Reduced mobility but unaffected startle response in female rats exposed to prenatal dexamethasone: different sides to a phenotype.
An adverse fetal environment is strongly associated with behavioral and emotional development in later life, and environmental interactions with the genome are essential in the development of pathophysiology. This implicates that a genetic vulnerability or other predisposition may interact with the environment and stressful life events to trigger mental disease. The startle reflex is highly sensitive to fear and anxiety in humans and animals. Elevated startle magnitude has been proposed as a marker for neurodevelopmental disorders. We have recently established an animal model for possible development of anxiety, where female rats are exposed to two stressful life events, during prenatal life and as adolescents, respectively. A blood sampling procedure 3 months prior to startle testing has previously been found to increase basal startle, but only in prenatally stressed rats. As the experimental procedure of acoustic startle response (ASR) measurement resembles the aversive blood sampling procedure, this suggests that effects on ASR may be caused by aversive contextual similarities between blood sampling under restraint and the ASR test. In the present study, postnatal blood sampling was replaced by another dissimilar stressful event. Animals exposed to a high prenatal glucocorticoid level (i.e. 150 mug dexamethasone/kg) were statistically significantly more immobile in the forced swim test (FST) than animals exposed to a lower level of dexamethasone (50 mug/kg) and control animals. Exposure to a novel contextual stressor at 3 months of age (FST) was unassociated with changes in basal startle. These data suggest, since the high prenatal dexamethasone group showed increased immobility in the FST but coped equally well with controls in the ASR, that the outcome of environmental influences is determined by the individual circumstances as different situations require different coping abilities in the same individual.


Photodynamic inactivation in experimental herpetic keratitis.
The effect of photodynamic inactivation on experimental herpes simplex keratitis in rabbits was investigated using neutral red as a photosensitizing dye followed by exposure to light at 425nm. Combined dye application and light exposure early in the disease (two days following infection) reduced to a minimal extent the severity and duration of the acute epithelial infection. The effect on well-established keratitis (three days postinfection) was negligible as evaluated by clinical grading, viral recovery, and histopathological study. In initial experiments, it was found that the dye and light did not have any observable deleterious effect on intact corneas or cause any noticeable delay in healing of injured cornias. Further, when light or dye were utilized alone, neither changed the severity or duration of the keratitis. In vitro treatment of the virus with light and dye destroys its ability to produce experimental keratitis.


Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions.
Corticosteroids and non-steroidal anti-inflammatory drugs are widely used for the treatment of rheumatic conditions, but their gastrointestinal damage significantly limits their use. Sigmoid diverticular abscess perforation (SDAP) is a very serious complication of diverticular disease. To determine the aetiology of large bowel SDAP in rheumatic conditions. 64 patients with SPAD and 320 controls from a similar geographical area and of similar socioeconomic status were studied. The results showed that independently of rheumatic diagnosis corticosteroid treatment is strongly associated with SDAP (OR 31.9 (95% CI 6.4 to 159.2; p<0.001), and non-steroidal anti-inflammatory drugs only weakly associated (OR 1.8 (95% CI 0.96 to 3.4); p = 0.069). A rheumatic diagnosis is also strongly associated with the development of SDAP (OR 3.5 (95% CI 1.9 to 6.7); p<0.001). SDAP has serious implications for patients and consumes many healthcare resources. Patients and physicians should be warned of this potential complication.


Chronic kidney disease as an independent risk factor for new-onset atrial fibrillation in hypertensive patients.
Chronic kidney disease (CKD) has recently been recognized to be a powerful predictor of cardiovascular morbidity and mortality. Atrial fibrillation (AF), which is a common arrhythmia in hypertensives, is associated with increased risks of cardiovascular events and death. However, the association between CKD and the onset of AF has not been fully elucidated. The present study assessed the hypothesis that CKD may influence the onset of AF in hypertensives. A total of 1118 hypertensive patients (mean age, 63 years) without previous paroxysmal AF, heart failure, myocardial infarction, or valvular disease were enrolled. CKD was defined as decreased glomerular filtration rate (<60 ml/min per 1.73 m) and/or the presence of proteinuria (>or=1+). During follow-up periods (mean, 4.5 years), 57 cases of new-onset AF were found (1.1% per year). Kaplan-Meier curves revealed that the cumulative AF event-free rate was decreased in the CKD group (log-rank test P < 0.001). By univariate Cox regression analysis, age, smoking, left atrial dimension, left ventricular mass index, and the presence of CKD were significantly associated with the occurrence of AF. Among these possible predictors, CKD (hazard ratio 2.18, P = 0.009) was an independent determinant for the onset of AF in multivariate analysis. Advanced stages of CKD (stages 4 and 5) were strongly related to the increased occurrence of AF. The present study demonstrated that the complication of CKD, especially progressed renal dysfunction, was a powerful predictor of new-onset AF in hypertensive patients, independently of left ventricular hypertrophy and left atrial dilatation.


[Characteristics of the rat nystagmic reaction after a flight on the Kosmos-1129 biosatellite].
The vestibular nystagmus of rats flown for 18.5 days on Cosmos-1129 was examined with reference to the latent period, number of beats, duration and the average velocity. The nystagmus was elicited by increasing angular acceleration of 10, 20, 30 degrees/sec2. As compared to the controls, the flown animals showed a significant inhibition of the nystagmic reaction (P less than less than 0.001). The inhibition can be attributed to the desynchronosis which developed inflight.


Mental illness and the dental patient.
Virtually every oral health care practice includes patients with mental illness. This continuing education (CE) course gives a practical overview of common psychiatric disorders, their effects on oral and dental health, and conditions associated with mental illness that affect oral health treatment. Following a brief description of mental illnesses, information on conducting a mental health interview and making a psychiatric referral are provided. Oral health problems associated with mental illness and factors affecting treatment delivery are discussed, as well as ideas for avoiding potentially dangerous medication interactions and working with fearful, suspicious, or cognitively impaired patients. Ways in which dental hygienists can work with case managers to provide much needed oral health care to patients whose illness is severe or chronic are covered. Examples are given of work with clients illustrating principles described in the text. The purpose of this course is to provide oral health personnel the information they need to knowledgeably care for patients who have mental illness. Successful completion will be assessed with a post-test to be completed after reading the article in its entirety, including figures and case-reports. Two continuing education course credit hours will be awarded following successful completion of the post-test.


Prospective comparison of small bowel meal with pneumocolon versus ileo-colonoscopy for the diagnosis of ileal Crohn's disease.
Both endoscopy and barium radiography are used routinely to diagnose terminal ileal (TI) Crohn's disease (CD). A prospective study was undertaken to compare ileoscopy with biopsy to small bowel meal with pneumocolon (SBMP) in patients with suspected TI CD. A cohort of outpatients investigated for diarrhea with features of TI disease underwent SBMP followed by colonoscopy with ileal intubation and biopsy within 21 days. All results were reported in a standardized, sequential format to assign SBMP TI diagnoses by the duty radiologist and by dual reading with consensus, ileoscopy by the attending endoscopist, and ileoscopy with biopsy by a blinded panel of endoscopists and pathologists. Reference standard TI diagnoses were determined by a consensus panel with full access to medical records. Among 120 subjects, the reference standard TI diagnosis was normal in 47 (39.1%), lymphoid nodular hyperplasia (LNH) in 24 (20.0%), CD in 48 (40.0%), and NSAID enteropathy in 1 (0.9%). Colonoscopy provided TI images and/or biopsies in 97 cases (80.8%), while SBMP provided TI images in 119 (99.1%). When ileoscopy with biopsy succeeded, its accuracy was similar to SBMP with dual reading (89.7%vs 89.9%, p = NS) but superior to SBMP if interpreted only by the duty radiologist (80.0%, p < 0.05). Biopsy improved the accuracy of ileoscopy, while dual reading improved that of SBMP. Both ileoscopy with biopsy and SBMP with dual reading are highly accurate for diagnosing TI CD. Choice of initial test should reflect local expertise and availability, and the likelihood of associated disease in the proximal small bowel or colon.


Triplet-Induced Lesion Formation at CpT and TpC Sites in DNA.
UV irradiation induces DNA lesions particularly at dipyrimidine sites. Using time-resolved UV pump (250 nm) and mid-IR probe spectroscopy the triplet pathway of cyclobutane pyrimidine dimer (CPD) formation within TpC and CpT sequences was studied. The triplet state is initially localized at the thymine base but decays with 30 ns under formation of a biradical state extending over both bases of the dipyrimidine. Subsequently this state either decays back to the electronic ground state on the 100 ns time scale or forms a cyclobutane pyrimidine dimer lesion (CPD). Stationary IR spectroscopy and triplet sensitization via 2'-methoxyacetophenone (2-M) in the UVA range shows that the lesions are formed with an efficiency of approximately 1.5 %. Deamination converts the cytosine moiety of the CPD lesions on the time scale of 10 hours into uracil which gives CPD(UpT) and CPD(TpU) lesions in which the coding potential of the initial cytosine base is vanished.


