Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells.
The effects of triterpene compounds on cadmium toxicity were investigated in HepG2 cells. Ten triterpene compounds were examined, namely, betulin, soyasapogenol A, soyasapogenol B, ursolic acid, uvaol, oleanolic acid, friedelin, glycyrrhizin, 18alpha-glycyrrhetinic acid, and 18beta-glycyrrhetinic acid, and betulin, soyasapogenol A, and uvaol were found to reduce the toxicity of CdCl(2). In particular, betulin almost completely abolished the cytotoxicity of CdCl(2) at concentrations as low as 0. 1 microg/ml. The effects of betulin were particularly apparent when added to the culture medium before the addition of CdCl(2). Moreover, when HepG2 cells were incubated with betulin and then incubated in fresh betulin-free medium before the addition of CdCl(2), the toxic effects of cadmium were reduced. Betulin had no significant effect on the intracellular accumulation of cadmium, nor did it bind to cadmium, at least not in a test tube. When HepG2 cells were treated first with cycloheximide or actinomycin D, the subsequent protective effect of betulin against cadmium toxicity was significantly reduced, suggesting that betulin might protect cells against cadmium toxicity by inducing the synthesis of a certain protein or proteins. The synthesis of metallothionein, a protein that is known to reduce the toxicity of heavy metals, was not induced by betulin. However, using the differential display method, we confirmed that betulin promoted the expression of several genes. Our findings suggest that betulin might reduce cadmium toxicity by promoting the synthesis of certain proteins that protect cells against the toxic effects of cadmium.


Pelvic displacement osteotomy for chronic hip dislocation in myelodysplasia.
Twelve children with lumbar-level myelodysplasia (average age, eight and three-quarter years) underwent twenty-one pelvic displacement osteotomies for subluxated or dislocated hips. Nineteen of the twenty-one hips remained reduced on three-year follow-up. Gains in gait pattern, ease of bracing, and reduced pelvic obliquity were noted. Active function about the hips was not improved, nor was there a decrease in the amount of bracing needed following the osteotomy. Pelvic displacement osteotomy can be utilized in selected cases as part of the over-all management of chronic hip dislocation in myelodysplasia.


Can the urine dipstick test reduce the need for microscopy for assessment of systemic lupus erythematosus disease activity?
Urine microscopic examination is an important component of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). We investigated whether the urine dipstick test can reduce the need for microscopy for the assessment of SLEDAI. We studied 269 urine samples from 259 SLE patients with Albustix and Hemastix reagent strips. The results were compared to concomitant microscopic examination of urinary sediment. When trace red blood cell was defined as the cutoff, the sensitivity, specificity, and negative predictive value (NPV) of the Hemastix urine test were 0.98, 0.53, and 0.99, respectively, for hematuria; 0.82, 0.47, and 0.90, respectively, for the presence of pyuria; and 0.91, 0.44, and 0.98, respectively, for the presence of casts by microscopic examination. When proteinuria of 1+ was defined as the cutoff, the sensitivity, specificity, and NPV of the Albustix test were 1.00, 0.46, and 0.99, respectively, for urinary casts; and 0.82, 0.49, and 0.90, respectively, for the presence of pyuria. When both Albustix and Hemastix were applied as screening test, urine microscopy could be reduced by 27%; however, 8% of cases with normal Albustix and Hemastix tests had at least one abnormality on urine microscopy examination. In patients with SLE, a combination of Albustix and Hemastix urine tests showed reasonable sensitivity to detect abnormalities in urine sediment. Based on these results, routine urine microscopy can be limited to SLE patients with abnormal Albustix or Hemastix tests. Rarer causes of abnormal renal function in lupus, such as tubulointerstitial nephritis or drug induced interstitial nephritis, would be manifested by pyuria and therefore would not necessarily be detected by changes in the blood and protein detectors on the urine dipstick.


Age-related changes in the ease of dynamical transitions in human brain activity.
Executive functions, a set of cognitive processes that enable flexible behavioral control, are known to decay with aging. Because such complex mental functions are considered to rely on the dynamic coordination of functionally different neural systems, the age-related decline in executive functions should be underpinned by alteration of large-scale neural dynamics. However, the effects of age on brain dynamics have not been firmly formulated. Here, we investigate such age-related changes in brain dynamics by applying "energy landscape analysis" to publicly available functional magnetic resonance imaging data from healthy younger and older human adults. We quantified the ease of dynamical transitions between different major patterns of brain activity, and estimated it for the default mode network (DMN) and the cingulo-opercular network (CON) separately. We found that the two age groups shared qualitatively the same trajectories of brain dynamics in both the DMN and CON. However, in both of networks, the ease of transitions was significantly smaller in the older than the younger group. Moreover, the ease of transitions was associated with the performance in executive function tasks in a doubly dissociated manner: for the younger adults, the ability of executive functions was mainly correlated with the ease of transitions in the CON, whereas that for the older adults was specifically associated with the ease of transitions in the DMN. These results provide direct biological evidence for age-related changes in macroscopic brain dynamics and suggest that such neural dynamics play key roles when individuals carry out cognitively demanding tasks.


Phase and amplitude, two sides of functional connectivity.
The dynamics of the human brain can be captured by estimating time-resolved functional network connectivity (trFNC). The most used method for estimating trFNC is sliding window Pearson correlation (SWPC). Methods based on instantaneous phase synchrony, which uses phase information for estimating trFNC are being increasingly used. These two approaches are similar under specific assumptions. Prior works have focused on which of these approaches is the best. Some works argue that SWPC can capture amplitude information and therefore we believe that instantaneous phase synchrony methods and SWPC capture different aspects of connectivity since phase synchrony methods work with the phase of the signal. Here we show that these two approaches result in different time-resolved information and therefore should be viewed as complimentary views of connectivity.


Noninvasive prenatal testing for early sex identification: a few benefits and many concerns.
A new technology, noninvasive prenatal testing (NIPT), can identify fetal sex early in pregnancy, five weeks after conception, with a high degree of accuracy through analysis of maternal blood plasma. This article considers the possibility that NIPT will encourage greater sex selection in developed countries and discusses the implications. Sex selection raises serious social and ethical issues unless it is done for medical reasons. The article also assesses options to discourage sex-selective abortions, including the effectiveness of potential legal measures.


Massive ear keloids: Natural history, evaluation of risk factors and recommendation for preventive measures - A retrospective case series.
Keloid disorder (KD) is an inherited wound healing ailment, frequently seen among Africans /African Americans and Asians. Genetics of this disorder continues to be obscure and poorly understood. Clinical manifestation of KD is quite variable and very diverse, spanning from individuals with one or very few small keloidal lesions, to those with numerous and very large lesions covering large portion of their skin. Ears are common locations for development of keloids. Ear piercing is by far the leading triggering factor for ear keloid formation in genetically predisposed individuals. Although there are numerous publications about ear and earlobe keloids, there is a void in medical literature about massive ear keloids. This paper focuses on the natural history of massive ear keloids and risk factors that lead to formation of these life-changing and debilitating tumors and recommendations for prevention.


Electrophile Scanning Reveals Reactivity Hotspots for the Design of Covalent Peptide Binders.
Protein-protein interactions (PPIs) are intriguing targets in drug discovery and development. Peptides are well suited to target PPIs, which typically present with large surface areas lacking distinct features and deep binding pockets. To improve binding interactions with these topologies and advance the development of PPI-focused therapeutics, potential ligands can be equipped with electrophilic groups to enable binding through covalent mechanisms of action. We report a strategy termed electrophile scanning to identify reactivity hotspots in a known peptide ligand and demonstrate its application in a model PPI. Cysteine mutants of a known ligand are used to install protein-reactive modifiers via a palladium oxidative addition complex (Pd-OAC). Reactivity hotspots are revealed by cross-linking reactions with the target protein under physiological conditions. In a model PPI with the 9-mer peptide antigen VL9 and major histocompatibility complex (MHC) class I protein HLA-E, we identify two reactivity hotspots that afford up to 87% conversion to the protein-peptide conjugate within 4 h. The reactions are specific to the target protein in vitro and dependent on the peptide sequence. Moreover, the cross-linked peptide successfully inhibits molecular recognition of HLA-E by CD94-NKG2A possibly due to structural changes enacted at the PPI interface. The results illustrate the potential application of electrophile scanning as a tool for rapid discovery and development of covalent peptide binders.


Complete amino acid sequence and in vitro expression of rat NF-M, the middle molecular weight neurofilament protein.
A lambda gtII expression library was prepared from rat brain and screened with a polyclonal antiserum, which recognizes both NF-H and NF-M. An NF-M cDNA clone (pNF-M3C = 1.6 kb) was isolated and characterized. The fusion protein of NF-M3C, when used as an affinity matrix for the anti-neurofilament serum, isolated a subpopulation of antibodies specific for NF-M. Northern analysis demonstrates a single band of approximately 3000 nt and a constant message level for NF-M during postnatal development from postnatal day 0 (PO) to adulthood. Using pNF-M3C as a probe, a second cDNA clone was isolated from a lambda gtII rat brain expression library (pNF-M2D = 2.7 kb). The 2 clones were sequenced and pNF-M2D was found to encode the entire rat NF-M protein. The calculated molecular weight is 95,600, which is only 65% of the molecular weight determined by SDS-PAGE. The amino acid sequence of rat NF-M shows the conserved rod segment present in all intermediate filament proteins. The molecule also contains an unusual C-terminal extension with stretches of glutamic acid, which could contribute to the anomalous migration of this protein on SDS-PAGE and the fact that NF-M does not readily assemble into filaments. The pNF-M2D clone was transcribed and translated in vitro utilizing a rabbit reticulocyte lysate system. The resulting radiolabeled translation products were unexpectedly shown to comigrate with purified rat NF-M on 1- and 2-dimensional gels, even though the translated protein is not phosphorylated.


