beta-blockers.
The tolerability and effectiveness of amiodarone in patients with advanced heart failure (HF) who are intolerant of beta-blockers was investigated in 22 patients (13 with and 9 without 180+/-26 mg/day of amiodarone). Heart rate (HR), blood pressure (BP), left ventricular diastolic dimension and fractional shortening (FS) using echocardiography, plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and norepinephrine concentrations were determined at baseline and after 1 and 3 months of therapy. Although 9 patients tolerated amiodarone without any signs of HF, it was exacerbated in 4 patients. In 10 patients taking amiodarone who could be followed medically for 3 months, HR decreased after 1 month and remained unchanged until after 3 months (81+/-12 vs 65+/-7 vs 65+/-7beats/min), accompanied by decreased concentration of BNP (688+/-485 vs 392+/-203 vs 261+/-192pg/ml). FS increased significantly only after 3 months (0.12+/-0.05 vs 0.14+/-0.05 vs 0.16+/-0.04). Amiodarone may be used in patients with advanced HF who are intolerant of beta-blockers.


Special Issue: Mycorrhizal Fungi in Sensitive Environments.
The scope of this special issue is to understand whether and how mycorrhizal symbiosis can be included as an agriculture and agroforestry tool that promotes more environmentally friendly practices, and whether it promotes the protection of sensitive areas. Three papers are included in this special issue, each dealing with a different sensitive environment. These papers present fundamental aspects that should be taken into account when planning or reporting studies related to mycorrhizal fungi in sensitive environments.


Improved method for gas chromatographic-mass spectrometric analysis of 1-(13)C-labeled long-chain fatty acids in plasma samples.
Gas chromatographic-mass spectrometric (GC/MS) tracking of stable-isotope-labeled substrates is useful in metabolic studies. However, GC/MS analysis of long-chain fatty acid methyl esters yields results that mostly depend on their concentration in the system. We describe a protocol aimed to obviate this and other drawbacks in plasma [1-(13)C]palmitic and [1-(13)C]oleic acid measurements. Lipoproteins were separated by sequential ultracentrifugation. Free or esterified heptadecanoic acid was used as internal standard. Fatty acids were derivatized to trimethylsilyl (TMS) esters. GC separation was in isothermal mode at 210 degrees C for 27 min. For both TMS-palmitate and TMS-oleate, M and [M + 1] signals were simultaneously acquired with a dual acquisition program in single-ion monitoring mode. Calibration mixtures containing increasing amounts of labeled fatty acids were prepared gravimetrically to construct calibration curves for isotopic enrichment. Likewise, five calibration curves (for increasing concentrations) were constructed for each fatty acid; this allowed selection of the most appropriate curve for the concentration in a plasma sample. Oleic acid-TMS ester was clearly separated from that of its stereoisomer, elaidic acid. Within a 10-fold concentration range, the isotopic ratio was independent on the amount of the analyte in the sample, with a maximum uncertainty of 0.34% in terms of molar percent excess. In addition, the within- and between-day imprecision (CV) of the method was <1%. Results obtained with this method are independent of concentration and sufficiently precise for tracking 1-(13)C-labeled palmitic and oleic acids in biological samples


Small bowel bacterial overgrowth. An underrecognized cause of malnutrition in older adults.
Small bowel bacterial overgrowth (SBBO) is an important and under-recognized clinical syndrome in the elderly. It is the most common cause of malabsorption among older adults. Presentation of SBBO syndrome is often occult, which makes it imperative to maintain a high index of suspicion for this disorder. When symptomatic bacterial overgrowth is appropriately identified and treated there can be positive dramatic results. This article discusses the importance of considering a diagnosis of bacterial overgrowth in those predisposed to its development and the mechanisms by which nutrient malabsorption occurs. Signs and symptoms of bacterial overgrowth, differential diagnosis, investigation, and current treatment options are discussed.


Lack of Knowledge About Hepatitis C Infection Rates Among Patients With Inherited Coagulation Disorders in Countries Under the Eastern Mediterranean Region Office of WHO (EMRO): A Meta-Analysis.
Hepatitis C virus (HCV) infection is a public health problem. HCV alone is responsible for 90% cases of acute hepatitis among multiply transfused patients who are at risk of cirrhosis and hepatocellular carcinoma (HCC). To provide a clear picture of available data, we performed a systematic review of the epidemiological characteristics of HCV infection among patients with inherited coagulation disorders in the countries under the Eastern Mediterranean Region Office (EMRO). Meta-analysis was carried out on the basis of results of electronic and manual search. This analysis included studies in English, French, and Persian that met with the following criteria: (1) appropriate study design: cross-sectional, case-control, and cohort; (2) studies reporting HCV prevalence according to enzyme immune assay; (3) studies in which the sample population was enrolled from EMRO countries. According to the results of the heterogeneity tests, we used fixed-effect/random-effect model for our meta-analysis, with the "Metan" command. We included 30 studies, most of which were from Iran. The mean age of the subjects ranged from 13 to 27.1 years. The majority of the patients were male (range, 81% to 100%). The pooled estimate of HCV infection among patients with inherited coagulation disorders was 48.07% (95% confidence interval [CI], range: 27.39-55.68) in Iran, 36.03% (95% CI, range: 4.466-67.598) in Pakistan, and 48.27% (95% CI, range: 36.12-60.43) in all the EMRO countries taken together. In Iran and other EMRO countries, the HCV infection rate among patients with inherited coagulation disorders is high. Our study shows that there is a lack of knowledge about infections in such patients in most of the EMRO countries. It is the responsibility of health-policy makers to address this knowledge gap and provide safe and adequate treatment for patients in high-risk groups.


Anatomic design of a sensate plantar flap.
To date, full-thickness skin ulcers of the heel of the foot are still difficult wounds to cover. Many choices of coverage are available, but few provide long-term coverage due to bone exposure, deficient sensibility, and subsequent breakdown. An advancement flap based on the medial plantar artery with sensory nerve branches is presented with long-term follow-up. This flap is available and expendable, with an excellent are of rotation. Reliable circulation and sensibility are the key factors for successful reconstruction.


Jacobian-free variational method for computing connecting orbits in nonlinear dynamical systems.
One approach for describing spatiotemporal chaos is to study the unstable invariant sets embedded in the chaotic attractor of the system. While equilibria, periodic orbits, and invariant tori can be computed using existing methods, the numerical identification of heteroclinic and homoclinic connections between them remains challenging. We propose a robust matrix-free variational method for computing connecting orbits between equilibrium solutions. Instead of a common shooting-based approach, we view the identification of a connecting orbit as a minimization problem in the space of smooth curves in the state space that connect the two equilibria. In this approach, the deviation of a connecting curve from an integral curve of the vector field is penalized by a non-negative cost function. Minimization of the cost function deforms a trial curve until, at a global minimum, a connecting orbit is obtained. The method has no limitation on the dimension of the unstable manifold at the origin equilibrium and does not suffer from exponential error amplification associated with time-marching a chaotic system. Owing to adjoint-based minimization techniques, no Jacobian matrices need to be constructed. Therefore, the memory requirement scales linearly with the size of the problem, allowing the method to be applied to high-dimensional dynamical systems. The robustness of the method is demonstrated for the one-dimensional Kuramoto-Sivashinsky equation.


Blood pressure, pulse, and neurohumoral responses to nitroprusside-induced hypotension in normotensive aging men.
In order to assess the effects of age on blood pressure, pulse, and neurohumoral responses to hypotensive stress, we infused nitroprusside into healthy young and old men until mean arterial blood pressure was reduced 20% from basal. Elderly subjects were much more sensitive to nitroprusside. Pulse increases in response to this hypotensive stress were markedly reduced in the elderly, but renin, vasopressin, and norepinephrine responses were not different between young and old. We conclude that cardioacceleration, one of the primary defenses against hypotension, is impaired with age. However, neurohumoral responses to hypotension are intact in the elderly.


Camelina sativa Oil, Fatty Fish, and Lean Fish Do Not Markedly Affect Urinary Prostanoids in Subjects with Impaired Glucose Metabolism.
Dietary fatty acids are suggested to affect oxidative stress; however, results from interventions have been inconclusive. The aim was to examine if fatty fish, lean fish, and Camelina sativa oil (CSO) affect the urinary prostanoid levels in subjects with impaired glucose metabolism. Altogether 79 participants aged 43-72 years completed a randomized controlled study lasting 12 weeks. There were four parallel groups, fatty fish, lean fish (four fish meals/week in both), CSO providing 10 g/day alpha-linolenic acid (ALA), and control diet with limited fish and ALA containing oil consumption. Urinary prostanoids (prostaglandin F2α , 5-F2t -isoprostanes and 15-F2t -isoprostane metabolites, isofuran, 8-F3t -isoprostanes, and 4-(RS)-4-F4t -neuroprostane) of 72 participants (age: mean (±SD) 58.9 ± 6.5 years; body mass index: 29.3 ± 2.5 kg/m2 ) collected over 12-h were measured using liquid chromatography tandem-mass spectrometry. Plasma phospholipid fatty acids were determined using gas chromatography. Our study showed that the proportion of ALA in plasma phospholipids increased in the CSO group (overall difference among the groups p-value <0.001). In the fatty fish group, proportions of eicosapentaenoic and docosahexaenoic acids increased (overall p-value <0.001 for both). Prostaglandin F2α was higher in the CSO group than in the control group (p < 0.05), however, there were no other significant changes in urinary excretion of other prostanoids among the study groups. At baseline, arachidonic acid in plasma phospholipids was positively (r = 0.247, p < 0.05) and ALA negatively (r = -0.326, p < 0.05) associated with urinary total isoprostanes. In conclusion, CSO, fatty fish, and lean fish consumption do not cause major changes in oxidative stress markers in subjects with impaired glucose tolerance.