Ionic currents in two strains of rat anterior pituitary tumor cells.
The ionic conductance mechanisms underlying action potential behavior in GH3 and GH4/C1 rat pituitary tumor cell lines were identified and characterized using a patch electrode voltage-clamp technique. Voltage-dependent sodium, calcium, and potassium currents and calcium-activated potassium currents were present in the GH3 cells. GH4/C1 cells possess much less sodium current, less voltage-dependent potassium current, and comparable amounts of calcium current. Voltage-dependent inward sodium current activated and inactivated rapidly and was blocked by tetrodotoxin. A slower-activating voltage-dependent inward calcium current was blocked by cobalt, manganese, nickel, zinc, or cadmium. Barium was substituted for calcium as the inward current carrier. Calcium tail currents decay with two exponential components. The rate constant for the slower component is voltage dependent, while the faster rate constant is independent of voltage. An analysis of tail current envelopes under conditions of controlled ionic gradients suggests that much of the apparent decline of calcium currents arises from an opposing outward current of low cationic selectivity. Voltage-dependent outward potassium current activated rapidly and inactivated slowly. A second outward current, the calcium-activated potassium current, activated slowly and did not appear to reach steady state with 185-ms voltage pulses. This slowly activating outward current is sensitive to external cobalt and cadmium and to the internal concentration of calcium. Tetraethylammonium and 4-aminopyridine block the majority of these outward currents. Our studies reveal a variety of macroscopic ionic currents that could play a role in the initiation and short-term maintenance of hormone secretion, but suggest that sodium channels probably do not make a major contribution.


A new office-based procedure for treatment of snoring: The S.I.Le.N.C.E. study.
Demonstrate the safety and effectiveness of palatal foreshortening and stiffening in reducing snoring severity in nonobstructive sleep apnea (non-OSA) patients complaining of chronic disruptive snoring. In a US-based 8-center, open-label, prospective, single-arm cohort study, 52 consenting adults with chronic disruptive snoring (snoring impacting a patient's life and causing patient or bed partner to seek medical intervention) were treated via office-based placement of resorbable, bidirectional, barbed suture implants into the soft palate under local anesthesia. Prior to intervention, home sleep tests (HSTs) were performed to rule out OSA and to document snoring noise level. Both subject and their bed/sleep partners (also consented) completed questionnaires including: bed/sleep partner's scored visual analog scale (VAS) for subjects' snoring severity, and subject scoring for Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Following intervention, HSTs, VAS, ESS and PSQI were repeated at 30, 90 and 180 days. Mean baseline bed/sleep partner VAS was 7.81 ± 1.59. Mean postimplant VAS scores decreased significantly at each measured interval; to 5.77±2.35 (P < .001) at 30 days, 4.48 ± 1.81 (P < .001) at 90 days, and 5.40 ± 2.28 (P < .001) at 180 days. Post treatment improvements in daytime sleepiness and QOL were also observed. Two partial extrusions were reported. No further adverse events were identified. The current study demonstrates the safety and efficacy of the Elevoplasty procedure in reducing snoring severity over a follow-up period of 6 months. 2b.


Adaptive template filtering for signal-to-noise ratio enhancement in magnetic resonance imaging.
In this paper, a local shape-adaptive template filtering is proposed for the enhancement of the signal-to-noise ratio (SNR) without the loss of resolution in magnetic resonance (MR) imaging. Unlike conventional filtering, where the template shape and coefficients are fixed, multiple templates are defined in the proposed algorithm. An optimal template is selected and optimal filtering, based on the template, is applied on a pixel-by-pixel basis. Using the proposed process, edge blurring is minimized and SNR enhancement is maximized by selecting the optimally matched template. Compared to existing two-dimensional (2-D) adaptive linear least square error (LLSE) filters or direction-adaptive recursive filters, the proposed adaptive template filter provides higher SNR and sharper edges for both MR and artificial resolution phantom images.


Because the machine can discriminate: How machine learning serves and transforms biological explanations of human difference.
Research on scientific/intellectual movements, and social movements generally, tends to focus on resources and conditions outside the substance of the movements, such as funding and publication opportunities or the prestige and networks of movement actors. Drawing on Pinch's theory of technologies as institutions, I argue that research methods can also serve as resources for scientific movements by institutionalizing their ideas in research practice. I demonstrate the argument with the case of neuroscience, where the adoption of machine learning changed how scientists think about measurement and modeling of group difference. This provided an opportunity for members of the sex difference movement by offering a 'truly categorical' quantitative methodology that aligned more closely with their understanding of male and female brains and bodies as categorically distinct. The result was a flurry of publications and symbiotic relationships with other researchers that rescued a scientific movement which had been growing increasingly untenable under the prior methodological regime of univariate, frequentist analyses. I call for increased sociological attention to the inner workings of technologies that we typically black box in light of their potential consequences for the social world. I also suggest that machine learning in particular might have wide-reaching implications for how we conceive of human groups beyond sex, including race, sexuality, criminality, and political position, where scientists are just beginning to adopt its methods.


The impact of removing snacks of low nutritional value from middle schools.
Removing low nutrition snacks from schools is controversial. Although the objective is to decrease the consumption of these foods at school, some critics argue that children will compensate by eating more of these foods at home. Others worry that school-based obesity prevention programs will increase student preoccupation with weight. The present study examines these concerns. Three middle schools replaced snacks and beverages that did not meet nutrition guidelines, whereas three comparison schools made no systematic changes. Students were surveyed about dietary intake and weight concerns before and after implementation of the intervention. Findings indicate that removing low nutrition items from schools decreased students' consumption with no compensatory increase at home. Furthermore, there were no differences in students' reported weight concerns. These results support the value of strengthening school nutrition standards to improve student nutrition and provide evidence dispelling concerns that such efforts will have unintended negative consequences.


Recombinant gamma interferon increases the binding of peripheral blood mononuclear leukocytes and a Leu-3+ T lymphocyte clone to cultured keratinocytes and to a malignant cutaneous squamous carcinoma cell line that is blocked by antibody against the LFA-1 molecule.
Because keratinocytes (KCs) express HLA-DR in a wide variety of skin diseases in which mononuclear leukocytes are observed in close apposition to KCs (i.e., graft-versus-host disease), and since gamma interferon (IFN-gamma) induces HLA-DR expression on KCs, we asked whether IFN-gamma treatment of KCs would influence the adherence of mononuclear leukocytes. When allogeneic peripheral blood mononuclear leukocytes (PBML) and a Leu-3+ T cell clone were coincubated with IFN-gamma-treated KCs (300 U/ml, 3 days), there was a marked increase in binding compared with nontreated KCs. Similar binding results were obtained using a cutaneous squamous carcinoma cell line (SCL-1) after IFN-gamma treatment. The IFN effect was relatively specific for IFN-gamma, as neither IFN-alpha nor -beta had any effect. Tumor necrosis factor exposure (500 U/ml, 3 days) increased the binding of the Leu-3+ T cell clone to both KCs and SCL-1 cells. Neutrophils displayed a less marked (but statistically significant) increase in binding to IFN-gamma-treated KCs. Using the Leu-3+ cell clone and SCL-1 cells, detailed kinetic analysis of the effect of IFN-gamma on binding was performed. The increased adherence between the cells began to appear after only 7 hours of treatment with r-IFN-gamma (300 U/ml) and reached a plateau at 48 hours, with significantly enhanced binding continuing for at least 48 hours after removal of IFN-gamma. The mechanism of binding was explored by preincubation of the PBML/Leu-3+ T cells with anti-LFA-1 (lymphocyte function-associated antigen) antibody (0.6-6.0 micrograms/ml), which totally inhibited the binding with no effect by anti-LFA-2 or -3 or class I or II antibodies despite documented binding of these antibodies to the cells. These results suggest that, after exposure to IFN-gamma, the ability of KCs to bind mononuclear leukocytes is strongly enhanced, and this adherence may be important in leukocyte trafficking in the skin as well as contributing to altered KC-leukocyte interaction, which may be of fundamental importance in a variety of skin disease.


Branded versus generic clozapine: bioavailability comparison and interchangeability issues.
Clozapine has been the treatment of choice for patients with refractory schizophrenia. Generic clozapine has recently become available, because of a waiver of the usual criteria for establishing bioequivalence. However, there are biopharmaceutical, bioavailability, and clinical concerns related to the generic formulation raised by both clinicians and academic researchers. We conducted a prospective, randomized, crossover study to evaluate steady-state pharmacokinetics, pharmacodynamics, and tolerability of generic clozapine (Zenith Goldline Pharmaceuticals) versus Clozaril (Novartis Pharmaceuticals) in schizophrenic patients. A preliminary report of the pertinent bioavailability results is presented here. Despite comparable mean plasma concentration-time curves, significant differences were found in the primary pharmacokinetic parameters of the 2 formulations in almost 40% of patients. Such intraindividual differences raise the issue of average bioequivalence versus individual bioequivalence and the implication for interchangeability of different clozapine formulations. The decision to switch a patient from branded to generic clozapine should be made on an individual basis with special emphasis on clinical outcome, and patients should be monitored closely during the transition.