Oil and gas projects in the Western Amazon: threats to wilderness, biodiversity, and indigenous peoples.
The western Amazon is the most biologically rich part of the Amazon basin and is home to a great diversity of indigenous ethnic groups, including some of the world's last uncontacted peoples living in voluntary isolation. Unlike the eastern Brazilian Amazon, it is still a largely intact ecosystem. Underlying this landscape are large reserves of oil and gas, many yet untapped. The growing global demand is leading to unprecedented exploration and development in the region. We synthesized information from government sources to quantify the status of oil development in the western Amazon. National governments delimit specific geographic areas or "blocks" that are zoned for hydrocarbon activities, which they may lease to state and multinational energy companies for exploration and production. About 180 oil and gas blocks now cover approximately 688,000 km(2) of the western Amazon. These blocks overlap the most species-rich part of the Amazon. We also found that many of the blocks overlap indigenous territories, both titled lands and areas utilized by peoples in voluntary isolation. In Ecuador and Peru, oil and gas blocks now cover more than two-thirds of the Amazon. In Bolivia and western Brazil, major exploration activities are set to increase rapidly. Without improved policies, the increasing scope and magnitude of planned extraction means that environmental and social impacts are likely to intensify. We review the most pressing oil- and gas-related conservation policy issues confronting the region. These include the need for regional Strategic Environmental Impact Assessments and the adoption of roadless extraction techniques. We also consider the conflicts where the blocks overlap indigenous peoples' territories.


Molecular cloning of partial cDNA copies of two distinct mouse IFN-beta mRNAs.
Two cDNA libraries were constructed, using respectively the 12S and the 16S sucrose gradient fractions of polysomal poly (A)+ RNA from mouse C243 cells induced with Newcastle disease virus. Screening of a part of both libraries by mRNA selection hybridization assays revealed the presence of two plasmids hybridizing to an mRNA, whose translation product was characterized as mouse IFN-beta. Blot analysis of RNA indicated that mRNA hybridizing to the DNA from both plasmids could be detected in induced but not in uninduced C243 cells. The two cDNA inserts did not cross hybridize and had distinct restriction maps. Sequencing revealed that both inserts represented the end of the coding region and the entire 3' non coding region of two district mRNAs. Although different, the putative 39 AA and 65 AA carboxy termini of both Mu IFN-beta s display some homology to human IFN-beta 1. Thus there are at least two different murine IFN-beta genes.


Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia.
1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary hyperalgesia in the normal surrounding skin. An intradermal injection of capsaicin in humans causes intense pain and hyperalgesia to heat and to mechanical stimuli in the surrounding skin. Psychophysical studies in humans supported the conclusions that the hyperalgesia was predominantly the secondary type and depended on one set of neurons sensitizing another ("neurogenic hyperalgesia") and that the latter set of neurons is located in the central and not the peripheral nervous system. To further test this hypothesis and to search for peripheral neural mechanisms contributing to the pain and neurogenic hyperalgesia from a local injury, we performed neurophysiological experiments in the monkey (Macaca fascicularis) and recorded the responses of cutaneous primary afferent fibers to an intradermal injection of capsaicin and to mechanical and heat stimuli delivered before and after the injection. 2. Most C- and A-fiber mechanoheat-sensitive nociceptive afferent fibers (CMHs and AMHs, respectively) responded too weakly or transiently to capsaicin to account quantitatively for the magnitude of capsaicin pain. Of the known primary afferents tested with capsaicin injections, only the responses of heat-selective nociceptors could potentially account for the pain measured psychophysically in the human. In addition, a novel type of primary afferent--tentatively termed "chemonociceptive"--may have contributed as well. 3. Nociceptive fibers did not become sensitized to either mechanical or heat stimulation after an injection of capsaicin either outside, adjacent to, or inside the receptive field (RF); any changes that occurred could not explain the hyperalgesia to mechanical or heat stimuli observed in humans. 4. The depressed responsiveness ("desensitization") of both myelinated and unmyelinated nociceptive fibers in the monkey to heat and/or mechanical stimulation of the injection site after capsaicin was injected inside their RFs correlated with the analgesia observed at the capsaicin injection site in the human. 5. Capsaicin, topically applied to the RF in a vehicle of dimethyl sulfoxide or alcohol, excited CMHs and AMHs and enhanced the responses of some of these fibers to heat and/or to stroking the skin. In some cases, similar results were produced by the vehicle alone. However, capsaicin and not the vehicle lowered the thresholds of some CMHs to heat. Thus the sensitization of CMHs contributes to the primary hyperalgesia known to occur within the area of skin directly exposed to topically applied capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)


The effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease.
To assess the effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease (COPD). A few recent studies have shown that unsupervised home-based pulmonary rehabilitation can improve the clinical outcome of patients with COPD. More studies are needed to prove its benefits. This study used a quasi-experimental design. Seventy-two admitted COPD patients were assigned to experimental group or control group through purposeful sampling. Data were collected from March 2016 to November 2017 in the Thoracic Intensive Care Unit of a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale and the Clinical COPD Questionnaire were measured before education and at the first, second and third months after discharge. The Medical Research Council dyspnea scale and COPD Self-Efficacy Scale results in the experimental group were significantly improved compared with the control group in the third month after discharge. The Clinical COPD Questionnaire score continued to improve in both groups in the third month after discharge, and there was no difference between the two groups. A short-term unsupervised home-based pulmonary rehabilitation with self- management program had significant benefits for patients with COPD. The long-term effects need to be confirmed.


Brain-derived neurotrophic factor-tropomyosin-related kinase B signaling contributes to activity-dependent changes in synaptic proteins.
The ability of synapses to undergo changes in structure and function in response to alterations of neuronal activity is an essential property of neural circuits. One way that this is achieved is through global changes in the molecular composition of the synapse; however, it is not clear how these changes are coupled to the dynamics of neuronal activity. Here we found that, in cultured rat cortical neurons, bidirectional changes of neuronal activity led to corresponding alterations in the expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor tropomyosin-related kinase B (TrkB), as well as in the level of synaptic proteins. Exogenous BDNF reversed changes in synaptic proteins induced by chronic activity blockade, while inhibiting Trk kinase activity or depleting endogenous BDNF abolished the concentration changes induced by chronic activity elevation. Both tetrodotoxin and bicuculline had significant, but opposite, effects on synaptic protein ubiquitination in a time-dependent manner. Furthermore, exogenous BDNF was sufficient to increase ubiquitination of synaptic proteins, whereas scavenging endogenous BDNF or inhibiting Trk kinase activity prevented the ubiquitination of synaptic proteins induced by chronic elevation of neuronal activity. Inhibiting the proteasome or blocking protein polyubiquitination mimicked the effect of tetrodotoxin on the levels of synaptic proteins and canceled the effects of BDNF. Our study indicates that BDNF-TrkB signaling acts upstream of the ubiquitin proteasome system, linking neuronal activity to protein turnover at the synapse.


Statistical Significance of Geographic Heterogeneity Measures In Spatial Epidemiologic Studies.
Assessing geographic variations in health events is one of the major tasks in spatial epidemiologic studies. Geographic variation in a health event can be estimated using the neighborhood-level variance that is derived from a generalized mixed linear model or a Bayesian spatial hierarchical model. Two novel heterogeneity measures, including median odds ratio and interquartile odds ratio, have been developed to quantify the magnitude of geographic variations and facilitate the data interpretation. However, the statistical significance of geographic heterogeneity measures was inaccurately estimated in previous epidemiologic studies that reported two-sided 95% confidence intervals based on standard error of the variance or 95% credible intervals with a range from 2.5th to 97.5th percentiles of the Bayesian posterior distribution. Given the mathematical algorithms of heterogeneity measures, the statistical significance of geographic variation should be evaluated using a one-tailed P value. Therefore, previous studies using two-tailed 95% confidence intervals based on a standard error of the variance may have underestimated the geographic variation in events of their interest and those using 95% Bayesian credible intervals may need to re-evaluate the geographic variation of their study outcomes.


PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise.
Ingesting protein and carbohydrate together during aerobic exercise suppresses the expression of specific skeletal muscle microRNA and promotes muscle hypertrophy. Determining whether there are independent effects of carbohydrate and protein on microRNA will allow for a clearer understanding of the mechanistic role microRNA serve in regulating skeletal muscle protein synthetic and proteolytic responses to nutrition and exercise. This study determined skeletal muscle microRNA responses to aerobic exercise with or without carbohydrate, and recovery whey protein (WP). Seventeen males were randomized to consume carbohydrate (CHO; 145 g; n = 9) or non-nutritive control (CON; n = 8) beverages during exercise. Muscle was collected before (BASE) and after 80 min of steady-state exercise (1.7 ± 0.3 V̇O2 L·min-1 ) followed by a 2-mile time trial (17.9 ± 3.5 min; POST), and 3-h into recovery after consuming WP (25 g; REC). RT-qPCR was used to determine microRNA and mRNA expression. Bioinformatics analysis was conducted using the mirPath software. Western blotting was used to assess protein signaling. The expression of six microRNA (miR-19b-3p, miR-99a-5p, miR-100-5p, miR-222-3p, miR-324-3p, and miR-486-5p) were higher (P < 0.05) in CHO compared to CON, all of which target the PI3K-AKT, ubiquitin proteasome, FOXO, and mTORC1 pathways. p-AKTThr473 and p-FOXO1Thr24 were higher (P < 0.05) in POST CHO compared to CON. The expression of PTEN was lower (P < 0.05) in REC CHO than CON, while MURF1 was lower (P < 0.05) POST CHO than CON. These findings suggest the mechanism by which microRNA facilitate skeletal muscle adaptations in response to exercise with carbohydrate and protein feeding is by inhibiting markers of proteolysis.


