Isolation and expression of a cDNA encoding Renilla reniformis luciferase.
Renilla reniformis is an anthozoan coelenterate capable of exhibiting bioluminescence. Bioluminescence in Renilla results from the oxidation of coelenterate luciferin (coelenterazine) by luciferase [Renilla-luciferin:oxygen 2-oxidoreductase (decarboxylating), EC 184.108.40.206]. In vivo, the excited state luciferin-luciferase complex undergoes the process of nonradiative energy transfer to an accessory protein, green fluorescent protein, which results in green bioluminescence. In vitro, Renilla luciferase emits blue light in the absence of any green fluorescent protein. A Renilla cDNA library has been constructed in lambda gt11 and screened by plaque hybridization with two oligonucleotide probes. We report here the isolation and characterization of a luciferase cDNA and its gene product. The recombinant luciferase expressed in Escherichia coli is identical to native luciferase as determined by SDS/PAGE, immunoblot analysis, and bioluminescence emission characteristics.


Bioengineered three-dimensional co-culture of cancer cells and endothelial cells: A model system for dual analysis of tumor growth and angiogenesis.
Angiogenesis marks the transformation of a benign local tumor into a life-threatening disease. Many in vitro assays are available on two-dimensional (2D) platforms, however, limited research has been conducted to investigate the behavior of tumors and endothelial cells (ECs) grown on three-dimensional (3D) platforms. This study provides a 3D co-culture spheroid of tumor cells with ECs to study the interplay between ECs and tumor cells. In a 3D co-culture with HepG2 hepatocellular carcinoma (HCC) cells, ECs differentiate to form tubule networks when in co-culture. Addition of angiogenic factors or angiogenesis inhibitors to the model system enhanced or inhibited endothelial differentiation in the 3D model, enabling investigations of the cellular signaling pathways utilized in HCC development. The 3D model demonstrated similar protein expression levels as a HCC xenograft, as well as exhibited upregulation of essential signaling proteins such as Akt/mTor in the 3D model, which is not reflected in the 2D model. The effects of several anti-angiogenic agents, such as sorafenib, sunitinib, and axitinib were analyzed in the 3D co-culture model by utilizing fluorescent proteins and a fluorescence resonance energy transfer (FRET)-based caspase-3 sensor in the ECs, which can detect apoptosis in real time. The apoptotic capability of a drug to inhibit angiogenesis in the 3D model can be easily distinguished via the FRET sensor, and dual screening of anti-angiogenesis and anti-tumor drugs can be achieved in a single step via the 3D co-culture model. In summary, a 3D co-culture model is constructed, where a HCC tumor microenvironment with a hypoxic core and true gradient penetration of drugs is achieved for drug screening purposes and in vitro studies utilizing a small HCC tumor. Biotechnol. Bioeng. 2017;114: 1865-1877. © 2017 Wiley Periodicals, Inc.


Design and computational optimization of compliance-matching aortic grafts.
Introduction: Synthetic vascular grafts have been widely used in clinical practice for aortic replacement surgery. Despite their high rates of surgical success, they remain significantly less compliant than the native aorta, resulting in a phenomenon called compliance mismatch. This incompatibility of elastic properties may cause serious post-operative complications, including hypertension and myocardial hypertrophy. Methods: To mitigate the risk for these complications, we designed a multi-layer compliance-matching stent-graft, that we optimized computationally using finite element analysis, and subsequently evaluated in vitro. Results: We found that our compliance-matching grafts attained the distensibility of healthy human aortas, including those of young adults, thereby significantly exceeding the distensibility of gold-standard grafts. The compliant grafts maintained their properties in a wide range of conditions that are expected after the implantation. Furthermore, the computational model predicted the graft radius with enough accuracy to allow computational optimization to be performed effectively. Conclusion: Compliance-matching grafts may offer a valuable improvement over existing prostheses and they could potentially mitigate the risk for post-operative complications attributed to excessive graft stiffness.


Peer assisted versus expert assisted learning: a comparison of effectiveness in terms of academic scores.
To compare the effectiveness of peer assisted learning versus expert assisted learning in terms of academic scores. Cross over-randomized control trial followed by a cross-sectional survey. Fatima Memorial Hospital, College of Medicine and Dentistry, Lahore, during January to October 2012. This study was conducted on 4th year MBBS students. The students were randomly divided in two groups by lottery method following their roll numbers. The groups A and B were dealt with Peer Assisted Learning (PAL) and Expert Assisted Learning (EAL) respectively. Effectiveness of both methods of learning was calculated on the basis of academic scores obtained in MCQ tests. One best answer type of MCQs were used and their construct validity was checked by other senior faculty members. After crossover of groups and altered teaching strategy, academic scores were compared again within the group and the comparable group. Student's views about this technique were measured by Likert's scale. P-values were obtained by applying independent and paired t-tests and considered statistically significant at ≥ 0.05. There were 70 students of 4th year MBBS which included 24 (34.3%) males and 46 (65.7%) females. TheCrohnbach's alpha value of these MCQs was 0.64. Scores of MCQ test were compared by applying independent t-test and p-value obtained was 0.971; after cross over p-value was 0.468 which was not significant between the results obtained by two learning strategies. Twenty five students (46.3%) said that PAL is an effective technique. Thirty eight (70.4%) students found it easy to communicate with a peer. For incorporation of PAL in curriculum of community medicine, 24 (44.4%) students voted in its favour. Peer assisted learning has proved of equivalent efficacy in terms of students score in MCQs test as expert assisted learning.


Genotyping of Bacillus cereus strains by microarray-based resequencing.
The ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. In this regard, Bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the B. cereus group that can cause diverse diseases. We employed custom-designed resequencing arrays (RAs) based on the genome sequence of Bacillus anthracis to generate 422 kb of genomic sequence from a panel of 41 Bacillus cereus sensu lato strains. Here we show that RAs represent a "one reaction" genotyping technology with the ability to discriminate between highly similar B. anthracis isolates and more divergent strains of the B. cereus s.l. Clade 1. Our data show that RAs can be an efficient genotyping technology for pre-screening the genetic diversity of large strain collections to selected the best candidates for whole genome sequencing.


Can genetically based clines in plant defence explain greater herbivory at higher latitudes?
Greater plant defence is predicted to evolve at lower latitudes in response to increased herbivore pressure. However, recent studies question the generality of this pattern. In this study, we tested for genetically based latitudinal clines in resistance to herbivores and underlying defence traits of Oenothera biennis. We grew plants from 137 populations from across the entire native range of O. biennis. Populations from lower latitudes showed greater resistance to multiple specialist and generalist herbivores. These patterns were associated with an increase in total phenolics at lower latitudes. A significant proportion of the phenolics were driven by the concentrations of two major ellagitannins, which exhibited opposing latitudinal clines. Our analyses suggest that these findings are unlikely to be explained by local adaptation of herbivore populations or genetic variation in phenology. Rather greater herbivory at high latitudes can be explained by latitudinal clines in the evolution of plant defences.


Prenatal screening for cystic fibrosis: an economic analysis.
Cystic fibrosis (CF) is the most common life-shortening genetically transmitted disease in Denmark with a birth prevalence of 1 in 4700, resulting in 12-15 new cases of cystic fibroses annually. The aim of this study is to disclose the societal resource implications of introducing a population wide prenatal screening programme for cystic fibrosis in Denmark. The present analysis is limited to the monetary consequences of introducing a screening programme, where costs of screening are compared to the potential benefits measured in cost savings involved if births of CF patients are avoided. Screening costs in a Danish setting were estimated at DKK 2 771 262 ( pound sterlings 231 438) per aborted affected fetus in the first screening round, stabilising at DKK 1 864 594 ( pound sterlings 155 383) per aborted affected fetus at subsequent screening rounds. Comparing this figure with the estimated benefits of avoiding a CF case (DKK 2.1-4.4 million; pound sterlings 175 000-366 667) suggests that introducing a screening programme for cystic fibrosis will be net cost saving irrespective of the perspective of the analysis, assumptions on replacement children and method of estimating long-term production gains/losses.


β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.
Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility in the aging brain. βHB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate βHB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-β, and exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We have generated a comprehensive atlas of the βHB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within βHB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among βHB targets and the clearance of these targets from mouse brain, likely via βHB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.


Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp.
Three new analogues of dolastatin 13, termed lyngbyastatins 5-7 ( 1- 3), were isolated from two different collections of marine cyanobacteria, Lyngbya spp., from South Florida. Their planar structures were deduced by a combination of NMR techniques, and the absolute configurations were established by modified Marfey's analysis of the acid hydrolyzates. The related cyclodepsipeptide somamide B ( 4), previously reported from a Fijian cyanobacterium, has also been found in one of the extracts, and its absolute stereochemistry was unambiguously assigned for the first time. Compounds 1- 4 were found to selectively inhibit elastase over several other serine proteases, with IC50 values for porcine pancreatic elastase ranging from 3 to 10 nM.


[Reactive lymph-node hyperplasia and pseudolymphomas with hypergammaglobulinemia. II. Pseudolymphoma and prelymphoma].
In this second part, the dysimmunitary conditions which associate a polyclonal hypergammapathy and adenopathy are studied. The latter simulate a malignant lymphoma both clinically and histologically, hence the term sometimes used: "pseudo-lymphoma". Above all, these dysimmunitary states should be considered as real pretumoral states, and a malignant lymphoma or Kaposi sarcoma can arise at any time during the evolution of the illness. Finally, all these illnesses, even apart from the appearance of malignant tumors, have a severe evolution and death can occur due to consequences of immune disorders and particularly to infection. The different histopathological and evolutive aspects of the following are successively studied: angio-immunoblastic lymphadenopathy; the association of adenopathy with Kaposi's sarcoma; the syndrome of epidemic immune deficiency of T cells (acquired immune deficiency syndrome; frequent in homosexuals; the Gougerot-Sjögren syndrome; adenopathy due to medicaments; and the lymphomatoid granulomatosis of Liebow. The similarity of the histopathological lymph node lesions observed in these different dysimmunitary states suggests an identical physiopathology. Also, the existence of frequent associations between these different diseases suggests a common triggering mechanism. The role of virus on a favourable hereditary ground is discussed.


Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France.
Owing to its low incidence, the management of Mycobacterium xenopi pulmonary infections is not clearly defined. A multicentre retrospective study was performed to describe the features of the disease and to evaluate its prognosis. All patients with M xenopi satisfying the 1997 ATS/IDSA criteria from 13 hospitals in north-east France (1983-2003) were included in the study. Clinical, radiological and bacteriological characteristics and data on the management and outcome were collected. 136 patients were included in the analysis, only 12 of whom presented with no co-morbidity. Three types of the disease were identified: (1) a classical cavitary form in patients with pre-existing pulmonary disease (n = 39, 31%); (2) a solitary nodular form in immunocompetent patients (n = 41, 33%) and (3) an acute infiltrate form in immunosuppressed patients (n = 45, 36%). 56 patients did not receive any treatment; the other 80 patients received first-line treatment containing rifamycin (87.5%), ethambutol (75%), isoniazid (66.2%), clarithromycin (30%) or fluoroquinolones (21%). After a follow-up of 36 months, 80 patients (69.1%) had died; the median survival was 16 months (range 10-22). Two independent prognostic factors were found: the acute infiltrate form was associated with a bad prognosis (hazard ratio 2.6, p = 0.001) and rifamycin-containing regimens provided protection (hazard ratio 0.325, p = 0.006). Clarithromycin-containing regimens did not improve the prognosis. In contrast to recent guidelines, this study showed three different types of the disease (cavitary, nodular or diffuse infiltrate forms) with a different prognosis. In order to improve survival, all patients with M xenopi infection should be treated with a rifamycin-containing regimen. The usefulness of clarithromycin remains to be evaluated.


The spinal accessory nerve plexus, the trapezius muscle, and shoulder stabilization after radical neck cancer surgery.
A clinical and anatomic study of the spinal accessory, the eleventh cranial nerve, and trapezius muscle function of patients who had radical neck cancer surgery was conducted. This study was done not only to document the indispensibility of the trapezius muscle to shoulder-girdle stability, but also to clarify the role of the eleventh cranial nerve in the variable motor and sensory changes occurring after the loss of this muscle. Seventeen male patients, 49-69 years of age, (average of 60 years of age) undergoing a total of 23 radical neck dissections were examined for upper extremity function, particularly in regard to the trapezius muscle, and for subjective signs of pain. The eleventh nerve, usually regarded as the sole motor innervation to the trapezius, was cut in 17 instances because of tumor involvement. Dissection of four fresh and 30 preserved adult cadavers helped to reconcile the motor and sensory differences in patients who had undergone loss of the eleventh nerve. The dissections and clinical observations corroborate that the trapezius is a key part of a "muscle continuum" that stabilizes the shoulder. Variations in origins and insertions of the trapezius may influence its function in different individuals. As regards the spinal accessory nerve, it is concluded that varying motor and sensory connections form a plexus with the eleventh nerve, accounting, in part, for the variations in motor innervation and function of the trapezius, as well as for a variable spectrum of sensory changes when the eleventh nerve is cut. For this reason, it is suggested that the term "spinal accessory nerve plexus" be used to refer to the eleventh nerve when it is considered in the context of radical neck cancer surgery.


SELECTION AND THE "SEX-RATIO" POLYMORPHISM IN NATURAL POPULATIONS OF DROSOPHILA PSEUDOOBSCURA.
"Sex-ratio" (SR) is a naturally occurring X-linked meiotic drive system, where the SR-X chromosome is transmitted to nearly all progeny of SR males. It occurs at frequencies of up to 25% in some populations of Drosophila pseudoobscura. Because of the twofold drive advantage, SR should rapidly fix in populations, causing the extinction of the species, unless opposed by strong selection. I examine several of the adult components of fitness, including the frequencies of all genotypic mating combinations, fertilities, and fecundities of flies from two populations in southeastern Arizona. Significant reduction of fecundity of SR/SR females was observed in the Tucson population. No evidence was found for either lower fertility or reduced mating success of SR males, relative to standard males. Most selection opposing SR appears to be operating at the larval stages in nature.


Coding of specific subgroups of myelodysplastic syndromes in a population-based cancer registry: prospects for improvement.
Myelodysplastic syndromes (MDS), reportable to US cancer registries for diagnoses since 2001, are a group of myeloid neoplasms heterogeneous in prognosis and treatment, and of growing importance in an aging population. In US registries that have reported incident MDS cases by subgroup, about 50%-67% of cases have been coded as MDS "not otherwise specified" (NOS) in the International Classification of Diseases for Oncology Version 3 (ICD-O-3). For this study, MDS cases diagnosed in 2001-2009 and reported to the population-based Connecticut Tumor Registry (CTR) were analyzed. MDS was coded as NOS for 573 (56.7%) of 1,011 cases, but the proportion varied among reporting facilities hospitals (ie, from 0 to 100%), with several statistical outliers. In pathology reports obtained for 130 CTR patients diagnosed with MDS in 2008-2009, 84% of the 62 patients coded as NOS had information on a key element (ie, % of blasts in bone marrow) in ICD-O-3 coding and other classifications of MDS subgroups. These findings suggest that central cancer registries may want to work with hospital tumor registrars in improving reporting of specific MDS subgroups using ICD-O-3. The addition of % blasts from pathology reports to the site-specific factors for MDS in the Collaborative Staging System could be proposed.


Diagnostic potential of hepcidin testing in pediatrics.
Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children. Serum hepcidin was measured by using an automated commercial immunoassay. Reference values were obtained from 86 healthy children. Hepcidin was then evaluated in 52 children with diseases where this hormone was expected to be differently regulated. Hepcidin values were 43.6 ng/mL median; 32-52.7 1-3 q: in males and 36.4 ng/mL median; 28.5-45.7 1-3 q: in females (P = 0.039). Hepcidin was significantly higher in postpubertal normal females than in normal males. Hepcidin resulted up-regulated in anemia of chronic disease of children affected by systemic Juvenile Idiopathic Arthritis and decreased after treatment with anakinra, an anti-interleukin-1 receptor antagonist. In iron deficiency anemia patients on oral iron supplementation and in β-thalassemia subjects, hepcidin levels were similar to those found in healthy subjects. This study sets up reference values for pediatric population and shows that in normal controls serum hepcidin react differently to puberty in females vs. males. In addition, it suggests that serum hepcidin may discriminate microcytic inflammatory anemia of Juvenile Idiopathic Arthritis from iron deficiency anemia. Overall these findings may represent a helpful tool for future studies tailored to understand the role of hepcidin in management of iron disorders in children.


No effects of 1 Hz offline TMS on performance in the stop-signal game.
Stopping an already initiated action is crucial for human everyday behavior and empirical evidence points toward the prefrontal cortex playing a key role in response inhibition. Two regions that have been consistently implicated in response inhibition are the right inferior frontal gyrus (IFG) and the more superior region of the dorsolateral prefrontal cortex (DLPFC). The present study investigated the effect of offline 1 Hz transcranial magnetic stimulation (TMS) over the right IFG and DLPFC on performance in a gamified stop-signal task (SSG). We hypothesized that perturbing each area would decrease performance in the SSG, albeit with a quantitative difference in the performance decrease after stimulation. After offline TMS, functional short-term reorganization is possible, and the domain-general area (i.e., the right DLPFC) might be able to compensate for the perturbation of the domain-specific area (i.e., the right IFG). Results showed that 1 Hz offline TMS over the right DLPFC and the right IFG at 110% intensity of the resting motor threshold had no effect on performance in the SSG. In fact, evidence in favor of the null hypothesis was found. One intriguing interpretation of this result is that within-network compensation was triggered, canceling out the potential TMS effects as has been suggested in recent theorizing on TMS effects, although the presented results do not unambiguously identify such compensatory mechanisms. Future studies may result in further support for this hypothesis, which is especially important when studying reactive response in complex environments.


Papillary carcinoma of the breast. A cytomorphologic analysis.
For the past 15 years at Lankenau Hospital, Philadelphia, more than 10,000 breast lesions have been aspirated; the distinctive cytomorphologic features of common carcinomas have been previously reported. This study is a cytomorphologic analysis of eight invasive papillary carcinomas. The parameters include the pattern and morphology of the tumor cells, and their measurements by ocular micrometry. The distinctive features of this unusual neoplasm are its papillary configuration, tall columnar cells, naked nuclei, and blood. The study is especially important because these neoplasms may be misinterpreted as benign tumors.


[On an official message for Hishio and Umakasu, as written on a wooden tablet excavated at the site of the Imperial Nagaya-ō residence].
A large number of wooden tablets (narrow strips of wood on which official messages are written) from the Nara-period were excavated at the site of the Imperial Nagaya-ō residence in Heijōkyō, during the years 1988 and 1989. On one of these tablets a message is written calling for hishio and umakasu for urgent medical use. As a cited paragraph of the "Geshi Fang" in the "Ishinpō" shows, both hisio and sake were used for the treatment of burns. It can be assumed that hishio and umakasu mentioned on the wooden tablet, were also used for the same treatment at that time. Therefore, this wooden tablet is of precious value as a historical document giving evidence of the acceptance and actual usage of Chinese medicine early in the 8th century.


