Benign Paroxysmal Positional Vertigo: Management and Its Impact on Falls.
Benign paroxysmal positional vertigo (BPPV) is the most common cause of dizziness in the elderly. This has been identified as a risk factor in falls. Falls are the leading cause of disability and the leading cause of death from injury among people over 75 in the UK. We assessed the effect of BPPV treatment on falls in an elderly population by retrospectively reviewing one unit's experience of BPPV management over an 8-year period from June 2008 to June 2016. We specifically assessed patients who were referred for the primary reason of falls and were aged over 65 years. These patients were evaluated and treated with particle repositioning maneuvers if their positional tests were positive. The frequency of falls prior to their visit and at 6-month clinic follow-up were reviewed. The total number of falls in the cohort reduced significantly ( P < .0001) after the procedure, from 128 to 46 falls (64% reduction). Associated comorbidities were also evaluated in this group. A prompt and effective treatment of BPPV is prudent to prevent devastating falls in older people in our communities.


A magnetron sputtering system for the preparation of patterned thin films and in situ thin film electrical resistance measurements.
We describe a versatile three gun magnetron sputtering system with a custom made sample holder for in situ electrical resistance measurements, both during film growth and ambient changes on film electrical properties. The sample holder allows for the preparation of patterned thin film structures, using up to five different shadow masks without breaking vacuum. We show how the system is used to monitor the electrical resistance of thin metallic films during growth and to study the thermodynamics of hydrogen uptake in metallic thin films. Furthermore, we demonstrate the growth of thin film capacitors, where patterned films are created using shadow masks.


Active cytomegalovirus infection in patients with atopic dermatitis.
Atopic dermatitis (AD) is a complex immunologic skin disorder that is expressed when genetically predisposed individuals are exposed to certain environmental stimuli. Inspite of the high prevalence of cytomegalovirus (CMV) infection and its potent immunomodulatory activities, the relation of CMV to AD is still poorly understood and is still to be clarified. The aim of the present study was to evaluate the frequency of active CMV infection in patients with AD and its possible etiologic role in the pathogenesis of the disease. Also, we tried to find if a relation between active CMV infection and disease severity exists. The present study was carried on 31 patients with AD with various degrees of disease severity. Ten apparently healthy subjects were enrolled in the study as a control group. Anti CMV IgG antibodies were estimated by quantitative enzyme immunoassay to discriminate between recent CMV infection and CMV reactivation. Active CMV infection was diagnosed by using nested PCR to detect CMV DNA in the sera of the studied subjects. The detection rate of CMV genome was higher in patients with AD in comparison to the control group. Cytomegalovirus genome was detected in the sera of 52% (16/31) of patients with AD (87.5% of them were seropositive for anti-CMV IgG antibodies). On the other hand no CMV DNA was detected in any of the serum samples of the control subjects. The difference was statistically significant. No significant relation was found between active CMV infection and disease severity. Also, no significant statistical difference was found between the two studied groups as regards the prevalence of latent CMV infection. In addition, no significant difference was detected between anti-CMV IgG antibody levels in all seropositive subjects. Our results denote that active subclinical CMV infection is more frequent in patients with AD and may have possible immunomodulatory role in the etiopathogenesis of AD but it is not related to disease severity.


[Video-assisted Thoracoscopic Pericardial Fenestration for Pericardial Effusion in a Patient with Crow-Fukase Syndrome].
A 65-year-old woman was referred to our department with recurrent pericardial effusion. Her serum vascular endothelial growth factor was high, serum M-protein was positive, and nerve conduction velocity of extremities was decreased. Therefore, she was diagnosed with Crow-Fukase (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes:POEMS) syndrome, which is characterized by the presence of plasma cell dyscrasia with them. We performed video-thoracoscopic pericardial fenestration with 4×4 cm window. The postoperative course was uneventful, and the pericardial effusion completely disappeared. Video-assisted thoracoscopic pericardial fenestration was a safe and effective treatment for recurrent pericardial effusion.


The origins of gene instability in yeast.
Two unstable mutations at the his4 locus of yeast are due to the insertion of the transposable elements Ty912 and Ty917 into the his4 regulatory region. The two transposons are related, one being derived from the other by a substitution of 4000 base pairs of DNA. Element Ty912 includes identical terminal repeats, whereas the terminal repeats of Ty917 are not identical. Transposition of Ty912 or Ty917 generates 5-base-pair duplications of the target DNA at either end of the element. Expression and reversion of a his4 gene containing Ty912 or Ty917 is controlled by three unlinked regulatory genes. The properties of these regulatory genes are similar to those described for the controlling elements in maize.


Loss of a Cardiolipin Synthase in Helicobacter pylori G27 Blocks Flagellum Assembly.
Helicobacter pylori uses a cluster of polar, sheathed flagella for motility, which it requires for colonization of the gastric epithelium in humans. As part of a study to identify factors that contribute to localization of the flagella to the cell pole, we disrupted a gene encoding a cardiolipin synthase (clsC) in H. pylori strains G27 and B128. Flagellum biosynthesis was abolished in the H. pylori G27 clsC mutant but not in the B128 clsC mutant. Transcriptome sequencing analysis showed that flagellar genes encoding proteins needed early in flagellum assembly were expressed at wild-type levels in the G27 clsC mutant. Examination of the G27 clsC mutant by cryo-electron tomography indicated the mutant assembled nascent flagella that contained the MS ring, C ring, flagellar protein export apparatus, and proximal rod. Motile variants of the G27 clsC mutant were isolated after allelic exchange mutagenesis using genomic DNA from the B128 clsC mutant as the donor. Genome resequencing of seven motile G27 clsC recipients revealed that each isolate contained the flgI (encodes the P-ring protein) allele from B128. Replacing the flgI allele in the G27 clsC mutant with the B128 flgI allele rescued flagellum biosynthesis. We postulate that H. pylori G27 FlgI fails to form the P ring when cardiolipin levels in the cell envelope are low, which blocks flagellum assembly at this point. In contrast, H. pylori B128 FlgI can form the P ring when cardiolipin levels are low and allows for the biosynthesis of mature flagella.IMPORTANCEH. pylori colonizes the epithelial layer of the human stomach, where it can cause a variety of diseases, including chronic gastritis, peptic ulcer disease, and gastric cancer. To colonize the stomach, H. pylori must penetrate the viscous mucous layer lining the stomach, which it accomplishes using its flagella. The significance of our research is identifying factors that affect the biosynthesis and assembly of the H. pylori flagellum, which will contribute to our understanding of motility in H. pylori, as well as other bacterial pathogens that use their flagella for host colonization.


Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: the possible role of ponatinib.
In spite of the proven efficacy of the tyrosine kinase inhibitor (TKI), imatinib, in chronic myeloid leukemia (CML), many patients develop intolerance and discontinue therapy in the long-term. Second-generation TKIs (dasatinib, nilotinib, bosutinib) and the third-generation TKI, ponatinib, have added opportunities but also complexity in the settings of CML treatment. Different definitions of intolerance have been used through several clinical trials, making the published data non homogenous. In most cases, only the severity of acute adverse events (AEs), graded by conventional scales such as Common Terminology Criteria for Adverse Events, was reported. Limited attention to long-term events or more in general, to the impact of AEs on patient quality of life (QoL), remains a problem. Ponatinib is active against all BCR-ABL1 mutants, including T315I, and is widely used to treat patients who developed resistance to other TKIs in any CML phase; however, only limited data is available on the possible role of ponatinib for intolerant patients. We review the different definitions of intolerance used in sponsored trials and in clinical practice, and we discuss how such definitions impact on the management of AEs. We summarize how to evaluate QoL during treatment with TKIs and how to include ponatinib among possible option for intolerant patients.


Child Intelligence and Reductions in Water Arsenic and Manganese: A Two-Year Follow-up Study in Bangladesh.
Arsenic (As) exposure from drinking water is associated with modest intellectual deficits in childhood. It is not known whether reducing exposure is associated with improved intelligence. We aimed to determine whether reducing As exposure is associated with improved child intellectual outcomes. Three hundred three 10-year-old children drinking from household wells with a wide range of As concentrations were enrolled at baseline. In the subsequent year, deep community wells, low in As, were installed in villages of children whose original wells had high water As (WAs ≥ 50 μg/L). For 296 children, intelligence was assessed by WISC-IV (Wechsler Intelligence Scale for Children, 4th ed.), with a version modified for the study population, at baseline and approximately 2 years later; analyses considered standardized scores for both Full Scale IQ and Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed Indices. Creatinine-adjusted urinary arsenic (UAs/Cr), blood As (BAs), and blood manganese (BMn) were assessed at both times. UAs/Cr concentrations declined significantly by follow-up for both the high (≥ 50 μg/L) and low (< 50 μg/L) WAs subgroups. At baseline, adjusting for maternal age and intelligence, plasma ferritin, head circumference, home environment quality, school grade, and BMn, UAs/Cr was significantly negatively associated with Full Scale IQ, and with all Index scores (except Processing Speed). After adjustment for baseline Working Memory scores and school grade, each 100-μg/g reduction in UAs/Cr from baseline to follow-up was associated with a 0.91 point increase in Working Memory (95% CI: 0.14, 1.67). The change in UAs/Cr across follow-up was not significantly associated with changes in Full Scale IQ or Index scores. Installation of deep, low-As community wells lowered UAs, BAs, and BMn. A greater decrease in UAs/Cr was associated with greater improvements in Working Memory scores, but not with a greater improvement in Full Scale IQ. Wasserman GA, Liu X, Parvez F, Factor-Litvak P, Kline J, Siddique AB, Shahriar H, Uddin MN, van Geen A, Mey JL, Balac O, Graziano JH. 2016. Child intelligence and reductions in water arsenic and manganese: a two-year follow-up study in Bangladesh. Environ Health Perspect 124:1114-1120; http://dx.doi.org/10.1289/ehp.1509974.


