The demonstration of the spindle fiber attachments in the amphibian liver and sperm nuclei by the sera from scleroderma patients.
The isolated liver nuclei and the mature sperm nuclei from Rana nigromaculata and Bufo bufo asiaticus had been investigated by indirect immunofluorescence method with anti serum specific to the spindle fiber attachments (SFAs) from the scleroderma patients with CREST syndrome. It was found that in the isolated liver nuclei and the mature sperm nuclei of these animals there are discrete speckles which bind the antibody specific to the SFAs. The maximum number of these speckles counted in a single sperm nuclei of the frog corresponds with the haploid chromosome number of this animal (n = 13). The haploid chromosome complement of the toad is 11 and the maximum number of the speckles counted in a single sperm nucleus of this species is also 11. These findings suggest that the scleroderma serum can be used to identify the SFAs of the amphibias and the antigens of SFAs are conserved in the mature sperms of these animals. The implication of these conclusions is discussed.


Concentrations of 5-hydroxyindoleacetic acid and homovanillic acid in the cerebrospinal fluid of chronic therapy-resistant schizophrenics before and after hemodialysis therapy.
The concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been determined by high-performance liquid chromatography in samples of lumbar cerebrospinal fluid from chronic therapy-resistant schizophrenics, both before and after either inactive or active hemodialysis for 10 weeks. A reasonable test-retest reliability was found for 5-HIAA during the inactive dialysis, but this was not found during active dialysis.


Cross-sectional investigation of adolescent perceptions of gender roles.
Data from a sample of youngsters, 12 through 18 years old, are analysed to examine the difference in gender role perceptions across age groups. A series of multivariate correlational analyses are employed to examine the relationship between respondent gender, age and self-reported perceptions of gender identity. The results of the study indicate indirect support for Erikson's speculations about resolution of Identity "Crisis". The youngest respondents showed the greatest disparity between male and female role perceptions. The older subjects, those in adolescence, displayed greater ambiguity toward gender roles. Finally, the oldest respondents, approaching adulthood, indicated a stronger perceived gender identity.


Downregulation of c-fos gene transcription in cells transformed by E1A and cHa-ras oncogenes: a role of sustained activation of MAP/ERK kinase cascade and of inactive chromatin structure at c-fos promoter.
REF cells transformed by oncogenes E1A and cHa-ras reveal high and constitutive DNA-binding activity of AP-1 factor lacking in c-Fos protein. Consistently, the transcription of c-fos gene has been found to be downregulated. To elucidate the mechanisms of c-fos downregulation in E1A+cHa-ras transformants, we studied the levels of activity of ERK, JNK/SAPK and p38 kinases and phosphorylation state of Elk-1 transcription factor involved in regulation of c-fos gene. Using two approaches, Western blot analysis with phospho-specific antibodies to MAP kinases and in vitro kinase assay with specific substrates, we show here that ectopic expression of E1A and ras oncogenes leads to a sustained activation of ERK and p38 kinases, whereas JNK/SAPK kinase activity is similar to that in non-transformed REF52 cells. Due to sustained activity of the MAP kinase cascades, Elk-1 transcription factor is being phosphorylated even in serum-starved E1A+cHa-ras cells; moreover, serum does not additionally increase phosphorylation of Elk-1, which is predominant TCF protein bound to SRE region of c-fos gene promoter in these cells. Although the amount of ternary complexes SRE/SRF/TCF estimated by EMSA was similar both in serum-starved and serum-stimulated transformed cells, serum addition still caused a modest activation of c-fos gene transcription at the level of 20% to normal REF cells. In attempt to determine how serum caused the stimulatory effect, we found that PD98059, an inhibitor of MEK/ERK kinase cascade, completely suppressed serum-induced c-fos transcription both in REF and E1A+cHa-ras cells, implicating the ERK as primary kinase for c-fos transcription in these cells. In contrast, SB203580, an inhibitor of p38 kinase, augmented noticeably serum-stimulated transcription of c-fos gene in REF cells, implying the involvement of p38 kinase in negative regulation of c-fos. Furthermore, sodium butyrate, an inhibitor of histone deacetylase activity, was capable of activating c-fos transcription both in serum-stimulated and even in serum-starved E1A+cHa-ras cells. Conversely, serum-starved REF cells fail to respond to sodium butyrate treatment by c-fos activation confirming necessity of prior Elk-1 phosphorylation. Taken together, these data suggest that downregulation of c-fos in E1A+cHa-ras cells seems to occur due to a maintenance of a refractory state that arises in normal REF cells after serum-stimulation. The refractory state of c-fos in E1A+cHa-ras cells is likely a consequence of Ras-induced sustained activation of MAPK (ERK) cascade and persistent phosphorylation of TCF (Elk-1) bound to SRE. Combination of these events eventually does contribute to formation of an inactive chromatin structure at c-fos promoter mediated through recruitment of histone deacetylase activity.


Frontal EEG Asymmetry as a Promising Marker of Depression Vulnerability: Summary and Methodological Considerations.
Frontal EEG asymmetry is a promising neurophysiological marker of depression risk. It predicts emotional response and negative affect hours to years later. Yet, inconsistencies in the literature may be due to differing methodological approaches between research groups. Within the past two years, a number of studies have shown this line of research may be strengthened by augmenting resting assessments with emotionally evocative tasks, utilizing optimal recording montages, and taking an integrative neuroscience approach that links frontal asymmetry to other indices of neural function. This review will focus on recent work in frontal asymmetry and depression with a particular focus on promising future directions and methodological considerations that may increase consistency between research groups.


Prophylactic cranial irradiation in limited-stage small-cell lung cancer: a retrospective analysis.
It is well established that prophylactic cranial irradiation (PCI) decreases significantly the incidence of brain metastases (BM) and increases overall survival in limited-stage small-cell lung cancer (LS-SCLC) patients with complete response to induction therapy. The aim of this study was to complete a review analysis of PCI use among patients diagnosed with LS-SCLC in a community hospital. A retrospective review of medical charts of patients diagnosed with LS-SCLC between January 1997 and December 2002 at a local community hospital in Fargo, North Dakota, was done to determine which of these patients subsequently received PCI. Data on patient's age, gender, body mass index at diagnosis, SCLC anatomical site, other comorbidies at diagnosis, treatment of SCLC, chemotherapeutic agents used at diagnosis of SCLC, response to induction treatment, PCI use, reason(s) for no PCI, BM status, BM site, metastases to other sites, and survival were abstracted. A total of 32 patients with LS-SCLC were identified. Twenty-three (71.9%) of the patients received concurrent chemotherapy and radiation therapy. Of the remaining 9 (28.1%) patients, 6 (18.7%) did not receive any treatment because of poor performance status, and 3 (9.4%) received only chemotherapy because of coexisting comorbidity. Thirteen (40.6%) of the patients achieved a complete response but only 4 (30.8%) patients had PCI. Among the 9 (69.2%) patients who appeared eligible to receive PCI, 1 (11.2%) refused, 4 (44.4%) had coexisting comorbidities, and 4 (44.4%) had no notes indicating why they did not receive PCI. Of those who had PCI, only 1 (25%) patient developed BM 35 months later. This review found that although only a few patients were eligible to receive PCI, nevertheless, the benefits could be significant. We concluded that oncologists should be more willing to offer this procedure.


isma: an R package for the integrative analysis of mutations detected by multiple pipelines.
Recent comparative studies have brought to our attention how somatic mutation detection from next-generation sequencing data is still an open issue in bioinformatics, because different pipelines result in a low consensus. In this context, it is suggested to integrate results from multiple calling tools, but this operation is not trivial and the burden of merging, comparing, filtering and explaining the results demands appropriate software. We developed isma (integrative somatic mutation analysis), an R package for the integrative analysis of somatic mutations detected by multiple pipelines for matched tumor-normal samples. The package provides a series of functions to quantify the consensus, estimate the variability, underline outliers, integrate evidences from publicly available mutation catalogues and filter sites. We illustrate the capabilities of isma analysing breast cancer somatic mutations generated by The Cancer Genome Atlas (TCGA) using four pipelines. Comparing different "points of view" on the same data, isma generates a unique mutation catalogue and a series of reports that underline common patterns, variability, as well as sites already catalogued by other studies (e.g. TCGA), so as to design and apply filtering strategies to screen more reliable sites. The package is available for non-commercial users at the URL https://www.itb.cnr.it/isma .