Theory of solvation in polar nematics.
We develop a linear response theory of solvation of ionic and dipolar solutes in anisotropic, axially symmetric polar solvents. The theory is applied to solvation in polar nematic liquid crystals. The formal theory constructs the solvation response function from projections of the solvent dipolar susceptibility on rotational invariants. These projections are obtained from Monte Carlo simulations of a fluid of dipolar spherocylinders which can exist both in the isotropic and nematic phases. Based on the properties of the solvent susceptibility from simulations and the formal solution, we have obtained a formula for the solvation free energy which incorporates the experimentally available properties of nematics and the length of correlation between the dipoles in the liquid crystal. The theory provides a quantitative framework for analyzing the steady-state and time-resolved optical spectra and makes several experimentally testable predictions. The equilibrium free energy of solvation, anisotropic in the nematic phase, is given by a quadratic function of cosine of the angle between the solute dipole and the solvent nematic director. The sign of solvation anisotropy is determined by the sign of dielectric anisotropy of the solvent: solvation anisotropy is negative in solvents with positive dielectric anisotropy and vice versa. The solvation free energy is discontinuous at the point of isotropic-nematic phase transition. The amplitude of this discontinuity is strongly affected by the size of the solute becoming less pronounced for larger solutes. The discontinuity itself and the magnitude of the splitting of the solvation free energy in the nematic phase are mostly affected by microscopic dipolar correlations in the nematic solvent. Illustrative calculations are presented for the equilibrium Stokes shift and the Stokes shift time correlation function of coumarin-153 in 4-n-pentyl-4'-cyanobiphenyl and 4,4-n-heptyl-cyanopiphenyl solvents as a function of temperature in both the nematic and isotropic phases.


The human LGALS3 (galectin-3) gene: determination of the gene structure and functional characterization of the promoter.
Galectin-3 is a beta-galactoside-specific lectin that is a pre-mRNA splicing factor. Here we report the genomic organization of the human LGALS3 (galectin-3) gene and functional characterization of the promoter. Southern blot analysis of genomic DNA revealed that galectin-3 is coded by a single gene in the human genome. The gene is composed of six exons and five introns, spanning a total of approximately 17 kilobases (kb). Based on primer extension and ribonuclease protection analyses, there are two transcription initiation sites located 52 and 50 nucleotides (nt) upstream of the exon I-intron 1 border, and defined here as +1a and +1b, respectively. The translation start site is in exon II. The ribonucleoprotein-like N-terminal domain, containing the proline-glycine-alanine-tyrosine (PGAY) repeat motif, is found entirely within exon III. The carbohydrate recognition sequence is found entirely within exon V. Genomic fragments encompassing -836 to +141 nt (relative to +1a) have significant promoter activity when linked to the luciferase reporter gene and transiently transfected into HeLa cells or human diploid fibroblasts. Quiescent fibroblasts have low promoter activity but the activity increases 100-fold following serum addition. Serum responsive activation regions in the promoter are located between -513 and -339 nt and between -339 and -229 nt; an additional activation region may be located between -105 and -15 nt. Because galectin-3 is an immediate-early gene whose expression is dependent on the proliferative state of the cell, this study provides the basis for determining the molecular mechanisms of transcriptional regulation in neoplasia or cellular senescence.


Argentophilicity-dependent colossal thermal expansion in extended prussian blue analogues.
The thermal expansion behavior of isostructural variants of the colossal thermal expansion material Ag3[CoIII(CN)6] has been investigated using variable temperature X-ray and neutron powder diffraction. It was found that substitution at the octahedral transition metal site did not strongly affect the thermal expansion behavior, giving Ag3[FeIII(CN)6] as a new colossal thermal expansion material. Substitution at the Ag site (by D) was shown to reduce the thermal expansion coefficients by an order of magnitude. It was proposed that this correlation between the presence of argentophilic interactions and extreme thermal expansion behavior may explain a variety of thermal effects in flexible framework materials containing metallophilic interactions.


[Bilateral renal solitary fibrous tumor].
We report the first case of bilateral renal solitary fibrous tumor diagnosed in a patient suffering from tuberous sclerosis. From the bibliographic review, only 15 cases of solitary fibrous tumor have been described in the kidney. We did not find any case of simultaneous bilateral involvement. We did not find any case described in a patient with tuberous sclerosis either, as the present case, being a 51-year-old female with presenting with a big abdominal mass arising from the left kidney (25 cm) and another 2 cm mass in the right kidney. We emphasize the extreme rarity of this tumor in the kidney. It has benign characteristics and behavior, and good prognosis, but requires surgical treatment to obtain a proper histopathologic diagnosis, based on immuno-histochemical studies.


Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients.
Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined. Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft-Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression. Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8-113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5-14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype. Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.


Temporal trends and molecular epidemiology of HIV-1 infection in Taiwan from 1988 to 1998.
Eight hundred and seventy-nine HIV-1-infected patients (comprising 46% of reported HIV-1/AIDS cases in Taiwan) were recruited for this study of the molecular epidemiology of HIV-1 in Taiwan from 1988 to 1998. HIV-1 subtypes were determined using a modified peptide-enzyme immunoassay complemented with DNA sequencing and phylogenetic analysis. Of the 807 HIV-1 infected men, 68.2% were infected with HIV-1B, 29.5% with HIV-1 circulating recombinant form (CRF)01_AE and 2.3% with other subtypes. Of the 72 HIV-1-infected women, 72.2% were infected with HIV-1 CRF01_AE, 13.9% with HIV-1B, and 13.9% with other subtypes. All of 8 foreign-born, Southeast Asian women and 6 of 7 (85.7%) Taiwan-native female commercial sex workers were infected with HIV-1 CRF01_AE. Fourteen of the 33 (42.4%) heterosexual married men with CRF01_AE had transmitted HIV-1 to their wives, whereas only 1 of 17 (5.9%) men with HIV-1 B had transmitted HIV-1 to their spouses (p < .01). Of 18 heterosexual male injecting drug users, 1 of 12 (8.5%) with HIV-1B and 5 of 6 (83.3%) with HIV-1 CRF01_AE had had sexual contact with female commercial sex workers (p < .01). Therefore, in this population, CRF01_AE was preferentially associated with heterosexual risk groups, a finding compatible with differences in transmission capability between B and non-B subtypes.


Gas-phase fragmentation study of novel synthetic 1,5-benzodiazepine derivatives using electrospray ionization tandem mass spectrometry.
The fragmentation patterns of a series of three novel synthesized 3-hydroxy-4-phenyl-tetrahydro-1,5-benzodiazepin-2-ones (1-3), possessing the same backbone structure, were investigated using electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) techniques. A simple methodology, based on the use of ESI (positive ion mode) and by increasing the declustering potential in the atmospheric pressure/vacuum interface, collision-induced dissociation (CID), was used to enhance the formation of the fragment ions. In general, the novel synthetic 1,5-benzodiazepine derivatives afforded, in the gas phase, both protonated and sodiated molecules. This led to the confirmation of the molecular masses and chemical structures of the studied compounds. Exact accurate masses were measured using a high-resolution ESI-quadrupole orthogonal time-of-flight (QqToF)-MS/MS hybrid mass spectrometer instrument. The breakdown routes of the protonated molecules were rationalized by conducting low-energy collision CID-MS/MS analyses (product ion- and precursor ion scans) using a conventional quadrupole-hexapole-quadrupole (QhQ) tandem mass spectrometer. All the observed major fragmentations for the 1,5-benzodiazepines occurred in the saturated seven-membered ring containing the nitrogen atoms. These formed a multitude of product ions by different breakdown routes. All the major fragmentations involved cleavages of the N-1-C-2 and C-3-C-4 bonds. These occurred with concomitant eliminations of glyoxal, benzene and ethyl formate, forming the product ion at m/z 119, which was observed in all the studied compounds. In addition, an unique simultaneous CID-MS/MS fragmentation was noticed for the 1,5-benzodiazepines 1 and 3, which occurred by a pathway dictated by the substituent located on the N-1-position. It was evident that the aromatic ring portion of the 1,5-benzodiazepines was resistant to CID-MS/MS fragmentation. Re-confirmation of the various geneses of the product ions was achieved by conducting a series of precursor ion scans. ESI-MS and CID-MS/MS analyses have thus proven to be a specific and very sensitive method for the structural identification of these novel 1,5-benzodiazepine derivatives.


Analysis of Cardiovascular Disease Angiography Process Based on Rough Set and Internet of Things.
The angiography image enhancement technology has the potential to enhance the vascular structure in the image while suppressing the background and nonvascular structures simultaneously. This technology has the ability to enhance the result as close to the real structure of blood vessels as possible. Angiographic image processing is one of the essential contents in the field of medical image processing and analysis. However, the existing cardiovascular angiography schemes suffer from various issues. In this paper, the detection process of cardiovascular angiography is studied by combining the Internet of Things and rough set technology. Firstly, this paper designs the architecture design of the cardiovascular angiography process combined with the Internet of Things technology. Secondly, this paper uses a rough set algorithm to optimize the background noise and boundary shrinkage because of the sensitivity of the contrast background noise and boundary shrinkage. Simulation results verified the applicability and efficiency of the proposed model in the cardiovascular angiography scheme. The model has been optimized during implementation. Compared with the traditional algorithm, the same image data processing speed is significantly improved to ensure the enhancement effect.


Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702).
Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives.Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. Of 107 women enrolled, 67 patients (median age 49, range 24-75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10-3 vs.1.47 × 10-3; P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65-0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10-3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%-31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10-3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers. DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.


