Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study.
To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995-2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.


Starvation and osmotic stress induced multiresistances. Influence of extracellular compounds.
Growth restriction due to stasis and/or hyperosmolarity is a common situation encountered by microorganisms in nature. Therefore, they have developed defence systems allowing them to withstand these periods. Bacteria respond to these conditions by a metabolic reprogramming which leads to a cellular state of enhanced resistance. This communication reviews recent advances in knowledge of the molecular basis of this phenomenon in different bacteria.


The role of inadequate health literacy skills in colorectal cancer screening.
Colorectal cancer is ideally suited for early detection strategies that are likely to improve survival rates. Screening with either a fecal occult blood test (FOBT) or flexible sigmoidoscopy has been shown to identify precancerous polyps or cancers in early stages. However, persons with limited education and of lower socioeconomic status infrequently participate in screening programs in general and have very low rates of colorectal screening. Low literacy, which is common among persons with limited education and low income, may be an overlooked factor in understanding patients' decision making about colorectal cancer screening. This article provides information from focus groups about colorectal cancer screening, which we examine in the context of relevant literature on cancer screening and literacy. Using the health belief model, we examine the association between inadequate health literacy skills and low rates of colorectal cancer screening. The theoretical model also provides insights into strategies for improving knowledge, attitudes, and beliefs and screening rates for this challenging patient population.


Far-red fluorescence gene reporter tomography for determination of placement and viability of cell-based gene therapies.
Non-invasive injectable cellular therapeutic strategies based on sustained delivery of physiological levels of BMP-2 for spinal fusion are emerging as promising alternatives, which could provide sufficient fusion without the associated surgical risks. However, these injectable therapies are dependent on bone formation occurring only at the specific target region. In this study, we developed and deployed fluorescence gene reporter tomography (FGRT) to provide information on in vivo cell localization and viability. This information is sought to confirm the ideal placement of the materials with respect to the area where early bone reaction is required, ultimately providing three dimensional data about the future fusion. However, because almost all conventional fluorescence gene reporters require visible excitation wavelengths, current in vivo imaging of fluorescent proteins is limited by high tissue absorption and confounding autofluorescence. We previously administered fibroblasts engineered to produce BMP-2, but is difficult to determine 3-D information of placement prior to bone formation. Herein we used the far-red fluorescence gene reporter, IFP1.4 to report the position and viability of fibroblasts and developed 3-D tomography to provide placement information. A custom small animal, far-red fluorescence tomography system integrated into a commercial CT scanner was used to assess IFP1.4 fluorescence and to demark 3-D placement of encapsulated fibroblasts with respect to the vertebrae and early bone formation as assessed from CT. The results from three experiments showed that the placement of the materials within the spine could be detected. This work shows that in vivo fluorescence gene reporter tomography of cell-based gene therapy is feasible and could help guide cell-based therapies in preclinical models.


Altered gene dosage confirms the genetic interaction between FIAT and αNAC.
Factor inhibiting ATF4-mediated transcription (FIAT) interacts with Nascent polypeptide associated complex and coregulator alpha (αNAC). In cultured osteoblastic cells, this interaction contributes to maximal FIAT-mediated inhibition of Osteocalcin (Ocn) gene transcription. We set out to demonstrate the physiological relevance of this interaction by altering gene dosage in compound Fiat and Naca (encoding αNAC) heterozygous mice. Compound Naca(+/-); Fiat(+/-) heterozygous animals were viable, developed normally, and exhibited no significant difference in body weight compared with control littermate genotypes. Animals with a single Fiat allele had reduced Fiat mRNA expression without changes in the expression of related family members. Expression of the osteocyte differentiation marker Dmp1 was elevated in compound heterozygotes. Static histomorphometry parameters were assessed at 8weeks of age using microcomputed tomography (μCT). Trabecular measurements were not different between genotypes. Cortical thickness and area were not affected by gene dosage, but we measured a significant increase in cortical porosity in compound heterozygous mice, without changes in biomechanical parameters. The bone phenotype of compound Naca(+/-); Fiat(+/-) heterozygotes confirms that FIAT and αNAC are part of a common genetic pathway and support a role for the FIAT/αNAC interaction in normal bone physiology.


The effects of denervation on protein turnover of rat skeletal muscle.
The effects of denervation on muscle weight, rates of protein synthesis and breakdown, and RNA concentraitons were studied in the soleus and extensor digitorum longus muscle. Althrough the soleus underwent a true atrophy after section of the sciatic nerve, the extensor digitorum longus continued to grow, albeit at a lower rate than innervated controls. At 24h after nerve section protein breakdown was increased in both muscle types when compared with internal controls, and remained so throughout the 10 days studied. The possibility that this increased catabolism might arise from conformational changes of proteins after denervation was not substantiated, as myofibrillar or soluble proteins of denervated and control tissues were equally susceptible to degradation in vitro by three proteinases. Tyrosine uptake into the denervated extensor digitorum longus was decreased throughout the 10 days studied, whereas two phases of increased transport of the amino acid were found in the soleus. Significant decreases in rates of protein synthesis were found 1 and 2 days after denervation and results are presented that suggest that these changes may result from a decrease in ribosomal involvement in the translation process. These initial decreases were not maintained and the rate of protein synthesis was in fact increased when compared with controls, at 7 and 10 days. The increased synthetic rates of the 7-day denervated tissues were reflected as proportional increases in both myofibrillar and soluble proteins. It is suggested that the increase in synthesis at this time may result from an increase in both the abailability and active involvement of ribosomes, and that these anabolic trends may be caused by spontaneous fibrillation and/or the amount of passive stretching of the denervated muscles.


Voltage gradient mapping and electrophysiologically guided cryoablation in children with AVNRT.
Recently, voltage gradient mapping of Koch's triangle to find low-voltage connections, or 'voltage bridges', corresponding to the anatomic position of the slow pathway, has been introduced as a method to ablate atrioventricular nodal reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the effectiveness of voltage mapping of Koch's triangle, combined with the search for the slow potential signal in 'low-voltage bridges', to guide cryoablation of AVNRT in children. From June 2015 to May 2016, 35 consecutive paediatric patients (mean age 12.1 ± 4.5 years) underwent 3D-guided cryoablation of AVNRT at our Institution. Fifteen children were enrolled as control group (mean age 14 ± 4 years). A voltage gradient mapping of Koch's triangle was obtained in all patients, showing low-voltage connections in all children with AVNRT but not in controls. Prior to performing cryoablation, we looked for the typical 'hump and spike' electrogram, generally considered to be representative of slow pathway potential within a low-voltage bridge. In all patients the 'hump and spike' electrogram was found inside bridges of low voltage. Focal or high-density linear lesions, extended or not, were delivered guided by low-voltage bridge visualization. Acute success rate was 100%, and no recurrence was reported at a mean follow-up of 8 ± 3 months. Voltage gradient mapping of Koch's triangle, combined with the search for the slow potential signal in low-voltage bridges, is effective in guiding cryoablation of AVNRT in paediatric patients, with a complete acute success rate and no AVNRT recurrences at mid-term follow-up.


[Pathogenesis of hemolytic-uremic syndrome].
Current literature on the pathogenesis of the hemolytic-uremic syndrome (HUS) is analyzed. A variety of etiologic factors and mechanisms of HUS development is considered. The emphasis is laid on the endotoxinemia, damage of the renal vessel and glomerular mesangium endothelium and other mechanisms.


Sample conditions determine the ability of thrombin generation parameters to identify bleeding phenotype in FXI deficiency.
Individuals with Factor XI (FXI) deficiency have a variable bleeding tendency that does not correlate with FXI:C levels or genotype. Comparing a range of sample conditions, we tested whether the thrombin generation assay (TGA) could discriminate between control subjects (n = 50) and FXI-deficient individuals (n = 97), and between those with bleeding tendency (n = 50) and without (n = 24). The comparison used platelet-rich plasma (PRP) and platelet-poor plasma (PPP), either with or without corn trypsin inhibitor (CTI) to prevent contact activation, over a range of tissue factor (TF) concentrations. When contact activation was inhibited and platelets were absent, FXI:C levels did not correlate with thrombin generation parameters, and control and FXI-deficient individuals were not distinguished. In all other sample types, the best discrimination was obtained using TF 0.5 pM and assay measures: endogenous thrombin potential (ETP) and peak height. We showed that although a number of conditions could distinguish differences between the groups tested, TGA measured in PRP with CTI best differentiated between bleeders and nonbleeders. These measures provided high sensitivity and specificity (peak height receiver operating characteristic [ROC] area under the curve [AUC] = 0.9362; P < .0001) (ETP ROC AUC = 0.9362; P < .0001). We conclude that by using sample conditions directed to test specific pathways of FXI activation, the TGA can identify bleeding phenotype in FXI deficiency.


Ebola, team communication, and shame: but shame on whom?
Examined as an isolated situation, and through the lens of a rare and feared disease, Mr. Duncan's case seems ripe for second-guessing the physicians and nurses who cared for him. But viewed from the perspective of what we know about errors and team communication, his case is all too common. Nearly 440,000 patient deaths in the U.S. each year may be attributable to medical errors. Breakdowns in communication among health care teams contribute in the majority of these errors. The culture of health care does not seem to foster functional, effective communication between and among professionals. Why? And more importantly, why do we not do something about it?