Single-Particle Cryo-EM at Crystallographic Resolution.
Until only a few years ago, single-particle electron cryo-microscopy (cryo-EM) was usually not the first choice for many structural biologists due to its limited resolution in the range of nanometer to subnanometer. Now, this method rivals X-ray crystallography in terms of resolution and can be used to determine atomic structures of macromolecules that are either refractory to crystallization or difficult to crystallize in specific functional states. In this review, I discuss the recent breakthroughs in both hardware and software that transformed cryo-microscopy, enabling understanding of complex biomolecules and their functions at atomic level.


Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study.
Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis. In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test. There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated. Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis.


Gamma activity in schizophrenia: evidence of impaired network binding?
Gamma ('40 Hz') rhythms may play a role in the integration of sensory processing activity. Impaired temporal integration may be a key feature of the associated disturbances in schizophrenia. This is the first study to examine the time course of Gamma activity induced in response to stimuli in this disorder. Gamma activity induced in response to task-relevant and irrelevant auditory oddball stimuli was examined in 35 medicated schizophrenics and 35 age- and gender-matched normal controls. We employed a moving Welch window with short time FFT to examine the time course of Gamma amplitude. The amplitude spectrum for each time point was de-trended to eliminate any contribution of broad spectrum activity (EEG or EMG) to Gamma amplitude. For targets, schizophrenics showed a significant decrease in post-stimulus Gamma response amplitude in left hemisphere and frontal sites and an increase in right hemisphere and parieto-occipital sites (P<0.0009). The abnormalities correlated with PANSS general symptom scores. In the non-targets (at a different latency), schizophrenics showed a widespread Gamma decrease (P<0.0005). The Gamma findings in non-targets may reflect an abnormality in appropriately processing irrelevant stimuli. This could result in defective processing of the context (integration) of relevant target information.


Epidemiology and heterogeneity of hypertension in Iran: a systematic review.
There are many descriptive studies on hypertension in Iran, mostly assessing the prevalence of the disease and its associations with various risk factors. In order to gain a better insight into the epidemiology of hypertension in Iran and its heterogeneity around the country, we systematically reviewed all available studies and analyzed their findings using meta-analysis methods. All published papers in Iranian and international journals, final reports of research projects, papers presented in relevant congresses, and also all dissertations of medical students were reviewed using standard keywords. Studies published during 1996 - 2004, which met the eligibility criteria were entered into meta-analysis. We found 38 studies, of which 29 were eligible with a total sample size of 93,661 subjects. Also, we accessed the results of a very large national survey, which reported the prevalence of hypertension in 27 provinces. Our estimation for the overall prevalence of hypertension in 30 - 55 and >55-year-old population were around 23% and 50%, respectively. The prevalence in men was 1.3% less than that in women (P<0.0001). The mean diastolic blood pressure in men was 0.62 mmHg less than that in women while the mean systolic blood pressure was 0.67 mmHg greater.We found a sharp increase in the prevalence of hypertension by age, and also greater risk in females. It seems that the overall prevalence of hypertension in Iran is considerable. Iranian health system should pay more attention to control and treatment of hypertension in general population.


Cruciate and posterolateral corner injuries in the athlete: clinical and magnetic resonance imaging features.
With an increasing number of people participating in recreational and competitive sporting activities, sports-related injuries of the knee and knee ligaments have increased in incidence. The extent and severity of such injuries may have important implications with regard to potential return to athletic pursuits as well as impacting upon activities of daily life. This article discusses the MR imaging and clinical features of sports-related injuries of the cruciate ligaments and posterolateral corner of the knee, highlighting the implications of such injuries on joint function. MR imaging has the potential to accurately identify these ligamentous injuries, as well as other potential associated combined injuries of the knee, with information from MR imaging examination assisting in decision-making and planning with regard to potential clinical and/or surgical patient management.


Gibberellins and stem growth in Arabidopsis thaliana. Effects of photoperiod on expression of the GA4 and GA5 loci.
Arabidopsis thaliana (L.) Heynh. is a quantitative long-day (LD) rosette plant in which stem growth is mediated by gibberellins (CAs). Application of GAs to plants in short-day (SD) conditions resulted in rapid stem elongation and flower formation, with GA4 and GA9 being equally effective, and GA1 showing lower activity. The effects of photoperiod on the levels of endogenous GAs were measured by combined gas chromatography-mass spectrometry with selected ion monitoring. When plants were transferred from SD to LD conditions there was a slight decrease in the level of GA53 and an increase in the levels of C19-GAs, GA9, GA20, GA1, and GA8, indicating that GA 20-oxidase activity is stimulated in LD conditions. Expression of GA5, which encodes GA 20-oxidase, was highest in elongating stems and was correlated with the rate of stem elongation. By contrast, GA4, which encodes 3 beta-hydroxylase, showed low expression in stems and its expression was not correlated with the rate of stem elongation. We conclude that stem elongation in LD conditions is at least in part due to increased expression of GA5, whereas expression of GA4 is not under photoperiodic control.


Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives.
Anaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristics of MCT assays in anaphylaxis has been variable in previous studies, due to multiple factors including differences in the definition of anaphylaxis, methods of MCT interpretation, clinical setting of anaphylaxis, causative agents, and timing of blood sample. An international consensus equation for MCT to interpret mast cell activation has been proposed and recently validated in the context of peri-operative anaphylaxis during general anesthesia. There has been an interest in the detection of newer biomarkers in anaphylaxis including platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, and CCL-2. The key determinants of an ideal biomarker in anaphylaxis are half-life, sample handling and processing requirements, and cost. There may be a role for metabolomics and systems biology in the exploration of novel biomarkers in anaphylaxis. Future studies applying these approaches might provide greater insight into factors determining severity, clinical risk stratification, identification of mast cell disorders and improving our understanding of this relatively complex acute immunological condition. Post mortem MCT evaluation is used in Forensic Medicine during autopsy for cases involving sudden death or suspected anaphylaxis. Interpretation of post mortem MCT is challenging since there is limited published evidence and the test is confounded by multiple variables largely linked to putrefaction and site of sampling. Thus, there is no international consensus on a reference range. In this state of the art review, we will focus on the practical challenges in the laboratory diagnosis of anaphylaxis and critically appraise (a) performance characteristics of MCT in anaphylaxis in different clinical scenarios (b) the role for novel biomarkers and (c) post mortem MCT and its role in fatal anaphylaxis.


Peyer's patch M cells derived from Lgr5(+) stem cells require SpiB and are induced by RankL in cultured "miniguts".
Peyer's patches consist of domains of specialized intestinal epithelium overlying gut-associated lymphoid tissue (GALT). Luminal antigens reach the GALT by translocation through epithelial gatekeeper cells, the so-called M cells. We recently demonstrated that all epithelial cells required for the digestive functions of the intestine are generated from Lgr5-expressing stem cells. Here, we show that M cells also derive from these crypt-based Lgr5 stem cells. The Ets family transcription factor SpiB, known to control effector functions of bone marrow-derived immune cells, is specifically expressed in M cells. In SpiB(-/-) mice, M cells are entirely absent, which occurs in a cell-autonomous fashion. It has been shown that Tnfsf11 (RankL) can induce M cell development in vivo. We show that in intestinal organoid ("minigut") cultures, stimulation with RankL induces SpiB expression within 24 h and expression of other M cell markers subsequently. We conclude that RankL-induced expression of SpiB is essential for Lgr5 stem cell-derived epithelial precursors to develop into M cells.


A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells.
An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials. Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy. Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent. Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin.


A study of rDNA magnification phenomenon in a repair-recombination deficient mutant of Drosophila melanogaster.
The rDNA magnification process consists of a rapid and inheritable rDNA increase occurring in bobbed males: in a few generations the bb loci acquire the wild-type rDNA value and reach a bb+ phenotype.--We have analyzed the rDNA magnification process in the repair-recombination-deficient mutant mei9a, both at the phenotypical and rDNA content levels. In mei9a bb double mutants the recovery of bb+ phenotype is strongly disturbed and the rDNA redundancy value fails to reach the wild-type level. The strong effect of this meiotic mutation on rDNA magnification suggests a close relationship between this phenomenon and the repair-recombination processes.


Use of Iodine-131 to Tellurium-132 Ratios for Assessing the Relationships between Human Inhaled Radioactivity and Environmental Monitoring after the Accident in Fukushima.
Significant differences in findings were seen between the intake amounts of iodine-131 that were derived from direct measurements and the estimated intake from environmental monitoring data at the Fukushima accident. To clarify these discrepancies, we have investigated the iodine-131 and tellurium-132 body burdens of five human subjects, who after being exposed to a radioactive plume, underwent 21.5 h whole body counter measurements at Fukui Prefectural Hospital, so clear intake scenario and thyroid counter measurement data were available. To determine the iodine-131 and tellurium-132 body burdens, we introduced a new method of whole body counter calibration composed of a self-consistent approach with the time-dependent correction efficiency factors concept. The ratios of iodine-131 to tellurium-132, ranging from 0.96 ± 0.05 to 2.29 ± 0.38, were consistent with results of the environmental measurements. The 24 h iodine uptake values ranging from 12.1-16.0% were within euthyroid range in Japanese people. These results suggest, even if the relatively low thyroid iodine uptake in the Japanese population was taken into consideration, that there is no doubt about the consistency between direct measurements and environmental monitoring data. Adequate intake scenario is suggested to be principally important to estimate the inhaled radioactivity in areas in or around nuclear accidents.