Clinical Efficacy of a Digital Intervention for Patients with Atopic Dermatitis: a Prospective Single-Center Study.
Improving disease awareness and treatment adherence is key for the long-term management of atopic dermatitis (AD). Digital interventions can support patients in disease self-management and adopting a healthier lifestyle through behavioral modifications. We aimed to test the clinical efficacy of a digital program in patients with AD. Adults with mild-to-severe AD were recruited for a 6-week feasibility study. The intervention was delivered through a mobile app and consisted of symptom and trigger education, treatment reminders, lifestyle coaching, and healthy lifestyle support. Here we report the secondary outcomes of intervention efficacy on clinical symptoms, as assessed by Scoring Atopic Dermatitis (SCORAD) and Patient-Oriented Eczema Measure (POEM), on health-related quality of life (HR QoL) as assessed by Dermatology Life Quality Index (DLQI), and changes in behaviors related to disease management as assessed by a six-item questionnaire. Twenty of 21 patients (95.2%) completed the program (81% female, mean age 31.4 years, mean time from diagnosis 26.8 years). Clinical symptoms and patient-reported global severity improved by 44% and 46%, respectively, while HR QoL improved by 41% (p < 0.001 for all measures). Adherence to treatments and preventive measures improved from pre- to post-intervention, including skincare, avoidance of triggers, and disease-related knowledge. A significant interaction was observed between increased treatment adherence and clinical improvement, such that larger clinical improvements were observed in patients with higher treatment adherence. Patients with AD are open to and can benefit from a digitally delivered targeted intervention, as demonstrated by significant improvements in treatment adherence and related clinical outcomes.


Can atom-surface potential measurements test atomic structure models?
van der Waals (vdW) atom-surface potentials can be excellent benchmarks for atomic structure calculations. This is especially true if measurements are made with two different types of atoms interacting with the same surface sample. Here we show theoretically how ratios of vdW potential strengths (e.g., C₃(K)/C₃(Na)) depend sensitively on the properties of each atom, yet these ratios are relatively insensitive to properties of the surface. We discuss how C₃ ratios depend on atomic core electrons by using a two-oscillator model to represent the contribution from atomic valence electrons and core electrons separately. We explain why certain pairs of atoms are preferable to study for future experimental tests of atomic structure calculations. A well chosen pair of atoms (e.g., K and Na) will have a C₃ ratio that is insensitive to the permittivity of the surface, whereas a poorly chosen pair (e.g., K and He) will have a ratio of C₃ values that depends more strongly on the permittivity of the surface.


Checking pregnancy status in adolescent girls before procedures under general anaesthesia.
Surgery, ionising radiation and anaesthesia in the presence of an undetected pregnancy could be harmful. British guidelines state that female patients of 'childbearing age' should have their pregnancy status established before surgery. Approaching this topic with an adolescent girl can be challenging. The authors conducted an observational study and a survey in their institution and a national survey of Association of Paediatric Anaesthetists (APA) linkmen. Local: Southampton. National: UK. Both surveys demonstrate widespread concerns about inconsistent and informal practices. Only 45% of respondents in the authors' institution stated they ask adolescent girls if they could be pregnant. 40% of APA linkmen were unaware of national guidelines. This work illustrates the need for consistent national guidance. We propose that all girls who have reached menarche should be routinely offered a urine pregnancy test before any procedure under general anaesthesia.


In silico epitope prediction and immunogenic analysis for penton base epitope-focused vaccine against hydropericardium syndrome in chicken.
Certain strains of fowl adenovirus serotype 4 (FAdV-4) of the family Adenoviridae are recognized to be the causative agents of Hydropericardium Syndrome (HPS) in broiler chicken. Despite the significantly spiking mortality in broilers due to HPS, not much effort has been made to design an effective vaccine against FAdV-4. The combination of immuno- and bioinformatics tools for immunogenic epitope prediction is the most recent concept of vaccine design. It reduces the time and effort required for hunting a potent vaccine candidate and is economical. Previously, we have reported the penton base protein of FAdV-4 to be a candidate for subunit vaccine against HPS. In the present study, we have computationally pre-screened promising B- and T-cell epitopes of the penton base. Multiple methods were employed for linear B-cell epitope identification; BepiPred and five other methods based on physicochemical properties of the amino acids. The penton base was homology modeled by means of Modeller 9.17 and after refinement of the model (by GalaxyRefine web server) ElliPro web tool was used to predict the discontinuous epitopes. NetMHCcons 1.1 and NetMHCIIpan 3.1 servers were used for the likelihood of peptide binding to Major Histocompatibility Complex (MHC) class I & II molecules respectively for T-cell epitope forecast. As a result, we identified the peptide stretch of 1-225 as the most promiscuous B- and T-cell epitope region in penton base Full Length (FL) protein sequence. Escherichia coli based expression vectors were generated containing cloned peptide stretch 1-225 (penton base1-225) and penton base FL gene sequence. The recombinant penton base1-225 and penton base FL proteins were expressed and purified using Escherichia coli-based expression system. Purification yield of penton base1-225 was 3-fold higher compared to penton base FL. These proteins were injected in chickens to determine their competence in protection against HPS. The results showed equal protection level of the two proteins and the commercial inactivated vaccine against FAdV-4 infection. The results suggest the peptide stretch 1-225 of penton base as a valuable candidate for developing an epitope-driven vaccine to combat HPS.


"Being able to speak": What individuals in jail perceived as helpful about participating in alcohol-related brief interventions.
A significant proportion of individuals within the criminal justice system meet criteria for a substance use disorder. Treatments for individuals who are incarcerated with substance use disorders show minimal to no benefit on postrelease outcomes, suggesting a need to improve their effectiveness, particularly those that can be delivered in a brief format. The purpose of this study was to describe what individuals in jail with substance use disorders perceived as being helpful about 2 brief alcohol-focused interventions, which can be used to inform future treatments with this population. Data came from a parent study where 58 individuals in jail with substance use disorders received either a motivational or educational intervention focused on alcohol and other substance use and then completed a questionnaire assessing what was most and least helpful about the interventions. Qualitative responses were coded using a grounded theory approach. Results indicated that participants from both interventions reported that receiving individualized attention and talking one-on-one with someone was helpful, and that the interventions were encouraging and elicited hope. There also were specific components from each intervention that participants said were beneficial, including the opportunity to discuss plans for postrelease and to learn about addiction from psychoeducational videos. Participants noted areas for improving future interventions. Suggestions from participants were to offer tangible resources upon release, make session lengths flexible, and reduce assessment burden during research interviews. Findings align with established approaches for working with marginalized groups, namely, community-based participatory research methods and shared decision-making models for treatment. This study provided a voice to individuals in jail with substance use disorders, a group often underrepresented in the literature, and may offer an initial look at how to improve treatments for this high-risk population.


Superoxide dismutase and glutathione peroxidase enzyme activities in larynx carcinoma.
It can be concluded that these changes are related to damage at the DNA level or to the inhibitory effects of tumor promoters. Increases in GSH-Px activities may be related to the independence of this enzyme from the suppressive effects of tumor promoters. This study and others in the literature show that it is not possible to generalize the activities of SOD and GSH-Px in cancer. There has been growing interest in the role of free radicals as a cause of cancer. It has been suggested that an increase in activated forms of oxygen in cells due to overproduction and/or the inability to destroy them may lead to severe damage of cell structures. As a result of these changes, some chromosomal aberrations and carcinogenesis may develop. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are two important antioxidant enzymes involved in enzymatic antioxidant defense mechanisms. To our knowledge there have been no previous studies in the literature investigating the activities of SOD and GSH-Px in laryngeal cancer. The study subjects comprised 10 male patients (age range 43-76 years) with laryngeal carcinoma and 10 healthy controls (4 males, 6 females; age range 40-69 years) with intraoral hyperplastic fibrous tissue. Homogenate SOD and GSH-Px activities were measured using commercially available kits. GSH-Px levels were significantly increased in the cancerous tissues compared with cancer-free adjacent tissues and fibrous hyperplasia tissues (p < 0.05), whereas there was no significant difference between SOD activities (p > 0.05). There was also no significant difference between GSH-Px activity in cancer-free adjacent tissues and fibrous hyperplasia tissues (p > 0.05).


Expression of estrogen-receptor related receptors in amphioxus and zebrafish: implications for the evolution of posterior brain segmentation at the invertebrate-to-vertebrate transition.
Summary The evolutionary origin of vertebrate hindbrain segmentation is unclear since the amphioxus, the closest living invertebrate relative to the vertebrates, possesses a hindbrain homolog that displays no gross morphological segmentation. Three of the estrogen-receptor related (ERR) receptors are segmentally expressed in the zebrafish hindbrain, suggesting that their common ancestor was expressed in a similar, reiterated manner. We have also cloned and determined the developmental expression of the single homolog of the vertebrate ERR genes in the amphioxus (AmphiERR). This gene is also expressed in a segmented manner in a region considered homologous to the vertebrate hindbrain. In contrast to the expression of amphioxus islet (a LIM-homeobox gene that also labels motoneurons), AmphiERR expression persists longer in the hindbrain homolog and does not later extend to additional posterior cells. In addition, AmphiERR and one of its vertebrate homologs (ERRalpha) are expressed in the developing somitic musculature of amphioxus and zebrafish, respectively. Altogether, our results are consistent with fine structural evidence suggesting that the amphioxus hindbrain is segmented, and indicate that chordate ERR gene expression is a marker for both hindbrain and muscle segmentation. Furthermore, our data support an evolution model of chordate brain segmentation: originally, the program for anterior segmentation in the protochordate ancestors of the vertebrates resided in the developing axial mesoderm which imposed reiterated patterning on the adjacent neural tube; during early vertebrate evolution, this segmentation program was transferred to and controlled by the neural tube.