Nutritional requirements in cystic fibrosis: a review.
Food intake is often low in cystic fibrosis (CF), although the patient usually needs more than the standard recommended daily allowance (RDA). Clinics giving food supplementation from an early age report improved survival and nutritional status. Nutritional improvement has been facilitated by improved forms of pancreatin. An additional calorie intake in CF is required to compensate for losses due to malabsorption and to allow for catch-up growth when necessary. With advanced pulmonary disease there are additional requirements for infection and increased work of breathing. There is also evidence for an increased basal metabolic activity in CF, perhaps related to the fundamental intracellular biochemical disorder. Together these factors add to a daily need for 120%-150% RDA for optimum growth and homeostasis.


Reprint of: Assay Validation of the Cardiac Isoform of Troponin I in Double Crested Cormorant (Phalacrocorax auritus) Plasma for Diagnosis of Cardiac Damage.
Cardiac abnormalities, initially found in Deepwater Horizon weathered MC252 crude oil exposed Double Crested Cormorants (DCCOs) upon gross necropsy, were further investigated using echocardiography. Clinical and statistically significant changes including decreased ventricular myocardial contractility and arrhythmia were elucidated by echocardiography and interpreted by boarded cardiologists as potentially life threatening. The objective of this investigation was to initiate development of an antemortem, sensitive blood screening test for cardiac damage due to oil exposure of avian species. An assay for the cardiac isoform of troponin I (cTnI) which is known to be highly cross-reactive across mammalian species was chosen and analytically validated in DCCO. This is the first time this test has been analytically validated in avian species. All plasma samples from birds assessed as healthy had trace concentrations (<0.016ng/ml). The assays was precise and accurate revealing a coefficient of variation <3% and an R2>0.99. Diagnostic investigation revealed that the test appears to have diagnostic potential for the diagnosis of cardiomyocyte damage. Diagnostic sensitivity and specificity were 91% and 73% in this laboratory population. Due to an equivocal sample population in which health could not be proven, further investigation is needed to diagnostically validate troponin I in the assessment of oil exposure in DCCO.


A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder.
During the past years, clinical and epidemiological studies have indicated a close relationship between Alzheimer's disease (AD) and other mental disorders like major depressive disorder (MDD). At the same time, a number of genes genetically associated with AD or MDD have been detected. However, our knowledge on the mechanisms that link the two disorders is still incomplete, and controversies exist. In such a situation, a systematic analysis on these genes could provide clues to understand the molecular features of two disorders and their comorbidity. In this study, we compiled the genes reported to be associated with AD or MDD by a comprehensive search of human genetic studies and genes curated in disease-related database. Then, we investigated the features of the shared genes between AD and MDD using the functional enrichment analysis. Furthermore, the major biochemical pathways enriched in the AD- or MDD-associated genes were identified, and the cross talks between the pathways were analyzed. In addition, novel candidate genes related to AD and MDD were predicted in the context of human protein-protein interactome. We obtained 650 AD-associated genes, 447 MDD-associated genes, and 77 shared genes between AD and MDD. The functional analysis revealed that biological processes involved in cognition, neural development, synaptic transmission, and immune-related processes were enriched in the common genes, indicating a complex mechanism underlying the comorbidity of the two diseases. In addition, we conducted the pathway enrichment analysis and found 102 shared pathways between AD and MDD, which involved in neuronal development, endocrine, cell growth, and immune response. By using the pathway cross-talk analysis, we found that these pathways could be roughly clustered into four modules, i.e., the immune response-related module, the neurodevelopmental module, the cancer or cell growth module, and the endocrine module. Furthermore, we obtained 37 novel candidate genes potentially related to AD and MDD with node degrees > 5.0 by mapping the shared genes to human protein-protein interaction network (PPIN). Finally, we found that 37 novel candidate genes are significantly expressed in the brain. These results indicated shared biological processes and pathways between AD and MDD and provided hints for the comorbidity of AD and MDD.


Inhibitory effects evoked from the anterior hypothalamus are selective for the nociceptive responses of dorsal horn neurons with high- and low-threshold inputs.
The aim of the present study was to examine the selectivity of descending control of nociceptive information in the spinal dorsal horn following neuronal activation at "pressor" sites in the anterior hypothalamus. Extracellular single-unit activity was recorded from 11 dorsal horn neurons in the lower lumbar spinal cord of anesthetized rats. Neurons selected for investigation were those that responded to noxious (pinch and radiant heat >46 degrees C) and nonnoxious (prod, stroke, and/or brush) stimulation within their cutaneous receptive fields on the ipsilateral hind paw. These are referred to as Class 2 neurons. Micropipettes were inserted stereotaxically into the anterior hypothalamus at sites where injection of the excitatory amino acid L-homocysteic acid (L-HCA) evoked increases in arterial blood pressure. The effects of microinjection of L-HCA at "pressor" sites in the anterior hypothalamus were then tested on the responses of Class 2 neurons to noxious and nonnoxious stimulation of their excitatory receptive fields. The high-threshold (pinch and/or radiant heat) responses of 7/7 Class 2 neurons tested were inhibited by an average of 66.3 +/- 8.8% (mean +/- SE) by neuronal activation at hypothalamic pressor sites. The low-threshold (prod) responses of 10/10 Class 2 neurons tested were not inhibited by neuronal activation at hypothalamic pressor sites; in 6 of these cells the response to low-intensity stimulation was increased by between 4 and 20%. Control injections of the inhibitory amino acid gamma-aminobutyric acid (GABA) at the same hypothalamic pressor sites had no significant effects on arterial blood pressure or neuronal activity. With regard to sensory processing in the spinal cord, these data suggest that descending inhibitory control that originates from neurons in pressor regions of the anterior hypothalamus is highly selective for nociceptive inputs to Class 2 neurons.


Prevalence and costs of defensive medicine: a national survey of Italian physicians.
Objective To identify the prevalence of the practice of defensive medicine among Italian hospital physicians, its costs and the reasons for practising defensive medicine and possible solutions to reduce the practice of defensive medicine. Methods Cross-sectional web survey. Main outcome measures Number of physicians reporting having engaged in any defensive medicine behaviour in the previous year. Results A total of 1313 physicians completed the survey. Ninety-five per cent believed that defensive medicine would increase in the near future. The practice of defensive medicine accounted for approximately 10% of total annual Italian national health expenditure. Conclusions Defensive medicine is a significant factor in health care costs without adding any benefit to patients. The economic burden of defensive medicine on health care systems should provide a substantial stimulus for a prompt review of this situation in a time of economic crisis. Malpractice reform, together with a systematic use of evidence-based clinical guidelines, is likely to be the most effective way to reduce defensive medicine.


[Continuous-cycle technology of rehabilitation of patients with chronic obstructive pulmonary disease on an outpatient basis].
Of this study is to substantiate the effectiveness of continuous-cycle technology of rehabilitation of patients with chronic obstructive pulmonary disease (COPD) on an outpatient basis. 140 patients with moderate to severe (stage II-III) COPD were examined: 82% with chronic bronchitis phenotype and 18% - with emphysema phenotype. 44% of patients had frequent exacerbations. Patients were admitted to outpatient rehabilitation after stages I and II because of the exacerbation of the disease. 2 comparable groups were formed: the primary group included 68 patients who were engaged in active physical rehabilitation according to a continuous-cycle technique for 10-12 months; the comparison group consisted of 72 patients receiving only basic drug therapy. Continuous-cycle technique included: regular exercise therapy, cycling and procedures that improve tolerance to them (hardware chest vibration, chlorpromazine electrophoresis), oxygen cocktail, general ultraviolet radiation in the unfavorable period of the year. Diagnostics of early signs of an exacerbation of the disease and prophylactic prescription of physiotherapeutic procedures were carried out. During the year of observation during treatment, only 4 cases failed to prevent full exacerbation of the disease. During the year, in the patients of the primary group, in contrast to the comparison group, there was a significant improvement in the clinical signs of the disease, an increase in VC, an improvement in bronchial patency, an increase in physical performance and exercise tolerance, and a decrease in the activity of systemic inflammation. A year later, we registered an improvement in the course of the disease n 70% of patients of the primary group, and only stabilization of the process - in 82% of the comparison group. Frequency of exacerbations in the primary group decreased 5.1 times, which was 3.9 times more significant than in the comparison group.