Observing Solid-State Formation of Oriented Porous Functional Oxide Nanowire Heterostructures by in Situ TEM.
Transition metal oxide nanowires have attracted extensive attention because of their physical characteristics. Among them, ZnO nanowires have great potential. Due to the multifunctional properties of ZnO, devices built using ZnO-based heterostructures always perform well. In this study, interesting diffusion behavior between ZnO nanowires and Fe metal was observed by using in situ transmission electron microscopy. ZnO nanowires and Fe metal were annealed under ultrahigh vacuum (UHV) conditions at 800 K. By controlling the annealing time for the solid-state diffusion, porous Fe3O4 and unique ZnO/porous Fe3O4 nanowire heterostructures were formed. As-formed porous Fe3O4 nanowires with voids can be divided into two types by appearance: plate-like voids and zigzag-like hollow voids. From high-resolution transmission electron microscopy (HRTEM) images and fast Fourier transform (FFT) diffraction patterns, we found that plate-like voids formed along the {111} plane, which was the close-packed plane of Fe3O4, and that zigzag-like hollow voids formed along the {111}/{022} planes. Moreover, a transition region existed during diffusion, with a parallel relationship found between the Fe3O4 crystal with plate-like voids and the ZnO crystal. A sharp interface was determined to exist between the Fe3O4 crystal with zigzag-like hollow voids and ZnO. These oriented porous Fe3O4/ZnO axial nanowire heterostructures exhibited a unique appearance and interesting formation behavior. Furthermore, the structures had a high surface-area-to-volume ratio, which is promising for sensing applications.


Genetic polymorphisms and serum concentrations of adiponectin and resistin in anorexia nervosa and healthy controls - pilot study.
A possible role of adipokines in the regulation of body weight in patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes encoding adiponectin and resistin in AN have not been widely assessed, yet. 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T polymorphisms in adiponectin and RETN c.62G>A, RETN c.-180C>G in resistin genes in AN patients and control group (C) 2) Analysis of correlation between these polymorphisms and serum ADP or RETN. We examined 67 AN girls and 38 C aged 11-18. Analyses of polymorphisms in ADIPOQ and RETN genes were performed using RFLP method and adiponectin and resistin serum levels - with commercially available ELISA kits. In AN subjects, TT genotype in ADIPOQ c.276 polymorphism as well as GG genotype of RETN c.-180 were significantly more frequent than in CG. In ADIPOQ c.45 polymorphic site, TT alleles were the most frequent in both examined groups. In RETN c.62 GA and GG alleles distribution did not differ between the groups and the most frequently observed genotype was GG. The mean serum adiponectin level in AN was significantly higher and resistin - lower than in controls. There were no statistically significant relationships between serum adiponectin and resistin levels and allele frequency in polymorphisms ADIPOQ c.276 as well as RETN c.-180 in the examined groups. Differences in genotype frequencies of ADIPOQ c.276 and RETN c.-180 suggest a need for studies on a larger cohort of patients with AN.


An investigation of irreproducibility in maximum likelihood phylogenetic inference.
Phylogenetic trees are essential for studying biology, but their reproducibility under identical parameter settings remains unexplored. Here, we find that 3515 (18.11%) IQ-TREE-inferred and 1813 (9.34%) RAxML-NG-inferred maximum likelihood (ML) gene trees are topologically irreproducible when executing two replicates (Run1 and Run2) for each of 19,414 gene alignments in 15 animal, plant, and fungal phylogenomic datasets. Notably, coalescent-based ASTRAL species phylogenies inferred from Run1 and Run2 sets of individual gene trees are topologically irreproducible for 9/15 phylogenomic datasets, whereas concatenation-based phylogenies inferred twice from the same supermatrix are reproducible. Our simulations further show that irreproducible phylogenies are more likely to be incorrect than reproducible phylogenies. These results suggest that a considerable fraction of single-gene ML trees may be irreproducible. Increasing reproducibility in ML inference will benefit from providing analyses' log files, which contain typically reported parameters (e.g., program, substitution model, number of tree searches) but also typically unreported ones (e.g., random starting seed number, number of threads, processor type).


HIV leucoencephalopathy and TNFalpha expression in neurones.
Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor alpha (TNFalpha), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. To examine the clinical/neuroradiological features of HIVL and the expression of TNFalpha in HIVL. Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry. Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNFalpha was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNFalpha expression in neurones of the frontal cortex and basal ganglia. This study provides the first demonstration of staining for TNFalpha in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNFalpha.


The Mass Incarceration Trauma Framework: A Conceptual Model for Understanding Trauma among Individuals Who Experience Incarceration.
The Mass Incarceration Trauma (MIT) framework is a conceptual model for understanding the role of trauma in the lives of individuals who experience incarceration in the United States. This population faces poverty, violence, and discrimination across the life span. The MIT framework is guided by an ecological systems perspective, a foundational theoretical approach in social work that recognizes that effective assessment and intervention require an understanding of the complex contexts in which individuals live. The MIT framework presents the cumulative trauma exposures commonly faced by this population before, during, and after incarceration at the individual, social, environmental, and historical levels. Because traumatic stress undermines health and daily functioning, it is essential that interventions for this population address both the ongoing risk for trauma exposure and the consequences of multiple, repeated past exposures across ecological systems. It is to be hoped that a new and fundamental focus on the poverty, contexts of violence, and lifetime disadvantages experienced by those who cycle through prisons in the United States might reframe the question of how our society should prevent and respond to crime as well as respond to those swept into the criminal justice system.


Testing a vaccine candidate against Hepatitis C virus designed by combinatorial optimization.
This paper presents a new procedure for vaccine design against highly variable viruses such as Hepatitis C. The procedure uses an optimization algorithm to design vaccines that maximize the coverage of epitopes across different virus variants. Weighted epitopes based on the success ratio of immunological assays are used to prioritize the selection of epitopes for vaccine design. The procedure was successfully applied to design DC vaccines loaded with two HCV peptides, STG and DYP, which were shown to be safe, immunogenic, and able to induce significant levels of anti-viral cytokines, peptide-specific cellular immune responses and IgG antibodies. The procedure could potentially be applied to other highly variable viruses that currently lack effective vaccines.


Factors affecting trauma center utilization in Illinois.
The Illinois Trauma System has served as a prototype for many of the advanced emergency medical services systems developed during the past decade. The Illinois Trauma Study uses a cross-sectional research design to assess the trauma patient utilization patterns at hospitals in Illinois. Data were collected from 33 Trauma Centers and 43 nonsystem hospitals for the time interval July 1973-June 1974. Results indicated that 45.5 per cent of patients admitted with specified trauma conditions were hospitalized at Trauma Centers. When adjustment is made for differences in the size of hospitals, a 50 per cent excess in patient capture is found at Trauma Centers. This excess utilization found in Trauma Centers for this sample of trauma victims was not found among all patients admitted to these hospitals. Factors found to be associated with high Trauma Center use are race (high use among nonwhites), injury severity, evening admission to hospital and vehicular injury. Also, approximately two thirds of trauma patients that were admitted to intensive care units or transferred from other hospitals were hospitalized at Trauma Centers.


Where are the bodies? A transnational examination of state violence and its consequences.
This special issue of The Public Historian will examine what is a pressing, pervasive, traumatic, and very public contemporary issue in which history and historians are heavily involved in many countries around the globe. Authors will investigate a range of issues around the state involvement in death, including the role of the state as perpetrator and its responsibilities to the victims and their families; the process and significance of exhumation, of identification, and of repatriation; the status of refugees and displaced peoples who die when legally stateless and so without state protection; the differing transnational stances in tracing and punishing the perpetrators; the fraught issue of personal and official reparation; and the role and efficacy of international justice.


The spinal trigeminal nucleus--considerations on the structure of the nucleus caudalis.
The caudal part (nucleus caudalis) of the spinal trigeminal nucleus is considered to be the site of the second order neurons of the nociceptive pathways of the face. Recent studies have supported the co-participation in these circuits of the oral part of the same nucleus (nucleus oralis). The aims of the present study are: 1) to determine the morphology of the nucleus caudalis in human preparates; 2) to consider whether there is any structural basis for the pathways of signal transmission observed in animal experiments; 3) to provide evidence-based support for further consideration on the orofacial pathways. The studies were made using the Bielschowsky silver staining technique (on blocks) applied to drawn pieces of brainstems from human cadavers. On the sections the outer laminae of the nucleus are distinguishable, while the inner part hardly exposes any laminar configuration on transverse cuts. A marginal plexus with small polygonal or rounded small cells appears configured in 3 parts, namely dorsal, intermediate and ventral. Outer to the marginal plexus a clear band marks it off from the interstitial plexus, which appears more delicate. Within the marginal plexus is substantia gelatinosa with rare randomly distributed small or medium-sized cells. The inner magnocellular layers consist of clusters of small cells specifically allocated to fibre bundles, isolated small cells and large cells, pear-shaped or fusiform, appearing either bipolar or multipolar. The marginal and interstitial plexuses can represent the framework for modulation and vertical signal transmission within the spinal trigeminal nucleus, while the magnocellular layers seem to be mainly responsible for contralateral projection. It seems that the outer laminae of the spinal trigeminal nucleus may represent the receiver and the inner laminae the transmitter of the signal on the trigeminal pathway at brainstem level.