[Improving detection and treatment of early psychosis in Québec: the Quebec association of early psychosis (l'Association québécoise des programmes pour premiers épisodes psychotiques, AQPPEP), sees to it].
June 2004: the Quebec association of early psychosis programs, AQPPEP (Association québécoise des programmes pour premiers épisodes psychotiques), was created. The Association's objectives is to promote clinical and scientific discussions between health care professionals and researchers sharing an interest for people suffering from an early psychosis, and to improve earlier detection of psychosis. It also aims at increasing awareness of the problem in the general population and governments. To reach these goals, AQPPEP has organized the first early psychosis awareness day in Quebec and developed one of the rare French language web sites in this area. Finally, the Association is a tool to better face, in a concerted approach, some difficulties that many first episode clinics have to deal with, in order to share or develop common solutions.


Large tunability in the mechanical and thermal properties of carbon nanotube-fullerene hierarchical monoliths.
Carbon based materials have attracted much attention as building blocks in technologically relevant nanocomposites due to their unique chemical and physical properties. Here, we propose a new class of hierarchical carbon based nano-truss structures consisting of fullerene joints attached with carbon nanotubes as the truss forming a three-dimensional network. Atomistic molecular dynamics simulations allow us to systematically demonstrate the ability to simultaneously control the mechanical and thermal properties of these structures, elucidating their unique physical properties. Specifically, we perform uniaxial tensile and compressive loading to show that by controlling the length of the carbon nanotube trusses, the mechanical properties can be tuned over a large range. Furthermore, we utilize the Green-Kubo method under the equilibrium molecular dynamics simulations framework to show that the thermal conductivities of these structures can be manipulated by varying the densities of the overall structures. This work provides a computational framework guiding future research on the manipulation of the fundamental physical properties in these organic-based hierarchical structures composed of carbon nanotubes and fullerenes as building blocks.


Within-hemifield competition in early visual areas limits the ability to track multiple objects with attention.
It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex.


β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells.
Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. β-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.


Shape Factor of the Spinal Cord: A Possible Predictor of Surgical Outcome for Intradural Extramedullary Spinal Tumors in the Thoracic Spine.
Retrospective diagnostic analysis. To establish a new predictor of surgical outcome after surgery for intradural extramedullary spinal tumor (IDEMT) in the thoracic spine, we introduced shape factor (SF), a mathematical description of the morphology of the spinal cord. SF was calculated by dividing object area by the square of perimeter. Forty-three consecutive patients with IDEMT, detected by magnetic resonance imaging at the thoracic level with myelopathic signs, were included. Preoperative transverse cross-sectional area (CSA) and perimeter of the spinal cord (perimeter) at the level of maximal compression were measured. SF was calculated as 4π × CSA/(perimeter)2. The association between clinicoradiological factors and surgical outcome of IDEMT was statistically analyzed. Mean CSA, perimeter, and SF were 27.8 ± 15.8 mm2, 28.8 ± 6.1 mm, and 0.385 ± 0.14, respectively. A histogram distribution revealed that perimeter and SF, but not CSA, fit the normal distribution. The patients were subdivided into 2 groups according to postoperative modified Japanese Orthopedic Association Score (mJOA). [group F (favorable): n = 32, mJOA ≥ 9; group UF (unfavorable): n = 11, mJOA < 9). Group UF had significantly lower mean CSA and SF. In univariate analysis of possible predictive factors for IDEMT surgery, greater age, lower preoperative mJOA, and lower SF were significantly associated with unfavorable outcome. In multivariate analysis, lower SF was the only significant predictor of postoperative outcome (odds ratio = 2.66, 95% CI 1.10-6.39, p = 0.0115). Measurements of CSA and perimeter, followed by calculation of SF, may provide valuable quantitative information for the outcome of surgery for IDEMT.


Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer?
Older patients are increasingly undergoing allogeneic hematopoietic transplantation. A relevant question is whether outcomes can be improved with a younger allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD). Accordingly, transplants in leukemia/lymphoma patients age ≥50 years were analyzed comparing outcomes for recipients of MSD ≥50 (n = 1415) versus MUD <50 years (n = 757). Risks of acute graft-versus-host disease (GVHD) grade 2 to 4 (hazard ratio [HR], 1.63; P < .001), 3 to 4 (HR, 1.85; P < .001), and chronic GVHD (HR, 1.48; P < .0001) were higher after MUD compared with MSD transplants. The effect of donor type on nonrelapse mortality (NRM), relapse, and overall mortality was associated with performance score. For patients with scores of 90 or 100, NRM (HR, 1.42; P = .001), relapse (HR, 1.45; P < .001), and overall mortality (HR, 1.28; P = .001) risks were higher after MUD transplants. For patients with scores below 90, NRM (HR, 0.96; P = .76), relapse (HR, 0.86; P = .25), and overall mortality (HR, 0.90; P = .29) were not significantly different after MUD and MSD transplants. These data favor an MSD over a MUD in patients age ≥50 years.


[Effects of phosphatidylcholine pretreatment during acute experimental biliary reflux].
Biliary regurgitation plays important role in gastro-esophageal reflux disease and postoperative complications. Our major aims were to find out the consequences of short-term exposure with luminal bile on mucosal microcirculation and nitric oxide synthesis, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition. The experiments were performed on inbred mongrel dogs. Group 1 (n=5) served as a saline-treated control, while in group 2 (n=5) the esophagus was exposed to bile for 3 h. In group 3 (n=5) the animals were pre-treated with 7-nitroindazole (7-NI), to inhibit the neuronal isoform of nitric oxide synthase. In group 4 (n=5) phosphatidylcholine (PC) solution (50 mg/kg) was administered iv before the biliary challenge. The microcirculation of the mucosa was observed by intravital videomicroscopy; myeloperoxidase and nitric oxide synthase activities, the degree of mast cell degranulation and tissue damage were evaluated via tissue biopsies. Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation, and the red blood cell velocity (VRBC) and the diameter of the postcapillary venules (VD) increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared with the control values. 7-NI treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. In contrast, PC pretreatment reversed the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity increases, and the mast cell degranulation. The neuronal nitric oxide synthase--mast cell axis plays an important role in the esophageal mucosal defense system. Systemic PC pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.


Phase I and pharmacokinetic study of menogaril administered as a 72-hour continuous i.v. infusion.
Menogaril is a new anthracycline analog of nogalamycin. When administered as a 72-hour continuous iv infusion the dose-limiting toxic effect of menogaril was venous irritation at dose levels that cause only mild leukopenia and minimal gastrointestinal toxicity. Pharmacokinetic studies showed that the rise in plasma concentration during infusion was first-order, with a half-life of 11.9 hours. Total-body clearance of menogaril was 204 ml/minute/m2. There were no detectable metabolites of menogaril in plasma. Urinary excretion of unchanged menogaril was 17.3% of the dose and N-demethylmenogaril was 0.5% over 72 hours. Since menogaril does not appear to be metabolized, a high degree of tissue binding is likely.


Pseudodoping of a metallic two-dimensional material by the supporting substrate.
Charge transfers resulting from weak bondings between two-dimensional materials and the supporting substrates are often tacitly associated with their work function differences. In this context, two-dimensional materials could be normally doped at relatively low levels. Here, we demonstrate how even weak hybridization with substrates can lead to an apparent heavy doping, using the example of monolayer 1H-TaS2 grown on Au(111). Ab-initio calculations show that sizable changes in Fermi areas can arise, while the transferred charge between substrate and two-dimensional material is much smaller than the variation of Fermi areas suggests. This mechanism, which we refer to as pseudodoping, is associated with non-linear energy-dependent shifts of electronic spectra, which our scanning tunneling spectroscopy experiments reveal for clean and defective TaS2 monolayer on Au(111). The influence of pseudodoping on the formation of many-body states in two-dimensional metallic materials is analyzed, shedding light on utilizing pseudodoping to control electronic phase diagrams.


Does Digital Nature Enhance Social Aspirations? An Experimental Study.
Loneliness and social isolation are increasingly recognized as important challenges of our times. Inspired by research hinting at beneficial effects of interacting with nature on social connectedness and opportunities provided by ambient technology to simulate nature in a rich and engaging manner, this study explored to what extent digital nature projections can stimulate social aspirations and related emotions. To this end, participants (N = 96) were asked to watch, individually or in pairs, digital nature projections consisting of animated scenes which were either dense or spacious and depicting either wild or tended nature. Subsequently, they filled out a questionnaire comprising measures for social aspirations, awe and fascination. Results show that spacious scenes elicited significantly higher social aspiration and awe scores, especially when watching alone. Design implications are discussed for making digital nature accessible for people with limited access to real nature.


In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants.
mRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence content is insufficient for this purpose. Previous studies suggested that RNA structure affects mRNA processing. However, the regulatory role of RNA structure in mRNA processing remains unclear. Here, we perform in vivo selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemical profiling on Arabidopsis and generate the in vivo nuclear RNA structure landscape. We find that nuclear mRNAs fold differently from cytosolic mRNAs across translation start and stop sites. Notably, we discover a two-nucleotide single-stranded RNA structure feature upstream of 5' splice sites that is strongly associated with splicing and the selection of alternative 5' splice sites. The regulatory role of this RNA structure feature is further confirmed by experimental validation. Moreover, we find the single-strandedness of branch sites is also associated with 3' splice site recognition. We also identify an RNA structure feature comprising two close-by single-stranded regions that is specifically associated with both polyadenylation and alternative polyadenylation events. We successfully identify pre-mRNA structure features associated with splicing and polyadenylation at whole-genome scale and validate an RNA structure feature which can regulate splicing. Our study unveils a new RNA structure regulatory mechanism for mRNA processing.