Phenotype of Vascular Smooth Muscle Cells (VSMCs) Is Regulated by miR-29b by Targeting Sirtuin 1.
BACKGROUND Phenotypic switch of vascular smooth muscle cells (VSMCs) participates in the etiology of various vascular diseases. It has been proved that microRNAs (miRNAs) serve as crucial regulators of functions of VSMCs. This study aimed to discover how miR-29b regulates the transformation of VSMCs phenotypes in mice. MATERIAL AND METHODS Primary VSMCs of aorta in mice were cultured in DMEM medium. A series of experiments involving transfection of oligonucleotides in cultured VSMCs, quantitative reverse transcription PCR (qRT-PCR), luciferase reporter assay, and Western blotting analysis were performed in this study. RESULTS We found that in VSMCs cultured in presence of stimulator, platelet-derived growth factor-BB (PDGF-BB), miR-29b was upregulated significantly and expressions of VSMC-phenotype-related genes (α-SMA, calponin, and SM-MHC) were regulated by miR-29b. Moreover, through downregulation of sirtuin 1 (SIRT1), miR-29b affects phenotypic transformation of VSMCs. Luciferase report assay identified a significant increase of SIRT1 3'-UTR activity in treatment with miR-29b inhibitor, which, however, was reversed in the presence of miR-29b mimic. Suppression of miR-29b reversed the activation of NF-κB induced by PDGF-BB in VSMCs. CONCLUSIONS We concluded that miR-29b is an important regulator in the PDGF-BB-mediated VSMC phenotypic transition by targeting SIRT1. Interventions aimed at miR-29b may be promising in treating numerous proliferative vascular disorders.


[Sex differences in the penetrance and expressivity of interhemispheric asymmetry].
In 38 anesthetised cat of both sexes, homotopic transcallosal responses (HTR) were studied in somatosensory, visual, auditory and temporal cortex of the brain. High penetration in cases of interhemispheric asymmetry was more specific for males and found mostly in cortical projection areas. For the functional interhemispheric asymmetry of the HTR amplitude-temporal parameters a high degree of expressiveness was characteristic in female cats. Possible reasons of these phenomena are discussed.


[Evaluation of myocardial viability with contrast-enhanced magnetic resonance imaging--comparison of the late enhancement technique with positronemission tomography].
To compare contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET) in the evaluation of myocardial viability. [ (18)F]-FDG-PET, [ (201)Tl]-TlCl-SPECT and contrast-enhanced MRI were performed in 29 patients with proven coronary artery disease and impaired left ventricular function to assess myocardial viability. MRI scans were done on a 1.5 T scanner (Magnetom Sonata, Siemens, Germany). After the steady-state free precession cine study, 0.2 mmol/kg BW of Gd-DPTA (Magnevist(R), Schering, Germany) were administered i. v. For the detection of "late enhancement" (LE) indicating scar, left ventricular long axes and contiguous short axis slices of 8 mm thickness were scanned using an inversion recovery turbo gradient echo sequence (TR 8.0 ms; TE 4.0 ms; TI 180 - 240 ms; FA 20 degrees ). The evaluation of LE and FDG uptake in PET with perfusion defect in SPECT was done using an 8 (basal, mid) and 4 (apical) segment model in all short axes to cover the entire ventricle. The transmural extent of LE was assessed using a 4-point score system. Comparison between the two modalities was performed on a segmental basis. A total of 1753 segments were assessed. In MRI, 40 % of the segments showed myocardial scar, whereas PET revealed impaired uptake in 25 %. MRI obtained a very low interobserver variability in detecting myocardial scar (kappa 0.92). Using PET as the standard of reference in the segmental comparison, contrast-enhanced MRI yielded a sensitivity of 84 % and a specificity of 76 % for the detection of scar. 18 % of all segments showed LE but normal FDG uptake, 83 % of them referred to subendocardial scars. There is close agreement between contrast-enhanced MRI and PET in detecting transmural myocardial scars. Superior spatial resolution enables MRI to detect and quantify even subendocardial scar. Therefore, larger studies using functional recovery after revascularisation as an endpoint have to prove whether MRI might replace PET as the standard of reference in the assessment of myocardial viability.


Structural Microangiopathies in Skeletal Muscle Related to Systemic Vascular Pathologies in Humans.
It is unclear how microangiopathic changes in skeletal muscle vary among systemic vascular pathologies. We therefore analyzed the capillary fine structure in skeletal muscle from patients with arterial hypertension (HYPT), diabetes mellitus type 2 (T2DM) or intermittent claudication - peripheral arterial disease (IC/PAD). Tablet-based image analysis (TBIA) was carried out to largely re-evaluate 5,000 transmission electron micrographs of capillaries from 126 vastus lateralis biopsies of 75 individuals (HYPT, T2DM or IC/PAD patients as well as healthy individuals before and after endurance exercise training) used in previous morphometric studies, but assessed using stereological counting grids of different sizes. Serial block-face scanning electron microscopy (SBFSEM) of mouse skeletal muscle was used for validation of the particular fine structural events observed in human biopsies. The peri-capillary basement membrane (BM) was 38.5 and 45.5% thicker (P < 0.05) in T2DM and IC/PAD patients than in the other groups. A 17.7-39.6% lower (P < 0.05) index for intraluminal endothelial cell (EC) surface enlargement by projections was exclusively found in T2DM patients by TBIA morphometry. The proportion of capillaries with disrupted BM between pericytes (PC) and EC was higher (P < 0.05) in HYPT (33.2%) and T2DM (38.7%) patients than in the control group. Empty EC-sockets were more frequent (P < 0.05) in the three patient groups (20.6% in HYPT, 27.1% in T2DM, 30.0% in IC/PAD) than in the healthy individuals. SBFSEM confirmed that EC-sockets may exhibit close proximity to the capillary lumen. Our comparative morphometric analysis demonstrated that structural arrangement of skeletal muscle capillaries is more affected in T2DM than in HYPT or IC/PAD, although some similar elements of remodeling were found. The increased frequency of empty EC-sockets in the three patient groups indicates that the PC-EC interaction is commonly disturbed in these systemic vascular pathologies.


Peabody Picture Vocabulary Test: Proxy for Verbal IQ in Genetic Studies of Autism Spectrum Disorder.
This study assessed the utility of a brief assessment (the Peabody Picture Vocabulary Test-4th Edition; PPVT4) as a proxy for verbal IQ (VIQ) in large-scale studies of autism spectrum disorder (ASD). In a sample of 2,420 proband with ASD, PPVT4:IQ correlations were strong. PPVT4 scores were, on average, 5.46 points higher than VIQ; 79% of children had PPVT4 scores within one standard deviation (+/-15) of their VIQ and 90% were similarly classified as having abilities above or below 70 on both measures. Distributions of PPVT4 and VIQ by de novo mutation status were highly similar. These results strongly support the utility of PPVT4 as a proxy for VIQ in large-scale ASD studies, particularly for genetic investigations.


Refractory ceramic fiber: toxicology, epidemiology, and risk analyses--a review.
Refractory ceramic fiber (RCF) is an energy-efficient, high-temperature insulation, used principally in industrial furnaces, heaters, and reactors. Prior to the 1980s, there were few publications dealing with the potential health effects of this material. However, with the advent of higher energy costs and the need for thermally efficient high-temperature insulating materials, production of RCF grew rapidly, as did interest in its potential health effects. This article provides a comprehensive and integrated review of the toxicology (in vitro and in vivo), epidemiology, and risk analysis literature of RCF. Based on the available literature, we conclude that an occupational exposure of 0.5 fibers per cubic centimeter (cm(3)) [8-h time-weighted average (8-h TWA)] results in an occupational health risk no greater than 9.1 x 10(-5).


Role of P-glycoprotein and permeability upon the brain distribution and pharmacodynamics of etamicastat: a comparison with nepicastat.
1. This study explores the impact of permeability and P-glycoprotein (P-gp) efflux, upon brain exposure to etamicastat, a new dopamine-β-hydroxylase (DBH) inhibitor and consequently brain levels of catecholamines. 2. Brain exposure to etamicastat (10 mg/kg), following intravenous administration to mice, was residual and upon oral administration of the same dose no compound was detected, concurring with the absence of effects upon brain catecholamines. The intravenous co-administration of elacridar (1.0 mg/kg), a known P-gp/BCRP dual modulator, significantly increased brain etamicastat exposure, but the levels attained were very low when compared to those of nepicastat, a centrally active DBH inhibitor. 3. In vitro permeability studies from apical-to-basal direction conducted in Caco-2 cells and MDCK-II cells showed that etamicastat apparent permeability was 1.2 × 10(-5) and 1.1 × 10(-6 )cm/s, respectively, 5- and 50-fold lower as compared to nepicastat. The secretory efflux ratio in MDCK-II cells overexpressing human P-gp showed an efflux ratio greater than 2, for both compounds, which was significantly decreased by elacridar. Despite its lower bioavailability and higher clearance, as compared to nepicastat, etamicastat showed preferential distribution to peripheral tissues and high plasma free fraction (15.5%), which may explain its effects upon peripheral DBH and catecholamine levels. 4. Though P-gp-mediated efflux may contribute to the limited brain penetration of etamicastat, the low permeability along with the pharmacokinetic properties of etamicastat may be perceived as the main contributors for its peripheral selectivity, which is advantageous for a cardiovascular drug candidate.