The influence of net charge and charge distribution on cellular uptake and cytosolic localization of arginine-rich peptides.
Properties of different arginine-rich peptides, including net charge and charge distribution, were evaluated for their influence on surface binding, internalization, and intracellular localization. The peptides were radiolabeled and subsequently tested for surface binding and internalization in CHO-K1 cells. Subcellular fractionation assays were performed to separate the amount of peptides associated within vesicles from those inside the cytosol. Net neutral charged peptides, YGR(6)E(6) and YG(RE)(6), showed large decreases in both surface binding and cell uptake compared to their net positive charged counterparts, YGR(6)G(6) and YG(RG)(6). The peptides with clustered arginine residues, YGR(6)G(6) and YGR(6)E(6), exhibited significantly higher binding and uptake than those with alternating arginine and glycine/glutamate residues, YG(RG)(6) and YG(RE)(6). The intracellular distribution analysis for all of the peptides tested showed that, regardless of the net uptake, the arginine-rich peptides were preferentially localized in the cytosolic compartment of the cells. Both net positive charge and a clustered arginine sequence enhance the surface binding and internalization of peptides; however, the cytosolic versus vesicular intracellular distribution does not change. The results presented in this report provide important information regarding the specificity of binding and internalization of arginine-rich peptides, which is necessary for the future design of targeted drug delivery systems.


Tox: a multifunctional transcription factor and novel regulator of mammalian corticogenesis.
Major efforts are invested to characterize the factors controlling the proliferation of neural stem cells. During mammalian corticogenesis, our group has identified a small pool of genes that are transiently downregulated in the switch of neural stem cells to neurogenic division and reinduced in newborn neurons. Among these switch genes, we found Tox, a transcription factor with hitherto uncharacterized roles in the nervous system. Here, we investigated the role of Tox in corticogenesis by characterizing its expression at the tissue, cellular and temporal level. We found that Tox is regulated by calcineurin/Nfat signalling. Moreover, we combined DNA adenine methyltransferase identification (DamID) with deep sequencing to characterize the chromatin binding properties of Tox including its motif and downstream transcriptional targets including Sox2, Tbr2, Prox1 and other key factors. Finally, we manipulated Tox in the developing brain and validated its multiple roles in promoting neural stem cell proliferation and neurite outgrowth of newborn neurons. Our data provide a valuable resource to study the role of Tox in other tissues and highlight a novel key player in brain development.


Painful leg lesions: a case report.
We describe a case of Loefgren's syndrome where the characteristic history and physical exam allowed for the provisional diagnosis to be made in the emergency department. The diagnosis was subsequently confirmed by hilar lymph node biopsy demonstrating noncaseating granulomas. The prognosis and treatment are briefly reviewed.


[Sudeck's syndrome (author's transl)].
Though being not frequently seen now Sudeck's syndrome is still an undesirable painful complication of the healing and functional restitution in cases of injury to the wrist joint area. It is clear now that Sudeck's syndrome cannot be prevented only by correct surgical procedure, but that it is conditioned situationally and by the vegetative lability of the injured individual's personality and predisposed in this way. Besides routine rehabilitation the indication includes medication acting on the vegetative nervous system. Good healing conditions are obtained with a Chlorpromazine-Promethazine-Dihydroergotoxin combination for 6 to 8 weeks, blockade of the stellate ganglion and sufficient patience and consideration shown to the mentally upset and depressively reacting patient.


The Bacterial Ecosystem of Mother's Milk and Infant's Mouth and Gut.
The progressive building of the infants' gut microbiota is pivotal for educating their immune system. Human breast milk is among the first sources of microbes for the assembly of the infant's microbiota, but research struggles to give a demonstration for the origin of bacteria in milk. Aiming at contributing to the knowledge on assembly of the mother's milk and infant's microbiome, here we characterized the oral, gut and milk ecosystems in a homogeneous cohort of 36 healthy mother-infants pairs, by 16S rRNA next-generation sequencing. A limited number of operational taxonomic units (OTUs) was shared among the three ecosystems, including not only OTUs assigned to the well-known immune-modulating Bifidobacterium genus, but also specific Streptococcus and Staphylococcus OTUs, which were dominant in the infant's mouth ecosystem. The high conservation of these OTUs among the three ecosystems seems to call for a worth exploring ecological role through targeted and/or culture-dependent techniques. Notwithstanding the limitations of a 16S rRNA gene-based molecular characterization, we might hypothesize that the baby's mouth, being the transition point for the milk to reach the intestine, could play a role in both the gut microbiota assembly, via deglutition, and mother's milk duct colonization, during suction.


Proapoptotic Activity of Propolis and Their Components on Human Tongue Squamous Cell Carcinoma Cell Line (CAL-27).
Propolis has been used since ancient times in folk medicine. It is a popular medicine possessing a broad spectrum of biological activities. This material is one of the richest sources of polyphenolic compounds such as flavonoids and phenolic acids. The ethanolic extract of propolis (EEP) evokes antibacterial, antiviral, antifungal and anticancer properties. Due to pharmacological properties it is used in the commercial production of nutritional supplements. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was used to quantify main polyphenols in EEPs. The effect of EEPs, individual EEPs components (chrysin, galangin, pinocembrin, caffeic acid, p-coumaric acid, ferulic acid) and their mixture on viability of human tongue squamous cell carcinoma cell line (CAL-27) as well as the molecular mechanisms of the process were examined. The results of MTTs assay demonstrated that EEP, polyphenols and mixture of polyphenolic compounds were cytotoxic for CAL-27 cells in a dose dependent manner. The mechanism of cytotoxicity induced by these components undergoes through apoptosis as detected by flow cytometry. The ethanolic extracts of propolis activated caspases -3, -8, -9. Mixture of polyphenols was found as the most potent inducer of apoptosis thorough both intrinsic and extrinsic pathway. Therefore, we suggest that anticancer properties of propolis is related to synergistic activity of its main components.


A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release.
Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced 'medium-sized' EVs (CVB1i-mEVs). These mEVs (100-300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection.


Allergic necrotizing eosinophilic granulomatosis.
Allergic necrotizing eosinophilic granulomatosis (ANEG) is a rare entity characterized by peripheral eosinophilia, hepatosplenomegaly, dyspnea, and lymphadenopathy. An unusual patient with ANEG is described in which the presenting feature was an extensive granulomatous lesion of the face. The patient's condition progressively deteriorated despite multiple therapies, and she finally succumbed to her disease.


Complex interactions between the chaperonin 60 molecular chaperone and dihydrofolate reductase.
The spontaneous refolding of chemically denatured dihydrofolate reductase (DHFR) is completely arrested by chaperonin 60 (GroEL). This inhibition presumably results from the formation of a stable complex between chaperonin 60 and one or more intermediates in the folding pathway. While sequestered on chaperonin 60, DHFR is considerably more sensitive to proteolysis, suggesting a nonnative structure. Bound DHFR can be released from chaperonin 60 with ATP, and although chaperonin 10 (GroES) is not obligatory, it does potentiate the maximum effect of ATP. Hydrolysis of ATP is also not required for DHFR release since certain nonhydrolyzable analogues are capable of partial discharge. "Native" DHFR can also form a stable complex with chaperonin 60. However, in this case, complex formation is not instantaneous and can be prevented by the presence of DHFR substrates. This suggests that native DHFR exists in equilibrium with at least one conformer which is recognizable by chaperonin 60. Binding studies with 35S-labeled DHFR support these conclusions and further demonstrate that DHFR competes for a common saturable site with another protein (ribulose-1,5-bisphosphate carboxylase) known to interact with chaperonin 60.


Cryopreservation Induces Acetylation of Metabolism-Related Proteins in Boar Sperm.
Cryodamage affects the normal physiological functions and survivability of boar sperm during cryopreservation. Lysine acetylation is thought to be an important regulatory mechanism in sperm functions. However, little is known about protein acetylation and its effects on cryotolerance or cryodamage in boar sperm. In this study, the characterization and protein acetylation dynamics of boar sperm during cryopreservation were determined using liquid chromatography-mass spectrometry (LC-MS). A total of 1440 proteins were identified out of 4705 modified proteins, and 2764 quantifiable sites were elucidated. Among the differentially modified sites, 1252 were found to be upregulated compared to 172 downregulated sites in fresh and frozen sperms. Gene ontology indicated that these differentially modified proteins are involved in metabolic processes and catalytic and antioxidant activities, which are involved in pyruvate metabolism, phosphorylation and lysine degradation. In addition, the present study demonstrated that the mRNA and protein expressions of SIRT5, IDH2, MDH2 and LDHC, associated with sperm quality parameters, are downregulated after cryopreservation. In conclusion, cryopreservation induces the acetylation and deacetylation of energy metabolism-related proteins, which may contribute to the post-thawed boar sperm quality parameters.


The influence of firearms trafficking on gunshot injuries in a co-offending network.
Individuals at the greatest risk of gunshot victimization are often prohibited from legally acquiring guns in the U.S. due to prior felony convictions or other disqualifications. Prohibited persons often rely on others - such as friends, family members, fellow gang members, and gun brokers - to acquire firearms. This study examines whether the sources of guns recovered from high-risk individuals differ relative to the sources of guns recovered more generally in a major U.S. city, and whether illegally-diverted guns are associated with increased gunshot victimization risk. Using official data, we recreate the co-offending network of individuals in Boston who were arrested or contacted by the police with at least one other person between 2007 and 2014. Firearms trace data are then used to develop measures of the shortest distance between individuals and firearms in their immediate network. Results suggest guns with markers of illegal diversion are more likely to be recovered in the highest risk sector of the network and that the probability of gunshot victimization increases with decreased distance to an individual linked to firearms with markers of illegal trafficking.