Gleditsia sinensis fruit extract-induced apoptosis involves changes of reactive oxygen species level, mitochondrial membrane depolarization and caspase 3 activation.
Recently, we have shown that the anomalous fruit extract of Gleditsia sinensis (GSE) processes apoptotic activity on numerous solid tumour and leukaemia cell lines as well as primary cultured leukaemia cells obtained from bone marrow aspirate of patients. GSE treated cancer cells exhibited apoptotic features as readily illustrated by morphological investigation, DNA fragmentation analysis and TUNEL labelling methods. Elevation of intracellular superoxide dismutase activity was observed. However, the detailed mechanism still remains undefined. Here we further demonstrated that cell cycle arrest, increment of hydrogen peroxide production, changes of intracellular acid-base equilibrium and mitochondrial membrane potential depolarization (DeltaPsi(m)) were induced from cancer cells after GSE incubation. Caspase 3 protease activity was significantly enhanced upon GSE treatment. Taken together, a defined signaling pathway for the mechanistic action of GSE on cancer cells was worked out.


Survival, Growth, and Reproduction Responses in a Three-Generation Exposure of the Zebrafish (Danio rerio) to Perfluorooctane Sulfonate.
A prior multigenerational perfluorooctane sulfonic acid (PFOS) exposure investigation in zebrafish reported adverse effects at 0.734 µg/L, among the lowest aquatic effect levels for PFOS reported to date. The present three-generation PFOS exposure quantified survival, growth, reproduction, and vitellogenin (VTG; egg yolk protein) responses in zebrafish, incorporating experimental design and procedural improvements relative to the earlier study. Exposures targeting 0.1, 0.6, 3.2, 20, and 100 µg/L in parental (P) and first filial (F1) generations lasted for 180 days post fertilization (dpf) and the second filial generation (F2) through 16 dpf. Survival decreased significantly in P and F2 generation exposures, but not in F1, at the highest PFOS treatment (100 µg/L nominal, 94-205 µg/L, measured). Significant adverse effects on body weight and length were infrequent, of low magnitude, and occurred predominantly at the highest exposure treatment. Finally, PFOS had no significant effects on P or F1 egg production and survival or whole-body VTG levels in P or F1 male fish. Overall, the predominance and magnitude of adverse PFOS effects at <1 µg/L reported in prior research were largely nonrepeatable in the present study. In contrast, the present study indicated a threshold for ecologically relevant adverse effects in zebrafish at 117 µg/L (SE 8 µg/L, n = 10) for survival and 47 µg/L (SE 11 µg/L, n = 19) for all statistically significant negative effects observed. Environ Toxicol Chem 2023;00:1-17. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.


Slavery and jouissance: analysing complaints of suffering in UK and Australian nurses' talk about their work.
Nursing has a gendered and religious history where ideas of duty and servitude are present and shape its professional identity. The profession also promotes idealized notions of relationships with patients and of professional autonomy both of which are, in practice, highly constrained or even impossible. This paper draws on psychoanalytic concepts in order to reconsider nursing's professional identity. It does this by presenting an analysis of data from two focus group studies involving nurses in England and Australia held between 2010 and 2012. The studies gave rise to data where extremely negative talk about nursing work seemed to produce, or to be expressed with, a high degree of energy, and a particular kind of enjoyment. In our analysis, we focus on the nurses' apparent enjoyment derived from their expression of a position of powerlessness in which they describe themselves as 'slaves' or 'martyrs' in the health care system. We interpret this as jouissance and suggest that the positions of slave or martyr provide a possible response to what we argue is the impossibility of the nurse's role. We argue that a remnant of a quasi-religious ethic within the profession makes it acceptable for nurses to talk about self-sacrifice and powerlessness as part of their working subjectivity. We further argue that this analysis offers a new consideration of the issue of power and professional identity in nursing that goes beyond seeing nurses as simply overpowered by, or engaged in, a gendered power struggle with other professional groups. We suggest that powerlessness and victimhood hold particular attractions and advantages for nurses and are positions that are more available to nurses than to other occupational groups. This research shows how psychoanalytic theory can help produce new insights into the problems and complexity of nursing and extend existing study of the professions.


Ebstein's anomaly with non-patent ductus arteriosus aneurysm and bradycardiac atrial fibrillation in an 80-year-old man.
An 80-year-old man with Ebstein's anomaly and ductus arteriosus aneurysm is reported. He was admitted with bradycardiac atrial fibrillation and right ventricular failure. For the control of brady-arrhythmia, a permanent pacemaker was implanted. Two-dimensional echocardiogram revealed distal displacement of the septal tricuspid valve. Aortography and computed tomography showed ductus arteriosus aneurysm. This is the first report of the association of Ebstein's anomaly and non-patent ductus arteriosus aneurysm.


Assistive technologies for home NIV in patients with COPD: feasibility and positive experience with remote-monitoring and volume-assured auto-EPAP NIV mode.
Outcomes for patients with chronic obstructive pulmonary disease (COPD) with persistent hypercapnic respiratory failure are improved by long-term home non-invasive ventilation (NIV). Provision of home-NIV presents clinical and service challenges. The aim of this study was to evaluate outcomes of home-NIV in hypercapnic patients with COPD who had been set-up at our centre using remote-monitoring and iVAPS-autoEPAP NIV mode (Lumis device, ResMed). Retrospective analysis of a data set of 46 patients with COPD who commenced remote-monitored home-NIV (AirView, ResMed) between February 2017 and January 2018. Events including time to readmission or death at 12 months were compared with a retrospectively identified cohort of 27 patients with hypercapnic COPD who had not been referred for consideration of home-NIV. The median time to readmission or death was significantly prolonged in patients who commenced home-NIV (median 160 days, 95% CI 69.38 to 250.63) versus the comparison cohort (66 days, 95% CI 21.9 to 110.1; p<0.01). Average time to hospital readmission was 221 days (95% CI, 47.77 to 394.23) and 70 days (95% CI, 55.31 to 84.69; p<0.05), respectively. Median decrease in bicarbonate level of 4.9 mmol/L (p<0.0151) and daytime partial pressure of carbon dioxide 2.2 kPa (p<0.032) in home-NIV patients with no required increase in nurse home visits is compatible with effectiveness of this service model. Median reduction of 14 occupied bed days per annum was observed per patient who continued home-NIV throughout the study period (N=32). These findings demonstrate the feasibility and provide initial utility data for a technology-assisted service model for the provision of home-NIV therapy for patients with COPD.


A rare case: Retrocecal appendicitis adherent to the liver capsule.
The cases of appendicitis take an important place in the hospital emergency departments and it must be kept in mind in the differential diagnosis of patients presenting with abdominal pain. Related to cecum, the appendix can be found in many different positions; however, it is mostly observed descending intraperitoneally (31-74%) and at the retrocecal region (26-65%). In this case report, we present the case of a 26-year-old female patient admitted to the emergency room with a colic pain in the right upper quadrant for about 2 days. Computed tomography revealed contamination in the fatty plans around the cecum and adhesive retrocecal appendicitis from the liver to the retroperitoneum. Appendectomy was performed. The pathology result was gangrenous appendicitis. In the literature, there is no similar case of appendicitis with hepatic adhesions. In conclusion, we want to emphasize that physicians and surgeons in the emergency departments must be more careful during the differential diagnosis of a patient with appendicitis and atypical symptoms and a more detailed investigation is required.


The first human retroviruses: are there others?
Three related, but very different, retroviruses have recently been identified in man. Human T-cell leukaemia virus (HTLV) type I apparently causes adult T-cell leukaemia. HTLV type II has been isolated only rarely and has not been identified with a disease. HTLV type III is very likely the causative agent in acquired immunodeficiency syndrome.


Child health and social status.
Available evidence regarding the relationship between socioeconomic status and health in childhood has been summarized. Only studies that used income, education, or occupation as measures of socioeconomic status and provided data obtained subsequent to legislation facilitating access to care have been cited. Data are presented on the prevalence and severity of illness (mortality, acute conditions as a group, chronic conditions as a group, and hospitalization), sequelae of prematurity, and specific common health problems and their sequelae. These specific health problems are lead poisoning, vision problems, otitis media and hearing loss, cytomegalic inclusion disease, asthma, psychosocial and psychosomatic problems, and iron deficiency anemia. All of the above (with the possible exception of asthma) are more prevalent among poor children than among nonpoor children. Even more striking is the evidence for consistently greater severity of problems or likelihood of sequelae among poor children. Although causality cannot be inferred from these data, the findings suggest a need for more basic research on the social correlates of disease, on the effect of social progress on disease prevalence and severity, and on the effect of medical care in overcoming the disadvantage associated with low socioeconomic status.


Pesticide Spraying and Reduced Cholinesterase Activity among Hill Tribe Farmers in Thailand.
Farming is an important occupation in Thai hill tribe communities, which are often remote, and lack other economic opportunities along with basic educational, health care, and occupational health and safety services. Additionally, these communities have a unique culture and language. The present study was conducted in northern Thailand to evaluate pesticide exposures and associated health impacts among hill tribe farmers, and to compare them to Thai farmers. Lahu hill tribe farmers in a mountain community were recruited by public health hospital staff, along with a reference group of lowland Thai farmers. Participants completed a survey on demographic factors and work practices, and blood and urine samples were collected by a trained nurse. Acetylcholinesterase activity (AChE) was quantified to assess pesticide exposure, whereas liver and kidney functions were evaluated using clinical biomarkers. A large fraction (nearly 50%) of Lahu farmers were illiterate and could not speak Thai. Thai farmers worked fewer hours per week (39.4) than did Lahu farmers. Among Lahu farmers, AChE levels were significantly lower (worse) than those of Thai farmers. However, other health outcomes in these populations were similar. Formal education and language skills were not associated with pesticide exposures or health outcomes. Pesticide spraying was found to be a significant predictor of reduced AChE (OR=8.5, 95% CI 1.1-69.6). Pesticide exposures are a significant occupational health hazard among Thai hill tribe farmers. Training, potentially delivered by community health volunteers, is needed to communicate safe pesticide work practices to these farmers. Obtained. The study protocol was approved by the Institutional Review Board of Mae Fah Luang University (REH-61080). The authors declare no competing financial interests.