When has enough evidence accumulated to change neonatal practice?
Randomized clinical trials are the best method to assess the safety and efficacy of therapeutic interventions. However, it is not always clear how much evidence from randomized trials is required to change clinical practice. Throughout the history of neonatal medicine, some therapies were subject to excessive and unnecessary testing through replication of clinical trials. Other therapies were adopted into clinical practice with insufficient evidence. In only a few cases was the right amount of evidence accumulated to drive a change in practice. Here we present a case history for each of these three scenarios. Arising from these, we suggest principles to identify when enough evidence exists for a therapy to become standard practice.


Active Somatic and Psychic Ear Acupuncture Points in Newborn Infants with Neonatal Abstinence Syndrome.
Neonatal abstinence syndrome (NAS) occurs within the first days after birth in newborns of mothers with a history of drug abuse. It may also occur in newborns whose mothers are undergoing substitution therapy. To determine the presence of active ear acupuncture points in newborn infants with NAS. Among newborn infants with NAS admitted to the Division of Neonatology at the University Hospital Graz between March 2009 and November 2014, an acupuncture-point detector (PS3 Silberbauer, Vienna, Austria) was used to identify active ear acupuncture points. An integrated optical and acoustical signal detects the ear points, which were then assigned to the ear map. A total of 31 newborn infants were assessed; 1 infant was excluded, however, because the mother had already weaned herself off opiates before admission. The excluded infant did not develop signs of NAS, had a low Finnegan score (3 points), and did not present any detectable active psychic ear acupuncture points. In all included newborn infants with NAS, active ear acupuncture points were identified: The psychovegetative rim was the most common active somatic area in each infant, followed by a few somatic and psychic ear acupuncture points. In all infants with symptoms of NAS, active psychic ear points were identified, of which the most frequently found points were the Frustration point and the R point. The activity of psychic ear acupuncture points may be specific for neonates with NAS.


Impact of exposure to community violence and psychological symptoms on college performance among students of color.
This study examined longitudinal relationships among exposure to chronic community violence during high school, psychological distress during the first semester of college, and academic performance during the first three semesters of college. The sample comprised 385 students of color in a large city. Exposure to community violence and psychological distress were measured with additive scales; academic performance (school persistence, grade point average) was obtained from transcripts. It was found that exposure to community violence and academic performance were not related; exposure to community violence and psychological distress were related; psychological distress and college persistence were related; and psychological distress and grade point average were not related. The findings are consistent with the causal chain model; specifically, that the effects of exposure to community violence in high school on academic performance in college are mediated by psychological distress.


The Inflammatory Potential of the Diet Is Associated with Depressive Symptoms in Different Subgroups of the General Population.
Background: Low-grade chronic inflammation, which can be modulated by diet, has been suggested as an important risk factor for depression, but few studies have investigated the association between the inflammatory potential of the diet and depression.Objective: We investigated the prospective association between the inflammatory potential of the diet, measured by the Dietary Inflammatory Index (DII), and incident depressive symptoms and tested the potential modulating effect of sex, age, physical activity, and smoking status.Methods: This study included 3523 participants (aged 35-60 y) from the SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydants) cohort, who were initially free of depressive symptoms. Baseline DII (1994-1996) was computed by using repeated 24-h dietary records. Incident depressive symptoms were defined by a Center for Epidemiologic Studies-Depression Scale score ≥17 for men and ≥23 for women in 2007-2009. We used multivariable logistic regression models to estimate ORs and 95% CIs, and modeled the DII as a continuous variable and as sex-specific quartiles.Results: A total of 172 cases of incident depressive symptoms were identified over a mean follow-up of 12.6 y. The DII was not associated with incident depressive symptoms in the full sample. In sex-specific models, men with a higher DII had a higher risk of incident depressive symptoms (quartile 4 compared with quartile 1-OR: 2.32; 95% CI: 1.01, 5.35), but the association was only marginally significant (P-trend = 0.06). When analyses were performed across smoking status, current and former smokers with a higher DII had a higher risk of incident depressive symptoms (quartile 4 compared with quartile 1-OR: 2.21; 95% CI: 1.08, 4.52). A positive association was also observed among less physically active participants (quartile 4 compared with quartile 1-OR: 2.07; 95% CI: 1.05, 4.07).Conclusion: The promotion of a healthy diet with anti-inflammatory properties may help to prevent depressive symptoms, particularly among men, smokers, or physically inactive individuals. This trial was registered at clinicaltrials.gov as NCT0027242.


[Environmental factors associated with the decision time for seeking care in myocardial infarction].
The purpose was to estimate the decision time (DT) for searching for attendance for men and women suffering from acute myocardial infarction (AMI); and to analyze the influence of surrounding variables in the DT. Transversal study, involving one hundred patients interviewed in hospitals of Salvador-BA, Brazil. For data analysis, it was used the chi-squared or Fisher's exact test, and the Robust Linear Regression Model. AMI at the home predominated, with family members and patients receiving mistaken actions. A high DT was observed both, for women (0.9h) and men (1.4h). Those at home during the initial symptoms had higher DT, compared to those at work; and lower in relation to those in public spaces (p=0.047). Statistically significant interaction occurred among gender and the fact of living with company; and among gender and having a companion and children, for the outcome of the DT. Nursing care focused on the specificity of surrounding factors and gender can optimize early attendance.


The Chick Edema Factor.
A toxic factor in some feed grade fats and fatty acids produces hydropericardium and ascites in young chicks when 9 pg. per kilogram body weight are fed per day. There are a number of these toxic compounds, containing large amounts of chlorine. One has been characterized and synthesized.


Return to fertility in nulliparous and parous women after removal of the GyneFix intrauterine contraceptive system.
To evaluate the return to fertility following removal of the GyneFix intrauterine implant system in women wishing to conceive. A retrospective study was performed on a sample of healthy, sexually active nulligravid/nulliparous and parous women. The participants were 18-41 years of age, with no apparent infertility problem, living in a stable relationship and planning to become pregnant. Women who changed their mind and did not wish to become pregnant immediately after intrauterine device (IUD) removal were excluded from the study. Women were evaluated in terms of rates of conception and fertility outcome. A total of 128 women were evaluated. The study shows that 119 out of 128 (93%) past users of GyneFix have conceived, accounting for a net cumulative pregnancy rate of 88% at 12 months and 99% after 2 years' observation. No statistical differences in pregnancy rates were found for age and duration of use of the IUD. A strong significant difference in pregnancy rate was shown (p = 0.007) between parous and nulligravid/nulliparous women. Seventy-seven women (66.9%) gave birth to a term infant. There were no stillbirths. Twenty-five women (21.8%) are pregnant at the time of writing. Five (4.4%) spontaneous abortions occurred and in eight women (6.9%) the pregnancy was terminated. There were no ectopic pregnancies. The results obtained compare favorably with those obtained in previous studies conducted following the removal of copper IUDs. The use of the frameless IUD does not affect future fertility in nulligravid/nulliparous and parous women wishing to become pregnant following removal of the device. Nulliparous women conceive significantly earlier than parous women.


Effect of barley flour, crude cinnamon, and their combination on glycemia, dyslipidemia, and adipose tissue hormones in type 2 diabetic rats.
This study aimed to evaluate the effects of barley flour, crude cinnamon, and their combination on blood glucose, serum insulin, serum lipid profile, and serum adipose tissue hormones in streptozotocin-induced diabetic rats. Male Wistar rats (n=35) were divided into five groups: nondiabetic, diabetic, diabetic group fed 5% cinnamon, diabetic group fed 30% barley, and diabetic group fed 5% cinnamon and 30% barley. Fasting blood glucose, insulin, lipid profile, adiponectin, and leptin were measured after 8 weeks. Blood glucose significantly decreased in all treated diabetic rats compared with the diabetic group. Serum insulin and high-density lipoprotein significantly increased, while cholesterol, triglycerides, and low-density lipoprotein were significantly decreased after 8 weeks. Adiponectin significantly increased, while leptin significantly decreased with administration of either cinnamon, barley, or their combination. No significant differences were observed among the three treated groups on all parameters. A cinnamon and barley combination caused obvious improvement in insulin-positive cells of pancreatic tissue. In conclusion, consuming diets containing either cinnamon, barley, or their combination regulates blood glucose, lipid profile, and adipose tissue hormones in type 2 diabetic rats. The most effective treatment was the cinnamon and barley combination.


Selective degeneration of central photoreceptors after hyperbaric oxygen in normal and metallothionein-knockout mice.
Metallothioneins (MTs) in the brain and retina are believed to bind metals and reduce free radicals, thereby protecting neurons from oxidative damage. This study was undertaken to investigate whether retinal photoreceptor (PR) cells lacking MTs are more susceptible to hyperbaric oxygen (HBO)-induced cell death in vivo. Wild-type (WT) and MT-knockout (MT-KO) mice lacking metallothionein (MT)-1 and MT-2 were exposed to three atmospheres of 100% oxygen for 3 hours, 3 times per week for 1, 3, or 5 weeks. The control animals were not exposed. Histologic analysis of PR viability was performed by counting rows of nuclei in the outer nuclear layer (ONL). Ultrastructure studies verified PR damage. HBO exposure produced a major loss of PR cells in the central retinas of WT and MT-KO mice, with no effect on the peripheral retina even at the longest (5 weeks) exposures. The degree of PR damage and cell death increased with duration of HBO exposure. One week of HBO exposure was insufficient to cause PR death, but tissue damage was observed in the inner and outer segments. At 3 weeks, the rows of PR nuclei in the central retina were significantly reduced by 38% in WT and 28% in MT-KO animals. At 5 weeks, PR loss was identical in WT (34%) and MT-KO (34%) animals and was comparable to that in WT at 3 weeks. The data suggest that MT-1 and -2 alone are not sufficient for protecting PRs against HBO-induced cell death. The selective degeneration of central PRs may provide clues to mechanisms of oxidative damage in retinal disease.


