The influence of the dietary balance between energy and protein on milk urea concentration. Experimental trials assessed by two different protein evaluation systems.
Twenty-three dairy cows were fed rations with different proportions of energy and digestible crude protein (DCP). When the ration was balanced for energy and DCP according to Swedish standard the cows' milk urea concentration was 4.66-4.92 mmol/l (95% CI of mean). With increasing intakes of DCP, fed together with standard levels of energy, the mean milk urea concentration increased in proportion to the surplus of DCP. In contrast, the concentration of urea decreased when the cows were overfed with energy at the same time as they were underfed with protein. When the rations were recalculated in accordance with the AAT/PBV system for dietary protein evaluation the 95% CI for the mean milk urea concentration of the cows receiving a balanced ration was 3.76-4.56 mmol/l. The concentration of urea was dependent primarily on the PBV. When the 2 protein evaluation systems were compared there was a strong correlation between PBV and DCP. Ammonia was the only constituent of the rumen whose concentration was strongly correlated with the milk urea concentration. Taken together with earlier data the present results suggest that a milk urea concentration between 4.0 and 5.5 mmol/l should be regarded as normal at least when cows are fed conventional feedstuffs.


Serum and sputum alpha 2 macroglobulin in patients with chronic obstructive airways disease.
Serum alpha 2 macroglobulin concentrations were measured in patients with chronic obstructive airways disease and an age-matched group of control subjects. The mean serum level of alpha 2 macroglobulin was significantly lower in bronchitic subjects with acute chest infections than the mean value of the controls. No significant differences were observed between serum alpha 2 macroglobulin values in controls, subjects with "emphysema", and bronchitic patients who did not have chest infections. Sputum alpha 2 macroglobulin concentrations were compared in sputum samples from bronchitic patients with and without acute chest infections. The protein was detected (greater than 0.2 mg/l) in 94% of sputum samples from infected subjects but only 60% of non-infected sputum samples. Concentrations of alpha 2 macroglobulin in infected samples were significantly higher than the non-infected samples. Sputum/serum concentration ratios of alpha 2 macroglobulin were also significantly higher in infected samples but this difference was eliminated by "correcting" the values with the albumin sputum/serum ratios of the same samples. The results suggest that alpha 2 macroglobulin concentrations are higher in bronchial secretions during chest infection because of increased transudation from the blood rather than the presence of significant local secretion.


[Nosology and systems for data recording in child and adolescent psychiatry].
Thanks to a system of classification acceptable to a majority of child psychiatrists, recording mental problems has been a necessity since the 1960's. The two main classifications currently being used are that of the World Health Organization (CIM-9) and that of the American Association of Psychiatry (DSM-III), both of which categorize, with categories proper to children. There are also classifications dealing with dimensions which show child psychopathology better to psychologists. A system of French classification is being studied. The merits of a good classification are well set out. No existing system of classification has them completely. The CIM-9 and DSM-III are being fine-tuned. Whichever system used, date gathering on a particular patient must be rigorous. Studies carried out in Great Britain and the United States have led to the formulation of semi-structured interviews, an evaluation scale and questionnaires that now cover most child and adolescent psychiatry.


Cortical blood flow and +Gz acceleration in conscious rabbits.
We examined whether superficial cortical blood flow (CBF) of nonanesthetized rabbits (n = 11) is affected by gravitational (G) stress. Blood flow was measured by laser-Doppler flowmetry through a chronic Plexiglas window implanted over the parietal cortex. Mean arterial blood pressure (MABP) was recorded via an aortic catheter with the pressure transducer situated at the level of the head. The electrocorticogram (ECoG) was also studied in seven rabbits. The animals were exposed to tail-to-head acceleration [6, 10, 15, and 20 G acceleration (Gz) for 1 min]. MABP fell with increasing acceleration (regression line equation: MABP = -7.0 Gz + 129.1; P < 0.001, r = 0.85), whereas CBF was statistically either not different from or greater than control. In one rabbit exposed to 20 Gz, high voltage and slow waves were observed on the ECoG and these changes were preceded by a decrease in CBF to 66% of control. We conclude that the stress and the siphon effect may account for the maintenance of elevated CBF despite low or negative MABP until the occurrence of vascular collapse that induces loss of consciousness.


Analytical challenges in quantifying abiraterone with LC-MS/MS in human plasma.
A method was developed and validated to quantify abiraterone in human plasma. During assay development, several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, coelution with metabolites and carry-over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2-8°C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h. Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method. Carry-over was reduced to acceptable limits by incorporating a third mobile phase into the gradient. The chromatographic separation of abiraterone with its multiple metabolites was addressed by using a longer analytical column and adjusting the gradient. Abiraterone was extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadrupole mass spectrometry in positive ion mode. A stable deuterated isotope was used as the internal standard. The assay ranges from 1 to 500 ng/mL. Within- and-between-day precisions and accuracies were below 13.4% and within 95-102%. This bioanalytical method was successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care for patients with metastatic castration-resistant prostate cancer.


Immunoblotting for the serodiagnosis of Helicobacter pylori infection in Brazilian patients with and without gastric carcinoma.
We evaluated the performance of a commercial immunoblotting in the serodiagnosis of Helicobacter pylori infection in Brazilian patients. The presence of anti-H. pylori antibodies was also investigated in a group of 20 duodenal ulcer patients after successful treatment. One hundred and ninety one patients were studied. Among the 164 infected patients, 46 had gastric carcinoma. The duodenal ulcer patients were treated with antimicrobial drugs and the eradication of the microorganism was confirmed in all of them one month after the end of the treatment by the 13C-urea breath test. Sera were assayed for H. pylori antibodies using the Helicoblot 2.0 (Genelabs Diagnostics, Singapore). The sensitivity, specificity, positive, and negative predictive values of the test were 93.9%, 92.6%, 98.7%, and 71.4%, respectively. The sensitivity of the test was similar in patients with (93.5%) and without (95.7%) gastric carcinoma. Twenty-four months after the end of the treatment, the band of 116 kDa was still detected in one of the patients. In conclusion, the Helicoblot 2.0 is an accurate test to diagnose H. pylori infection and although it can not be employed to monitor the bacterium eradication, it may be useful for diagnosing past infection, especially in gastric carcinoma patients.


Transthoracic fine-needle aspiration biopsy cytology of pulmonary neoplasms.
The experience with 212 transthoracic fine-needle aspiration biopsy cytology specimens of mass lesions of the lung at a small Canadian hospital is reviewed. The technique showed a sensitivity of 78.0%, a specificity of 85.7%, a positive predictive value of 98.5%, and a negative predictive value of 25.0% when the cytological diagnoses were compared with the final clinicopathological diagnoses listed in the patients' charts. There was only one false positive diagnosis of malignancy. Diagnoses based on cytology of the aspirates were compared with histological diagnoses in 127 cases and the accuracy of typing of the major groups of carcinoma was assessed. Distinction between small-cell carcinoma and non-small-cell carcinoma was usually accurate and fairly good correlation was achieved for all major types of carcinoma. The results for typing of the neoplasm are not as good as those from larger centres in the world. The technique is considered to be useful even in the setting of a small hospital.


Preoperative planning and post-operative estimation of vertebroplasty using CT/CAD/CAE systems.
The aim of the work was to determine the stiffness of vertebral bodies after vertebroplasty by means of radiological examination (CT), computer-aided design (CAD) and computer-aided engineering (CAE) systems. Twenty-six patients with angiomata in vertebrae have been examined. A vertebra with pathological changes has been modeled twice, i.e., before operation and after the process of vertebral body filling with cement. The processing of CT images for the purposes of generation of 3D vertebral body models using Mimics software is also shown. In the analysis, non-homogeneous material properties of bone in the analysed areas are taken into consideration. Some problems related to the determination of non-homogeneous areas of particular material properties are discussed. FEM analyses described in the paper yielded the distributions of the stresses, strains and displacements in vertebral bodies. The stiffnesses of healthy vertebral bodies, bodies with pathological changes and bodies with bone cement injected were compared. The usefulness of the results obtained from the analyses of vertebral body stiffness for medical application in vertebroplasty was emphasized. The method presented above allows us to put forward a different approach to the problem consisting in individual examination of each patient and planning the surgery according to the case-by-case conditions. The computer-aided approach, using CT/CAD/CAE system, proposed above allows both improving the surgery performance and post-operative control of the patient's condition.


Thermal stress in Danio rerio: a link between temperature, light, thermo-TRP channels, and clock genes.
It is believed that the biological systems perceiving temperature and light daily cycles were subjected to the simultaneous selective pressures, which resulted in their co-evolutionary association. We investigated the influence of 1h 33°C heat shock on the expression of clock and heat shock protein genes, as well as the role of the thermo-TRP channel, TRPV1, in ZEM-2S cells of the teleost Danio rerio, in constant dark (DD) or light-dark cycles (LD). After heat shock, we observed an acute increase of hsp90 aa1 levels in both DD and LD conditions. Interestingly, the expression of hsp90 aa1 was two-fold lower in LD than in DD, what suggests an antagonistic effect of white light on heat shock action. Regarding clock genes, no effect was found in cells subjected to the heat shock in DD. When cells were kept in LD, the expression of per1, per2, cry1a, and cry1b increased in response to heat shock, indicating that heat shock only affects clock core of LD-synchronized ZEM-2S cells. We then evaluated whether TRPV1 played a role in heat-mediated hsp90 aa1 and per2 responses: hsp90 aa1 increase was unaffected whereas per2 increase was partially blocked by TRPV1 inhibitor, demonstrating the channel participation in clock gene regulation by heat shock. Taken together, our results open a novel investigative perspective regarding the relationship between temperature and clock genes, placing a new player in the regulation of this phenomenon: the TRPV1 channel.


Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide.
The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator with a long duration of action. CGRP is widely distributed and is present in perivascular nerves of tissues that include skin and the synovium. In this study we have investigated the possibility that CGRP can modulate the inflammatory actions of the cytokine IL-1 by using an inflammatory model in rabbit skin. The intradermal injection of IL-1 (1.4 x 10(-14) mol/site) alone stimulated little edema formation. However, when IL-1 was injected with CGRP (10(-11) mol/site), a highly significant edema was observed, and neutrophil accumulation induced by IL-1 was potentiated. These results suggest that the action of IL-1 as a potent mediator of increased microvascular permeability is only observed when skin blood flow is increased in this model. This was confirmed by experiments in which PGE2 (3 x 10(-9) mol/site) at a dose with a similar duration of vasodilator action as CGRP (10(-11) mol/site) also potentiated edema induced by IL-1. Further experiments investigated the mechanism by which IL-1 increased microvascular permeability. Edema induced by IL-1 was dependent on de novo protein synthesis and the presence of circulating neutrophils. However, selective platelet-activating factor and histamine H1 antagonists had no inhibitory effect on this response. Thus it appears that when a microvascular bed is dilated by the long-lasting vasodilator CGRP, edema induced by IL-1 is clearly observed. These results highlight a potentially important synergistic interaction between cytokines and neuropeptides in inflammation.


Metabolic Changes in Central Poststroke Pain Following Thalamic Intracerebral Hemorrhage: An 18F-FDG PET Study.
Central poststroke pain (CPSP) is one of the most refractory neuropathic pains following stroke. Injury in the spinothalamic pathway appears crucial for the development of CPSP, but changes in activity in multiple brain regions may also be related. We investigated brain metabolic changes in patients with CPSP following thalamic intracerebral hemorrhage (ICH). Forty-three patients with thalamic ICH were examined. Overall brain metabolism was measured with F-FDG PET. Images were analyzed with statistical parametric mapping (SPM12). Patients with CPSP (n = 20) were compared with patients without CPSP (n = 23). In addition, the association between regional brain metabolism and the severity of CPSP was investigated. In comparison to patients in the non-CPSP group, the CPSP group exhibited significant hypometabolism in the ipsilesional precentral, postcentral gyri, and the contralesional cuneus (Puncorrected < 0.001), whereas significant hypermetabolism was found in the medial dorsal nucleus of the contralesional thalamus (Puncorrected < 0.001). In addition, brain metabolism in the ipsilesional Crus I and Crus II of the cerebellum was positively correlated to pain intensity ratings (Puncorrected < 0.001). Our findings suggested that an altered state of resting brain metabolism in various brain regions related to sensory processing and cognitive functioning may be involved in the underlying mechanism of CPSP following thalamic ICH.


Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone.
Elafin and secretory leukocyte protease inhibitor (SLPI) are anti-protease and anti-microbial molecules present at mucosal surfaces. Both molecules are expressed in the female reproductive tract where they may be involved in innate immune defence. This study examines the role of progesterone in the regulation of SLPI and elafin. Progesterone treatment increases expression of SLPI mRNA and protein in the T47D breast epithelial cell line and this upregulation is attenuated in the presence of the anti-gestogens, RU486 and ZK98734, confirming the involvement of the nuclear progesterone receptor. A putative progesterone response element has been identified in the SLPI promoter. Progesterone also acts in synergy with the proinflammatory cytokines, IL-1beta and TNFalpha, to increase SLPI. In contrast, progesterone treatment has no direct effect on elafin mRNA expression. In summary, progesterone has a differential effect on SLPI and elafin expression and although both vary within the uterus throughout the menstrual cycle, progesterone is likely to contribute to the direct regulation of SLPI in the female reproductive tract even in the presence of inflammatory agents.


WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.
Overexpression of Wilms' tumor-1 (WT1) transcription factor facilitates proliferation in acute myeloid leukemia (AML). However, whether WT1 is enriched in the leukemia-initiating cells (LICs) and leukemia stem cells (LSCs) and facilitates the self-renewal of LSCs remains poorly understood. MLL-AF9-induced murine leukemia model was used to evaluate the effect of knockdown of wt1 on the self-renewal ability of LSC. RNA sequencing was performed on WT1-overexpressing cells to select WT1 targets. Apoptosis and colony formation assays were used to assess the anti-leukemic potential of a deubiquitinase inhibitor WP1130. Furthermore, NOD/SCID-IL2Rγ (NSG) AML xenotransplantation and MLL-AF9-induced murine leukemia models were used to evaluate the anti-leukemogenic potential of WP1130 in vivo. We found that wt1 is highly expressed in LICs and LSCs and facilitates the maintenance of leukemia in a murine MLL-AF9-induced model of AML. WT1 enhanced the self-renewal of LSC by increasing the expression of BCL2L2, a member of B cell lymphoma 2 (BCL2) family, by direct binding to its promoter region. Loss of WT1 impaired self-renewal ability in LSC and delayed the progression of leukemia. WP1130 was found to modify the WT1-BCL2L2 axis, and WP1130-induced anti-leukemic activity was mediated by ubiquitin proteasome-mediated destruction of WT1 protein. WP1130 induced apoptosis and decreased colony formation abilities of leukemia cells and prolonged the overall survival in the THP1-based xenograft NSG mouse model. WP1130 also decreased the frequency of LSC and prolonged the overall survival in MLL-AF9-induced murine leukemia model. Mechanistically, WP1130 induced the degradation of WT1 by positively affecting the ubiquitination of WT1 protein. Our results indicate that WT1 is required for the development of AML. WP1130 exhibits anti-leukemic activity by inhibiting the WT1-BCL2L2 axis, which may represent a new acute myeloid leukemia therapy target.


The future of theoretical evolutionary game theory.
Evolutionary game theory is a truly interdisciplinary subject that goes well beyond the limits of biology. Mathematical minds get hooked up in simple models for evolution and often gradually move into other parts of evolutionary biology or ecology. Social scientists realize how much they can learn from evolutionary thinking and gradually transfer insight that was originally generated in biology. Computer scientists can use their algorithms to explore a new field where machines not only learn from the environment, but also from each other. The breadth of the field and the focus on a few very popular issues, such as cooperation, comes at a price: several insights are re-discovered in different fields under different labels with different heroes and modelling traditions. For example, reciprocity or spatial structure are treated differently. Will we continue to develop things in parallel? Or can we converge to a single set of ideas, a single tradition and eventually a single software repository? Or will these fields continue to cross-fertilize each other, learning from each other and engaging in a constructive exchange between fields? Ultimately, the popularity of evolutionary game theory rests not only on its explanatory power, but also on the intuitive character of its models. This article is part of the theme issue 'Half a century of evolutionary games: a synthesis of theory, application and future directions'.


Evaluation of anti-atherosclerotic and vasculoprotective effect of long acting nifedipine in patients after PTCA.
The anti-atherosclerotic and vasculoprotective effect of long acting nifedipine (nicardia retard 20) was evaluated on patients undergoing percutaneous transluminal coronary angioplasty (PTCA). This was a randomised, controlled, prospective clinical trial. A total of 30 patients fulfilling inclusion criteria were divided randomly in 2 groups of 15 each. One group was given long acting nifedipine while other group did not receive long acting nifedipine. The rest of the treatment was similar for both the groups. Clinical and angiographic parameters were evaluated regularly for a period of one year. The group receiving long acting nifedipine showed 20% restenosis as against 33% in group not receiving long acting nifedipine. Thus, from this trial, it can be concluded that long acting nifedipine can reduce the progress of reocclusion and thus demonstrates the anti-atherosclerotic and vasculoprotective action.


Public Stranger Violence-What Makes You Vulnerable?A Comparison of Perspectives From Young Adults and Industry Experts.
The purpose of this study was to determine the situational and individual factors that influence vulnerability to public stranger violence (PSV) from the perspective of young adults and industry professionals. In total, 25 young adults aged between 18 and 29 years formed one sample and participated in one of four focus groups. The second sample consisted of 10 industry professionals with backgrounds in policing, corrections, and forensic psychology. Each professional participated in an individual semistructured interview. Both samples were asked questions regarding vulnerability and safety in public, where responses were analyzed using a thematic analysis. Multiple themes were identified and categorized into situational and individual factors associated with victimization. Situational factors referred to aspects of the environment that may influence vulnerability to PSV and included visibility, location, and level of support for potential victims. Individual factors referred to aspects about the person that may influence vulnerability to PSV and included unpredictability, ease of target, stereotypes, in-groups versus out-groups, distractions, and personality traits. Although both samples identified similar situational factors, young adults were found to be either unaware of individual factors identified by industry professionals as influencing vulnerability or at least misunderstood some of these factors. This is problematic as young adults may be basing their public behaviors on misinformation that may in fact increase, rather than decrease, vulnerability to PSV. The findings from this study have implications for the design of personal safety programs as well as community-based interventions to reduce vulnerability, the prevalence of PSV, and the negative outcomes associated with PSV, including anxiety and fear of crime.


Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice.
Escherichia coli Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.


Activation of transforming potential of the human insulin receptor gene.
A retrovirus containing part of the human insulin receptor (hIR) gene was constructed by replacing ros sequences in the avian sarcoma virus UR2 with hIR cDNA sequences coding for 46 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains of the beta subunit of hIR. The resulting virus, named UIR, contains the hIR sequence fused to the 5' portion of the UR2 gag gene coding for p19. UIR is capable of transforming chicken embryo fibroblasts and promoting formation of colonies in soft agar; however, it does not form tumors in vivo. A variant that arose from the parental UIR is capable of efficiently inducing sarcomas in vivo. UIR-transformed cells exhibit higher rates of glucose uptake and growth than normal cells. The 4-kilobase UIR genome codes for a membrane-associated, glycosylated gag-hIR fusion protein of 75 kDa designated P75gag-hir. P75gag-hir contains a protein tyrosine kinase activity that is capable of undergoing autophosphorylation and of phosphorylating foreign substrates in vitro; it is phosphorylated at both serine and tyrosine residues in vivo.