Characterization of ketolactia in dairy cows during early lactation.
Fourier transform infrared spectroscopy (FTIR) allows for the determination of milk acetone (mACE) and β-hydroxybutyrate (mBHB) concentrations, providing a potential herd monitoring tool for hyperketolactia, defined as elevated milk ketone bodies. The study aim was to characterize mACE and mBHB concentration dynamics during early lactation in Polish Holstein-Friesian cows. Milk samples (n = 3,867,390) were collected within 6 to 60 days in milk (DIM) over a 4-yr period (April 1, 2013 to March 31, 2017) from approximately 21,300 dairy herds (average 38.7 cows/herd). Fixed effects of parity, DIM, and their interaction on mACE and mBHB concentrations were determined using a mixed model with a herd-year-season fixed effect and random cow effect. Published hyperketolactic mACE (≥0.15 mmol/L) and mBHB (≥0.10 mmol/L) threshold concentrations were used to classify study milk samples into ketolactia groups of normal (mACE <0.15 mmol/L and mBHB <0.10 mmol/L) and hyperketolactic (HYKL; either mACE ≥0.15 mmol/L or mBHB ≥0.10 mmol/L). Additionally, HYKL samples were categorized into subpopulations as having elevated mBHB and mACE (HYKLACEBHB, mACE ≥0.15 mmol/L and mBHB ≥0.10 mmol/L), only elevated mBHB (HYKLBHB; mACE <0.15 mmol/L and mBHB ≥0.10 mmol/L), or only elevated mACE (HYKLACE; mACE ≥0.15 mmol/L and mBHB <0.10 mmol/L). Effects of parity, DIM, ketolactia group or subpopulation, and their interactions on mACE and mBHB concentrations were also determined using the mixed model that included ketolactia group or subpopulation as an independent variable. Across all data, mACE and mBHB concentrations were influenced by effects of parity, DIM, and their interaction as well as parity, DIM, ketolactia group or subpopulation, and their interactions. For all samples, mACE and mBHB concentrations decreased with increasing DIM, with mACE concentration declining more rapidly compared with mBHB. In the data set, 68% and 32% of all samples were defined as normal or HYKL, respectively. Among HYKL samples, mACE was elevated soon after calving and declined over time. In contrast, mBHB started lower after calving and increased reaching peak concentrations around 30 DIM, and then decreased. Within HYKL samples, 50.8, 41.3, and 7.9% were categorized as HYKLACEBHB, HYKLBHB, and HYKLACE respectively. Between 6 and 21 DIM, 11.3% of HYKL were classified as HYKLACE. Primiparous cows had greater (14.8%) HYKLACE samples in this time period. In conclusion, this study has characterized mACE and mBHB concentrations during early lactation and determined effects of parity, DIM, and their interaction. Using published criteria interpreting mACE and mBHB concentrations, it was intriguing to identify a unique population of samples having elevated mACE without mBHB in early lactation, especially in primiparous cows. Further research is needed to determine if this sample population represents an unhealthy metabolic status that adversely affects cow health and performance.


The characterization of the specific binding of [3H]-N-acetylaspartylglutamate to rat brain membranes.
[3H]-N-Acetylaspartylglutamate (NAAG) bound saturably and reversibly to crude synaptosomal rat brain membranes. Optimal binding occurred in Tris-HCl buffer, pH 7.2, at 37 degrees C using previously frozen, preincubated membranes. Saturation experiments revealed an apparent KD of 383 +/- 33 nM and a Bmax of 31 +/- 2 pmol/mg of protein. [3H]NAAG specific binding was displaceable by serine-o-sulfate, quisqualate, ibotenate, and glutamate with K1's in the nanomolar range, whereas the amino-phosphono analogues displaced [3H] NAAG in the micromolar range (APB greater than APV greater than APH). No specific binding was found in peripheral tissues. Within the central nervous system, the thalamus exhibited the greatest amount of binding, whereas binding was lowest in cortex. Calcium ions enhanced the specific binding, whereas sodium ions caused a concentration-dependent inhibition. These results suggest that [3H]NAAG labels an acidic amino acid receptor site designated "A-4," which recognizes the antagonist, 2-amino-4-phosphonobutyric acid, and that this receptor may mediate the neurophysiologic effects of endogenous NAAG.


Predicting embryonic patterning using mutual entropy fitness and in silico evolution.
During vertebrate embryogenesis, the expression of Hox genes that define anterior-posterior identity follows general rules: temporal colinearity and posterior prevalence. A mathematical measure for the quality or fitness of the embryonic pattern produced by a gene regulatory network is derived. Using this measure and in silico evolution we derive gene interaction networks for anterior-posterior (AP) patterning under two developmental paradigms. For patterning during growth (paradigm I), which is appropriate for vertebrates and short germ-band insects, the algorithm creates gene expression patterns reminiscent of Hox gene expression. The networks operate through a timer gene, the level of which measures developmental progression (a candidate is the widely conserved posterior morphogen Caudal). The timer gene provides a simple mechanism to coordinate patterning with growth rate. The timer, when expressed as a static spatial gradient, functions as a classical morphogen (paradigm II), providing a natural way to derive the AP patterning, as seen in long germ-band insects that express their Hox genes simultaneously, from the ancestral short germ-band system. Although the biochemistry of Hox regulation in higher vertebrates is complex, the actual spatiotemporal expression phenotype is not, and simple activation and repression by Hill functions suffices in our model. In silico evolution provides a quantitative demonstration that continuous positive selection can generate complex phenotypes from simple components by incremental evolution, as Darwin proposed.


[Jejunal atresia: contribution to prenatal ultrasonic diagnosis].
In a case report we present the prenatal diagnosis of an intestinal obstruction. The problem of locating exactly the area of obstruction is discussed. Prenatal diagnosis permits optimal management after birth and can lead to a better prognosis.


Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration.
The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge and model-independent SEDFIT-MSTAR analysis across a range of loading concentrations. The change in the weight average molar mass M w with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses M w(r) versus local concentration c(r) for different loading concentrations demonstrated a completely reversible equilibrium process. At the clinical infusion concentration of 5 mg.mL-1 all glycopeptide is dimerized whilst at 19 µg.mL-1 (a clinical target trough serum concentration), vancomycin was mainly monomeric (<20% dimerized). Analysis of the variation of M w with loading concentration revealed dissociation constants in the range 25-75 μM, commensurate with a relatively weak association. The effect of two-fold vancomycin (19 µg.mL-1) appears to have no effect on the monomeric enterococcal VanS kinase involved in glycopeptide resistance regulation. Therefore, the 30% increase in sedimentation coefficient of VanS on adding vancomycin observed previously is more likely to be due to a ligand-induced conformational change of VanS to a more compact form rather than a ligand-induced dimerization.


Brazilian dental students' intentions and motivations towards their professional career.
Investigating career motivations and intentions of dental students provides a better understanding of their role in society and contributes to the debate on dental education and practices. This study describes the profile, career choice motivations, and career intentions of Brazilian dental students and evaluates factors related to these choices. A cross-sectional study was carried out among dental students from three Brazilian public universities (N=915), with a response rate of 83.7 percent. Students (N=766) responded to a self-administered questionnaire about sociodemographic factors, reasons for choosing dentistry as a career, and future career intentions. Job conception was found to be the main reason for choosing dentistry as a profession. Most students intended to become specialists and work in both the public and private sectors simultaneously. Female students (OR 2.23, 95 percent CI=1.62-3.08), low-income students (OR 1.86, 95 percent CI=1.10-3.13), and students beginning their program (OR 1.87, 95 percent CI=1.22-2.85) were more likely to work in the public and private sectors simultaneously than other types of students. This study suggests that choice of career and career plans are influenced by factors related to the students' characteristics and their conception of the profession. The opportunity to combine private and public dental practice may be viewed as a way to achieve income and job security.


Phosphate transport in kidneys: effect of transmembrane electrical potential.
The effect of a transmembrane electrical potential on phosphate transport by kidney brush-border membrane vesicles was studied. The initial rate of Na(+)-dependent phosphate influx was twice as high as that of efflux. Generation of a negative transmembrane potential had a stimulatory effect on the rate of influx but had no effect on efflux. The Na+ saturation curve for phosphate influx was sigmoidal, and the Hill coefficients were similar, in the presence and absence of a transmembrane potential. The membrane potential increased both the affinity for phosphate and the maximal velocity (Vmax) of the transporter. In the absence of a Na+ gradient, the stimulation by the potential was 1.78-fold. When a proton gradient (in greater than out) was the driving force, the electrical potential stimulated phosphate transport 1.71-fold. Internal Na+ (trans) inhibited phosphate influx whether a potential was present or not. Internal phosphate (trans) stimulated phosphate influx in the absence of a potential but not in its presence. These results indicate that the electrical potential is an important driving force for the Na(+)-phosphate carrier and that the translocation of the carrier is a potential-dependent step.


A Comparison of Independent Event-Related Desynchronization Responses in Motor-Related Brain Areas to Movement Execution, Movement Imagery, and Movement Observation.
Electroencephalographic (EEG) event-related desynchronization (ERD) induced by movement imagery or by observing biological movements performed by someone else has recently been used extensively for brain-computer interface-based applications, such as applications used in stroke rehabilitation training and motor skill learning. However, the ERD responses induced by the movement imagery and observation might not be as reliable as the ERD responses induced by movement execution. Given that studies on the reliability of the EEG ERD responses induced by these activities are still lacking, here we conducted an EEG experiment with movement imagery, movement observation, and movement execution, performed multiple times each in a pseudorandomized order in the same experimental runs. Then, independent component analysis (ICA) was applied to the EEG data to find the common motor-related EEG source activity shared by the three motor tasks. Finally, conditional EEG ERD responses associated with the three movement conditions were computed and compared. Among the three motor conditions, the EEG ERD responses induced by motor execution revealed the alpha power suppression with highest strengths and longest durations. The ERD responses of the movement imagery and movement observation only partially resembled the ERD pattern of the movement execution condition, with slightly better detectability for the ERD responses associated with the movement imagery and faster ERD responses for movement observation. This may indicate different levels of involvement in the same motor-related brain circuits during different movement conditions. In addition, because the resulting conditional EEG ERD responses from the ICA preprocessing came with minimal contamination from the non-related and/or artifactual noisy components, this result can play a role of the reference for devising a brain-computer interface using the EEG ERD features of movement imagery or observation.