[Breast cancer in Mexican women under 40].
Breast cancer is the leading cause of death from malignancy in women. The incidence increases with age, but the relationship between age and survival of breast cancer patients is not well defined. It is observed that young women with breast cancer have patterns more aggressive biological. To determine the frequency, sociodemographic, clinical and histopathological features of breast cancer in women under 40 years attending a specialist breast unit in Mexico City. Transversal, descriptive and retrospective study of patients under 40 years of age with breast cancer treated between 2005 and 2010. 1430 cases were diagnosed with breast cancer five years with a mean age of 53.64 +/- 11.87 years (range 23 to 93 years), 142 cases were women under 40 years of age (10%). The auto-detection of a breast lump was the most frequent clinical manifestation (50%). The prevalence of clinical stage III in this age group suggests the difficulty of diagnosis, the high breast density, which is one factor limiting studies of screening with mammography, it diminishes their effectiveness in early detection of breast cancer.


Assessment of the relationship between rural non-point source pollution and economic development in the Three Gorges Reservoir Area.
This study investigates the relationship between rural non-point source (NPS) pollution and economic development in the Three Gorges Reservoir Area (TGRA) by using the Environmental Kuznets Curve (EKC) hypothesis for the first time. Five types of pollution indicators, namely, fertilizer input density (FD), pesticide input density (PD), agricultural film input density (AD), grain residues impact (GI), and livestock manure impact (MI), were selected as rural NPS pollutant variables. Rural net income per capita was used as the indicator of economic development. Pollution load was generated by agricultural inputs (consumption of fertilizer, pesticide, and agricultural film) and economic growth with invert U-shaped features. The predicted turning points for FD, PD, and AD were at rural net income per capita levels of 6167.64, 6205.02, and 4955.29 CNY, respectively, which were all surpassed. However, the features between agricultural waste outputs (grain residues and livestock manure) and economic growth were inconsistent with the EKC hypothesis, which reflected the current trends of agricultural economic structure in the TGRA. Given that several other factors aside from economic development level could influence the pollutant generation in rural NPS, a further examination with long-run data support should be performed to understand the relationship between rural NPS pollution and income level.


A new strategy to create ordered deletions for rapid nucleotide sequencing.
A method is described for generating ordered deletions using previously published techniques but a new strategy. This method is simpler than the published ones and has many advantages. Target DNA is cloned in both orientations into one of the unique restriction enzyme sites adjacent to the complementary region of the commercially available primers in bacteriophage M13. Ordered unidirectional deletions are created using BAL 31 nuclease and religating into M13 vector DNA without the need of purifying BAL 31-digested DNA from a gel.


Barriers to conducting clinical research in reproductive medicine: Latin America.
Societies in Latin America are not scientifically driven and therefore, the allocation of human and economic resources to research is meager, as a reflection of this as well as other cultural and economic realities.


Adaptative features of enzymes from family sciaenidae--II. Studies on phosphoglucose isomerase (PGI) of fishes from the south coast of Uruguay.
1. The electrokinetic and thermostability properties of phosphoglucose isomerase (PGI) in three species of temperate fishes (Perciformes, Acanthopterygii)--Cynoscion striatus, Macrodon ancylodon and Micropogonias furnieri--have been analyzed in order to study the adaptative 2. Unlike most diploid fishes the PGI of these species seemed to be encoded by three PGI loci. 3. The subunits encoded by these loci occurred at different levels in the different tissues and organs analyzed. 4. Genetic variants at two loci (Pgi-A and Pgi-B2) were detected in Cynoscion striatus, and at one (Pgi-A) in Micropogonias furnieri. 5. The product of these loci could be separated in three PGI regions based on their electrophoretic distribution and thermostability properties. 6. The more anodal region (including isozymes and allozymes) was more thermolabile than the less anodal one, which is predominant in a single tissue skeletal muscle. 7. Relative activities of PGI isozymes were compared by Klebe's method to determine pattern of divergence of duplicated gene expression in the three species studied.


Quantitative anatomy of the lungs of the red-eared turtle, Pseudemys scripta elegans.
Morphometric and sterological methods were employed to evaluate the anatomical gas-exchange potential of the lungs of the fresh-water turtle, Pseudemys scripta elegans. The total lung volume and lung wet weight increase with the 1.4 power of body weight. Right and left lungs are similar in size and shape, containing a tissue-free central lumen, which occupies 55 per cent of the maximally inflated lung. The remainder is parenchyma, composed of 90 per cent air and 10 per cent tissue, with an effective surface-to-volume ratio of 18 cm-1. The anatomical diffusion factor (ADF), or the ratio of respiratory surface area to mean diffusion distance in lung tissue, is 1 order of magnitude lower than in the mammalian lung. Taking interspecific differences in O2 consumption into account, the degree to which the lungs are exploited, deltaPtO2, is similar in Pseudemys and in mammals at basal, resting and exercising states.


Non-chewing diets and cerumen impaction in the external ear canal in a residential aged care population.
To examine whether diets involving reduced chewing affect the degree of cerumen impaction in older people in residential care. A total of 51 people (53% male) over 65 years (80.5 ± 9.3) were recruited from two residential aged care facilities in Perth, Australia. Participants were classified as "chewers" (on unrestricted or soft food diets), or "non-chewers" (on pureed or nil by mouth diets), and completed a survey about predisposing factors for cerumen impaction. Otoscopy and tympanometry were used to assess cerumen impaction and ear canal occlusion. Participants with excess cerumen were referred for wax removal. No significant difference in cerumen accumulation was found between groups. However, 57% of participants showed excess cerumen requiring removal. Diets involving reduced chewing are not associated with increased cerumen in older people in residential care. The prevalence of cerumen impaction is high in this population, and improved cerumen screening and management is needed in residential aged care.


[Contributions to the micromorphology of the miracidium of Schistosoma mansoni. I. Fine structure of the tegument and its "associated structures" (author's transl)].
The body wall of the miracidium of S. mansoni has been studied by light and electron microscope. It has been found that the tegument layer contains so-called membrane-bound bodies. The tegument layer will be separated from muscle layer by means of a basal membrane. Special attention was focused on the associated structures of the tegument; these are cilia, microvilli-like appendices amounting to six in number at our test-organisms and finally two types of sensory papillae on the so-called terebratorium. After treatment of the miracidium in antiserum, fine granulated precipitate was formed around the cilia.


Bioactive characterization and optimization of Tamarindus indica seed protein hydrolysate: technology and application of natural enzymes.
Tamarind seeds are one of the major sources of different nutrients and minerals and are used as antioxidant components in various food products. Bioactive peptides are released by enzymatic hydrolysis of major food proteins followed by different separation techniques to isolate them from the mixture of other components. Further incorporation of bioactive peptides in various food products may lead to more diversification, fulfilling different nutritional requirements, and promoting health benefits. The objective of this study was to optimize the parameters for the formation of tamarind protein hydrolysates with the use of pepsin and trypsin. It was observed that pepsin and trypsin derived hydrolysate showed the maximum degree of hydrolysis and other bioactive characteristics (DPPH activity, reducing power, ABTS activity, and antidiabetic activity) under optimized conditions. High-performance liquid chromatography was performed for amino acid profiling on trypsin derived protein hydrolysate. From this study, pepsin and trypsin derived hydrolysate can be considered as a rich source of natural antioxidants for developing food formulation.


TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis.
TREML4 and other members of the triggering receptor expressed in the myeloid cell family are associated with a risk of atherosclerosis and progression in coronary artery disease, acute coronary syndrome, and coronary artery calcification. Herein, the relationship between TREML4 expression and its polymorphisms (rs2803495 and rs280396) was evaluated in patients with subclinical atherosclerosis (n = 340) and heart failure post-acute myocardial infarction (MI) (n = 68) for the first time. TREML4 variants rs2803495 (A > G) and rs2803496 (T > C) and leukocyte mRNA expression was analyzed by qRT-PCR. The rs2803495 G allele was associated with TREML4 expression (OR 8.01, CI 3.78-16.99, p < 0.001). Patients carrying the rs2803496 C minor allele (TC/CC genotypes) were more likely to express TREML4 than those without the C allele (OR 10.42, CI 4.76-22.78, p < 0.001), as well as having higher levels of TREML4 expression (OR 4.88, CI 2.35-10.12, p < 0.001). Thus, we report for the first time that TREML4 is not associated with the early stages of atherosclerotic plaque formation and later stages after MI. In conclusion, TREML4 mRNA expression in blood leukocytes is influenced by minor alleles (G and C) and may regulate differently during the atherosclerosis progression stages, but not in asymptomatic atherosclerosis disease and post-MI.


[The therapeutic efficacy of the Russian bath].
Some mechanisms of steam inhalation effects in patients with nonspecific pulmonary diseases have been investigated. This type of aerosol therapy proved highly effective due to its broncholytic, antimicrobial and pulmonary hemodynamic stabilizing actions.


Pharmacological Influencing of The Cholinergic Anti-inflammatory Pathway in Infectious Diseases and Inflammatory Pathologies.
The cholinergic anti-inflammatory pathway is a part of the parasympathetic nervous system and it can also be entitled as an anti-inflammatory reflex. It consists of terminations of the vagal nerve into blood, acetylcholine released from the terminations, macrophages and other cells having α7 nicotinic acetylcholine receptor (α7 nAChR), calcium ions crossing through the receptor and interacting with nuclear factors, and erythrocytes with acetylcholinesterase (AChE) terminating the neurotransmission. Stopping of inflammatory cytokines production is the major task for the cholinergic antiinflammatory pathway. The cholinergic anti-inflammatory pathway can be stimulated or suppressed by agonizing or antagonizing α7 nAChR or by inhibition of AChE. This review is focused on cholinergic anti-inflammatory pathway regulation by drugs. Compounds that inhibit cholinesterases (for instance, huperzine, rivastigmine, galantamine), and their impact on the cholinergic anti-inflammatory pathway are discussed here and a survey of actual literature is provided.


Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women.
This study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Women (n=838) aged 25-65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression. HPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR=1.60, p=0.010). HIV co-infection (aOR=3.44, p<0.001) and hormonal contraception (aOR=1.97, p=0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR=0.15, p=0.029). CIN2-3 lesions were found in women younger than 50 years, with a median age of 36 years (31-44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p=0.015). Young, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30-50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.


Spontaneous splenic rupture due to occult signet-ring cell gastric cancer accompanied by a bulky splenic vein thrombosis and postoperative brain infarction: A case report.
Splenic rupture because of metastasis from a distant organ is extremely rare. An 80-year-old man presented with left flank pain. A computed tomography (CT) demonstrated a poorly enhanced enlarged spleen with bulky thrombus in the splenic vein without extravasations. A CT on the following day showed increased intraperitoneal hemorrhage; therefore, an emergency laparotomy was performed. The spleen was enlarged and ruptured with lacerations on its surface. Macroscopic examination showed congestion with a thrombus in the splenic vein around the hilum. Pathology revealed signet-ring cell carcinoma. On the third postoperative day, a massive cerebral infarction in the left middle cerebral artery was revealed. Endoscopic examination demonstrated normal gastric mucosa except for some erosions, for which biopsies were performed, and two of five specimens encompassed signet-ring cell carcinoma in the lamina propria. Occult cancer could result in a drastic manifestation of its metastasis accompanying systemic thrombotic events.


Survival analysis for pediatric heart transplant patients using a novel machine learning algorithm: A UNOS analysis.
Impact of pretransplantation risk factors on mortality in the first year after heart transplantation remains largely unknown. Using machine learning algorithms, we selected clinically relevant identifiers that could predict 1-year mortality after pediatric heart transplantation. Data were obtained from the United Network for Organ Sharing Database for years 2010-2020 for patients 0-17 years receiving their first heart transplant (N = 4150). Features were selected using subject experts and literature review. Scikit-Learn, Scikit-Survival, and Tensorflow were used. A train:test split of 70:30 was used. N-repeated k-fold validation was performed (N = 5, k = 5). Seven models were tested, Hyperparameter tuning performed using Bayesian optimization and the concordance index (C-index) was used for model assessment. A C-index above 0.6 for test data was considered acceptable for survival analysis models. C-indices obtained were 0.60 (Cox proportional hazards), 0.61 (Cox with elastic net), 0.64 (gradient boosting), 0.64 (support vector machine), 0.68 (random forest), 0.66 (component gradient boosting), and 0.54 (survival trees). Machine learning models show an improvement over the traditional Cox proportional hazards model, with random forest performing the best on the test set. Analysis of the feature importance for the gradient boosted model found that the top 5 features were the most recent serum total bilirubin, the travel distance from the transplant center, the patient body mass index, the deceased donor terminal Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT), and the donor PCO2. Combination of machine learning and expert-based methodology of selecting predictors of survival for pediatric heart transplantation provides a reasonable prediction of 1- and 3-year survival outcomes. SHapley Additive exPlanations can be an effective tool for modeling and visualizing nonlinear interactions.


Intracellular gold nanoparticles influence light scattering and facilitate amplified spontaneous emission generation.
Generation of amplified stimulated emission inside mammalian cells has paved the way for a novel bioimaging and cell sensing approach. Single cells carrying gain media (e.g., fluorescent molecules) are placed inside an optical cavity, allowing the production of intracellular laser emission upon sufficient optical pumping. Here, we investigate the possibility to trigger another amplified emission phenomenon (i.e., amplified spontaneous emission or ASE) inside two different cell types, namely macrophage and epithelial cells from different species and tissues, in the presence of a poorly reflecting cavity. Furthermore, the resulting ASE properties can be enhanced by introducing plasmonic nanoparticles. The presence of gold nanoparticles (AuNPs) in rhodamine 6G-labeled A549 epithelial cells results in higher intensity and lowered ASE threshold in comparison to cells without nanoparticles, due to the effect of plasmonic field enhancement. An increase in intracellular concentration of AuNPs in rhodamine 6G-labeled macrophages is, however, responsible for the twofold increase in the ASE threshold and a reduction in the ASE intensity, dominantly due to a suppressed in and out-coupling of light at high nanoparticle concentrations.