Enhancing EEG Artifact Removal Efficiency by Introducing Dense Skip Connections to IC-U-Net.
Electroencephalographic (EEG) data is considered contaminated with various types of artifacts. Deep learning has been successfully applied to developing EEG artifact removal techniques to increase the signal-to-noise ratio (SNR) and enhance brain-computer interface performance. Recently, our research team has proposed an end-to-end UNet-based EEG artifact removal technique, IC-U-Net, which can reconstruct signals against various artifacts. However, this model suffers from being prone to overfitting with a limited training dataset size and demanding a high computational cost. To address these issues, this study attempted to leverage the architecture of UNet++ to improve the practicability of IC-U-Net by introducing dense skip connections in the encoder-decoder architecture. Results showed that this proposed model obtained superior SNR to the original model with half the number of parameters. Also, this proposed model achieved comparable convergency using a quarter of the training data size.


The basic helix loop helix transcription factor Twist1 is a novel regulator of ATF4 in osteoblasts.
Parathyroid hormone (PTH) is an essential regulator of endochondral bone formation and an important anabolic agent for the reversal of bone loss. PTH mediates its functions in part by regulating binding of the bone-related activating transcription factor 4 (ATF4) to the osteoblast-specific gene, osteocalcin. The basic helix-loop-helix (bHLH) factors Twist1 and Twist2 also regulate osteocalcin transcription in part through the interaction of the C-terminal "box" domain in these factors and Runx2. In this study, we discovered a novel function of PTH: its ability to dramatically decrease Twist1 transcription. Since ATF4 is a major regulator of the PTH response in osteoblasts, we assessed the mutual regulation between these factors and determined that Twist proteins and ATF4 physically interact in a manner that affects ATF4 DNA binding function. We mapped the interaction domain of Twist proteins to the C-terminal "box" domain and of ATF4, to the N-terminus. Furthermore, we demonstrate that Twist1 overexpression in osteoblasts attenuates ATF4 binding to the osteocalcin promoter in response to PTH. This study thus identifies Twist proteins as novel inhibitory binding partners of ATF4 and explores the functional significance of this interaction.


Ultrafast Hole Transfer and Carrier Transport Controlled by Nanoscale-Phase Morphology in Nonfullerene Organic Solar Cells.
Nonfullerene acceptors (NFAs) have attracted great attention in high-efficiency organic solar cells (OSCs). While the effect of molecular properties including structures and energetics on charge transfer has been extensively investigated, the effect of macroscopic-phase properties is yet to be revealed. Here we have performed a correlation study of the nanoscale-phase morphology on the photoexcited hole transfer (HT) process and photovoltaic performance by combining ultrafast spectroscopy with high temporal resolution and photo-induced force microscopy (PiFM) with high spatial and chemical resolution. In PM6/IT-4F, we observe biphasic HT behavior with a minor ultrafast (<100 fs) interfacial process and a major diffusion-mediated HT process until ∼100 ps, which depends strongly on phase segregation. Because of the interplay between charge transfer and transport, a compromised domain size of 20-30 nm for NFAs shows the best performance. This study highlights the critical role of phase morphology in high-efficiency OSCs.


Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism.
Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension.


A Sarcocystis sp.-like protozoan and concurrent canine distemper virus infection associated with encephalitis in a raccoon (Procyon lotor).
A raccoon (Procyon lotor) with signs of weakness was captured in upstate New York (USA). Despite attempted care in a rehabilitation facility, the animal died and was examined because of suspected infectious neurologic disease. The cerebrum had a marked, locally extensive, neutrophilic, necrotizing encephalitis with numerous associated intralesional protozoal organisms, and a moderate to marked multifocal perivascular nonsuppurative meningoencephalitis. Based on morphology and immunohistochemical staining, the organism was a Sarcocystis sp.-like protozoan. Rabies antigen and canine distemper virus (CDV) inclusions were not detected. However, the animal was positive for canine distemper virus based on peroxidase anti-peroxidase staining.


Performance Differences Using a Vibro-Tactile P300 BCI in LIS-Patients Diagnosed With Stroke and ALS.
Patients with locked-in syndrome (LIS) are typically unable to move or communicate and can be misdiagnosed as patients with disorders of consciousness (DOC). Behavioral assessment scales are limited in their ability to detect signs of consciousness in this population. Recent research has shown that brain-computer interface (BCI) technology could supplement behavioral scales and allows to establish communication with these severely disabled patients. In this study, we compared the vibro-tactile P300 based BCI performance in two groups of patients with LIS of different etiologies: stroke (n = 6) and amyotrophic lateral sclerosis (ALS) (n = 9). Two vibro-tactile paradigms were administered to the patients to assess conscious function and command following. The first paradigm is called vibrotactile evoked potentials (EPs) with two tactors (VT2), where two stimulators were placed on the patient's left and right wrist, respectively. The patients were asked to count the rare stimuli presented to one wrist to elicit a P300 complex to target stimuli only. In the second paradigm, namely vibrotactile EPs with three tactors (VT3), two stimulators were placed on the wrists as done in VT2, and one additional stimulator was placed on his/her back. The task was to count the rare stimuli presented to one wrist, to elicit the event-related potentials (ERPs). The VT3 paradigm could also be used for communication. For this purpose, the patient had to count the stimuli presented to the left hand to answer "yes" and to count the stimuli presented to the right hand to answer "no." All patients except one performed above chance level in at least one run in the VT2 paradigm. In the VT3 paradigm, all 6 stroke patients and 8/9 ALS patients showed at least one run above chance. Overall, patients achieved higher accuracies in VT2 than VT3. LIS patients due to ALS exhibited higher accuracies that LIS patients due to stroke, in both the VT2 and VT3 paradigms. These initial data suggest that controlling this type of BCI requires specific cognitive abilities that may be impaired in certain sub-groups of severely motor-impaired patients. Future studies on a larger cohort of patients are needed to better identify and understand the underlying cortical mechanisms of these differences.


Isolation and characterization of human melanoma cell variants expressing high and low levels of CD44.
Variants of the human melanoma cell line LT5.1 were selected for high and low expression of the Mr 90,000 CD44 glycoprotein by using the Hermes-3 monoclonal antibody combined with fluorescence-activated cell sorting. Cells were single cell cloned and clones of CD44 high-expressing and CD44 low-expressing phenotype were isolated. The variants, which exhibited up to a 7-fold difference between high and low expression, have maintained a stable phenotype over a period of 3 months in tissue culture. Northern blot analysis of mRNA from the different clones showed correlation of levels of transcripts with fluorescence-activated cell sorting analysis data. Wound migration assays, utilizing the different clones, showed that the low-expressing clones manifested less motility than did cells showing high levels of CD44. Homotypic aggregation of cells was increased in those cells expressing high levels of CD44, and these variants were also better able to adhere to hyaluronate substrates. All of these activities were inhibited by the presence of anti-CD44 antibody. When injected i.v. into nu/nu BALB/c mice, the low-expressing clones gave significantly fewer lung nodules than the high-expressing clones, although the two variant types did not differ in their capacity to form s.c. tumors in similar mice. These results suggest that the CD44 molecule, possibly as a function of its activities as a hyaluronate receptor, may play a vital role in determining the fate of hematogenously disseminating melanoma cells.


[Diagnostic value of soluble interleukin-2 receptors in patients with alcoholic liver disease].
The medical inspection of the blood samples of 88 patients with alcoholic liver disease has revealed an increase in number of soluble receptors to interleukin-2, which was associated with the intensity of cytolytic and mesenchymal-inflammatory syndromes and in patients with cirrhosis of liver--the development of hepatocellular insufficiency.


Epidemiology to public health intervention for preventing cardiovascular diseases: the role of translational research.
Despite significant progress in medical research, cardiovascular diseases (CVDs) continue to be the largest contributors of morbidity and mortality both in developed and developing countries. The status of public health interventions related to CVDs prevention was reviewed to identify actions that are required to bridge the existing gap between the evidence and the policy. We used a framework comprising two steps - "bench to bedside" and from "bedside to community" to evaluate translational research. Available literature was reviewed to document the current status of CVD prevention and control at national level in India. Case studies of risk factor surveillance, tobacco control and blood pressure measurement were used to understand different aspects of translational research. National level initiatives in non-communicable diseases surveillance, prevention and control are a recent phenomena in India. The delay in translation of research to policy has occurred primarily at the second level, i.e., from 'bedside to community'. The possible reasons for this were: inappropriate perception of the problem by policy makers and programme managers, lack of global public health guidelines and tools, and inadequate nationally relevant research related to operationalization and cost of public health interventions. Public health fraternity, both nationally and internationally, needs to establish institutional mechanisms to strengthen human resource capacity to initiate and monitor the process of translational research in India. Larger public interest demands that focus should shift to overcoming the barriers at community level translation. Only this will ensure that the extraordinary scientific advances of this century are rapidly translated for the benefit of more than one billion Indians.