Lysine Acetyltransferase p300/CBP Plays an Important Role in Reproduction, Embryogenesis and Longevity of the Pea Aphid Acyrthosiphon pisum.
CREB-binding protein (p300/CBP) is a universal transcriptional co-regulator with lysine acetyltransferase activity. Drosophila melanogaster p300/CBP is a well-known regulator of embryogenesis, and recent studies in beetles and cockroaches have revealed the importance of this protein during post-embryonic development and endocrine signaling. In pest insects, p300/CBP may therefore offer a useful target for control methods based on RNA interference (RNAi). We investigated the role of p300/CBP in the pea aphid (Acyrthosiphon pisum), a notorious pest insect used as a laboratory model for the analysis of complex life-history traits. The RNAi-based attenuation of A. pisum p300/CBP significantly reduced the aphid lifespan and number of offspring, as well as shortening the reproductive phase, suggesting the manipulation of this gene contributes to accelerated senescence. Furthermore, injection of p300/CBP dsRNA also reduced the number of viable offspring and increased the number of premature nymphs, which developed in abnormally structured ovaries. Our data confirm the evolutionarily conserved function of p300/CBP during insect embryogenesis and show that the protein has a critical effect on longevity, reproduction and development in A. pisum. The potent effect of p300/CBP silencing indicates that this regulatory protein is an ideal target for RNAi-based aphid control.


Immunolocalization of the C-terminal and N-terminal regions of alpha-A and alpha-B crystallins.
The C-terminal and possibly the N-terminal regions of the alpha crystallins are thought to be involved in the molecular chaperone properties of the protein. To localize these regions within the 13-15 nm aggregate of native alpha crystallin, antisera specific for the C-terminal and N-terminal regions were used together with immunogold and transmission electron microscopy. The results demonstrate that the C-terminal regions of the alpha-A and alpha-B molecules and the N-terminal regions of the alpha-A and/or alpha-B molecules are localized to a central region of the native alpha aggregate. These findings demonstrate that the C-terminal and N-terminal regions of alpha crystallin are localized to a region of the alpha aggregate that has previously been hypothesized to be the binding site for partially denatured proteins.


How to measure quality in endoscopic retrograde cholangiopancreatography (ERCP).
Endoscopic retrograde cholangiopancreatography (ERCP) is invasive therapeutic procedure demanding specific individual approach for learning and mastering. It is associated with greater morbidity and mortality than any other procedure in gastroenterology. The risk for complications and harm for patient inevitably require strict guidelines to be followed regarding training, certification and proficiency. In an attempt to reduce the risk of complications, various endoscopic societies worldwide have established so called "Quality measures" which proved to be the back bone for safety and quality in ERCP. Recently developed ERCP quality network allowing data comparison between endoscopist is the key of reducing complications and creating a state of the art teaching program for beginner endoscopist. Further research is required regarding quality measures improvement and information exchange in the global ERCP quality network.


[Prospects and limitations of genetic engineering].
Examples for genetic engineering are the transfer of nuclei between cells of higher animals and the introduction of heterologous DNA into bacteria by means of plasmids. The former approach will help to establish new ways in animal breeding, the latter provides bacterial cells that produce proteins of medical importance. The moral justification of related studies in man is still open, but the possible risks of gene technology can be coped with by adhering to proper safety regulations.


Luminescent gold(I) metallo-acids and their hydrogen bonded supramolecular liquid crystalline derivatives with decyloxystilbazole as hydrogen acceptor.
Gold complexes of 4-isocyanobenzoic acid, [AuX(CNC(6)H(4)CO(2)H)] (X = C[triple bond]C-C(6)H(4)-C(9)H(19), C(6)F(5), C(6)F(4)OC(6)H(13), C(6)F(4)C(6)F(4)Br) and [(mu-4,4'-C(6)F(4)C(6)F(4)){Au(CNC(6)H(4)CO(2)H)}(2)], have been isolated. These metallo-acids are luminescent. The single crystal X-ray diffraction study of [Au(C(6)F(5))(CNC(6)H(4)CO(2)H)](infinity) confirms a rod-like structure of the molecule, with a linear coordination around the gold atom, which extends into a supramolecular entity supported by hydrogen bond, gold-gold, and fluorophilic (F(ortho) ... F(meta)) interactions. The carboxylic acid group of the gold isocyanide complexes acts also as a hydrogen donor towards the hydrogen acceptor decyloxystilbazole, affording some hydrogen-bonded supramolecular liquid crystals.


Nomenclatural status of the 'pocketknife fly': Stomoxoides Schaeffer, 1766 (Diptera: Conopidae).
The nomenclatural status of the genus Stomoxoides Schaeffer, 1766 is discussed and a timeline of usage is given. The name is shown to be available and date from Schaeffer's 1766 work, and by invoking Article 70.3 of the ICZN Code, the type species of Stomoxoides is fixed as Conops ferrugineus Linnaeus, 1761, misidentified as Conops testacea Linnaeus, 1767 in the fixation by subsequent monotypy as proposed by Linnaeus in 1767. Stomoxoides is thereby synonymous with Sicus Scopoli, 1763 as originally proposed by Yeats in 1773.


Antibiotic and Desiccation Resistance of Cronobacter sakazakii and C. malonaticus Isolates from Powdered Infant Formula and Processing Environments.
This study evaluated the antimicrobial and desiccation resistance of Cronobacter sakazakii and Cronobacter malonaticus isolates from powdered infant formula and processing environments. The antimicrobial susceptibility tests showed that the 70 Cronobacter strains, representing 19 sequence types, were susceptible to the most of the antibiotics except for amoxicillin-clavulanate, ampicillin, and cefazolin. Furthermore, the growth of six C. sakazakii and two C. malonaticus strains from different sequence types (STs) in hyperosmotic media was measured. The growth of the two C. sakazakii strains (CE1 and CE13) from the neonatal pathovars ST4 and ST8, were significantly higher (p < 0.05) than that of other strains. C. malonaticus strain CM35 (ST201) was the slowest grower in all strains, and most could not grow in more than 8% NaCl solution. Also the survival of these strains under desiccation conditions was followed for 1 year. The viable count of Cronobacter spp. under desiccation conditions was reduced on average by 3.02 log cycles during 1 year, with CE13 (ST8) being the most desiccation resistant strain. These results will improve our understanding of the persistence of the two closely related species C. sakazakii and C. malonaticus which are of concern for neonatal and adult health.


[Potential applications of deep learning-based technologies in Hungarian mammography].
The technology, named 'deep learning' is the promising result of the last two decades of development in computer science. It poses an unavoidable challenge for medicine, how to understand, apply and adopt the - today not fully explored - possibilities that have become available by these new methods. It is a gift and a mission, since the exponentially growing volume of raw data (from imaging, laboratory, therapy diagnostics or therapy interactions, etc.) did not solve until now our wished and aimed goal to treat patients according to their personal status and setting or specific to their tumor and disease. Currently, as a responsible health care provider and financier, we face the problem of supporting suboptimal procedures and protocols either at individual or at community level. The problem roots in the overwhelming amount of data and, at the same time, the lack of targeted information for treatment. We expect from the deep learning technology an aid which helps to reinforce and extend the human-human cooperations in patient-doctor visits. We expect that computers take over the tedious work allowing to revive the core of healing medicine: the insightful meeting and discussion between patients and medical experts. We should learn the revelational possibilities of deep learning techniques that can help to overcome our recognized finite capacities in data processing and integration. If we, doctors and health care providers or decision makers, are able to abandon our fears and prejudices, then we can utilize this new tool not only in imaging diagnostics but also for daily therapies (e.g., immune therapy). The paper aims to make a great mind to do this. Orv Hetil. 2019; 160(4): 138-143.


Interaction of liposome-associated all-trans-retinoic acid with squamous carcinoma cells.
Because of their antiproliferative and differentiation-inducing properties, retinoids have been used clinically as therapeutic and chemopreventive agents against squamous-cell carcinomas (SCC). As is the case for many therapeutic agents, however, the administration of retinoids is associated with toxic effects. Because encapsulation of certain drugs in lipid vesicles (liposomes) has been shown to result in reduced toxic effects, we studied the in vitro interaction of liposome-encapsulated all-trans-retinoic acid (L-ATRA) with a SCC line (MDA 886Ln) and its multicellular tumor spheroid (MTS) model. Various L-ATRA formulations were tested for incorporation of retinoic acid, toxic effects against human red blood cells, uptake and retention by tumor cells, and antiproliferative effects against SCC. Of the different formulations tested, L-ATRA containing diphosphatidyl palmitoylcholine (DPPC) and stearylamine (SA; 9:1, w/w) showed optimal drug incorporation, high stability, and minimal toxicity toward red blood cells and was highly efficacious in delivering ATRA and, thus, in inhibiting the growth of MDA 886Ln and its MTS model. DPPC: SA L-ATRA inhibited the expression of the enzyme keratinocyte transglutaminase in epidermal cells as effectively as did the free drug. These results suggest that liposomes can serve as an effective carrier system for the delivery of retinoids to SCC.


Neurocytological Advances in the Treatment of Glioblastoma Multiforme.
Glioblastoma multiforme (GBM) is an aggressive neoplasm of the brain that has commonly led to disappointing patient outcomes. Despite medical advancements and increasing research efforts, GBM studies reveal a stagnant survival rate at the global level with only sluggish improvement over time. Modern neuro-oncology research places a heavy emphasis on pharmacological therapies. Through a broad database search, we accumulated and synthesized the GBM-related neuroimmunocytological literature to create a comprehensive and contemporary review. Based on our findings, we discuss the recent neurocytological treatment strategies for GMB and the results of the studies. Regorafenib, paxalisib, and dianhydrogalactitol (VAL-083) are showing initial promise to decrease disease progression. VAL-083 is an alkylating agent that creates N7 methylation on DNA and has the ability to cross the blood-brain barrier (BBB). Selinexor, recombinant nonpathogenic polio-rhinovirus, and GBM-vaccine of autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector have all also shown initial clinical benefit in terms of prolonging survival. Most trials observe modest improvement in outcomes with a positive safety profile. Nevertheless, the need for further studies is warranted, along with the trending of post-therapeutic biomarkers in order to better access future patient outcomes.