Exocytosis of a single bovine adrenal chromaffin cell: the electrical and morphological studies.
Exocytosis of a single bovine adrenal chromaffin cell, triggered by histamine stimulation, was investigated via the electric responses detected with single-walled carbon-nanotube field-effect transistors (SWCNT-FET) and the morphological changes acquired by atomic force microscopy (AFM). Secretion of chromogranin A (CgA), stored in the vesicles of a single chromaffin cell, can be monitored in situ by the antibody against CgA (CgA-antibody) functionalized on the SWCNT-FET devices. The SWCNT-FET can further discriminate the amount of released CgA with different levels of histamine stimulations. The AFM morphological studies on a chromaffin cell indicate that the depression structures on the cell surface, caused by the histamine-evoked exocytotic fusion pores, appeared much more frequently than those without histamine stimulation or with the pretreatment of mepyramine before histamine stimulation. The vesicle diameters are about 50 nm calculated from the obtained three-dimensional AFM images. In comparison, the fusion pores of chromaffin cells stimulated by high-K (+) buffer solution were also investigated to have a wider-ranging distribution of vesicle diameters of 60-260 nm. This work demonstrates that the combination of novel techniques, SWCNT-FET and AFM, can provide further insights into the fundamental properties of exocytosis in neuroendocrine cells.


Improving robustness of gene ranking by multi-criterion combination with novel gene importance transformation.
Feature ranking, which ranks features via their individual importance, is one of the frequently used feature selection techniques. Traditional feature ranking criteria are apt to produce inconsistent ranking results even with light perturbations in training samples when applied to high dimensional and small-sized gene expression data, which brings troubles for further studies such as biomarker identification. A widely used strategy for solving the inconsistencies is the multicriterion combination, where score normalisation is crucial. In this paper, three problems in existing methods are first analyzed, and then a new feature importance transformation algorithm based on resampling and permutation is proposed for score normalisation. Experimental studies on four popular gene expression data sets show that the multi-criterion combination based on the proposed score normalisation produces gene rankings with improved robustness.


Late Gadolinium Enhancement of Left Ventricular Papillary Muscles in Patients with Mitral Regurgitation.
Arrhythmogenic mitral valve prolapse (MVP) is an important cause of sudden cardiac death characterized by fibrosis of the papillary muscles or left ventricle (LV) wall, and an association between late gadolinium enhancement (LGE) of the LV papillary muscles and ventricular arrhythmia in MVP has been reported. However, LGE of the papillary muscles may be observed in other causes of mitral regurgitation, and it is not limited to patients with MVP. This study was to evaluate the association of LGE of the LV papillary muscles or ventricular wall on cardiac magnetic resonance imaging (CMR) and ventricular arrhythmia in patients with mitral regurgitation. This study included 88 patients (mean age ± standard deviation, 58.3 ± 12.0 years; male, 42%) with mitral regurgitation who underwent CMR. They were allocated to the MVP (n = 43) and non-MVP (n = 45) groups, and their LGE images on CMR, clinical characteristics, echocardiographic findings, and presence of arrhythmia were compared. LV myocardial wall enhancement was more frequent in the MVP group than in the non-MVP group (28% vs. 11%, p = 0.046). Papillary muscle enhancement was observed in 7 (7.9%) patients. Of the 43 patients with MVP, 15 (34.8%) showed LGE in the papillary muscles or LV myocardium, including 12 (27.9%) with LV myocardial wall enhancement and 4 (9.3%) with papillary muscle enhancement. One patient with bilateral diffuse papillary muscle enhancement experienced sudden cardiac arrest due to ventricular fibrillation. Univariable logistic regression analysis showed that high systolic blood pressure (BP; odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = 0.027) and ventricular arrhythmia (OR, 6.84; 95% CI, 1.29-36.19; p = 0.024) were significantly associated with LGE of the papillary muscles. LGE of the papillary muscles was present not only in patients with MVP, but also in patients with other etiologies of mitral regurgitation, and it was associated with high systolic BP and ventricular arrhythmia. Papillary muscle enhancement on CMR should not be overlooked.


Age is just a number.
The naked mole rat defies the Gompertz law and shows no sign of increased mortality risk as it gets older.


Bivariate modelling of clustered continuous and ordered categorical outcomes.
Simultaneous observation of continuous and ordered categorical outcomes for each subject is common in biomedical research but multivariate analysis of the data is complicated by the multiple data types. Here we construct a model for the joint distribution of bivariate continuous and ordinal outcomes by applying the concept of latent variables to a multivariate normal distribution. The approach is then extended to allow for clustering of the bivariate outcomes. The model can be parameterized in a way that allows writing the joint distribution as a product of a standard random effects model for the continuous variable and a correlated cumulative probit model for the ordinal outcome. This factorization suggests convenient parameter estimation using estimating equations. Foetal weight and malformation data from a developmental toxicity experiment illustrate the results.


Unusual coronary artery ectasia and stenosis in a patient with systemic lupus erythematosus and acute myocardial infarction.
Acute myocardial infarction is an important and sometimes fatal complication of systemic lupus erythematosus (SLE). We describe a case of acute myocardial infarction in a 23-year-old woman with SLE. Angiography revealed coronary ectasia in the left main and proximal circumflex coronary arteries, as well as a stenotic lesion in the left anterior descending artery. The possible pathophysiology is discussed.


Drainage Tube Placement May Not Be Necessary During Endoscopic Thyroidectomy Bilateral Areola Approach: A Preliminary Report.
The endoscopic thyroidectomy bilateral areola approach (ETBAA) improved cosmetic outcomes significantly and is now widely applied. The usage of drainage tubes is controversial in conventional open thyroidectomy (COT), but studies about drainage placement decisions during ETBAA are still limited. This study aimed to determine the feasibility of having no drainage tube applied during ETBAA on patients with papillary thyroid carcinoma. The clinical data of patients undergoing ETBAA from July 2018 to May 2021 was retrospectively collected. The patients were divided into two groups based on drain placement: no-drain and drain. The two groups were matched at a ratio of 1:1. Fifty-five patients from each group were finally included. Postoperative complications and follow-up data were compared between the two groups. No significant difference was observed between the two groups in the incidence of postoperative complications, including hemorrhage, surgical site infection, and subcutaneous seroma. Compared with the drain group, the operation time of the no-drain group was significantly shorter [(107.75 ± 24.59) min vs. (119.91 ± 34.05) min, P < 0.05]. The total and postoperative hospital stay was significantly shorter in the no-drain group [(2.40 ± 0.71) days vs. (4.78 ± 1.33) days, P < 0.001, (2.04 ± 0.19) days vs. (2.15 ± 0.36) days, P < 0.05], and the costs of surgical consumables were also significantly lower [(6,820.83 ± 164.29) CNY vs. (7,494.13 ± 216.7) CNY, P < 0.05]. The postoperative pain score of the no-drain group was significantly lower than the drain group [(1.58 ± 0.63) vs. (1.89 ± 0.76), P < 0.05]. No drainage applied during ETBAA on papillary thyroid carcinoma is safe and feasible. This practice does not increase the risk of postoperative complications, but it does shorten the operation time and hospital stay, as well as reduce medical costs. Furthermore, it alleviates the suffering of patients.


Antibacterial Effects of Curcumin Nanocrystals against Porphyromonas gingivalis Isolated from Patients with Implant Failure.
Background. Despite their benefits, dental implants may sometimes fail for a diversity of causes; the most common reasons of failure are infection and bone loss. Porphyromonas gingivalis (P. gingivalis) bacteria show a major role in peri-implantitis infection and dental implant failure. Methods. In this study, the prevalence of P. gingivalis isolated from the gingival crevicular fluid (GCF) of fifteen Iranian patients with implant failure (more than 1/3 of the implant length), who had average oral and dental hygiene and no antibiotic use for at least one month, was determined. Moreover, the antimicrobial effects of curcumin nanocrystals against isolated P. gingivalis were investigated. The collected samples from patients were transferred to a microbiology laboratory to culture. The presence of P. gingivalis in the culture media was confirmed using a trypsin reagent test. An isolate from a patient with the highest colony count was selected to evaluate the antibacterial effects of curcumin nanoparticles. The inhibition zone diameter, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were determined. Results. Out of fifteen patients, eight (53.33%) were positive for the presence of P. gingivalis. The results of the microbial tests showed that curcumin nanoparticles had an MIC of 6.25 µg/mL and an MBC of 12.5 µg/mL. Conclusions. The use of curcumin nanoparticles may control the bacterial infection around the implant.