An animal model to detect the neuropsychological toxicity of anticancer agents.
The unexpected discovery that certain chemotherapeutic agents used in the treatment of childhood cancers have neurocognitive side effects has prompted a search for techniques that identify those medications that place children at risk. An animal model for the assessment of resultant neurocognitive toxicity is described which makes use of simple classical conditioning. We have shown that rats learn about environmental events more slowly following neonatal administration of methotrexate. The changes after methotrexate exposure are not related to stimulus characteristics or to perceptual abilities, but rather to damage to the neural systems involved in acquisition, retention, or recall. Similar problems with learning have been observed in children treated with methotrexate. An effective animal model such as the one described here may help detect and avoid antineoplastic agents that produce severe cognitive defects in childhood cancer patients.


Perceived Roles of Bhutanese Health Care Professionals in Improving Patient Safety: A Qualitative Exploratory Descriptive Study.
Patient safety is a vital component of high quality health care and all health care professionals have a responsibility for ensuring the delivery of safe care to patients. However, little is known about how Bhutanese health care professionals perceive their roles in improving patient safety. This study aimed to explore how Bhutanese health care professionals, educators, managers, and policy makers perceived their roles in improving patient safety. Undertaken as a naturalistic inquiry using a qualitative exploratory descriptive research approach, a criterion-based stratified purposive sample of 94 health care professionals and managers from the Ministry of Health, a training institute, and 3 levels of hospitals were interviewed. All interview data were analyzed using content and thematic analysis strategies. Data analysis identified 4 broad themes. Health care professionals' perceived role in safety and quality included formulating and implementing patient safety rules; management and administration of units and hospitals; patient assessment and management; and setting professional norms (including norms about peer influence and patient care/interaction). The findings revealed that Bhutanese health care professionals were aware of their roles in improving patient safety processes and practices, and providing interprofessional education or training to all levels of health care professionals could help improve communication and patient safety in the Bhutanese health care system.


The adenoviral E4orf6 protein induces atypical apoptosis in response to DNA damage.
Adenoviral proteins interact with host-cell proteins to either exploit or inhibit cellular functions for the purpose of viral propagation. E4orf6, the 34-kDa gene product of the E4 gene, interacts with the double-strand break repair (DSBR) protein DNA-dependent protein kinase and cooperates with binding partner E1B-55K to degrade MRE11, preventing viral DNA concatemer formation. We previously demonstrated that E4orf6 radiosensitizes human tumor cells through the inhibition of DSBR, notably in the absence of E1B-55K. Here, we report that E4orf6 prolongs the signaling of DNA damage by inhibiting the activity of protein phosphatase 2A (PP2A), the phosphatase responsible for dephosphorylating gammaH2AX. The inhibition of PP2A occurs without significant disruption of the DNA re-ligation rate. Prolonged signaling of DNA damage in the presence of E4orf6 initiates caspase-dependent and independent cell death. This is accompanied by poly(ADP-ribose) polymerase (PARP) hyperactivation and the translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Knockdown of AIF by shRNA rescues the radiosensitization induced by E4orf6. Taken together, these data suggest that E4orf6 disrupts cellular DSBR signaling by inhibiting PP2A, leading to prolonged H2AX phosphorylation, hyperactivation of PARP, and AIF translocation to the nucleus. The function of E4orf6 as an inhibitor of PP2A and activator of PARP in the absence of other adenoviral gene products is of importance in delineating the adenovirus-host cell interplay.


Bowhead whale localization using asynchronous hydrophones in the Chukchi Sea.
This paper estimates bowhead whale locations and uncertainties using non-linear Bayesian inversion of their modally-dispersed calls recorded on asynchronous recorders in the Chukchi Sea, Alaska. Bowhead calls were recorded on a cluster of 7 asynchronous ocean-bottom hydrophones that were separated by 0.5-9.2 km. A warping time-frequency analysis is used to extract relative mode arrival times as a function of frequency for nine frequency-modulated whale calls that dispersed in the shallow water environment. Each call was recorded on multiple hydrophones and the mode arrival times are inverted for: the whale location in the horizontal plane, source instantaneous frequency (IF), water sound-speed profile, seabed geoacoustic parameters, relative recorder clock drifts, and residual error standard deviations, all with estimated uncertainties. A simulation study shows that accurate prior environmental knowledge is not required for accurate localization as long as the inversion treats the environment as unknown. Joint inversion of multiple recorded calls is shown to substantially reduce uncertainties in location, source IF, and relative clock drift. Whale location uncertainties are estimated to be 30-160 m and relative clock drift uncertainties are 3-26 ms.


Engineering the Interface of Carbon Electrocatalysts at the Triple Point for Enhanced Oxygen Reduction Reaction.
The aqueous oxygen reduction reaction (ORR) has recently received increased attention due to its critical role in clean and sustainable energy-generation technologies, such as proton exchange membranes (PEM) fuel cells, alkaline fuel cells and Zn-air batteries. The sluggish kinetics associated with ORR result from multistep electron-transfer process. The slow kinetics are partially related to the O2 adsorption process onto the catalyst, which happens at the triple-phase boundary (TPB) of the electrocatalyst-electrolyte-oxygen interface. Hence, tremendous efforts have been devoted to improving the intrinsic properties of electrocatalysts such as active sites, electrical conductivity and porosity. Engineering the electrocatalyst's interfacial properties is another critical issue in ORR, however less described in the literature. The surface of the catalyst provides the microenvironment for the triple boundary interface reaction, which directly influences its electrocatalytic activity and the kinetics. This Minireview is a summary of the existing literature on manipulating the interfacial surface of non-precious metal catalysts at the triple point between the solid catalyst, the aqueous electrolyte and the O2 gas with the aim of improving the ORR efficiency. Various approaches towards improving the wettability and nanostructuring the catalyst surface to boost the activity of the surface-active sites and provide improved stability are discussed.


Bisphenol A release from orthodontic adhesives measured in vitro and in vivo with gas chromatography.
The objectives of this study were to quantify in vitro the Bisphenol A (BPA) release from 5 orthodontic composites and to assess in vivo the BPA level in patients' saliva and urine after bracket bonding with an orthodontic adhesive system. For the in-vitro portion of this study, 5 orthodontic composites were evaluated: Eagle Spectrum (American Orthodontics, Sheboygan, Wis), Enlight (Ormco, Orange, Calif), Light Bond (Reliance Orthodontic Products, Itasca, Ill), Mono Lok II (Rocky Mountain Orthodontics, Denver, Colo), and Transbond XT (3M Unitek, Monrovia, Calif). Simulating intraoral conditions, the specimens were immersed in a water/ethanol solution, and the BPA (ng.g-1) liberation was measured after 30 minutes, 24 hours, 1 day, 1 week, and 1 month by the gas chromatography system coupled with mass spectrometry. Twenty patients indicated for fixed orthodontic treatment participated in the in-vivo study. Saliva samples were collected before bracket bonding and then 30 minutes, 24 hours, 1 day, 1 week, and 1 month after bonding the brackets. Urine samples were collected before bonding and then at 1 day, 1 week, and 1 month after bonding. The results were analyzed statistically using analysis of variance and Tukey posttest, with a significance level of 5%. All composites evaluated in vitro released small amounts of BPA. Enlight composite showed the greatest release, at 1 month. Regarding the in-vivo study, the mean BPA level in saliva increased significantly only at 30 minutes after bonding in comparison with measurements recorded before bonding. All orthodontic composites released BPA in vitro. Enlight and Light Bond had, respectively, the highest and lowest BPA releases in vitro. The in-vivo experiment showed that bracket bonding with the Transbond XT orthodontic adhesive system resulted in increased BPA levels in saliva and urine. The levels were significant but still lower than the reference dose for daily ingestion.


Heavy drinking during periods of high unemployment: 15-year trend study of the role of race/ethnicity.
This study conceptualized high unemployment rate as a stressor deriving from the social structure. It tracked American adults' heavy drinking rates 1997-2011, intending to examine (1) whether heavy drinking escalates with rising unemployment, and (2) whether racial minorities, who feel economic downturns more than the majority, engage in heavy drinking at a higher level than Whites in times of high unemployment. Research questions were answered using data from the Combined National Health Interview Survey. The present final sample included only respondents classified as heavy drinkers: those reporting that, on days (in the preceding year) on which they had consumed alcohol, they had regularly had at least 5 drinks. The study, which considered individual-level social structural factors, overall found rising unemployment rate to be associated with high measures for heavy-drinking frequency but low measures for heavy-drinking quantity. It did not find race to moderate the unemployment-heavy-drinking relationship, although some empirical evidence has shown racial minorities to be relatively more responsive to fluctuating unemployment inherent in the economic cycle. Our results in general call for further research on roles of gender and race in heavy drinking, especially where Black females are concerned. Blacks' greater heavy-drinking frequency and greater heavy-drinking quantity (versus Whites) observed in this study may shed light on persistent racial disparities in Americans' health.


Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 2: Approaches Beyond First-Line Therapy, and Novel Biologic Agents Under Investigation.
A frequent quandary for oncologists is the selection of chemotherapy and biologic therapy for patients with metastatic colorectal cancer in second-line and higher treatment settings. While not approved by the US Food and Drug Administration (FDA) in the first-line setting, the vascular endothelial growth factor (VEGF)-targeting agents ziv-aflibercept and ramucirumab are appropriate treatment options in the second-line setting, as is continuation of first-line bevacizumab. Tumor RAS mutational status is helpful to determine which patients may benefit from epidermal growth factor receptor (EGFR)-directed therapies, and other novel biomarkers (BRAF, HER2, and mismatch repair deficiency) allow us to select patients who may benefit from biologic therapies that are FDA-approved for other malignancies. Maintenance therapy for patients with stable disease following first-line therapy is a unique clinical situation that warrants special attention. Immunotherapy has thus far been ineffective for patients with mismatch repair-proficient tumors, but novel combination strategies are being studied to break through this treatment barrier. Finally, several new biologic therapies with novel targets are under development and will likely contribute to the growing arsenal of treatment options for patients with metastatic colorectal cancer.


Clinical characteristics of myositis patients with isolated anti-U1 ribonucleoprotein antibody resemble immune-mediated necrotizing myopathy.
Anti-U1 ribonucleoprotein (U1RNP) antibodies were associated with connective tissue diseases (CTDs), but the clinical characteristics of this antibody in Chinese myositis patients have not been studied. We aim to analyze the clinical features of myositis patients who test positive for anti-U1RNP antibodies and delineate a subgroup of myositis. This is a retrospective cohort study. We reviewed the clinical data of myositis patients with anti-U1RNP antibodies and compared them to those with anti-signal recognition particle (SRP) and hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibody-associated immune-mediated necrotizing myopathy (IMNM). A total of 30 adult cases were identified; median age was 47.5 years and 24 (80%) were females, and 12 patients did not coexist with myositis-specific antibodies (MSAs) (isolated anti-U1RNP). The serum creatine kinase (CK) was significantly higher in patients with isolated anti-U1RNP (2182.5 U/L versus 289 U/L, p = 0.01), and the number of patients with CK > 2000 U/L was higher compared to that in anti-U1RNP antibody patients coexisting with MSAs (66.7% versus 16.7%, p = 0.009). The prevalence of IMNM in patients' muscle pathology with isolated anti-U1RNP was significantly higher (75%, p = 0.003). Skin rashes were less common in isolated anti-U1RNP group (p < 0.05). Of the 25 individuals with available pulmonary high-resolution CT (HRCT), 14 (56%) were diagnosed with interstitial lung disease (ILD). The incidence of muscular weakness, dysphagia, or levels of CK was not different between the isolated anti-U1RNP antibody individuals and the anti-HMGCR or SRP-IMNM groups (p > 0.05). But the frequency of Raynaud's phenomenon, arthritis, and membrane attack complex (MAC) deposits in myositis patients with isolated anti-U1RNP antibodies were higher than in anti-HMGCR and SRP-IMNM (all p < 0.005). There was no difference between anti-U1RNP patients with and without Ro-52 (p > 0.05). Isolated anti-U1RNP individuals showed marked improvements in muscle strength, and the remission rate in 1 and 2 years was significantly higher than that in anti-HMGCR and SRP-IMNM (p < 0.05). The clinical and pathological features of myositis patients with isolated anti-U1RNP antibodies were similar to IMNM. Arthritis and ILD are the most common extramuscular clinical features. Most respond well to treatment and have a good prognosis.


Near-wake structure behind two circular cylinders in a side-by-side configuration with heat release.
Flow around two circular cylinders in a side-by-side arrangement normal to the free stream with heat release from one of the cylinders is studied experimentally. This flow, with no heat release, is known to exhibit a range of flow regimes at different cylinder spacings. In particular, the wake exhibits well-known intermittently bistable behavior in the center-to-center spacing (normalized by cylinder diameter) range of 1.2-2.0. We present, for the first time, the effect of heat release from one of the cylinders on the near-wake structure of the two cylinder configuration. The experiments are performed at spacing ratios of 1.1, 1.7, and 3.0, Reynolds numbers of 250, 350, and 450 and Richardson number less than 0.14. The investigations are carried out in a water tunnel using hydrogen bubble technique for flow visualization and particle-image-velocimetry for quantitative measurements. The bistability of the wake at a spacing ratio of 1.7 is controlled with a threshold heat release from one of the cylinders resulting in a stable narrow wake behind the heated cylinder and a wider wake behind the unheated cylinder. The heat release resulted in deflection of the gap-bleeding flow toward the heated cylinder at spacing ratio of S/D=1.1 and did not produce any visual changes in the near-wake structure at spacing ratio of 3.0.


Medial lenticulostriate artery aneurysm presenting with isolated intraventricular hemorrhage.
Isolated intraventricular hemorrhage (IVH) secondary to lenticulostriate artery aneurysm rupture is extremely rare. Thus, the diagnostic imaging modalities and therapeutic interventions utilized in the management of such cases are not clearly defined. Here we describe a case of isolated or primary IVH (PIVH) in a 71-year-old woman presenting with severe headache. Emergent catheter cerebral angiography, performed after nondiagnostic computed tomography angiography (CTA), revealed the bleeding source to be a 4 × 2.6 mm distal medial lenticulostriate artery aneurysm that ruptured directly into the lateral ventricle. The poorly accessible location of the aneurysm for both endovascular and direct surgical treatment argued for conservative management. A good clinical outcome was obtained with rapid angiographic resolution of the ruptured aneurysm. Thus, lenticulostriate artery aneurysm rupture must be given diagnostic consideration in cases of isolated IVH. Emergent catheter cerebral angiography should be performed in cases such as this when noninvasive imaging is unrevealing. Conservative management may be a reasonable therapeutic option in patients with this kind of aneurysm, and spontaneous resolution can be observed.


Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling.
Upon activation by Wnt, the Frizzled receptor is internalized in a process that requires the recruitment of Dishevelled. We describe a novel interaction between Dishevelled2 (Dvl2) and micro2-adaptin, a subunit of the clathrin adaptor AP-2; this interaction is required to engage activated Frizzled4 with the endocytic machinery and for its internalization. The interaction of Dvl2 with AP-2 requires simultaneous association of the DEP domain and a peptide YHEL motif within Dvl2 with the C terminus of micro2. Dvl2 mutants in the YHEL motif fail to associate with micro2 and AP-2, and prevent Frizzled4 internalization. Corresponding Xenopus Dishevelled mutants show compromised ability to interfere with gastrulation mediated by the planar cell polarity (PCP) pathway. Conversely, a Dvl2 mutant in its DEP domain impaired in PCP signaling exhibits defective AP-2 interaction and prevents the internalization of Frizzled4. We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling.


Plasmin system regulation in an ovalbumin-induced rat model of asthma.
So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma. Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6). Control groups were saline-sensitized challenged with OVA (VEH/OVA, n = 6) and OVA-sensitized challenged with saline (OVA/VEH, n = 6). Plasmin system components were determined in the plasma by ELISA. Plasminogen activator inhibitor-1 (PAI-1) was localized by an immunohistochemical reaction. Sensitization and challenge with OVA caused thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions. Serum total IgE was significantly higher in OVA-sensitized rats as compared to VEH-sensitized control groups. Tissue plasminogen activator activity was significantly decreased in asthmatic animals (4.48 +/- 0.4 vs. 6.7 +/- 0.3 ng/ml for OVA/OVA and OVA/VEH; p < 0.05), and PAI-1 activity was statistically significantly higher in asthma rats (0.8 +/- 0.05 vs. 0.5 +/- 0.03 ng/ml for OVA/OVA vs. OVA/VEH; p < 0.05). alpha2-Antiplasmin was higher in rats receiving OVA sensitization than in those that were sham sensitized (p < 0.05). Immunohistochemical staining for PAI-1in the lungs of asthmatic animals showed very strong PAI-1 expression in lung inflammatory cells. We have demonstrated for the first time the existence of PAI-1 in lung inflammatory cells of rats with asthma. This finding was consistent with the superiority of plasmin system inhibition over activation in plasma.


An investigation into the characteristics of reperfusion-induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents.
Reperfusion-induced arrhythmias were elicited in the pentobarbitone-anaesthetized rat by occlusion of the left main coronary artery and subsequent release. These arrhythmias were rapid in onset, occurring within 20 s after release of the ligature, and were of short duration (1-2 min). Their severity was dependent upon the duration of the preceding occlusion. A 5 or 15 min occlusion period produced the most severe arrhythmias on release, the incidence of ventricular fibrillation being 56 and 50% respectively. Evidence that reperfusion had occurred was provided by fluorescein dye distribution and intramyocardial temperature studies. The severity of reperfusion arrhythmias and mortality was unaffected by bilateral vagotomy, beta-adrenoceptor blockade by atenolol (2 mg kg-1 i.v.) or a combination of the two. The incidence of reperfusion-induced ventricular fibrillation was significantly reduced by Org 6001 (which blocks the fast inward sodium current), melperone (which acutely prolongs the cardiac action potential duration) and bepridil (which blocks both fast and slow inward currents). It was unaffected by nitroglycerine and the calcium antagonists verapamil, prenylamine and nifedipine. We have shown that reperfusion-induced cardiac arrhythmias can be consistently elicited in the anaesthetized rat and that they are particularly susceptible to drugs that can block the fast inward sodium current.