Shape variation of micelles in polymer thin films.
The equilibrium properties of block copolymer micelles confined in polymer thin films are investigated using self-consistent field theory. The theory is based on a model system consisting of AB diblock copolymers and A homopolymers. Two different methods, based on the radius of gyration tensor and the spherical harmonics expansion, are used to characterize the micellar shape. The results reveal that the morphology of micelles in thin films depends on the thickness of the thin films and the selectivity of the confining surfaces. For spherical (cylindrical) micelles, the spherical (cylindrical) symmetry is broken by the presence of the one-dimensional confinement, whereas the top-down symmetry is broken by the selectivity of the confining surfaces. Morphological transitions from spherical or cylindrical micelles to cylinders or lamella are predicted when the film thickness approaches the micellar size.


Enzymatic manipulations of DNA oligonucleotides on microgel: towards development of DNA-microgel bioassays.
We demonstrate that DNA oligonucleotides covalently coupled to colloidal microgel can be manipulated by T4 DNA ligase for DNA ligation and by Phi29 DNA polymerase for rolling circle amplification (RCA). We also show that the long single-stranded RCA product can generate intensive fluorescence upon hybridization with complementary fluorescent DNA probe. We believe DNA-microgel conjugates can be explored for the development of DNA based bioassays and biosensors.


Perceptions about the sexuality of women with fibromyalgia syndrome: a phenomenological study.
The aim of this study was to explore and understand the perceptions and experiences of women with fibromyalgia syndrome regarding their sexuality. Fibromyalgia syndrome is a chronic pathology, which compromises a woman's physical, mental and emotional health. Although concerns related to sexuality are commonly reported, research has tended to focus on the physical symptoms. An interpretive qualitative research methodology using Gadamer's philosophical hermeneutics was carried out. This qualitative study explores the sexuality of women with fibromyalgia syndrome. A focus group and semi-structured interviews were conducted with 13 women with fibromyalgia syndrome. Data were collected between April - June 2014. Participants were recruited until findings reached saturation. Three themes define the perception of sexuality for these women: (i) Physical impact: don't touch, don't look; (ii) Sexuality and identity: fighting against their loss; (iii) Impact on the relationship: sexuality as a way of connecting the couple. Despite limitations, sexuality is important for the identity and quality of life of women with fibromyalgia syndrome. Together with the physical symptomology, guilt, fear and a lack of understanding compromise the coping process. Women need the support of their partner, their socio-family environment and health professionals. Nurses can aid the successful adjustment to sexual problems related to fibromyalgia syndrome.


[Effect of specific treatment on the evolution of antibody titers against Chlamydia trachomatis measured by the immunofluorescence and complement fixation tests].
We have evaluated the results of a serologic study of 34 patients with a possible chlamydial infection, obtaining three successive serum samples that were assessed with microimmunofluorescence (IIF) and complement fixation (CF) tests, so as to establish a comparison between the antibody titer measured by each of them. CF detects antibodies against the genus antigen, whereas IIF detects antibodies against the type-specific antigen. The antibodies against both antigens decrease in a parallel fashion, although somewhat more slowly in those against group antigen. This difference is significant (p less than 0.05).


Optic nerve head circulation determined by pulse wave analysis is significantly correlated with cardio ankle vascular index, left ventricular diastolic function, and age.
To determine whether there is a significant correlation between optic nerve head circulation determined by pulse wave analysis of laser speckle flowgraphy (LSFG), and the cardio-ankle vascular index (CAVI), left ventricular (LV) function, and age. Forty-nine men who visited the Vascular Function Section of Toho University Sakura Medical Center, Chiba, Japan were studied. The mean age of the subjects was 60.7±10.6 years (range 29 to 80 years). The CAVI, left ventricular ejection fraction (LVEF) as a function of the systolic LV function, early diastolic mitral annulus velocity (e'), and the ratio of transmitral early peak velocity (E) to e' (E/e' ratio) as the diastolic LV function, and the optic nerve head circulation determined by pulse wave analysis of the LSFG. This parameter was named the blowout time (BOT). The BOT was significantly correlated with age, heart rate, body mass index (BMI), triglyceride, LVEF, e' velocity, E/e' ratio, and CAVI. The results of multiple regression analysis showed that age was significantly associated with CAVI (r= 0.36, p=0.002), BOT (r=-0.30, p=0.01) and e' velocity (r=-0.21, p=0.04). The BOT of the optic nerve head circulation determined by LSFG was significantly correlated with age but was independent of cardiac diastolic function and arterial stiffness. This suggests that the damage to different organs increases with age. Our results confirmed that BOT can be helpful in evaluating physiological aging of the microcirculation.


[Dynamics of focal seizure activity during induced sleep in epileptics with uni- and bitemporal foci].
SEEG examination was conducted in 65 patients with temporal epilepsy during hexabarbitone-, diazepam- and sombrevin-induced sleep. It was found that hexabarbitone promotes manifestation of the dependent epileptic foci, while diazepam and sombrevin reveal the determinant epileptic foci and contribute to inhibition of dependent epileptic foci, mainly those localized in the cortex. The fusiform rhythm is mainly marked by cortical representation and is not recorded in the deep structures of the temporal lobes on the side of the determinant epileptic focus. The principal epileptic foci were localized in the limbic structures of the temporal lobes, which possibly determined their determinant role in epileptogenesis. In bilateral independent epileptic foci with a high level of spastic activity, focal epileptic discharges were preserved in the various methods of sleep activation. The possibility of topical diagnosis of the determinant and dependent epileptic foci provides for adequate tactics of surgical management of epilepsy.


Role of phase information and eye pursuit in the detection of moving objects in noise.
As part of an ongoing study that uses objective image quality measures to optimize medical imaging x-ray fluoroscopy, we investigated two basic features of the detection of moving cylinders that mimic arteries, catheters, and guide wires. First, we compared detection with and without a phase cue consisting of a nearby alternating light and dark square. Depending on object size and velocity, phase cuing improved detection from 1% to 15% and gave an average of 6%, an effect much smaller than the 38% predicted from a Monte Carlo simulation of the ideal observer. Evidently, humans were limited in their ability to incorporate knowledge of the phase cue. Second, we evaluated the effect of eye pursuit of a fixation point that moved with the target. In general, motion at the highest velocity degraded (74%) and enhanced (68%) detection of small and large objects, respectively. With eye pursuit, both effects were substantially reduced in a manner consistent with a reduced retinal velocity. Our data compared favorably with a human observer model that included a spatiotemporal contrast sensitivity response and smooth-pursuit eye movements with a gain of 0.8. These mechanisms of perception are thought to be present in coronary artery x-ray fluoroscopy imaging, where phase information is available from the moving heart and where motion markers are available from x-ray opaque markers incorporated in thin catheters and guide wires.


[Clinical study of endoscopy-assisted lithectomy of parotid gland calculi via a transoral approach].
Objective: To investigate the indications and long-term outcomes of endoscopy-assisted removal of parotid gland calculi via a transoral approach. Methods: From August 2005 to December 2016, 158 consecutive patients with parotid gland calculi underwent endoscopy-assisted lithectomy transorally. They included 71 males and 87 females, with an age of 5-84 years. The immediate safety and effectiveness were evaluated. After surgery, the patients were followed up, and gland function was analyzed on the basis of clinical manifestations, sialography, scintigraphy and sialometry. Postoperative sialograms were categorized into 2 types: ①type Ⅰ, the main duct was normal or had ectasia and stenosis, but no persistent contrast was seen on the functional film; ②type Ⅱ, the main duct had ectasia or stenosis, with persistent contrast media on the functional film. Results: Under one endoscopic procedure, the stones (or foreign bodies) were completely removed in 134 cases and almost completely removed in 10 cases, with a success rate of 91.1% (144/158). Of the 144 successful cases, the treatment options included direct basket retrieval or forceps grasping in 77 cases, basket entrapment with direct ostium incision in 36, basket capture with perio-ostium incision in 23 and perio-ostium incision in 8 cases with impacted stones. In two of the initial 14 failure cases, the stones were discharged spontaneously 3 months after operation. During 3-120 months' follow-up (mean 36 months) of the 146 patients, one had recurrent stone, two developed ductal obturation, 16 had mild symptoms, and the remaining 127 cases were asymptomatic. Of the postoperative sialograms in 34 stone-free patients 25 were type Ⅰ, 9 were type Ⅱ. Both scintigraphy and saliva flow rate indicated an improvement of the affected gland function in some degree (P<0.05). Conclusions: Transoral endoscopy-assisted removal of parotid gland calculi is a safe and effective technique. It is mainly indicated for mobile stones in the main duct or impacted stones in the anterior third of the Stensen's duct. Sialography, scintigraphy and sialometry show postoperative improvement of gland function in most of the cases.


Pathogenesis, newly recognized etiologies, and management of idiopathic anaphylaxis.
Idiopathic anaphylaxis (IA) is a life-threatening allergic disease and the most common diagnosis given to patients following an anaphylactic event. The inability of the healthcare provider and the patient to identify the trigger for anaphylaxis makes standard allergen avoidance measures ineffectual. IA is diagnosed after other causes of anaphylaxis have been excluded. Mast cell activation syndromes (MCAS), mastocytosis, IgE to galactose-alpha-1,3-galactose (α-gal), and certain medications have recently been recognized as causes of anaphylaxis that were previously labeled idiopathic. This review will describe the epidemiology and proposed theories of pathogenesis for IA, its diagnostic approach, its clinical management, and examine newly recognized disorders that were previously labeled as idiopathic anaphylaxis.