Multi-resolution speech analysis for automatic speech recognition using deep neural networks: Experiments on TIMIT.
Speech Analysis for Automatic Speech Recognition (ASR) systems typically starts with a Short-Time Fourier Transform (STFT) that implies selecting a fixed point in the time-frequency resolution trade-off. This approach, combined with a Mel-frequency scaled filterbank and a Discrete Cosine Transform give rise to the Mel-Frequency Cepstral Coefficients (MFCC), which have been the most common speech features in speech processing for the last decades. These features were particularly well suited for the previous Hidden Markov Models/Gaussian Mixture Models (HMM/GMM) state of the art in ASR. In particular they produced highly uncorrelated features of small dimensionality (typically 13 coefficients plus deltas and double deltas), which was very convenient for diagonal covariance GMMs, for dealing with the curse of dimensionality and for the limited computing resources of a decade ago. Currently most ASR systems use Deep Neural Networks (DNN) instead of the GMMs for modeling the acoustic features, which provides more flexibility regarding the definition of the features. In particular, acoustic features can be highly correlated and can be much larger in size because the DNNs are very powerful at processing high-dimensionality inputs. Also, the computing hardware has reached a level of evolution that makes computational cost in speech processing a less relevant issue. In this context we have decided to revisit the problem of the time-frequency resolution in speech analysis, and in particular to check if multi-resolution speech analysis (both in time and frequency) can be helpful in improving acoustic modeling using DNNs. Our experiments start with several Kaldi baseline system for the well known TIMIT corpus and modify them by adding multi-resolution speech representations by concatenating different spectra computed using different time-frequency resolutions and different post-processed and speaker-adapted features using different time-frequency resolutions. Our experiments show that using a multi-resolution speech representation tends to improve over results using the baseline single resolution speech representation, which seems to confirm our main hypothesis. However, results combining multi-resolution with the highly post-processed and speaker-adapted features, which provide the best results in Kaldi for TIMIT, yield only very modest improvements.


Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET.
Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.


[Studies on the gamma delta T lymphocytes in the peripheral blood in healthy adults].
Since gamma delta T lymphocytes has been found to be increased in patients with some immunological disorders, there exists clinical needs to determine the population of the cells in peripheral blood in normal subjects. We counted the number of gamma delta T lymphocytes in samples obtained from 151 healthy volunteers, aged from 20 to 69 years, by using a dual-color flow cytometry with fluorescence-conjugated CD3 and anti-TCR-gamma delta antibodies. Distribution ratio of gamma delta T lymphocytes among peripheral blood lymphocytes was 3.8 +/- 2.5% (range, 0.6-16.1%). Difference in the ratio and the number of gamma delta T lymphocytes among sex was not significant, but those decreased slightly but significantly with age.


Asperity characteristics of the Olami-Feder-Christensen model of earthquakes.
Properties of the Olami-Feder-Christensen (OFC) model of earthquakes are studied by numerical simulations. The previous study indicated that the model exhibited "asperity"-like phenomena, i.e., the same region ruptures many times near periodically [T. Kotani, Phys. Rev. E 77, 010102(R) (2008)]. Such periodic or characteristic features apparently coexist with power-law-like critical features, e.g., the Gutenberg-Richter law observed in the size distribution. In order to clarify the origin and the nature of the asperity-like phenomena, we investigate here the properties of the OFC model with emphasis on its stress distribution. It is found that the asperity formation is accompanied by self-organization of the highly concentrated stress state. Such stress organization naturally provides the mechanism underlying our observation that a series of asperity events repeat with a common epicenter site and with a common period solely determined by the transmission parameter of the model. Asperity events tend to cluster both in time and in space.


Proteoglycans in Articular Cartilage and Their Contribution to Chondral Injury and Repair Mechanisms.
Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.


Influence of dose rate on carcinogenesis resulting from x-ray, 113In, and 198Au irradiation.
The potential hazards from internally administered radionuclides used in nuclear medicine are usually compared with one another and with diagnostic x-rays on the basis of the absorbed dose in rads, with no regard to the dose rate of the radiation. This study compared the carcinogenic potential of a dose of 250 rads delivered at different dose rates to rat livers by x-ray, 113mIn, and 198Au. The chemical carcinogen N-2-fluorenyldiacetamide was administered after irradiation to reduce the latent period and increase the number of radiogenic liver tumors. No significant difference in tumor incidence was observed among groups of animals treated with either 198Au, 113mIn, or x-irradiation.


Catalytic Role of Adsorption of Electrolyte/Molecules as Functional Ligands on Two-Dimensional TM-N4 Monolayer Catalysts for the Electrocatalytic Nitrogen Reduction Reaction.
Two-dimensional single-atom catalysts (2D SACs) have been widely studied on the nitrogen reduction reaction (NRR). The characteristics of 2D catalysts imply that both sides of the monolayer can be catalytic sites and adsorb electrolyte ions or molecules from solutions. Overstrong adsorption of electrolyte ions or molecules on both sides of the catalyst site will poison the catalyst, while the adsorbate on one side of the catalytic site will modify the activity and selectivity of the other side for NRR. Discovering the influence of adsorption of electrolyte ions or molecules as a functional ligand on catalyst performance on the NRR is crucial to improve NRR efficiency. Here, we report this work using the density functional theory (DFT) method to investigate adsorption of electrolyte ions or molecules as a functional ligand. Among all of the studied 18 functional ligands and 3 transition metals (TMs), the results showed that Ru&F, Ru&COOH, and Mo&H2O combinations were screened as electrocatalysis systems with high activity and selectivity. Particularly, the Mo&H2O combination possesses the highest activity with a low ΔGMAX of 0.44 eV through the distal pathway. The superior catalytic performance of the Mo&H2O combination is mainly attributed to the electron donation from the metal d orbital. Furthermore, the functional ligands can occupy the active sites and block the competing vigorous hydrogen evolution reaction. Our findings offer an effective and practical strategy to design the combination of the catalyst and electrolyte to improve electrocatalytic NRR efficiency.


A nano-microstructured artificial-hair-cell-type sensor based on topologically graded 3D carbon nanotube bundles.
A design for a unique artificial-hair-cell-type sensor (AHCTS) based entirely on 3D-structured, vertically aligned carbon nanotube (CNT) bundles is introduced. Standard microfabrication techniques were used for the straightforward micro-nano integration of vertically aligned carbon nanotube arrays composed of low-layer multi-walled CNTs (two to six layers). The mechanical properties of the carbon nanotube bundles were intensively characterized with regard to various substrates and CNT morphology, e.g. bundle height. The CNT bundles display excellent flexibility and mechanical stability for lateral bending, showing high tear resistance. The integrated 3D CNT sensor can detect three-dimensional forces using the deflection or compression of a central CNT bundle which changes the contact resistance to the shorter neighboring bundles. The complete sensor system can be fabricated using a single chemical vapor deposition (CVD) process step. Moreover, sophisticated external contacts to the surroundings are not necessary for signal detection. No additional sensors or external bias for signal detection are required. This simplifies the miniaturization and the integration of these nanostructures for future microsystem set-ups. The new nanostructured sensor system exhibits an average sensitivity of 2100 ppm in the linear regime with the relative resistance change per micron (ppm μm(-1)) of the individual CNT bundle tip deflection. Furthermore, experiments have shown highly sensitive piezoresistive behavior with an electrical resistance decrease of up to ∼11% at 50 μm mechanical deflection. The detection sensitivity is as low as 1 μm of deflection, and thus highly comparable with the tactile hair sensors of insects, having typical thresholds on the order of 30-50 μm. The AHCTS can easily be adapted and applied as a flow, tactile or acceleration sensor as well as a vibration sensor. Potential applications of the latter might come up in artificial cochlear systems. In particular, the stable mechanical bending of the sensor up to 90° opens up unique application opportunities.


Role of the vestibular commissure in gaze-holding in the cat: a pharmacological evaluation.
Recent theoretical studies have proposed that the vestibular commissure is a major component of the horizontal gaze-holding system. In order to test this hypothesis, we injected either bicuculline, a GABA receptor antagonist, or strychnine, a glycine receptor antagonist, into the medial vestibular nucleus of alert cats. The intervestibular connection is indeed inhibitory and mediated by GABA and glycine. As neither bicuculline nor strychnine caused serious deficit of the gaze-holding system, we conclude that the vestibular commissure is not essential for gaze-holding.


Vibrating H3(+) in a uniform magnetic field.
Potential energy surfaces are obtained for singlet H3(+) in magnetic fields of up to 2350 T. The magnetic interaction was treated by first-order perturbation theory and the interaction terms computed ab initio. They were then fitted to a functional form and added to a recent, highly accurate adiabatic potential energy surface. In its most stable orientation, the molecule is arranged such that the magnetic field vector is in the molecular plane. The most stable configuration is no longer D3h as in the field-free case, but C2v, though the stabilization energy is extremely small, of the order of 0.01 cm(–1) for a 2350 T field. Finally, we have calculated, for a range of magnetic field strengths and orientations, all the vibrational eigenvalues that are below the barrier to linearity in the field-free case.


Modulation of rat lung Na+,K(+)-ATPase gene expression by hyperoxia.
Rats exposed to 85% O2 for 5-7 days develop tolerance to otherwise lethal hyperoxia (100% O2). The rate of alveolar fluid clearance increases during adaptation to hyperoxia, due in part to increased alveolar epithelial sodium channel activity. In these studies, we have investigated molecular mechanisms leading to increased lung Na+,K(+)-ATPase activity in hyperoxia. We exposed adult rats to 85% O2 (sublethal hyperoxia) for 7 days, followed by 2, 3, or 4 days in 100% O2. Steady-state levels of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNA messages in whole lung RNA did not change significantly. Thus, lung Na+,K(+)-ATPase gene expression in sublethal hyperoxia appears to be regulated in part at the transcriptional level. Alveolar epithelial type II (ATII) cell Na+,K(+)-ATPase alpha 1 and beta 1 subunit proteins, measured by quantitative immunofluorescence, increased significantly after sublethal hyperoxia and 100% O2 exposures. Increases in lung fluid clearance after sublethal hyperoxia are associated with increased ATII cell Na+,K(+)-ATPase protein and whole lung Na+,K(+)-ATPase mRNA expression, which correspond to previously described increases in epithelial sodium channel expression under these conditions.


