HIV-1 reverse transcriptase artificially targeted for proteasomal degradation induces a mixed Th1/Th2-type immune response.
Targeting of a DNA vaccine encoded protein for degradation via the proteasome is attempted since it may enhance the immunogenicity of the vaccine. We have fused HIV-1 reverse transcriptase (RT) to mouse ornithine decarboxylase (ODC), a protein rapidly degraded by proteasome in an ubiquitine-independent fashion, to enhance the introduction of RT into the MHC class I pathway. We also designed a fusion of RT with two short signals from the C-terminus of ODC (ODCsig) representing a minimal proteasome-targeting moiety of ODC (PEST signal). Fusion to ODC or ODC signal domain led to a marked enhancement of RT degradation. Plasmids encoding RT-ODC and RT-ODCsig chimera were used to immunize BALB/c mice. The administration of the plasmids was not associated with autoimmune disease. Moreover, mice receiving RT-ODCsig gene mounted a mixed Th1/Th2 response characterized by the in vitro secretion of IFN-gamma, IL-2, TNF-alpha, IL-4, and IL-10 upon stimulation of splenocytes with RT protein or RT derived peptides. Serum titers of 10(2) to 10(3) were observed in more than 50% of animals in that group, whereas fewer animals mounted an anti-RT response in the RT-ODC gene immunized group. Chimeras of the type described here can, therefore, be used in vaccinations aiming to induce HIV-1 RT-specific immune response.


Functions and mechanisms of retrograde neurotrophin signalling.
Neuronal connections are established and refined through a series of developmental programs that involve axon and dendrite specification, process growth, target innervation, cell death and synaptogenesis. Many of these developmental events are regulated by target-derived neurotrophins and their receptors, which signal retrogradely over long distances from distal-most axons to neuronal cell bodies. Recent work has established many of the cellular and molecular events that underlie retrograde signalling and the importance of these events for both development and maintenance of proper neural connectivity.


Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats.
Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer's solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 ± 420 vs. 724 ± 75 AU) and in liver (474 ± 57 vs. 261 ± 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p < 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 ± 2 vs. 14 ± 0.5 RLU). Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions.


Complex effects of inhibitors on cyclic GMP-stimulated cyclic nucleotide phosphodiesterase.
We have investigated the effects of several phosphodiesterase inhibitors on the activity of a cGMP-stimulated cyclic nucleotide phosphodiesterase purified from calf liver supernatant. Theophylline, RO 20-1724, and MY 5445 were not effective inhibitors. With 0.5 microM [3H]cGMP as substrate or with 0.5 microM [3H]cAMP in the presence of 1 microM cGMP, activity was inhibited by papaverine, dipyridamole, isobutylmethylxanthine (IBMX), and cilostamide. With 0.5 microM [3H]cAMP as substrate, however, only cilostamide was inhibitory; papaverine, dipyridamole, and IBMX increased activity. The increase was dependent on both drug and substrate concentration with maximal stimulation (150-180%) at concentrations of cAMP between 0.5 and 2.5 microM. At higher cAMP concentrations, the three drugs were inhibitory; inhibition was maximal at approximately 40 microM and decreased at higher cAMP concentrations. Inhibition of cGMP hydrolysis was maximal at approximately 3 microM and decreased at higher concentrations. Papaverine, IBMX, dipyridamole, and cilostamide inhibited [3H] cGMP hydrolysis competitively with Ki values of 3, 6.5, 7, and 11.5 microM, respectively. Papaverine, IBMX, or dipyridamole reduced the Hill coefficient for cAMP hydrolysis from 1.8 to 1.1-1.2, and Lineweaver-Burk plots were linear or nearly linear. With cilostamide, however, Lineweaver-Burk plots remained curvilinear. Thus, three competitive inhibitors, papaverine, dipyridamole, and IBMX, can mimic substrate and effect allosteric transitions that increase catalytic activity, whereas another, cilostamide, apparently cannot. Differences in the actions of these inhibitors presumably reflect differences in the molecular requirements for effective interaction at catalytic and allosteric sites on phosphodiesterase, i.e. differences in the structure of these sites.


Climate change and daily outpatient visits for dermatomyositis in Hefei, China: a time-series study.
With the deepening of research on the correlation between meteorological factors and autoimmune diseases, the relationship between climate change and dermatomyositis (DM) has come to our attention. This study aimed to explore the short-term correlation between meteorological factors and DM outpatient visits. Daily records of hospital outpatient visits for DM, air pollutants, and meteorological factor data in Hefei from January 1, 2018 to December 31, 2021 were obtained. The mean temperature (MT), relative humidity (RH), diurnal temperature range (DTR), and temperature change between neighboring days (TCN) were used to quantify environmental temperature and humidity and their variations. And we performed a time series analysis using a generalized linear model (GLM) in combination with a distributed lag nonlinear model (DLNM). Furthermore, gender and age were further stratified for the analysis. The sensitivity analysis was also performed. A total of 4028 DM outpatient visits were recorded during this period. There were statistically significant associations of low temperature (5th, 1.5 °C), low RH (1st, 48.6%), high RH (99th, 99%), high DTR (75th, 12.6°c), and low TCN (10th, -2.7 °C) that were associated with risk of DM outpatient visits, with lag days of 30, 16, 16, 10, and 14, respectively. Moreover, women were more susceptible to high RH exposure and low TCN exposure, while the elderly were more susceptible to low temperature. This study concluded that exposure to low temperature, extreme RH, and temperature changes (especially high DTR and low TCN) was associated with an increased risk of DM outpatient visits.


Child maltreatment data in the state of New Mexico across space and time.
Child maltreatment is a serious public health problem. Previous research demonstrates that child maltreatment clusters in low-income, racially homogenous neighborhoods. Little is known, however, about the structural correlates of spatial risk in small areas such as census tracts. Here we present additional information regarding the data and methods used in the recent article published in Child Abuse & Neglect entitled "Variability and stability in child maltreatment risk across time and space and its association with neighborhood social & housing vulnerability in New Mexico: A Bayesian space-time model" [1]. The present dataset merges child maltreatment data from the New Mexico Department of Public Health with multiple sources of publicly available data to create a novel public health analysis. Bayesian spatio-temporal modeling techniques were used to map the relative risk of substantiated child maltreatment across census tracts in the state, and to elucidate spatial and temporal heterogeneity in risk. The data was initially collected by the New Mexico Children, Youth and Families Department, the state organization that suspected child abuse and neglect cases are reported to and the organization that then substantiates these cases. The data were then sent to the New Mexico Community Data Collaborative, a data analytic organization under the umbrella of the New Mexico Department of Health. The point file consisting of home addresses of substantiated cases of child abuse was then aggregated by census tract, mapped for the entire state of New Mexico and made available to the public for research and analysis by different public health organizations and researchers (including the present researchers). The very purpose of making the data available to the public was to allow deeper investigations into trends and associations with other social determinants of health. This analysis demonstrates the public health importance of data sharing and accessibility.


The Development and Enhancement of FRAP as a Key Tool for Investigating Protein Dynamics.
The saga of fluorescence recovery after photobleaching (FRAP) illustrates how disparate technical developments impact science. Starting with the classic 1976 Axelrod et al. work in Biophysical Journal, FRAP (originally fluorescence photobleaching recovery) opened the door to extraction of quantitative information from photobleaching experiments, laying the experimental and theoretical groundwork for quantifying both the mobility and the mobile fraction of a labeled population of proteins. Over the ensuing years, FRAP's reach dramatically expanded, with new developments in GFP technology and turn-key confocal microscopy, which enabled measurement of protein diffusion and binding/dissociation rates in virtually every compartment within the cell. The FRAP technique and data catalyzed an exchange of ideas between biophysicists studying membrane dynamics, cell biologists focused on intracellular dynamics, and systems biologists modeling the dynamics of cell activity. The outcome transformed the field of cellular biology, leading to a fundamental rethinking of long-held theories of cellular dynamism. Here, we review the pivotal FRAP studies that made these developments and conceptual changes possible, which gave rise to current models of complex cell dynamics.


The polarized epithelia-specific mu 1B-adaptin complements mu 1A-deficiency in fibroblasts.
The heterotetrameric AP-1A adaptor complex of clathrin-coated vesicles is ubiquitously expressed. The mu 1-adaptin subunit of the complex exists as the ubiquitous mu 1A and the polarized epithelia-specific mu 1B, which are 80% identical. In polarized epithelia, mu 1B is incorporated into the AP-1B complex, which is required for basolateral plasma membrane sorting of the low-density lipoprotein receptor. Binding of AP-1B to subdomains of the trans-Golgi network (TGN) appears to be part of the mechanism by which protein sorting is mediated. We expressed mu 1B in mu 1A-deficient fibroblasts to test for mu 1B function in non-polarized cells. AP-1B complexes were formed and bound to the TGN and to endosomes. Moreover, AP-1B restored the AP-1A-dependent sorting of mannose 6-phosphate receptors between endosomes and the TGN. This demonstrates that mu 1A and mu 1B do have overlapping sorting functions and indicates that AP-1A and AP-1B mediate protein sorting along parallel pathways between the TGN and endosomes in polarized epithelia.


Characteristics of basilar artery atherosclerotic plaques in pontine infarctions: A high-resolution magnetic resonance imaging study.
This study used a 3.0T high-resolution magnetic resonance imaging approach to explore basilar artery plaque characteristics in patients suffering from acute isolated pontine infarction. 30 consecutive patients suffering from acute isolated pontine infarction were enrolled in this study and underwent examinations including high-resolution MRI assessment of the basilar artery within 7 days following infarction. The basilar artery plaque burden of 16 patients with paramedian pontine infarction was 0.26±0.085, while the reconstruction index and enhancement rate index values in these patients were 1.097±0.133 and 1.750±0.447, respectively. In the 14 patients suffering from deep pontine infarction, these three values were 0.21±0.055, 0.896±0.223, and 1.285±0.611, respectively.These values differed significantly when comparing patients suffering from paramedian pontine infarction to those suffering from deep pontine infarction. This study suggests that the characteristics of basilar artery plaques differ between the two subtypes of pontine infarctions, which may account for the differences in prognosis associated with these two infarct subtypes.