Antisocial Disorders in Adolescence and Youth, According to Structural, Emotional, and Cognitive Transdiagnostic Variables: A Systematic Review.
Transdiagnostic causal variables have been identified that have allowed understanding the origin and maintenance of psychopathologies in parsimonious explanatory models of antisocial disorders. However, it is necessary to systematize the information published in the last decade. The aim of the study was to identify through a systematic review, the structural, emotional and cognitive transdiagnostic variables in antisocial disorders of adolescence and youth. Recommendations for systematic reviews and meta-extraction and analysis of information according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), the Cochrane Collaboration and Campbell were followed. We found 19 articles from 110 reviewed documents. The results indicated that at a structural level there is a general psychopathological factor (psychopathy or externalizing), non-emotional callousness and impulsivity from behavioral inhibition and activation systems, and negative affect traits as base structures. In the emotional level, the study found a risk component from emotional dysregulation and experiential avoidance. In the cognitive level, a key role of anger-rumination and violent ideation as explanatory variables of antisocial disorders. We concluded that the interaction of these identified variables makes it possible to generate an evidence-based transdiagnostic model.


Elemental mercury vapor interaction with individual gold nanorods.
We show that single gold nanorods can act as highly sensitive mercury vapor sensors with attogram resolution. We exposed assorted gold nanorods, with aspect ratios ranging from 2.8-4.1, to μg m(-3) concentrations of mercury vapor in air for 1 hour. Pre- and post-exposure, the nanorods were examined with a combination of dark field spectroscopy and transmission electron microscopy. Because we isolated individual particles, we can describe the shape and size effects distinctly rather than statistically (a constraint of studying heterogeneous nanoparticle films). No measurable changes occurred to the shape and size of the nanorods due to their saturation with mercury vapor. The localized surface plasmon resonance (LSPR) of the mercury-saturated nanorods blue shifted 2.6-3.8 nm; the magnitude of the shift depended on the initial shape and size of the nanorod. Larger aspect ratios and surface-area-to-volume ratios both enhance the LSPR shift seen in saturated nanoparticles. The predictions of a core-shell model mirrors the shape and size effects observed experimentally. These results increase our understanding of mercury-adsorption by gold surfaces, and help to optimize nanoparticle-based plasmonic mercury sensing.


Screen-printed carbon electrodes modified with cobalt phthalocyanine for selective sulfur detection in cosmetic products.
Cobalt phthalocyanine (CoPc) films were deposited on the surface of a screen-printed carbon electrode using a simple drop coating method. The cyclic voltammogram of the resulting CoPc modified screen-printed electrode (CoPc/SPE) prepared under optimum conditions shows a well-behaved redox couple due to the (Co(I)/Co(II)) system. The CoPc/SPE surface demonstrates excellent electrochemical activity towards the oxidation of sulfur in a 0.01 mol·L(-1) NaOH. A linear calibration curve with the detection limit (D(L), S/N = 3) of 0.325 mg·L(-1) was achieved by CoPc/SPE coupled with flow injection analysis of the sulfur concentration ranging from 4 to 1120 mg·L(-1). The precision of the system response was evaluated (3.60% and 3.52% RSD for 12 repeated injections), in the range of 64 and 480 mg·L(-1) sulfur. The applicability of the method was successfully demonstrated in a real sample analysis of sulfur in anti-acne creams, and good recovery was obtained. The CoPc/SPE displayed several advantages in sulfur determination including easy fabrication, high stability, and low cost.


Interferon treatment of anti-HBe positive and HBV DNA positive chronic hepatitis B.
The efficacy of human lymphoblastoid interferon (Wellferon) was studied in 25 patients with anti-HBe positive, HBV DNA positive chronic hepatitis B. The patients were randomized to receive 5 MU/m2, three times weekly or no treatment for 6 months. The study is ongoing and to date 19 patients have been followed up for more than 3 months and 14 for more than 6 months. At 9 months, serum HBV DNA had become negative and ALT levels normalized in 57% of interferon-treated patients. This compared with 33% becoming serum HBV DNA negative and 16% with ALT normalization in the untreated group. Clearance of HBV DNA in interferon treated patients was not consistently associated with the appearance of transaminase peaks during therapy, in contrast with those seen in HBeAg positive patients. The preliminary results of this trial suggest that interferon reduces HBV replication in anti HBe/HBV DNA positive patients with chronic hepatitis B.


A molecular diagnostic approach able to detect the recurrent genetic prognostic factors typical of presenting myeloma.
Risk stratification in myeloma requires an accurate assessment of the presence of a range of molecular abnormalities including the differing IGH translocations and the recurrent copy number abnormalities that can impact clinical behavior. Currently, interphase fluorescence in situ hybridization is used to detect these abnormalities. High failure rates, slow turnaround, cost, and labor intensiveness make it difficult and expensive to use in routine clinical practice. Multiplex ligation-dependent probe amplification (MLPA), a molecular approach based on a multiplex polymerase chain reaction method, offers an alternative for the assessment of copy number changes present in the myeloma genome. Here, we provide evidence showing that MLPA is a powerful tool for the efficient detection of copy number abnormalities and when combined with expression assays, MLPA can detect all of the prognostically relevant molecular events which characterize presenting myeloma. This approach opens the way for a molecular diagnostic strategy that is efficient, high throughput, and cost effective.


Role of pH-induced structural change in protein aggregation in foam fractionation of bovine serum albumin.
For reducing protein aggregation in foam fractionation, the role of pH-induced structural change in the interface-induced protein aggregation was analyzed using bovine serum albumin (BSA) as a model protein. The results show that the decrease in pH from 7.0 to 3.0 gradually unfolded the BSA structure to increase the molecular size and the relative content of β-sheet and thus reduced the stability of BSA in the aqueous solution. At the isoelectric point (pH 4.7), BSA suffered the lowest level in protein aggregation induced by the gas-liquid interface. In the pH range from 7.0 to 4.7, most BSA aggregates were formed in the defoaming process while in the pH range from 4.7 to 3.0, the BSA aggregates were formed at the gas-liquid interface due to the unfolded BSA structure and they further aggregated to form insoluble ones in the desorption process.


Supercomputer description of human lung morphology for imaging analysis.
A supercomputer code that describes the three-dimensional branching structure of the human lung has been developed. The algorithm was written for the Cray C94. In our simulations, the human lung was divided into a matrix containing discrete volumes (voxels) so as to be compatible with analyses of SPECT images. The matrix has 3840 voxels. The matrix can be segmented into transverse, sagittal and coronal layers analogous to human subject examinations. The compositions of individual voxels were identified by the type and respective number of airways present. The code provides a mapping of the spatial positions of the almost 17 million airways in human lungs and unambiguously assigns each airway to a voxel. Thus, the clinician and research scientist in the medical arena have a powerful new tool to be used in imaging analyses. The code was designed to be integrated into diverse applications, including the interpretation of SPECT images, the design of inhalation exposure experiments and the targeted delivery of inhaled pharmacologic drugs.


Seizure clusters.
Acute repetitive seizures, also called seizure clusters, are common phenomena in patients with epilepsy. They are a burden on patients and their caregivers and may be very disruptive to the patients' lives. They may progress to prolonged seizures or status epilepticus if they are not aborted as soon as possible. However, their definition, recognition, and classification still suffer from a lack of consensus among healthcare professionals in the field. This review aims to shed light on various aspects of seizure clusters with particular attention to their treatments.


Capturing the 'art' of emergency medicine: Does film foster reflection in medical students?
Integrating arts and humanities-based pedagogy into curricula is of growing interest among medical educators, particularly how it promotes reflection and empathy. Our aim was to explore whether a 2.50 min film titled 'The Art of the ED' stimulated reflective learning processes in a group of first year medical students. The film was shown prior to their first clinical placement in an ED. Student participation was voluntary and not assessable. Using an exploratory qualitative research approach, this study drew on data collected from students' individual written reflections, exploring their perceptions towards clinical experience in an emergency medicine (EM) attachment. A total of 123 (51% of 240) students submitted a reflection. The qualitative data revealed three main themes: the opportunity for students to preview EM ('While watching the film, I felt like I was the patient and the doctor all at once, in that I was living the experience both from within and as an observer …'); exposed the reality of ED; and fostered a growing awareness of the fragility of human life. These findings highlight how visual methodologies (like film) create a safe, non-threatening space to access, experience and process emotion around their perceptions towards EM, and to anticipate and emotionally prepare for their impending clinical experience in the ED. These data support the use of visual methodologies to foster reflective processes that assist medical students to integrate the 'art' of EM, and the development and commitment of core doctoring values of empathy, service and respect for patients.