[Use of a pair of blood culture bottles for sterility testing of corneal organ culture media].
To test the effectiveness and rapidity of a pair of blood culture bottles in the diagnosis of bacterial and fungal contamination of corneal organ culture media. and methods: Seven hundred and sixty one microbiological analysis of storage media (Inosol(R) and Exosol(R), Opsia, Toulouse, France), sampled in all phases of the organ culture at 31 degrees C of 410 consecutive corneas, were analyzed. Each medium was inoculated in a pair of Bactec Plus Aerobic/F(R) and Bactec Lytic/10 Anaerobic/F(R) blood bottles (Becton Dickinson, Cockeysville, MD) and placed in a Bactec 9240 incubator for 14 days at 37 degrees C and in a Sabouraud broth at 20 degrees C. Changes in color or turbidity of storage media were evaluated daily at the corneal bank. Recipients were screened after graft for signs of infection. The overall contamination rate was 2.4% (18/761). Contamination was detected in less than 1 day in 78% (14/18) and in less than 2 days in 94% (17/18). Positivity of the microbiological controls of starting media preceded medium color changes in 10 out of 14 cases. Bactec blood bottles allowed detection of bacteria as well as Candida sp. yeasts. The use of a pair of aerobic and anaerobic blood culture bottles is a simple, effective and rapid method for the diagnosis of a wide range of microbiological contaminations of organ-cultured corneas during banking. The validation of this protocol will require a prospective study to compare it with the conventional microbiological method.


Salmonella aortitis successfully treated with antibiotics without surgery.
Aortitis is an inflammation of the aorta that is linked to large vessel vasculitis and other rheumatologic cases. Less often, an infectious etiology of aortitis is diagnosed. Aortitis is associated with high mortality and morbidity and requires a high index of suspicion. Here we present a rare case of aortitis secondary to Salmonella Septicemia treated with six weeks of antibiotics in the hospital without and remained asymptomatic and inflammatory markers normalized at 2 weeks follow up (ESR, CRP, and WBCs).


Understanding and Interpreting Pharmacy College Admission Test Scores.
To fairly and accurately interpret candidates' Pharmacy College Admission Test (PCAT) scores as listed on their official transcripts, it is important to understand how these scores reflect candidates' performances on cognitive tasks involving the identification, interpretation, analysis, and evaluation of information assumed to have been covered in pre-pharmacy science, math, and general education coursework. This paper attempts to facilitate this understanding by explaining how candidates' responses to PCAT test items relate to their scaled scores and percentile ranks and how their writing scores reflect their performance. This paper also suggests how differences between candidates' PCAT subtest scores may reflect different personal experiences, educational backgrounds, and cognitive abilities.


The continuing evolution of the Journal of Neurophysiology: 2018 update.
The Journal of Neurophysiology continues to evolve to meet the needs of its authors and readers. This article summarizes recent changes intended to improve our evaluation and communication of neuroscience research.


Current trends in paediatric regional anaesthesia.
Regional anaesthesia is a cornerstone in paediatric anaesthesia today. Many paediatric anaesthetists include regional anaesthetic techniques in their daily clinical practice to provide superior and long-lasting analgesia without the risk of respiratory depression. The first part this article reviews new scientific findings in the field of paediatric regional anaesthesia. The second part focuses on safety aspects and on the impact of ultrasound on paediatric regional anaesthesia.


EGFR mutation heterogeneity and the mixed response to EGFR tyrosine kinase inhibitors of lung adenocarcinomas.
Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations have mixed responses to tyrosine kinase inhibitors (TKIs). Intertumor heterogeneity in EGFR mutations is one potential explanation for this phenomenon. We performed direct sequencing to identify EGFR mutations in 180 pairs of lung adenocarcinoma samples (from 3,071 patients). The high-resolution melting method was used in discordant cases to confirm EGFR mutation status. Matching samples were divided into four groups: primary lesions detected at different times, primary tumors with matched metastatic lymph nodes, multiple pulmonary nodules, and primary tumors with matched distant metastases. Multivariate analyses were performed to evaluate correlations between heterogeneity and patient characteristics. In the study population, the discordance rate was 13.9% (25 of 180). The multiple pulmonary nodules group had the highest discordance rate of 24.4% (10 of 41; odds ratio for heterogeneity in primary lesions detected at different times, 6.37; 95% confidence interval, 1.71-23.72; p = .006). Discordance rates in the metachronous and synchronous settings were 15.7% (22 of 140) and 7.5% (three of 40), respectively. In the 34 patients who developed EGFR TKI resistance, 10 (29.4%) cases exhibited heterogeneity and five (14.7%) patients exhibited a mixed response to the drug. Three (8.8%) of the patients with a mixed response also exhibited discordant EGFR mutations. The overall discordance rate of EGFR mutation heterogeneity in Asian patients with pulmonary adenocarcinoma is relatively low, but the rate in patients with multiple pulmonary nodules is significantly higher. This observation may explain the mixed tumor response to EGFR TKIs.


Aerosol bolus dispersion in acinar airways--influence of gravity and airway asymmetry.
The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter particle boluses in three-dimensional computational models of the lung periphery, ranging from a single alveolar sac to four-generation (g4) structures of bifurcating airways that deformed homogeneously during breathing. Boluses were introduced at the beginning of a 2-s inhalation, immediately followed by a 3-s exhalation. Dispersion was estimated by the half-width of the exhaled bolus. Dispersion was significantly affected by the spatial orientation of the models in normal gravity and was less in zero gravity than in normal gravity. Dispersion was strongly correlated with model volume in both normal and zero gravity. Predicted pulmonary dispersion based on a symmetric g4 acinar model was 391 ml and 238 ml under normal and zero gravity, respectively. These results accounted for a significant amount of dispersion measured experimentally. In zero gravity, predicted dispersion in a highly asymmetric model accounted for ∼20% of that obtained in a symmetric model with comparable volume and number of alveolated branches, whereas normal gravity dispersions were comparable in both models. These results suggest that gravitational sedimentation and not geometrical asymmetry is the dominant factor in aerosol dispersion in the lung periphery.


Consistency of diagnostic criteria for asthma from Laënnec (1819) to the National Asthma Education Program (1991).
Interpretation of longitudinal trends in asthma incidence, prevalence, and mortality must assume consistency in the diagnostic criteria used by clinicians. This review samples the textbook and clinical literature on clinical recognition and diagnosis of asthma from Laënnec (1819) to the National Asthma Education Program (1991), which introduced as a standard for clinical care a set of diagnostic criteria based on laboratory confirmation. There is great consistency among authors in descriptions of the cardinal diagnostic criteria of asthma as episodic dyspnea punctuating periods of normal breathing, generally associated with expiratory wheezing and prolonged expiration. In contrast, there is much greater variation in the formal definitions or explanations of the presumed pathophysiology of the disorder. It is much more difficult to document the actual diagnostic criteria used by practicing clinicians in the past, but these findings indicate a high degree of consistency over 172 years in what was taught and was considered acceptable practice. The literature on asthma contains several medical classics, a few gems of insight, and some unusual authors; some of these are noted in the discussion, as is the strong tradition of reciprocity in American and British medicine.


Highly sensitive trace gas detection based on a miniaturized 3D-printed Y-type resonant photoacoustic cell.
We report, what we believe to be, a novel miniaturized 3D-printed Y-type resonant photoacoustic cell (YRPAC) consisting of a frustum of cone-type buffer chamber and a cylindrical resonant chamber. The volume of the designed YRPAC is about 7.0 cm3, which is only about a half of the T-resonant photoacoustic cell (TRPAC). The finite element simulation of the sound field distribution of the TRPAC and YRPAC based on COMSOL shows that the photoacoustic signal is enhanced with the shape of the buffer chamber changing from the traditional cylinder to a frustum of cone. The photoacoustic spectroscopy (PAS) system, utilizing the YRPAC and TRPAC as the photoacoustic reaction units, a 1653.7 nm distributed feedback (DFB) laser as the excitation light source, a cantilever beam acoustic sensor as the acoustic sensing unit, and a high-speed spectrometer as the demodulation unit, has been successfully developed for high-sensitivity trace CH4 sensing. When the CH4 concentration is 1000 ppm, the 2f signal of YRPAC in the first-order resonance mode is 2.3 nm, which is 1.7 times higher than the 2f signal amplitude of TRPAC. The detection sensitivity and minimum detection limit for the PAS system are 2.29 pm/ppm and 52.8 parts per billion (ppb) at 100 s of averaging time. The reported YRPAC has higher sensitivity, smaller size, and faster response time compared to the conventional TRPAC, which can provide a new solution for PAS development.