Factors influencing the hemolysis of human erythrocytes by cardiotoxins from Naja naja kaouthia and Naja naja atra venoms and a phospholipase A2 with cardiotoxin-like activities from Bungarus fasciatus venom.
The effects of red blood cell age and incubation conditions (temperature, divalent cation type and concentration, pH and glucose) on hemolysis induced by cardiotoxin fractions from Naja naja atra and Naja naja kaouthia venoms, a phospholipase A2 with cardiotoxin-like activities from Bungarus fasciatus venom and bee venom phospholipase A2 were examined. Hemolysis by the snake venom toxins was dependent on red blood cell age (aged more susceptible than fresh) and the temperature of incubation (37 degrees C greater than 20 degrees C). Divalent cations at 0.5-2.0 mM enhanced (Ca2+) or slightly decreased (Sr2+, Ba2+) hemolysis due to N. n. kaouthia and N. n. atra toxins, and greatly decreased (Ca2+, Sr2+, Ba2+) hemolysis by these toxins at higher concentrations (5-40 mM). For the B. fasciatus phospholipase A2, Ba2+ and Sr2+ could not fully support hemolysis in any concentration while both low (less than 0.5 mM) and high (greater than 40 mM) Ca2+ enhanced hemolysis. Bee venom phospholipase A2 only induced hemolysis (greater than 10% at greater than 40 mM) at high concentrations of Ca2+. Increasing the pH from 7.5 to 8.5 greatly increased the levels of hemolysis by the snake venom toxins and enzyme. Glucose (5.3 mM) increased hemolysis by the snake venom components at low concentrations of divalent cations (2 mM) and slightly decreased hemolysis at high concentrations (40 mM). Treatment with p-bromophenacyl bromide abolished phospholipase A2 activity of bee venom and B. fasciatus phospholipases, but did not affect hemolytic potency of N. n. kaouthia or B. fasciatus toxins. A similar mechanism, which is independent of phospholipase A2 activity, may be involved in hemolysis by the N. n. kaouthia and N. n. atra cardiotoxins. The B. fasciatus cardiotoxin-like phospholipase A2 appears to have two mechanisms of hemolysis; the first is similar to that of the two typical cardiotoxins and the second appears dependent on phospholipase A2 activity and is only evident at high Ca2+ concentrations.


Are schistosomes socially and genetically monogamous?
Monogamy is a mating system with pairs made of only one male and only one female. But social monogamy cannot inevitably imply the sexual exclusivity between mates, which is yet the case in genetic monogamy on which the offspring results only from the observed pair. The genetic monogamy is today considered as an exception in monogamous animals but the possibility to store sperm for females in some monogamous species makes co-occurrence of genetic monogamy with extensive mate changes possible. Schistosome is a socially monogamous endoparasite with female living inside the gynecophoric canal of its male. If mate changes have been demonstrated in this parasite, resulting offspring needs to be proven, especially if we consider the presence of a receptaculum seminis in female schistosomes. In this paper, we show the first evidence of rapid offspring production resulting from mate change in a monogamous invertebrate despite the potential ability for the female schistosome to store sperm. Thus, we conclude that schistosomes are socially but not genetically monogamous.


[The influence of gravity on the distribution of fat embolism in the eye (author's transl)].
In human fat embolism we often find different grades of changes in both eyes of a patient. This was experimentally verified in rabbits. The anesthetized animals were held in lateral position so that one eye was continuously higher than the other. Labelled fat was injected intravenously, and then the activity in each eye was measured by a scintillation-counter. By this method a significantly higher rate of fat embolism was found in the upper eye.


The role of host microfilaments and microtubules during opsonin-independent interactions of Cryptococcus neoformans with mammalian lung cells.
The purpose of this investigation was to characterise the interactions of Cryptococcus neoformans with mammalian host alveolar epithelial cells and alveolar macrophages, with emphasis on the roles of the cryptococcal capsule and the host cell cytoskeletons. The adherence and internalisation of C. neoformans into mammalian lung cells and the roles of host cell cytoskeletons in host-pathogen interactions were studied using in vitro models coupled with a differential fluorescence assay, fluorescence staining, immunofluorescence and drug inhibition of actin and microtubule polymerisation. Under conditions devoid of opsonin and macrophage activation, C. neoformans has a high affinity towards MH-S alveolar macrophages, yet associated poorly to A549 alveolar epithelial cells. Acapsular C. neoformans adhered to and internalised into the mammalian cells more effectively compared to encapsulated cryptococci. Acapsular C. neoformans induced prominent actin reorganisation at the host-pathogen interface in MH-S alveolar macrophages, but minimally affected actin reorganisation in A549 alveolar epithelial cells. Acapsular C. neoformans also induced localisation of microtubules to internalised cryptococci in MH-S cells. Drug inhibition of actin and microtubule polymerisation both reduced the association of acapsular C. neoformans to alveolar macrophages. The current study visualises and confirms the interactions of C. neoformans with mammalian alveolar cells during the establishment of infection in the lungs. The acapsular form of C. neoformans effectively adhered to and internalised into alveolar macrophages by inducing localised actin reorganisation, relying on the host's actin and microtubule activities.


Biotyping of Candida strains with regard to the epidemiology of candidosis. A practical approach.
In 62 strains of Candida albicans cultivated from specimens of patients with recurrent vaginal candidosis or with renal transplants, the biotypes were determined according to several characters: colony morphology, production of chlamydospores, auxanogram of C- and N-substances, zymogram, growth kinetics, adherence capability, proteolytic activity, sensitivity to 6 antimycotics, and serotypes. On the basis of this typing system the endogenous and exogenous sources of chronic vaginal candidosis as well as the sources of systemic candidosis in patients with renal transplants could be evaluated.


The Costs and Benefits of Goal-Directed Attention in Deep Convolutional Neural Networks.
People deploy top-down, goal-directed attention to accomplish tasks, such as finding lost keys. By tuning the visual system to relevant information sources, object recognition can become more efficient (a benefit) and more biased toward the target (a potential cost). Motivated by selective attention in categorisation models, we developed a goal-directed attention mechanism that can process naturalistic (photographic) stimuli. Our attention mechanism can be incorporated into any existing deep convolutional neural networks (DCNNs). The processing stages in DCNNs have been related to ventral visual stream. In that light, our attentional mechanism incorporates top-down influences from prefrontal cortex (PFC) to support goal-directed behaviour. Akin to how attention weights in categorisation models warp representational spaces, we introduce a layer of attention weights to the mid-level of a DCNN that amplify or attenuate activity to further a goal. We evaluated the attentional mechanism using photographic stimuli, varying the attentional target. We found that increasing goal-directed attention has benefits (increasing hit rates) and costs (increasing false alarm rates). At a moderate level, attention improves sensitivity (i.e. increases d ' ) at only a moderate increase in bias for tasks involving standard images, blended images and natural adversarial images chosen to fool DCNNs. These results suggest that goal-directed attention can reconfigure general-purpose DCNNs to better suit the current task goal, much like PFC modulates activity along the ventral stream. In addition to being more parsimonious and brain consistent, the mid-level attention approach performed better than a standard machine learning approach for transfer learning, namely retraining the final network layer to accommodate the new task.


Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.
The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.


Fluvastatin reduces modification of low-density lipoprotein in hyperlipidemic rabbit loaded with oxidative stress.
The in vivo antioxidant effect of fluvastain, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was investigated using Watanabe heritable hyperlipidemic (WHHL) rabbits subjected to nicotine-free cigarette smoke extracts as oxidative stress. Fluvastatin was given orally at doses of 10 and 30 mg/kg per day for 5 months. The cigarette smoke extracts were prepared by bubbling the gas phase of smoke into phosphate-buffered saline and was injected daily into the rabbit ear vein. The rabbits chronically treated with the cigarette smoke extracts showed an increase in plasma lipid peroxide levels, estimated as thiobarbituric acid-reactive substances. Oxidative modification of plasma low-density lipoprotein (LDL) was assessed by anion-exchange high-performance liquid chromatographic analysis, LDL susceptibility to oxidation, LDL incorporation into macrophages and thiobarbituric acid-reactive substances levels in LDL. Treatment with fluvastatin significantly reduced these effects induced by the cigarette smoke extracts in a dose-related manner and exerted a cholesterol-lowering effect. At the end of the experiment, the cigarette smoke extracts caused accumulation of cholesteryl ester in the thoracic aorta, while fluvastatin significantly prevented this accumulation. These results indicate that fluvastatin can exert an antioxidant effect in vivo, with a strong effect on oxidative stress such as smoking, a major risk factor of atherosclerosis.


Pain in tones - Is it possible to hear the pain quality? A pilot trial.
The adequate treatment of chronic pain also calls for measuring its quality not only its intensity. For this reason, this pilot study investigated the non-verbal description of pain quality based on tones, distinguishing between nociceptive and neuropathic pain. A nociceptive and a neuropathic pain stimulus were applied to 80 chronic pain patients and 80 healthy subjects. Using a tone generator, all participants matched both pain stimuli to an appropriate tone (in Hz). The stimulus intensity was measured using the NRS-scale, and the PainDETECT questionnaire was completed. Both groups matched a significantly higher tone to the neuropathic than to the nociceptive pain stimulus. Compared to healthy participants, chronic pain patients allocated higher tones to both pain stimuli. Higher values were also shown for the neuropathic pain stimulus, and chronic pain patients indicated an overall higher intensity of pain as healthy participants. It is possible to differentiate pain stimuli non-verbally through tones, however, whether quality or intensity, was the key factor remains unknown. Future studies could investigate the influence of additional factors. A practical tool using tones should be developed to detect pain quality in patients - without verbal descriptions - quickly and more precisely.


Incidence and consequences of falls among elderly people living in the community.
To evaluate the incidence of falls according to socio-demographic and health factors, and to determine their physical, psychological and social consequences. SUBJETS AND METHOD: Population-based prospective study, which included a representative cohort of 448 elderly community-dwellers, aged 65 or more living in the city of Mataró (Spain). We made a baseline evaluation, which was repeated after a one-year follow up, consisting of a standardized questionnaire on socio-demographic characteristics, physical activity, tests of physical and cognitive function, history of falls during the previous year, the Falls Efficacy Scale, and associated chronic conditions. Follow-up interviews at intervals of one month over 12 months, consisting of a standardized questionnaire aimed at detecting and describing any fall occurred during the previous month. 25.1% (95% CI, 18.8-31.4) of males and 37.0% (95% CI, 31.2-42.8) of females fell. Multiple falls were observed in 3.8% of men and 10.9% of women. 203 falls were reported, providing a crude incidence rate of 30.9 falls per 100 men-years (95% CI, 23.3-41.0) and 56.5 falls per 100 women-years (95% CI, 46.5-68.8). A positive association with falls was found with age, reduced physical and cognitive function, associated chronic conditions and previous falls. 71.1% of falls had physical consequences, with 7.7% of fractures, and 21.7% needed medical aid. 64.4% of fallers feared of falling again. Our study shows a pattern of high incidence of falls among the elderly living in the Spanish non-institutionalized community. Our data confirm that adverse consequences derived from the falls are frequent and often severe, which makes falls one of the major problems of elderly people.


The management of congenital cholesteatoma: surgical results of 42 cases.
Radical surgery for congenital cholesteatoma leaves the patient, usually a child, with an ear that requires care for life. At the Otologic Medical Group, the intact canal wall technique has been used for many patients with cholesteatoma. To determine results of this management in the treatment of congenital cholesteatoma, we reviewed records of all patients treated between 1974 and 1985. Forty-two ears were studied in 41 patients. A closed middle-ear space was achieved in all cases, and an intact canal wall was maintained in 41 (98%). Follow-up averaged 4.3 years. Of the 41 cases with serviceable hearing before surgery, 28 (68%) had postoperative hearing within 10 dB of the best preoperative bone conduction threshold. Thirty-eight of the 41 achieved a final hearing result within 20 dB of the best bone conduction threshold.


Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis.
We report on the experimental measurement of the backscattering matrix of a weakly scattering medium in optics, composed of a few dispersed gold nanobeads. The decomposition of the time-reversal operator is applied to this matrix and we demonstrate selective and efficient focusing on individual scatterers, even through an aberrating layer. Moreover, we show that this approach provides the decomposition of the scattering pattern of a single nanoparticle. These results open important perspectives for optical imaging, characterization, and selective excitation of nanoparticles.


Analysis of Water State and Gelation of Methylcellulose Thermo-reversible Hydrogels by Thermal Analysis and NMR.
The gelation of aqueous methylcellulose (MC) solutions containing polyethylene glycol (PEG) was studied by the combination of differential scanning calorimetry (DSC) and Raman spectrometry. The gelation of MC hydrogels containing PEG occurred in two-steps. First, the gel network was formed by the hydrophobic interaction between MC and PEG at 310 - 313 K, and then, the gel network was formed between MC chains at 323 K. On the other hand, in the MC hydrogels containing PEG and NaCl, sodium ion assumed to be enclosed by PEG, forming a helix with the hydrophobic groups outward. The sodium ion in the gel was expected to be surrounded by the ether oxygen of PEG as crown ether.


Covert visual attention and extrafoveal information use during object identification.
Three experiments are reported that examined the relationship between covert visual attention and a viewer's ability to use extrafoveal visual information during object identification. Subjects looked at arrays of four objects while their eye movements were recorded. Their task was to identify the objects in the array for an immediate probe memory test. During viewing, the number and location of objects visible during given fixations were manipulated. In Experiments 1 and 2, we found that multiple extrafoveal previews of an object did not afford any more benefit than a single extrafoveal preview, as assessed by means of time of fixation on the objects. In Experiment 3, we found evidence for a model in which extrafoveal information acquired during a fixation derives primarily from the location toward which the eyes will move next. The results are discussed in terms of their implications for the relationship between covert visual attention and extrafoveal information use, and a sequential attention model is proposed.


Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?
Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.


Distribution of rubella antibodies in Nigeria.
A total of 1,847 serum samples obtained from human subjects in various areas of Nigeria (North, East and West) were tested for the presence of rubella haemagglutination inhibition antibodies. The results showed that an average of 68% of the Nigerian population studied possessed rubella antibody.


Tracking changes in atmospheric particulate matter at a semi-urban site in Central France over the past decade.
Nearly 10-year (2013-2022) data on atmospheric particulate matters (PMs) were collected to investigate the air quality in a suburban site of Orléans city (France). The PM10 concentration decreased slightly between 2013 and 2022. PMs concentrations showed a monthly variation with higher concentration in cold periods. PM10 presented a clear bimodal diurnal variation peaking at morning rush hour and midnight, whereas the fine PMs such as PM2.5 and PM1.0 only had significant peaks during nighttime. Further, PM10 had more pronounced week-end effect than other fine PMs. COVID-19 lockdown impact on PMs levels was further investigated, showing that the lockdown during cold season could result in an increase of PMs concentrations because of the enhanced household heating. We concluded that PM10 could originate from biomass burning and fossil fuel related activities, air parcels from the western Europe through Paris were also important source of PM10 in the investigated area. Fine PMs, such as PM2.5 and PM1.0, originated mainly from biomass burning in addition to secondary formation at the local scale. This study provides a long-term PMs measurement database to explore the sources and characterization of PMs in central France, which could support future regulation and formulation of air quality standards.


Determination of reduced homocysteine in human serum by elemental labelling and liquid chromatography with ICP-MS and ESI-MS detection.
Analytical methods allowing sensitive determination of reduced homocysteine (rHcy), one of the so-called biothiols, in human serum is a topic of growing interest due to its close relation to several human disorders, mainly cardiovascular diseases. Although most widely used analytical strategies to determine total Hcy involve derivatization by means of fluorescent labels, this work proposes the use of ebselen, a Se-containing labelling agent to derivatize the reactive sulfhydryl group of the Hcy molecule in its "free" reduced form, which is more likely to play different roles in disease pathogenesis. Optimization of the derivatization and separation conditions by high-performance liquid chromatography (HPLC) to isolate the excess of derivatizing reagent is carried out here using UV/VIS detection. Further, the study of the Se labelling reaction by electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides a stoichiometry of the derivative of 1:1. The main advantage of using ebselen as a labelling agent is the presence of the Se atom in the molecule that allows the use of inductively coupled plasma mass spectrometry (ICP-MS) as a sensitive and selective Se detector. The coupling of HPLC with ICP-MS provided excellent features for the determination of Se-derivatized rHcy (detection limit of 9.6 nM) in real samples. Quantification was accomplished by using post-column isotope dilution (ID) of Se in serum samples, after precipitation of the main serum proteins. Quantitative results for "free" rHcy turned out to be around 0.18-0.22 μM in serum samples from healthy individuals that could be directly analyzed without sample preconcentration.


Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA.
We report a patient with a clinical picture consisting of small birth weight, connatal hypoplastic anaemia, vacuolised bone marrow precursors, failure to thrive, and, subsequently, by insulin-dependent diabetes, renal Fanconi syndrome, lactic acidosis, complex organic aciduria, and elevation of haemoglobin F and of adenosine deaminase activity. The clinical course was progressive and death occurred at age 19 months. A high proportion of mitochondrial (mt) DNA molecules with a deletion of nucleotides 9238 to 15575 were identified in several tissues; about half of the shortened mtDNA molecules were concatenated to form circular dimers. The clinical and laboratory findings support recent conclusions that Pearson syndrome is not confined to bone marrow and pancreas, as originally described, but is a multi-organ disorder associated with deletions in part of the mtDNA molecules. The tissue distribution and the relative proportions of the abnormal mtDNA molecules apparently determine the phenotype and clinical course.


Paving the way to the future: Mapping historical patterns and future trends of road material stock in Japan.
Roads are a fundamental component of societal infrastructure, whose decades-long lifespan has far-reaching implications for developmental decisions. The road construction and development have profound impacts on economic growth, social dynamics, and environmental sustainability. Therefore, comprehensive measurement of the current road material stock (MS) and the projection of expected future road scale based on regional socio-economic scenarios that can reflect unique local conditions are necessary. This study examined the historical changes and progression patterns of the road network across Japan from 1965 to 2020 through material flow and material stock analysis. By using the road MS time series, along with explanatory socioeconomic variables, several models including Autoregressive Integrated Moving Average with explanatory variables (ARIMAX), Support Vector Regression (SVR), hybrid ARIMAX-SVR, Multiple Linear Regression (MLR), Artificial Neural Networks (ANN), and Random Forest (RF) were compared. After comparison analysis, ARIMAX and hybrid ARIMAX-SVR models were employed to forecast expected road MS in each prefecture of Japan by 2050 based on national shared socioeconomic pathways (SSP) scenarios. The study found that the total road MS of Japan increased 5.5-fold over 55 years. Aggregate was the dominant material, comprising over 70 % among the four materials of the total road MS. The forecast results for each prefecture were classified into three different patterns. Expected MS in most prefectures still displayed increasing trends in the five scenarios, but the projection of road MS in eight prefectures revealed a notable downward trend across each SSP scenario. For most prefectures, SSP5 displayed the highest expected road MS, followed by SSP1. SSP3 was the scenario with the lowest MS. This approach provided a more thorough understanding of the likely evolution of road MS across different SSP scenarios and could help inform decisions for resource allocation and policy formulation concerning road infrastructure management.


Methods of analysis for toxic elements in food products. 1. Mineralization methods to determine heavy metals and arsenic according to the USSR standard.
Results of the work of 22 laboratories in the USSR on optimizing methods for mineralizing foods to determine Pb, Cd, As, Zn, Cu, Sn, and Fe are summarized. Recommendations are given on dry and wet mineralization as related to the analyte and the kind of food product. Optimum amounts of test portions for 22 food groups are also recommended according to the element of interest.


Effect of exogenous interferon on neonatal infection with murine cytomegalovirus.
One dose of interferon given before inoculation of MCMV to the neonatal mouse resulted in less virus in the submaxillary glands and reduced tissue damage due to MCMV infection, probably by modulating the immune system.


HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress.
Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme thought to make a major contribution to the antioxidant capacity of the lipoprotein. In previous studies, we proposed that HDL promoted PON1 secretion by transfer of the enzyme from its plasma membrane location to HDL transiently anchored to the hepatocyte. This study examined whether PON1 can be transferred into cell membranes and retain its enzymatic activities and functions. Using Chinese hamster ovary and human endothelial cells, we found that recombinant PON1 as well as PON1 associated with purified human HDL was freely exchanged between the external medium and the cell membranes. Transferred PON1 was located in the external face of the plasma membrane of the cells in an enzymatically active form. The transfer of PON1 led to a gain of function by the target cells, as revealed by significantly reduced susceptibility to oxidative stress and significantly increased ability to neutralize the bacterial virulence agent 3-oxo-C(12)-homoserine lactone. The data demonstrate that PON1 is not a fixed component of HDL and suggest that the enzyme could also exert its protective functions outside the lipoprotein environment. The observations may be of relevance to tissues exposed to oxidative stress and/or bacterial infection.


Neuroprotective Effects of Rhodiola Sacra on Transient Global Cerebral Ischemia Through Activating AMPK/Nrf2 Pathway in Rats.
Aims: Rhodiola sacra is a widely used pharmaceutical component with multiple functions, including anti-oxidation and anti-inflammation. However, the exact mechanisms involved in neuroprotection against transient global cerebral ischemia (tGCI) remain to be elucidated. Herein, we aim at closing the gap in understanding on whether rhodiola sacra reduces neuronal death in hippocampal CA1 and at demonstrating how rhodiola sacra offers neuroprotection after tGCI. Results: The results show that rhodiola sacra (2.4 g/kg/d by feeding) pretreatment or/and postreatment significantly alleviated neuronal injury, inhibited glial activation, and improved cognitive function in male rats subjected to tGCI. The neuroprotection of prophylaxis with rhodiola sacra is equivalent to that of therapeutics. The binding mode of adenosine monophosphate-activated protein kinase (AMPK) α2-subunit with rhodiola sacra was predicted by molecular docking. Further, rhodiola sacra upregulates phosphorylated AMPK and promotes nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2). In addition, rhodiola sacra increases heme oxygenase-1 (HO-1) expression and activity and reduces malondialdehyde (MDA) content in CA1 after tGCI. However, the neuroprotection of rhodiola sacra is abolished by Nrf2 knockdown with small interfering RNA (siRNA) after tGCI. Similarly, the inhibition of AMPK with Compound C or siRNA against AMPK α2 aggravates neuronal death after tGCI through decreasing nuclear Nrf2 and the expression and activity of HO-1, and by increasing the release of MDA. Innovation and Conclusion: For the first time, this study demonstrates that as a prophylactic or therapeutic agent rhodiola sacra prevents oxidant stress, protects neurons, and improves cognitive function through activating the AMPK/Nrf2 pathway in tGCI rats. Antioxid. Redox Signal. 36, 567-591.


Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma.
A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy. A total of 65 courses was given, with the median being 2 (range, 1-9 courses). None of the patients achieved a partial or complete response; however, 3 patients achieved a minor response and 14 had stable disease. The frequent toxic effects of DFMO included thrombocytopenia (which was dose-limiting), malaise, nausea, vomiting, reversible hearing loss, and diarrhea. Our data suggest that continuous-infusion DFMO therapy is feasible and results in only mild gastrointestinal toxicity. Although DFMO proved to be ineffective as a single agent in this trial, it could probably best be used in combination with cytotoxic agents known to enhance its antitumor activity in a preclinical setting.


Determination of acetylcholine concentration in cerebrospinal fluid of patients with neurologic diseases.
Acetylcholine (ACh) is a well known neurotransmitter in the central nervous system, but determining its level in cerebrospinal fluid (CSF) is very difficult and the origin of CSF ACh is still unknown. In this study, we attempted to measure CSF ACh by a specific and sensitive radioimmunoassay (RIA) from patients with neurologic diseases. Patients with cerebral infarction (n = 7), Parkinson's disease (n = 6), spinocerebellar degeneration (n = 6), Alzheimer's disease (n = 3), amyotrophic lateral sclerosis (n = 3) and disc herniation with no central nervous involvement (n = 8) participated to determine the CSF ACh levels. Of these 33 patients, the mean ACh level in CSF was 282.2 +/- 61.7 fmol/ml (mean +/- SE, range 20-1505.8 fmol/ml). The mean ACh level of spinocerebellar degeneration group was lower than others, but not statistically significant. We conclude that an amount of ACh detectable by RIA is certainly present in CSF.


Paraganglioma of the urinary bladder: Case report and literature review.
Paraganglioma of the urinary bladder is a very rare disease accounting for 0.06% of all bladder tumors. Owing to their rarity and symptomatic variability, preoperative diagnosis is often difficult. A 70-year-old male was referred to our department for hematuria. Cystoscopy showed a non-papillary broad-based tumor. Computed tomography and magnetic resonance imaging revealed a 32-mm bladder tumor at the top of the bladder, which suggested muscle-invasive bladder tumor. We diagnosed muscle-invasive bladder cancer or urachal carcinoma, and transurethral resection of the bladder tumor was performed. At the initiation of transurethral resection of the bladder tumor, the systolic blood pressure was elevated to over 200 mmHg. The pathological findings revealed paraganglioma of the urinary bladder, and afterward, a partial cystectomy was performed. We herein reported the case of paraganglioma in the bladder whose blood pressure became extremely elevated during transurethral resection of the bladder tumor. In addition, we analyzed important factors for preoperative diagnosis using 162 cases reported in Japan.


[Radiobiology of stem cells in intestinal epithelium. Effect of single and multiple preliminary sublethal irradiation of mice on the dose dependence of the survival of stem cells in small intestine epithelium].
After a single or three-fold whole body irradiation of mice with a dose of 4 Gy and the time interval for the proliferation to be restored (5 days or 3 weeks) the survival curve for stem cells of small intestine epithelium with regard to radiation dose was the same as that for non-preirradiated mice. This indicated that the proliferative potential of stem cells in these experimental conditions was not reduced.


Antimicrobial susceptibilities of Clostridium difficile isolated in Japan.
Clostridium difficile is a common causative organism of antimicrobial-associated diarrhea and is often responsible for nosocomial infection. C. difficile infection has traditionally been treated with metronidazole (MNZ) or vancomycin (VCM); however, MNZ-resistant strains have reported in some countries. In this study the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of 15 drugs against 157 clinical isolates of C. difficile in Japan. All C. difficile isolates tested were susceptible to MNZ; MIC50 was 0.25 μg/ml, MIC90 was 0.5 μg/ml, and MIC range was 0.06-1 μg/ml. C. difficile isolates were also susceptible to VCM; MIC50 was 0.5 μg/ml, MIC90 was 1 μg/ml, and MIC range was 0.12-2 μg/ml. Susceptibility to teicoplanin was also similar: MIC50 was 0.12 μg/ml, MIC90 was 0.12 μg/ml, and MIC range was 0.03-0.25 μg/ml. The susceptibility of C. difficile isolates must be monitored continuously because a strain with reduced susceptibility to MNZ or VCM might emerge in the future.


Sialosylcholesterol effects on reconstitution of microfilament and glia filament.
The effects of alpha-sialosylcholesterol (alpha-SC) on formation of either microfilament or glia filament of rat astrocytes were investigated using a reconstitution system. Polymerization of the depolymerized microfilament preparation that had been extracted from a crude cytoskeletal fraction of rat astrocytes, in the presence of 100 mM KCl and 10 mM MgCl2, was suppressed in a dose-dependent manner by alpha-SC. alpha-SC inhibited polymerization of G-actin in a similar manner. The intensity of alpha-SC inhibition of G-actin polymerization was as great as that of microfilament polymerization, suggesting that the inhibition of microfilament polymerization by alpha-SC was due to the direct action of alpha-SC on actin, the main component of microfilament. alpha-SC depolymerized partly the polymerized microfilament preparation, which resembled F-actin (microfilament-like filaments). alpha-SC suppressed, in a dose-dependent manner, polymerization of a glia filament preparation that had been extracted from astrocyte cytoskeletons in the presence of phalloidin. An increase in the amount of added alpha-SC (up to 15 microM) decreased the amount of the larger glia filament-like filaments, which were 10 nm thick and centrifuged down at 16,000 g for 30 min, and increased that of smaller ones precipitated only after centrifugation at 100,000 g for 1 h. The lower the concentration of the depolymerized glia filament extract, the greater was the inhibition by alpha-SC of the polymerization. alpha-SC repressed polymerization of vimentin, the dominant component of glia filament. Vimentin polymerization was more strongly inhibited by alpha-SC than polymerization of glia filament was.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of a single dose of fluoride on calcium metabolism.
Fluoride 27 mg was given perorally to 14 subjects. It was found that the serum fluoride concentration increased followed by a decrease to normal levels during 24 h. Serum concentrations of calcium and phosphate decreased initially whereas those of serum immunoreactive parathyroid hormone increased. After 24 h the measured quantities were within normal limits. The results are discussed with reference to mineralization of hard tissues and to fluoride treatment of osteoporotic patients.


United States Medical Licensing Examination Step 1 and 2 Scores Predict Neuroradiology Fellowship Success.
Many neuroradiology programs use United States Medical Licensing Examination (USMLE) scores to assess fellowship candidates. The authors hypothesized that because they are taken several years before fellowship, USMLE scores would correlate poorly with success in fellowship training as measured by faculty evaluations. USMLE scores from 10 years of neuroradiology fellows (n = 73) were compared with their cumulative mean E*Value scores from their fellowship years and their best-to-worst rankings within their fellowship years. If available, subspecialty certification scores were also factored as an outcome. Linear correlation and regression analyses were performed adjusting for gender, medical school site, and practice setting after fellowship. USMLE Step 1, 2, and 3 scores were available for 69, 64, and 56 fellows, respectively. Fellowship E*Value scores and rankings showed statistically significant (P < .05) correlations with all USMLE scores, but most strongly for Step 1 scores and E*Value grade (r = 0.443) and rank (r = 0.370). The mean USMLE Step 1 score of the top-ranked fellows (234.5) was significantly higher than that of the bottom-ranked fellows (217.7). The correlations of E*Value score and rank with USMLE Step 1 and 2 scores remained after adjusting for gender and American versus foreign medical school, but the medical school site attended also was an independent predictor of fellowship evaluations. Subspecialty certification scores did not show correlations but were underpowered (n = 28). USMLE Step 1 and 2 scores correlated significantly with success in neuroradiology fellowship, measured by faculty assessments of the six core competencies. Using the scores as a means of assessing candidates for positions is justified.


[Angiomatoid fibrous histiocytoma in children: 6 cases].
Angiomatoid fibrous histiocytoma (AFH) is a soft-tissue tumour of uncertain differentiation most often arising in the extremities of children and young adults. AFH is a little-known neoplasm and its rarity may result in it being misdiagnosed as either a reactive lesion or a benign or higher-grade tumour. We report 6 cases of AFH in children and we review the clinicopathological and molecular features of this neoplasm published in the literature. The children (aged 4 to 16 years) presented a single nodule involving the forearm (4/6), the trunk or the buttock, and all 5 nodules appeared spontaneously. Microscopic examination revealed well-circumscribed nodular lesions comprising a fibrous pseudo-capsule, haemorrhagic non-endothelial-lined pseudocystic spaces, and sheets of spindle and ovoid cells with dense surrounding lymphoplasmacytic infiltrate. Tumours were positive for desmin, CD68, CD99 and smooth-muscle actin markers. A fusion gene (EWSR1-ATF1) was found in the 3 cases in which molecular investigation was performed. In our series, a diagnosis of AFH had in no event been evoked after clinical examination and radiological investigation. The diagnosis was based in all cases on recognition of characteristic features during histological examination and it was confirmed in 3 cases by the recognition of fusion genes. Complete excision with wide margins allowed complete cure in all cases, supporting a good prognosis of AFH, although long-term follow-up is still mandatory to rule out relapse or metastases, which although rare, are responsible for fatal cases. To avoid unnecessary surgery in patients with AFH, an ultrasound core-needle biopsy should be performed as a first step in order to provide precise diagnosis enabling complete excision to be performed, with the margins being decided in multidisciplinary meetings involving teams specialised in soft-tissue tumours.


Underutilization of Blue Light Cystoscopy for Bladder Cancer in the United States.
Blue light cystoscopy (BLC) during transurethral resection of bladder tumor (TURBT) is guideline-recommended as it improves cancer detection and decreases recurrence of the disease. However, the extent to which BLC is used has not been established. We studied BLC use in the Premier Healthcare Database, a large, national sample that captured 158 870 index TURBT procedures between January 2011 and March 2020. Billing data were queried for the administration of hexaminolevulinate at TURBT as a proxy for BLC, and logistic regression models were constructed to identify variables associated with BLC use. BLC was used in 1.2% of index TURBT procedures over the study period. Its use increased following the American Urological Association non-muscle-invasive bladder cancer guideline publication in October 2016 but plateaued in late 2018. After adjusting for patient characteristics, higher odds for BLC use were found for academic hospitals and hospitals with higher TURBT volumes and higher radical cystectomy volumes. Within hospitals with BLC capability, predictors of a surgeon never using BLC included low surgeon TURBT volumes, low surgeon radical cystectomy volumes, and lack of mitomycin C use. Our findings highlight a concerning underutilization and stagnation in the adoption of evidence and guideline-supported intervention. PATIENT SUMMARY: Use of blue light visualization of the bladder improves the detection of cancer during removal of bladder tumors via the urethra. We reviewed records in a large US database for use of this technique and found that it is being underutilized. Since this technique improves detection of cancer in the bladder so that it can be removed to reduce recurrence, blue light visualization should be more widely used.


The Effect of Shortening-induced Torque Depression on Fatigue-related Sex Differences.
Residual torque depression (rTD) is the decrease in isometric (ISO) torque after active shortening of skeletal muscle compared with a purely ISO contraction performed at the same muscle length and level of activation. Performance fatigability is defined as any exercise-induced reduction in voluntary force or power, and females are typically more fatigue resistant than males at low-intensity ISO contractions. This study investigated performance fatigability in males and females during ISO contractions and ISO contractions after active shortening (rTD). Fourteen females (22 ± 2 yr) and 14 males (23 ± 2 yr) performed three baseline maximal voluntary contractions (MVCs) of the dorsiflexors. The MVCs were used to determine a 30% submaximal torque target, which participants matched as steadily as possible until task failure. The ISO fatigue task was performed at 10° plantar flexion. In the rTD session, the participants' ankle was rotated from 40° to 10° plantar flexion before performing the same fatigue task. MVCs were performed immediately after task failure, 30 s, and 1, 2, 3, 4, 5, 10, 20, and 30 min after task failure to track recovery. The baseline MVC torque amplitude for males (32.1 ± 6.6 N·m) was 31% greater than that for females (22.3 ± 3.1 N·m; P < 0.001, ηp = 0.490). Females' time to task failure was 44% longer than that of males in the ISO state (P = 0.032, ηp = 0.164). However, there was no sex difference in the rTD state (P = 0.142). It seems that the sex differences in fatigue resistance observed in a low-intensity ISO task are abolished in the ISO state after an active shortening contraction.


Transcriptome and genome sequencing elucidates the molecular basis for the high yield and good quality of the hybrid rice variety Chuanyou6203.
The yield heterosis of rice is sought by farmers and strong contributes to food safety, but the quality of hybrid rice may be reduced. Therefore, developing new varieties with both high yield and good quality is a heavily researched topic in hybrid rice breeding. However, the molecular mechanism governing yield heterosis and high rice quality has not been elucidated to date. In this study, a comparative transcriptomics and genomic analysis was performed on a hybrid rice variety, Chuanyou6203 (CY6203), and its parents to investigate the molecular mechanism and gene regulation network governing the formation of yield and quality stages. A total of 66,319 SNPs and InDels between CH3203 and C106B were detected in the 5'-UTR, exon, intronic, and 3'-UTR regions according to the reference genome annotation, which involved 7473 genes. A total of 436, 70, 551, 993, and 1216 common DEGs between CY6203 and both of its parents were identified at the same stage in panicles and flag leaves. Of the common DEGs, the numbers of upregulated DEGs between CY6203 and CH3203 were all greater than those of upregulated DEGs between CY6203 and C106B in panicles and flag leaves at the booting, flowering, and middle filling stages. Approximately 40.61% of mRNA editing ratios were between 0.4 and 0.6, and 1.68% of mRNA editing events (editing ratio ≥ 0.8) in CY6203 favored one of its parents at three stages or a particular stage, suggesting that the hypothetical heterosis mechanism of CY6203 might involve dominance or epistasis. Also 15,934 DEGs were classified into 19 distinct modules that were classified into three groups by the weighted gene coexpression network analysis. Through transcriptome analysis of panicles and flag leaves in the yield and quality stages, the DEGs in the green-yellow module primarily contributed to the increase in the source of CY6203 due to an in increase in photosynthetic efficiency and nitrogen utilization efficiency, and a small number of DEGs related to the grain number added spikelet number per panicle amplified its sink. The balanced expression of the major high-quality alleles of C106B and CH3203 in CY6203 contributed to the outstanding quality of CY6203. Our transcriptome and genome analyses offer a new data set that may help to elucidate the molecular mechanism governing the yield heterosis and high quality of a hybrid rice variety.


Outcomes in Ixekizumab Patients Following Exposure to Secukinumab and Other Biologics in the CorEvitas Psoriasis Registry.
The aim of this work is to describe real-world biologic-experienced psoriasis patients initiating ixekizumab by prior biologic therapy status and compare the effectiveness of ixekizumab between patients who previously failed secukinumab and those who failed other biologics. We hypothesized that (1) clinical outcomes and patient-reported outcomes would improve following a switch to IXE, and (2) there would be no differences in responses between patients who previously failed secukinumab and those who failed other biologics. Participants (n = 419) included adult psoriasis patients enrolled in the CorEvitas Psoriasis Registry through 9/10/20 who switched to ixekizumab after discontinuing another biologic. Patients were classified by the biologic used immediately prior to ixekizumab and reason for discontinuation: prior secukinumab failure; prior secukinumab non-failure; prior other biologic failure; and prior other biologic non-failure. Discontinuations for efficacy reasons were considered failures; all others were considered non-failures. Baseline descriptive statistics were calculated. Multivariable Poisson regression models estimated the likelihood of response of other failure relative to secukinumab failure. Mean age was 51 years; 48% were women. Psoriasis disease characteristics were similar across prior biologic groups. At 6-month follow-up, disease severity improved for all who initiated ixekizumab after discontinuing another biologic. Secukinumab failure patients who switched to ixekizumab achieved BSA ≤ 1 (49%), BSA ≤ 3 (59%), PASI75 (46%), PASI ≤ 3 (64%), and IGA ≤ 1 (40%). Other failure patients achieved BSA ≤ 1 (55%), BSA ≤ 3 (72%), PASI75 (59%), PASI ≤ 3 (74%), and IGA ≤ 1 (54%). In regression modeling, we observed patients in the other biologics failure group had an increased likelihood of achieving response for BSA ≤ 3, PASI75, PASI90, PASI100, and IGA ≤ 1 compared to patients who failed secukinumab. These findings suggest that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity after six months. Patients who discontinued biologics other than secukinumab may be more likely to respond to ixekiziumab compared to those who switched from secukinumab.


[Phonocardiographic and auscultatory patterns in patients with normally functioning Lillehei-Kaster aortic prosthesis (author's transl)].
42 patients who had undergone aortic valve replacement with the Lillehei-Kaster prosthesis were studied. Phonocardiographic and physical examinations were carried out on these patients to determine the typical auscultatory pattern of this prosthesis. In the majority of the cases, the first sound was slight. The second sound was made up of two components, both produced by the artificial valve. A prosthetic opening sound was also detected. Moreover, a sistolic ejection murmur was present in all of the patients, and a diastolic murmur in 25%.


8-Methyl-3-methyl-sulfanyl-8a,8b-di-hydro-5H-1-oxa-2,4-di-aza-ace-naphthyl-ene.
In the tricyclic title compound, C11H12N2OS, the 2,3,4,5-tetra-hydro-pyridine ring adopts a half-chair conformation. This ring makes dihedral angles of 27.72 (7) and 45.17 (7)°, respectively, with the isoxazole and the cyclo-hexa-1,3-diene rings while the isoxazole ring is oriented at an acute angle of 63.46 (7)° with respect to the cyclo-hexa-1,3-diene ring. In the crystal, mol-ecules associate via C-H⋯N hydrogen bonds and C-H⋯π inter-actions, forming a three-dimensional network.


Chemosignalling of musth by individual wild African elephants (Loxodonta africana): implications for conservation and management.
Elephants have extraordinary olfactory receptive equipment, yet this sensory system has been only minimally investigated in wild elephants. We present an in-depth study of urinary chemical signals emitted by individual, behaviourally characterized, wild male African elephants, investigating whether these compounds were the same, accentuated, or diminished in comparison with captive individuals. Remarkably, most emitted chemicals were similar in captive and wild elephants with an exception traced to drought-induced dietary cyanates among wild males. We observed developmental changes predominated by the transition from acids and esters emitted by young males to alcohols and ketones released by older males. We determined that the ketones (2-butanone, acetone and 2-pentanone, and 2-nonanone) were considerably elevated during early musth, musth and late musth, respectively, suggesting that males communicate their condition via these compounds. The similarity to compounds released during musth by Asian male elephants that evoke conspecific bioresponses suggests the existence of species-free 'musth' signals. Our innovative techniques, which allow the recognition of precise sexual and musth states of individual elephants, can be helpful to managers of both wild and captive elephants. Such sampling may allow the more accurate categorization of the social and reproductive status of individual male elephants.


Allograft interference screw fixation in meniscus transplantation.
Allograft meniscus transplantation is indicated to restore proper knee biomechanics and prevent subsequent articular degeneration in patients with a meniscus-deficient knee. A variety of techniques for fixation of meniscal transplants exist, with some techniques using soft-tissue fixation of the meniscal horns and others using bony fixation. The authors present a technique of meniscus transplantation using a tibial slot with allograft interference screw fixation. We have had excellent early results with this technique and believe that a cortical allograft interference screw reliably maintains the anatomic position of the meniscal attachments that are critical to the biomechanics and functional outcome of meniscus transplantation.


The Far-Lateral Suboccipital Approach to the Lesions of the Craniovertebral Junction.
The far-lateral suboccipital approach and its variants, including the transcondylar, supracondylar, and paracondylar approaches, are essential skull base techniques for the neurosurgeon to expose and treat pathologies located at the ventral and ventrolateral craniovertebral junction. An understanding of the surgical anatomy and technical nuances of these approaches is vital for preventing catastrophic brainstem or spinal cord injury, neurovascular injury, and/or cranial nerve injury. This is achieved by carefully studying the location, the rostral-caudal and lateral extents of the lesion itself, and the anatomy of the surrounding structures on preoperative imaging. The amount of bony exposure should be tailored to each specific lesion to avoid unnecessary bone drilling and therefore decrease the risk of potential craniocervical instability. Minimizing retraction of the cerebellum, brainstem, and spinal cord is important for preventing neurologic injury; therefore, appropriate intraoperative head positioning and adequate bony exposure should be ensured, especially for more ventrally located lesions. A thorough knowledge of the anatomy of the extradural and intradural segments of the vertebral artery, and the lower cranial nerves, in relation to the lesion is also critical. For almost all lesions, the far-lateral suboccipital route with no or minimal condylar drilling is more than adequate for removing the most ventral lesions. Herein, we discuss the indications, general and preoperative considerations, and surgical anatomy and technical nuances of this approach.


Slight Elongation of the Scaphoid and Cancellous Bone Graft Without Compression for Treatment of Scaphoid Nonunions.
In treating scaphoid nonunion, we have developed a technique of bone grafting and elongation of the scaphoid stabilizing the construct with K wires without compression. Bony union was achieved in the large majority of scaphoids as demonstrated on computed tomography (CT) scans. We advocate slight lengthening of the scaphoid with bone graft and K-wire fixation without compression of the grafted bone when treating scaphoid waist nonunion.


Centralized data analysis of a large interlaboratory proteomics project: a feasibility study.
The human Plasma Proteome Project (PPP) is a large-scale collaboration between many laboratories. One of the most demanding tasks in the PPP involved the analysis of very large amounts of raw MS/MS data produced by the participants. The main approach for managing this task was letting the participants analyze their own data and submit the results to the central PPP repository as lists of identified proteins and peptides. To complement this distributed approach, we also performed centralized analysis of the raw MS/MS data provided by the participants. Due to the data redundancy inherent in such a project, centralized analysis has the potential to reduce the computational effort by reducing redundancy before the analysis. Centralized analysis can also unify the process and take advantage of data sharing among laboratories to improve protein identification and validation. The process we employed included removing low-quality spectra, clustering spectra by mutual similarity, and applying uniform peptide and protein identification procedures. To demonstrate the process, we analyzed 5.28 million MS/MS spectra derived by eight laboratories from tryptic peptides of serum and plasma proteins.


Production of enterotoxins and thermonuclease by Staphylococcus aureus in cooked egg-noodles.
Production of enterotoxin A (SEA), enterotoxin C (SEC), and thermonuclease (TNase) by Staphylococcus aureus was determined during growth in cooked egg-noodles at different temperatures (15-37 degrees C). Both SEA and SEC and TNase were detected when greater than or equal to 4.0 x 10(7) colony forming units (cfu)/g were present. The contents of SEA, SEC, and TNase in egg-noodles mainly increased at the end of the exponential growth phase. In contrast with SEA and SEC the production of TNase always continued till the end of each experiment. Recovery rates of SEA and TNase in cooked noodles were dependent on their amounts. High amounts (64 ng SEA/g; 1 unit TNase/g) were recovered at a rate of 93% (SEA) and 54% (TNase) respectively, whereas low concentrations (1 ng SEA/g; 0.004 units TNase/g) were recovered at a rate of only 45% (SEA) and 1.1% (TNase). TNase usually is produced at all conditions which allow growth of S. aureus. Evidence of TNase was proposed for screening for staphylococcal enterotoxins (SE) in foods. But sometimes foods contain no TNase but SE. For this reason the ELISA-test which is simple and sensitive should be used for determination of SE-production in foods.


The Proportion of Meniscus Tears Considered Repairable, and Thus Repaired, Increased During a Single Surgeon's Practice of 20 Years.
The purpose of this study was to evaluate practice patterns of a single surgeon with respect to meniscectomy and meniscal repair over a 20-year period at a single institution. A cross-sectional descriptive study was carried out by reviewing the surgical data from the past 20 years (2002-2021) of patients who underwent arthroscopic primary meniscal surgery. Age, sex, knee and meniscus affected, morphology of the meniscal tear, meniscal radial location, location on the axial plane, tissue quality, and associated injuries were recorded. An analysis of the evolution of the characteristics of the meniscal lesions was performed according to the presence of degenerative tissue, the repairability of the lesion, and the treatment performed. Categorical data were represented in contingency tables and compared using the χ2 test for significance of differences, which was set at P < .05. In total, 1,892 cases were included. A decrease in degenerative meniscal tears was found, from 63.2 in 2002 to 2006 to 9.7% in 2017 to 2021 (P < .001), while repairable tears increased from 1.6% to 82.3% P < .001); in the same periods, arthroscopic partial meniscectomy procedures declined from 75.7% to 17.7% (P < .001) while meniscal repair increased from 0.4% to 81.3% (P < .001). All types of tears increased significantly their repairability, although longitudinal tears, root tears, and ramp lesions showed the highest possibilities for repair. In the present study, a drastic change in the attitude toward meniscal preservation in the past 20 years was observed, with a large increase in the proportion of tears considered repairable found in primary arthroscopic surgery (to 80% of cases) and a decrease in degenerative meniscus tears (to less than 10%). In the past 2 decades, arthroscopic knee surgery has evolved such that more meniscus tears are deemed repairable, and fewer tears considered degenerative are indicated for arthroscopy.


Developmental changes in the protein composition of Manduca sexta lipid droplets.
The lipid droplets (LDs) are intracellular organelles mainly dedicated to the storage and provision of fatty acids. To accomplish these functions the LDs interact with other organelles and cytosolic proteins. In order to explore possible correlations between the physiological states of cells and the protein composition of LDs we have determined and compared the proteomic profiles of lipid droplets isolated from the fat bodies of 5th-instar larvae and adult Manduca sexta insects and from ovaries. These LD-rich tissues represent three clearly distinct metabolic states in regard to lipid metabolism: 1) Larval fat body synthesizes fatty acids (FA) and accumulates large amounts as triglyceride (TG); 2) Fat body from adult insects provides FA to support reproduction and flight; 3) Ovaries do not synthesize FA, but accumulate considerable amounts of TG in LDs. Major qualitative and semi-quantitative variations in the protein compositions of the LDs isolated from these three tissues were observed by MS/MS and partially validated by immuno-blotting. The differences observed included changes in the abundance of lipid droplet specific proteins, cytosolic proteins, mitochondrial proteins and also proteins associated with the machinery of protein synthesis. These results suggest that changes in the interaction of LDs with other organelles and cytosolic proteins are tightly related to the physiological state of cells. Herein, we summarize and compare the protein compositions of three subtypes of LDs and also describe for the first time the proteomic profile of LDs from an insect ovary. The compositions and compositional differences found among the LDs are discussed to provide a platform for future studies on the role of LDs, and their associated proteins, in cellular metabolism.


High-dose Oral Ambroxol for Early Treatment of Pulmonary Acute Respiratory Distress Syndrome: an Exploratory, Randomized, Controlled Pilot Trial.
To evaluate efficacy of high-dose oral ambroxol in acute respiratory distress syndrome (ARDS) with respect to ventilator-free days (VFD). Prospective, randomized, placebo-controlled, blinded pilot trial. Sixty-six mechanically ventilated patients (1 month to 12 years) with ARDS who were hand-ventilated for <24 hr before pediatric intensive care unit admission. Patients randomized to oral ambroxol (40 mg/kg/day, in four divided doses) (n = 32) or placebo (n = 34) until 10 days, extubation or death whichever is earlier. Majority (91%) had pneumonia and bronchiolitis. Two study groups were similar in baseline characteristics. Mean partial pressure of arterial oxygen/fraction of inspired oxygen and oxygenation index were >175 and <10, respectively, with no difference in the two study groups. VFD were similar in the two study groups. Overall mortality was 26%. No adverse events were noted with ambroxol. Among ventilated pulmonary ARDS patients with oxygenation index of <10, mortality was 26%. Ambroxol did not improve VFD. Study with higher and more frequently administered doses of ambroxol in larger sample is suggested after having generated relevant pharmacokinetic data among critically ill children.


Direct evidence for ATP release from non-adrenergic, non-cholinergic ("purinergic") nerves in the guinea-pig taenia coli and bladder.
Demonstration of release of ATP from smooth muscle preparations during stimulation of purinergic nerves is complicated by the difficulty in showing whether it comes from nerve or muscle. ATP released during relaxation of the guinea-pig taenia coli and contraction of bladder strips in response to purinergic nerve stimulation was measured in the superfusate using the luciferin-luciferase ATP assay method. The amount of ATP increased 2-6 fold during isometric responses to purinergic nerve stimulation. This release was blocked by tetrodotoxin but not by adrenergic nerve destruction with 6-hydroxydopamine. No significant release of ATP was detected during comparable responses elicited by direct muscle stimulation. These results provide further support for the purinergic nerve hypothesis.


A Rare Case of Obstructive Uropathy in an Elderly Male From Rural India - A Case Report.
Ureterocele is a rare congenital anomaly often believed to be caused due to incomplete dissolution of the Chwalla membrane. In this pathology, the distal end of the ureter is invaginated in the bladder and is dilated. We present a case of an 81-year-old male from rural India who came with complaints of hematuria and was diagnosed with ureterocele.


Melatonin attenuates posttransplant lung ischemia-reperfusion injury.
Melatonin, a pineal hormone, is a free radical scavenger and an antioxidant. The purpose of this study was to assess the protective effect of melatonin on posttransplant lung ischemia-reperfusion injury. Rat single-lung transplantation was performed in two (n = 10) experimental groups after 18 hours of cold (4 degrees C) ischemia. Group I animals consisted of the ischemic control group. In group II, donor and recipient animals were treated with intraperitoneal injection of 10 mg/kg melatonin 10 minutes before harvest and reperfusion, respectively. After 2 hours of reperfusion, oxygenation, plasma, and bronchoalveolar lavage nitrite levels were measured. Lung tissue was assessed for thiobarbituric acid reactive substances and myeloperoxidase activity. Peak airway pressure was recorded throughout the reperfusion period. The melatonin-treated group showed significantly better oxygenation (321.8+/-33.8 mm Hg versus 86.1+/-17.4 mm Hg; p < 0.001), reduced lipid peroxidation (0.65+/-0.3 nmol/g versus 1.63+/-0.8 nmol/g; p = 0.032), and reduced myeloperoxidase activity (0.56+/-0.1 deltaOD x mg(-1) x min(-1) versus 1.01+/-0.2 deltaOD x mg(-1) x min(-1); p = 0.032). Bronchoalveolar lavage nitrite levels in the transplanted lungs were significantly lower in group II than in group I (0.34+/-0.06 micromol/L versus 1.65+/-0.6 micromol/L; p = 0.016). In group II significant reduction in peak airway pressure was noted compared with group I (p = 0.002). In this model, exogenously administered melatonin effectively protected lungs from reperfusion injury after prolonged ischemia.


[An evidence-based healthcare system and the role of the healthcare professions].
An evidence-based healthcare system necessitates a new role allocation and new role definitions of the players. By means of professional delegation, physician-nurse substitution and adoption of new professional functions, which so far have not been part of their professional profiles, nurses, midwives and allied health professionals will adopt a broad spectrum of new responsibilities. At present, nurses, midwives and allied health professionals lack basic scientific competencies and opportunities to acquire skills in evidence-based practice. A reliable link between evidence-generating sciences in nursing, midwifery and allied health professions and clinical practice is missing. In the future, an increase of academically qualified health professionals and a new skills mix within each profession might promote active and effective participation in an evidence-based healthcare system. (As supplied by author).


Restriction fragment length polymorphisms associated with the gene for the major intrinsic protein of eye-lens fibre cell membranes in mice with hereditary cataracts.
Cloned cDNAs coding for eye-lens fibre cell-membrane proteins, MIP and MP70, were used to detect restriction fragment length polymorphisms (RFLPs) in genomic DNA from inbred mice with autosomally inherited cataracts. Whereas distinct RFLPs associated with the MIP gene were identified in the Cba Cat and Nct mutants, no such genetic variation was associated with the MP70 gene. RFLPs associated with the mouse MIP gene may provide informative DNA markers in gene linkage studies of murine hereditary cataracts.


Hydrogen peroxide biosensor based on microperoxidase-11 immobilized in a silica cavity array electrode.
Hydrogen peroxide biosensor based on the silica cavity array modified indium-doped tin oxide (ITO) electrode was constructed. An array of silica microcavities was fabricated by electrodeposition using the assembled polystyrene particles as template. Due to the resistance gradient of the silica cavity structure, the silica cavity exhibits a confinement effect on the electrochemical reactions, making the electrode function as an array of "soft" microelectrodes. The covalently immobilized microperoxidase-11(MP-11) inside these SiO2 cavities can keep its physiological activities, the electron transfer between the MP-11 and electrode was investigated through electrochemical method. The cyclic voltammetric curve shows a quasi-reversible electrochemical redox behavior with a pair of well-defined redox peaks, the cathodic and anodic peaks are located at -0.26 and -0.15V. Furthermore, the modified electrode exhibits high electrocatalytic activity toward the reduction of hydrogen peroxide and also shows good analytical performance for the amperometric detection of H2O2 with a linear range from 2×10(-6) to 6×10(-4)M. The good reproducibility and long-term stability of this novel electrode not only offer an opportunity for the detection of H2O2 in low concentration, but also provide a platform to construct various biosensors based on many other enzymes.


Development and Optimisation of Hydrogel Scaffolds for Microvascular Network Formation.
Traumatic injuries are a major cause of morbidity and mortality worldwide; however, there is limited research on microvascular traumatic injuries. To address this gap, this research aims to develop and optimise an in vitro construct for traumatic injury research at the microvascular level. Tissue engineering constructs were created using a range of polymers (collagen, fibrin, and gelatine), solvents (PBS, serum-free endothelial media, and MES/NaCl buffer), and concentrations (1-5% w/v). Constructs created from these hydrogels and HUVECs were evaluated to identify the optimal composition in terms of cell proliferation, adhesion, migration rate, viability, hydrogel consistency and shape retention, and tube formation. Gelatine hydrogels were associated with a lower cell adhesion, whereas fibrin and collagen ones displayed similar or better results than the control, and collagen hydrogels exhibited poor shape retention; fibrin scaffolds, particularly at high concentrations, displayed good hydrogel consistency. Based on the multipronged evaluation, fibrin hydrogels in serum-free media at 3 and 5% w/v were selected for further experimental work and enabled the formation of interconnected capillary-like networks. The networks formed in both hydrogels displayed a similar architecture in terms of the number of segments (10.3 ± 3.21 vs. 9.6 ± 3.51) and diameter (8.6446 ± 3.0792 μm vs. 7.8599 ± 2.3794 μm).


[Analysis of microsatellite variation in the rainbow trout (Parasalmo (Oncorhynchus) mykiss) from Kamchatka].
Genetic variation of Kamchatka rainbow trout Parasalmo (O.) mykiss was examined using 10 microsatellite DNA loci, and phylogeographic comparison with other representatives of the species across the distribution range was performed. It was demonstrated that Kamchatka populations differed from other geographic groups of rainbow trout in a number of microsatellite loci. These populations also displayed distinct clustering and were characterized by lower genetic diversity. Analysis of a set of 26 different microsatellite loci (personal and literature data) demonstrated that most of the populations within the Kamchatka region were separated from one another, characterized by marked geographic differentiation, and affiliation to certain river basins. In Kamchatka rainbow trout, with high degree of probability, three geographic clusters (northwestern, southwestern, and eastern) were identified. In general, analysis of microsatellite DNA supported the data on low genetic diversity of the Kamchatka group Parasalmo (O.) mykiss, based on the variation estimates for a number of genes of nuclear and mitochondrial DNA, and allozyme loci.


Perphenazine decanoate in sesame oil vs. perphenazine enanthate in sesame oil: a comparative study of pharmacokinetic properties and some clinical implications.
Ten schizophrenic inpatients were each treated with perphenazine enanthate (PE) and perphenazine decanoate (PD). Following a cross-over study design it was possible to evaluate differences in plasma profiles between the two preparations, and to relate these to encountered side effects. All patients had previously been receiving neuroleptic treatment and had been diagnosed according to DSM-III. The dosage and intervals between injections were on an individual basis. The results indicate that at all dosage levels, the decanoate preparation showed significantly lower peak plasma concentrations of perphenazine. Extrapyramidal side effects and sedation were also less pronounced after the administration of PD. The more even and flat plasma concentrations obtained with PD, may facilitate plasma monitored therapy by using minimum concentration values.


The characteristics of open-tubular capillary electrochromatography columns with series/mixed stationary phases constructed with magnetic nanoparticle coating.
Novel open-tubular capillary electrochromatography (OT-CEC) systems with core/shell magnetic nanoparticles modified by amino or C18 groups as stationary phase were constructed by immobilizing nanoparticles in the capillary with permanent magnets. Influence of preparation method of OT-CEC column with series stationary phases (continuous two-dimension) on column performance and effect of dispersant on capability of OT-CEC column prepared by stationary phases with mixed functionalities (mixed stationary phases) were investigated in details to achieve stable preparation. Organic acids were used to evaluate the OT-CEC systems, and the relative column efficiency of salicylic acid was 420,000 plates/m for series stationary phases, while that of benzoic acid reached 480,000 plates/m for mixed stationary phases. The excellent within-column and between-column repeatability (n=5) testified with the RSDs of retention time were less than 0.44% and 10.20% for series stationary phases and 1.65% and 4.29% for mixed stationary phases. The two OT-CEC systems were further applied to separation of the aqueous extract of Rhizoma gastrodiae. Comparing with normal OT capillary column, the new systems show extra high column efficiency due to large surface areas of nanoparticles and multiple separation mechanisms, and they have great potential in the method development for the analysis of complicated samples.


Diagnostic validation and interpretation of longitudinal circulating biomarkers using a biomarker response characteristic plot.
Serum-based tumor biomarkers are used to monitor cancer treatment, while clear guidance on the clinical usage is often lacking. We describe a graphical presentation to support diagnostic accuracy studies and clinical interpretation of longitudinal biomarker data. A biomarker response characteristic (BReC) plot was designed. To allow demonstration of the BReC plot application, software was developed that supported 1) dynamic generation of BReC plots, and 2) diagnostic accuracy studies of biomarker response-based medical tests. The BReC plot application was demonstrated using serial carcinoembryonic antigen (CEA) and Cyfra 21.1 results from 216 patients with metastasized non-small cell lung cancer, treated with Nivolumab in routine clinical practice. The developed software supported the generation of BReC plots and diagnostic validation of biomarker response-based medical tests by generating the sensitivity, specificity and predictive values. Obtained BReC plots showed a clear relationship between clinical outcome and CEA and Cyfra 21.1 responses. Furthermore, using BReC plots, CEA and Cyfra 21.1 based medical tests were designed with a sensitivity for detection of treatment failure of 0.34 and 0.35 and a specificity of 0.96. The BReC plot appears to support diagnostic validation studies and the interpretation of longitudinal biomarkers though further validation is warranted.


Healthy immigrants, unhealthy ageing? Analysis of health decline among older migrants and natives across European countries.
The probability of having multiple chronic conditions simultaneously, or multimorbidity, tends to increase with age. Immigrants face a particularly high risk of unhealthy ageing. This study investigates the immigrant-native disparities in the speed of age-related chronic disease accumulation, focusing on the number of chronic health conditions; and considers the heterogeneity of this trajectory within immigrant populations by origin and receiving country. We use data from the Survey of Health, Ageing and Retirement in Europe from 2004 to 2020 on adults aged 50 to 79 from 28 European countries and employ both cross-sectional and longitudinal analyses. For longitudinal panel analyses, we use fixed-effects regression models to account for the unobserved heterogeneity related to individual characteristics including migration background. Our results indicate that immigrants report a higher number of chronic conditions at all ages relative to their native-born peers, but also that the immigrant-native differential in the number of chronic conditions decreases from age 65 onwards. When considering differences by origin country, we find that the speed of chronic disease accumulation is slower among immigrants from the Americas and the Asia and Oceania country groups than it is among natives. When looking at differences by receiving country group, we observe that the speed of accumulating chronic diseases is slower among immigrants in Eastern Europe than among natives, particularly at older ages. Our findings suggest that age-related trajectories of health vary substantially among immigrant populations by origin and destination country, which underscore that individual migration histories play a persistent role in shaping the health of ageing immigrant populations throughout the life course.


Scenarios, personas and user stories: user-centered evidence-based design representations of communicable disease investigations.
Despite years of effort and millions of dollars spent to create unified electronic communicable disease reporting systems, the goal remains elusive. A major barrier has been a lack of understanding by system designers of communicable disease (CD) work and the public health workers who perform this work. This study reports on the application of user-centered design representations, traditionally used for improving interface design, to translate the complex CD work identified through ethnographic studies to guide designers and developers of CD systems. The purpose of this work is to: (1) better understand public health practitioners and their information workflow with respect to CD monitoring and control at a local health agency, and (2) to develop evidence-based design representations that model this CD work to inform the design of future disease surveillance systems. We performed extensive onsite semi-structured interviews, targeted work shadowing and a focus group to characterize local health agency CD workflow. Informed by principles of design ethnography and user-centered design we created persona, scenarios and user stories to accurately represent the user to system designers. We sought to convey to designers the key findings from ethnographic studies: (1) public health CD work is mobile and episodic, in contrast to current CD reporting systems, which are stationary and fixed, (2) health agency efforts are focused on CD investigation and response rather than reporting and (3) current CD information systems must conform to public health workflow to ensure their usefulness. In an effort to illustrate our findings to designers, we developed three contemporary design-support representations: persona, scenario, and user story. Through application of user-centered design principles, we were able to create design representations that illustrate complex public health communicable disease workflow and key user characteristics to inform the design of CD information systems for public health.


Video-assisted thoracic surgery lobectomy for right lung cancer in a patient with right aortic arch: report of a case.
A 57-year-old man with an anomalous right aortic arch presented with cancer of the right lung. The right recurrent laryngeal nerve was found to be hooked around the right aortic arch. Right lower lobectomy with systematic mediastinal lymph node dissection was successfully performed using video-assisted thoracic surgery to provide close intraoperative attention to the branching of recurrent laryngeal nerve.


The role of molecular markers and tumor histological type in central lymph node metastasis of papillary thyroid carcinoma.
To look for genetic mutations that might predict central compartment lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) using strict criteria for N0 and N1 disease. We identified patients with PTC from our institution's pathology archives. Strict criteria were used for assessing the presence or the absence of central neck LNM. Disease was classified as N0 only if a comprehensive ipsilateral and pretracheal central neck dissection was performed and if pathological analysis revealed no evidence of LNM. Primary tumor samples were analyzed for a panel of known or suspected PTC-associated molecular markers, including BRAF, RET -PTC, KRAS, NRAS, HRAS, PIK3CA, and their variants. Academic medical center. Three hundred eighty-nine patients with PTC. Molecular mutations in tumors with and without LNM. Of 389 identified cases, 209 fit the inclusion criteria, with 158 classified as node positive (N1) and 51 as node negative (N0). The follicular variant histological type was present in 7 of 158 N1 tumors (4.4%) and 24 of 51 N0 tumors (47.1%) and thus was strongly associated with lack of central neck metastasis in this study (odds ratio, 0.05; 95% CI, 0.02-0.14). Predictive factors for central LNM included extracapsular extension, angiolymphatic invasion, and higher T stage (T3 and T4). The BRAF mutation was more prevalent in the classic PTC histological type than the follicular variant. None of the molecular marker mutations that were analyzed in this study, including the BRAF mutation, predicted LNM in classic PTC. Positive risk factors for central LNM include male sex, extracapsular extension, angiolymphatic invasion, and advanced T stage. The follicular variant histological type has a significantly lower incidence of central neck metastasis. In contrast to recent studies, the BRAF mutation was not significantly associated with central neck LNM from PTC when using a strict definition of a central neck dissection.