Changes in Na+/K+-ATPase activity, unsaturated fatty acids and metallothioneins in gills of the shore crab Carcinus aestuarii after dilute seawater acclimation.
We have assessed the activity of Na(+)/K(+)-ATPase, cAMP, free fatty acids (FFA) and metallothionein (MT) in the posterior gills of the brackish water shore crab Carcinus aestuarii during acclimation to 10 ppt dilute seawater (DSW). Following 3-18 days acclimation in DSW specific activity of Na(+)/K(+)-ATPase in native gill homogenates and partially purified membrane vesicles was progressively increased, from 1.7- to 3.9-fold. After short-term acclimation of crabs in DSW with added sucrose to make media isosmotic with the haemolymph the specific Na(+)/K(+)-ATPase activity in homogenates was not increased, relative to SW enzyme activity. Moreover, hyposmotic conditions led to depletion of cAMP in gills. In partially purified membrane vesicles isolated from posterior gills, fatty acids with compositions 16:0, 18:0, 18:1, 20:4 and 20:5 dominated in both SW- and DSW-acclimated Carcinus. During a year in which the metabolic activity of crabs was increased, the arachidonic/linoleic acids ratio (ARA/LA) for DSW-acclimated crabs was markedly increased relative to that in SW. Increased Na(+)+K(+)-ATPase activity under hyposmotic stress may be modulated at least partially by the changed proportion of fatty acids in the purified membranes of posterior gills. Long-term acclimation of shore crabs to DSW resulted in a 2.6-fold increase in cytosolic metallothionein (MT) content in posterior gills over those in SW crabs. Assuming an antioxidant role of MT associated with intracellular zinc partitioning, the observed MT induction in posterior gills may be considered an adaptive response of C. aestuarii to hyposmotic stress.


Rheumatology: it's truly a joint effort now.
As outpatient care predominates, hospitals solidify their role in the care continuum. Part of our Clinical Management series.


Biological physics in México: Review and new challenges.
Biological and physical sciences possess a long-standing tradition of cooperativity as separate but related subfields of science. For some time, this cooperativity has been limited by their obvious differences in methods and views. Biological physics has recently experienced a kind of revival (or better a rebirth) due to the growth of molecular research on animate matter. New avenues for research have been opened for both theoretical and experimental physicists. Nevertheless, in order to better travel for such paths, the contemporary biological physicist should be armed with a set of specialized tools and methods but also with a new attitude toward multidisciplinarity. In this review article, we intend to somehow summarize what has been done in the past (in particular, as an example we will take a closer look at the Mexican case), to show some examples of fruitful investigations in the biological physics area and also to set a proposal of new curricula for physics students and professionals interested in applying their science to get a better understanding of the physical basis of biological function.


[Analysis of evolution features of whole genome of influenza virus H3N2 in Qingdao between year 2007 and 2011].
To investigate the evolution features of whole-genome of influenza virus H3N2 prevalent in Qingdao from year 2007 to 2011. The RNA of 58 strains of influenza virus H3N2 prevalent in Qingdao between 2007 and 2011 was extracted and all segments amplified by RT-PCR. The sequence was then detected and assembled by software Sequencer. A total of 589 strains of influenza virus H3N2 with more than 300 amino acid recorded by GenBank were selected. The phylogeny and molecular features of all gene segments were analyzed by software Mega 5.0, referred by the heavy chain of hemagglutinin (HA1). Hemagglutinin (HA) genes of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 formed a single trunk of phylogenetic tree. Every prevalent strain originated in last season. The analysis of the evolution of whole genome found that reassortment virus strains were prevalent between year 2009 and 2010, but between 2010 and 2011 there were two series of prevalent strains, which showed complicated reassortment. Compared with the vaccine strains, the variant amino acids of protein of virus HA1 between year 2007 and 2011 were 8, 6, 6, 8 and 11, involving 13 antigenic sites. The sequence analysis of M2 protein showed that the isolated influenza virus H3N2 mutated in amino acid site 31, from serine to asparagine (S31N). HA1 gene of influenza virus H3N2 isolated in Qingdao between 2007 and 2011 shared the similar phylogenetic tree with the globally prevalent strain. The comparison of the sequence and the analysis of the antigenicity found co-infection between H3N2 and A/H1N1 in the strain A/Qingdao/F521/2011. The evolution features of all segments of influenza virus H3N2 prevalent in Qingdao between year 2007 and 2011 were complicated.


A dilated surface appearance on basiparallel anatomic scanning-magnetic resonance imaging is a useful tool for the diagnosis of spontaneous vertebral artery dissection in lateral medullary infarction.
Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion causing lateral medullary infarction (LMI). A dilated surface appearance of the VA is a feature of VA dissection and can be observed on basiparallel anatomic scanning (BPAS)-magnetic resonance imaging (MRI). The aim of this study was to validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The subjects of the present study were 41 consecutive patients with LMI within 7 days of onset. The diagnosis of VA dissection was made with the clinical criteria-based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by comparing the maximum surface diameter of the intracranial VA to the diameter of the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with VA dissection. The optimal cutoff % dilatation of the VA for dissection was more than 169%. The sensitivity and specificity of % dilatation of VA more than 169% and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI combined with time-of-flight-MRA is a useful tool for the diagnosis of VA dissection in patients with acute LMI.


Hypofractionated Stereotactic Radiation Therapy to the Resection Bed for Intracranial Metastases.
To retrospectively report the outcomes of a large multicenter cohort of patients treated with surgery and hypofractionated stereotactic radiation therapy (HFSRT) to the resection cavities of brain metastases (BMs). Between March 2008 and February 2015, 181 patients with no prior whole-brain radiation therapy (WBRT) were treated by HFSRT to the surgical bed of BM at the dose of 33 Gy (3 × 11 Gy). The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS), risk of radionecrosis, and leptomeningeal disease (LMD). Of the 189 resected lesions, 44% were metastatic from a non-small cell lung cancer primary tumor, and 76% of patients had a single BM at the time of treatment. With a median follow-up of 15 months, the 6- and 12-month local control rates were 93% and 88%, respectively. On multivariate analysis, planning target volume (P=.005), graded prognostic assessment score (P=.021), and meningeal contact of BM (P=.032) were predictive of local failure. The 6- and 12-month distant brain control rates were 70% and 61%, respectively. Twenty-six patients (14%) developed signs of LMD at a median time of 3.8 months. The preoperative tumor volume was predictive of LMD (P=.029). The median OS was 17 months. The 6-, 12-, and 24-month OS rates were 79%, 62%, and 39%, respectively. Recursive partitioning analysis class 3 (P=.02), piecemeal resection (P=.017), and an increasing number of BMs (P<.01) were independent unfavorable prognostic factors for OS. Fifty-four patients (30%) were subsequently treated with salvage WBRT at a median time of 6.5 months, and 41% were reirradiated with SRT. Radionecrosis occurred in 19% of cases at a median time of 15 months and was associated with the infratentorial location of the BM (P=.0025). This study demonstrated the safety and efficacy of a 3 × 11 Gy HFSRT regimen for the irradiation of BMs resection cavities. It was an alternative to adjuvant WBRT.


Culture of the primary corneal epithelium as a potential component of test batteries for eye irritancy testing.
One of the main goals for toxicologists working on the development of in vitro tests is to replace the animal-based eye irritation test. Inflammation is one of the mechanisms which have not been covered sufficiently by the existing in vitro ocular irritancy test systems. As there are major species differences between the human and rabbit eye inflammation mechanisms, the most relevant test system is the human eye itself. The current study focused on an evaluation of the practical availability of human corneal epithelial cells for routine eye irritancy testing. Human corneal epithelium cell cultures were used to assess the effects of lipopolysaccharide on IL-1 beta release. The findings indicated that cytokine release can be augmented by the presence of the complement system, which is normally found in tears. However, the corneal cells were found to be highly resistant to the complement system, which can be attributed to the very high expression of CD59, a powerful complement regulatory protein found in the corneal epithelium. It is estimated that discarded corneas from tissue banks could provide enough material for routine testing by this method.