The intention to leave among nurses: the role of job satisfaction, self-efficacy and work engagement.
Retaining nursing staff within hospitals is essential to limit the negative impact of excessive voluntary turnover on the quality of care and organization costs. The purpose of this study is to explain voluntary turnover in the nursing profession by analyzing the influence of job satisfaction and, in particular, self-efficacy and work engagement on turnover intention. 210 nurses working in three hospitals in Southern Italy have completed a self-report questionnaire. A correlation analysis was applied in order to test the relationship between variables, while the role of age, professional and organizational seniority was estimated through partial correlations. A multiple linear regression was performed to verify the role of self-efficacy and work engagement in predicting turnover intention. Job satisfaction, self-efficacy and work engagement are positively correlated. These dimensions are negatively correlated with the intention to change the hospital; furthermore, age, professional and organizational seniority have an effect on this relationship. Work engagement fully mediates the relationship between self-efficacy and turnover intention. Results highlight the importance of considering not only job satisfaction, but also self-efficacy and work engagement, in studies on turnover intentions. These findings suggest to implement actions to increase self-efficacy, and especially work engagement, to reduce the voluntary turnover of nursing staff.


Masked auditory thresholds in sciaenid fishes: a comparative study.
Western Atlantic sciaenids comprise a taxonomically diverse teleost family with significant variations in the relationship between the swim bladder and the otic capsule. In this study, the auditory brainstem response (ABR) was used to test the hypothesis that fishes with different peripheral auditory structures (black drum, Pogonias chromis and Atlantic croaker, Micropogonias undulatus) show differences in frequency selectivity. In a black drum the swim bladder is relatively distant from the otic capsule while the swim bladder in Atlantic croaker possesses anteriorly-directed diverticulas that terminate relatively near the otic capsule. Signals were pure tones in the frequency range, 100 Hz to 1.5 kHz, and thresholds were determined both with and without the presence of simultaneous white noise at two intensity levels (124 dB and 136 dB, re: 1 microPa). At the 124 dB level of white noise background, both the black drum and Atlantic croaker showed similar changes in auditory sensitivity. However, in the presence of the 136 dB white noise masker, black drum showed significantly greater shifts in auditory thresholds between 300 and 600 Hz. The results indicate that the two species differ in frequency selectivity since the Atlantic croaker was less susceptible to auditory threshold shifts, particularly at the higher level of masking. This difference may be linked to peripheral auditory mechanisms.


Immunization status of hospitalized preschool children: risk factors associated with inadequate immunization.
The purposes of this study were to determine the accuracy of the immunization histories of hospitalized preschool children, assess the sociodemographic factors associated with delayed immunizations, and interview parents or guardians concerning their views on ways of improving immunization delivery. The immunization status of 215 preschool children admitted to a pediatric hospital was determined by interviewing parents or guardians regarding their children's immunization histories. The patient's immunization records were subsequently reviewed for confirmation. The admitting physician's history also was reviewed to determine whether the patient's immunization status had been noted. Finally, parents or guardians of all children studied were interviewed to assess their views on ways of improving the delivery of immunization services. Only 44% of the 215 preschoolers evaluated were adequately immunized. Among those between 2 and 5 years of age, 52% were fully immunized. Only 17% of those who were inadequately immunized could have been completely updated if given an immunization at discharge. The admitting physician failed to document the immunization status of 22% of the patients. Thirty percent of the parents gave inaccurate information concerning the immunization status of their children. Most parents felt that the provision of transport (30%) or formal remainders (21%) would enhance immunization rates. Multiple regression analysis showed that a history of missed opportunity to immunize, male gender, lack of transportation, and lack of day care attendance were significant predictors of delayed immunization. Resident physicians should be more stringent in documenting the immunization status of all admitted preschoolers so that those found to be delayed could be updated before discharge. A hospital policy of updating underimmunized children at discharge and reporting the immunization status of all discharged patients to their primary care provider could help improve the immunization coverage in this population. Transportation for routine health maintenance and telephone or mailed remainders might further improve the immunization status of inner-city children.


Intracranial cavernous hemangiomas: neuroradiologic review of 36 operated cases.
Neuroradiologic studies in 36 cases of histologically verified intracranial cavernous hemangiomas were reviewed. Radionuclide brain scans were positive in 17 of 19 examinations. Angiography, performed in 35 cases, usually showed an avascular area with absent or moderate mass effect. Capillary blush and/or early draining veins, often mentioned in single case reports, were observed in only seven cases. Computed tomography (18 cases) usually demonstrated a hyperdense, nodular, or irregular lesion without significant mass effect and always enhancing after contrast injection. The combination of a long clinical history of focal epilepsy with computed tomographic and angiographic findings should suggest the diagnosis of cavernous hemangioma. In all cases of so-called spontaneous hematoma with negative angiography, computed tomography should be repeated after a long interval to exclude the presence of a cavernous hemangioma or other cryptic vascular malformation.


Isolation and FTIR-ATR and 1H NMR Characterization of Alginates from the Main Alginophyte Species of the Atlantic Coast of Morocco.
Alginates are widely used as gelling agents in textile print pastes, medical industries, impression material in dentistry, and anticoagulant material in toothpaste. In the present study, the content and spectroscopic characterization (1H NMR and FT-IR) of the sodium alginates were investigated in the eight brown seaweeds Sargassum muticum, Fucus vesiculosus f. volubilis, Carpodesmia tamariscifolia, Bifurcaria bifurcata, Laminaria ochroleuca, Cystoseira humilis, Saccorhiza polyschides, and Fucus guiryi harvested from the NW Atlantic coast of Morocco. The results proved that the most studied algae depicted alginate yields higher than 18% dry weight. The FT-IR analysis showed that the spectra of the extracted alginates exhibited significant similarities to the commercial alginate from Sigma-Aldrich. The 1H NMR spectroscopy indicated that the extracted alginates have a high content of β-d-mannuronic (M) than α-l-guluronic acid (G) with M/G ratio values ranging from 1.04 to 4.41. The homopolymeric fractions FMM are remarkably high compared to the FGG and heteropolymeric fractions (FGM = FMG) especially for F. guiryi, C humilis, C. tamariscifolia, L. ochroleuca, and S. polyschides. Nevertheless, the heteropolymeric fractions (FGM/FMG) are quite abundant in the alginates of S. muticum, F. vesiculosus f. volubilis, and B. bifurcata accounting for more than 52% of the polymer diads. Based on these results, the investigated algal species (except Fucus guiryi and Bifurcaria bifurcata) could be regarded as potential sources of alginates for industrial uses.


Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells.
Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERβ that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ERα-positive breast cancer, is considered as an ERα antagonist and GPER agonist. TAM was shown to possess "off-target" cytotoxicity, not related to ER in various tumor types. The present work was designed to study biological effects of TAM on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL). We have shown that T-ALL cell lines, in contrast to healthy T cells, express only GPER, but not ERα or ERβ. TAM compromised mitochondrial function and reduced the viability and proliferation of Jurkat cells. Additionally, TAM induced autophagy in a GPER-dependent manner. Gene expression profiling revealed the up-regulation of autophagy-related gene ATG5. Interestingly, TAM sensitized Jurkat cells to dexamethasone (DEX) treatment, which may be related to its capacity to cause autophagy. We suggest that TAM-based adjuvant therapy may represent a novel strategy in T-ALL patients handling.


Molecular targets for disrupting leukocyte trafficking during multiple sclerosis.
Autoimmune diseases of the central nervous system (CNS) involve the migration of abnormal numbers of self-directed leukocytes across the blood-brain barrier that normally separates the CNS from the immune system. The cardinal lesion associated with neuroinflammatory diseases is the perivascular infiltrate, which comprises leukocytes that have traversed the endothelium and have congregated in a subendothelial space between the endothelial-cell basement membrane and the glial limitans. The exit of mononuclear cells from this space can be beneficial, as when virus-specific lymphocytes enter the CNS for pathogen clearance, or might induce CNS damage, such as in the autoimmune disease multiple sclerosis when myelin-specific lymphocytes invade and induce demyelinating lesions. The molecular mechanisms involved in the movement of lymphocytes through these compartments involve multiple signalling pathways between these cells and the microvasculature. In this review, we discuss adhesion, costimulatory, cytokine, chemokine and signalling molecules involved in the dialogue between lymphocytes and endothelial cells that leads to inflammatory infiltrates within the CNS, and the targeting of these molecules as therapies for the treatment of multiple sclerosis.