A multi-centre, randomised, double-blind, placebo-controlled clinical trial on the efficacy and tolerability of GeloMyrtol® forte in acute bronchitis.
GeloMyrtol® forte (Myrtol®) is a phytomedicine obtained by distillation from essential oils. The trial was conducted to confirm the efficacy of Myrtol® in the treatment of acute bronchitis. Patients with acute bronchitis and without confounding co-morbidity or co-medication were randomly assigned to treatment with either Myrtol® 300 mg 4 times daily or matched placebo in double-blind, parallel-group fashion. Signs and symptoms were evaluated by the investigator at baseline and after 7, 10 and 14 days of treatment; intake of medication, wellbeing and symptoms were recorded daily by the patient in the patients' diaries. 413 patients were enrolled and randomised (Myrtol®: 202; Placebo: 211); 398 had at least one on-treatment efficacy evaluation (Myrtol®: 196; Placebo: 202). The mean change in coughing fits from D01 (baseline) to D07-D09 (after about one week treatment) was 62.1% (95% CI: 57.6-66.6%) and 49.8% (95% CI: 44.6-55.0%) for treatment with Myrtol® and placebo, respectively (p<0.0001). With Myrtol®, the median time to 50% reduction in coughing fits was statistically significantly shorter and there were more patients without day-time coughing fits; there also were statistically significantly less day-time coughing fits, less difficulty coughing up, less sleep disturbance due to night-time coughing; with Myrtol® there was less symptomatic impairment (composite bronchitis severity score and subscores) and significant more patients had a clinically satisfying response to the investigational treatment.Both treatments were generally well tolerated. Myrtol® is statistically significantly superior to placebo in treating acute bronchitis.


Alternative conformational states in the ribosome-associated 5.8S RNA.
Two conformations of the 5.8S rRNA have been distinguished by gel electrophoresis. Diethyl pyrocarbonate and dimethyl sulphate reactivity were used to probe these conformational states in both the free molecule and those associated with 28S RNA or the ribosome. Both conformations could be demonstrated in each case and in every instance four residues, C50, A52, G53, C54, which were strongly reactive in the faster-migrating conformation were essentially unreactive in the slower-migrating form. These results suggest that the two conformations differ in the degree to which the tertiary structure is folded and raise the possibility that the 5.8S rRNA functions in translation by switching between alternative conformational states.


Inhibition of human gastric lipase secretion by glucagon-like peptide-1.
Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted in vagotomized patients, suggesting that fundic chief cells, from which gastric lipase is released, or neighboring inhibitory cells could be equipped with GLP-1 receptors. Vagotomized patients had significantly higher plasma concentrations of gastrin and secretin. No significant changes of gastrin, secretin, and CCK secretion were seen during GLP-1 infusion in the vagotomized patients, whereas secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal mechanism. Our results indicate that gastric lipase secretion is subject to hormonal stimulatory as well as inhibitory mechanisms.


Analysis of Adjuvant Endocrine Therapy in Practice From Electronic Health Record Data of Patients With Breast Cancer.
Adjuvant endocrine therapy is a long-term drug therapy prescribed to prevent recurrence of hormone receptor-positive breast cancer. Data on adjuvant endocrine therapy are reported though clinical trials, which may differ from treatment practice and outcomes in the general population of patients with breast cancer. With secondary use of electronic health record (EHR) data, we summarize adjuvant endocrine treatment practice and outcomes in real-world settings. We analyzed treatment data derived from EHR data on 1,587 patients with stage I to III breast cancer at a National Cancer Institute-designated comprehensive cancer center to learn the frequencies of real-world adjuvant endocrine drug switches and discontinuation and to explore the potential cause for drug switches and discontinuation from medical records. We measured rates of drug use, drug switches, early drug discontinuation, adverse events, recurrence, and death. We also measured adverse events and change in menopause status as potential causes for drug switch and discontinuation. Within the study population, approximately 49% of patients were lost to follow-up or did not complete adjuvant treatment through 5 years. Fifty-two percent of patients switched to a different endocrine therapy drug during their treatment. We found that age is correlated with drug switches and that adverse events are correlated with drug switches and discontinuation. We also found that patients who switched to an alternative endocrine therapy during treatment were more likely to complete 5 years of treatment. This study describes long-term adjuvant endocrine treatment in real-world settings and demonstrates the ability to leverage longitudinal EHR data to characterize oral medication treatment patterns in patients with cancer.


Profile of immediate early gene expression in the lumbar spinal cord of low-thoracic paraplegic mice.
Induction of immediate early gene (IEG) expression is believed to constitute one of the earliest steps in plasticity and long-term modification of neuronal properties. Although behavioral evidence of neuronal plasticity at the sublesional level after spinal cord injury exists, spatiotemporal changes of IEGs in spinal segments located caudally to such an injury have never been examined. Here, the authors studied spatiotemporal changes of c-fos, nor-1, nur77, nurr1, and retinoid x receptor (rxr) messenger RNA expression in the lumbar segments L1-L2 after low-thoracic spinal transection (Tx). C-fos expression generally increased in the dorsal horn with significant levels reached at 3 days and 14 days post-Tx. Basal nor-1 transcript levels decreased in the intermediate zone and dorsal horn areas at 7 days. Nur77 levels were nonsignificantly depressed throughout that period of time, whereas nurr1 and rxr transcripts were not detected before or after Tx. In conclusion, the results provide evidence of distinct roles for c-fos and nor-1 in reorganization and plasticity of neuronal networks typically involved in sensorimotor integration and locomotor control.


Evidence for phospholipid microdomain formation in liquid crystalline liposomes reconstituted with Escherichia coli lactose permease.
The well-characterized integral membrane protein lactose (lac) permease from Escherichia coli was reconstituted together with trace amounts (molar fraction X = 0.005 of the total phospholipid) of different pyrene-labeled phospholipid analogs into 1-palmitoyl-2-oleoyl-sn-glycero-3-sn-glycero-3-phospho-rac'-glycerol (POPG) liposomes. Effects of lac permease on bilayer lipid dynamics were investigated by measuring the excimer-to-monomer fluorescence intensity ratio IE/IM. Compared to control vesicles, the presence of lac permease (at a protein:phospholipid stoichiometry P/L of 1:4.000) increased the rate of excimer formation by 1-palmitoyl-2[6-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) by approximately fivefold. Decreasing P/L from approximately 1:4.000 to 1:7.600 decreased the IE/IM for PPDPC from 0.16 to 0.05, respectively. An increase in bilayer fluidity due to permease is unlikely, thus implying that the augmented IE/IM should arise from partial lateral segregation of PPDPC in the vesicles. This notion is supported by the further 38% increase in IE/IM observed for the pyrene-labeled Cys-148 lac permease reconstituted into POPG vesicles at P/L 1:4000. The importance of the length of the lipid-protein boundary is implicated by the reduction in IE/IM resulting from the aggregation of the lac permease in vesicles by a monoclonal antibody. Interestingly, excimer formation by 1-palmitoyl-2[6-(pyren-1-yl)hexanoyl-sn-glycero-3-phosphocholine (PPHPC) was enhanced only fourfold in the presence of lac permease. Results obtained with the corresponding pyrenyl phosphatidylglycerols and -methanols were qualitatively similar to those above, thus indicating that lipid headgroup-protein interactions are not involved. Inclusion of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamino-N-(5-fluoresce inthio- carbamoyl) (DPPF, X = 0.005) into reconstituted lactose permease vesicles containing PPDPC caused a nearly 90% decrease in excimer fluorescence, whereas in control vesicles lacking the reconstituted protein only 40% quenching was evident. The addition of 1,2-dipalmitoyl-sn-glycero-3-phospho-rac'-glycerol (DPPG) decreased IE/IM for PPDPC, revealing the driving force for the lateral segregation of this probe to become attenuated. More specifically for protein-free bilayers at XDPPG = 0.10 the rate of lateral diffusion of PPDPC in POPG is diminished, as evidenced by the 24% decrement in IE/IM, under these conditions the increase in IE/IM due to lac permease was strongly reduced, by approximately 84%. The present data are interpreted in terms of the hydrophobic mismatch theory, which predicts that integral membrane proteins will draw lipids of similar hydrophobic thickness into their vicinity. In brief, the approximate lengths of most of the predicted 12 hydrophobic, membrane-spanning alpha-helical segments of lactose permease range between 28.5 and 37.5 A and thus exceed the hydrophobic thickness of POPG of approximately 25.8 A. Therefore, to reduce the free energy of the assembly, longer lipids such as PPDPC and DPPF are accumulated in the immediate vicinity of lactose permease in fluid, liquid crystalline POPG bilayers.


Vision-based body tracking: turning Kinect into a clinical tool.
Vision-based body tracking technologies, originally developed for the consumer gaming market, are being repurposed to form the core of a range of innovative healthcare applications in the clinical assessment and rehabilitation of movement ability. Vision-based body tracking has substantial potential, but there are technical limitations. We use our "stories from the field" to articulate the challenges and offer examples of how these can be overcome. We illustrate that: (i) substantial effort is needed to determine the measures and feedback vision-based body tracking should provide, accounting for the practicalities of the technology (e.g. range) as well as new environments (e.g. home). (ii) Practical considerations are important when planning data capture so that data is analysable, whether finding ways to support a patient or ensuring everyone does the exercise in the same manner. (iii) Home is a place of opportunity for vision-based body tracking, but what we do now in the clinic (e.g. balance tests) or in the home (e.g. play games) will require modifications to achieve capturable, clinically relevant measures. This article articulates how vision-based body tracking works and when it does not to continue to inspire our clinical colleagues to imagine new applications. Implications for Rehabilitation Vision-based body tracking has quickly been repurposed to form the core of innovative healthcare applications in clinical assessment and rehabilitation, but there are clinical as well as practical challenges to make such systems a reality. Substantial effort needs to go into determining what types of measures and feedback vision-based body tracking should provide. This needs to account for the practicalities of the technology (e.g. range) as well as the opportunities of new environments (e.g. the home). Practical considerations need to be accounted for when planning capture in a particular environment so that data is analysable, whether it be finding a chair substitute, ways to support a patient or ensuring everyone does the exercise in the same manner. The home is a place of opportunity with vision-based body tracking, but it would be naïve to think that we can do what we do now in the clinic (e.g. balance tests) or in the home (e.g. play games), without appropriate modifications to what constitutes a practically capturable, clinically relevant measure.