[Transformation of the kidney lymphatic system in clinical pathology].
The nature of transformations in the renal lymphatic system in the clinical pathology of the kidneys, mainly in the final stage of chronic glomerulonephritis, hypertension, atherosclerosis, hydronephrotic transformation (45 autopsy kidneys) is demonstrated. The controls consisted of kidneys from patients dying with non-renal pathology (12 organs). In the final stages of the above diseases progressive reduction of the intraorgan lymphatic capillaries and vessels with simultaneous marked vascularization of the fibrous renal capsule due to an increase in the amount of lymphatic capillaries (their growth) and formation of new abducting lymph stems, numerous anastomoses between them, as well as distention in the vessel lumens and the development of varicosis of the wall. These morphological changes indicate high plastic properties of the lymphatic system and its role in the retention of the renal function in developing "local" lymph congestions in the organ because of outgrowth of the connective tissue. On the other hand, they are universal and reflect the time course of the progress.


A GABAergic inhibitory component within the hippocampal commissural pathway.
Previous results from immunocytochemical and retrograde transport studies indicated that some GABAergic neurons in the hilus of the dentate gyrus may have axonal projections through the hippocampal commissure. This study has utilized a combined immunocytochemical and retrograde transport method as well as 2 anterograde electron-microscopic methods to determine the existence of this projection in rats. Combined tracer and immunofluorescence studies showed several double-labeled GABAergic neurons in the hilus contralateral to the injection site. The electron-microscopic studies revealed both degenerating and HRP-labeled commissural axons that formed symmetric synapses, the type shown to be formed by GABAergic terminals in the hippocampus. These data demonstrate a GABAergic component within the hippocampal commissural pathway and add further evidence that cortical GABAergic terminals are not derived exclusively from intrinsic neurons.


Melatonin triggers metabolic and gene expression changes leading to improved quality traits of two sweet cherry cultivars during cold storage.
Sweet cherry is a valuable non-climacteric fruit with elevated phytonutrients, whose fruit quality attributes are prone to rapid deterioration after harvest, especially peel damage and water loss of stem. Here the metabolic and transcriptional response of exogenous melatonin was assessed in two commercial cultivars of sweet cherry (Santina and Royal Rainier) during cold storage. Gene expression profiling revealed that cuticle composition and water movement may underlie the effect of melatonin in delaying weight loss. An effect of melatonin on total soluble solids and lower respiration rate was observed in both cultivars. Melatonin induces overexpression of genes related to anthocyanin biosynthesis, which correlates with increased anthocyanin levels and changes in skin color (Chroma). Our results indicate that along with modulating antioxidant metabolism, melatonin improves fruit quality traits by triggering a range of metabolic and gene expression changes, which ultimately contribute to extend sweet cherry postharvest storability.


Suitability of a Low-Cost Wearable Sensor to Assess Turning in Healthy Adults.
Background: Turning is a complex measure of gait that accounts for over 50% of daily steps. Traditionally, turning has been measured in a research grade laboratory setting, however, there is demand for a low-cost and portable solution to measure turning using wearable technology. This study aimed to determine the suitability of a low-cost inertial sensor-based device (AX6, Axivity) to assess turning, by simultaneously capturing and comparing to a turn algorithm output from a previously validated reference inertial sensor-based device (Opal), in healthy young adults. Methodology: Thirty participants (aged 23.9 ± 4.89 years) completed the following turning protocol wearing the AX6 and reference device: a turn course, a two-minute walk (including 180° turns) and turning in place, alternating 360° turn right and left. Both devices were attached at the lumbar spine, one Opal via a belt, and the AX6 via double sided tape attached directly to the skin. Turning measures included number of turns, average turn duration, angle, velocity, and jerk. Results: Agreement between the outcomes from the AX6 and reference device was good to excellent for all turn characteristics (all ICCs > 0.850) during the turning 360° task. There was good agreement for all turn characteristics (all ICCs > 0.800) during the two-minute walk task, except for moderate agreement for turn angle (ICC 0.683). Agreement for turn outcomes was moderate to good during the turns course (ICCs range; 0.580 to 0.870). Conclusions: A low-cost wearable sensor, AX6, can be a suitable and fit-for-purpose device when used with validated algorithms for assessment of turning outcomes, particularly during continuous turning tasks. Future work needs to determine the suitability and validity of turning in aging and clinical cohorts within low-resource settings.


Characteristics of Hospitalized Children With a Diagnosis of Malnutrition: United States, 2010.
Malnutrition is common in hospitalized patients in the United States. In 2010, 80,710 of 6,280,710 hospitalized children <17 years old had a coded diagnosis of malnutrition (CDM). This report summarizes nationally representative, person-level characteristics of hospitalized children with a CDM. Data are from the 2010 Healthcare Cost and Utilization Project, which contains patient-level data on hospital inpatient stays. When weighted appropriately, estimates from the project represent all U.S. hospitalizations. The data set contains up to 25 ICD-9-CM diagnostic codes for each patient. Children with a CDM listed during hospitalization were identified. In 2010, 1.3% of hospitalized patients <17 years had a CDM. Since the data include only those with a CDM, malnutrition's true prevalence may be underrepresented. Length of stay among children with a CDM was almost 2.5 times longer than those without a CDM. Hospital costs for children with a CDM were >3 times higher than those without a CDM. Hospitalized children with a CDM were less likely to have routine discharge and almost 3.5 times more likely to require postdischarge home care. Children with a CDM were more likely to have multiple comorbidities. Hospitalized children with a CDM are associated with more comorbidities, longer hospital stay, and higher healthcare costs than those without this diagnosis. These undernourished children may utilize more healthcare resources in the hospital and community. Clinicians and policymakers should factor this into healthcare resource utilization planning. Recognizing and accurately coding malnutrition in hospitalized children may reveal the true prevalence of malnutrition.


Efficacy of a new fixed-dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) in Australian cattle against artificial infections of gastrointestinal nematodes.
We describe a new fixed-dose combination injectable (FDCI) formulated with doramectin and levamisole hydrochloride (HCl) to target broad and overlapping spectra of gastrointestinal nematodes (GINs) through two distinct modes of action. Here, we demonstrate the superior efficacy of the FDCI against mixed populations of cattle GINs in two dose confirmation studies conducted in Australia using artificially induced adult (Study 1) and immature (Study 2) GIN infections. Artificial infections consisted of Cooperia spp., Haemonchus placei, Ostertagia ostertagi, and Trichostrongylus axei. In both studies, cattle were inoculated with third-stage larvae and infections were confirmed by fecal egg count (FEC). Treatment groups in both studies were as follows: (1) negative control (saline, 0.9% sodium chloride), (2) positive control injectable endectocide (Study 1-0.2 mg/kg ivermectin; Study 2-0.2 mg/kg doramectin), (3) positive control injectable anthelmintic (7.5 mg/kg levamisole HCl), and (4) FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole HCl). Cattle were treated either 28 days (Study 1) or 6 days (Study 2) post-infection. On Days 14-16 (Study 1) or Days 20-21 (Study 2) post-treatment, cattle were euthanized and necropsied for the recovery, identification, and enumeration of worms. Treatment efficacy was calculated as reduction in worm burdens of treated cattle compared to saline-treated cattle, and treatments were considered effective if the geometric mean worm burden in the treatment group was reduced by ≥ 95% compared to the negative control group. In both studies, saline-treated cattle remained positive for GIN infections for the study duration. Ivermectin was less than 95% effective against Cooperia spp. (80.2%) and H. placei (24.8%) in Study 1, and levamisole HCl was less than 95% effective against Ostertagia spp. (47.1%) in Study 2. In contrast, the novel FDCI was 100% effective in treating adult and immature life stages of all cattle GINs included in the artificial infections, with no worms recovered at necropsy from doramectin + levamisole HCl-treated cattle. These data show a single administration of the FDCI provides broad-spectrum treatment of economically important cattle GINs.


Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors.
The ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of islet allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. However, transient transgene expression and the tendency to induce host inflammatory responses have limited previous gene delivery studies using viral transfer vectors. We demonstrate here that recombinant adeno-associated virus (rAAV) serotype 2, a vector that can overcome these limitations, effectively transduces both human and murine pancreatic islet cells with reporter genes as well as potentially important immunoregulatory cytokine genes (interleukin-4, interleukin-10), although a very high multiplicity of infection (10,000 infectious units/islet equivalent) was required. This requirement was alleviated by switching to rAAV serotype 5, which efficiently transduced islets at a multiplicity of infection of 100. Although adenovirus (Ad) coinfection was required for efficient ex vivo expression at early time points, islets transduced without Ad expressed efficiently when they were transplanted under the renal capsule and allowed to survive in vivo. The rAAV-delivered transgenes did not interfere with islet cell insulin production and were expressed in both beta- and non-beta-cells. We believe rAAV will provide a useful tool to deliver therapeutic genes for modulating immune responses against islet cells and markedly enhance longterm graft survival.


Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer's disease.
Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine treatment on regional brain activity was measured with fMRI in patients with mild AD. Eleven patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. There was an increase in task-related brain activity after treatment with activations more like those of normal healthy elderly. Behaviorally, however, there were no significant differences between baseline and retest scores, with a range of performance probably reflecting variation in drug efficacy across patients. Variable patient response and drug dynamic/kinetic factors in small patient groups will inevitably bias (either way) the effect size of any relevant drug related changes in activation. Future studies should take drug response into account to provide more insight into the benefits of ChEI drugs at the individual level.


[Mandibular advancement orthoses used in the treatment of obstructive sleep apnea syndrome].
Mandibular advancement devices represent a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proven in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated decrease in snoring frequency and intensity. The effect of these ortheses on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases. Although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3 and 4 and rapid eye movement sleep. Micro-arousals are also decreased in number certainly with the decrease in the occurrence of respiratory events. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done.


Localization in the brain of the inhibition by GABA of luteinizing hormone release that follows orchidectomy in rats.
The possible participation of GABA (gamma-aminobutyric acid) in the enhanced release of luteinizing hormone that follows orchidectomy was examined. The GABA-transaminase inhibitor, gamma vinyl GABA, injected stereotaxically into the locus ceruleus area blocked the postcastration rise of luteinizing hormone in plasma. In contrast, this response developed normally when the drug was administered either to the medial or the dorsal preoptic area and to the mediobasal hypothalamus. The present preliminary results suggest that the increase of GABA at synaptic sites affects luteinizing hormone release in castrated male rats through an action on the noradrenergic cell bodies of the locus ceruleus system.


Isolation of human synovial-fluid hyaluronate by density-gradient ultracentrifugation and evaluation of its protein content.
1. A compound of hyaluronate and protein, called hyaluronate-protein was isolated from pooled human synovial fluids by caesium chloride density-gradient ultracentrifugation. 2. The isolated hyaluronate-protein was labelled with [(125)I]iodide and the following studies were done. (a) Ultracentrifugation in caesium chloride showed that the protein moiety ((125)I counts) and hyaluronate (hexuronate) sedimented together in the middle of the gradient. (b) The labelled hyaluronate-protein was treated with trypsin, and ultracentrifugation showed that peptide fragments ((125)I counts) were dispersed throughout the gradient, indicating proteolytic digestion. Hyaluronate sedimented in the middle of the gradient. (c) The labelled hyaluronate-protein was digested with streptococcal hyaluronidase, and ultracentrifugation showed that hyaluronate fragments were dispersed throughout the gradient, indicating digestion of the polysaccharide. The protein moiety, without attached hyaluronate, now sedimented at the top of the gradient. (d) Ultracentrifugation of labelled hyaluronate-protein in 4m-guanidinium chloride showed that protein and hyaluronate sedimented together. 3. These studies confirm that hyaluronate is combined with a small quantity of protein in normal human synovial fluid. A mild method for the rapid isolation of hyaluronate-protein in good yield is described.


The prevalence and socio-demographic correlates of khat chewing in Butajira, Ethiopia.
A house-to-house survey was carried out in a rural Ethiopian community to determine the prevalence and socio-demographic correlates of khat use. A total of 10,468 adults were interviewed. Of these, 58% were female, and 74% were Muslim. More than half of the study population (55.7%) reported lifetime khat chewing experience and the prevalence of current use was 50%. Among current chewers, 17.4% reported taking khat on a daily basis; 16.1% of these were male and 3.4% were female. Various reasons were given for chewing khat; 80% of the chewers used it to gain a good level of concentration for prayer. Muslim religion, smoking and high educational level showed strong association with daily khat chewing.


Acute death associated with Citrobacter freundii infection in an African elephant (Loxodonta africana).
A 21-year-old male African elephant (Loxodonta africana) died suddenly with no previous medical history. Grossly, there were severe multifocal epicardial and endocardial hemorrhages of the atria and ventricles, hydropericardium, multifocal pleural hemorrhages, and severe pulmonary congestion and edema. Histologically, there was fibrinoid vasculitis and thrombosis in the heart and lung and myocardial necrosis. Citrobacter freundii was isolated in abundance in pure culture from liver and heart samples. Low levels of multiples types of elephant endotheliotropic herpesvirus (EEHV-6, EEHV-2B, and EEHV-3A) were detected in spleen samples, but not in heart samples. The levels of EEHV DNA found were much lower than those usually associated with acute EEHV hemorrhagic disease, and many other genomic loci that would normally be found in such cases were evidently below the level of detection. Therefore, these findings are unlikely to indicate lethal EEHV disease. Polymerase chain reaction for encephalomyocarditis virus (EMCV) and toxicology for oleander (Nerium oleander) were negative. Stress, resulting from recent transport, and antimicrobial therapy may have contributed to the death of this animal.


Subsidised oocyte donation in Israel (1998-2000): results, costs and lessons.
Israeli law stipulates that all women aged 45-51 who need oocyte donation are entitled to as many donations as necessary, up to the birth of one child. Only oocytes donated by women who themselves are undergoing assisted reproduction are allowed. The government subsidizes all oocyte donation cycles through the medical insurer of the recipient, whether or not the procedure is performed in a public or private institution. The aim of the present study was to investigate the success of oocyte donation cycles in Israel for the period 1998-2000 and to estimate costs and pregnancy rates. Data were derived from the Dan District Registry of the General Health Services (Sheirutei Bri'ut Clalit), the largest medical insurer in Israel. 171 women underwent 254 oocyte donation cycles within these 3 years, and 45 babies were born, for a positive outcome of 17.7%. Average annual cycle cost was US$1742 and average annual cost per patient, US$2521. The total annual cost for the district accounted for only 0.05% of the budget. These findings suggest that IVF with donated oocytes is relatively efficient and that government funding of oocyte donation cycles ensures a reasonable cost.


Temporal patterns in ambient noise of biological origin from a shallow water temperate reef.
A systematic study of the ambient noise in the shallow coastal waters of north-eastern New Zealand shows large temporal variability in acoustic power levels between seasons, moon phase and the time of day. Ambient noise levels were highest during the new moon and the lowest during the full moon. Ambient noise levels were also significantly higher during summer and lower during winter. Bandpass filtering (700-2,000 Hz and 2-15 kHz), combined with snap counts and data from other studies show that the majority of the sound intensity increases could be attributed to two organisms: the sea urchin and the snapping shrimp. The increased intensity of biologically produced sound during dusk, new moon and summer could enhance the biological signature of a reef and transmit it further offshore. Ambient noise generated from the coast, especially reefs, has been implicated as playing a role in guiding pelagic post-larval fish and crustaceans to settlement habitats. Determining a causal link between temporal increases in ambient noise and higher rates of settlement of reef fish and crustaceans would provide support for the importance of ambient underwater sound in guiding the settlement of these organisms.


Development and validation of a disease extent index for Wegener's granulomatosis.
The quantitative assessment of disease extent (staging) and activity (grading) in patients with ANCA-associated vasculitides is one prerequisite for the comparison of outcomes in different patient cohorts. We present a validation study of the Disease Extent Index (DEI). 66 patients with Wegener's granulomatosis were examined to assess the validity, reliability and sensitivity to change of the DEI. Correlation coefficients were calculated to estimate associations between DEI and BVAS (Birmingham Vasculitis Activity Score), a previously established activity score, and between DEI and serological markers. Among patients with active disease, DEI correlated significantly with cANCA titer (r = 0.46), leukocyte count (r = 0.38) and platelet count (r = 0.53). Among patients in remission, DEI correlated significantly with cANCA titer (r = 0.61), CRP (r = 0.47) and sIL2R (r = 0.47). Additionally, a high association of DEI and BVAS (r = 0.9) confirmed a rather high convergent validity. The effect size of DEI equals 2.37 standard deviation units and indicates a considerable change from active disease to remission. The DEI is valid, reliable, easy, quick to perform and highly reproducible. Although it correlates with some surrogate markers of disease activity and the BVAS, the DEI quantifies different domains of the disease than the BVAS and should therefore be used in conjunction with the BVAS.


Recyclization of 5-Amino- oxazoles as a Route to new Functionalized Heterocycles (Developments of V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine).
The recyclizations of 5-amino- and 5-hydrazine-1,3-oxazoles mainly with electron-withdrawing group in 4th position are considered. The chemical behavior of these heterocycles is due to the presence of two hidden amide fragments; therefore, the recyclization processes include a stage of nucleophile attack on 2nd or 5th position of the oxazole cycle. When the nitrile group is present in 4th position, it is often involved in the recyclization forming α-aminoazoles. 5-Amino/hydrazine-1,3-oxazoles undergo recyclization both in nucleophilic (amines, hydrazine, thionating agents) and electrophilic medium ((trifluoro)acetic acid, other acylating agents). The numerous types of functionalized heterocycles can be easily obtained with the usage of these recyclizations, such as the derivatives of 3-amino-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole, imidazolidine-2,4-dione, 1H-pyrazole-3,4,5-triamine, 5,6-diamino-2,3-diphenylpyrimidin-4(3H)-one, 2-(2-R-7-oxo-5-(trifluoromethyl)oxazolo[5,4-d]pyrimidin-6(7H)-yl)acetic acid, 2-R-4-(5-R'-1,3,4-oxadiazol-2-yl)oxazol-5-amine, (amino(5-amino-1,3,4-thiadiazol-2-yl)methyl)phosphonate.