ACR Appropriateness Criteria® Radiologic Management of Lower Gastrointestinal Tract Bleeding: 2021 Update.
Diverticulosis remains the commonest cause for acute lower gastrointestinal tract bleeding (GIB). Conservative management is initially sufficient for most patients, followed by elective diagnostic tests. However, if acute lower GIB persists, it can be investigated with colonoscopy, CT angiography (CTA), or red blood cell (RBC) scan. Colonoscopy can identify the site and cause of bleeding and provide effective treatment. CTA is a noninvasive diagnostic tool that is better tolerated by patients, can identify actively bleeding site or a potential bleeding lesion in vast majority of patients. RBC scan can identify intermittent bleeding, and with single-photon emission computed tomography, can more accurately localize it to a small segment of bowel. If patients are hemodynamically unstable, CTA and transcatheter arteriography/embolization can be performed. Colonoscopy can also be considered in these patients if rapid bowel preparation is feasible. Transcatheter arteriography has a low rate of major complications; however, targeted transcatheter embolization is only feasible if extravasation is seen, which is more likely in hemodynamically unstable patients. If bleeding site has been previously localized but the intervention by colonoscopy and transcatheter embolization have failed to achieve hemostasis, surgery may be required. Among patients with obscure (nonlocalized) recurrent bleeding, capsule endoscopy and CT enterography can be considered to identify culprit mucosal lesion(s). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Perioperative blood transfusions and delayed wound healing after hip replacement surgery: effects on duration of hospitalization.
Patients who receive allogeneic blood transfusions after orthopedic surgery have a longer duration of hospitalization, and this cannot be explained by a more frequent incidence of infections in transfused patients. To determine whether transfusion of allogeneic blood interferes with wound healing and therefore increases the duration of hospitalization, we performed an observational study in 444 consecutive patients scheduled for elective primary hip surgery. Transfusion, wound, and infection variables were collected at five time points during treatment. Of the 444 consecutive patients studied, 92 received blood transfusions during their perioperative course. Thirty-one percent of transfused patients developed wound-healing disturbances versus 18% of the nontransfused group (P < 0.05); allogeneic blood transfusion was the only significant predictor for development of minor wound-healing disturbances. Duration of hospitalization was prolonged in transfused patients (12.3 versus 9.8 days) and could be predicted by 4 significant variables: requirement for blood transfusion (adds 2.7 +/- 0.5 days), presence of wound-healing disturbances (adds 1.3 +/- 0.5 days), duration of surgery (adds 0.2 +/- 0.1 days/10 min), and patient's age (adds 0.9 +/- 0.2 days/10 yr). These data suggest that allogeneic blood transfusion is associated with an increased incidence of wound-healing disturbances and that prevention of allogeneic blood transfusion may be relevant in limiting the duration of admission after elective orthopedic surgery.


Superior sagittal sinus thrombosis in a patient with systemic lupus erythematosus.
Cerebral venous thrombosis is a rare cause of focal neurological damage in patients with SLE. We describe a patient with SLE who presented with a focal neurological deficit and subsequently developed increased intracranial pressure. A superior sagittal sinus thrombosis was diagnosed by MRI. The association between SLE and superior sagittal sinus thrombosis is discussed. Early diagnosis is essential because treatment leads to a positive clinical outcome.


Atomistic simulations of the structure of highly crosslinked sulfonated poly(styrene-co-divinylbenzene) ion exchange resins.
The microscopic structures of highly crosslinked sulfonated poly(styrene-co-divinylbenzene) resins have been modeled by generating atomistic microstructures using stochastic-like algorithms, which are subsequently relaxed using molecular dynamics. Two different generation algorithms have been tested. The relaxation of the microstructures generated by the first algorithm, which is based on a homogeneous construction of the resin, leads to a significant overestimation of the experimental density as well as to an unsatisfactory description of the porosity. In contrast, the generation approach that combines algorithms for the heterogeneous growing and branching of the chains enables the formation of crosslinks with different topologies. In particular, the intrinsic heterogeneity observed in these resins is efficiently reproduced when the topological loops, which are defined by two or more crosslinks closing a cycle, are present in their microscopic description. Thus, the apparent density, porosity and pore volume estimated using microstructures with these topological loops, called super-crosslinks, are in very good agreement with the experimental results. Although the backbone dihedral angle distribution of the generated and relaxed models is not influenced by the topology, the number and type of crosslinks affect the medium- and long-range atomic disposition of the backbone atoms and the distribution of sulfonic groups. An analysis of the distribution of the local density indicates that super-crosslinks are responsible for the heterogeneous homogenization observed during the MD relaxation. Finally the π-π stacking interactions have been analyzed. Results indicate that those in which the two rings adopt a T-shaped disposition are considerably more abundant as compared to those with the co-facially oriented rings, independently of the resin topology.


Perioperative guidelines for elective surgery in the human immunodeficiency virus-positive patient.
Human immunodeficiency virus (HIV)-positive patients with changes in body morphology can be challenging for the plastic surgeon. Uncertainty about the advisability of elective procedures for these patients and fears of infection transmission may cause trepidation. Plastic surgeons are likely to encounter these patients in increasing numbers. The authors provide an overview of HIV lipodystrophy and treatment options. Clinical parameters are established that must be met before elective procedures on HIV-positive patients. In addition, ethical and legal considerations are discussed. A literature review was conducted to identify articles reporting specific, identifiable factors influencing operative risk in HIV-positive patients. Legal and ethical experts were consulted. Specific risk factors influencing operative morbidity include an absolute CD4 count of less than 200 cells/cc3 or viral load greater than 10,000 copies/ml. Patients with CD4 counts greater than 200 cells/cc3 and a low viral load have a risk of postoperative complications similar to that of the general population and should therefore be evaluated on established preoperative parameters (e.g., American Society of Anesthesiologists class, nutrition, and age). Patients with HIV-associated body morphology changes can be safely treated by the plastic surgeon, provided that a thorough preoperative workup is performed. There is minimal risk of disease transmission. There is an ethical and legal obligation to treat these patients if the patient is suitable and the procedure in question falls under the expertise of the consulting surgeon.


An audit of general dental practitioners' referral practice following the distribution of third molar guidelines.
Oral and maxillofacial surgery waiting lists are amongst the longest of any surgical specialty. The majority of patients on these waiting lists have been referred for removal of their third molars (wisdom teeth). With increasing pressure to reduce the size of both out-patient and surgical waiting lists, it is important to ensure that only those patients with a recognised clinical need are referred and accepted for treatment. In April 1998, local general dental practitioners were issued guidelines for the management of patients with impacted third molars. This paper describes an audit that assessed the impact of this intervention. The results suggest that referral guidelines are an effective means of changing general dental practitioners' referral practice and that, used along with other strategies, could be effective in reducing oral and maxillofacial surgery out-patient and surgical waiting lists.


An investigation of contextual factors in the application of multisensory illusions for analgesia in hand osteoarthritis.
Emerging evidence suggests that multisensory illusions can modulate pain and can lead to changes in body perception. The aim of this study was to investigate whether contextual factors could explain the analgesic effects of multisensory body illusions on pain and body perception in people with hand OA (HOA). In a crossover study, 28 individuals with painful HOA viewed their most affected hand in and outside of a real-time mediated reality system, with illusory stretching of the hand and changes in sensory input. The outcome measures were pain ratings, pressure pain thresholds, hand function and the subjective experience of the illusion. Stretching the hand both inside and outside the virtual environment led to a reduction in subjective pain ratings (all P < 0.05). Virtual stretching led to changes in body perception (P < 0.05) with no changes in pressure pain threshold (all P > 0.05). Higher pain at baseline predicted susceptibility to the stretch illusion and mean susceptibility ratings were greatest after the stretch illusion. The current study highlights the importance of the context in which pain occurs and in which potential treatments may be applied. In this case, virtual and physical stretching modulated pain, but not viewing the hand alone. The research opens important implications for future research, including the use of contextual control conditions and the development of visual feedback interventions for a range of similarly visible chronic conditions for which pain, body image disturbances and body dissatisfaction may be apparent.


The effects of paeoniflorin on LPS-induced liver inflammatory reactions.
Paeoniflorin (PF), a monoterpene glucoside, is a primary bioactive component of paeony, the root extract of Paeonia lactiflora. We tested the antioxidant effects of PF and its ability to prevent lipopolysaccharide (LPS)-induced oxidative stress. We intraperitoneally administered PF (2.5, 5, or 10 mg/kg) to rats for 20 days. On day 21, we injected the rats with LPS 4 h before sacrifice and measured serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase as well as the levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase in liver whole-cell homogenates and mitochondrial fractions. LPS treatment increased levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, and malondialdehyde, but PF treatment blocked these increases. LPS treatment also decreased antioxidant levels of superoxide dismutase, catalase, and glutathione peroxidase, but PF blocked these decreases. PF also protected liver tissue, as shown by histopathology. These results suggest that PF can protect against LPS-induced liver inflammation.