The correlation between transcranial magnetic stimulation parameters and neuromuscular properties in children with cerebral palsy.
We studied the correlation between corticospinal signaling and neuromuscular properties in children with Cerebral Palsy (CP). Corticospinal signaling was evaluated using Transcranial Magnetic Stimulation (TMS). Neuromuscular properties were quantified using Hoffmann reflex (H-reflex), sonoelastography, clinical measurements, and isokinetic measures. In particular, we determined the relationship between the TMS parameters of the ankle joint and the neuromuscular features of ankle extensors and flexors as well as popular clinical measures of gait speed, endurance, balance and mobility. Seventeen CP patients and twelve healthy control subjects were evaluated. Our findings showed that the motor evoked potential (MEP) latency of TMS was significantly longer in CP than in healthy subjects. The MEP-latency was significantly correlated with the H-reflex response (r=0.71, p-value=0.04) and isokinetic features; i.e. max acceleration extension time (r=0.5, p-value=0.005), and max flexion time in the cycle (r=0.5, p-value =0.002). No significant correlation was observed between MEP-latency and clinical measurements of gait and sonoelastography of ankle muscles. The results suggest that the changes in corticospinal signaling could contribute to muscle weakness and hyperexcitability of reflexes observed in children with CP.


Intra-abdominal location of peritoneal catheters during CAPD.
Thirteen patients were studied on two random occasions in order to evaluate the relationship between 1) volume and rate of dialysis outflow and the subsequent inflow, 2) patient's impression of the location of the catheter tip, and 3) stability of the catheter tip location. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p less than 0.02). No catheter tips were located in the far upper regions of the abdomen. Only one patient was able to state the exact location identical to fluoroscopy. 92% of the fluoroscopic evaluations showed that catheter tips were located in the same anatomical region in the upright as well as in the supine position. If vertical "neighbour" anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located in the same or the vertical "neighbour" region at the two study periods.


Cerebellopontine angle epidermoid in a noise-exposed patient.
A cerebellopontine angle epidermoid was identified in a noise-exposed patient as part of an occupational hearing conservation program. The patient is a 24-year-old employee of a major national newspaper who, because of workplace noise levels, was required to be part of a hearing conservation program. A shift in thresholds in 1 year was identified by the audiologic reviewer and referral for audiologic and otologic services was recommended and carried out. The steps leading from the initial air-conduction, pure-tone audiogram to final neurosurgical removal of the epidermoid CPA lesion was described. Such referral is essential if potentially health and life threatening conditions are to be identified and managed, although the primary objectives of the hearing conservation program remains the prevention of sensorineural hearing loss from workplace noise exposure.


Extraction of Haemoproteus columbae (Haemosporina: Haemoproteidae) antigen from rock dove pigeons (Columba livia) and its use in an antibody ELISA.
Erythrocytic stages of Haemoproteus columbae were extracted from the cytoplasm of nucleated red blood cells (RBC) of Rock dove pigeons (Columba livia) using cationic detergent (N,N',N'-polyoxyethylene(10)-N-tallow-1,3-diaminopropane [EDTA-20]) and discontinuous Percoll gradient density. Crude RBC extract (CRBCE) antigen was prepared. Parasitized RBCs were more resistant to EDTA-20 action than unparasitized cells. An enzyme-linked immunosorbent assay (ELISA) was developed for detection of anti-H. columbae immunoglobulins in 30 wild-captured C. livia. Whole blood, serum, and dried blood on filter paper gave similar results; the latter was selected for sampling convenience. Optimal antigen concentration was 5 micrograms/ml, and anti-H. columbae immunoglobulins were detectable at a 10(-4.11) dilutions. The binding efficacy of anti-chicken IgG to the pigeon immunoglobulins was significantly higher than anti-duck IgG or anti-turkey IgG. Parasitemia by Giemsa-stained thin blood smears ranged from 20.0 to 47.5%, mean = 32.4 +/- 8.3%; 17 of 30 birds had multiply infected RBCs with a mean parasitemia of 2.4 +/- 1.1%, range 0.7-4.9%; 27 birds were positive by the ELISA. No clinical signs of infection were observed. ELISA absorbance values were not correlated with the level of parasitemia in individual birds. All pigeons were negative for anti-Plasmodium relictum and anti-P. elongatum immunoglobulins as determined by ELISA. The pigeons were not subclinically infected with Plasmodium spp. as determined by inoculation of domestic ducklings with blood from dexamethasone-immunosuppressed pigeons.


Complete Genome Sequence of a Novel Reassortant Avian Influenza H9N9 Virus Isolated from Chicken in Eastern China.
The genome sequence of the strain A/chicken/Changzhou/C08/2013 (H9N9) shows that the hemagglutinin (HA) genes of this strain are closely related to those of the strain A/chicken/Shanghai/1107/2013 (H9N2) and share 99.2% nucleotide homology, while the other seven genes had the greatest sequence identities with the novel H7N9 virus. We speculate that this strain may be a novel natural reassortant avian influenza virus (AIV).


Cooperation, competition, individualism and interpersonalism in Japanese fifth and eighth grade boys.
The study compared the expression of cooperation, competition, individualism and interpersonalism in Japanese youth. Forty-two 5th grade boys and 42 8th grade boys first completed two questionnaires about cooperation/competition and group/individualized activities. Their group structure was then coded (as working in trios, in duos, or separately) as trios of boys built houses with playing cards. The experimental design crossed instructions (1) to work individually or in a group and (2) compete or do one s own best. Subjects were questioned about their awareness of, liking for and prefercnces for the cooperative, individualistic, and group-centered aspects of the experimental tasks. On orientation scales, 8th graders chose equal numbers of individualistic and group-centered activities, while 5th graders chose more group activities. Both age groups strongly favored cooperative over competitive items. In group trials of the experiment, 8th graders tended to work alone for greater proportions of time than did 5th graders. Questionnaire data indicated that (1) 8th graders reponed greater enjoyment of the individualistic aspect of the task than did 5th graders, (2) both age groups evidenced a strong sense of interpersonalism, and (3) cooperation was rated more positively than competition at both ages. The study was discussed in relation to recent studies on Japanes school socialization and cooperation/competition.


The early intracellular production of a reactive oxygen intermediate mediates apoptosis in dexamethasone-treated thymocytes.
Many conditions that induce an oxidative stress are capable of evoking apoptosis. This has lead to the proposal of oxidative stress as a mediator of apoptosis. We show that, in murine thymocytes, oxidative stress and apoptosis occur in the same cell. We identified four distinct apoptotic subpopulations that appeared sequentially in time. Catalase protected from dex-amethasone-induced death in the initial stages of apoptosis, while iron chelators and Vitamin E did not. Further studies provided evidence supporting the early production of an intracellular oxidative intermediate as an obligatory step for the efficient induction of apoptosis. We propose that at least one of the molecules capable of filling this role is hydrogen peroxide.


Non-asthmatic eosinophilic bronchitis and its relationship with asthma.
Non-asthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough. NAEB shares similar eosinophilic inflammation of airway and response to corticosteroids with asthma. However, in contrast to asthma, NAEB subjects have no airflow obstruction and airway hyperresponsiveness. The pathogenesis of NAEB are involved with many inflammatory cells such as eosinophils, lymphocytes, mast cells, cytokines and inflammatory mediators, includingTh2 cytokines, histamine, leukotrines, prograndins and oxidative stress. The different locations of inflammatory cells and the inflammatory mediators level may explain this difference between EB and asthma. There is no study on dose and duration of treatment. On the prognosis of NAEB, long term follow-up study suggested that NAEB should be a distinct entity rather than an early stage of asthma or COPD. The relapse rate is high after treatment. Assessing sputum eosinophils after treatment is useful to identify those at risk of relapse.


[Role of EuroSCORE and SinoSCORE in prediction of early postoperative quality of life in patients after coronary artery bypass surgery].
To investigate the predicting value of European system for cardiac operative risk evaluation (EuroSCORE) and sino system for coronary operative risk evaluation (SinoSCORE) in early quality of life of patients after coronary artery bypass surgery (CABG). A total of 218 consecutive patients who underwent CABG from March 2010 to January 2013 were evaluated with both systems before operation. Health related quality of life (QoL) was estimated by using 36-item short form health survey (SF-36) preoperatively and postoperatively in order to evaluate the predicting value of the two systems in early post-operative QoL. Calibration was evaluated by Hosmer-l,emeshow goodness-of-fit test.Discrimination was tested by determining the area under the receiver operating characteristic (ROC) curve. There was no significant difference between the accumulation of the EuroSCORE and SinoSCORE in the all patients (t=-0.904, P=0.368), When using Wilcoxon test on life quality in the preoperative and postoperative patients respectively,the data showed that the quality of life improved significantly in various dimensions of the postoperative patients (Z=-2.886, P<0.001).Except for bodily pain (BP) and mental health (MH), statistically significant correlation was found between the preoperative risk evaluation scores and the postoperative QoL scores (r:-0.203 to -0.493, P<0.05). Logistic regression analyses indicated that both the scores emerged as the independent predictor for a relatively worse QoL (OR>1, P<0.05). Furthermore, the EuroSCORE predicted the outcome with a higher OR. For SinoSCORE the Hosmer-Lemeshow test was significant (P=0.628) and the area under ROC curve was 0.754.For the EuroSCORE the Hosmer-Lemeshow test was significant (P=0.538) and the area under ROC curve was 0.854. Both EuroSCORE and SinoSCORE could be viewed as a predictor for several aspects of postoperative QoL, while EuroSCORE might have a greater predicting value.