10- or 30-minute treadmill exercise rescues motor behaviors through inhibiting apoptosis in a rat MCAo model.
Ischemic stroke, one of the world's leading fatal diseases, has a high recurrence and incidence that can lead to severe mortality and disability. In this study, we investigated whether exercise can treat ischemic stroke to prevent recurrence and improve functional impairment. Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAo) in rats, and the effect of 10- or 30-minute training for two weeks was evaluated. Following cylinder and rota-rod behavioral tests, we found that motor function was improved compared to the non-exercise group. In addition, the brain infarct volume was decreased after exercise following TTC staining. Further examination of the cell signaling mechanisms involved in the improvement showed that the immune reactivity significantly decreased the expression of the pro-apoptotic protein, Bax, and increased that of the anti-apoptotic protein, Bcl-2. Our results suggest that exercise has a beneficial effect on ischemic stroke for short- or long-term training.


Numerical modeling of the releases of (90)SR from Fukushima to the ocean: an evaluation of the source term.
A numerical model consisting of a 3D advection/diffusion equation, including uptake/release reactions between water and sediments described in a dynamic way, has been applied to simulate the marine releases of (90)Sr from the Fukushima power plant after the March 2011 tsunami. This is a relevant issue since (90)Sr releases are still occurring. The model used here had been successfully applied to simulate (137)Cs releases. Assuming that the temporal trend of (90)Sr releases was the same as for (137)Cs during the four months after the accident simulated here, the source term could be evaluated, resulting in a total release of 80 TBq of (90)Sr until the end of June, which is in the lower range of previous estimates. Computed vertical profiles of (90)Sr in the water column have been compared with measured ones. The (90)Sr inventories within the model domain have also been calculated for the water column and for bed sediments. Maximum dissolved inventory (obtained for April 10th, 2011) within the model domain results in about 58 TBq. Inventories in bed sediments are 3 orders of magnitude lower than in the water column due to the low reactivity of this radionuclide. (90)Sr/(137)Cs ratios in the ocean have also been calculated and compared with measured values, showing both spatial and temporal variations.


[Neuropsychological symptomatology in normal pressure hydrocephalus].
The neuropsychological observations of 63 patients undergoing surgery for "normal pressure hydrocephalus" (NPH) have been analyzed retrospectively. To make a semiological picture of mental disturbances in NPH, the level of consciousness, behaviour and cognitive functions were studied. A neuropsychological investigation of the main cognitive functions (language, gnosis, praxis, calculation, memory) enables us to specify the characteristics of dementia shown by these patients. A mental picture of the most frequent neuropsychological signs is described. The mental syndrome which characterized NPH reveals an alteration of alertness and concentration, a deficiency in memory, a disorganization of graphism (writing and drawing), a dyscalculia and behaviour problems (bradypsychy, apathy, indifference). Such a syndrome points out a bilateral frontal lesion. On the other hand, the less frequent signs are largely verbal and show different stages of aphasia. These signs can usually be found in patients who don't improve after ventricular drainage and are more suggestive of a degenerative disease of the Alzheimer type. The results are compared with the psychometric and neuropsychological data of the literature. More specific attention is accorded to differential diagnosis.


The value of spectrophotometric intracutaneous analysis in the noninvasive diagnosis of nonmelanoma skin cancers.
Spectrophotometric intracutaneous analysis (SIAscopy) is a recently introduced, noninvasive, rapid and practical method for monitoring pigmented lesions, which calculates the amount of collagen, melanin and haemoglobin deep in the papillary dermis. To evaluate the value of SIAscopy in the diagnosis of nonmelanoma skin cancers (NMSC). In total, 80 lesions of 76 patients were clinically evaluated by the first investigator, and the data recorded. Eight months after the clinical evaluation, all lesions were evaluated again by the same investigator, using images (SIAgraphs) obtained by the SIAscope. All SIAgraphs were also evaluated by a second investigator, and all dermatoscopic images by a third, independently of each other. All diagnoses were compared with histopathological diagnoses. The clinical diagnosis was calculated to have a sensitivity of 79% and specificity of 84%. The SIAscopic diagnoses of the first and second investigators had a sensitivity of 55% and 93%, and a specificity of 88% and 53%, respectively, while the dermatoscopic diagnoses of the third investigator had a sensitivity of 86% and specificity of 80%. There was no statistical accordance between the first and second investigators according to the accuracy of SIAscopic diagnoses (P < 0.01). The area under the curve for the receiver operator characteristic was 0.82 for clinical diagnosis, 0.73 and 0.80 for the SIAscopic evaluation of the first and the second investigators, respectively, and 0.87 for the dermatoscopic evaluation of the third investigator. Our findings show that dermatoscopic findings are more valuable than SIAscopic and clinical findings for the noninvasive diagnosis of NMSC. We consider that SIAscopy makes no substantial contribution towards the differential diagnosis of NMSC.


Versatile chromatic dispersion measurement of a single mode fiber using spectral white light interferometry.
We present a versatile and accurate chromatic dispersion measurement method for single mode optical fibers over a wide spectral range (200 nm) using a spectral domain white light interferometer. This technique is based on spectral interferometry with a Mach-Zehnder interferometer setup and a broad band light source. It takes less than a second to obtain a spectral interferogram for a few tens of centimeter length fiber sample. We have demonstrated that the relative group velocity, the chromatic dispersion and the dispersion slope of a sample fiber can be obtained very accurately regardless of the zero-dispersion wavelength (ZDW) of a sample after frequency dependent optical phase was directly retrieved from a spectral interferogram. The measured results with our proposed method were compared with those obtained with a conventional time-domain dispersion measurement method. A good agreement between those results indicates that our proposed method can measure the chromatic dispersion of a short length optical fiber with very high accuracy.


Correlates of 2009 pandemic H1N1 influenza vaccine acceptance among middle and high school teachers in rural Georgia.
Teachers play an essential role in the school community, and H1N1 vaccination of teachers is critical to protect not only themselves but also adolescents they come in contact within the classroom through herd immunity. School-aged children have a greater risk of developing H1N1 disease than seasonal influenza. The goal of this study was to assess the relationship between attitudes toward H1N1 vaccination and vaccine acceptance among middle and high school teachers in rural Georgia. Participants were recruited from 2 counties participating in a school-based influenza vaccination intervention in rural Georgia. Data were collected from surveys distributed to middle and high school teachers in participating counties in September 2009 prior to implementing the interventions to increase vaccination against seasonal influenza. Multivariate logistic regression was used to assess the association between teachers' attitudes toward H1N1 vaccination and H1N1 vaccine acceptance, controlling for demographic variables. Among participants, 52.9% indicated that they would get the H1N1 vaccine. In multivariate analyses, H1N1 vaccine acceptance was associated with male gender (odds ratio[OR] = 3.67, p = .016), fear of contracting H1N1 (OR = 3.18, p = .025), and receipt of a seasonal influenza vaccine in the past year (OR = 3.07, p = .031). H1N1 vaccine acceptance was not significantly associated with age, race, perceived severity of H1N1, belief that the H1N1 vaccine would cause illness, or talking about H1N1 with friends. Teachers may play a pivotal role in school-based H1N1 vaccinations. Understanding and addressing teachers' attitudes toward H1N1 vaccination may assist in future immunization efforts.


[The importance of bovine neosporosis for abortion in Switzerland].
The protozoan parasite Neospora caninum is one of the most important infectious abortion causes in cattle worldwide. In a Swiss case-control-study we investigated 113 abortion problem farms and 113 control farms. It was possible to detect N. caninum in 21% of 242 investigated aborted fetuses by PCR upon brain samples. Eighty-four % of mothers aborting N. caninum positive fetuses were serologically positive for this parasite. The seroprevalence for N. caninum of all aborting mothers was 44%. Within a period of 3 to 12 months 4,505 cattle from the participating farms were investigated serologically at two different time points. Strong fluctuations of the specific antibody concentration could be observed, resulting in a conversion to seronegativity in the second blood sample in 39% of formerly seropositive animals. Eighteen months after the end of the study, 42 case- and 42 controlfarms were questioned about their present abortion-status. Analysis of the questionnaire revealed that 80% of the former abortion problem farms observed an improvement of the situation. However, in 43% of those farms no preventive measures had been taken and no significant differences in hygiene, forage and animal turnover could be observed between case- and control-farms. Additionally, no significant differences were detected concerning risk factors such as the presence of farm dogs and the disposal procedure for placental and fetal material.