Neurological and vascular injury associated with supracondylar humerus fractures and ipsilateral forearm fractures in children.
Approximately 5% of supracondylar humerus fractures in children are associated with an ipsilateral forearm fracture, often referred to as a floating elbow when both injuries are displaced. Historically, these patients have higher complication rates than patients with an isolated supracondylar humerus fracture. The purpose of this study was to review the acute neurologic and vascular injuries in patients with ipsilateral, operative supracondylar humerus and forearm fractures and compare the findings with a cohort of isolated, operative supracondylar humerus fractures. We performed an IRB-approved, retrospective review of all pediatric patients with ipsilateral, operative supracondylar humerus and forearm fractures from a single institution and compared our findings to a cohort of isolated, operative supracondylar humerus fractures. A total of 150 patients with operative supracondylar humerus and ipsilateral forearm fractures were compared with 1228 patients with isolated, operative supracondylar humerus fractures. Twenty-two of the 150 (14.7%) floating elbow patients had documented pretreatment nerve palsies compared with 96/1228 (7.8%) of isolated injury patients (P=0.006). Eighteen of 22 nerve palsies were in patients with forearm fractures that required reduction. The overall incidence of nerve palsy was 18.9% (18/95) when a forearm fracture required reduction compared with only 7.3% (4/55) in a forearm fracture that was not reduced (P=0.05). We did not find a significant difference in the rate of pulseless extremities when comparing the ipsilateral (6/150 4%) and isolated (50/1228 4.1%) injury patients. No compartment syndromes were identified in any patient with an ipsilateral injury. The rate of acute neurologic injury in ipsilateral supracondylar humerus and forearm fractures is almost twice than that found in patients with isolated supracondylar humerus fractures. This rate increases further when the forearm fracture requires a manipulative reduction. The likelihood of a pulseless extremity was not dependent upon the presence of a forearm injury in our study. The presence of an ipsilateral forearm fracture should alert the surgeon to carefully assess the preoperative neurovascular status of patients with supracondylar humerus injuries. Level III.


Effect of n-butanol on Na+, K+-ATPase.
The effect of n-butanol on the activity of Na+, K+-ATPase has been found different at different temperatures. Below the phase-transition temperature, n-butanol has a stimulating effect provided the concentration is not higher than 0.3 M. But if the activity is determined above the phase-transition temperature, n-butanol has an inhibitory effect. The p-nitrophenyl phosphatase activity has been found to be inhibited by n-butanol even at comparatively low temperatures. This is in accord with the finding that the Arrhenius plot for p-nitrophenyl phosphatase did not show any break. It is suggested that at lower temperatures the conformational change involved in the transport of Na+, K+ ions may be the rate-limiting factor in the overall reaction, and n-butanol may be used as a probe for perturbation of the membrane to elucidate the mechanism of Na+, K+-ATPase.


HIV disclosure among HIV positive individuals: a concept analysis.
This paper is a report of an analysis of the concept of HIV disclosure. There is a growing interest among healthcare providers and researchers in HIV disclosure as an effective HIV prevention and early disease management initiative. However, the concept still remains unclear. Conceptual clarity is important for providing an expanded theoretical definition and understanding of attributes of HIV disclosure. This information is useful in constructing better HIV disclosure measures in HIV/AIDS nursing practice and research. A computer search of the following databases was conducted to capture the meaning and processes of HIV disclosure among HIV-positive individuals: PubMed, CINAHL and PSYCINFO. Only English language journals were used. Publication dates of the literature review ranged from 1999 to 2009. The following key words were used: HIV disclosure, self-disclosure, disclosure and serostatus disclosure. The Walker and Avant (2005) concept analysis model (Strategies for Theory Construction in Nursing, Pearson Prentice Hall, River, NJ, 2005) was used to guide the analysis process, which was completed in 2009. The concept analysis revealed that HIV disclosure is a complex process characterized by the following attributes: experiencing an event, communicating something, timing, and contextual environment, protecting someone, relationship status and improving something or being therapeutic. In addition, the process of HIV disclosure varies across time. The proposed HIV disclosure attributes provide nursing scholars and researchers with new directions on how to reframe research questions, develop measurement tools to reflect better the diversity and fluidity of the process of HIV disclosure among HIV-positive individuals. Policy implications include the need to develop approaches that protect individual and public rights.


Identification of PCNA-interacting protein motifs in human DNA polymerase δ.
DNA polymerase δ (Polδ) is a highly processive essential replicative DNA polymerase. In humans, the Polδ holoenzyme consists of p125, p50, p68 and p12 subunits and recently, we showed that the p12 subunit exists as a dimer. Extensive biochemical studies suggest that all the subunits of Polδ interact with the processivity factor proliferating cell nuclear antigen (PCNA) to carry out a pivotal role in genomic DNA replication. While PCNA-interacting protein motif (PIP) motifs in p68, p50 and p12 have been mapped, same in p125, the catalytic subunit of the holoenzyme, remains elusive. Therefore, in the present study by using multiple approaches we have conclusively mapped a non-canonical PIP motif from residues 999VGGLLAFA1008 in p125, which binds to the inter-domain-connecting loop (IDCL) of PCNA with high affinity. Collectively, including previous studies, we conclude that similar to Saccharomyces cerevisiae Polδ, each of the human Polδ subunits possesses motif to interact with PCNA and significantly contributes toward the processive nature of this replicative DNA polymerase.


Apoptosis is mediated by FeHV-1 through the intrinsic pathway and interacts with the autophagic process.
Although FeHV-1 is a primary feline pathogen, little is known about its interactions with host cells. Its relationship with several cellular pathways has recently been described, whereas its interplay with the apoptotic process, unlike other herpesviruses, has not yet been clarified. The aim of this work was to evaluate whether FeHV-1 induces apoptosis in its permissive cells, as well as the pathway involved and the effects of induction and inhibition of apoptosis on viral replication. Monolayers of CRFK cells were infected at different times with different viral doses. A cytofluorimetric approach allowed the quantification of cells in early and late apoptosis. All infections and related controls were also subjected to Western blot analysis to assess the expression of apoptotic markers (caspase 3-8-9, Bcl-2, Bcl-xL, NF-κB). An inhibitor (Z-VAD-FMK) and an inducer (ionomycin) were used to evaluate the role of apoptosis in viral replication. Finally, the expression of autophagy markers during the apoptosis inhibition/induction and the expression of apoptosis markers during autophagy inhibition/induction were evaluated to highlight any crosstalk between the two pathways. FeHV-1 triggered apoptosis in a time- and dose-dependent manner. Caspase 3 cleavage was evident 48 h after infection, indicating the completeness of the process at this stage. While caspase 8 was not involved, caspase 9 cleavage started 24 h post-infection. The expression of other mitochondrial damage markers also changed, suggesting that apoptosis was induced via the intrinsic pathway. NF- κB was up-regulated at 12 h, followed by a gradual decrease in levels up to 72 h. The effects of apoptosis inhibitors and inducers on viral replication and autophagy were also investigated. Inhibition of caspases resulted in an increase in viral glycoprotein expression, higher titers, and enhanced autophagy, whereas induction of apoptosis resulted in a decrease in viral protein expression, lower viral titer, and attenuated autophagy. On the other hand, the induction of autophagy reduced the cleavage of caspase 3. In this study, we established how FeHV-1 induces the apoptotic process, contributing to the understanding of the relationship between FeHV-1 and this pathway.


Lessons Learned From the COVID-19 Pandemic in the United States by Domestic Violence Coalition Leaders.
This U.S. study explores lessons learned about domestic violence service delivery during the COVID-19 pandemic identified by state, territory, and tribal coalition leadership to advance preparedness and guide structural improvements for future disasters. Semi-structured interviews with 25 Coalition leaders identified public health control measures and victim-centered strategies used to mitigate the pandemic's impacts on services and advocacy. Three main themes emerged: workforce innovations, system empowerment, and the simultaneous pandemic of racial injustice. The COVID-19 pandemic inspired Coalitions to respond creatively and highlighted resources needed to support survivors and the domestic violence (DV) workforce going forward, including reassessing the current state of the DV movement.


Characterization of the conjugation system associated with the Staphylococcus aureus plasmid pJE1.
The conjugation system of Staphylococcus aureus that is conferred, at least in part, by plasmid pJE1, requires cell-to-cell contact. Optimum transfer was found when the numbers of donor and recipient cells were equal. Certain antibiotics increased the conjugation frequency. Fragments of plasmid pJE1 were cloned into a staphylococcal plasmid vector; although separate clones were isolated that conferred ethidium bromide resistance and gentamicin resistance, none of the clones carried the ability to conjugate. Transposon mutagenesis with Tn551 was used to create 26 mutants of pJE1. These were analysed for the position of the insertion and for their ability to conjugate. The sites of insertion were non-random. Only six mutants were unaffected in their conjugability; one showed increased ability to conjugate whilst the rest were either unable to conjugate or showed a reduced frequency. It is concluded that there are at least two separate regions necessary for conjugation and that the system is not obviously similar to that reported in streptococci.


[Profound study of respiratory biomechanics for diagnosis of chronic dust bronchitis].
Respiratory function studies play an important role in diagnosis of chronic dust bronchitis, both for the diagnosis verification and for determining the disease advance. The study is characterized by step-by-step assessment of respiratory function with body plethysmogram, flow/volume chart and bronchial spasmolytic test. Discrimination and regression analysis revealed leading functional parameters in chronic dust bronchitis: respiratory pathways resistance, pulmonary residual volume, bronchial spasmolytic test, forced vital lungs capacity, peak output flow.