A new sampler to assess dermal exposure during wet working.
In the UK, approximately 30% of cases of dermatitis reported to the national surveillance scheme are associated with wet working or exposure to aqueous mixtures. There is evidence that the duration and frequency that hands are wet are key determinants of risk, but there are no objective methods to measure these exposure factors. This research aimed to develop a practical tool to measure the duration and the number of occasions hands are wet. We developed an electronic sensor that is worn on the finger, which detects wetness from evaporative cooling. The output signal is recorded in electronic memory and the frequency and duration of exposure calculated using a simple data processing algorithm. The device has been tested in a variety of environmental conditions and for a standardized wet-work task. Wetting events were detectable in all the standardized tests, with the proportion of time the hands were wet ranging from 15 to 49% (mean 30%). The electronic sensor is slightly affected by abrupt changes in air temperature and rapid air movements, but these do not seem to impose any practical limitations. This IOM Wet-Work sampler has the potential to provide reliable measurements of exposure that may be used to assess the risk of contact dermatitis.


Inhibition of hepatitis B virus expression and replication by RNA interference in HepG2.2.15.
To observe the inhibition of hepatitis B virus replication and expression by transfecting vector-based small interference RNA (siRNA) pGenesil-HBV X targeting HBV X gene region into HepG2.2.15 cells. pGenesil-HBV X was constructed and transfected into HepG2.2.15 cells via lipofection. HBV antigen secretion was determined 24, 48, and 72 h after transfection by time-resolved immunofluorometric assays (TRFIA). HBV replication was examined by fluorescence quantitative PCR, and the expression of cytoplasmic viral proteins was determined by immunohistochemistry. The secretion of HBsAg and HBeAg into the supernatant was found to be inhibited by 28.5% and 32.2% (P < 0.01), and by 38.67% (P < 0.05) and 42.86% (P < 0.01) at 48 h and 72 h after pGenesil-HBV X transfection, respectively. Immunohistochemical staining for cytoplasmic HBsAg showed a similar decline in HepG2.2.15 cells 48 h after transfection. The number of HBV genomes within culture supernatants was also significantly decreased 48 h and 72 h post-transfection as quantified by fluorescence PCR (P < 0.05). In HepG2.2.15 cells, HBV replication and expression is inhibited by vector-based siRNA pGenesil-HBV X targeting the HBV X coding region.


Infection and Pulp Regeneration.
The regeneration of the pulp-dentin complex has been a great challenge to both scientists and clinicians. Previous work has shown that the presence of prior infection may influence the characteristics of tissues formed in the root canal space after regenerative endodontic treatment. The formation of ectopic tissues such as periodontal ligament, bone, and cementum has been observed in the root canal space of immature necrotic teeth with apical periodontitis, while the regeneration of dentin and pulp has been identified in previously non-infected teeth. The current regenerative endodontic therapy utilizes disinfection protocols, which heavily rely on chemical irrigation using conventional disinfectants. From a microbiological point of view, the current protocols may not allow a sufficiently clean root canal microenvironment, which is critical for dentin and pulp regeneration. In this article, the significance of root canal disinfection in regenerating the pulp-dentin complex, the limitations of the current regenerative endodontic disinfection protocols, and advanced disinfection techniques designed to reduce the microorganisms and biofilms in chronic infection are discussed.


Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas.
Salivary gland carcinomas (SGCs) exhibit heterogeneous biological behaviors, including the formation of distant metastases, which is a critical event associated with poor prognosis. Ezrin, which is a member of the ezrin-radixin-moesin family of plasma membrane-cytoskeleton linker proteins, may provide a marker for metastasis and poor survival of patients with cancer. The aim of the present study was to investigate the relationship between ezrin expression and the expression of HER2, p53, and Ki-67 as well as clinicopathological factors in SGCs. For this purpose, we used immunohistochemistry to analyze the expression of these proteins in tissue microarrays prepared from formalin-fixed, paraffin-embedded primary tumor tissues of 221 patients with SGCs. Using receiver operating characteristic curves, we determined cut-off values of 30% and 5.0% for high expression of ezrin and Ki-67, respectively. High ezrin expression detected in samples from 63 (28.5%) patients with SGCs significantly correlated with male sex, high-grade histopathology, high Ki-67 labeling index, HER2 overexpression, aberrant expression of p53, and distant metastasis. Multivariate analysis demonstrated that high ezrin expression was an independent prognostic factor for shorter overall survival (hazard ratio, 2.11 [1.09-4.05]; P=.027). Furthermore, concomitant high expression of ezrin and HER2 overexpression correlated significantly with shorter disease-free survival and overall survival as well as a high incidence of distant metastasis (P<.001). These findings indicate that ezrin and HER2 expression in patients with SGCs represents a high-grade histopathological subtype that requires adjuvant therapy, including molecularly targeted therapies, to decrease the risk of subsequent metastasis.


A close relationship between Cercozoa and Foraminifera supported by phylogenetic analyses based on combined amino acid sequences of three cytoskeletal proteins (actin, alpha-tubulin, and beta-tubulin).
Recently, there has been increasing molecular evidence of phylogenetic affinity between Cercozoa and Foraminifera in the eukaryotic lineage. We performed phylogenetic analyses based on the combined (concatenated) amino acid sequence data of actin, alpha-tubulin, and beta-tubulin from a wide variety of eukaryotes, including the foraminifers Planoglabratella opercularis and Reticulomyxa filosa, as well as cercomonad and chlorarachniophyte members of Cercozoa. A monophyletic lineage composed of two foraminiferan species branched with the centroheliozoan species Raphidiophrys contractilis was reconstructed in both Bayesian and maximum-likelihood (ML) analyses under 'linked' models, enforcing a single set of the parameters (the parameter for among-site rate variation and branch lengths) on the entire combined alignment. Considering the extremely divergent nature of Foraminifera and Raphidiophyrs tubulins, the union of these lineages recovered is most probably a long-branch attraction artifact due to ignoring gene-specific evolutionary processes. On the other hand, the foraminiferan lineage was within the radiation of Cercozoa in Bayesian analyses under 'unlinked' model conditions, accommodating differences in evolutionary processes across the three genes in the combined alignment. The Foraminifera+Cercozoa affinity recovered in the latter multi-gene analyses is most likely genuine, and thus our data presented here provide further support for the close relationship between these two protist lineages.


[A bone metastasis of hepatocellular carcinoma].
Reported is a case of a bone metastasis of a hepatocellular carcinoma (HCC). A 61-year-old man with an unresectable HCC, which had been detected on spontaneous rupture, complained of a severe neck pain and numbness of both arms. A roentgenogram of the cervix showed destruction in the spinous process of the third cervical vertebra, and an MRI revealed a vertebral tumor compressing the spinal cord. Thus, the tumor was surgically removed. A pathological examination of the tumor revealed it to have the characteristic features on an HCC. One month after its removal, however, an iliac bone metastasis that was causing pain was found, and, again, an excision of the new tumor was performed. Pain symptoms disappeared after these operations. Treatment of an HCC bone metastasis is palliative, however, it is beneficial in maintaining the quality of the patient's remaining life.


A randomized clinical study of the heated lidocaine/tetracaine patch versus subacromial corticosteroid injection for the treatment of pain associated with shoulder impingement syndrome.
Treatment for pain due to shoulder impingement syndrome (SIS) typically begins conservatively with nonsteroidal anti-inflammatory drugs and physical therapy and can include subacromial injection of corticosteroids, particularly in patients unresponsive to conservative measures. The heated lidocaine/tetracaine (HLT) patch has been reported to reduce SIS pain in a small case series. This was a prospective, randomized, open-label clinical trial in which adult patients with SIS pain lasting at least 14 days, with an average intensity of ≥4 on a 0-10 scale (0= no pain, 10= worst pain) were randomized to treatment with the HLT patch or a single subacromial injection of triamcinolone acetonide (10 mg). Patients in the HLT patch group applied a single HLT patch to the shoulder for 4 hours twice daily, with a 12-hour interval between treatments during the first 14 days, and could continue to use the patch on an as-needed basis (up to twice daily) during the second 14-day period. No treatment was allowed in the final 14-day period. At baseline and at days 14, 28, and 42, patients rated their pain and pain interference with specific activities (0-10 scale). Sixty patients enrolled in the study (average age =51 years, range 18-75, n=21 female). Average pain scores declined from 6.0±1.6 at baseline to 3.5±2.4 at day 42 in the HLT patch group (n=29, P<0.001) and from 5.6±1.2 to 3.2±2.6 in the injection group (n=31, P<0.001). Similar improvements were seen in each group for worst pain; pain interference with general activity, work, or sleep; and range of motion. No significant between-group differences were seen for any pain or pain interference scores at any time point. These results suggest that short-term, noninvasive treatment with the HLT patch has similar efficacy to subacromial corticosteroid injections for the treatment of pain associated with SIS.