Factors Associated with Pre- and Post-Educational Intervention Knowledge Levels of HPV and Cervical Cancer Among the Male and Female University Students, Northwest Ethiopia.
Human papillomavirus (HPV) infections are sexually transmitted and most frequently associated with cervical cancer in women, but they are also a public health concern in men. There is rising evidence that HPV's role in other cancers, such as anal, vulva, vaginal, penis, head, and neck cancers. The present study aimed to understand the factors associated with HPV and cervical cancer knowledge levels of university students before and after an educational intervention. An Institutional-based cross-sectional study was conducted from October to November 2018. A total of 638 study participants were selected using a simple random multistage sampling technique. A pretested questionnaire was used, consolidated the data, and analyzed with SPSS version 23. Bivariate and multivariate logistic regression analyses were performed to identify which variables were associated with the knowledge levels. Six hundred thirty-eight study participants with a 100% response rate, and the mean age was 21.07 years (±SD, 1.96). Initial awareness of various broad categories was 4.09, and after the intervention, it increased to 23.4, with an average increase of 19.31 at 99% CI, p≤0.001 significance level. Before the educational intervention, students with <21 years of age [6.16, 95% CI: (2.21-17.18)] and ≤2.5 CGPA [3.44, 95% CI: (1.51-7.81)] were less knowledgeable over other counterparts. After educational intervention, the year of study was significantly associated with increased knowledge of overall and different broad categories of cervical cancer and HPV. Year of study, 1st-year students [AOR: 0.27, 95% CI: (0.14-0.51)] over third years and above are less knowledgeable. First-year students and CGPA ≤2.5 were less improved awareness over others. The educational intervention improved more than fourfold increase knowledge on cervical cancer and HPV, and the year of study was a key factor associated with overall improvement. This study suggests that educational intervention effectively strengthens our understanding of the spread of HPV and cervical cancer disease burden.


Cardiac Autonomic System Response to Submaximal Test in Children With Cerebral Palsy.
To describe the heart rate (HR) and heart rate variability at rest, during a submaximal treadmill test and at rest posttreadmill in children with cerebral palsy (CP). Twenty children (6-11 years) with CP participated, who had Gross Motor Function Classification System levels I to III. The HR was monitored for 5 minutes seated, during a submaximal treadmill test, and after 5 minutes rest posttreadmill. Outcome variables were HR and the square root of the mean squared differences of successive differences between adjacent heart beats (RMSSD). HR increased during the last stage of the treadmill test compared with rest. RMSSD was reduced during the last 2 minutes of the treadmill test compared with rest. The HR and RMSSD mean value at the second minute posttest were not significantly different from the pretreadmill rest value. The cardiac system in children with CP responded to the submaximal testing.


CRISPRTarget: bioinformatic prediction and analysis of crRNA targets.
The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are essential for target recognition, and for type III, mismatches in the flanking sequences are important in the antiviral response. In this study, we examine the properties of each class of CRISPR. We use this information to provide a tool (CRISPRTarget) that predicts the most likely targets of CRISPR RNAs (http://bioanalysis.otago.ac.nz/CRISPRTarget). This can be used to discover targets in newly sequenced genomic or metagenomic data. To test its utility, we discover features and targets of well-characterized Streptococcus thermophilus and Sulfolobus solfataricus type II and III CRISPR/Cas systems. Finally, in Pectobacterium species, we identify new CRISPR targets and propose a model of temperate phage exposure and subsequent inhibition by the type I CRISPR/Cas systems.


Association of History of Dizziness and Long-term Adverse Outcomes With Early vs Later Orthostatic Hypotension Assessment Times in Middle-aged Adults.
Guidelines recommend assessing orthostatic hypotension (OH) 3 minutes after rising from supine to standing positions. It is not known whether measurements performed immediately after standing predict adverse events as strongly as measurements performed closer to 3 minutes. To compare early vs later OH measurements and their association with history of dizziness and longitudinal adverse outcomes. This was a prospective cohort study of middle-aged (range, 44-66 years) participants in the Atherosclerosis Risk in Communities Study (1987-1989). Orthostatic hypotension, defined as a drop in blood pressure (BP) (systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg) from the supine to standing position, was measured up to 5 times at 25-second intervals. We determined the association of each of the 5 OH measurements with history of dizziness on standing (logistic regression) and risk of fall, fracture, syncope, motor vehicle crashes, and all-cause mortality (Cox regression) over a median of 23 years of follow-up (through December 31, 2013). In 11 429 participants (mean age, 54 years; 6220 [54%] were women; 2934 [26%] were black) with at least 4 OH measurements after standing, after adjustment OH assessed at measurement 1 (mean [SD], 28 [5.4] seconds; range, 21-62 seconds) was the only measurement associated with higher odds of dizziness (odds ratio [OR], 1.49; 95% CI, 1.18-1.89). Measurement 1 was associated with the highest rates of fracture, syncope, and death at 18.9, 17.0, and 31.4 per 1000 person-years. Measurement 2 was associated with the highest rate of falls and motor vehicle crashes at 13.2 and 2.5 per 1000 person-years. Furthermore, after adjustment measurement 1 was significantly associated with risk of fall (hazard ratio [HR], 1.22; 95% CI, 1.03-1.44), fracture (HR, 1.16; 95% CI, 1.01-1.34), syncope (HR, 1.40; 95% CI, 1.20-1.63), and mortality (HR, 1.36; 95% CI, 1.23-1.51). Measurement 2 (mean [SD], 53 [7.5] seconds; range, 43-83 seconds) was associated with all long-term outcomes, including motor vehicle crashes (HR, 1.43; 95% CI, 1.04-1.96). Measurements obtained after 1 minute were not associated with dizziness and were inconsistently associated with individual long-term outcomes. In contrast with prevailing recommendations, OH measurements performed within 1 minute of standing were the most strongly related to dizziness and individual adverse outcomes, suggesting that OH be assessed within 1 minute of standing.


Functional screening of antibiotic resistance genes from human gut microbiota reveals a novel gene fusion.
The human gut microbiota has a high density of bacteria that are considered a reservoir for antibiotic resistance genes (ARGs). In this study, one fosmid metagenomic library generated from the gut microbiota of four healthy humans was used to screen for ARGs against seven antibiotics. Eight new ARGs were obtained: one against amoxicillin, six against d-cycloserine, and one against kanamycin. The new amoxicillin resistance gene encodes a protein with 53% identity to a class D β-lactamase from Riemerella anatipestifer RA-GD. The six new d-cycloserine resistance genes encode proteins with 73-81% identity to known d-alanine-d-alanine ligases. The new kanamycin resistance gene encodes a protein of 274 amino acids with an N-terminus (amino acids 1-189) that has 42% identity to the 6'-aminoglycoside acetyltransferase [AAC(6')] from Enterococcus hirae and a C-terminus (amino acids 190-274) with 35% identity to a hypothetical protein from Clostridiales sp. SSC/2. A functional study on the novel kanamycin resistance gene showed that only the N-terminus conferred kanamycin resistance. Our results showed that functional metagenomics is a useful tool for the identification of new ARGs.


Levetiracetam Alters Oscillatory Connectivity in Alzheimer's Disease.
Seizures occur at a higher frequency in people with Alzheimer's disease (AD) but overt, clinically obvious events are infrequent. Evidence from animal models and studies in mild cognitive impairment suggest that subclinical epileptic discharges may play a role in the clinical and pathophysiological manifestations of AD. In this feasibility study, the neurophysiological and cognitive effects of acute administration of levetiracetam (LEV) are measured in patients with mild AD to test whether it could have a therapeutic benefit. AD participants were administered low dose LEV (2.5 mg/kg), higher dose LEV (7.5 mg/kg), or placebo in a double-blind, within-subject repeated measures study with EEG recorded at rest before and after administration. After administration of higher dose of LEV, we found significant decreases in coherence in the delta band (1-3.99 Hz) and increases in the low beta (13-17.99 Hz) and the high beta band (24-29.99 Hz). Furthermore, we found trends toward increased power in the frontal and central regions in the high beta band (24-29.99 Hz). However, there were no significant changes in cognitive performance after this single dose administration. The pattern of decreased coherence in the lower frequency bands and increased coherence in the higher frequency bands suggests a beneficial effect of LEV for patients with AD. Larger longitudinal studies and studies with healthy age-matched controls are needed to determine whether this represents a relative normalization of EEG patterns, whether it is unique to AD as compared to normal aging, and whether longer term administration is associated with a beneficial clinical effect.


Epitope approach in molecular imprinting of antibodies.
Herein an approach to prepare molecularly imprinted polymer nanoparticles (nanoMIPs) with specific binding affinity for antibodies is reported. The process relied on the covalent immobilization of the template (whole immunoglobulin G (IgG), Fc domain of human IgG and peptide epitope) onto the surface of a solid support, polymerization and affinity separation of nanoMIPs. The binding between nanoMIPs and their corresponding templates was analyzed and evaluated as being in sub-nanomolar and nano-molar range. The nanoMIPs prepared for Fc domain and epitope demonstrated a specific recognition of both human and goat IgGs, therefore they could be considered as a synthetic analogue of protein A and benefit from its intrinsic stability, short time and low cost of preparation.


Is a specialised training of phonological awareness indicated in every preschool child?
In a prospective study 218 preschool children were enrolled (stratified in 2 training programs, one specialized for phonologic awareness in order to prevent dyslexia, the other consisting in training of general perception) during the last year of kindergarten. After finishing the first grade 131 children were compared in their reading and writing abilities. In the whole group only a slight difference was found between both training modalities concerning their writing abilities. However, children with a history of hearing loss, actual hearing loss or pathologic middle ear findings profited most from the specialized training program compared to the control in their reading abilities. A specialized training program to improve phonologic awareness as a basis for reading and writing in every kindergarten and preschool child seems to be unnecessary. However, children with temporary hearing deficits benefit from such a program. For all other children general perception training may be sufficient.