Kinetic analysis of NAD(+)-isocitrate dehydrogenase with altered isocitrate binding sites: contribution of IDH1 and IDH2 subunits to regulation and catalysis.
NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is an allosterically regulated enzyme that exists as an octamer composed of two nonidentical subunits, designated IDH1 and IDH2. To determine the contribution of each subunit to regulation and catalysis, a conserved serine residue at the proposed active site of each subunit was mutated to alanine. This mutation in IDH1 resulted in a 6-fold decrease in Vmax and a decrease in cooperativity, but little change in S0.5 for isocitrate. The mutant IDH2, in contrast, exhibited a 60-fold decrease in maximal velocity and a 2-fold reduction in S0.5 for isocitrate, but the cooperativity was unaffected. Responses to the allosteric modifier AMP also differed for the two mutant enzymes. The IDH1 mutant enzyme was not activated by AMP, whereas the IDH2 mutant enzyme exhibited an increase in isocitrate affinity in the presence of AMP similar to that observed with the wild-type enzyme. On the basis of these kinetic results, a model is presented which proposes that IDH1 functions as a regulatory subunit while IDH2 functions in catalysis. To determine if IDH1 or IDH2 alone is catalytically active, we also expressed the individual subunits in yeast strains in which the gene encoding the other subunit had been disrupted. Mitochondrial extracts from strains overexpressing solely IDH1 or IDH2 contained no detectable activity in the presence or absence of AMP. Gel filtration of these extracts showed that both IDH1 and IDH2 behaved as monomers, suggesting that the major subunit interactions within the octamer are between IDH1 and IDH2.


Regenerative therapy in the treatment of maxillary molar Class II furcations: case reports.
This report demonstrates the use of regenerative therapy in the treatment of maxillary molar Class II furcations. The predominant therapy provided was open debridement in combination with DFDBA, e-PTFE membranes, and citric acid root conditioning. Case reports of consecutively treated patients that include radiographs and reentry photographs demonstrate that maxillary molar furcations can be successfully treated with predictability.


[Persistent polyadenopathic syndrome secondary to cytomegalovirus infection in an immunocompetent host].
A case of polyadenopathic syndrome is presented which involved practically all the ganglionar territories and hepatosplenomegaly in a 15 year old male without a relevant previous history, non immunedepressed, without drug addiction or having received blood er blood derivatives. The clinical picture caused by a cytomegalovirus infection has persisted for 24 months with no modification of adenopathies. The inclusion of CMV infections in the differential diagnosis of generalized adenopathic syndromes is proposed.


Stature estimation in prehistoric Native Americans of Ohio.
In the present report we investigate stature estimation techniques in a sample of 64 (35 male, 29 female) prehistoric Native Americans from Ohio. Because living stature is unknown for these 64 individuals, we use Fully's (1956) anatomical method to provide the best estimates of living stature. In this method all osseous components of skeletal height are measured and soft tissue correction is added. Comparisons of regression equations commonly used for stature estimation in prehistoric Eastern Woodland Native American populations, but developed for East Asian and East Asian-derived populations (using lower extremity components), show that these commonly used equations consistently yield stature estimates 2 to 8 cm in excess of the best estimates from Fully's method. Based on the skeletal height measures of the 64 individuals in the present sample, we develop regression equations for the estimation of stature. These equations yield stature estimates virtually identical to estimates from Fully's method and may prove useful for stature reconstruction in other prehistoric Eastern Woodland Native American populations.


NIR luminescent nanomaterials for biomedical imaging.
Luminescent labels have been widely used for biological applications, primarily in bioimaging and assays. Recently much attention has been focused on the development of luminescent nanoprobes with excitation/emission maxima falling in the region of minimal tissue absorbance/autofluorescence between 650 and 1450 nm, an "imaging window". Tissues have minimal absorbance in this wavelength range allowing for deep penetration of light. This enables whole animal imaging with high sensitivity in core organs in real time without the need for dissection. While several excellent reviews cover various aspects of imaging, there has not been a review that covers NIR imaging nanomaterials adequately. In the present review, we will focus on nanomaterials which can be excited or emitted in NIR I (650-900 nm) and NIR II (1000-1450 nm) regions, including lanthanide based nanoparticles, carbon based nanoparticles, quantum dots and noble metal nanomaterials. We systematically summarize the recent progress in their fabrication and application in biomedical imaging, and discuss the shortcomings, challenges and opportunities in it.


Extraction, separation, and partial characterization of Brucella abortus antigens.
Brucella abortus isolates strain 19 (a vaccinal strain) and 458 (a virulent field isolate) were analyzed for antigenic differences. Whole cell preparations were extracted with detergents, salt solutions, and phenol-acetic acid-water (PAW). Antigens were separated by starch block electrophoresis and sucrose density gradient centrifugation, serotested, and chemically analyzed. Six distinct precipitin lines were observed for the PAW extract against hyperimmune bovine antisera. With sucrose density centrifugation or starch block electrophoresis, antigens were separated into (i) complement-fixing (CF) antigens and (ii) antigens that did not fix complement but formed precipitin bands. Reciprocal CF tests with purified CF antigen could not differentiate between the antigens from either isolate of Brucella.


Estimating the nonlinear association of online somatic cell count, lactate dehydrogenase, and electrical conductivity with milk yield.
Reduction of milk yield is one of the principal components in the cost of mastitis. However, past research into the association between milk yield and mastitis indicators is limited. Past research has not been based on online or in-line daily measurements and has not fully explored nonlinearity and the thresholds at which milk yield starts to decrease. In dairy herds with automated milking systems equipped with sensors, mastitis indicators of individual cows are measured on an intraday frequency, which provides unprecedented avenues to explore such effects in detail. The aim of this observational study was primarily to investigate the nonlinear associations of lactate dehydrogenase (LDH), electrical conductivity (EC), and somatic cell count (SCC) with milk yield at various stages of lactation, parity, and mastitis chronicity status (i.e., whether the cow had SCC ≥200,000 SCC/mL for the last 28 d). We also investigated thresholds at which mastitis indicators (LDH, EC, and SCC) started to be negatively associated with milk yield. We used data from 21 automated milking system herds measuring EC and online SCC. Of these herds, 7 of the 21 additionally measured online LDH. We operationalized milk yield as milk synthesis rate in kilograms per hour. Applying a generalized additive model, we estimated the milk synthesis rate as a function of the 3 mastitis indicators for 3 different subgroups based on parity, stage of lactation, and mastitis chronicity. Partial dependence plots of the mastitis indicators were used to evaluate the milk synthesis rate to study if the milk synthesis rate was associated with mastitis indicators at a specific level. Results showed that milk synthesis rate decreased with increasing SCC, LDH, and EC, but in a nonlinear fashion. The thresholds at which milk synthesis rate started to decrease were 2.5 LnSCC (12,000 SCC/mL) to 3.75 LnSCC (43,000 SCC/mL), 0 to 1 LnLDH (1-2.7 U/L), and 5.0 to 6.0 mS/cm for EC. Additionally, another substantial decrease of milk synthesis rate was observed at thresholds of 5.625 LnSCC (277,000 SCC/mL) and 3 LnLDH (20 LDH U/L) but not for EC. Having chronic mastitis decreased milk synthesis rate in all models. The identified nonlinearities between mastitis indicators and milk synthesis rate should be incorporated in statistical models for more accurate estimations of milk loss due to mastitis.


Fertilization potential of spermatozoa with abnormal morphology.
One of the best discriminators for the fertilization potential of human spermatozoa is sperm morphology. The problem in the assessment of the sperm morphological characteristics is their pleiomorphism. Examination of spermatozoa with the light microscope can provide only limited information on their internal structure. More detailed examination of sperm structure using electron microscopy can reveal major, often unsuspected ultrastructural abnormalities. Results and cut-off values for sperm analysis depend on the criteria for normal morphology. World Health Organization recommendations provide a classification suitable for clinical practice. Clinically reliable cut-off limits for normal sperm morphology according to strict Tygerberg criteria were suggested to be 4% in in-vitro fertilization procedures. Patients with severe sperm head abnormalities have a lower chance of establishing successful pregnancies, even though fertilization may be achieved. The outcome of intracytoplasmic sperm injection is not related to any of the standard semen parameters or to sperm morphology. Sperm decondensation defects and DNA anomalies may be underlying factors for the unrecognized derangements of the fertilizing capacity of spermatozoa, regardless of sperm morphology. Centrosome dysfunction may also represent a class of sperm defects that cannot be overcome simply by the insertion of a spermatozoon into the ooplasm. In this article an overview on the composition and ultrastructure of spermatozoa is presented, while emphasizing sperm ultrastructural and sperm DNA anomalies and their effects on fertilization.


[A case of infant epidural hematoma treated by continuous drainage of cephalohematoma].
A female infant was born at 36 weeks with vacuum extraction. Her weight was 2.216 g and Apgar score was 9. She had a cephalohematoma at right parietal region. The cephalohematoma grew during 6 days after birth, then she came to our hospital. On arrival, her consciousness was alert and there were no neurological deficits. Her head circumference was 22.5 cm, and she had a pulsatile soft cephalohematoma, 7 cm in diameter, at right parietal region. Ultrasound examination showed a midline shift of the brain and CT scan revealed an epidural hematoma with bone fracture and cephalohematoma. We chose the puncture and continuous drainage of cephalohematoma as a primary therapy, because cephalohematoma was considered to be liquified and to be continuous to the epidural hematoma. The reason was that the pulsatile cephalohematoma became harder when she cried. The epidural hematoma was completely reduced on the next day's CT and then drainage was removed. She discharged on 15th post-operative day. We conclude that the puncture and continuous drainage of cephalohematoma may be one of the good therapeutic methods for the mild symptomatic neonate who has epidural hematoma with the cephalohematoma and bone fracture.