No telomere shortening in marrow stroma from patients with MDS.
Telomere shortening with age may lead to genomic instability and an increased risk of cancer. Given the role of the microenvironment in the pathophysiology of the myelodysplastic syndrome (MDS), primarily a disease of older age, we determined telomere length in primary cultured marrow stroma cells using quantitative fluorescent in situ hybridization (qFISH) and quantitative polymerase chain reaction (qPCR). qFISH showed comparable rates of decrease in telomere length with age in MDS patients and age-matched healthy controls. Telomere length assessment by qPCR showed similar results. These findings suggest a lack of significant differences between MDS patients and healthy controls in terms of telomere stability in marrow stroma in contrast to that observed in hematopoietic cells. In conclusion, this demonstrates that, although MDS stroma cells and hematopoietic cells share the same microenvironment, the stromal cells do not share the processes that contribute to accelerated telomere attrition, suggesting that stromal cell proliferative potential is not limiting in MDS.


Classification of bathing water quality based on the parametric calculation of percentiles is unsound.
Analyses of Irish bathing water quality data sets are reported to investigate whether the parametric calculations proposed in the draft Bathing Water Directive are valid. Faecal coliforms (assumed to be Escherichia coli) and faecal streptococci (assumed to be intestinal enterococci) have been analysed separately. It was noted that classifications based on the parametric 95th percentile calculations disagreed with those based on percentage compliance with the standards on 13.8% of occasions. When these disagreements were studied, it was found that the datasets frequently contained many censored data points (Result < 1). Also, the datasets were not log normally distributed on at least 85% of occasions. Both these findings fatally undermine the validity of using a parametric method for calculating 95th percentiles to classify bathing water quality. By contrast the non-parametric Hazen method is a better estimate of true population 95th percentiles, but essentially gives very similar classifications to the percentage compliance approach, fully agreeing on over 95% of occasions. The same is also true when considering 90th percentiles. A series of Monte Carlo studies were also conducted to determine the impact of small numbers. It was ascertained that small sample sizes are very undependable in determining bathing water classification and the parametric method in particular is particularly unreliable. In conclusion, the parametric method for calculating bathing water compliance is so severely and fatally flawed statistically that it should not form the basis of any legislation. The Hazen method gives a better estimate of true 90th or 95th percentiles, though as the resultant classifications agree with percentage compliance so closely it is doubtful that there is any statistical value in using a percentile approach over the long established and well understood percentage compliance approach.


van der Waals-Tonks-type equations of state for hard-hypersphere fluids in four and five dimensions.
Recently, we developed accurate van der Waals-Tonks-type equations of state for hard-disk and hard-sphere fluids by using the known virial coefficients. In this paper, we derive the van der Waals-Tonks-type equations of state. We further apply these equations of state to hard-hypersphere fluids in four and five dimensions. In the low-density fluid regime, these equations of state are in good agreement with the simulation results and existing equations of state.


High Mobility Group Box 1 in Preterm Infants with Intraventricular Hemorrhage.
We studied the level of high mobility group box 1(HMGB1) in preterm infants with intraventricular hemorrhage (IVH). Using enzyme-linked immunosorbent assay (ELISA), the concentration of HMGB1 in cord blood obtained from 41 infants with IVH and 67 infants without IVH were measured. The cord blood concentration of HMGB1 in infants with IVH were significantly higher than those without IVH (P=0.041). Increased levels of HMGB1 might be associated with IVH in preterm infants.


Nitrosylation of GAPDH augments pathological tau acetylation upon exposure to amyloid-β.
Acetylation of the microtubule-associated protein tau promotes its polymerization into neurofibrillary tangles that are implicated in the pathology of Alzheimer's disease (AD). The gaseous neurotransmitter nitric oxide (NO) regulates cell signaling through the nitrosylation of proteins. We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD.


Cyst formation associated with porous polyethylene orbital floor implant.
A 28-year-old female presented with hyperglobus and inferior scleral show after the repair of an orbital floor fracture using a porous polyethylene (Medpor) implant. CT revealed a large inferior orbital cystic mass displacing the globe. The cyst was explored and excised and the implant was found to be free from any attachment to surrounding tissues and hence, removed without difficulty. The reason for the cyst development was most likely inadvertent epithelial inclusion at the time of surgery-a recognized risk with insertion of any foreign body via transconjunctival approach. Porous implants when placed in the subperiosteal space might not get incorporated with surrounding tissues and therefore behave like any traditional nonporous alloplastic material.


Teclistamab-cqyv in multiple myeloma.
Multiple myeloma (MM) is an incurable neoplasm characterized by significant morbidity and mortality. Despite advances in treatment, MM patients eventually experienced a relapse of the disease. Penta-drug refractory patients continue to be the hard core of relapsed/refractory (RR) settings. Teclistamab-cqyv is a humanized IgG4 antibody and a bispecific BCMA-director CD3 T-cell engager. It recruits endogenous T cells, by targeting CD3 receptors expressed on their surface, resulting in their activation against BCMA, an antigen expressed by plasma cells. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Teclistamab-cqyv in monotherapy for the treatment of RRMM patients who have received at least three prior therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (MoAbs) and have demonstrated disease progression during the last therapy. Its effectiveness was demonstrated in a pivotal clinical trial where the overall response rate (ORR) reached 60%. Other clinical studies are currently ongoing to investigate the association of the bispecific antibody with novel drugs with encouraging preliminary results, especially in the setting of heavily pretreated patients. In this review, the authors will provide a comprehensive overview of the drug, including its mechanism of action, major clinical trials, and future perspectives.


Comparative evaluation of three flow cytometers for reticulocyte enumeration.
Flow cytometric determination of reticulocytosis is progressively replacing the manual microscopic method. We evaluated three flow cytometers (Becton Dickinson FACScan, Coulter EPICS Profile II, Ortho Cytoron Absolute) for reticulocyte enumeration, using thiazole orange. For each sample, 30,000 cells were analysed. In order to comparatively evaluate the three instruments, reticulocytes were counted by manually gating the erythroid population and evaluating the gated population for fluorescence characteristics. The different instruments showed good linearity and precision. No carry-over was observed. Orthogonal regression analysis of reticulocyte counts of 100 healthy blood donor samples and 108 haematological patient samples showed a good mutual comparability between all three instruments tested, although the paired t-test showed a significant difference between the Cytoron and both the FACScan and the Profile. Despite minor statistical differences, the three instruments can be considered equivalent for daily routine reticulocyte enumeration.


Work experience program at a metropolitan paediatric hospital: assisting rural and metropolitan allied health professionals exchange clinical skills.
The needs of rural allied health professionals (AHPs) have been widely documented. In particular, problems of professional isolation, lack of professional development opportunities and limited support systems have been highlighted as problems associated with working in rural and remote areas. This research aimed to provide rural and remote AHPs with an opportunity to gain experience in paediatric clinical areas of their choice, to provide rural/remote and metropolitan AHPs with an opportunity to share clinical knowledge and expertise, and to develop networks between rural/remote and metropolitan AHPs. A clinical experience program was developed to meet these aims. Twenty-nine AHPs from rural and remote areas of Queensland participated in the program. Participants completed questionnaires at the end of clinical experience program and 4-8 weeks after the visit. A focus group was also conducted. Analyses found the program met the majority of participants goals and expectations. Enhanced clinical skills in specialist paediatric areas, increased networking and access to resources were reported by rural/remote AHPs as benefits of the program. The role of a clinical consultant was found to be critical to the success of the program.


The independent and combined effects of dietary and sleep patterns on the risk of metabolic dysfunction-associated fatty liver disease: a population-based cohort study.
Background & aims: accumulating evidence shows that various sleep behaviors are related to metabolic dysfunction-associated fatty liver disease (MAFLD), and that diet plays an important role in both preventing and treating this condition. However, the overall effect of a healthy sleep pattern and its joint effect with diet on the risk of MAFLD remain unclear. The aim of this study is to explore the independent and combined effects of dietary and sleep patterns on the MAFLD risk. Methods: this population-based prospective cohort study was conducted in China with a sample size of 13 687 participants. MAFLD was diagnosed through abdominal ultrasound and international expert consensus. Five healthy sleep behaviors were identified to create a healthy sleep pattern, while factor analysis was used to determine dietary patterns. Cox proportional hazards regression was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: during a total of 49 912 person-years of follow-up, 2977 new cases of MAFLD were identified. The adjusted HRs (95% CIs) of MAFLD in relation to the healthy sleep pattern score were 0.87 (0.78-0.97), 0.83 (0.75-0.92), and 0.77 (0.68-0.87) for scores of 3, 4, and 5, respectively, compared to participants with the lowest score (0-2). A higher intake of animal food (adjusted HR4th quartile vs. 1st quartile, 1.15, 95% CI, 1.03-1.27) and a lower intake of vegetables (adjusted HR4th quartile vs. 1st quartile, 0.88, 95% CI, 0.78-0.99) were associated with a higher risk of MAFLD. Participants who adhered to both healthy dietary and sleep patterns had the lowest MAFLD risk compared to those who followed only one or neither of them. Conclusions: a healthy sleep pattern, especially in combination with a healthy diet, was associated with a lower risk of MAFLD. Future prevention strategies for MAFLD should include consideration of sleep behaviors, in addition to the current recommendations.


Ultrasonography and dual-energy computed tomography provide different quantification of urate burden in gout: results from a cross-sectional study.
Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT. Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%). Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1-1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47-0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1-0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23). DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition.


Increased content of glucocorticoid receptors in mouse muscular dystrophy.
An analysis of the glucocorticoid receptor population of skeletal muscle and liver from dystrophic and control mice was performed. These data demonstrate that the cytosol of muscles from dystrophic animals contain a significantly higher concentration of glucocorticoid receptors (approximately 100%) relative to the cytosols of muscles from control mice. No differences in the glucocorticoid receptor population was noted in the livers removed from these animals. These data are consistent with previous observations on the chicken dystrophic model, and may suggest a general phenomenon associated with dystrophy regardless of species or type.