Gingival pemphigus vulgaris preceding cutaneous lesion: A rare case report.
Pemphigus is a group of autoimmune diseases characterized by formation of intraepithelial bullae in skin and the mucous membrane. Pemphigus vulgaris affects the oral mucosa in nearly all cases. Pemphigus vulgaris is characterized by auto antibodies directed against desmosome-associated protein antigens (desmoglein-3) found in epithelial and epidermal intercellular substance. We report here a case of pemphigus vulgaris of gingiva in an adult female patient at an early stage followed by dermatologic involvement. Perilesional incision was taken and histopathological and direct immunofluorescence was done for identification of specific antibodies. The oral lesions were treated with 0.1% Triamcinolone acetonide ointment and Prednisolone 20 mg twice daily with multivitamins was administered systemically for skin lesion.


Mother's education and offspring asthma risk in 10 European cohort studies.
Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.


Carbohydrate-binding modules promote the enzymatic deconstruction of intact plant cell walls by targeting and proximity effects.
Cell wall degrading enzymes have a complex molecular architecture consisting of catalytic modules and noncatalytic carbohydrate-binding modules (CBMs). The function of CBMs in cell wall degrading processes is poorly understood. Here, we have evaluated the potential enzyme-targeting function of CBMs in the context of intact primary and secondary cell wall deconstruction. The capacity of a pectate lyase to degrade pectic homogalacturonan in primary cell walls was potentiated by cellulose-directed CBMs but not by xylan-directed CBMs. Conversely, the arabinofuranosidase-mediated removal of side chains from arabinoxylan in xylan-rich and cellulose-poor wheat grain endosperm cell walls was enhanced by a xylan-binding CBM but less so by a crystalline cellulose-specific module. The capacity of xylanases to degrade xylan in secondary cell walls was potentiated by both xylan- and cellulose-directed CBMs. These studies demonstrate that CBMs can potentiate the action of a cognate catalytic module toward polysaccharides in intact cell walls through the recognition of nonsubstrate polysaccharides. The targeting actions of CBMs therefore have strong proximity effects within cell wall structures, explaining why cellulose-directed CBMs are appended to many noncellulase cell wall hydrolases.


Prevalence of CD20+ cutaneous epitheliotropic T-cell lymphoma in dogs: a retrospective analysis of 24 cases (2011-2018) in the USA.
Limited information is known about the baseline frequency of canine CD20 positive (+ ) cutaneous epitheliotropic T-cell lymphoma. A single canine case report has been published. To characterize the baseline frequency of CD20+ staining in cases of canine cutaneous epitheliotropic T-cell lymphoma; to assess its values as a prognostic indicator. Skin biopsies from 24 client-owned animals diagnosed with cutaneous epitheliotropic lymphoma were assessed. A retrospective review of medical records from 2011 to 2018. Clinical histories and previous histological and immunohistochemical slides were collected from 24 dogs and additional immunohistochemical staining was performed as needed to assess cases of cutaneous epitheliotropic T-cell lymphoma for CD3, CD20, CD79a and PAX5 staining characteristics. Staining characteristics were assessed for their statistical relationship to median survival time. Overall median survival time was 189 days following the onset of clinical signs and 99 days following definitive diagnosis; 54% of cases had CD20+ staining. There was no statistically significant correlation between staining characteristics and median survival time from onset of signs (P = 0.54) or from diagnosis (P = 0.61). Canine cutaneous epitheliotropic lymphoma has a higher instance of CD20 positivity than documented previously. This indicates that CD20 staining may be unsuitable to differentiate T-cell and B-cell cutaneous epitheliotropic lymphoma. This also may have therapeutic implications with the advent of canine CD20 monoclonal antibody therapies.


Quality of life can be good after slide tracheoplasty for long-segment tracheal stenosis.
The objectives of this study were to measure 'health-related quality of life' (HRQoL) in children following slide tracheoplasty for long-segment tracheal stenosis (LSTS) and to explore the relationship of comorbidities and parental mental health with HRQoL outcomes. A cross-sectional study was undertaken with children who had undergone slide tracheoplasty. Participants included parents and children (age 5-15 years) recruited over a 13-month period, who were asked to complete validated measures of HRQoL, development and behaviour. Scores were compared to published norms. Forty-two children (male 69%; n = 29) were included; mean age was 5.3 (standard deviation 3.5) years and mean follow-up was 45 (range 4-179) months. Mean total HRQoL scores for children with repaired LSTS did not differ from those of healthy norms other than for children aged 13-23 months, but 10 children (24%) had scores >2 SD below the mean for healthy children. HRQoL was poorer in children with non-cardiac congenital comorbidities than in those with isolated LSTS (mean scores 60.34 ± 17.19 and 85.52 ± 12.19, respectively, P = 0.01). There was good agreement between children's and parents' scores, although children rated their HRQoL as better than their parents did. Anxious parents rated their children's HRQoL as significantly worse than non-anxious parents (P<0.001). Older children with isolated LSTS can have excellent HRQoL after surgery. Younger children, at an earlier time point postoperatively, and those with non-cardiac congenital comorbidities have poorer HRQoL. Further longitudinal evaluation is required to identify psycho-social (including parental) predictors of outcome which may inform, or be amenable to, intervention.


The enhancement of amyloid precursor protein and beta-site amyloid cleavage enzyme 1 interaction: amyloid-beta production with aging.
Aging is considered a high risk factor for Alzheimer's disease (AD), which is one of the most prevalent neurodegenerative disorders in the elderly population. The major pathologic feature of AD is senile plaques mainly containing amyloid-beta (Abeta) components. However, little direct evidence has shown aging in association with Abeta. Here we show that the protein-protein interaction of amyloid precursor protein (APP) and beta -site amyloid cleavage enzyme 1 (BACE1) is enhanced by the fluorescence resonance energy transfer (FRET) assay during the aging process, and the APP-BACE1 complex accumulates in the endosome in the IMR-90 fibroblast (NHF) cellular aging models. Moreover, enhanced Abeta is observed in aged cells, rat brain homogenates and human serum. Interestingly, addition of the dominant-negative mutant of Rab5, a small G-protein Rab5 involved in the endocytic process, inhibits the aging-related APP-BACE1 interaction and Abeta production, suggesting that endocytosis contributes to AD progression.


Temperature-dependent conjugative transfer of R27: role of chromosome- and plasmid-encoded Hha and H-NS proteins.
IncHI plasmids encode multiple-antibiotic resistance in Salmonella enterica serovar Typhi. These plasmids have been considered to play a relevant role in the persistence and reemergence of this microorganism. The IncHI1 plasmid R27, which can be considered the prototype of IncHI plasmids, is thermosensitive for transfer. Conjugation frequency is highest at low temperature (25 to 30 degrees C), decreasing when temperature increases. R27 codifies an H-NS-like protein (open reading frame 164 [ORF164]) and an Hha-like protein (ORF182). The H-NS and Hha proteins participate in the thermoregulation of gene expression in Escherichia coli. Here we investigated the hypothetical role of such proteins in thermoregulation of R27 conjugation. At a nonpermissive temperature (33 degrees C), transcription of several ORFs in both transfer region 1 (Tra1) and Tra2 from R27 is upregulated in cells depleted of Hha-like and H-NS-like proteins. Both chromosome- and plasmid-encoded Hha and H-NS proteins appear to potentially modulate R27 transfer. The function of R27-encoded Hha-like and H-NS proteins is not restricted to modulation of R27 transfer. Different mutant phenotypes associated with both chromosomal hha and hns mutations are compensated in cells harboring R27.


Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia.
Variant ataxia-telangiectasia is caused by mutations that allow some retained ataxia telangiectasia-mutated (ATM) kinase activity. Here, we describe the clinical features of the largest established cohort of individuals with variant ataxia-telangiectasia and explore genotype-phenotype correlations. Cross-sectional data were collected retrospectively. Patients were classified as variant ataxia-telangiectasia based on retained ATM kinase activity. The study includes 57 individuals. Mean age at assessment was 37.5 years. Most had their first symptoms by age 10 (81%). There was a diagnostic delay of more than 10 years in 68% and more than 20 years in one third of probands. Disease severity was mild in one third of patients, and 43% were still ambulant 20 years after disease onset. Only one third had predominant ataxia, and 18% had a pure extrapyramidal presentation. Individuals with extrapyramidal presentations had milder neurological disease severity. There were no significant respiratory or immunological complications, but 25% of individuals had a history of malignancy. Missense mutations were associated with milder neurological disease severity, but with a higher risk of malignancy, compared to leaky splice site mutations. Individuals with variant ataxia-telangiectasia require malignancy surveillance and tailored management. However, our data suggest the condition may sometimes be mis- or underdiagnosed because of atypical features, including exclusive extrapyramidal symptoms, normal eye movements, and normal alpha-fetoprotein levels in some individuals. Missense mutations are associated with milder neurological presentations, but a particularly high malignancy risk, and it is important for clinicians to be aware of these phenotypes. ANN NEUROL 2019;85:170-180.


Ecology. The advantages of togetherness.
What would be the advantage of unicellular organisms becoming multicellular? For organisms that feed on organic food (heterotrophs), the most efficient way to produce energy is to metabolize the food by aerobic respiration, but the fastest way is to metabolize it by fermentation. In their Perspective, Cox and Bonner discuss a mathematical model (Pfeiffer et al.), which shows that when these two kinds of organisms (respirators and fermenters) compete for a limited food source, the respirators manage best when they are grouped in clusters rather than remaining as separate cells. In this way, multicellularity could have originated.