Muscle fatigue due to changes beyond the neuromuscular junction.
A number of changes in function occur beyond the neuromuscular junction during activity; three main types are described. (a) During high frequency stimulation there is a rapid loss of force accompanied by a slowing of the action potential waveform and an increase in the excitation threshold of the muscle. It is suggested that accumulation of K+ in the extracellular spaces of the muscle may be responsible for these changes. (b) Slowing of relaxation is a feature of fatigued muscle. The slowing allows a reduction in activation frequency (minimizing high frequency fatigue) without resulting in an appreciable loss of force. (c) Changes in shape and amplitude of the twitch have considerable effects on the force generated by low frequencies of stimulation. After a brief tetanus there is a reduction in the width of the twitch which increases the fusion frequency of the muscle and may account for the "sag' seen at the start of low frequency contractions. After a prolonged series of contractions the twitch amplitude is reduced and remains so for several hours. This may be the result of some structural damage to the sarcoplasmic reticulum or transverse tubular system.


Quantification of mammary gland tissue size and composition changes after weaning in sows.
The objectives of this study were to characterize the tissue compositional changes in porcine mammary glands after weaning and to determine whether administration of estradiol alters the profile of these tissue changes. Forty-five primiparous sows were assigned randomly to one of two treatment groups after weaning, control or estrogen treated. Estrogen-treated sows received twice-daily injections of estradiol-17beta (0.125 mg/kg of BW); control sows received vehicle injections. Sows were weaned at d 21 of lactation and killed on either d 0 (d of weaning; n = 5) or on d 2, 3, 4, 5, or 7 after weaning (n = 4 per treatment on each day). Teat order relative to suckling behavior was observed on the day before weaning to determine which mammary glands the piglets suckled. Suckled and non-suckled glands were identified from the teat order observation, and individual mammary glands were collected at slaughter. Mammary glands were trimmed of skin and extraneous fat pad, individually weighed, and bisected to measure cross-sectional area. The remaining half of each gland was ground and stored at -20 degrees C for chemical analyses. Frozen tissue was used for measuring tissue DNA, DM, protein, fat, and ash contents. Suckled mammary glands of sows undergo significant and dramatic changes during the initial 7 d after weaning, with significant changes occurring even by d 2 after weaning. Mean cross-sectional area of parenchymal tissue in suckled mammary glands decreased from 59.7 +/- 2.1 cm2 on the day of weaning to 26.8 +/- 2.3 cm2 by d 7 after weaning (P < 0.0001). Mammary gland wet weight decreased from 485.9 +/- 22.0 g on the day of weaning to 151.5 +/- 24.8 g by d 7 after weaning (P < 0.0001), whereas DNA decreased from 838.8 +/- 46.2 g on the day of weaning to 278.4 +/- 52.5 g by d 7 after weaning (P < 0.0001). The changes in gland wet weight and DNA during the period of mammary gland involution in the sow represent loses of over two-thirds of the parenchymal mass and nearly two-thirds of the cells that were present on the day of weaning. Estrogen treatment did not affect overall mammary involution during the first 7 d after weaning. Mammary glands that were not suckled during lactation had no further loss of parenchymal tissue during the first 7 d after weaning. Mammary gland involution in the sow is a rapid process and is probably irreversible within 2 or 3 d after weaning.


Implicit exchanges in family caregiving for frail elders in Taiwan.
In this study, the authors use in-depth interviews with inductive analysis to develop a conceptual framework for exploring social exchanges and their implicit calculations for caregivers in Taiwan. They interviewed 12 caregivers, based on theory-based sampling and maximum variation. They found some components of implicit exchanges of the caregivers, and drew a framework to describe it. At the beginning of care, motivations were mostly from obligation accompanied by reciprocity or repaying motives. In the process of caregiving, some unique, implicit cultural implicit exchanges were found, such as karma, a demonstrative behavior to investment, equitable share of responsibility, and the pressure or rewards from public opinion. These implicit exchanges might be intermediary factors in helping caregivers cope with their burden or even in influencing their continuation of care. The findings are implicated to help family caregivers continue their care and not damage their quality of care.


The P.F.C. sigma RP-F TKA designed for improved performance: a matched-pair study.
The press fit condylar P.F.C. Sigma RP-F (rotating-platform, high flexion) knee is designed to provide a range of motion (ROM) of 155 degrees without compromising wear, polyethylene contact stresses, patellofemoral tracking, or stability. The first 50 TKA surgeries using the Sigma RP-F knee performed at the author's institution were matched to 50 rotating-platform knees for age, sex, body mass index, preoperative diagnosis, duration of follow-up, and preoperative ROM to determine the effect of design on postoperative ROM. The mean increase in active ROM in the Sigma RP-F group was 17 degrees, compared with 6 degrees in the rotating-platform group (P =.0011). The mean increase in active ROM in patients who had less than 120 degrees of preoperative motion was 27 degrees in the Sigma RP-F group, compared with 16 degrees in the rotating-platform group (P = .006). With the new P.F.C. Sigma RP-F design, greater ROM can be achieved independent of preoperative ROM.


Designing 3D-Printed Mesh-Covered Fluid Collecting Racks (MFCRs) to Prevent Moisture-Related COVID-19 Sampling Interruptions in Taiwan.
Background: A sampling platform (or table) set at the patient's side in a zero-exposure screening center (booth) might be used for specimen collection during public health crises such as the COVID-19 pandemic. However, repeated sanitization causes moisture problems. Such moisture problems would not only be noted by patients but also interrupt the sampling process. In this study, we aimed to develop 3D-printed mesh-covered fluid collecting racks (MFCRs) to address surface moisture problems to determine whether MFCRs can shorten the sampling time. Methods: This was an observational, descriptive, and cross-sectional study. We observed the reasons for sampling interruptions related to surface moisture problems among patients who used MFCRs or did not (April 28-30, 2022). We used a 3D printer to make an MFCR, which measured 14.5 cm in width and length and 1.0 cm in height. The MFCR allows the ethanol to drain through the mesh into the fluid collection rack below to leave a relatively dry surface on the mesh. Finally, we calculated the median time to finish sampling between MFCRs and non-MFCRs. Results: A total of 400 patients were randomly observed (using MFCRs, n = 200; non-MFCRs, n = 200). Patients in the non-MFCR group were more likely to interrupt the sampling process (n = 39, 19.5%) by noting surface moisture problems than those in the MFCR group (n = 3, 1.5%). Two of the major interruptions, "asking questions about the moist surface" (from 12% to 1%) and "slowing down their actions" (from 4.5% to 0.5%), were obviously improved by using MFCRs. Overall, the median sampling time was significantly shorter (p < 0.001) in the group using MFCRs (0.6 min) than in the group using non-MFCRs (1.5 min). The MFCRs shortened the sampling time by 60%, which might be associated with decreasing interruptions caused by surface moisture problems. Conclusions: The 3D printed MFCRs are suitable for handling surface moisture problems caused by repeated sanitizations. More importantly, the MFCRs might be associated with decreasing interruptions caused by moisture problems.


Débridement of extremity war wounds.
The extent of surgery appropriate for limb wounds agreed on at the Inter-Allied Surgical Conference in 1917 included excision of the skin margin, generous extension of the wound, exploration through all layers, and excision of damaged muscle--techniques recognizable by all trauma surgeons today. The criteria for muscle viability (the four C's) include contraction on being pinched, consistency (not waxy or "stewed"), capillary bleeding when cut, and color (red, not pale or brown). Skin is excised with a narrow margin, fascia is generously released, all layers of the wound are explored and gross contamination removed, and nonviable muscle is excised. Some low-energy transfer wounds (eg, civilian handgun injury, military shrapnel wounds) involve little tissue damage and can safely be managed nonsurgically, provided that there is confidence in the assessment of wound severity. Questions remain regarding the safest and most effective way to assess wounds and select patients for surgical versus nonsurgical management.


The impact of amortization of gene therapies funding on the results and conclusions of CEMs and BIMs.
Gene replacement therapy (GRT) is a treatment method used to combat or prevent various diseases. Its high one-off cost constitutes a major obstacle for successful market access. This paper aims to assess and discuss the applicability of amortization in models, such as cost-effectiveness models (CEMs) and budget impact models (BIMs) informing HTA recommendations and reimbursement decisions. A hypothetical CEA and BIA were considered. The objective was to compare the GRT with and without amortization. A straight-line amortization model was used. The CEM and BIM were considered and assessed based on two set of scenarios: considering different amortization duration or different discounting rate. The impact of amortization against the total cost of gene therapy was assessed for all the scenarios. The cost difference between GRT with and without amortization in relation to its total cost was -$58,855, thus amortization does not have a significant impact on the results and conclusions of the cost-effectiveness analysis. For BIM in the base case, amortization had no impact on the results. Amortization has negligible impact on the results of CEM and total BIM and no impact on the conclusions from the model. One exception is the budget impact in case of an amortization period longer than the time horizon of BIM, where a half of the GRT price is moved beyond the model time horizon. Amortization has a distinguishing effect from an accounting perspective, but it does not have any implication for payers.


Micropuncture study on urea movements in the kidney cortical tubules of low protein fed sheep.
Micropuncture studies of late proximal, early and late distal cortical tubules were carried out on kidneys of normal (NP) and low (LP) protein fed sheep in order to investigate the participation of these segments in the urea sparing induced by protein restriction in the diet. A low protein diet induced significant reductions in the fractional (-54%) and total (-84%) urea excretion, revealing an enhanced capacity for urea conservation. Micropuncture data did not show any difference in the proximal tubule functions between both groups of sheep. In distal cortical tubules the fractional delivery of urea (early distal, 0.61 +/- 0.06 for NP and 0.77 +/- 0.06 for LP sheep, not significant (NS); late distal, 0.45 +/- 0.07 for NP and 0.71 +/- 0.09 for LP sheep, P < 0.05) showed a relatively larger amount of urea present in the late distal tubule of protein restricted sheep. The tubular fluid-to-plasma inulin ratio in the late distal tubule was found to be lower in LP sheep (4.33 +/- 0.23 versus 8.58 +/- 0.9 in NP sheep, P < 0.01). The tubular flow rate, reduced in the early distal tubules of LP sheep (10.87 +/- 0.99 versus 18.92 +/- 2.58 nL.min-1 in NP sheep, P < 0.05), was not different in the late distal tubules from values in normally fed animals (6.65 +/- 0.90 versus 7.73 +/- 0.94 nL.min-1 in NP sheep, NS). These findings suggest a decreased distal water reabsorption coincident with the relatively larger amounts of intraluminal urea in LP sheep. This relatively larger urea delivery to the initial collecting duct could increase the subsequent urea reabsorption in protein restricted sheep.


Biofactors regulating mitochondrial function and dynamics in podocytes and podocytopathies.
Podocytes are terminally differentiated kidney cells acting as the main gatekeepers of the glomerular filtration barrier; hence, inhibiting proteinuria. Podocytopathies are classified as kidney diseases caused by podocyte damage. Different genetic and environmental risk factors can cause podocyte damage and death. Recent evidence shows that mitochondrial dysfunction also contributes to podocyte damage. Understanding alterations in mitochondrial metabolism and function in podocytopathies and whether altered mitochondrial homeostasis/dynamics is a cause or effect of podocyte damage are issues that need in-depth studies. This review highlights the roles of mitochondria and their bioenergetics in podocytes. Then, factors/signalings that regulate mitochondria in podocytes are discussed. After that, the role of mitochondrial dysfunction is reviewed in podocyte injury and the development of different podocytopathies. Finally, the mitochondrial therapeutic targets are considered.


PTB binds to the 3' untranslated region of the human astrovirus type 8: a possible role in viral replication.
The 3' untranslated region (3'UTR) of human astroviruses (HAstV) consists of two hairpin structures (helix I and II) joined by a linker harboring a conserved PTB/hnRNP1 binding site. The identification and characterization of cellular proteins that interact with the 3'UTR of HAstV-8 virus will help to uncover cellular requirements for viral functions. To this end, mobility shift assays and UV cross-linking were performed with uninfected and HAstV-8-infected cell extracts and HAstV-8 3'UTR probes. Two RNA-protein complexes (CI and CII) were recruited into the 3'UTR. Complex CII formation was compromised with cold homologous RNA, and seven proteins of 35, 40, 45, 50, 52, 57/60 and 75 kDa were cross-linked to the 3'UTR. Supermobility shift assays indicated that PTB/hnRNP1 is part of this complex, and 3'UTR-crosslinked PTB/hnRNP1 was immunoprecipitated from HAstV-8 infected cell-membrane extracts. Also, immunofluorescence analyses revealed that PTB/hnRNP1 is distributed in the nucleus and cytoplasm of uninfected cells, but it is mainly localized perinuclearly in the cytoplasm of HAstV-8 infected cells. Furthermore, the minimal 3'UTR sequences recognized by recombinant PTB are those conforming helix I, and an intact PTB/hnRNP1-binding site. Finally, small interfering RNA-mediated PTB/hnRNP1 silencing reduced synthesis viral genome and virus yield in CaCo2 cells, suggesting that PTB/hnRNP1 is required for HAstV replication. In conclusion, PTB/hnRNP1 binds to the 3'UTR HAstV-8 and is required or participates in viral replication.


Bryant's sign as a manifestation of a retroperitoneal paraduodenal bleed and subsequent small bowel obstruction.
Bryant's sign is defined as ecchymosis at the base of the penis and scrotum and is usually associated with a retroperitoneal bleed or ruptured aortic aneurysm. We report the case of a retroperitoneal paraduodenal bleed which presented with Bryant's sign. Imaging confirmed a pancreaticoduodenal arcade microaneurysm and associated low-grade coeliac artery stenosis (Sutton-Kadir syndrome). Retroperitoneal bleeding can be life threatening and requires prompt diagnosis and management. However, diagnosis can be challenging due to the clinical variation in presentation. The rarity of presentation in this case caused significant uncertainty necessitating a multidisciplinary approach for diagnostic clarity and safe patient care.


Bmi-1 regulation of INK4A-ARF is a downstream requirement for transformation of hematopoietic progenitors by E2a-Pbx1.
Loss-of-function alterations of INK4A are commonly observed in lymphoid malignancies, but are consistently absent in pre-B cell leukemias induced by the chimeric oncoprotein E2a-Pbx1 created by t(1;19) chromosomal translocations. We report here that experimental induction of E2a-Pbx1 enhances expression of BMI-1, a lymphoid oncogene whose product functions as a transcriptional repressor of the INK4A-ARF tumor suppressor locus. Bmi-1-deficient hematopoietic progenitors are resistant to transformation by E2a-Pbx1; however, the requirement for Bmi-1 is alleviated in cells deficient for both Bmi-1 and INK4A-ARF. Furthermore, the adverse effects of E2a-Pbx1 on pre-B cell survival and differentiation are partially bypassed by forced expression of p16(Ink4a). These results link E2a-Pbx1 with Bmi-1 on an oncogenic pathway that is likely to play a role in the pathogenesis of human lymphoid leukemias through downregulation of the INK4A-ARF gene.


[Dramatic improvement of urinary retention and the left lower limb paresis with methylprednisolone in a case of regional encephalitis following varicella zoster infection].
We report a previously well 14-year-old male who developed left-sided hemiconvulsion, urinary retention and hemiplegia 1 months after varicella-zoster virus (VZV) infection. Brain T2-weighted MRI showed hyperintensity in medial fronto-parietal area including cyngulate gyrus, foot division of the motor cortex, para-central lobule and corpus callosum with right predominance, which corresponded to hyperperfusion area in SPECT study. MR angiography revealed no occlusion or narrowing of vessels. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. After methylprednisolone pulse tharapy under diagnosis of regional encephalitis, the patient recovered completely. Although polymerase chain reaction(PCR) could not detect VZV-DNA in CSF, antecedent VZV infection might be closely related to pathomechanism of the regional encephalitis. Dramatic response to steroid, rapid recovery on MRI and good prognosis supported that the underlying pathology was mainly vasogenic edema rather than cytotoxic edema.


Hearing loss and volumetric growth rate in untreated vestibular schwannoma.
In this study, the authors aimed to clarify the relationship between hearing loss and tumor volumetric growth rates in patients with untreated vestibular schwannoma (VS). Records of 128 treatment-naive patients diagnosed with unilateral VS between 2012 and 2018 with serial audiometric assessment and MRI were reviewed. Tumor growth rates were determined from initial and final tumor volumes, with a median follow-up of 24.3 months (IQR 8.5-48.8 months). Hearing changes were based on pure tone averages, speech discrimination scores, and American Academy of Otolaryngology-Head and Neck Surgery hearing class. Primary outcomes were the loss of class A hearing and loss of serviceable hearing, estimated using the Kaplan-Meier method and with associations estimated from Cox proportional hazards models and reported as hazard ratios. Larger initial tumor size was associated with an increased risk of losing class A (HR 1.5 for a 1-cm3 increase; p = 0.047) and serviceable (HR 1.3; p < 0.001) hearing. Additionally, increasing volumetric tumor growth rate was associated with elevated risk of loss of class A hearing (HR 1.2 for increase of 100% per year; p = 0.031) and serviceable hearing (HR 1.2; p = 0.014). Hazard ratios increased linearly with increasing growth rates, without any evident threshold growth rate that resulted in a large, sudden increased risk of hearing loss. Larger initial tumor size and faster tumor growth rates were associated with an elevated risk of loss of class A and serviceable hearing.


Immunohistochemistry-based comparative study in detection of Hirschsprung's disease in infants in a Tertiary Care Center.
Hirschsprung's disease (HD) is the major cause of pediatric intestinal obstruction with a complex pattern of inheritance. The absence of ganglion cells along with an analysis of hypertrophy and hyperplasia of nerves in the nerve plexus of submucosa and muscularis mucosae is regarded as a potential hallmark for its diagnosis. This study was undertaken to ascertain the (1) clinical profile, (2) mode of presentation, and (3) to compare the role of calretinin immunostaining with acetylcholinesterase in the diagnosis of HD. This prospective and observational study was conducted in the Department of Pathology, IPGME & R from June 2014 to May 2015. One hundred and four patients clinically and radiologically diagnosed with HD underwent surgery were included in the study. The data of every patient including age, sex, and presenting symptoms were recorded. Eventually, histopathological, calretinin, and acetylcholinesterase immunohistochemical examination were done. Total numbers of cases studied were 104, which aged between 0 days and 365 days. Male preponderance (76.92%) was noted. The overall sensitivity, specificity, positive, and negative predictive value of acetylcholinesterase were 100%, 86.44%, 84.91%, and 100%, respectively. The concordance of detection of ganglion cells and nerve fibers, and thereby diagnosis of Hirschsprung's and non-HD using calretinin and the gold standard was statistically in strong agreement (κ = 0.749, 95% confidence interval: 0.635-0.863). Calretinin stands out as the single and indispensable tool that differentiates HD from other mimickers.


Metabolic consequences of HIV: pathogenic insights.
With the advances in antiretroviral therapy (ART), HIV infection has been transformed into a chronic medical condition that can be effectively managed like diabetes or hypertension. For HIV care providers, the focus of care for many patients has shifted from prevention of opportunistic infection and AIDS-related conditions to age-related cardiometabolic comorbidities, including cardiovascular disease, diabetes, obesity, and frailty. Numerous reports have highlighted that these diseases are occurring at an earlier age among HIV-infected persons. However, there is an ongoing debate regarding the role of HIV infection, ART, and other factors that may underlie the accelerated occurrence of these diseases. Herein, we review the epidemiology of the US HIV epidemic with regards to several metabolic comorbidities and address mechanisms that likely contribute to the current nature of HIV disease.


The endoscopic forehead lift.
Endoscopic techniques are being successfully applied to address eyebrow and forehead ptosis. The methods rely on extensive subperiosteal and subgaleal release of the forehead and scalp flap, allowing the elevation of soft tissues. Ablation of the depressor supercilli and procerus can be performed to address skin folding in the glabellar region. The mobilized frontotemporal flap is then elevated to the desired level and fixated with microscrews to the outer table of the skull. Laterally, the flap is fixed to the deep temporalis fascia. The technique relies upon a solid knowledge of the regional anatomy and the use of specialized instruments now available for dissecting under the flap. The endoscopic forehead lift can achieve results comparable to those obtained by the open coronal forehead lift while minimizing the incidence and extent of postoperative cutaneous anesthesia and telogenic hair loss, which frequently follows open coronal forehead surgery. In addition, the endoscopic technique is able to address eyebrow ptosis in the balding male without causing disfiguring scarring.


Spatiotemporal Memories for Missing Samples Reconstruction.
We develop a systematic theory to reconstruct missing samples in a time series using a spatiotemporal memory based on artificial neural networks. The Markov order of the input process is learned and subsequently used for learning temporal correlations from data difference sequences. We enforce the Lipschitz continuity criterion in our algorithm, leading to a regularized optimization framework for learning. The performance of the algorithm is analyzed using both theory and simulations. The efficacy of the technique is tested on synthetic and real life data sets. Our technique is analytic and uses nonlinear feedback within an optimization setup. Simulation results show that the algorithm presented in this article significantly outperforms the state-of-the-art algorithms for missing samples reconstruction with the same data set and similar training conditions.


Test-retest reliability of regression dynamic causal modeling.
Regression dynamic causal modeling (rDCM) is a novel and computationally highly efficient method for inferring effective connectivity at the whole-brain level. While face and construct validity of rDCM have already been demonstrated, here we assessed its test-retest reliability-a test-theoretical property of particular importance for clinical applications-together with group-level consistency of connection-specific estimates and consistency of whole-brain connectivity patterns over sessions. Using the Human Connectome Project dataset for eight different paradigms (tasks and rest) and two different parcellation schemes, we found that rDCM provided highly consistent connectivity estimates at the group level across sessions. Second, while test-retest reliability was limited when averaging over all connections (range of mean intraclass correlation coefficient 0.24-0.42 over tasks), reliability increased with connection strength, with stronger connections showing good to excellent test-retest reliability. Third, whole-brain connectivity patterns by rDCM allowed for identifying individual participants with high (and in some cases perfect) accuracy. Comparing the test-retest reliability of rDCM connectivity estimates with measures of functional connectivity, rDCM performed favorably-particularly when focusing on strong connections. Generally, for all methods and metrics, task-based connectivity estimates showed greater reliability than those from the resting state. Our results underscore the potential of rDCM for human connectomics and clinical applications.


Selective hydrogenolysis of raw glycerol to 1,2-propanediol over Cu-ZnO catalysts in fixed-bed reactor.
The catalytic properties of Cu-ZnO catalysts for glycerol hydrogenolysis to 1,2-propanediol (1,2-PDO) were tested in a fixed-bed reactor at 250 °C and 2.0 MPa H2. The relation between composition, surface properties, and catalytic performance of glycerol hydrogenation of Cu-ZnO catalysts was studied using nitrogen adsorption (BET methods), XRD, H2 temperature-programmed reduction, and N2O chemisorptions. It was found that there was a close link between the surface CuO amount of Cu-ZnO catalyst and the reactivity for glycerol hydrogenation. The Cu-ZnO catalyst (Cu/Zn = 1.86) which had the highest surface Cu amount showed the best catalytic activity for glycerol hydrogenolysis. Furthermore, Cu-ZnO catalyst presented good stability and remarkable catalytic activity for glycerol hydrogenolysis to 1,2-PDO using raw glycerol derived from the fat saponification as feedstock.


Left ventricular contractility using isovolumic phase indices during PEEP in ARDS patients.
The effects of incremental increases in PEEP during mechanical ventilation on left ventricular (LV) contractility before and after intravascular volume expansion (IVE) were studied in 10 patients treated for ARDS. A pulmonary artery (PA) catheter, a LV catheter-tip micromanometer, and an esophageal balloon catheter were inserted in these patients. We measured transmural right atrial and PA pressures, transmural LV end-diastolic and systemic arterial pressures, the first derivative of LV pressure (LV dP/dt), the ratio of LV dP/dt at transmural developed LV pressure (dP/dt/DPt) with DPt = 5, 10, 40 mm Hg, cardiac index (CI) at every level of PEEP and after IVE at the highest PEEP. Stepwise increases in PEEP (from 0-20 cm H2O) were associated with progressive fall in CI whereas heart rate remained unchanged. Transmural right atrial and PA pressures did not change; transmural LV end-diastolic and systemic arterial pressures and peak dP/dt decreased significantly with PEEP, except for dT/dt/dPt. IVE reversed this fall in CI and peak dP/dt. Whereas transmural LV end-diastolic pressure rose markedly. We conclude that the observed fall in LV performance during PEEP is not the result of a depressed LV contractility because PEEP does not induce a decrease in dP/dt/DPt, the least sensitive to change in preload isovolumic phase indices of contractility.


Creatine kinase as a prognostic indicator in electrical injury.
Serial serum creatine kinase (CK) and creatine kinase myocardial band isoenzyme (CK-MB) levels were obtained from 116 of 125 electrical burn patients admitted from 1976 through 1986. We divided patients into three groups (peak CK within 2 days after admission) as follows: group 1, CK less than 400 U/L; group 2, CK = 400 to 2500 U/L; group 3, CK greater than 2500 U/L. Clinical myocardial infarction (MI) was determined by ischemic ECG changes, LDH isoenzyme patterns, and clinical course. Skin grafts occurred in 2 of 24 patients from group 1, in 15 of 31 from group 2, and in 37 of 61 from group 3. Hospital stay (mean +/- SEM) was 4.6 +/- 1.3 days for group 1, 20.2 +/- 5.4 for group 2, and 37.7 +/- 3.6 for group 3. Group 1 patients required no amputations; group 2 had 1 limb and 5 digit amputations; group 3 had 22 limb and 16 digit amputations. Only three clinical MIs were found (all in group 3), although 1 of 31 patients from group 2 and 32 of 61 from group 3 had CK-MB greater than 4%. Highly elevated CK and CK-MB are associated with longer hospitalization, and a greater risk of skin grafting or amputation, than with levels less than 400 U/L. Clinical MI is rare and cannot be diagnosed by elevated CK-MB alone.


Robust analysis in joint models: an application to a study on muscular dystrophy.
Generalized partial ordinal models occur frequently in biomedical investigations where, along with ordinal longitudinal outcomes, there are time-dependent covariates that act nonparametrically. In these studies, an association between such outcomes and time to an event is of considerable interest to medical practitioners. The primary objective in the present article is to study the robustness of estimators of the parameters of interest in a joint generalized partial ordinal models and a time-to-event model, because in many situations, the estimators in such joint models are sensitive to outliers. A Monte Carlo Metropolis-Hastings Newton Raphson algorithm is proposed for robust estimation. A detailed simulation study was performed to justify the behavior of the proposed estimators. By way of motivation, we consider a data set concerning longitudinal outcomes of children involved in a study on muscular dystrophy. Our analysis revealed some interesting findings that may be useful to medical practitioners.


Diacylhydrazone-assembled {Ln11} nanoclusters featuring a "double-boats conformation" topology: synthesis, structures and magnetism.
A family of novel Ln nanoclusters, namely, [Ln11(ovpho)4(μ-CH3O)2(μ-H2O)2(μ3-OH)6(CH3OH)4(H2O)2(NO3)8](OH)·xH2O·yCH3OH [Ln = Gd (1), x = 1, y = 3; Ln = Tb (2), x = 1, y = 3; Ln = Dy (3), x = 0, y = 3], was obtained via solvothermal reactions of Ln(NO3)3 with a diacylhydrazone ligand N,N'-bis(o-vanillidene)pyridine-2,6-dicarbohydrazide N-oxide (H4ovpho). Their isostructural molecular structures are composed of two crystallographically symmetric {Ln6} rings sharing a Ln3+ ion, and display an unprecedented "double boat conformation" topology that, to our knowledge, has not yet been reported. Ophenol, Oenol and Ooxynitride from ovpho4- ligands, as well as Omethanol, Owater and Ohydroxyl help to bridge the Ln3+ ions. The structural variation between these {Ln11} clusters and a previously reported {Gd18} nanowheel, both of which are assembled by H4ovpho under the same synthetic method and reaction conditions, is caused only by changing the anions of Ln salts. Magnetic investigations revealed a large magnetocaloric effect (MCE) of 1, whose maximum -ΔSm value reaches 30.1 J kg-1 K-1 for ΔH = 50 kOe at 2.0 K. Additionally, it was found that 3 shows single-molecule magnets (SMMs) behavior, with an approximated energy barrier Ueff = 6.13 K and pre-exponential factor τ0 = 1.70 × 10-6 s.


Modeling cost-effectiveness and health gains of a "universal" versus "prioritized" hepatitis C virus treatment policy in a real-life cohort.
We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814-1825).


[The effect of 3-oxypyridine and succinic acid derivatives on obsessive-compulsive activity of mice in marble-burying test].
The effect of domestic derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin, and mexidol) on obsessive-compulsive behavior of mice was studied in the marble-burying test. Additionally the effect of these drugs on the behavior of animals was assessed in the open field test. Amitriptylin and alpha-lipoic acid were used as reference drugs. It was established that single administration of the investigated drugs in optimal doses, corresponding to therapeutic range in humans, inhibits obsessive-compulsive behavior of mice in the marble-burying test. Amitriptylin and alpha-lipoic acid produced similar effects. It is established that emoxipine stimulates the behavior of mice in the open field after single administration. An increase in the emoxipine dose led to decrease of stimulation and gradual development of sedative effect. Reamberin and mexidol, as well as alpha-lipoic acid and amitriptyline, caused sedation in mice tested in the open field. Inhibiting effect of emoxipine, reamberin, mexidol and alpha-lipoic acid on the obsessive-compulsive behavior in mice directly depended on sedative action of these drugs.


Eradicating Quiescent Tumor Cells by Targeting Mitochondrial Bioenergetics.
The presence of quiescent cell populations in solid tumors represents a major challenge for disease eradication. Such cells are generally present in poorly vascularized tumor areas, show limited sensitivity to traditional chemotherapeutical drugs, and tend to resume proliferation, resulting in tumor reseeding and growth. There is growing recognition of the importance of developing therapies that target these quiescent cell populations to achieve long-lasting remission. Recent studies have shown that the combination of hypoxia and reduced nutrient availability in poorly vascularized areas results in limited tumor metabolic plasticity coupled with an increased sensitivity to perturbations in mitochondrial flux. Targeting of mitochondrial bioenergetics in these quiescent cell tumor populations may enable tumor eradication and improve the prognosis of patients with cancer.


[Analysis of gingival crevicular fluid. Relation of isoelectric focusing protein patterns to clinical evaluation].
The purpose of this study was to determine the protein patterns in gingival crevicular fluid relation to the isoelectric focusing protein patterns of GCF and to clinical evaluations. GCF was collected with filter paper from 105 subjects. The probing depth, the gingival index (Löe & Silness) and the plaque index (Silness & Löe) as clinical evaluations The results follow: 1. The main isoelectric focusing protein patterns of GCF were between pH 5.5 and 7.5. In comparison, the GCF and the serum from the same patients showed patterns to similar serum albumin. 2. Between of GCF pH 5.5 and 7.5 the protein patterns that ranged over 60% was pI 5.65, 6.45, 6.55, 6.75 and 7.00. The frequencies of the ranges of protein patterns and clinical evaluation were compared by the X2 test. pI 5.65, 6.45, 6.55 and 6.75 and PD were significant different, as were pI 6.45, 6.55 and 6.75 and GI. But each pI and PIl. were not significantly different.


Roles of Transepithelial Electrical Resistance in Mechanisms of Retinal Pigment Epithelial Barrier and Retinal Disorders.
Transepithelial/transendothelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of endothelial and epithelial monolayers. The value of TEER reflects the physical structure and characteristics of epithelial/endothelial cells. TEER value is a preferred physiological indicator reflecting transport rate of ions and macromolecules through the paracellular pathway, which is used to evaluate permeability of paracellular pathway. TEER value has a high specificity for the permeability of reactive tightly connected complex. TEER value is an effective indicator to evaluate the integrity of cell barrier. The cell barrier not only controls the diffusion penetration of various substances in adjacent intercellular spaces, but also regulates the transport of ions and macromolecules across. On one hand, the cell barrier protects the body from harmful substances; on the other hand, it restricts the entry of therapeutic drugs. Therefore, with the increase of permeability in paraepithelial pathway, the TEER value decreased, otherwise, it increased. In this review article, we compared the advantages and disadvantages of the existing methods for measuring TEER and summarized the factors affecting TEER accuracy, as well as the roles of TEER in mechanisms of retinal pigment epithelial barrier and retinal disorders such as proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa.


Molecular mechanisms of constitutive activity: mutations at position 111 of the angiotensin AT1 receptor.
A possible molecular mechanism for the constitutive activity of mutants of the angiotensin type 1 receptor (AT1) at position 111 was suggested by molecular modeling. This involves a cascade of conformational changes in spatial positions of side chains along transmembrane helix (TM3) from L112 to Y113 to F117, which in turn, results in conformational changes in TM4 (residues I152 and M155) leading to the movement of TM4 as a whole. The mechanism is consistent with the available data of site-directed mutagenesis, as well as with correct predictions of constitutive activity of mutants L112F and L112C. It was also predicted that the double mutant N111G/L112A might possess basal constitutive activity comparable with that of the N111G mutant, whereas the double mutants N111G/Y113A, N111G/F117A, and N111G/I152A would have lower levels of basal activity. Experimental studies of the above double mutants showed significant constitutive activity of N111G/L112A and N111G/F117A. The basal activity of N111G/I152A was higher than expected, and that of N111G/Y113A was not determined due to poor expression of the mutant. The proposed mechanism of constitutive activity of the AT(1) receptor reveals a novel nonsimplistic view on the general problem of constitutive activity, and clearly demonstrates the inherent complexity of the process of G protein-coupled receptor (GPCR) activation.


Stapes surgery in profound hearing loss due to otosclerosis.
This study was designed to determine the effectiveness of stapes surgery in patients with profound hearing loss related to far-advanced otosclerosis and if improvement in hearing is sufficient to avoid the need for cochlear implantation. Retrospective chart review. We retrospectively studied the charts of 16 patients who had stapes surgery in 1 or 2 ears between 2005 and 2010 for far-advanced otosclerosis. These patients were all candidates for a cochlear implant according to our institution's criteria but were offered stapes surgery first. Preoperative and postoperative audiologic data, surgical data, postoperative satisfaction, and telephone use were noted. Sixteen patients were included, 3 of which had had bilateral surgery. Status of the oval window was evaluated at the time of surgery. Sixteen footplates had bipolar otosclerosis, and 3 had obliterative otosclerosis. Average gain in air-conduction threshold pure-tone average was 33 dB (range, 13-52 dB) and average gain in speech perception scores was 54.4% (range, 0%-93%); 94% of the patients were satisfied by the surgery, and 94% were able to use the phone postoperatively. Overall, 87% of the patients had sufficient improvement to no longer be candidates for cochlear implantation. Stapes surgery in patients with profound hearing loss due to otosclerosis is safe and can restore enough hearing to make ears aidable and averting the need to consider cochlear implantation. 3, Retrospective series.


Trusting the record.
This paper aims to contribute to a longstanding interest in documents and paperwork in healthcare work through an examination of everyday work with patient records in a clinic. An ethnographic study of record keeping practices in a deliberate self harm clinic was conducted to consider the role that document work plays in the development of trust in the routine social interactions of a working division of labor. Issues of trust are seen to play central roles within the complexities of organizational working and some consequent implications for the deployment and use of electronic medical record systems are considered.


Retinoic Acid Negatively Impacts Proliferation and MCTC Specific Attributes of Human Skin Derived Mast Cells, but Reinforces Allergic Stimulability.
The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were exposed to RA for seven days and investigated by flow-cytometry (BrdU incorporation, Annexin/PI, FcεRI), microscopy, RT-qPCR, histamine quantitation, protease activity, and degranulation assays. We found that while MC size and granularity remained unchanged, RA potently interfered with MC proliferation. Conversely, a modest survival-promoting effect from RA was noted. The granule constituents, histamine and tryptase, remained unaffected, while RA had a striking impact on MC chymase, whose expression dropped by gene and by peptidase activity. The newly uncovered MRGPRX2 performed similarly to chymase. Intriguingly, RA fostered allergic MC degranulation, in a way completely uncoupled from FcεRI expression, but it simultaneously restricted MRGPRX2-triggered histamine release in agreement with the reduced receptor expression. Vitamin-A-derived hormones thus re-shape skin-derived MCs numerically, phenotypically, and functionally. A general theme emerges, implying RA to skew MCs towards processes associated with (allergic) inflammation, while driving them away from the skin-imprinted MCTC ("MCs containing tryptase and chymase") signature (chymase, MRGPRX2). Collectively, MCs are substantial targets of the skin retinoid network.


Multiple marker evaluation in human prostate cancer with the use of tissue-specific antigens.
Serum prostate-specific antigen and prostatic acid phosphatase were simultaneously evaluated in 22 healthy males, 29 patients with benign prostatic hypertrophy, and 192 patients with prostate cancers at various stages as well as in 30 patients with cancers other than prostate cancer. Both markers were quantitated by specific sandwich-type, enzyme-linked, immunosorbent assays with the use of specific antiserum reagents. Serum assays revealed a discordance between these two markers; thus expressions of these two biochemically and immunologically distinct prostate-specific proteins may reflect different aspects in the biology of prostate cancer. A combination test with the use of 7.5 ng of prostate antigen and 15.5 ng of prostatic acid phosphatase/ml of serum, respectively, as cutoff values resulted in a positive detection rate of 58% for prostate cancers of stages A (7/12) and B (21/36) each, 68% for prostate cancer of stage C (19/28), 92% for prostate cancer of stage D (106/116), and only 10% for benign prostatic hypertrophy (3/29). None of 52 other cancers or healthy controls was registered as positive. This study demonstrates that a multiple marker test of tissue-specific antigens can be of an additive value in the immunodiagnosis of cancer and may be a logical and effective approach at this time, in light of the unavailability of human tumor-specific markers.