An Information-Theoretic-Cluster Visualization for Self-Organizing Maps.
Improved data visualization will be a significant tool to enhance cluster analysis. In this paper, an information-theoretic-based method for cluster visualization using self-organizing maps (SOMs) is presented. The information-theoretic visualization (IT-vis) has the same structure as the unified distance matrix, but instead of depicting Euclidean distances between adjacent neurons, it displays the similarity between the distributions associated with adjacent neurons. Each SOM neuron has an associated subset of the data set whose cardinality controls the granularity of the IT-vis and with which the first- and second-order statistics are computed and used to estimate their probability density functions. These are used to calculate the similarity measure, based on Renyi's quadratic cross entropy and cross information potential (CIP). The introduced visualizations combine the low computational cost and kernel estimation properties of the representative CIP and the data structure representation of a single-linkage-based grouping algorithm to generate an enhanced SOM-based visualization. The visual quality of the IT-vis is assessed by comparing it with other visualization methods for several real-world and synthetic benchmark data sets. Thus, this paper also contains a significant literature survey. The experiments demonstrate the IT-vis cluster revealing capabilities, in which cluster boundaries are sharply captured. Additionally, the information-theoretic visualizations are used to perform clustering of the SOM. Compared with other methods, IT-vis of large SOMs yielded the best results in this paper, for which the quality of the final partitions was evaluated using external validity indices.


A new RFLP marker, SP282, at the btk locus for genetic analysis in X-linked agammaglobulinaemia families.
X-linked agammaglobulinaemia is an inherited recessive disease in which the primary defect lies in the failure of pre-B cells to develop into mature circulating B cells, due to a defective B-cell cytoplasmic tyrosine kinase (btk). For this study we introduced a new RFLP marker, SP282, which is tightly linked to the XLA locus. In conjunction with the marker DXS178, SP282 was used to identify a carrier female and predict her male offspring to be normal. Subsequently the fetus was shown to have a normal number of circulating B cells, and at 2.5 years of age, the non-affected phenotype of the child was confirmed.


Differential diagnosis of substance-induced psychosis and schizophrenia in patients with substance use disorders.
We derived a statistical model that discriminates between substance-induced psychosis (i.e., DSM-III-R organic delusional disorder or organic hallucinosis; ODD-OH) and DSM-III-R schizophrenia in patients who have both DSM-III-R psychoactive substance use disorders (PSUD) and prominent delusions or hallucinations. A sample of 211 PSUD inpatients was divided by year of admission into data sets A and B, each of which was divided between those with concurrent schizophrenia and those with concurrent ODD-OH. A six-predictor discriminant function correctly classified 76.2 percent of all set A patients, including 83.1 percent with schizophrenia. Formal thought disorder and bizarre delusions significantly predict a diagnosis of schizophrenia, with odds ratios (OR) of 3.55:1 and 6.09:1, respectively. Suicidal ideation (OR = 0.32:1), intravenous cocaine abuse (0.18:1), and a history of drug detoxification (0.26:1) or methadone maintenance (0.18:1) demonstrate inverse relationships with a schizophrenia diagnosis. The model was validated in set B, correctly predicting the diagnostic status of 70.4 percent of patients (72.5% with schizophrenia). The pattern of presenting symptoms and clinical history differs in patients with psychosis due to PSUD and in those whose psychosis is due to schizophrenia. The model presented here contributes to the differential diagnosis of schizophrenia and ODD-OH among patients with PSUD.


ES-MION-Based Dual-Modality PET/MRI Probes for Acidic Tumor Microenvironment Imaging.
Among all characteristics of the tumor microenvironment (TME), which are caused by abnormal proliferation of solid tumors, extracellular acidity is an important indicator for malignancy grading. pH-low insertion peptides (pHLIPs) are adopted to discern the acidic TME. To date, different imaging agents including fluorescent, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance (MR) contrast agents with pHLIPs to target the acidic TME have been used to image various tumor models successfully. In this article, a PET/MRI dual-modality probe, based on extremely small magnetic iron oxide nanoparticles (ES-MIONs) with pHLIPs as a targeting unit, was proposed for the first time. In the phantom study, the probe showed relatively high r 1 relaxivity (r 1 = 1.03 mM-1 s-1), indicating that it could be used as a T1-weighted MR contrast agent. The 68Ga-radiolabeled probe was further studied in vitro and in vivo to evaluate pHLIP targeting efficacy and feasibility for PET/MRI. PET with intratumoral injection and T1-weighted MRI with intravenous injection both showed pHLIP-specific delivery of the probe. Therefore, we successfully designed and developed a radiolabeled ES-MION-based dual-modality PET/MRI agent to target the acidic tumor microenvironment. Although the accumulation of the probe in tumors with intravenous injection was not high enough to exhibit signals in the PET imaging study, our study still provides further insights into the ES-MION-based PET/MRI strategy.


Postpartum Human Immunodeficiency Virus Care Among Women Diagnosed During Pregnancy.
To identify factors associated with continuity of care and human immunodeficiency virus (HIV) virologic suppression among postpartum women diagnosed with HIV during pregnancy in New York State. This retrospective cohort study was conducted among 228 HIV-infected women diagnosed during pregnancy between 2008 and 2010. Initial receipt of HIV-related medical care (first CD4 or viral load test after diagnosis) was evaluated at 30 days after diagnosis and before delivery. Retention in care (2 or more CD4 or viral load tests, 90 days or greater apart) and virologic suppression (viral load 200 copies/mL or less) were evaluated in the 12 months after hospital discharge. Most women had their initial HIV-related care encounter within 30 days of diagnosis (74%) and before delivery (87%). Of these women, 70% were retained in the first year postpartum. Women waiting more than 30 days for their initial HIV-related care encounter were more likely diagnosed in the first (29%) compared with the third (11%) trimester and were of younger (younger than 25 years, 32%) compared with older (35 years or older, 13%) age. Loss to follow-up within the first year was significantly greater among women diagnosed in the third compared with the first trimester (adjusted relative risk 2.21, 95% confidence interval [CI] 1.41-3.45) and among women who had a cesarean compared with vaginal delivery (adjusted relative risk 1.76, 95% CI 1.07-2.91). Of the 178 women with one or more HIV viral load test in the first year postpartum, 58% had an unsuppressed viral load. Despite the high proportion retained in care, many women had poor postpartum virologic control. Robust strategies are needed to increase virologic suppression among newly diagnosed postpartum HIV-infected women.


Disease burden of psittacosis in the Netherlands.
Psittacosis (infection with Chlamydia psittaci) can have diverse presentations in humans, ranging from asymptomatic infection to severe systemic disease. Awareness of psittacosis and its presentations are low among clinicians and the general public. Therefore, underdiagnosis and thereby underestimation of the incidence and public health importance of psittacosis is very likely. We used the methodology developed for the Burden of communicable diseases in Europe toolkit of the European Centre for Disease Prevention and Control, to construct a model to estimate disease burden in disability-adjusted life years (DALYs) attributable to psittacosis. Using this model, we estimated the disease burden caused by psittacosis in the Netherlands to have been 222 DALY per year (95% CI 172-280) over the period 2012-2014. This is comparable with the amount of DALYs estimated to be due to rubella or shigellosis in the same period in the Netherlands. Our results highlight the public health importance of psittacosis and identify evidence gaps pertaining to the clinical presentations and prognosis of this disease.


Role of the polymorphonuclear leukocyte in periodontal health and disease.
This review presents evidence for lysosomal enzymes being at least partly responsible for the tissue destruction seen in periodontal disease. However, many other inflammatory and immunologic mechanisms have been identified that can contribute to tissue destruction (Nisengard 1977). The relationship of PMN to the periodontal tissues is equivalent to the proverbial double-edged sword. The localized tissue destruction that may be due to the extracellular release of PMN enzymes in individuals with normal cell function must be weighed against the role of PMN in containment of gingival bacteria and their products. The consequences of qualitative and/or quantitative abnormalities of neutrophils are far more undesirable for the periodontium. It therefore seems logical to propose that the role of polymorphonuclear leukocytes in the gingival tissues is primarily a defensive one. The presence of neutrophils in the gingival crevice has been shown to reflect the inflammatory condition of the tissues. Due to their availability, it may prove beneficial to use gingival crevicular PMN activity as a reliable clinical index of disease activity. The development of appropriate tests to measure PMN may eventually lead to better diagnostic criteria, including the definition of active versus inactive disease.


A Systematic Review of Community-wide Media Physical Activity Campaigns: An Update From 2010.
Mass media campaign is an integral tool to influence physical activity participant behaviors. The purpose of the systematic review was to identify the effectiveness of mass media campaigns in promoting physical activity. Literature update from January 2010 to September 2016 was conducted in 13 databases. Full text articles of 128 were screened, and 23 articles (18 campaigns) were selected from the initial 1692 articles. All campaigns involved mass media advertisements to promote physical activity to general individuals (n = 2), adults (8), children (4), older adults (2), and parents of children (n = 2). The campaign evaluation designs included clustered RCT (2), cohort (3), quasi-experimental (9), and cross-sectional (9). Eight articles demonstrated significant campaign impact on proximal, 6 on intermediate, 5 on distal outcomes, and 6 on distal change based on either proximal or intermediate outcome. The current review assessed the outcome evaluation of mass media physical activity campaigns that varied in their respective scope, target population and outcomes measured to identify individual changes at proximal, intermediate, and distal level. Results from formative and process evaluation as well as dose-response and cost-effective analysis are suggested to provide valuable evidence for campaign stakeholders and planners.