Genome-wide expression profiling, in vivo DNA binding analysis, and probabilistic motif prediction reveal novel Abf1 target genes during fermentation, respiration, and sporulation in yeast.
The autonomously replicating sequence binding factor 1 (Abf1) was initially identified as an essential DNA replication factor and later shown to be a component of the regulatory network controlling mitotic and meiotic cell cycle progression in budding yeast. The protein is thought to exert its functions via specific interaction with its target site as part of distinct protein complexes, but its roles during mitotic growth and meiotic development are only partially understood. Here, we report a comprehensive approach aiming at the identification of direct Abf1-target genes expressed during fermentation, respiration, and sporulation. Computational prediction of the protein's target sites was integrated with a genome-wide DNA binding assay in growing and sporulating cells. The resulting data were combined with the output of expression profiling studies using wild-type versus temperature-sensitive alleles. This work identified 434 protein-coding loci as being transcriptionally dependent on Abf1. More than 60% of their putative promoter regions contained a computationally predicted Abf1 binding site and/or were bound by Abf1 in vivo, identifying them as direct targets. The present study revealed numerous loci previously unknown to be under Abf1 control, and it yielded evidence for the protein's variable DNA binding pattern during mitotic growth and meiotic development.


High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer.
The radiobiology of prostate cancer appears to favor large fractions. Accelerated hypofractionation treatments may therefore be used to improve the therapeutic ratio, particularly when the doses to rectum and bladder are kept below the prostate dose. The 5-year experience at William Beaumont Hospital (WBH) and the California Endocurietherapy Center (CET) with accelerated-hypofractionated high-dose-rate (HDR) monotherapy in favorable prostate cancer is presented. Between 1993 and 2004, 454 patients were treated with brachytherapy of which 248 treated with HDR and 206 patients treated with low-dose-rate Palladium (LDR-Pd¹⁰³). The WBH-HDR dose was 38 Gy, in 4 fractions, twice a day. The CET-HDR dose was 42 Gy in 6 fractions in 2 separate implants 1 week apart. The WBH-LDR dose was 120 Gy. Median follow-up was 4.8 years. The 5-year Phoenix biochemical control (BC) was 89%, 91%, and 88% for WBH-LDR, WBH- HDR, and CET-HDR, respectively. The majority of complications were grade 1. HDR was associated with less acute grade 1 to 3 dysuria 60% versus 39%, (P < 0.001), urinary frequency/urgency 90% to58% (P < 0.001), and rectal pain 17% to 6.5% (P < 0.001). Long-term urinary frequency/urgency 54% versus 43%, (P = 0.03) and dysuria 22% versus 15% were less with HDR. The 5-year actuarial impotence rate was 30% for LDR and 20% for HDR (P = 0.23). Although the same 5-year BC rates were achieved with HDR (248 patients) and LDR (206 patients) monotherapy, HDR brachytherapy was associated with less acute and chronic genitourinary and gastrointestinal toxicities. As another accepted standard of care, accelerated hypofractionated HDR monotherapy is target specific and efficient radiobiologically than EBRT which has many smaller doses per fraction. It could be considered today as the best option in accelerated hypofractionated prostate cancer treatment.


Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.
Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas.


Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors.
MicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in parathyroid tumors remains poorly understood. To identify differentially expressed miRNAs between sporadic and hereditary parathyroid tumors and to analyze their correlation with clinicopathological features, a microarray containing 887 miRNAs was performed; then, the differentially expressed miRNAs were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors and 24 normal parathyroid tissue samples. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the utility of the miRNAs for distinguishing parathyroid tumor types. Compared to the miRNAs in the normal parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR-125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated and negatively associated with PTH levels (γ = -0.579, P = 0.002) in the sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed 67% sensitivity and 100% specificity for distinguishing sporadic and hereditary parathyroid tumors. These results reveal altered expression of a miRNA between sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p as a novel biomarker for distinguishing these two types of parathyroid tumors.


Health care-associated pneumonia: identification and initial management in the ED.
Traditionally, pneumonia is categorized by epidemiologic factors into community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Microbiologic studies have shown that the organisms which cause infections in HAP and VAP differ from CAP in epidemiology and resistance patterns. Patients with HAP or VAP are at higher risk for harboring resistant organisms. Other historical features that potentially place patients at a higher risk for being infected with resistant pathogens and organisms not commonly associated with CAP include history of recent admission to a health care facility, residence in a long-term care or nursing home facility, attendance at a dialysis clinic, history of recent intravenous antibiotic therapy, chemotherapy, and wound care. Because these "risk factors" have health care exposure as a common feature, patients presenting with pneumonia having these historical features have been more recently categorized as having health care-associated pneumonia (HCAP). This publication was prepared by the HCAP Working Group, which is comprised of nationally recognized experts in emergency medicine, infectious diseases, and pulmonary and critical care medicine. The aim of this article is to create awareness of the entity known as HCAP and to provide knowledge of its identification and initial management in the emergency department.


OGT-1 regulates synaptic assembly through the insulin signaling pathway.
The formation and maintenance of synapses are precisely regulated, and the misregulation often leads to neurodevelopmental or neurodegenerative disorders. Besides intrinsic genetically encoded signaling pathways, synaptic structure and function are also regulated by extrinsic factors, such as nutrients. O-GlcNAc transferase (OGT), a nutrient sensor, is abundant in the nervous system and required for synaptic plasticity, learning, and memory. However, whether OGT is involved in synaptic development and the mechanism underlying the process are largely unknown. In this study, we found that OGT-1, the OGT homolog in C. elegans, regulates the presynaptic assembly in AIY interneurons. The insulin receptor DAF-2 acts upstream of OGT-1 to promote the presynaptic assembly by positively regulating the expression of ogt-1. This insulin-OGT-1 axis functions most likely by regulating neuronal activity. In this study, we elucidated a novel mechanism for synaptic development, and provided a potential link between synaptic development and insulin-related neurological disorders.


Influence of water in the lamellar rearrangement of internal wool lipids.
Small angle X-ray scattering (SAXS) was applied to a new lipid model arrangement, which was achieved by concentrating or diluting internal wool lipid liposome suspensions in varying water concentrations. The influence of the water content in the lamellar structure of the internal wool lipids is compared with the lamellar structure of phosphatidylcholine bilayers present in the membranes of the living cells. The high increase in the lamellar distances with the water content indicates that large amounts of water can be retained in the lipid wool membrane in contrast to the case of phosphatidylcholine liposomes. A transition temperature between 40 and 50 degrees C tends to eliminate the ordered lamellar structure when more than 60% of water is present in the bilayer structure. This could account for the increase in the permeability of the wool fibres when these are soaked in water at temperatures exceeding 40 degrees C.


Dosimetric and radiobiological investigation of permanent implant prostate brachytherapy based on Monte Carlo calculations.
Permanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose calculations via retrospective dosimetric and radiobiological analysis for a new patient cohort. A cohort of 155 patients treated with permanent implant prostate brachytherapy from The Ottawa Hospital Cancer Centre is considered. Monte Carlo (MC) dose calculations are performed using tissue-based virtual patient models. Dose-volume histogram (DVH) metrics (target, organs at risk) are extracted from 3D dose distributions and compared with those from calculations under TG-43 assumptions (TG43). Equivalent uniform biologically effective dose and tumor control probability are calculated. For the target, D90 (V100) is 136.7 ± 20.6 Gy (85.8% ± 7.8%) for TG43 and 132.8 ± 20.1 Gy (84.1% ± 8.2%) for MC; D90 is 3.0% ± 1.1% lower for MC than TG43. For organs at risk, MC D1cc = 104.4 ± 27.4 Gy (TG43: 106.3 ± 28.3 Gy) for rectum and 80.8 ± 29.7 Gy (TG43: 78.4 ± 28.4 Gy) for bladder; D1cc = 185.9 ± 30.2 Gy (TG43: 191.1 ± 32.0 Gy) for urethra. Equivalent uniform biologically effective dose and tumor control probability are generally lower when evaluated using MC doses. The largest dosimetric and radiobiological discrepancies between TG43 and MC are for patients with intraprostatic calcifications, for whom there are low doses (cold spots) in the vicinity of calcifications within the target, identified with MC but not TG43. DVH metrics and radiobiological indices evaluated with TG43 are systematically inaccurate by upward of several percent compared with MC patient-specific models. Mean cohort DVH metrics and their MC:TG43 variances are sensitive to patient cohort and clinical practice, underlining the importance of further retrospective MC studies toward widespread clinical adoption of advanced model-based dose calculations.


Tolerance of chronic hypercapnia by the European eel Anguilla anguilla.
European eels were exposed for 6 weeks to water CO(2) partial pressures (P(CO)(2)) from ambient (approx. 0.8 mmHg), through 15+/-1 mmHg and 30+/-1 mmHg to 45+/-1 mmHg in water with a total hardness of 240 mg l(-1) as CaCO(3), pH 8.2, at 23+/-1 degrees C. Arterial plasma P(CO)(2) equilibrated at approximately 2 mmHg above water P(CO)(2) in all groups, and plasma bicarbonate accumulated up to 72 mmol l(-1) in the group at a water P(CO)(2) of 45 mmHg. This was associated with an equimolar loss of plasma Cl(-), which declined to 71 mmol l(-1) at the highest water P(CO)(2). Despite this, extracellular acid-base compensation was incomplete; all hypercapnic groups tolerated chronic extracellular acidoses and reductions in arterial blood O(2) content (Ca(O)(2)), of progressive severity with increasing P(CO)(2). All hypercapnic eels, however, regulated the intracellular pH of heart and white muscle to the same levels as normocapnic animals. Hypercapnia had no effect on such indicators of stress as plasma catecholamine or cortisol levels, plasma osmolality or standard metabolic rate. Furthermore, although Ca(O)(2) was reduced by approximately 50% at the highest P(CO)(2), there was no effect of hypercapnia on the eels' tolerance of hypoxia, aerobic metabolic scope or sustained swimming performance. The results indicate that, at the levels tested, chronic hypercapnia was not a physiological stress for the eel, which can tolerate extracellular acidosis and extremely low Cl(-) levels while compensating tissue intracellular pH, and which can meet the O(2) requirements of routine and active metabolism despite profound hypoxaemia.