Primate polemic: commentary on Smith, Couchman, and Beran (2014).
Smith, Couchman, and Beran (2014, pp. 115-131) take issue with recent attempts to account for so-called metacognitive behavior in nonhuman animals in terms of simple processes of associative reinforcement learning. Their arguments rely on appeals to unconvincing and equivocal empirical evidence, and a misrepresentation of the nature of associative learning. Although the existing data do not rule out the possibility that animals possess "true" metacognitive abilities, neither do they currently mandate this conclusion. The suggestion that simple mechanisms might give rise to complex behaviors ties in with recent attempts in cognitive and social psychology, and behavioral neuroscience, to explain human behavior in terms of similar, simple mechanisms. As such this perspective should be seen as an opportunity for comparative psychology, not a threat.


Adipose tissue-derived stromal cells express neuronal phenotypes.
Adipose tissue-derived stromal cells (ADSCs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons. Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE). Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies. The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.


Trends in the prevalence of malignancy among patients admitted with acute heart failure and associated outcomes: a nationwide population-based study.
Cancer is the second leading cause of death in the USA, and cardiovascular disease is the second leading cause of morbidity and mortality among cancer survivors. Cancer survivors share common risk factors for cardiovascular disease with non-cancer patients. With improved survival, cancer patients become susceptible to treatment-related toxicity often involving the heart. The impact of concurrent malignancy on outcomes particularly among heart failure patients is an area of active research. We studied the trends in the prevalence of a concurrent diagnosis of breast, prostate, colorectal, and lung cancer among admissions for acute heart failure and the associated trends for in-hospital mortality. Patients aged ≥ 18 years who were admitted with a primary diagnosis of "congestive heart failure" (CCS codes 99 and 108) from years 2003 to 2014 were included. We analyzed the rate of admission and in-hospital mortality among patients who had a concurrent diagnosis for either lung cancer, colorectal cancer, breast cancer (among females), or prostate cancer (among males). We performed a multivariate analysis to assess the role of a concurrent diagnosis of any cancer in predicting in-hospital mortality among HF admissions. From 2003 to 2014 across over 12 million HF admissions, ≈ 7% had a concurrent diagnosis of either lung, breast, colorectal, or prostate cancer. The prevalence was highest for breast cancer (2.3%) followed by prostate cancer (2.1%) and colorectal cancer (1.5%) and lowest with lung cancer (1.1%). The prevalence of cancer increased over the duration of study among all four cancer types with the largest increase in prevalence of breast cancer. Baseline comorbidities including hypertension, diabetes, smoking, chronic kidney disease, and coronary artery disease increased over time among patients with and without cancer. In-hospital mortality was higher among those with a diagnosis of lung cancer (5.9%) followed by colorectal cancer (4.0%), prostate cancer (3.5%), no diagnosis of cancer (3.3%), and breast cancer (3.2%). In-hospital mortality declined across HF admissions with and without a cancer diagnosis from 2003 to 2014. Decline in such mortality among heart failure was highest for patients with lung cancer (8.1 to 4.6% from 2003 to 2014; p < 0.001). Multivariate analysis showed that a concurrent diagnosis of cancer was associated with a marginally lower hospital mortality compared with controls (adjusted odds ratio 0.95, 95% confidence interval 0.94-0.96; p < 0.001). Among HF admissions, the prevalence of a concurrent cancer diagnosis increased over time for breast, lung, colorectal, and prostate cancer. Baseline in-hospital mortality was higher among HF admissions with either lung cancer, colorectal cancer, or prostate cancer and lower with breast cancer compared with controls without a cancer diagnosis. Adjusted analysis revealed no evidence for higher hospital mortality among HF admissions with any accompanying cancer diagnosis.


Fabrication and surface characterization of single crystal PtBi and PtPb (100) and (001) surfaces.
High quality single crystal PtM (M = Bi or Pb) (100) and (001) surfaces have been generated from solid state bulk materials. The specific orientation was determined via X-ray Laue back-reflection and the miscut angles of the single crystal surfaces were ∼0.3° which was limited by instrumental resolution. The PtM (001) electrode had a Pt termination based on cyclic voltammetric (CV) profiles. The surface structure and composition of single crystal PtM surfaces have been studied by synchrotron-based in situ X-ray grazing incidence diffraction (GID) under active electrochemical control. Cycling of the potential to increasingly high values resulted in dramatic changes to the surface crystalline structure and composition of these single crystal electrodes. Well-defined Pt nano-domains in a hexagonal pattern with a 23° offset angle to the substrate were formed on the PtM (001) surface after electrochemical pretreatment in supporting electrolyte (0.1M H(2)SO(4)), especially for E(ulp) (E(ulp) = upper limit potential) of +0.80 V or beyond. From an analysis of the diffraction peaks, the size of the Pt domains was estimated to be ∼15 nm. The Pt domain formation on the single crystal surfaces, similar to results on polycrystalline intermetallic phases, was due to leaching of the less-noble elements (Bi or Pb) from the intermetallic matrix and sintering of the Pt atoms on the surfaces. On the other hand, Pt domains with a preferential direction but no offset angle to the substrate were formed on PtM (100) surface after similar electrochemical pretreatment. PtBi and PtPb single crystal surfaces exhibited different anisotropic electrocatalytic activities towards the electrooxidation of formic acid and other potential fuels for fuel cell applications. The reactivities of these single crystal electrodes towards the oxidation of small organic molecules were a function of E(ulp) values and maximal activities were around +0.60 V for PtBi(001) surface which might be due to formation of partially oxidized surfaces but around +1.20 V for PtPb(100) and (001) surfaces which might be due to the increasing boundary lines of Pt and PtPb grains.


Targeted ischemic stroke induction and mesoscopic imaging assessment of blood flow and ischemic depolarization in awake mice.
Despite advances in experimental stroke models, confounding factors such as anesthetics used during stroke induction remain. Furthermore, imaging of blood flow during stroke is not routinely done. We take advantage of in vivo bihemispheric transcranial windows for longitudinal mesoscopic imaging of cortical function to establish a protocol for focal ischemic stroke induction in target brain regions using photothrombosis in awake head-fixed mice. Our protocol does not require any surgical steps at the time of stroke induction or anesthetics during either head fixation or photoactivation. In addition, we performed laser speckle contrast imaging and wide-field calcium imaging to reveal the effect of cortical spreading ischemic depolarization after stroke in both anesthetized and awake animals over a spatial scale encompassing both hemispheres. With our combined approach, we observed ischemic depolarizing waves (3 to [Formula: see text]) propagating across the cortex 1 to 5 min after stroke induction in genetically encoded calcium indicator mice. Measures of blood flow by laser speckle were correlated with neurological impairment and lesion volume, suggesting a metric for reducing experimental variability. The ability to follow brain dynamics immediately after stroke as well as during recovery may provide a valuable guide to develop activity-dependent therapeutic interventions to be performed shortly after stroke induction.


Levels of Peripheral Circulating IL-6 and IL-10 Decrease Over Time Despite High Depression Burden in PTSD Patients.
Patients with combined depression symptoms and post-traumatic stress disorder (PTSD) often exhibit high levels of circulating inflammatory biomarkers as either a cause or consequence of their disease. We aimed to investigate how cytokines and depression symptoms develop with one-year follow-up and compare them with non-PTSD patients. The study had a longitudinal design with one-year follow-up measurements in an inpatient treatment setting at a psychiatric center in Norway. PTSD diagnoses were set using the Mini International Neuropsychiatric Interview (MINI). The first three measurements were at baseline (T0), halfway (T1) and at discharge (T2) from a 12-week main stay, followed by a final measurement one year after discharge (T3). Serum blood samples were collected on all four occasions. The Beck Depression Inventory-II (BDI-II) was administered at T0, T2 and T3. Levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in PTSD patients were higher than in patients without PTSD at T0 (p = 0.005 and 0.042). The PTSD patients had a higher average level of IL-10 across all four measurements (B = 1.62, Standard Error (SE) = 0.78, p = 0.037). The IL-10 levels in PTSD patients declined from T0 to T3 (p = 0.039). The PTSD patients were more depressed than non-PTSD patients at T3 (p = 0.019). The levels of IL-10 and IL-6 in PTSD patients more closely resembled the levels in non-PTSD patients at one-year follow-up, despite level of depression being unchanged in the PTSD patients. This calls into question the close relationship between level of circulating cytokines and depressive symptoms, at least in PTSD patients. Further research is needed to investigate what appears to be a complex relationship between immune markers and depression in patients with PTSD.