Passive transport of K+ and Na+ in human red blood cells: sulfhydryl binding agents and furosemide.
Passive transport pathways for K+ and Na+ were studied in fresh human red blood cells (pretreated with ouabain) by measuring unidirectional influxes. The effects of the sulfhydryl binding agents N-ethylmaleimide (NEM) and p-chloromercuribenzene sulfonate (p-CMBS) and the loop diuretic furosemide were studied. Influxes were measured at equimolar K+ and Na+ concentrations (50 mM) with both ions present and also in K+-free or Na+-free media. Some experiments were carried out in Cl--free media (with NO-3 as the substitute). NEM stimulated K+ influx twofold; the stimulation required Cl- but not Na+. NEM inhibited Na+ influx 20%. Furosemide inhibited both K+ and Na+ influxes. All of furosemide-inhibitable Na+ influx required the presence of K+. However 30% of furosemide-inhibitable K+ influx did not require Na+. All of furosemide-inhibitable K+ influx required Cl-. The ratio of Na+-dependent K+ influx to K+-dependent Na+ influx was 3:1. p-CMBS stimulated both Na+ and K+ influxes. K+ influx in p-CMBS cells required neither Na+ nor Cl-. Likewise p-CMBS-promoted Na+ influx did not require K+. These various results are consistent with two Cl--dependent pathways for K+ transport, one requiring Na+ [perhaps (Na + K + Cl) cotransport] and one independent of Na+ [perhaps (K + Cl) cotransport]. The pathways promoted by p-CMBS are probably independent of the apparent cotransport systems.


The case for cautious consumption: NSAIDs in chronic kidney disease.
Strong epidemiological and pathologic evidence associates NSAIDs with kidney disease, both acute and chronic. Hence, the usage of NSAIDs has decreased in patients with, or at risk for, chronic kidney disease (CKD). Coupled with this has been a rise in use of opioids and other non-NSAID alternatives, which do come with significant, and underrecognized, risk of nonrenal adverse events. We review the literature to understand if this shift is appropriate or deleterious. NSAIDs do have a low but tangible risk in causing acute kidney injury, electrolyte imbalances, and increasing blood pressure. However, their role in causing progressive kidney disease is due to long-term usage in high cumulative dosages, and the use of NSAIDs in combination with other agents. Alternatives such as opioids, tramadol, gabapentin and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD. Tradeoffs are inherent in using active pharmaceuticals, and NSAIDs are no exception. Balancing potential benefits with possible adverse effects around pain management should be a part of every conversation for patients with kidney disease.


Are side effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?
Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements, to avoid the strict rules of medicinal products. Side-effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychoactive Δ 9-tetrahydrocannainol (THC). However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the side-effects of CBD products may be residual THC concentrations in the products as contamination, because most of them are based on crude hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 28 food products of the German market containing hemp extract as an ingredient (mostly CBD oils) confirmed this hypothesis: 10 products (36%) contained THC above the lowest observed adverse effects level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe THC levels, full-spectrum hemp extracts as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety must obviously be challenged.


Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer.
Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment. They may drive tumor progression, although the mechanisms involved are still poorly understood. Exosomes have emerged as important mediators of intercellular communication in cancer. They mediate horizontal transfer of microRNAs (miRs), mRNAs and proteins, thus affecting breast cancer progression. Differential expression profile analysis identified three miRs (miRs -21, -378e, and -143) increased in exosomes from CAFs as compared from normal fibroblasts. Immunofluorescence indicated that exosomes may be transferred from CAFs to breast cancer cells, releasing their cargo miRs. Breast cancer cells (BT549, MDA-MB-231, and T47D lines) exposed to CAF exosomes or transfected with those miRs exhibited a significant increased capacity to form mammospheres, increased stem cell and epithelial-mesenchymal transition (EMT) markers, and anchorage-independent cell growth. These effects were reverted by transfection with anti-miRs. Similarly to CAF exosomes, normal fibroblast exosomes transfected with miRs -21, -378e, and -143 promoted the stemness and EMT phenotype of breast cancer cells. Thus, we provided evidence for the first time of the role of CAF exosomes and their miRs in the induction of the stemness and EMT phenotype in different breast cancer cell lines. Indeed, CAFs strongly promote the development of an aggressive breast cancer cell phenotype.


Cytomegalovirus associated haemophagocytic lymphohistiocytosis in the immunocompetent adult managed according to HLH-2004 diagnostic using clinical and serological means only.
Haemophagocytic lymphohistiocytosis (HLH) describes a rare, poorly recognised and under-diagnosed immunopathological syndrome whereby there is a highly stimulated yet ineffective multisystem inflammatory response [1]. I present the first case in English literature of Cytomegalovirus (CMV) associated HLH diagnosed by clinical and serological means, and the fourth case of CMV associated haemophagocytic lymphohistiocytosis in an immunocompetent adult, according to HLH-2004 diagnostic guidelines. I include a literature review of CMV associated HLH in adults and raise awareness of checking serum ferritin in patients who present with a sepsis like syndrome. Additionally, this article discusses the merits of HLH-2004 diagnostic work-up without bone marrow biopsy, using clinical and serological means only. I support the reclassification of HLH alongside the other hyperinflammatory syndromes of SIRS, sepsis, septic shock, and MODS to improve understanding and recognition.


Three-dimensional nano-heterojunction networks: a highly performing structure for fast visible-blind UV photodetectors.
Visible-blind ultraviolet photodetectors are a promising emerging technology for the development of wide bandgap optoelectronic devices with greatly reduced power consumption and size requirements. A standing challenge is to improve the slow response time of these nanostructured devices. Here, we present a three-dimensional nanoscale heterojunction architecture for fast-responsive visible-blind UV photodetectors. The device layout consists of p-type NiO clusters densely packed on the surface of an ultraporous network of electron-depleted n-type ZnO nanoparticles. This 3D structure can detect very low UV light densities while operating with a near-zero power consumption of ca. 4 × 10-11 watts and a low bias of 0.2 mV. Most notably, heterojunction formation decreases the device rise and decay times by 26 and 20 times, respectively. These drastic enhancements in photoresponse dynamics are attributed to the stronger surface band bending and improved electron-hole separation of the nanoscale NiO/ZnO interface. These findings demonstrate a superior structural design and a simple, low-cost CMOS-compatible process for the engineering of high-performance wearable photodetectors.


New MYC IHC Classifier Integrating Quantitative Architecture Parameters to Predict MYC Gene Translocation in Diffuse Large B-Cell Lymphoma.
A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the "percentage of MYC IHC-positive nuclei" methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts "permanent overexpressed MYC protein status," it might identify nontranslocation-related chromosomal anomalies missed by FISH.


Surgery for acute gallbladder disease in Sweden 1989-2006--a register study.
Since early 1970s, prospective randomized controlled trials have emphasized the advantages of early cholecystectomy in patients with acute cholecystitis, compared to elective delayed cholecystectomy. The aim of this investigation was to study surgery for acute gallbladder disease in Sweden during a 15-year period when open cholecystectomy was replaced by a laparoscopic procedure. Data from the Swedish National Patient Register and the Cause of Death Register 1988-2006 comprising hospital stays with a primary diagnosis of gallbladder/gallstone disease in Sweden were retrieved. Patients were analyzed with reference to timing of cholecystectomy, length of hospital stay, and mortality. Emergency cholecystectomy at index (first) admission or at readmission within 2 years of index admission was performed in 32.2% and 6.1% of patients, respectively. Elective cholecystectomy within 2 years of index admission was performed in 20.3% patients, whereas 41.3% of all patients did not undergo cholecystectomy within 2 years. Standardized mortality ratio did not significantly change during the audit period. Total hospital stay (days at index stay and subsequent stay(s) for biliary diagnoses within 2 years) was shorter for patients who had emergency cholecystectomy at first admission compared to patients with later or no cholecystectomy within 2 years. Around 30% of patients with acute gallbladder disease were operated with cholecystectomy during the first admission with no time trend from 1990 through 2004. A total of 40% of patients with acute gallbladder disease were not cholecystectomized within 2 years. Analysis of outcome of long-term conservative treatment is warranted.


Changes in proteoglycan biosynthesis following leukocyte elastase treatment of bovine articular cartilage in culture.
Treatment of bovine articular cartilage in culture with a low molecular weight elastase purified from rabbit polymorphonuclear leukocytes resulted in degradation and release of proteoglycans from the tissue, coupled with a prolonged inhibition of proteoglycan biosynthesis. These observations are consistent with those seen in experimental arthritis induced in rabbits. Comparison of the size of the proteoglycan degradation products extracted from elastase-treated cartilage in culture with that from arthritic cartilage showed marked similarities. The results strongly suggest that leukocyte elastase is a contributing factor in proteoglycan degradation and inhibition of synthesis in inflammatory joint disease.


Cell clarification and size separation using continuous countercurrent magnetophoresis.
Nonmagnetic microparticles (e.g., cells, polymer beads) immersed in a magnetic fluid (ferrofluid) under a nonuniform magnetic field experience a magnetophoretic force in the direction of decreasing magnetic field strength. This phenomenon was exploited in the development of a continuous magnetophoretic countercurrent separation for the removal and concentration of micron-sized particles from aqueous suspensions, and in particular as a viable approach for cell clarification of raw fermentation broth. A magnetic fluid is added to the cell suspension, the mixture is introduced to the magnetic separator, which consists of an open flow tube passing between pairs of magnets that move in a direction counter to the flow of the suspension. The cells are pushed ahead of the magnet pairs owing to the magnetophoretic forces acting on them, collected in a tube upstream of the feed injection point, and removed as a concentrated suspension for further treatment.