[The characteristics of the fetal-maternal-placental blood flow in habitual abortion].
Dopplerometry of uterofetoplacental blood flow in 59 women at pregnancy terms of 24 to 40 weeks with a history of habitual abortions revealed disordered blood flow in approximately 60% of cases. Pathologic shifts first develop in a fetus as a rule. Moderate disorders of the uterofetoplacental blood flow in women with a history of habitual abortions do not result in the majority of cases in chronic disorders of fetal status, whereas marked disorders of blood flow often lead to fetal intrauterine suffering.


Treatment of optic neuritis with megadose corticosteroids.
Difficulty in distinguishing between monosymptomatic optic neuritis due to autoimmune disease or to intrinsic demyelination in young adults prompted a trial administration of megadose corticosteroids in a series of patients. Treatment with 1 g daily of intravenous methylprednisolone (Solu-Medrol) for 2 to 5 days led to the rapid resolution and restoration of visual function in five patients. Two untreated patients suffered irreversible loss of vision. One patient with known autoimmune disease required a higher dose. The author suggests a trial of megadose, intravenous corticosteroids in patients between the ages of 21 and 45 years with optic neuropathies of uncertain or suspected autoimmune etiology after appropriate neuro-ophthalmologic evaluation.


[Relationship of maternal malnutrition caused by Di(2-ethylhexyl) phthalate exposure with lifestyle disease in offspring].
The hypothesis that offspring growing up malnourished during their fetal period have a high risk of lifestyle diseases in later life has been attracting great attention. Although animal experiments and epidemiological studies have been reported, most of them focused on the deficiency of maternal malnutritional elements or starvation. We found that di(2-ethylhexyl) phthalate (DEHP) decreased maternal plasma triglyceride levels, which is a significant source of nutrients for fetuses, in mice. Therefore, we analyzed how offspring exposed to malnutritional status during their fetal period develop potential adverse effects in later life. Male and female wild-type (mPPARα), Pparα-null, and hPPARα mice were treated with diets containing 0 or 0.05% DEHP. After 4 weeks, males and females in the same genotype and dose group were mated. After continued exposure until weaning, each group was divided into two groups, and one of them was dissected. The remaining was further divided into two subgroups; one was fed normal feed (control-diet group), while the other was fed a high-fat diet (HFD group). After 8-week feeding, all the mice were dissected. In the control-diet group, DEHP exposure at the fetal and pup stages increased food consumption in mPPARα and hPPARα mice, but not in Ppara-null mice. In contrast, DEHP exposure decreased plasma leptin levels in mPPARα and hPPARα mice at the weaning stage. In the HFD group, DEHP exposure at the fetal and pup stages influenced neither food consumption nor leptin levels. These findings suggest that maternal malnutrition may be caused by not only nutritional deficiency but also exposure to some chemicals such as DEHP, and the latter case may also influence feeding behavior in offspring. These effects may be related to hepatic PPARα and diminished by HFD feeding. Further study is warranted as to whether such feeding behavior influences the risk of lifestyle diseases such as obesity.


Heat-induced accumulation and futile cycling of trehalose in Saccharomyces cerevisiae.
Heat shock resulted in rapid accumulation of large amounts of trehalose in Saccharomyces cerevisiae. In cultures growing exponentially on glucose, the trehalose content of the cells increased from 0.01 to 1 g/g of protein within 1 h after the incubation temperature was shifted from 27 to 40 degrees C. When the temperature was readjusted to 27 degrees C, the accumulated trehalose was rapidly degraded. In parallel, the activity of the trehalose-phosphate synthase, the key enzyme of trehalose biosynthesis, increased about sixfold during the heat shock and declined to the normal level after readjustment of the temperature. Surprisingly, the activity of neutral trehalase, the key enzyme of trehalose degradation, also increased about threefold during the heat shock and remained almost constant during recovery of the cells at 27 degrees C. In pulse-labeling experiments with [14C]glucose, trehalose was found to be turned over rapidly in heat-shocked cells, indicating that both anabolic and catabolic enzymes of trehalose metabolism were active in vivo. Possible functions of the heat-induced accumulation of trehalose and its rapid turnover in an apparently futile cycle during heat shock are discussed.


Neuronal interactions during epileptic events in vitro.
Epileptic events can be produced in in vitro brain slices after perfusion with convulsant agents such as penicillin or picrotoxin. These events consist of one or more synchronized neuronal bursts. In this experimental system, epileptic events occur because of blockade of synaptic inhibition by the convulsant agent. A sparse network of excitatory synaptic interconnections in the hippocampus serves to synchronize a population of neurons, each of which is capable of bursting after appropriate stimulation.


The mir-221/222 Cluster is a Key Player in Vascular Biology via the Fine-Tuning of Endothelial Cell Physiology.
The discovery of small RNAs has shed new light on microRNA (mRNA) regulation and a range of biological processes. The recognition that miRNAs-221 and -222 are sensitive regulators in the endothelium may enable the identification of novel biomarkers and therapeutic targets. Given that endothelial dysfunction precedes the development of atherosclerosis and contributes to the development of cardiovascular damage, circulating miRNAs produced by Endothelial Cells (ECs) are putative biomarkers for a wide range of cardiovascular diseases. Furthermore, EC proliferation and migration have a critical role in the formation of new blood vessels (angiogenesis), an important component of physiological processes and tumour growth. Hence, the use of anti-angiogenic miRNAs might constitute a novel therapeutic strategy. Along with endothelial angiogenesis, several other processes involving ECs (such as neointimal lesion formation, vascular inflammation, lipoprotein metabolism and hypertension) are critical factors in atherogenesis and atherosclerosis. The fact that human blood-derived progenitor cells, endothelial progenitor cells, umbilical vein ECs and quiescent ECs express high levels of miR-221/222 suggests an important role for this miRNA cluster in endothelial (patho) physiology. The present article reviews current knowledge on miRNAs-221/222's regulation roles in endothelial function and disease in general and angiogenesis in particular.


Attenuation of atherosclerotic complications by modulating inflammatory responses in hypercholesterolemic rats with dietary Njavara rice bran oil.
Atherosclerosis is a chronic inflammatory disease. The role of inflammation in atherosclerosis is well established, with all stages of disease progression being assessed as inflammatory response to injury. Preventive treatments and drugs identified so far are based on lipid lowering strategies which also involves functional foods and dietary supplementation. The present study investigated the effect of supplementation of Njavara rice bran oil (NjRBO), extracted from a medicinal rice variety, to high cholesterol diet (HCD) fed rats on atherosclerosis by attenuating the inflammatory responses in PBMCs, aortic endothelial cells and macrophages. Adult male rats (Sprague-Dawley strain, weighing 100-120g) were grouped into 3 of six rats each. Group I served as control, Group II were fed high cholesterol diet (HCD) and Group III were fed a HCD and NjRBO (100mg/kg body weight). The experimental duration was 60days. Activities of cyclooxygenase, lipoxygenase, nitric oxide synthase, and myeloperoxidase, expression of Tumor necrosis factor-α, Interleukin-6, Interferon γ, monocyte chemoattractant protein-1, and cytosolic phospholipase A2 were found to be decreased on NjRBO supplementation which were increased in HCD fed rats. Expression of ICAM-1 and VCAM-1 in aortic endothelial cells was decreased significantly in NjRBO treatment than HCD fed rats. This attenuations were mainly due to inhibition in translocation of NF-κB into nucleus in aortic endothelial cells. Also, NjRBO treatment significantly decreased the gene expressions of TLR-2, TLR-4, and CD36 in both macrophages and endothelial cells than HCD fed rats indicates its anti-inflammatory effect via TLR - NF-κB signaling pathway. NjRBO has thereby shown to possess anti-atherogenic property by effectively modulating inflammatory mechanisms.


Fisher-KPP with time dependent diffusion is able to model cell-sheet activated and inhibited wound closure.
The popular 2D Fisher-KPP equation with constant parameters fails to predict activated or inhibited cell-sheet wound closure. Here, we consider the case where the collective diffusion coefficient is time dependent, with a 3-parameter sigmoid profile. The sigmoid is taken S-shaped for the activated assays, and Z-shaped for the inhibited ones. For two activated and two inhibited assays, our model is able to predict with a very good accuracy features of the wound closure like as the time evolution of the wound area and migration rate. The calibrated parameters are consistent with respect to different subsets of the experimental datasets used for the calibration. However, the assumption of sigmoid time profile for the proliferation rate yields calibrated parameters critically dependent on the dataset used for calibration.


Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020.
There's an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.