Responsiveness of gill Na+/K+-ATPase to cortisol is related to gill corticosteroid receptor concentration in juvenile rainbow trout
A positive relationship between receptor concentration and tissue responsiveness is an often-assumed and rarely tested principle in endocrinology. In salmonids, seasonal changes in levels of plasma cortisol and gill corticosteroid receptors (CRs) during the spring indicate a potential role for this hormone in the parr-smolt transformation. It is not known whether these seasonal changes result in alterations in gill responsiveness to cortisol. The relationship between CR concentration and tissue responsiveness was, therefore, examined in the gills of juvenile rainbow trout (Oncorhynchus mykiss). Gill CR concentration (Bmax) and affinity (Kd) were assessed using a radioligand binding assay with the synthetic glucocorticoid triamcinolone acetonide. Gill responsiveness to cortisol was quantified by measuring in vitro Na+/K+-ATPase activity. Gill CR concentration was manipulated by stress or hormonal treatments. Repeated handling stresses resulted in a significant reduction in CR numbers. The decrease in CR Bmax corresponded to a reduction in gill responsiveness to cortisol. Triiodothyronine, but not growth hormone, treatment was found to increase CR Bmax significantly. The increase in CR numbers was correlated with a marked increase in gill responsiveness to cortisol. A significant positive linear relationship exists between the in vitro gill Na+/K+-ATPase activity response to cortisol and CR Bmax (r2=0.614, P<0.001). We have demonstrated that binding sites for cortisol in the gills of rainbow trout have high affinity, high specificity and saturable binding and that the number of binding sites is correlated with the tissue response to cortisol.


Changes in Emergency Department Encounters for Vomiting After Cannabis Legalization in Colorado.
Cannabis hyperemesis syndrome is an emerging clinical issue associated with cannabis use. Legalization of cannabis has led to an increase in vomiting-related illnesses in health care settings. To examine whether legalization of cannabis in Colorado has been associated with increases in vomiting-related emergency department (ED) visits. A cross-sectional design was used to assess the increase in ED claims for vomiting reported to the Colorado Hospital Association between January 1, 2013, and December 31, 2018, in counties that had no prior cannabis dispensaries before legalization compared with those that did. A total of 820 778 patients seeking care through Colorado EDs were included in the analysis. The number of medical and recreational cannabis dispensaries per county per quarter. County per capita rate of vomiting-related ED claims per quarter. Vomiting-related ED health care encounters increased from 119 312 in 2013 to 153 699 in 2018 (29% increase). Over this period, 203 861 patients (25%) were aged 0 to 18 years; 114 201 (14%) were aged 19 to 25 years, and 502 771 (61%) were aged 26 years or older; 510 584 patients (62%) were female. Additional recreational dispensaries were associated with increased vomiting-related ED visits (incidence rate ratio, 1.03; 95% CI, 1.01-1.05), but counties with high baseline medical dispensary exposure experienced smaller increases in vomiting-related ED visits than counties with no baseline medical dispensary exposure (incidence rate ratio, 0.97; 95% CI, 0.95-0.99). Counties with a high number of medical marijuana dispensaries had increases at a 5.8% slower rate than counties with none. The findings of this study suggest that cannabis legalization in Colorado is associated with an increase in annual vomiting-related health care encounters with regard to exposure to these markets. It may be useful for health care clinicians to be aware of cannabis hyperemesis syndrome and inquire about cannabis use when appropriate.


Clinical manifestations of Cape cobra (Naja nivea) bites. A report of 2 cases.
Two cases of proven bites by the Cape cobra (Naja nivea) are reported. Both patients developed areflexic flaccid paralysis and required ventilation from 2 1/4 and 2 1/2 hours after the bite for 4 1/2 and 7 days respectively. Antivenom is of value before the onset of paralysis but of no value once paralysis is established. Both patients developed a non-depolarizing neuromuscular block which was little affected by prostigmine. Early treatment in identified Cape cobra bites should be the immediate application of an arterial tourniquet, followed by intravenous administration of 80-100 ml polyvalent antivenom if signs of neurotoxicity develop. This may need to be repeated. Treatment once paralysis is established is largely supportive, prolonged ventilation frequently being required, following which recovery should be complete.


The location of a mutator factor in a strain of Drosophila melanogaster by assaying male recombination.
In a set of "mutation accumulation lines," of Drosophila melanogaster that had originated from two different wild-caught lethal-carrying second chromosomes (Yamaguchi and Mukai 1974; Mukai and Cockerham 1977; Voelker, Schaffer and Mukai 1980) a correlation exists between high rates of reverse mutation at two visible loci and the ability to induce male recombination (Scobie and Schaffer 1982). The second and third chromosomes were extracted from the lines demonstrating these phenomena and tested for independent ability to induce male recombination. When the wild chromosome being tested was of male origin extracted second chromosome lines were found to induce moderate to high levels of male recombination and reduced transmission frequency of the wild chromosome (the k value). The recombinants recovered in these crosses also demonstrated a high level of double-crossover recombination without the recovery of the reciprocal double-recombinant types. In addition, identifiable portions of extracted second chromosomes of male origin have been placed on very similar, marked genetic backgrounds and tested for their ability to induce male recombination. Results of this procedure have identified two regions of the second chromosome that induce male recombination and reduce k values. These results are consistent with the hypothesis that there exist two mutator factors and the second chromosome, each associated with a "mutation accumulation line" with an unstable locus.


Ecological characterization of the aquatic habitats of mosquitoes (Diptera: Culicidae) in enzootic foci of Venezuelan equine encephalitis virus in western Venezuela.
We studied the aquatic mosquito habitats in and around enzootic foci of Venezuelan Equine Encephalitis virus (VEE) in western Venezuela. Specimens were sampled for 5 mo in three types of vegetation: tall lowland tropical forests, short inundated/secondary growth forests, and pastures/herbaceous vegetation around forests. Ground pools, flooded pastures, swamps, ponds, and canals predominated. We used a multivariate statistical approach to quantitatively assess the relationships of mosquito species with broad categories of the landscape, and with environmental variables within each aquatic habitat. Twenty-four mosquito species in the genera Aedes, Psorophora, Culex, Mansonia, and Uranotaenia were collected. Species richness was higher in the tall forests than in other types of vegetation. Discriminant Function Analysis showed a strong association between landscape category and mosquito species assemblage and identified Culex erraticus Dyar & Knab and Mansonia titillans Walker as indicator species of open areas, and Aedes serratus Theobald as an indicator of tall forests. M. titillans, Uranotaenia geometrica Theobald, Cx. erraticus, and Culex dunni Dyar were associated with unshaded, warm, vegetated waters in flooded pastures and swamps, whereas Ae. serratus, Aedes fulvus (Wiedemann), Psorophora albipes Theobald, Psorophora ferox (Humboldt), Culex caudelli Dyar & Knab, and Culex pedroi Sirivanakarn & Belkin were associated with small, shaded ground pools within the tall forests. Culex coronator Dyar & Knab was associated with partially exposed sites within short forests. These results allowed us to interpret better our previous studies on mosquito adult spread in the study area and their possible role as VEEV disseminators.


BMI and severity of clinical and radiographic signs of hip osteoarthritis.
Obesity might be involved in the pathogenesis of osteoarthritis (OA) not only via increased mechanical loading, but also via an inflammatory component possibly causing increased pain and functional disability. The study aim was to examine the relationship between BMI and clinical symptoms as well as radiographic severity of OA in patients scheduled for primary total hip arthroplasty (THA). We conducted a cross-sectional study of 855 patients scheduled for a first THA for primary OA at a single centre between November 2001 and December 2006. The primary outcome was clinical and radiographic severity of OA, which was evaluated in four BMI categories (18.5-24.9, 25-29.9, 30-34.9 and > or =35 kg/m(2)). We used the Harris Hip Score (HHS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) to assess pain and function. The severity of radiographic hip joint damage was evaluated using the Kellgren-Lawrence classification. Multivariate analyses were performed to adjust for potential confounders. In patients scheduled for THA, increasing BMI was associated with significantly higher levels of pain and functional disability on both HHS (P for trend <0.001) and WOMAC (P for trend <0.001). However, the degree of radiographic joint damage remained similar across BMI categories. These findings emphasize the need to further investigate the potential pathogenic role of obesity and low-grade inflammation in OA and underscore the importance of obesity prevention to avoid early prosthetic replacement of the hip.


Lung transplantation: candidate selection and timing of transplant.
Over the past two decades, lung transplant has become the mainstay of treatment for several end-stage lung diseases. As the field continues to evolve, the criteria for referral and listing have also changed. The last update to these guidelines was in 2014 and several studies since then have changed how patients are transplanted. Our article aims to briefly discuss these updates in lung transplantation. This article discusses the importance of early referral of patients for lung transplantation and the concept of the 'transplant window'. We review the referral and listing criteria for some common pulmonary diseases and also cite the updated literature surrounding the absolute and relative contraindications keeping in mind that they are a constantly moving target. Frailty and psychosocial barriers are difficult to assess with the current assessment tools but continue to impact posttransplant outcomes. Finally, we discuss the limited data on transplantation in acute respiratory distress syndrome (ARDS) due to COVID19 as well as extracorporeal membrane oxygenation bridge to transplantation. The findings discussed in this article will strongly impact, if not already, how we select candidates for lung transplantation. It also addresses some aspects of lung transplant such as frailty and ARDS, which need better assessment tools and clinical data.


Online gaming addiction: the role of sensation seeking, self-control, neuroticism, aggression, state anxiety, and trait anxiety.
Research into online gaming has steadily increased over the last decade, although relatively little research has examined the relationship between online gaming addiction and personality factors. This study examined the relationship between a number of personality traits (sensation seeking, self-control, aggression, neuroticism, state anxiety, and trait anxiety) and online gaming addiction. Data were collected over a 1-month period using an opportunity sample of 123 university students at an East Midlands university in the United Kingdom. Gamers completed all the online questionnaires. Results of a multiple linear regression indicated that five traits (neuroticism, sensation seeking, trait anxiety, state anxiety, and aggression) displayed significant associations with online gaming addiction. The study suggests that certain personality traits may be important in the acquisition, development, and maintenance of online gaming addiction, although further research is needed to replicate the findings of the present study.


Fine frequency tuning in monkey auditory cortex and thalamus.
The frequency resolution of neurons throughout the ascending auditory pathway is important for understanding how sounds are processed. In many animal studies, the frequency tuning widths are about 1/5th octave wide in auditory nerve fibers and much wider in auditory cortex neurons. Psychophysical studies show that humans are capable of discriminating far finer frequency differences. A recent study suggested that this is perhaps attributable to fine frequency tuning of neurons in human auditory cortex (Bitterman Y, Mukamel R, Malach R, Fried I, Nelken I. Nature 451: 197-201, 2008). We investigated whether such fine frequency tuning was restricted to human auditory cortex by examining the frequency tuning width in the awake common marmoset monkey. We show that 27% of neurons in the primary auditory cortex exhibit frequency tuning that is finer than the typical frequency tuning of the auditory nerve and substantially finer than previously reported cortical data obtained from anesthetized animals. Fine frequency tuning is also present in 76% of neurons of the auditory thalamus in awake marmosets. Frequency tuning was narrower during the sustained response compared to the onset response in auditory cortex neurons but not in thalamic neurons, suggesting that thalamocortical or intracortical dynamics shape time-dependent frequency tuning in cortex. These findings challenge the notion that the fine frequency tuning of auditory cortex is unique to human auditory cortex and that it is a de novo cortical property, suggesting that the broader tuning observed in previous animal studies may arise from the use of anesthesia during physiological recordings or from species differences.


Relationships among coarse-grained field theories of fluctuations in polymer liquids.
Two closely related field-theoretic approaches have been used in previous work to construct coarse-grained theories of corrections to the random phase approximation for correlations in block copolymer melts and miscible polymer blends. The "auxiliary field" (AF) approach is based on a rigorous expression for the partition function Z of a coarse-grained model as a functional integral of an auxiliary chemical potential field. The "effective Hamiltonian" (EH) approach is instead based on an expression for Z as a functional integral of an observable order parameter field. The exact effective Hamiltonian H(eff) in the EH approach is defined as the free energy of a system with a constrained order parameter field. In practice, however, H(eff) has often been approximated by a mean-field free energy functional, yielding what we call a mean-field effective Hamiltonian (MFEH) approximation. This approximation was the starting point of both the Fredrickson-Helfand analysis of fluctuation effects in diblock copolymers and earlier work on the Ginzburg criterion in polymer blends. A more rigorous EH approach by Holyst and Vilgis used an auxiliary field representation of the exact H(eff) and allowed for Gaussian fluctuations of this field. All applications of both AF and EH approaches have thus far relied upon some form of Gaussian, or "one-loop" approximation for fluctuations of a chemical potential and/or order parameter field about a mean-field saddle-point. The one-loop EH approximation of Holyst and Vilgis and the one-loop AF theory are equivalent to one another, but not to the one-loop MFEH theory. The one-loop AF and MFEH theories are shown to yield predictions for the inverse structure factor S(-1)(q) that (in the absence of further approximations to either theory) differ by a function that is independent of the Flory-Huggins interaction parameter χ. As a result, these theories yield predictions for the peak scattering intensity that exhibit a similar χ-dependence near a spinodal. The Fredrickson-Helfand theory for the structure factor in disordered diblock copolymer melts is an asymptotic approximation to the MFEH one-loop theory that captures the dominant asymptotic behavior of very long, symmetric copolymers very near the order-disorder transition.


Disappearance of calcium and other electrolytes from microvolume samples.
Studies involving micropuncture and microperfusion of single nephrons require the handling of very small fluid samples. To facilitate handling, the tubule fluids are normally manipulated under paraffin oil. Calcium and, to a lesser extent, magnesium and phosphate concentrations may change significantly when placed in hydrated paraffin oil. Fluids of alkaline pH (about 7.4), either intrinsic or because of loss of CO2, may very quickly lose calcium in paraffin oil. Evidence suggests that this is due to a reversible binding of calcium and perhaps magnesium to the aqueous-oil interface that is dependent on the pH of the sample. It is recommended that tubule fluid samples be kept acidic to prevent calcium loss. A convenient method is by equilibrating the paraffin oil, prior to placement of aqueous samples, with a CO2 tension sufficient to lower the sample pH to below 7.0.


Gamma-hydroxybutyric acid as hypnotic. Clinical and pharmacokinetic evaluation of gamma-hydroxybutyric acid as hypnotic in man.
Gamma-Hydroxybutyric acid (GOH) was administered to three groups of four patients in 50, 75 or 100 mg/kg dose respectively, and sleep effects were scored, by sleep observation and questionnaire; GOH plasma levels were determined at 75-100 mg/kg, saliva and urine excretion at 100 mg/kg. Sleep induction was rapid and irresistible, subjects awoke at plasma levels of 90 micrograms/ml; sleep scores were good for 75 mg/kg, excellent for 100 mg/kg, notably on mood. For 75 or 100 mg/kg GOH had virtually disappeared from the blood eight hours after intake; twelve hours after intake no more GOH was detectable in urine; no correlation between plasma- and saliva levels was found. Plasma levels for 100 mg/kg dose were not at an anaesthetic level. So, GOH is a safe and good hypnotic at 75 or 100 mg/kg in clinical use.


Novel optineurin mutations in patients with familial and sporadic amyotrophic lateral sclerosis.
Optineurin (OPTN), a causative gene of hereditary primary open-angle glaucoma, has been recently associated with amyotrophic lateral sclerosis (ALS) with mainly autosomal recessive, but also dominant, traits. To further define the contribution of OPTN gene in ALS, we performed a mutational screening in a large cohort of Italian patients. A group of 274 ALS patients, including 161 familial (FALS) and 113 sporadic (SALS) cases, were screened for OPTN mutations by direct sequencing of its coding sequence. All patients fulfilled the El Escorial criteria for probable or definite ALS and were negative for mutations in SOD1, ANG, TARDBP and FUS/TLS genes. The genetic analysis revealed six novel variants in both FALS and SALS patients, all occurring in an heterozygous state. We identified three missense (c.844A→C p.T282P, c.941A→T p.Q314L, c.1670A→C p.K557T), one nonsense (c.67G→T p.G23X) and two intronic mutations (c.552+1delG, c.1401+4A→G). The intronic c.552+1delG variant determined a splicing defect as demonstrated by mRNA analysis. All mutations were absent in 280 Italian controls and over 6800 worldwide glaucoma patients and controls screened so far. The clinical phenotype of OPTN-mutated patients was heterogeneous for both age of onset and disease duration but characterised by lower-limb onset and prevalence of upper motor neuron signs. In this cohort, OPTN mutations were present both in FALS (2/161), accounting for 1.2% cases, and in SALS patients (4/113), thereby extending the spectrum of OPTN mutations associated with ALS. The study further supports the possible pathological role of optineurin protein in motor neuron disease.


Simultaneous HPLC-DAD-MS (ESI+) determination of structural and geometrical isomers of carotenoids in mature grapes.
Carotenoids are uniquely functional polyene pigments ubiquitous in nature; aside from being responsible for the color of a wide variety of vegetables, interest is being focused on food carotenoids due to their likely health benefits. From analytical point of view, it is important to unequivocally identify individual carotenoid compounds in many food stuffs. Therefore, isolation of standards from natural sources must be encouraged for accurate identifications. Like many fruits, mature grape berries contain numerous carotenoid compounds, mostly found in the skin at levels two to three times higher than in the pulp. Carotenoid compounds in a typical wine grape variety (Negroamaro) grown in Apulian region were investigated by reversed-phase C(30) (RP-30) HPLC-DAD-MS (ESI(+)) analysis. As a consequence of an unusual ionization process of carotenoids, their mass spectra registered in the positive ion mode comprised both protonated molecules and molecular ion radicals with little fragmentation. Additionally, selective collision-induced dissociation (CID) experiments, together with fine structures of the UV-vis spectra, were used to differentiate structural and geometrical isomers. This technique allowed the simultaneous determination of regio- and cis-isomers of lutein (zeaxanthin, 9Z and 9'Z-lutein) and a cis-isomer of β-carotene (9Z- β-carotene), 5,6-epoxy xanthophylls (violaxanthin, (9'Z)-neoxanthin, lutein-5,6-epoxide) and 5,8-epoxy xanthophylls diasteroisomers (neochrome, auroxanthin, luteoxanthin, flavoxanthin, chrysanthemaxanthin).


The Social, Mental, and Physical Health Impacts of the COVID-19 Pandemic on People With HIV: Protocol of an Observational International Multisite Study.
As the COVID-19 pandemic spread across the world, immunocompromised individuals such as people with HIV (PWH) may have faced a disproportionate impact on their health and HIV outcomes, both from COVID-19 and from the strategies enacted to contain it. Based on the SPIRIT guidelines, we describe the protocol for an international multisite observational study being conducted by The International Nursing Network for HIV Research, with the Coordinating Center based at the University of California, San Francisco (UCSF) School of Nursing. Site Principal Investigators implement a standardized protocol to recruit PWH to complete the study online or in-person. Questions address demographics; HIV continuum of care indicators; mental and social health; COVID-19 and vaccination knowledge, attitudes, behaviors, and fears; and overall outcomes. Results of this study will contribute to knowledge that can inform responses to future public health crises to minimize their impacts on vulnerable populations such as PWH.