Controllable microfluidic production of multicomponent multiple emulsions.
A hierarchical and scalable microfluidic device constructed from a combination of three building blocks enables highly controlled generation of multicomponent multiple emulsions. The number, ratio and size of droplets, each with distinct contents being independently co-encapsulated in the same level, can be precisely controlled. The building blocks are a drop maker, a connector and a liquid extractor; combinations of these enable the scale-up of the device to create higher-order multicomponent multiple emulsions with exceptionally diverse structures. These multicomponent multiple emulsions offer a versatile and promising platform for precise encapsulation of incompatible actives or chemicals, for synergistic delivery and biochemical and chemical reactions, and for engineering multicompartment materials with controlled internal phases.


Analysis of Error Potentials generated by a lower limb exoskeleton feedback in a BMI for gait control.
Brain-machine interfaces (BMIs) based on motor imagery (MI) for controlling lower-limb exoskeletons during the gait have been gaining importance in the rehabilitation field. However, these MI-BMI are not as precise as they should. The detection of error related potentials (ErrP) as a self-tune parameter to prevent wrong commands could be an interesting approach to improve their performance. For this reason, in this investigation ErrP elicited by the movement of a lower-limb exoskeleton against subject's will is analyzed in the time, frequency and time-frequency domain and compared with the cases where the exoskeleton is correctly commanded by motor imagery (MI). The results of the ErrP study indicate that there is statistical significative evidence of a difference between the signals in the erroneous events and the success events. Thus, ErrP could be used to increase the accuracy of BMIs which commands exoskeletons.Clinical Relevance- This investigation has the purpose of improving brain-machine interfaces (BMIs) based on motor imagery (MI) by means of the detection of error potentials. This could promote the adoption of robotic exoskeletons commanded by BMIs in rehabilitation therapies.


Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL).
Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.


Paravertebral block for forelimb anesthesia in the dog--an anatomic study.
To determine the anatomic landmarks for performing paravertebral forelimb block in the dog. Technique description. Nine canine cadavers. Each intervertebral foramen between the C5 and T2 vertebrae was targeted. With the dog in lateral recumbency, a 20 SWG 3'' spinal needle was placed at a 45 degree angle from a vertical transverse plane (with the dog standing this plane would be perpendicular to the ground) 2-3 cm lateral to the median plane for the three cranial intervertebral foramina and at a 90 degree angle with the same transverse plane 2-3 cm lateral to the median plane for the T1-T2 intervertebral foramina. Three out of nine (33%) of the cadavers had successful staining of all four desired nerves and the remaining six (66%) cadavers had successful staining of three of the four nerves. The C6-C7 spinal nerve was successfully stained in all nine cadavers. The other three nerves were each successfully stained in seven out of nine (78%) cadavers. The landmarks allow reliable placement of a solution at the nerves comprising the brachial plexus, allowing anesthesia of the entire forelimb in the dog.


Cellular adaptation to chronic ethanol results in altered compartmentalization and function of the scaffolding protein RACK1.
Previously, we found that acute ethanol induces the translocation of the scaffolding protein RACK1 to the nucleus. Recently, we found that nuclear RACK1 mediates acute ethanol induction of immediate early gene c-fos expression. Alterations in gene expression are thought to lead to long-term changes that ultimately contribute to the development of alcohol addiction and toxicity. Therefore, we sought to determine the effects of chronic exposure of cells to ethanol on the cellular compartmentalization of RACK1 and on c-fos messenger RNA (mRNA) and protein expression. Rat C6 glioma cells were used as the cell culture model. Immunohistochemistry was implemented to visualize the localization of RACK1 and to monitor the protein level of c-fos. Reverse-transcription polymerase chain reaction was used to measure c-fos mRNA levels. The Tat-protein transduction method was used to transduce recombinant Tat-RACK1 into cells as previously described. Chronic exposure of cells to 200 mM ethanol for 24 and 48 hr resulted in the gradual re-distribution of RACK1 out of the nucleus. It is interesting to note that acute ethanol re-challenge immediately after chronic treatment did not result in RACK1 translocation to the nucleus, and nuclear compartmentalization of RACK1 in response to acute ethanol was detected only after 24 hr of withdrawal. Similar patterns were obtained for c-fos expression. Chronic exposure to ethanol did not result in an increase in mRNA or protein levels of c-fos. Furthermore, acute ethanol exposure did not increase c-fos protein levels in cells that were first treated chronically with ethanol. However, transduction of exogenous RACK1 expressed as a Tat-fusion protein was able to rescue c-fos mRNA expression after chronic ethanol exposure. Our data suggest that RACK1 nuclear compartmentalization and ethanol-induced c-fos expression are transient and are desensitized to ethanol during prolonged exposure to high concentrations. The desensitization is temporary, and RACK1 can respond to acute ethanol treatment after a 24-hr withdrawal period. Our data further suggest that the altered compartmentalization of RACK1 leads to differences in c-fos expression upon acute or chronic exposure to ethanol. In summary, RACK1 is an important molecular mediator of the acute and chronic actions of ethanol on the expression of c-fos. These findings could have implications for the molecular signaling pathways leading to pathologic states associated with alcoholism, including toxicity.


Urgent intubation without neuromuscular blocking agents and the risk of tracheostomy.
Neuromuscular blocking agents play a significant role in improving the success rate for urgent intubation, although there is limited evidence about the effect on subsequent outcomes, such as the incidence of tracheostomy. In this retrospective cohort study, we aimed to examine the association between avoidance of neuromuscular blocking agents for urgent tracheal intubation and incidence of tracheostomy among patients in the intensive care unit (ICU). The setting of this study was an eight-bed ICU at a tertiary-care hospital in Okayama, Japan. We included patients who underwent urgent tracheal intubation at the emergency department or the ICU and were admitted to the ICU between April 2013 and November 2017. We extracted data on methods and medications of intubation, predictors for difficult intubation, Cormack-Lehane grade, patient demographics, primary diagnoses, reintubation. We estimated odds ratios and their 95% confidence intervals for elective tracheostomy during the ICU stay using logistic regression models. Of 411 patients, 46 patients underwent intubation without neuromuscular blocking agents and 61 patients underwent tracheostomy. After adjusting for potential confounders, patients who avoided neuromuscular blocking agents had more than double the odds of tracheostomy (odds ratio 2.59, 95% confidence interval 1.06-6.34, p value = 0.04). When stratifying the subjects by risk status for tracheostomy, the association was more pronounced in high-risk group, while we observed less significant association in the low-risk group. Avoidance of neuromuscular blocking agents for urgent intubation increases the risk of tracheostomy among emergency patients, especially those who have a higher risk for tracheostomy.


Investigating the Role of Brain Lateralization and Gender in Paranormal Beliefs.
Brain lateralization is associated with human behavior. Therefore, this study aimed at investigating the effects of brain lateralization on the scores of paranormal beliefs. The study population included 180 students of Sanandaj universities, Sanandaj City, Iran who were selected with convenience sampling method (100 left-brained males, 6 left-brained females, 56 both left- and right-brained males and 22 both left- and right-brained females). The research tools were the paranormal belief scale developed by Blackmore (1994), as well as the brain lateralization questionnaire (1985). The obtained findings suggested a significant difference between the left-brain and right-brained people in terms of paranormal beliefs. A significant difference was also found between the left-brained males and both left- and right-brained females in terms of paranormal beliefs. The paranormal beliefs of the left-brained cases were different from both left- and right-brained subjects, which can be seen between the left-brained males and both left- and right-brained females.


Importance of considering soils in seed transfer zone development: evidence from a study of the native Bromus marginatus.
Seed transfer zones, which define the geographical relationship between adaptive traits and environmental factors, are increasingly used to determine the source populations that can be combined in restoration and revegetation. Climatic variables have been the most commonly used environmental data in transfer zone development, even though soils are also a primary selective force on plants. We assessed the importance of including soils in seed transfer zones using Bromus marginatus, a native grass used for restoration and revegetation in the western United States, as an example. Seeds were collected from 64 populations across Montana and Idaho and grown in a common garden for two years. We assessed among-population variation based on 11 traits related to germination rate, plant size, vigor, inflorescence number, survival, and carbon isotope discrimination (∆13 ), and used this variation to develop seed transfer zone maps using two approaches: (1) a conventional approach, using only climatic variables (climate only) and (2) an expanded approach that included soils and climatic variables (soils + climate). The most influential drivers of trait variation were factors related to soil water availability: soil order, available water content (AWC), and organic carbon levels. Populations from areas with andic soils, which have high soil AWC and soil organic carbon, had low germination, limited first-year survival, low ∆13 , and small seeds. Growing season length and winter temperatures were also predictive of trait variation. In comparison to climate-only models, soils + climate models explained 11% more variance (120% relative increase) for ∆13 and an average of 4.5% more (27% relative increase) for growth traits and survival. The transfer zone map developed using soils + climate differed from the climate-only map in both spatial pattern of ecotypic variation and number of transfer zones; the soils + climate map had more zones and a higher proportion of small (<4 km2 ) transfer zone patches, while the climate-only map had more large patches >37 km2 . Including soils in transfer zone development may identify adaptive trait variation that is obscured by large-scale differences in climate and could improve plant materials used for ecosystem management.


Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors.
Malignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are therapy resistant and are frequently fatal. The molecular changes underlying the malignant transformation in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. MicroRNA expression profiles were determined from a series of archival, paired samples of plexiform neurofibroma and MPNST. Ninety differentially expressed microRNAs were identified between the paired samples. Three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) in MPNST were selected for functional characterization. In general, their differential expression was validated in a relevant cell line panel but only partly in a series of unpaired, fresh frozen tumor samples. As part of the validation process we also analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs. The role of microRNAs in cancer progression was examined in NF1-derived MPNST cell lines by transiently modulating microRNA levels. Our findings indicate that some microRNAs affect migratory and invasive capabilities and Wnt signaling activity but the effects are distinct in different cell lines. We conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression.