Treatment with coumarin to prevent or delay recurrence of malignant melanoma.
Both coumarin (1,2-benzopyrone) and warfarin (4-hydroxycoumarin) have been shown to prevent the recurrence of malignant melanoma. Their action is macrophage-dependent and the dosage is critical. In 1984 a multicentre, prospective, randomised, double-blind trial of coumarin, given as a daily 50-mg dose for 2 years after surgery in patients with high-risk melanoma, was started. the patients had lesions greater than 1.70 mm thick and TNM stage IB or stage II disease. To date there are 4 recurrences in the coumarin-treated group of 13 patients, and 10 recurrences in the placebo-treated group of 14 patients (P < 0.01). There were no toxic effects.


Recent advances in arsenic mitigation in rice through biotechnological approaches.
Arsenic (As) is a major threat to the environment and human health due to its toxicity and carcinogenicity. Occurrence of alarming concentrations of As in water and soil leads to its bioaccumulation in crops which is a major health concern globally. Rice (Oryza sativa) is a staple food for a large population staying in As contaminated areas so, it is of utmost importance to reduce As levels in rice, especially grains. Amongst several strategies in practice, biotechnology may provide an effective option to reduce As accumulation in rice grains. Genetic engineering can be a viable approach to exploit potential genes playing roles in As metabolism pathway in plants. Besides, developing low As accumulating rice varieties through breeding is also an important area. Identifying genotypic variation in rice is a crucial step toward the development of a safe rice cultivar for growing in As-affected areas. Significant genotypic variation has been found in rice varieties for As accumulation in grains and that is attributable to differential expression of transporters, radial oxygen loss, and other regulators of As stress. This review provides recent updates on the research advances leading to transgenic and breeding approaches adopted to reduce As levels in rice, especially grains.


Single Molecule Approaches in RNA-Protein Interactions.
RNA-protein interactions govern every aspect of RNA metabolism, and aberrant RNA-binding proteins are the cause of hundreds of genetic diseases. Quantitative measurements of these interactions are necessary in order to understand mechanisms leading to diseases and to develop efficient therapies. Existing methods of RNA-protein interactome capture can afford a comprehensive snapshot of RNA-protein interaction networks but lack the ability to characterize the dynamics of these interactions. As all ensemble methods, their resolution is also limited by statistical averaging. Here we discuss recent advances in single molecule techniques that have the potential to tackle these challenges. We also provide a thorough overview of single molecule colocalization microscopy and the essential protein and RNA tagging and detection techniques.


Epigeic spiders, their potential prey and competitors: Relationship between size and frequency.
In an analysis of 67 pitfall trap studies in different environments a positive correlation is found between the abundance of spiders and their potential prey, individual main prey groups and individual predator groups. The body-size of spiders and potential prey is significantly correlated both during the day in one locality and between five different localities. Spiders match the size spectrum of their potential prey by an almost equally broad spectrum, whilst the size spectrum of other predator groups is narrower. Therefore, in all size classes spiders exercise optimal predator pressure upon their potential prey. It is suggested that there may be a significant role for spiders as a multi-predator complex in reducing a multi-prey complex.


Percutaneous angioplasty of portal vein stenosis that complicates liver transplantation: the mid-term therapeutic results.
We wanted to evaluate the mid-term therapeutic results of percutaneous transhepatic balloon angioplasty for portal vein stenosis after liver transplantation. From May 1996 to Feb 2005, 420 patients underwent liver transplantation. Percutaneous transhepatic angioplasty of the portal vein was attempted in six patients. The patients presented with the clinical signs and symptoms of portal venous hypertension or they were identified by surveillance doppler ultrasonography. The preangioplasty and postangioplasty pressure gradients were recorded. The therapeutic results were monitored by the follow up of the clinical symptoms, the laboratory values, CT and ultrasonography. The overall technical success rate was 100%. The clinical success rate was 83% (5/6). A total of eight sessions of balloon angioplasty were performed in six patients. The mean pressure gradient decreased from 14.5 mmHg to 2.8 mmHg before and after treatment, respectively. The follow up periods ranged from three months to 64 months (mean period; 32 months). Portal venous patency was maintained in all six patients until the final follow up. Combined hepatic venous stenosis was seen in one patient who was treated with stent placement. One patient showed puncture tract bleeding, and this patient was treated with coil embolization of the right portal puncture tract via the left transhepatic portal venous approach. Percutaneous transhepatic balloon angioplasty is an effective treatment for the portal vein stenosis that occurs after liver transplantation, and our results showed good mid-term patency with using this technique.


Effects of dosimetric and clinical uncertainty on complication-free local tumor control.
A mathematical description is developed to demonstrate the effects of uncertainty on complication-free local tumor control. Responses of tumors and normal tissues are modeled by conventional radiobiological models. Uncertainties are considered in the delivery of absorbed dose to the target volume and the normal tissue at risk for complications. The degree by which uncertainties compromise complication-free local control for target volumes with various tumor cell burdens is calculated.


Preceptorship: using an ethical lens to reflect on the unsafe student.
Patient safety has become a worldwide health concern, and health care professionals have a moral and ethical responsibility to promote patient safety. The clinical education of many health care professionals often involves a preceptorship or field experience wherein students are assigned to work one-to-one with a preceptor or field educator so that they can be socialized into the profession and receive a reality-oriented experience. Health care professionals who accept the responsibility of being a preceptor face additional workload and stress, especially when the students to whom they are assigned are not meeting the expectations of safe, professional practice. Taking a stand against unsafe students is an important way for preceptors to promote patient safety. Given the nature of the stress and the inherent ethical issues associated with precepting an unsafe student, it is useful to examine this experience through an ethical lens. Included in this article is a brief overview of preceptorship as a model of clinical education, together with a discussion of the nature of the ethical decisions that preceptors face when precepting an unsafe student. Ethical theories, namely, virtue ethics and utilitarianism, are also explored and serve to provide the ethical lens through which preceptors can reflect upon their experiences with unsafe students.


Predictors of outcome of chest tube drainage of nonpurulent exudative pleural effusions.
Although chest tube drainage is the primary management method for many pleural effusions, it has a failure rate of 9.4-48%. In this study, we examined the factors that predict the outcome of management of nonpurulent exudative effusions. The aim of this study was to determine the predictors of outcomes of chest tube drainage of pleural effusions. Consecutive patients who had a chest tube drainage of nonpurulent exudative pleural effusions were followed up in a prospective observational cohort study until extubation and discharge. Data on the management of the patients were recorded, analysed and compared between groups of patients with good and poor outcomes. Of the 52 patients studied, 38 had good outcomes, while 14 had poor outcomes. The mean±sd age was 39.7±15.9 years. Multivariate analysis demonstrated that empyema thoracis complicating drainage was an independent predictor of a poor outcome, while the duration of drainage ≤14 days and duration of illness before presentation <30 days were predictive of a good outcome. Our results show that the development of empyema thoracis during drainage, a long duration of drainage and a prolonged period of illness before presentation are predictive of the outcome of chest tube drainage.


MDCC-Net: Multiscale double-channel convolution U-Net framework for colorectal tumor segmentation.
Multiscale feature fusion is a feasible method to improve tumor segmentation accuracy. However, current multiscale networks have two common problems: 1. Some networks only allow feature fusion between encoders and decoders of the same scale. It is obvious that such feature fusion is not sufficient. 2. Some networks have too many dense skip connections and too much nesting between the coding layer and the decoding layer, which causes some features to be lost and means that not enough information will be learned from multiple scales. To overcome these two problems, we propose a multiscale double-channel convolution U-Net (MDCC-Net) framework for colorectal tumor segmentation. In the coding layer, we designed a dual-channel separation and convolution module and then added residual connections to perform multiscale feature fusion on the input image and the feature map after dual-channel separation and convolution. By fusing features at different scales in the same coding layer, the network can fully extract the detailed information of the original image and learn more tumor boundary information. The segmentation results show that our proposed method has a high accuracy, with a Dice similarity coefficient (DSC) of 83.57%, which is an improvement of 9.59%, 6.42%, and 1.57% compared with nnU-Net, U-Net, and U-Net++, respectively. The experimental results show that our proposed method has good performance in the segmentation of colorectal tumors and is close to the expert level. The proposed method has potential clinical applicability.


Immunocytochemical detection of the onco-developmental protein oncomodulin in pre-neoplastic and neoplastic hepatocellular lesions during hepatocarcinogenesis in rats.
Oncomodulin is a calcium-binding protein, detectable in extra-embryonic human and rat placental cells and in a wide variety of tumors, but not in any normal embryonic or adult rodent or human tissues. It is also absent from proliferatively active fetal or regenerating adult rat liver. The presence of this oncodevelopmental marker was investigated in pre-neoplastic and neoplastic liver lesions during hepatocarcinogenesis induced in rats by DENA treatment, using an antibody raised against purified oncomodulin. Positive immunostaining was observed in foci of altered hepatocytes, in neoplastic nodules and in HC, but not in the histologically normal surrounding liver parenchyma. The proportion of oncomodulin-positive foci gradually rose from 20-25% at 2-3 months after DENA treatment, to about 88% at 6 months and later. The proportion of positive neoplastic nodules increased from 50% at 5 months to about 73% (range 36-100) at 9 months and later; 88% of the HC found 10 to 20 months after DENA treatment were also positive. That early neoplastic nodules are oncomodulin-positive in a proportion (50%) similar to that of foci after the same duration of treatment is consistent with a lineage relationship between them but makes it unlikely that oncomodulin expression conditions the focus-nodule transition. The role, if any, of oncomodulin in malignant progression remains to be elucidated. It seems out of the question that it is a simple correlate of proliferative activity.


Adherens junction assembly and function in the Drosophila embryo.
Adherens junctions are essential for the development and physiology of epithelial tissues. The Drosophila embryo is an excellent model for understanding adherens junction assembly, maintenance, and regulation during tissue development. Here, I review our current state of knowledge in this model system. The review begins by outlining the structure of the cadherin-catenin complex in Drosophila including core (DE-cadherin, Armadillo, α-catenin, and p120-catenin) and peripheral proteins. Then, it summarizes adherens junction assembly at cellularization and maturation at gastrulation. Finally, the regulation of adherens junctions during tissue morphogenesis is discussed. This discussion compares major morphogenetic events in the embryo (invagination of the ventral furrow, convergent extension of the germband, flattening of the amnioserosa, maintenance of tissue borders, epithelial branching, lumen formation, cell delamination, cell division, apoptosis, and dorsal closure) and common mechanisms involved (myosin activity, endocytosis, and mesenchymal-to-epithelial transitions).


The hippocampal formation is necessary for rats to learn and remember configural discriminations.
A negative patterning discrimination problem was arranged by reinforcing rats for bar pressing when either a light or tone was presented (L+/T+) but not reinforcing the response when the compound stimulus, light and tone, was presented (LT-). To solve this problem, the animal must be able to construct a unique configural representation of the compound that can be distinguished from the representations of the individual elements. We have proposed that the hippocampal formation is essential for the acquisition and retention of associations involving configural representations. Thus, our theory predicts that animals with hippocampal formation damage will not learn the negative patterning problem and that animals who learned this problem before receiving hippocampal formation damage will not retain the solution. These predictions were confirmed by the results of two experiments. The animals with hippocampal formation damage were unable to solve the negative patterning problem. These animals were able to solve a simple discrimination in which responding in the presence of a light was rewarded but responding in the presence of a tone was not rewarded. These results are discussed in relation to several other theories of hippocampal formation function.


Dehydroepiandrosterone alters phospholipid profiles in Zucker rat muscle tissue.
Insulin-resistant muscle tissue contains low proportions of arachidonic acid (AA), and increased proportions of muscle AA correlate with improved insulin sensitivity. Dehydroepiandrosterone (DHEA) and AA, like the thiazolidinedione drugs that decrease insulin resistance (IR), are peroxisome proliferators. Long-chain fatty acids (FA) have been named the "one true" endogenous ligand for activating the peroxisome proliferator-activator receptor (PPAR), and DHEA has been named a "good candidate" as a naturally occurring indirect activator of PPAR. This study was conducted to determine DHEA's effects on lipid profiles of skeletal and cardiac muscle in lean and obese Zucker rats (ZR), a model of IR, type 2 diabetes mellitus, and obesity. We hypothesize that DHEA may alter long-chain FA profiles in muscle tissue of obese rats such that they more closely resemble that of the lean. In our experiments, we employed a DHEA and a pair-fed (PF) group (n = 6) for 12 lean and 12 obese ZR. For 30 d, the diet of the two DHEA groups was supplemented with 0.6% DHEA; PF groups were given the average daily calories consumed by their corresponding treatment group. Hearts and gastrocnemius muscles were assayed for phospholipid (PL), free FA, and triglyceride (TG) FA profiles. The proportion of PL AA was significantly greater in both muscle types of lean compared to obese rats. Hearts from both DHEA groups had greater PL proportions of AA and less oleic (18:1) acid than their PF controls. Likewise, 18:1 proportions were significantly lower in the gastrocnemius; however, AA proportions were not significantly different. Similar phenotypic profile differences were observed in the TG fraction of both muscle types. There were no DHEA-related TG FA profile alterations.


Cardiovascular health behavior and health factor changes (1988-2008) and projections to 2020: results from the National Health and Nutrition Examination Surveys.
The American Heart Association's 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health. We included 35 059 cardiovascular disease-free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988-1994 and subsequent 2-year cycles during 1999-2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0-14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7-9.1]; women=8.8 [95% confidence interval, 7.6-9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1). The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.


Recognition of purified beta 1,3/1,6 glucan and molecular signalling in the intestine of Atlantic salmon.
Atlantic salmon was orally intubated with a highly purified β-glucan product (MacroGard(®)) to study the recognition of the molecule by the receptor genes, the regulation of the downstream signalling genes and global proteins, and the micromorphological changes in the intestine. The β-glucan receptor genes of Atlantic salmon, sclra, sclrb, sclrc and cr3, seem to recognize the molecule, and initiate the downstream ITAM-motif signalling, as evident from the significantly high mRNA levels of ksyk, mapkin2, il1b and mip2a levels. Among the altered proteins, the Apoa4 (involved in carbohydrate and lipid metabolism); Tagln, Actb (uptake of β-glucan); Psma2 (associated with substrate recognition); and Ckt (energy metabolism-related) were the overexpressed ones. The underexpressed proteins included the Uk114, Rpl9, Ctsb and Lgal that are connected to proliferation, LPS-stimulation, Il1b and lactose recognition, respectively. Furthermore, the mRNA levels of igt and the number of immune cells in the distal intestine were found to increase upon β-glucan uptake by the fish. This study provides some clues on the mechanisms by which the β-glucan evokes response in Atlantic salmon, particularly at the intestinal level.


Venturing out safely: The biogeography of Homo erectus dispersal out of Africa.
The dispersal of Homo erectus out of Africa at some 1.9 million years ago is one of the most important, crucial, and yet controversial events in human evolution. Current opinions about this episode expose the contrast between those who see H. erectus as a highly social, cooperative species seeking out new ecological opportunities to exploit, and those preferring a passive, climate driven explanation for such an event. By using geostatistics techniques and probabilistic models, we characterised the ecological context of H. erectus dispersal, from its East African origin to the colonization of Eurasia, taking into account both the presence of other large mammals and the physical characteristics of the landscape as potential factors. Our model indicated that H. erectus followed almost passively the large herbivore fauna during its dispersal. In Africa, the dispersal was statistically associated with the presence of large freshwater bodies (Rift Valley Lakes). In Eurasia, the presence of H. erectus was associated with the occurrence of geological outcrops likely yielding unconsolidated flint. During the early phase of dispersal, our model indicated that H. erectus actively avoided areas densely populated by large carnivores. This pattern weakened as H. erectus dispersed over Europe, possibly because of the decreasing presence of carnivores there plus the later acquisition of Acheulean technology. During this later phase, H. erectus was associated with limestone and shaley marl, and seems to have been selecting for high-elevation sites. While our results do not directly contradict the idea that H. erectus may have been an active hunter, they clearly point to the fact that predator avoidance may have conditioned its long-distance diffusion as it moved outside Africa. The modelled dispersal route suggests that H. erectus remained preferentially associated with low/middle latitude (i.e., comparatively warm) sites throughout its colonization history.


Nuclear beta-globin RNA transcripts initiated in vitro with gamma-thio nucleoside triphosphate.
We have been able to obtain significant levels of apparently in vitro-initiated beta-globin transcripts from isolated nuclei using mouse Friend cells. The level of hybrid selected beta-globin transcripts was increased 3-9-fold in nuclei after the cells were induced with dimethylsulfoxide. The newly initiated transcripts were detected through incorporation of gamma-thio ATP and isolation by Hg-agarose chromatography. The 5'-terminus was identified by recovery of the thio tetraphosphate in hydrolysis products from in vitro initiated RNA using gamma-35S ATP.


[An uncommon property of a rhenium (V) complex containing nicotinamide to increase the conductivity of lipid membranes].
Under influence of a binuclear complex compound [Re2(Ph3P)2(ANA)2O3Cl4] a sharp increase (on 2-3 ranges) of conductivity of bilayer lipid membranes (BLM) was found. Then it slowly decreased to some stable level. Similar properties were earlier discovered among some detergents of polyethylene ether nature. A supposition is made about structure rebuilding in BLM, that had place between detergents and lipid molecules of cell membranes.


Insulin resistance in spontaneously hypertensive rats but not in deoxycorticosterone-salt or renal vascular hypertension.
To investigate whether the reported association between insulin resistance and hypertension in spontaneously hypertensive rats (SHR) is a primary defect or a secondary phenomenon in hypertension. Comparisons of glucose metabolism between three groups of hypertensive rats: deoxycorticosterone (DOCA)-salt hypertensive rats; two-kidney, one clip renovascular hypertensive (RVH) rats; SHR; and their respective control groups. There was also an additional group of weight-matched SHR and respective Wistar-Kyoto (WKY) controls. A trace amount of 3H-deoxyglucose (3H-DOG) was administered in vivo to evaluate its plasma half-life and tissue uptake. In vitro adipose tissue segments were incubated with 14C-glucose and increasing doses of insulin. Compared with age-matched WKY rats, SHR had significantly higher insulin levels, longer plasma half-life and lower 3H-DOG uptake by heart and striated muscle. Plasma glucose levels and incorporation of 14C-glucose into CO2, triglycerides and glycogen by adipose tissue in response to increasing insulin concentrations was similar for both groups of SHR and WKY rats. No differences were found between hypertensive rats and controls in either the DOCA or RVH groups. Evidence of insulin resistance in spontaneous, but not secondary, rat hypertension indicates that the resistance is a primary rather than a secondary event in hypertension.


Opportunities to expand postpartum support for those in recovery from opioid use disorder: Results from a qualitative study.
Over the past two decades the national prevalence of opioid use disorder (OUD) during pregnancy has increased more than 600%. Managing recovery from OUD during the postpartum period can be particularly challenging. Thus, we sought to identify ways to expand perinatal OUD treatment to ultimately reduce risk of postpartum return to opioid misuse. We conducted in-depth semi-structured interviews with pregnant or postpartum (i.e., gave birth within the past year) mothers who have OUD, as well as with professionals who work with this population. Interviews were audio-recorded, transcribed, and coded for themes using Dedoose software using an eco-social framework. Participants included 7 mothers (median age 32 years old; 100% receiving treatment for OUD) and 11 professionals (average of 12.5 years in the field; n=7 healthcare providers, n=4 child safety caseworkers). A total of 10 major themes emerged in three levels. First, at an individual level themes included mental health, personal responsibility, and individual agency. Second, at the inter-individual level themes included support from friends and family, and other sources of support. Next, at the systems/institutional level themes included culture of healthcare systems, an ill-equipped healthcare system, social determinates of health, and continuum of care. Finally, a theme identified across all three levels included keeping mother and baby together. Several opportunities to enhance the support and clinical care of OUD during the perinatal period were identified. Additional work is needed to explore how these themes may be incorporated into existing programs and/or the development of new interventions.


Development and validation of multivariate models integrating preoperative clinicopathological and radiographic findings to predict HER2 status in gastric cancer.
The combination of trastuzumab and chemotherapy is recommended as first-line therapy for patients with human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancers (GCs). Successful trastuzumab-induced targeted therapy should be based on the assessment of HER2 overexpression. This study aimed to evaluate the feasibility of multivariate models based on hematological parameters, endoscopic biopsy, and computed tomography (CT) findings for assessing HER2 overexpression in GC. This retrospective study included 183 patients with GC, and they were divided into primary (n = 137) and validation (n = 46) cohorts at a ratio of 3:1. Hematological parameters, endoscopic biopsy, CT morphological characteristics, and CT value-related and texture parameters of all patients were collected and analyzed. The mean corpuscular hemoglobin concentration value, morphological type, 3 CT value-related parameters, and 22 texture parameters in three contrast-enhanced phases differed significantly between the two groups (all p < 0.05). Multivariate models based on the regression analysis and support vector machine algorithm achieved areas under the curve of 0.818 and 0.879 in the primary cohort, respectively. The combination of hematological parameters, CT morphological characteristics, CT value-related and texture parameters could predict HER2 overexpression in GCs with satisfactory diagnostic efficiency. The decision curve analysis confirmed the clinical utility.


STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming.
The cohesin complex participates in the organization of 3D genome through generating and maintaining DNA loops. Stromal antigen 2 (STAG2), a core subunit of the cohesin complex, is frequently mutated in various cancers. However, the impact of STAG2 inactivation on 3D genome organization, especially the long-range enhancer-promoter contacts and subsequent gene expression control in cancer, remains poorly understood. Here we show that depletion of STAG2 in melanoma cells leads to expansion of topologically associating domains (TADs) and enhances the formation of acetylated histone H3 lysine 27 (H3K27ac)-associated DNA loops at sites where binding of STAG2 is switched to its paralog STAG1. We further identify Interferon Regulatory Factor 9 (IRF9) as a major direct target of STAG2 in melanoma cells via integrated RNA-seq, STAG2 ChIP-seq and H3K27ac HiChIP analyses. We demonstrate that loss of STAG2 activates IRF9 through modulating the 3D genome organization, which in turn enhances type I interferon signaling and increases the expression of PD-L1. Our findings not only establish a previously unknown role of the STAG2 to STAG1 switch in 3D genome organization, but also reveal a functional link between STAG2 and interferon signaling in cancer cells, which may enhance the immune evasion potential in STAG2-mutant cancer.


Measuring Anxiety in Children: The Importance of Separate Mother and Father Reports.
Previous research suggests that it is important to use parental reports when assessing children's anxiety, but it remains unclear to what extent there are differences between mothers' and fathers' scores and whether these potential differences have any repercussions for the psychometric properties of the scale being used. This study was conducted to investigate parental differences on the Parent version of the Screen for Child Anxiety Related Emotional Disorders-Revised (SCARED-RP), a rating scale for measuring child anxiety symptoms. The second aim was to re-examine the reliability and validity of the SCARED-RP, in light of these possible differences. The SCARED-RP and the Child Behaviour Checklist (CBCL) were administered to parents of clinically anxious children (n = 81), and control children (n = 108). All children (n = 189) completed the SCARED-R. Significant correlations between mother and father reports were found within the clinically anxious sample. Mothers showed significantly more correspondence with their children in the control group than fathers. The SCARED-RP internal consistency on total scale was excellent (mothers: .94; fathers: .94) and moderate to good for all subscales (from .66 Situational-Environmental Phobia to .93 Animal Phobia). The SCARED-RP differentiated well between clinically anxious and control children (mother and father data). The concurrent validity was supported by strong correlations with the CBCL anxious-depressed scale. Differences between mother and father reports suggest the importance of obtaining information from both parents separately. Furthermore, the SCARED-RP is a useful instrument for assessing children's anxiety disorder symptoms in clinical and research settings.


FGF-2-induced functional improvement from neonatal motor cortex injury via corticospinal projections.
The administration of basic fibroblast growth factor (FGF-2) to rats with postnatal 10 (P10) motor cortex (MCx) lesions results in functional improvements accompanied with filling of the previously lesioned area with tissue. In the present experiment, we tested the prediction that FGF-2 induces functional recovery by promoting meaningful reconnection of neurons from the filled region to the periphery. Rats received bilateral MCx lesions on P10 and subcutaneous injections of either vehicle or FGF-2 for 7 days beginning on P11. In adulthood, we evaluated the physiology and anatomy of corticospinal projections using intracortical microstimulation together with recordings of evoked electromyographic (EMG) activity in wrist extensors, and anterogradely tracing projecting axons using biotin dextran amine. We found that activity could be induced in the wrist extensors following stimulation of the filled region with onset delays comparable to undamaged corticospinal tract fibers in 5 out of 7 lesioned, FGF-2 treated rats. Furthermore, in the rats in which EMG activity could be elicited, long descending axons were labeled with projections into the spinal cord comparable to corticospinal tracts from undamaged motor cortex. Our results demonstrate that FGF-2 treatment restores the connectivity of the filled region in neonatal rats. This provides a possible mechanism for FGF-2-induced functional recovery.


Corrigendum: Brief Mindfulness Meditation Improves Attention in Novices: Evidence From ERPs and Moderation by Neuroticism.
[This corrects the article DOI: 10.3389/fnhum.2018.00315.].


[The hygienic validation of the principles of dispensary care for workers in industrial enterprises engaged in the processing of hydrocarbon raw material with a high content of sulfur compounds].
The article justified hygienic principles for occupational screening in workers of Astrakhan gas-processing plant. The authors described algorithm to determine the jeopardy and hazard levels (ratings) for the individual workplaces, in accordance with the actual levels and concentrations of occupational hazards. The studies helped to assign the workers to several dispensary groups according to the occupational risk, length of service at every workplace and health state by the examination.


Sex-specific cytotoxicity of ostarine in cardiomyocytes.
Ostarine is the most popular compound in the selective androgen receptor modulator group (SARMs). Ostarine is used as a physical performance-enhancing agent. The abuse of this agent in higher doses may lead to severe side effects. Here, we evaluate the effects of ostarine on the heart. We utilized a cardiomyocyte H9C2 cell line, isolated primary female and male cardiac fibroblast cells, as well as hearts obtained from rats. Ostarine increased the accumulation of two fibrosis protein markers, αSMA and fibronectin (p < 00.1) in male, but not in female fibroblast cells. Ostarine increased the expression of the cardiomyopathy marker βMhc in the H9C2 cell line (p < 0.05) and in the heart in rats (p < 0.01). The unfavorable changes were observed at high ostarine doses. Moreover, a decrease in viability and an increase in cytotoxicity marker LDH were observed already at lowest dose (1 nmoL/l). Taken together, our results suggest that ostarine is cardiotoxic which may be more relevant in males than in females.


Iron transport in Francisella in the absence of a recognizable TonB protein still requires energy generated by the proton motive force.
The mechanism of iron transport in Francisella is still a puzzle since none of the sequenced Francisella strains appears to encode a TonB protein, the energy transducer of the proton motive force necessary to act on the bacterial outer membrane siderophore receptor to allow the internalization of iron. In this work we demonstrate using kinetic experiments of radioactive Fe(3+) utilization, that iron uptake in Francisella novicida, although with no recognizable TonB protein, is indeed dependent on energy generated by the proton motive force. Moreover, mutants of a predicted outer membrane receptor still transport iron and are sensitive to the iron dependent antimicrobial compound streptonigrin. Our studies suggest that alternative pathways to internalize iron might exist in Francisella.


Effects of rapamycin-induced oligomerization of parvalbumin, Stim1 and Orai1 in puncta formation.
Elevations of cytosolic Ca2+ from the endoplasmic reticulum (ER) regulate a diverse range of cellular processes. When these luminal stores become depleted, the transmembrane ER protein Stim1 oligomerizes and translocates within the ER membrane to puncta junctions to couple with Orai1 channels, activating store-operated calcium entry (SOCE). Stim1 oligomerization and puncta formation have generally been associated with its luminal domains, however, studies have implicated that the cytoplasmic domains may contribute to this oligomerization. Studies have also suggested that intermediate or regulating elements may be required to fine-tune puncta formation and activation of SOCE. Here we made fusion proteins of Stim1 and Orai1 with FRB and FKBP12 domains that associate in the presence of rapamycin. Rapamycin-induced coupling of Stim1 to Stim1, Orai1 to Orai1 and Stim1 to Orai1 was found to be insufficient for puncta formation. Rapamycin was then used to recruit the cytosolic Ca2+ buffer protein parvalbumin (Pav) to Stim1 in order to buffer the local cytosolic Ca2+ near the ER membrane. Interestingly, Pav buffering near the ER caused puncta formation that was indistinguishable from those caused by thapsigargin. Our results suggest that Stim1 oligomerization and puncta formation may be additionally regulated either by local Ca2+ levels near the ER membrane or by as yet unidentified Ca2+-dependent proteins interacting with the cytoplasmic domains of Stim1.


Xanthine biosensor based on the direct oxidation of xanthine at an electrogenerated oligomer film.
Poly(o-aminophenol-co-pyrogallol) (PAP) was first synthesized via the electrochemical copolymerization of o-aminophenol and pyrogallol in the acidic solution, using a reduced graphene oxide/glassy carbon (RGO/GC) electrode as a working electrode. Reduced graphene oxide played an important role in increasing PAP amount deposited on the RGO/GC electrode compared to that on the bare GC electrode, which is due to that RGO has the large specific surface area. The results from the spectra of IR, (1)H NMR and ESR and the measurement of molecular weight demonstrated that PAP is an oligomer with the free radicals and exhibited good redox activity in a wide pH range from pH<1-9.0 and can effectively catalyze xanthine oxidation due to the presence of the free radicals and the reversible redox groups in the copolymer chain. On the basis of the direct oxidation of xanthine on PAP, the PAP/RGO/GC electrode was used as a xanthine biosensor. The biosensor showed a linear range from 1.0 to 120μM xanthine at pH 6.0 with a correction coefficient of 0.9965 and fast response to xanthine oxidation. The peak potential of xanthine oxidation shifted from 0.814 to 0.668V as pH increased from 5.0 to 7.5.


Genetic analysis of MC1R variants in Chinese Han patients with sporadic Parkinson's disease.
Parkinson's disease (PD, OMIM 168600) is a neurodegenerative disorder featured by degeneration of melanin-positive dopaminergic neurons. Epidemiologic studies have suggested that PD and malignant melanoma (MM) might share common genetic components. Recently, the p.R160W variant in the melanocortin 1 receptor gene (MC1R, OMIM 155555), a risk factor for MM, has been identified to be associated with PD in Spanish population. To explore whether the MC1R variants are associated with sporadic PD in Chinese population, we designed a case-control comparison study and studied three variants, including rs3212366 (p.F196L), rs33932559 (p.I120T) and rs34090186 (p.R67Q), in the MC1R gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls. For rs3212366, only the TT genotype was identified in both PD and control cohorts. For variants rs33932559 and rs34090186, we did not identify any statistically significant difference in either genotypic distribution or allelic distribution between the PD cohort and control cohort, and in addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that none of the three variants of the MC1R gene and related haplotypes be associated with sporadic form of PD in Chinese Han population from Mainland China.


The Swedish version of the Lumbar Spine Instability Questionnaire: A clinimetric study of validity and reliability.
The Lumbar Spine Instability Questionnaire (LSIQ) is a patient-reported outcome measure (PROM) suggested to measure clinical instability of the spine. The aim was to translate and cross-culturally adapt the LSIQ into Swedish and to test its measurement properties. We included people with low back pain (LBP) seeking primary care (n = 101). The LSIQ was translated using international recommendations. Construct validity was investigated via the Roland Morris Disability Questionnaire (RM) and the Numeric Pain Rating Scale (NPRS). Reliability was tested via test-retest (Intra Class Correlation, ICC2.1) (n = 50) and by analyzing internal consistency (Cronbach Alpha). A suggested cutoff score was used to study discriminative ability. The LSIQ was successfully translated into Swedish. For construct validity, a moderate correlation was shown with the RM (rho 0.58) and the NPRS (rho 0.47). Test-retest demonstrated high reliability for the total score (ICC2.1 0.94, 95% CI 0.86-0.96). Internal consistency reached a Cronbach Alpha of 0.64. Participants scoring higher on the LSIQ (≥9) showed significantly higher pain and lower disability levels, were of higher age and less physically active. The Swedish LSIQ shows acceptable measurement properties regarding test-retest reliability and validity. To further study the usefulness of the LSIQ and the suggested cutoff score, the dimensionality needs to be investigated.


Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: A cross-sectional observation.
Trabecular bone score (TBS) is a parameter of bone quality that has been shown to be related to vertebral fractures. This study aimed to analyze the difference in discriminatory power of TBS for vertebral fractures according to the bone mineral density (BMD) T-score. Areal BMD at the lumbar spine (LS, L1-L4), femur neck (FN) and total hip were assessed using dual x-ray absorptiometry (Discovery W, Hologic, Bedford, MA) in 929 women aged 50years or older. TBS was analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the thoracic and lumbar spine using a semi-quantitative method. The study subjects consisted of 158 subjects (17.0%) with normal BMD, 461 (49.6%) with osteopenia and 310 (33.4%) with osteoporosis. The incident vertebral fractures were observed in 92 (9.9%) subjects, including 59 fractures in osteoporosis, 29 fractures in osteopenia, and only 4 fractures in normal BMD. We stratified study subjects into two groups according to their BMD T-scores, osteoporosis or osteopenia/normal BMD. The logistic regression model showed that LS BMD values per each 1 standard deviation (SD) decrease were significantly associated with increased risk of vertebral fracture in both osteoporosis and osteopenia/normal BMD group with stronger association in osteoporosis group. However, a TBS value that was lower by 1SD was significantly associated with vertebral fracture risk only in the osteopenia/normal BMD group. The TBS use in addition to FN BMD and age also showed significantly better discriminatory power for vertebral fracture only in the osteopenia/normal BMD group, but not osteoporosis group. In conclusion, TBS is significantly associated with vertebral fractures in subjects with osteopenia/normal BMD levels. Additional assessment of bone microarchitecture using TBS is better able to identify women at risk of fracture, in particular, those with relatively higher BMD.


Discovering pathway biomarkers of hepatocellular carcinoma occurrence and development by dynamic network entropy analysis.
Gene expression profiling techniques measure the transcription of thousands of genes in a parallel manner. With more and more hepatocellular carcinoma (HCC) transcriptomic data becoming available, the high-throughput data provides an unprecedented opportunity to discover HCC diagnostic biomarkers. In this work, we propose a bioinformatics method based on dynamic network entropy analysis, called DNEA, to identify potential pathway biomarkers for HCC occurrence and development by integrating transcriptome and interactome. We firstly collect the pathways documented in different knowledge-bases and then impose the genome-wide human transcriptomic data of multistage cancerous tissues during the development and progression of HCC. After linking the gene sets of pathways into individual connected networks, we map the corresponding gene expression information onto these pathways. The dynamic network entropy of individual pathways is calculated to evaluate its activities and dysfunctionalities during the disease occurrence and development. We use the overall significant difference in the entropic dynamics during the time course to prioritize distinctive pathways during disease progression. Then machine learning classification methods are employed to screen out pathway biomarkers with the classification ability to distinguish different-stage samples of HCC progression. Pathway biomarkers discovered based on DNEA demonstrate good classification performance in measuring HCC progression. The classification accuracy is as follows: DNA replication pathway (mean AUC = 0.82, 20 genes) from KEGG, FMLP pathway (mean AUC = 0.84, 14 genes) from BioCarta, and downstream signaling of activated FGFR pathway (mean AUC = 0.80, 15 genes) from Reactome. At the same time, previous studies have shown that these genes and pathways screened are closely related to the occurrence and development of HCC in terms of oncogenesis dysfunctions. Our method for cancer biomarker discovery based on dynamic network entropy analysis is effective and efficient in identifying pathway biomarkers related to the progression of complex diseases.


The calcium accumulation in a microsomal fraction from porcine coronary artery smooth muscle. A study of the heterogeneity of the fraction.
1. Microsomes prepared from the combined media and intima of pig coronary artery, take up Ca in an ATP-dependent way. This uptake is stimulated by oxalate. 2. Conditions have been determined to optimize the preparation of the microsomes in terms of their Ca accumulation activity. Careful homogenization of the tissue mince in 0.25 M sucrose by means of a Potter-Elvehjem homogenizer gives microsomal preparations with the highest specific activity for Ca accumulation. 3. Arguments are presented to support the hypothesis that, even in the absence of oxalate, Ca accumulation occurs into the lumen of the vesicles, and that these vesicles have a low Ca permeability. 4. Density gradient analysis shows that the microsomal fraction prepared from pig coronary artery media and intima is composed of vesicles that are heterogeneous in enzymatic composition. 5. Adenylate cyclase appears to be a predominantly plasma membrane-bound enzyme. Rotenone-insensitive NADH-cytochrome c reductase and choline phosphotransferase, two putative markers for internal membranes, give distinct banding patterns on on isopycnic centrifugation, indicating different intracellular localization. 6. There is a difference between the density gradient distribution pattern of Ca uptake measured in the presence or absence of oxalate. The latter coincides more closely with plasma membrane markers. The former resembles more the distribution of rotenone-insensitive NADH-cytochrome c reductase.


Review and resolution of some nomenclatural issues regarding the genus Psoroptes (Acari: Psoroptidae), scab-mites of domestic and wild mammals.
Some classifications recognize a number of species in the scab-mite genus, Psoroptes, mites that are of considerable importance in livestock production and veterinary medicine. However, modern studies suggest that populations from some host species are not morphologically or genetically distinct, creating taxonomic confusion with older names, which treated mites from different hosts as separate species. We review the taxonomy and nomenclature of the genus and the two oldest binomens, most recently known as Psoroptes ovis and Psoroptes equi. Prior authors have attributed these names to various authorities, with most attributing both names to Hering (Nova Acta Phys-Med Acad Caesar Leopold-Carol Nat Curios 18(2):573-624, 1838). In particular, the priority between these names was recently a point of contention, with P. ovis being treated as junior synonym of P. equi. A review of all relevant nineteenth and twentieth century publications indicates, however, that these binomens should be cited as P. ovis (Viborg in Veterinair-Selskabets Skrifter 2:139-152, 1813) and P. equi (Raspail in Bull gener Theraput Med Chir 7:169-184, 1834), with the former having priority over the latter assuming their conspecificity. We also clarify attribution of the authorship and the type species of the genus Psoroptes.


Monoclonal rat anti-Torpedo electroplax nicotinic acetylcholine receptor antibodies: immunochemical characterization.
The interaction of Torpedo californica nicotinic acetylcholine receptor (nAcChoR) with three rat monoclonal antibodies (mcab) directed against nAcChoR (Gomez et al., 1979) was studied by use of four different radioimmunoassay protocols. Each mcab reacts poorly with formalin-fixed Staphylococcus aureus or S. aureus Protein A, which requires that an additional incubation with second antibody (goat anti-rat immunoglobulin G) is included in each radioimmunoassay paradigm. One mcab inhibits 125I-labeled alpha-bungarotoxin binding to nAcChoR, recognizes a subset of solubilized nAcChoR-toxin complexes, and shows higher titer against nAcChoR in the absence of toxin. Thus, it appears to be directed against nAcChoR antigenic determinants that at least partially overlap with toxin binding sites. Two other mcab react with nAcChoR in a toxin-independent manner. Receptor-mcab dissociation constants are less than 10 nM, according to each assay paradigm. Estimates of antibody titer or concentrations of antibody in stock hybridoma supernatants vary according to the assay used. This predictable result is attributed to differences in design and sensitivity of assay protocols. The data provide a basis for further utilization of monospecific antibodies as probes in characterization of nAcChoR structure and function.


Gene expression dynamics of natural assemblages of heterotrophic flagellates during bacterivory.
Marine heterotrophic flagellates (HF) are dominant bacterivores in the ocean, where they represent the trophic link between bacteria and higher trophic levels and participate in the recycling of inorganic nutrients for regenerated primary production. Studying their activity and function in the ecosystem is challenging since most of the HFs in the ocean are still uncultured. In the present work, we investigated gene expression of natural HF communities during bacterivory in four unamended seawater incubations. The most abundant species growing in our incubations belonged to the taxonomic groups MAST-4, MAST-7, Chrysophyceae, and Telonemia. Gene expression dynamics were similar between incubations and could be divided into three states based on microbial counts, each state displaying distinct expression patterns. The analysis of samples where HF growth was highest revealed some highly expressed genes that could be related to bacterivory. Using available genomic and transcriptomic references, we identified 25 species growing in our incubations and used those to compare the expression levels of these specific genes. Video Abstract CONCLUSIONS: Our results indicate that several peptidases, together with some glycoside hydrolases and glycosyltransferases, are more expressed in phagotrophic than in phototrophic species, and thus could be used to infer the process of bacterivory in natural assemblages.


A rational approach towards selective ethylene oligomerization via PNP-ligand design with an N-triptycene functionality.
Novel PNP ligands bearing an N-triptycene backbone were developed and evaluated for selective ethylene oligomerization. Upon activation with MMAO-3A, the pre-catalyst mixture containing Cr(acac)3/ligand efficiently promotes ethylene tetramerization with remarkably high productivities (up to 1733 kg gCr-1 h-1) and C8 olefin selectivities (up to 74.1 wt%). More importantly, ligands with a PNP moiety connecting at the 1- or 1,4-position of the triptycene molecule could achieve exceptionally high alpha (1-C6 + 1-C8) selectivities, exceeding 90 wt%, as a result of high 1-C6 purity (>90 wt%) in the C6 fraction. Based on comparative catalytic studies employing various PNP ligands with or without an N-triptycene backbone, we illustrate the fact that a rational design of PNP ligands with an optimum degree of steric profile around the N-center could provide C6 cyclics controlled highly α-selective ethylene oligomerization.


Adherence to the ambulatory peritoneal dialysis procedure and limitations of care of older adults or their caregivers.
Continuous Ambulatory Peritoneal Dialysis is an appropriate technique for older adults and its success is mainly based on the correct exchange technique. However, individuals may present barriers to compliance, due to deterioration of physical and cognitive function, depression, and prevalence of visual impairments. A descriptive correlational study was conducted to determine the relationship between adherence to the continuous ambulatory peritoneal dialysis procedure and the limitations of care for older adults with chronic renal failure or their caregivers. For convenience, 54 participants from two institutions were selected. A home visit was made at exchange times and a certificate of sociodemographic variables was applied, data such as training days, time of performing the procedure and number of home visits they received were included. Adherence to the procedure was evaluated with a checklist of correctly performed steps in the dialysis technique with Ultra Bag® twin bag equipment (from Baxter). To measure care limitations, we evaluated near visual acuity with Jaeger's equivalent primer, visual fields with the confrontational visual field test, manual sensory dexterity and acuity with Moberg's Pick-Up test, cognitive function using Folstein's MMSE, and depressive symptoms using the CES-D20 instrument. In adherence to the procedure, participants correctly performed an average of 23.42 (SD ± 5.54) steps, which corresponds to 71.72% of the technique. Regarding care limitations, 55.6% presented impaired near visual acuity, 29.6% visual field deficit, 33.3% impaired manual dexterity, 14.8% alteration in manual sensory acuity, 46.3% possible impairment of cognitive function, and 18.5% depressive symptomatology. Participants with greater adherence to the CAPD procedure had better dexterity in the dominant (p = 0.010) and non-dominant (p = 0.010) hand, better sensory acuity of the non-dominant hand (p = 0.023), and greater cognitive function (p = 0.044). It is concluded that the care limitations (manual dexterity, manual sensory acuity, and cognitive function) are related to adherence to the dialytic procedure.


World-wide Prevalence of Substitutions in HCV Genome Associated With Resistance to Direct-Acting Antiviral Agents.
The efficacy of direct-acting antiviral agents against hepatitis C virus (HCV) infection can be compromised by substitutions in the HCV genome that occur before treatment (resistance-associated substitutions [RASs]). We performed a meta-analysis to determine the prevalence of RASs and their effects. We searched publication databases for studies of HCV RNA substitutions that mediate resistance to direct-acting antiviral agents. Findings from 50 studies of the prevalence of RAS in HCV, from 32 countries, were used in a meta-analysis. We retrieved the HCV RNA sequence from the Los Alamos HCV sequence database to estimate the prevalence of the RASs. The degree of resistance to treatment conferred by each RAS was determined based on fold-change in the 50% effective concentration of the drugs. Our final analysis included data from 49,744 patients with HCV infection and 12,612 HCV sequences. We estimated the prevalence of 56 RASs that encoded amino acids and 114 specific RASs. The average prevalence of RASs was highest in HCV genotype (GT) 6, followed by HCV GT1a, GT2, GT1b, GT3, and GT4. The highest prevalence of RASs observed encoded Q80K in NS3 to NS4A of HCV GT1a, Y93T in NS5A of GT1a, and C316N in NS5B of GT1b. The greatest number of RASs were observed at D168 in NS3 to NS4A, at Y93 in NS5A, and at C316 in NS5B. The prevalence of RASs and mutation burdens were high in Japan, the United States, Germany, Thailand, and the United Kingdom; low in Russia, Brazil, Egypt, and India; and intermediate in China, Canada, Australia, Spain, and France. In a meta-analysis, we found evidence for 114 RASs in HCV of different genotypes. Patients with HCV infection should be tested for RASs before treatment is selected, especially in regions with a high prevalence of RASs.


Analysis of the pharmacological properties of chicken melanocortin-2 receptor (cMC2R) and chicken melanocortin-2 accessory protein 1 (cMRAP1).
The chicken (Gallus gallus) melanocortin-2 receptor (cMC2R) can be functionally expressed in CHO cells when chicken melanocortin-2 receptor accessory protein 1 (cMRAP1) is co-expressed. The transiently transfected CHO cells responded in a robust manner to stimulation by hACTH(1-24) (EC50 value=2.7 × 10(-12)M +/- 1.3 × 10(-12)), but the transfected CHO cells could not be stimulated by NDP-MSH at concentrations as high as 10(-7)M. Incubation of cMC2R/cMRAP1 transfected cells with alanine substituted analogs of hACTH(1-24) at amino acid positions F(7) or W(9) completely blocked stimulation of the transfected cells. Similarly, incubation of cMC2R/cMRAP1 transfected cells with an analog of hACTH(1-24) with alanine substitutions at amino acid positions R(17)R(18)P(19) resulted in a 276 fold shift in EC50 value relative to the positive control (p<0.004). Collectively these observations suggest that cMC2R has binding sites for the HFRW motif and KKRRP motif of hACTH(1-24), and both motifs are required for full activation of the receptor. While previous studies had shown that Anolis carolinensis MC2R and Xenopus tropicalis MC2R could be functionally expressed in CHO cells that co-expressed mouse MRAP1, co-expression of these non-mammalian tetrapod MC2Rs with cMRAP1 resulted in a significant increase in sensitivity to hACTH(1-24), as measured by EC50 value, for A. carolinensis MC2R (p<0.005) and X. tropicalis MC2R (p<0.007). The implications of these observations are discussed.


Belief and sign, true and false: the unique of false belief reasoning.
For a long time, a controversy has been proposed that whether the process of theory of mind is a result of domain-specific or domain-general changes (Wellman in The handbook of childhood cognitive development. Blackwell Publication, New Jersey, 2011). This event-related potential study explored the neural time course of domain-general and domain-specific components in belief reasoning. Fourteen participants completed location transfer false belief (FB), true belief (TB), false sign (FS) and true sign (TS) tasks, in which two pictures told a story related to a dog that ran from a green into a red box. In the TB and FB tasks, a boy saw or did not see the transfer of the dog, respectively. In the FS and TS tasks, an arrow that pointed to the green box either altered its direction to the red box or did not alter following the transfer of the dog. Participants then inferred where the boy thought of, or the arrow indicated the location of the dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning, which is associated with domain-general components, the detection, and classification. The late slow wave (LSW) for FB was more positive at frontal, central, and parietal sites than FS because of the domain-specific component involved in FB reasoning. However, the LSW was less positive for TB than for FB but did not differ from the TS condition, which implies that mental representation might not be involved in TB reasoning.


A retrospective review of 34,109 epidural anesthetics for obstetric and gynecologic procedures at a single private hospital in Turkey.
We examined the safety of the routine use of epidural anesthesia by an experienced anesthetic team in a select group of obstetric and gynecologic patients. All anesthetic records and an obstetric department database from 1993 to 2006 were retrospectively reviewed (n = 35,628 cases). Success rate, major complication rates, and mortality rates were the major end-points of the study. We performed 34,109 epidural blocks in obstetric and gynecologic anesthesia. The epidural rate increased from 57% to 96% over a 14-yr period. Permanent neurological sequel, cardiac arrest, or mortality and maternal mortality were not seen during this period. Epidural anesthesia/analgesia, as performed in a private hospital in Turkey by five experienced anesthesiologists for a select group of patients, was a reliable and safe procedure.


Dietary intake and plasma concentrations of PUFAs in childhood and adolescence in relation to asthma and lung function up to adulthood.
PUFAs may influence the risk of asthma; however, long-term prospective studies including objective biomarkers of PUFA intake are lacking. The objective was to investigate the role of dietary intake and plasma concentrations of n-3 and n-6 (ω-3 and ω-6) PUFAs in childhood and adolescence for the development of asthma and lung function up to young adulthood. The study included participants from the Swedish prospective birth cohort BAMSE. Dietary intake of PUFAs was calculated from FFQs (n = 1992) and plasma proportions of PUFAs were measured in phospholipids (n = 831). We analyzed the n-3 PUFA α-linolenic acid (ALA; 18:3n-3); the sum of very-long-chain (VLC) n-3 PUFAs: EPA (20:5n-3), DHA (22:6n-3), and docosapentaenoic acid (22:5n-3); and the n-6 PUFAs linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6). Asthma was assessed by questionnaires at 8, 16, and 24 y and lung function was measured by spirometry at 24 y. A high (≥median) self-reported dietary intake of LA at 8 y and AA at 16 y was associated with increased risk of prevalent asthma at 24 y (OR: 1.41; 95% CI: 1.10, 1.82 and OR: 1.32; 95% CI: 1.02, 1.70, respectively). In contrast, plasma proportions of ALA, ∑VLC n-3 PUFAs, and AA at 8 y, as well as LA at 16 y, were inversely associated with prevalent asthma at 24 y (e.g., OR: 0.55; 95% CI: 0.38, 0.81 for ∑VLC n-3 PUFAs). No consistent associations were observed with lung function. High dietary intake of certain n-6 PUFAs in childhood or adolescence may be associated with increased risk of asthma up to young adulthood, whereas dietary biomarkers of certain n-3 and n-6 PUFAs in plasma may be associated with decreased risk. Thus, the role of diet compared with altered metabolism of PUFAs needs further investigation to improve dietary preventive strategies for asthma.


Brand-specific rates of pertussis disease among Wisconsin children given 1-4 doses of pertussis Vaccine, 2010-2014.
Acellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population. This prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2). 1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92-1.15) and 0.99 (adjusted; 90% CI, 0.89-1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39-96%). Pertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study. Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362.


Andean Tectonics and Mantle Dynamics as a Pervasive Influence on Amazonian Ecosystem.
The Amazonian landscape evolution is the result of the combined effect of Andean tectonism, climate and the Earth's interior dynamics. To reconstruct the landscape evolution and its influence on paleoenvironmental variations within Amazonia since the Oligocene, we conducted numerical experiments that incorporate different surface and geodynamic processes, reproducing many paleogeographic features as inferred from the sedimentary record. We show that the evolution of the drainage pattern gradually reduced the area of sedimentation derived from the Guiana and Brazilian shields while expanded the Andean derived deposits during the Miocene, affecting the nutrient availability. First order biotic habitats were inferred from these paleogeographical reconstructions, showing an eastward expansion of várzea and terra firme forests and consequent retraction of igapó forests, with a millennial-scale reconfiguration of a mosaic of habitats in the lowlands. We conclude that this dynamism probably guided the observed patterns of speciation in the most biodiverse biome on Earth.


Development of a wireless blood pressure measuring device with smart mobile device.
Today, smart mobile devices (telephones and tablets) are very commonly used due to their powerful hardware and useful features. According to an eMarketer report, in 2014 there were 1.76 billion smartphone users (excluding users of tablets) in the world; it is predicted that this number will rise by 15.9% to 2.04 billion in 2015. It is thought that these devices can be used successfully in biomedical applications. A wireless blood pressure measuring device used together with a smart mobile device was developed in this study. By means of an interface developed for smart mobile devices with Android and iOS operating systems, a smart mobile device was used both as an indicator and as a control device. The cuff communicating with this device through Bluetooth was designed to measure blood pressure via the arm. A digital filter was used on the cuff instead of the traditional analog signal processing and filtering circuit. The newly developed blood pressure measuring device was tested on 18 patients and 20 healthy individuals of different ages under a physician's supervision. When the test results were compared with the measurements made using a sphygmomanometer, it was shown that an average 93.52% accuracy in sick individuals and 94.53% accuracy in healthy individuals could be achieved with the new device.


Effects of different operating room temperatures on the body temperature undergoing live liver donor hepatectomy.
We sought to compare the effects of operation room temperature (ORT) at typical ambient environment (19-21 degrees C) and ORT at 24 degrees C on the core temperature of patients undergoing living donor hepatectomy. Sixty-two patients undergoing living donor hepatectomy were divided into 2 groups. In group I (n = 31), surgery was performed at typical ambient ORT, and in group II (n = 31) in ORT at 24 degrees C. Anesthesia and measures to prevent heat loss, except ORT, were all the same. Nasopharyngeal temperature (NT) was recorded after anesthesia induction, then hourly until completion of the operation. Changes in NTs were analyzed as well as patient age, weight, anesthetic duration, blood loss, intravenous fluids, total urine output, and pre- and postoperative hemoglobin and hematocrit values. The Mann-Whitney U test was used for comparisons between groups. The patient's characteristics between groups were not statistically different. However, a significantly higher core temperature was noted in group II compared with group I. Increased ORT from 19 to 21 degrees C to 24 degrees C resulted in an increased core temperature of at least 0.5 degrees C during living donor hepatectomy.


Multisite recording of brain field potentials and unit activity in freely moving rats.
A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.


Enhanced recovery after surgery is safe for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective, aggressive approach to treating intraperitoneal carcinomatosis. This study aimed to test the efficacy/safety of an enhanced recovery (ERAS) program after CRS-HIPEC surgery. Review of an IRB-approved prospectively maintained HIPEC database from 2003 to 2019. Adverse events and outcomes related to the primary operation were noted. 125 HIPEC procedures performed met inclusion criteria, with 20 treated through ERAS. There was an improvement in LOS (ERAS: 9, 6.0-28.0; non-ERAS: 11.0, 6.0-45.1, P = 0.5), a significant reduction in opioid use during hospitalization (ERAS Total Morphine Equivalents 156 vs Non-ERAS of 856, p < 0.001), and a significant reduction in discharge opioid requirements (ERAS 55% of patients, non-ERAS 97%, p < 0.02). ERAS for CRS-HIPEC is safe, while maintaining quality outcomes, and leads to significant reductions in hospital opioid use and discharge narcotic usage. Our experience supports the full implementation of an ERAS protocol for HIPEC.


Quantitative analysis of extension-torsion coupling of actin filaments.
Actin filaments have a double-helix structure consisting of globular actin molecules. In many mechanical cellular activities, such as cell movement, division, and shape control, modulation of the extensional and torsional dynamics of the filament has been linked to regulatory actin-binding protein functions. Therefore, it is important to quantitatively evaluate extension-torsion coupling of filament to better understand the actin filament dynamics. In the present study, the extension-torsion coupling was investigated using molecular dynamics simulations. We constructed a model for the actin filament consisting of 14 actin subunits in an ionic solvent as a minimal functional unit, and analyzed longitudinal and twisting Brownian motions of the filament. We then derived the expected value of energy associated with extension and torsion at equilibrium, and evaluated the extension-torsion stiffness of the filament from the thermal fluctuations obtained from the MD simulations. The results demonstrated that as the analyzed sampling-window duration was increased, the extension-torsion coupling stiffness evaluated on a nanosecond scale tended to converge to a value of 7.6×10(-11) N. The results obtained from this study will contribute to the understanding of biomechanical events, under mechanical tension and torque, involving extension-torsion coupling of filaments.


The use of solar energy for powering a portable autoclave.
Climate change and the depletion of fossil fuels have forced the developed world to look for clean energy alternatives. Solar cooking is developing in Asian and African countries blessed with ample sun, but is still at an early stage. A portable autoclave was developed in India using this technology. The Prince-40 Concentrator provided adequate capacity to autoclave culture media and treat biomedical waste in a small laboratory set-up, and could save electricity worth Rs. 15,000 (188.10 GBP)/year or LPG worth Rs. 37,500 (470.25 GBP)/year. This technology would be of immense use in health centres in rural areas with frequent power cuts or no power supply.


A recombinant lipoprotein antigen against Lyme disease expressed in E. coli: fermentor operating strategies for improved yield.
Decorin-binding lipoprotein, lpp-DBP, a bacterial surface adhesin, shows promise as a vaccine against Lyme disease. It is expressed in recombinant E. coli as an undesirable 20.5 KDa apoprotein that is subsequently lipidated in vivo to the desired 22 KDa lpp-DBP form. This study defines fermentation conditions for maximizing lpp-DBP yield. Super broth medium, a low post-induction temperature (30 degrees C), and a glucose feed based on dissolved oxygen resulted in high lpp-DBP yield and minimized apoprotein formation. Since cells lysed within 2-3 h after induction, the cell yield was maximized by growing cells to high cell density prior to induction. Compared to a glucose feed based on maintaining a constant fermentor glucose concentration (Glucose-Stat), feeding based on maintaining a constant dissolved oxygen level (DO-Stat) improved yields. Also, a dissolved oxygen level of 60% (air saturation) was best, as no product degradation was detected by Western blotting and SDS-PAGE. Acetic acid levels under both modes of glucose feed were sufficiently low, and no adverse growth effects were observed.


Unexpected rapid symptom response after praziquantel to intestinal Schistosoma mansoni symptoms: A case report from Rwanda.
The clinical effect of praziquantel on chronic intestinal schistosomiasis in the literature is lacking. We report a patient who presented with 3 years of non-specific abdominal pain and underwent colonoscopy, which revealed colon polyps that, on biopsy, were confirmed to be due to Schistosoma mansoni. The patient was given a single dose of praziquantel, and his abdominal symptoms disappeared within 24 h. Patients with abdominal pain in the setting of chronic Schistosoma infection should be given praziquantel and assess response clinically.


Feto-maternal interface of human placenta inhibits angiogenesis in the chick chorioallantoic membrane (CAM) assay.
The rapidly growing chorionic villi of the human placenta characteristically show constant blood vessel growth and differentiation. In contrast, the underlying decidua reveals tissue remodeling without apparent angiogenesis. Using the chick chorioallantoic membrane (CAM) assay, we found marked inhibition of angiogenesis by the feto-maternal interface tissue derived from nine human placentas obtained minutes after delivery. Inhibition was prevented by the addition of monensin, which blocks the release of synthesized cell products, and was markedly reduced by drying or freezing the tissue before the assay. Histology, combined with statistical analysis of the constituent cell types, correlated inhibition of angiogenesis with the number of fetally-derived extravillous trophoblasts in the feto-maternal interface tissue. Electron microscopy revealed endothelial cell damage in preexisting small (but not large) CAM vessels. We conclude that decidual tissue inhibited angiogenesis by releasing a water soluble factor which was under apparent constant production by vaible trophoblast on the CAM. The extravillous trophoblast population resembles tumor cells in its migratory and invasive properties but, in contrast to tumor induced angiogenesis, it is angiostatic, perhaps to counteract angiogenic proteins leaking from the intervillous space which could be detrimental to the maternal organism if active.


New insights into the epidemiology of enteropathogenic Escherichia coli infection.
Enteropathogenic Escherichia coli (EPEC) are among the most important pathogens infecting children worldwide and are one of the main causes of persistent diarrhea. EPEC were originally serogroup-defined E. coli associated with infantile diarrhea. As various mechanisms of pathogenesis have been discovered, EPEC classification has come to be based on the presence of specific genes. The eae (intimin) and bfpA (bundle-forming pilus) genes have both been used for identification of EPEC and for subdivision of this group of bacteria into typical and atypical strains. For many years typical EPEC have been considered to be the leading cause of infantile diarrhea in developing countries and were considered rare in industrialized countries. However, current data suggests that atypical EPEC are more prevalent than typical EPEC in both developing and developed countries. Moreover, the duration of diarrhea in patients infected with atypical EPEC is significantly longer than that caused by other pathogens. When comparing the isolation rates of EPEC among children with diarrhea and healthy controls without diarrhea, in general, there is a higher isolation rate in diarrhea, although not significantly higher in all studies. These inconsistencies probably are related to the study patient populations, reflecting a possible age-related susceptibility to infection.


Greedy adaptive walks on a correlated fitness landscape.
We study adaptation of a haploid asexual population on a fitness landscape defined over binary genotype sequences of length L. We consider greedy adaptive walks in which the population moves to the fittest among all single mutant neighbors of the current genotype until a local fitness maximum is reached. The landscape is of the rough mount Fuji type, which means that the fitness value assigned to a sequence is the sum of a random and a deterministic component. The random components are independent and identically distributed random variables, and the deterministic component varies linearly with the distance to a reference sequence. The deterministic fitness gradient c is a parameter that interpolates between the limits of an uncorrelated random landscape (c=0) and an effectively additive landscape (c→∞). When the random fitness component is chosen from the Gumbel distribution, explicit expressions for the distribution of the number of steps taken by the greedy walk are obtained, and it is shown that the walk length varies non-monotonically with the strength of the fitness gradient when the starting point is sufficiently close to the reference sequence. Asymptotic results for general distributions of the random fitness component are obtained using extreme value theory, and it is found that the walk length attains a non-trivial limit for L→∞, different from its values for c=0 and c=∞, if c is scaled with L in an appropriate combination.


DIP1 modulates stem cell homeostasis in Drosophila through regulation of sisR-1.
Stable intronic sequence RNAs (sisRNAs) are by-products of splicing and regulate gene expression. How sisRNAs are regulated is unclear. Here we report that a double-stranded RNA binding protein, Disco-interacting protein 1 (DIP1) regulates sisRNAs in Drosophila. DIP1 negatively regulates the abundance of sisR-1 and INE-1 sisRNAs. Fine-tuning of sisR-1 by DIP1 is important to maintain female germline stem cell homeostasis by modulating germline stem cell differentiation and niche adhesion. Drosophila DIP1 localizes to a nuclear body (satellite body) and associates with the fourth chromosome, which contains a very high density of INE-1 transposable element sequences that are processed into sisRNAs. DIP1 presumably acts outside the satellite bodies to regulate sisR-1, which is not on the fourth chromosome. Thus, our study identifies DIP1 as a sisRNA regulatory protein that controls germline stem cell self-renewal in Drosophila.Stable intronic sequence RNAs (sisRNAs) are by-products of splicing from introns with roles in embryonic development in Drosophila. Here, the authors show that the RNA binding protein DIP1 regulates sisRNAs in Drosophila, which is necessary for germline stem cell homeostasis.


Regional Challenges in the Prevention of Human Immunodeficiency Virus Drug Resistance.
In diverse global regions with significant human immunodeficiency virus (HIV) burden, programmatic, cultural, and provider-, patient-, and virus-related factors may result in HIV drug resistance, with global implications. This article reviews such common and unique challenges in Russia, Latin America and the Caribbean, China, and India, to suggest potential solutions.


Natural History of Leigh Syndrome: A Study of Disease Burden and Progression.
This observational cohort study aims to quantify disease burden over time, establish disease progression rates, and identify factors that may determine the disease course of Leigh syndrome. Seventy-two Leigh syndrome children who completed the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) at baseline at 3.7 years (interquartile range [IQR] = 2.0-7.6) and follow-up assessments at 7.5 years (IQR = 3.7-11.0) in clinics were enrolled. Eighty-two percent of this cohort had a confirmed genetic diagnosis, with pathogenic variants in the MT-ATP6 and SURF1 genes being the most common cause. The total NPMDS scores denoted mild (0-14), moderate (15-25), and severe (>25) disease burden. Detailed clinical, neuroradiological, and molecular genetic findings were also analyzed. The median total NPMDS scores rose significantly (Z = -6.9, p < 0.001), and the percentage of children with severe disease burden doubled (22% → 42%) over 2.6 years of follow-up. Poor function (especially mobility, self-care, communication, feeding, and education) and extrapyramidal features contributed significantly to the disease burden (τb ≈ 0.45-0.68, p < 0.001). These children also deteriorated to wheelchair dependence (31% → 57%), exclusive enteral feeding (22% → 46%), and one-to-one assistance for self-care (25% → 43%) during the study period. Twelve children (17%) died after their last NPMDS scores were recorded. These children had higher follow-up NPMDS scores (disease burden; p < 0.001) and steeper increase in NPMDS score per annum (disease progression; p < 0.001). Other predictors of poor outcomes include SURF1 gene variants (p < 0.001) and bilateral caudate changes on neuroimaging (p < 0.01). This study has objectively defined the disease burden and progression of Leigh syndrome. Our analysis has also uncovered potential influences on the trajectory of this neurodegenerative condition. ANN NEUROL 2022;91:117-130.


Juvenile sex offenders: development and correction.
This paper addresses the developmental nature of sexually abusive behaviors as they apply to juvenile male sexual offenders. Socialization and sexual victimization are discussed. Three case histories elucidate and support the discussion of the development of victim offending. Significant treatment issues of juvenile male sexual offenders center around the sexual assault cycle which provides a framework for sexual offenders to conceptualize and understand the cognitive, behavioral, psychological, and situational factors which have resulted in their offense(s). Although sexual offenders and sexual offenses are each unique, the sexual assault cycle offers a means of addressing essential commonalities in the treatment of juvenile sexual offenders. Sexual offender specific treatment is viewed as essential for decreasing the risk of further sexual offenses, and thus decreasing the incidence of sexual victimization.


A new road to neuroinflammation in Parkinson's disease?
Common architecture of cytokine receptors and G-protein coupled receptors (GPCRs) may underlie pathological receptor heteromer formation and signaling. Here, we clarify how chemokines and cytokines can participate in pathogenic processes of Parkinson's disease, especially in dopaminergic neurons of substantia nigra. Possible common architecture of GPCRs and cytokine receptors suggests that they may act as molecular switches similar to the prototypical innate immune receptors: Toll-like receptors. Thus, pathological signaling (as well as trafficking and internalization) of receptors may be initiated by their incorrect dimerization depending on direct or indirect (via adaptor proteins) receptor-receptor interactions, leading to neuroinflammatory responses.


The significance of the HER-2 status in esophageal adenocarcinoma for survival: an immunohistochemical and an in situ hybridization study.
In esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization. One hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™. HER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218-36.234; P = 0.029 and HR 3.231; 95% CI 1.092-9.563; P = 0.034). HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.


Rapid resolution of infantile acute subdural hematoma: a case report.
Subdural hematomas in infants are uncommon but usually result from non-accidental trauma or from trauma associated with motor vehicle accidents. This report describes the case of an infant with a traumatic acute subdural hematoma that resolved within 65 hours. A 23-month-old boy fell from a height of approximately 10 m. Brain computed tomography disclosed a left subdural hematoma with midline shift. The associated clots resolved spontaneously within 65 hours of the injury. Although they may mimic more clinically significant subdural hematomas, such collections of clots are likely to be located at least partly within the subarachnoid space. Their recognition may influence decisions regarding both surgical evacuation and the likelihood of non-accidental injury. Clinical and radiographic features distinguishing these "disappearing subdural hematomas" from more typical subdural hematomas are discussed.


Cardiovascular disease and resuscitated septic shock lead to the downregulation of the H2S-producing enzyme cystathionine-γ-lyase in the porcine coronary artery.
Downregulation of the hydrogen sulfide (H2S)-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and/or 3-mercaptopyruvate sulfurtransferase (3-MST) is associated with chronic cardiovascular pathologies. Nevertheless, equivocal data are available on both the expression and function of these enzymes in coronary arteries (CA). We recently reported that atherosclerotic pigs subjected to sepsis developed impaired cardiac function, which coincided with decreased myocardial CSE expression and increased nitrotyrosine formation. To define the endogenous source(s) of H2S in the CA, we studied the expression of CBS, CSE, or 3-MST in the CA of pigs subjected to septic shock with/without pre-existing cardiovascular co-morbidity. Anesthetized and instrumented FBM "familial hypercholesterolemia Bretoncelles Meishan" pigs with high-fat diet-induced hypercholesterolemia and atherosclerosis were subjected to polymicrobial septic shock, or sham procedure, and subsequent intensive care therapy for 24 h. Young German domestic pigs were used as naïve controls. CSE, CBS, 3-MST, HO-1, eNOS, and nitrotyrosine expression was quantified by immunohistochemistry of formalin-fixed paraffin sections. FBM pigs, in the absence of septic shock, showed decreased CSE expression in the media. This decrease became more pronounced after sepsis. The expression pattern of HO-1 resembled the pattern of CSE expression. CBS protein was not detected in the media of any of the CA examined but was localized to the adventitia and only in the atheromatous plaques containing foam cells of the CA, in regions that also displayed abundant nitrotyrosine formation. The CBS expression in the adventitia was not associated with nitrotyrosine formation. 3-MST expression was not found in any of the CA samples. We hypothesize that (i) the reduced CSE expression in FBM pigs may contribute to their cardiovascular disease phenotype and moreover (ii) the further decrease in CA CSE expression in sepsis may contribute to the sepsis-associated cardiac dysfunction.


Requirement for PINCH in skeletal myoblast differentiation.
PINCH, an adaptor of focal adhesion complex, plays essential roles in multiple cellular processes and organogenesis. Here, we ablated PINCH1 or both of PINCH1 and PINCH2 in skeletal muscle progenitors using MyoD-Cre. Double ablation of PINCH1 and PINCH2 resulted in early postnatal lethality with reduced size of skeletal muscles and detachment of diaphragm muscles from the body wall. PINCH mutant myofibers failed to undergo multinucleation and exhibited disrupted sarcomere structures. The mutant myoblasts in culture were able to adhere to newly formed myotubes but impeded in cell fusion and subsequent sarcomere genesis and cytoskeleton organization. Consistent with this, expression of integrin β1 and some cytoskeleton proteins and phosphorylation of ERK and AKT were significantly reduced in PINCH mutants. However, N-cadherin was correctly expressed at cell adhesion sites in PINCH mutant cells, suggesting that PINCH may play a direct role in myoblast fusion. Expression of MRF4, the most highly expressed myogenic factor at late stages of myogenesis, was abolished in PINCH mutants that could contribute to observed phenotypes. In addition, mice with PINCH1 being ablated in myogenic progenitors exhibited only mild centronuclear myopathic changes, suggesting a compensatory role of PINCH2 in myogenic differentiation. Our results revealed a critical role of PINCH proteins in myogenic differentiation.


Epidermal growth factor receptor targeting in cancer: a review of trends and strategies.
The epidermal growth factor receptor (EGFR) is a cell-surface receptor belonging to ErbB family of tyrosine kinase and it plays a vital role in the regulation of cell proliferation, survival and differentiation. However; EGFR is aberrantly activated by various mechanisms like receptor overexpression, mutation, ligand-dependent receptor dimerization, ligand-independent activation and is associated with development of variety of tumors. Therefore, specific EGFR inhibition is one of the key targets for cancer therapy. Two major approaches have been developed and demonstrated benefits in clinical trials for targeting EGFR; monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors like, cetuximab, panitumumab, etc. (mAbs) and gefitinib, erlotinib, lapatinib, etc. (TKIs) are now commercially available for treatment of variety of cancers. Recently, many other agents like peptides, nanobodies, affibodies and antisense oligonucleotide have also shown better efficacy in targeting and inhibiting EGFR. Now a days, efforts are being focused to identify molecular markers that can predict patients more likely to respond to anti-EGFR therapy; to find out combinatorial approaches with EGFR inhibitors and to bring new therapeutic agents with clinical efficacy. In this review we have outlined the role of EGFR in cancer, different types of EGFR inhibitors, preclinical and clinical status of EGFR inhibitors as well as summarized the recent efforts made in the field of molecular EGFR targeting.


Emulsion templated scaffolds with tunable mechanical properties for bone tissue engineering.
Polymerised High Internal Phase Emulsions (PolyHIPEs) are manufactured via emulsion templating and exhibit a highly interconnected microporosity. These materials are commonly used as thin membranes for 3D cell culture. This study uses emulsion templating in combination with microstereolithography to fabricate PolyHIPE scaffolds with a tightly controlled and reproducible architecture. This combination of methods produces hierarchical structures, where the microstructural properties can be independently controlled from the scaffold macrostructure. PolyHIPEs were fabricated with varying ratios of two acrylate monomers (2-ethylhexyl acrylate (EHA) and isobornyl acrylate (IBOA)) and varying nominal porosity to tune mechanical properties. Young's modulus, ultimate tensile stress (UTS) and elongation at failure were determined for twenty EHA/IBOA compositions. Moduli ranged from 63.01±9.13 to 0.36±0.04MPa, UTS from 2.03±0.33 to 0.11±0.01MPa and failure strain from 21.86±2.87% to 2.60±0.61%. Selected compositions were fabricated into macro-porous woodpile structures, plasma treated with air or acrylic acid and seeded with human embryonic stem-cell derived mesenchymal progenitor cells (hES-MPs). Confocal and two-photon microscopy confirmed cell proliferation and penetration into the micro- and macro-porous architecture. The scaffolds supported osteogenic differentiation of mesenchymal cells and interestingly, the stiffest IBOA-based scaffolds that were plasma treated with acrylic acid promoted osteogenesis more strongly than the other scaffolds.


RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease.
To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3β silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.


The experiences of nursing master's students with dialogic case-based learning in an evidence-based nursing course: A qualitative study.
Evidence-based nursing (EBN) is a complex subject for teachers and students due to the abstract concepts involved. It requires combining theory with practice and is included in the major courses required for a master's education in many countries. Case-based learning (CBL), which is a student-centred teaching method, has been widely used in numerous disciplines because it can bridge the gap between theory and practice and foster critical thinking and communication skills. However, to adapt CBL to EBN coursework for a Master of Nursing degree, improve evidence-based practice (EBP) and enhance core competencies, the case design and operational procedures of CBL need to be further examined. To explore nursing master's students' experiences of dialogic CBL and case design and operational procedures regarding dialogic CBL. A descriptive-qualitative study design was used. The study was carried out in the nursing master's programme at a university in China. Twenty first-year nursing master's students who completed a 10-week EBN course were recruited using purposive sampling. Data were collected between September and December 2020 via in-depth semistructured interviews. The data were analysed using thematic analysis. Four themes were identified: (1) 'learning theoretical EBN knowledge'; (2) 'improving clinical nursing ability'; (3) 'enhancing core competencies'; and (4) 'barriers to implementing dialogic CBL'. The study provided a standardised CBL procedure based on students' experiences, which included preparation, group discussions, presentations, and teachers' feedback following the presentations, and these operational procedures were shown to be indispensable. The student experiences in this study should be referenced by nursing educators who apply this teaching method in other graduate and undergraduate nursing courses such as surgical nursing and nursing research.