PKCɛ mediates serine phosphorylation of connexin43 induced by lysophosphatidylcholine in neonatal rat cardiomyocytes.
Lysophosphatidylcholine (LPC) is a potent pro-arrhythmic derivative of the membrane phosphotidylcholine, which is accumulated in heart tissues during cardiac ischemia. However, the cellular mechanism underlying LPC-induced cardiomyocyte damage remains to be elucidated. This study focuses on the effects of LPC on cardiomyocyte gap junction. At 30μM, LPC decreased the spontaneous contraction rates of cardiomyocytes, and caused arrhythmic contraction without affecting cell viability. Connexin43 (Cx43) was seen as large plaques at cell junctions in control cells, whereas upon LPC treatment, the intensity of Cx43 staining was decreased in a concentration-sensitive manner and Cx43 staining appeared as tiny dots at cell junctions with a corresponding increase in cytoplasmic punctate staining. This distributional change of Cx43 was accompanied by an impairment of the gap junction intercellular communication (GJIC). Further, LPC treatment induced protein kinase C (PKC) activation, and PKC-dependent Cx43 phosphorylation at serine (Ser) 368. Pre-treatment with a specific PKCɛ inhibitor, eV1-2, prevented the LPC-induced Cx43 phosphorylation at Ser368 and the loss of Cx43 from gap junctions, both of which may disturb GJIC functions. Furthermore, siRNA knockdown of PKCɛ in H9c2 cells prevented LPC-induced serine phosphorylation of Cx43, confirming the role of PKCɛ in Cx43 serine phosphorylation. Double labeling immunofluorescence showed that LPC increased the colocalization of Cx43 with ubiquitin, and pretreatment with MG132 effectively prevented LPC-induced gap junction disassembly. LPC increased the ubiquitination of Cx43, which was blocked by eV1-2 pretreatment, suggesting that LPC accelerated the intracellular degradation of Cx43 via the ubiquitin-proteasomal pathway. It can be concluded that LPC destroyed the structure and function of gap junctions via PKCɛ-mediated serine phosphorylation of Cx43. PKCɛ inhibitors might therefore be effective in prevention of LPC-related diseases.


Anxiety, past trauma and changes in relationships in Japan during COVID-19.
Widely shared traumas have the potential to both improve and impair our relationships with others. During COVID-19 anxiety has been seen as a major individual vulnerability associated with relationship change, as have the wider economic, situational factors facing families and communities. In this national sample of 997 Japanese respondents we assessed perceived relationship changes in couple relations, neighbourhood relations, and wider relations with Japanese nationals, alongside anxiety, exposure to previous mass traumas, household economics, education, and vulnerability to COVID-19. Whilst most respondents reported little change in their relationships during this year there was a small overall improvement in couple relationships and a decline in relations with wider communities. Participant's economic resources were positively associated with an improvement in couple relationships, while anxiety was associated with a decline in relations with both the neighbourhood and the wider society. While neither prior experience of mass trauma, nor education or health vulnerability to COVID-19, were associated with relationship change, having time to talk, and younger age, was positively associated with improvement in couple relations. Findings suggest that anxiety can function to distance relationships during a time of stress, but perceived changes in relationships are little effected by experience of previous trauma. Relationship growth is likely to be greatest in those with better economic conditions. Practitioners need to be mindful of the impact of enhanced anxiety during the pandemic on interpersonal relations, and a potential threat to the relationships of older couples during this time of pandemic threat.


Structures of complexes comprised of Fischerella transcription factor HetR with Anabaena DNA targets.
HetR is an essential regulator of heterocyst development in cyanobacteria. Many mutations in HetR render Anabaena incapable of nitrogen fixation. The protein binds to a DNA palindrome upstream of hetP and other genes. We have determined the crystal structures of HetR complexed with palindromic DNA targets, 21, 23, and 29 bp at 2.50-, 3.00-, and 3.25-Å resolution, respectively. The highest-resolution structure shows fine details of specific protein-DNA interactions. The lower-resolution structures with longer DNA duplexes have similar interaction patterns and show how the flap domains interact with DNA in a sequence nonspecific fashion. Fifteen of 15 protein-DNA contacts predicted on the basis of the structure were confirmed by single amino acid mutations that abolished binding in vitro and complementation in vivo. A striking feature of the structure is the association of glutamate 71 from each subunit of the HetR dimer with three successive cytosines in each arm of the palindromic target, a feature that is conserved among all known heterocyst-forming cyanobacteria sequenced to date.


Development and validation of a predictive model for the growth of Vibrio vulnificus in postharvest shellstock oysters.
Postharvest growth of Vibrio vulnificus in oysters can increase risk of human infection. Unfortunately, limited information is available regarding V. vulnificus growth and survival patterns over a wide range of storage temperatures in oysters harvested from different estuaries and in different oyster species. In this study, we developed a predictive model for V. vulnificus growth in Eastern oysters (Crassostrea virginica) harvested from Chesapeake Bay, MD, over a temperature range of 5 to 30°C and then validated the model against V. vulnificus growth rates (GRs) in Eastern and Asian oysters (Crassostrea ariakensis) harvested from Mobile Bay, AL, and Chesapeake Bay, VA, respectively. In the model development studies, V. vulnificus was slowly inactivated at 5 and 10°C with average GRs of -0.0045 and -0.0043 log most probable number (MPN)/h, respectively. Estimated average growth rates at 15, 20, 25, and 30°C were 0.022, 0.042, 0.087, and 0.093 log MPN/h, respectively. With respect to Eastern oysters, bias (B(f)) and accuracy (A(f)) factors for model-dependent and -independent data were 1.02 and 1.25 and 1.67 and 1.98, respectively. For Asian oysters, B(f) and A(f) were 0.29 and 3.40. Residual variations in growth rate about the fitted model were not explained by season, region, water temperature, or salinity at harvest. Growth rate estimates for Chesapeake Bay and Mobile Bay oysters stored at 25 and 30°C showed relatively high variability and were lower than Food and Agricultural Organization (FAO)/WHO V. vulnificus quantitative risk assessment model predictions. The model provides an improved tool for designing and implementing food safety plans that minimize the risk associated with V. vulnificus in oysters.


Effects of Cd, Cu, Zn and their combined action on microbial biomass and bacterial community structure.
Heavy metal pollution can decrease the soil microbial biomass and significantly alter microbial community structure. In this study, a long-term field experiment (5 years) and short-term laboratory experiment (40 d) were employed to evaluate the effects of heavy metals (Cd, Cu, Zn), and their combinations at different concentrations, on the soil microbial biomass and the bacterial community. The ranges of heavy metal concentration in the long-term and short-term experiments were similar, with concentration ranges of Cd, Cu and Zn of about 0.3-1.5, 100-500, and 150-300 mg kg-1, respectively. Microbial biomass decreased with increasing soil heavy metal concentrations in both the long-term and short-term experiments. The interaction between soil physicochemical factors (pH, TN, TC) and heavy metals (Cd, Cu, Zn) played a major role in change in the bacterial community in long-term polluted soil. In the laboratory experiment, although each heavy metal had an adverse effect on the microbial biomass and community structure, Cu appeared to have a greater role in the changes compared to Cd and Zn. However, the synergistic effects of the heavy metals were greater than those of the single metals and the synergistic effect between Cu and Cd was greater than that of Cu and Zn.


Syphilis: the international challenge of the great imitator.
Syphilis is a systemic disease caused by the spirochete Treponema pallidum. The name of this ancient but pervasive infection is proverbial to health care providers. The worldwide recognition of this term, however, argues with the intricacy of the disease in addition to the diagnostic and therapeutic challenges that persistently affect the global control of syphilis up to the present. This article focuses on the varied presentations of the infection, earning the title the "great imitator." The article also tackles other significant concerns regarding this malady.


Intronic RNA: Ad'junk' mediator of post-transcriptional gene regulation.
RNA splicing, the process through which intervening segments of noncoding RNA (introns) are excised from pre-mRNAs to allow for the formation of a mature mRNA product, has long been appreciated for its capacity to add complexity to eukaryotic proteomes. However, evidence suggests that the utility of this process extends beyond protein output and provides cells with a dynamic tool for gene regulation. In this review, we aim to highlight the role that intronic RNA plays in mediating specific splicing outcomes in pre-mRNA processing, as well as explore an emerging class of stable intronic sequences that have been observed to act in gene expression control. Building from underlying flexibility in both sequence and structure, intronic RNA provides mechanisms for post-transcriptional gene regulation that are amenable to the tissue and condition specific needs of eukaryotic cells. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.


Presence of galanin in dopaminergic neurons of the sheep infundibular nucleus: a double staining immunohistochemical study.
The distribution of tyrosine hydroxylase (TH) and of galanin immunoreactive (IR) neurons were examined in the sheep infundibular nucleus. Antisera raised against TH and galanin were used on adjacent sections and for double immunohistochemical staining of the same sections. There was considerable overlap in the distribution of TH and galanin-IR neurons in the medial part of the nucleus. Most of the galanin-IR neurons were also TH-IR, but less than 50% of the TH-IR neurons also expressed galanin immunoreactivity. Neurons immunoreactive to TH alone were observed close to the third ventricle and in the rostral part of the infundibular nucleus. In the median eminence, TH and galanin-IR fibres overlapped mainly in the lateral and dorsal parts of the external layer, but the colocalisation of both antigens could not be assessed on the available material. Thus, in sheep, the population of catecholaminergic neurons of the infundibular nucleus may be subdivided into different subpopulations according to their peptide content, but does not appear segregated as in rat and human.


Flavour physics and the Large Hadron Collider beauty experiment.
An exciting new era in flavour physics has just begun with the start of the Large Hadron Collider (LHC). The LHCb (where b stands for beauty) experiment, designed specifically to search for new phenomena in quantum loop processes and to provide a deeper understanding of matter-antimatter asymmetries at the most fundamental level, is producing many new and exciting results. It gives me great pleasure to describe a selected few of the results here-in particular, the search for rare B(0)(s)-->μ+ μ- decays and the measurement of the B(0)(s) charge-conjugation parity-violating phase, both of which offer high potential for the discovery of new physics at and beyond the LHC energy frontier in the very near future.


Incident CHD and ischemic stroke associated with lipoprotein(a) by levels of Factor VIII and inflammation.
Inflammation and coagulation may contribute to the increased risk for atherosclerotic cardiovascular disease (ASCVD) associated with high lipoprotein(a). The association of lipoprotein(a) with ASCVD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hs-CRP), a marker of inflammation. Determine the association of lipoprotein(a) with incident ASCVD by levels of coagulation Factor VIII controlling for hs-CRP. We analyzed data from 6,495 men and women 45 to 84 years of age in the Multi-Ethnic Study of Atherosclerosis (MESA) without prevalent ASCVD at baseline (2000-2002). Lipoprotein(a) mass concentration, Factor VIII coagulant activity, and hs-CRP were measured at baseline and categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident coronary heart disease (CHD) and ischemic stroke through 2015. Over a median follow-up of 13.9 years, there were 390 CHD and 247 ischemic stroke events. The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) (≥40.1 versus <40.1 mg/dL) including adjustment for hs-CRP among participants with low and high Factor VIII was 1.07 (0.80-1.44) and 2.00 (1.33-3.01), respectively (p-value for interaction 0.016). The hazard ratio (95%CI) for CHD associated with high lipoprotein(a) including adjustment for Factor VIII was 1.16 (0.87-1.54) and 2.00 (1.29-3.09) among participants with low and high hs-CRP, respectively (p-value for interaction 0.042). Lp(a) was not associated with ischemic stroke regardless of Factor VIII or hs-CRP levels. High lipoprotein(a) is a risk factor for CHD in adults with high levels of hemostatic or inflammatory markers.


"It all depends on why it's red": qualitative interviews exploring patient and professional views of a traffic light system for IVF add-ons.
Background IVF add-ons are techniques, medicines or procedures used in addition to standard IVF with the aim of improving the chance of success. The United Kingdom's IVF regulator, ( the Human Fertilisation Embryology Authority (HFEA) developed a traffic light system to categorise add-ons as either green, amber, or red, based on results of randomised controlled trials. Method Qualitative interviews were undertaken to explore understanding and views of the HFEA traffic light system among IVF clinicians, embryologists and IVF patients across Australia and the United Kingdom. Results A total of 73 interviews were conducted. Overall, participants were supportive of the intention of the traffic light system, however many limitations were raised. It was widely recognized that a simple traffic light system necessarily omits information which may be important to understanding the evidence base. In particular, the red category was used in scenarios that patients viewed as having different implications for their decision-making, including 'no evidence' and 'evidence of harm'. Patients were surprised at the absence of any green add-ons and questioned the value of a traffic light system in this context. Many participants considered the website a helpful starting point, but desired more detail, including the contributing studies, results specific to patient demographics (e.g., <35 years and >35 years), and inclusion of more options (e.g. acupuncture). Overall, participants believed the website to be reliable and trustworthy, particularly due to the Government affiliation, and despite some concerns regarding transparency and an overly cautious regulator. Conclusion Participants identified many limitations with the current application of the traffic light system. These could be considered in any future updates to the HFEA website and for others developing similar decision support tools.


Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?
Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function. We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01). Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.


Host visitation sequence as a determinant of search persistence in fruit parasitic tephritid flies.
We tested, through field experiments and simulation models, the hypothesis that fruit-searching tephritid fruit flies adjust their within-tree search persistence according to the sequence and timing of encounters with parasitized (i.e. egg-infested) and unparasitized Crataegus sp. host fruit. In the field, we presented flies with 4 different sequences of unparasitized [=C] and parasitized [=M] fruit: 5M+0C; 1C+5M; 5M+1C, 1C+0M. Following fruit presentation, flies were permitted to forage freely within trees, which harboured no fruit, until emigration occurred. Under these conditions, flies that encountered the aforementioned different sequences of hosts, displayed differences in Giving Up Time, measured as active foraging time and number of leaf visits, in a manner predicted prior to testing. These differences were, however, not statistically significant. Based upon the results described above, we then built 3 simulation models that predicted within-tree Giving Up Times for individual flies: Model 1-Giving Up Time is incremented and decremented by fixed amounts following encounters by the fly with suitable (i.e. for oviposition) and unsuitable hosts, respectively; Model 2-similar to Model 1, but increment and decrement values are variable and are dependent upon the time since previous encounters by the fly with suitable and unsuitable hosts; Model 3-Giving Up Time is fixed. Comparison with previously reported field data for tephritid flies showed that Model 2 predicted rather well, and significantly better than Models 1 and 3, Giving Up Time for wild type tephritid flies under seminatural field conditions. We discuss our results in light of contemporary foraging theory.


Experiential learning--a theoretical framework for perioperative education.
A PERIOPERATIVE NURSING COURSE that uses Kolb's experiential learning theory and learning cycle as a framework was developed to provide nurses new to the OR with a solid knowledge base with which to further their practice. THIS FRAMEWORK can be used to leverage learning style, promote critical thinking, and encourage active learning.


Erratum to: Transthoracic mini-open approach for anterior monosegmental stabilization and fusion.
Unfortunately, the title of the above mentioned article was incorrectly published on the original version. The complete correct title should read as follows: "Transthoracic mini-open approach for anterior monosegmental stabilization and fusion".


Heart involvement in hepatolenticular degeneration.
The case of a 10-year-old boy with a mild abdominal form of hepatolenticular degeneration, showing clinical, laboratory and histological manifestations of heart involvement is reported. The microscopical examination of myocardial fragments collected by intracavitary puncture biopsy, using hematoxylin-eosine and the histochemical method with rubeanic acid, showed a medium degree of myocardial damage and the presence of copper deposition in the tissue. Copper concentration on a myocardial biopsy fragment was almost 10 times the normal heart content. Comments are made on the relationship of the clinical, laboratory and pathological findings with the degree of copper storage on the myocardium.


Basement membrane assembly, stability and activities observed through a developmental lens.
Basement membranes are cell surface associated extracellular matrices containing laminins, type IV collagens, nidogens, perlecan, agrin, and other macromolecules. Biochemical and ultrastructural studies have suggested that basement membrane assembly and integrity is provided through multiple component interactions consisting of self-polymerizations, inter-component binding, and cell surface adhesions. Mutagenesis in vertebrate embryos and embryoid bodies have led to revisions of this model, providing evidence that laminins are essential for the formation of an initial polymeric scaffold of cell-attached matrix which matures in stability, ligand diversity, and functional complexity as additional matrix components are integrated into the scaffold. These studies also demonstrate that basement membrane components differentially promote cell polarization, organize and compartmentalize developing tissues, and maintain adult tissue function.


Synthesis and biological evaluation of new 4beta-anilino- and 4beta-imido-substituted podophyllotoxin congeners.
A series of C-4-anilino- and C-4-imido-substituted new podophyllotoxin congeners have been designed, synthesized, and evaluated for their cytotoxicity and DNA topoisomerase-II (topo-II) inhibition potential. Some of these compounds have exhibited promising in vitro anticancer and topo-II inhibition activity.


Oxygen dependence of two-photon activation of zinc and copper phthalocyanine tetrasulfonate in Jurkat cells.
Photodynamic therapy (PDT), the use of light-activated drugs, is a promising treatment of cancer as well as several nonmalignant conditions. However, the efficacy of one-photon (1-gamma) PDT is limited by hypoxia, which can prevent the production of the cytotoxic singlet oxygen ((1)O(2)) species, leading to tumor resistance to PDT. To solve this problem, we propose an irradiation protocol based on a simultaneous, two-photon (2-gamma) excitation of the photosensitizer (Ps). Excitation of the Ps triplet state leads to an upper excited triplet state T(n) with distinct photochemical properties, which could inflict biologic damage independent of the presence of molecular oxygen. To determine the potential of a 2-gamma excitation process, Jurkat cells were incubated with zinc or copper phthalocyanine tetrasulfonate (ZnPcS(4) or CuPcS(4)). ZnPcS(4) is a potent (1)O(2) generator in 1-gamma PDT, while CuPcS(4) is inactive under these conditions. Jurkat cells incubated with either ZnPcS(4) or CuPcS(4) were exposed to a 670 nm continuous laser (1-gamma PDT), 532 nm pulsed-laser light (2-gamma PDT), or a combination of 532 and 670 nm (2-gamma PDT). The efficacy of ZnPcS(4) to photoinactivate the Jurkat cells decreased as the concentration of oxygen decreased for both the 1-gamma and 2-gamma protocols. In the case of CuPcS(4), cell phototoxicity was measured only following 2-gamma irradiation, and its efficacy also decreased at a lower oxygen concentration. Our results suggest that for CuPcS(4) the T(n) excited state can be populated after 2-gamma irradiation at 532 nm or the combination of 532 and 670 nm light. Dependency of phototoxicity upon aerobic conditions for both 1-gamma and 2-gamma PDT suggests that reactive oxygen species play an important role in 1-gamma and 2-gamma PDT.


Excitability of spinal neural function during several motor imagery tasks involving isometric opponens pollicis activity.
It is unclear whether mental simulation without actual muscle contraction associated with actual motion can increase the excitability of the spinal neural function. To determine the best method for mental simulation without actual muscle contraction, we analyzed the F-wave of thenar muscles after stimulating the median nerve by motor imagery whilst holding the sensor of a pinch meter between the thumb and index finger and without holding the sensor. Healthy volunteers (n = 11; mean age, 34 years) participated in this study after providing informed consent. We examined the F-wave of the left thenar muscles after stimulating the left median nerve at the wrist at rest and under holding and motor imagery conditions. For the motor imagery condition, the subjects were asked to establish 50% maximal voluntary contraction (MVC) of isometric contraction while holding the sensor between the thumb and index finger (motor imagery with the sensor condition) and without holding the sensor on another day (motor imagery without the sensor condition). The persistence and amplitude ratio of F/M during motor imagery with or without the sensor was better than that during relaxation. In particular, this ratio was significantly higher under the with sensor condition than under the without sensor condition. Movement preparation for a motor imagery task involving 50% MVC isometric contraction of the opponens pollicis is important.


Arterialization of the portal vein in cirrhosis: the findings at wedge hepatic venography.
A new operation for the treatment of cirrhosis and portal hypertension has recently been described involving arterialization of the portal vein in combination with an end-to-side portacaval shunt. We present, for the first time, the appearances at wedge hepatic venography. No significant change is seen in the wedge hapatic pressure as a result of this technique, and the sinusoidal pattern is preserved. Filling of the portosplanchnic collaterals is not as frequent as after end-to-side shunts alone, and the appearances seem to reflect improved sinusoidal perfusion. The clinical results have been encouraging.


Detection and elimination of motion artifacts by regeneration of k-space.
A method has been developed using techniques from partially parallel imaging (PPI) to detect localized inconsistencies in k-space that are caused by certain types of motion. The inconsistent data are discarded and consistent data regenerated from the remaining data using PPI techniques. The price is a small decrease in signal-to-noise ratio (SNR) and additional postprocessing. An iterative scheme is presented which does not require separately acquired coil sensitivity information for the PPI reconstructions. This method has been found to reduce artifact levels in phantom and in vivo test studies.


Room-Temperature Chemoselective Hydrogenation of Nitroarene Over Atomic Metal-Nonmetal Catalytic Pair.
Constructing atomic catalytic pair emerges as an attractive strategy to achieve better catalytic performance. Herein, an atomic Ir1 ─P1 /NPG catalyst with asymmetric Ir─N2 P1 sites that delivers superb activity and selectivity for hydrogenation of various functionalized nitrostyrene is reported. In the hydrogenation reaction of 3-nitrostyrene, Ir1 ─P1 /NPG (NPG refers to N, P-codoped graphene) shows a turnover frequency of 1197 h-1 , while the reaction cannot occur over Ir1 /NG (NG refers to N-doped graphene). Compared to Ir1 /NG, the charge density of the Ir site in Ir1 ─P1 /NPG is greatly elevated, which is conducive to H2 dissociation. Moreover, as revealed by density functional theory calculations and poisoning experiments, the P site in Ir1 ─P1 /NPG is found able to bind nitrostyrene, while the neighboring Ir site provides H to reduce the nitro group in chemoselective hydrogenation of nitrostyrene. This work offers a successful example of establishing atomic catalytic pair for driving important chemical reactions, paving the way for the development of more advanced catalysts to further improve the catalytic performance.


MR-PheWAS for the causal effects of serum magnesium on multiple disease outcomes in Caucasian descent.
Magnesium is integral to many physiological processes, whereas variations in its levels, even within the normal range, can have critical implications for health. To explore the broad clinical effects of varying serum magnesium levels, we performed a two-sample Mendelian randomization and phenome-wide association study (MR-PheWAS) in the UK Biobank cohort. In total, MR-PheWAS analysis implicated a causal role of serum magnesium levels in five disease groups and six disease outcomes. In addition, our study indicated the gender-specific effects of nine disease groups/outcomes in MR estimated effects. The protein-protein interaction network demonstrated an interaction between the serum magnesium-associated gene DCDC1 and the cataract- associated gene PAX6. The present study verified several previously reported disease outcomes and identified novel potential disease outcomes for serum magnesium levels. The DCDC1 gene and the PAX6 gene may be the new targets for promoting the treatments of cataracts using magnesium intervention.


CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement.
To assess the time to disease progression (TTP), long-term survival benefit and safety of patients with unresectable hepatocellular carcinoma (HCC) treated with computed tomography (CT)-guided radiofrequency ablation (RFA) with transarterial chemoembolization chemoembolization (TACE). This study was approved by the institutional review board. We reviewed the records of patients with intermediate and advanced HCC treated with CT-guided RFA with TACE between January 2000 and December 2009. Median TTP, overall survival (OS) and hepatic function were analyzed with the Kaplan-Meier method and log-rank tests. One hundred and twenty-two patients (112 men and 10 women, mean age 53 years, range 18-86 years) were included in the study. The median follow-up time was 42 months (range 6-89 months), TTP was 6.8 months, the median OS was 31 months, and the 1-, 3-, and 5-year OS were 88.5%, 41.0%, and 10.7%. The results of the univariate analysis revealed that intrahepatic lesion, AJCC stage, and Child-Pugh stage were predictors of OS (P<0.01). In the multivariate analysis, the AJCC stage system showed a statistically significant difference for prognosis. Procedure-related death was 0.21% (1/470) within 1 month, and a statistical difference was found between the TACE and RFA of liver decompensation and Child-Pugh stage (P<0.05). The survival probabilities of OS increased with CT-guided RFA with TACE, as observed in randomized studies from Europe and Asia. The longest TTP was observed for the intermediate stage HCC. The procedures were well tolerated with acceptable minor and major complications in unresectable HCC patients.


Computer skills in patients with movement disorders.
Electronic communication is important in healthcare, but the level of computer proficiency among patients with neurological disorders is unknown. This study sought to determine the proportion of a movement disorder clinic population that was able to perform basic computer skills, and the effect of specific cognitive and motor features on computer proficiency. One hundred and four movement disorder patients participated. Seventy-four completed both paper and computerized questionnaires to evaluate data entry skills and thirty subjects completed paper questionnaires only. Basic e-mail messaging and Internet skills were evaluated. Demographic information, Mini-Mental Status Examination (MMSE) score, and Hoehn and Yahr stage were assessed. Ninety-six percent of subjects successfully completed computerized data entry tasks, and over 70% completed e-mail and Internet tasks. Computer data entry had an average accuracy of nearly 95% when compared to paper data entry. Poorer performance on computer tasks was associated with older age, less education, and cognitive impairment. Computer performance was reduced in subjects with a history of parkinsonism and when both tremor and dyskinesia were present during task performance. Nearly three-quarters of subjects have access to a computer. Subjects who completed the paper questionnaire but refused to complete the computer questionnaire were older, less educated and more cognitively impaired. The majority of patients visiting a tertiary movement disorders center were able to perform computer data entry, e-mail messaging and Internet usage. These results reinforce the potential value of electronic communication and information systems in neurology practice.


The effects of calcium and magnesium on inhibitory junctional transmission in smooth muscle of guinea pig small intestine.
The membrane potential of smooth muscle cells in the circular layer of the guinea pig ileum was recorded using intracellular electrodes. Transmural stimulation, in the presence of atropine, caused a transient hyperpolarization, an inhibitory junction potential (IJP). IJP's are thought to result from the action of transmitter released from intramural inhibitory nerves. It has been reported that, in the guinea pig jejunum, the amplitude of the IJP resulting from field stimulation is not altered by changes in the calcium and magnesium ion concentration in the bathing solution. Experiments reported here have shown that the IJP amplitude decreased markedly on reducing the calcium ion concentration and or increasing the magnesium ion concentration. Indirect evidence is presented suggesting that the decrease in amplitude of the IJP is due to a decrease in the amount of transmitter released.


A novel dichromate-sensitive fluorescent nano-chemosensor using new functionalized SBA-15.
A novel fluorescence nano-chemosensor for Cr(2)O(7)(2-) anion has been developed by assembly of fluorescent aluminum complex of 8-hydroxyquinoline (AlQ(x)) within the channels of modified SBA-15. SBA-SPS-AlQ(x) shows a fluorescence emission at 486 nm. The observed remarkable fluorescence of SBA-SPS-AlQ(x) quenches in presence of Cr(2)O(7)(2-) anion. The results showed that this fluorescent nano-material can be a useful chemo-sensor for determination of dichromate anions in aqueous solutions. The linear detecting range of fluorescent nano-chemosensor for Cr(2)O(7)(2-) anion was 0.16-2.9 μmol L(-1). The lowest limit of detection (LDL) was also found to be 0.2 ng mL(-1) in aqueous solutions. SBA-SPS-AlQ(x) showed selectively and sensitively fluorescent quenching response toward Cr(2)O(7)(2-) ion in comparison with I(3)(-), NO(3)(-), CN(-), CO(3)(2-), Br(-), Cl(-), F(-), H(2)PO(4)(-) and SO(4)(2-) ions, which was because of the higher stability of its inorganic complex with dichromate ion.


Statistical moment analysis of hepatobiliary transport of phenol red in the perfused rat liver.
A new experimental system was applied to study hepatobiliary transport of drugs. Rat livers were perfused using a single-pass technique, and phenol red was momentarily introduced to this system from the portal side. Outflow dilution patterns of phenol red were analyzed using statistical moment theory, and kinetic parameters of hepatic distribution and elimination of phenol red were calculated from moments, namely, the hepatic extraction ratio (Ei) and elimination rate constant (kel,i). A larger distribution volume (Vi) was obtained for phenol red than for 131I-human serum albumin (HSA) and 51Cr-red blood cells (RBC), indicating its extravascular diffusivity. The biliary excretion of conjugated phenol red was delayed relative to that of the free agent. The larger biliary mean transit time (tbile,conj.) represents the processes of biliary transport and intrahepatic metabolism. Further, the effects of dose and perfusion temperature on the hepatobiliary transport of phenol red were determined. With high doses or low perfusion temperatures (20 and 27 degrees C), Ei, kel,i, and intrinsic clearance (CLint,i) of phenol red and biliary recovery of free and conjugated phenol red (Fbile,free, Fbile,conj) significantly decreased. The temperature-dependent and saturable processes in hepatic uptake, metabolism, and biliary excretion of phenol red were assessable to moment analysis.


A reverse-transcription PCR method for detecting all known ephemeroviruses in clinical samples.
Bovine ephemeral fever virus (BEFV) is an economically important vector-borne pathogen of cattle in tropical and sub-tropical regions of Australia, Asia, Africa and the Middle East. Although clinical cases of bovine ephemeral fever are usually attributed to BEFV, definitive diagnosis is rarely performed and at least two other related viruses, kotonkon virus (KOTV; an ephemerovirus) and Fukuoka virus (FUKAV; an unassigned rhabdovirus), can cause similar clinical signs. As vaccines have been developed against BEFV but not against KOTV or FUKAV, a test capable of detecting and differentiating these pathogens would be useful. In the present study, an RT-PCR method using degenerate primers designed to a region of block III of the polymerase (L) gene was developed and optimised for primer annealing temperature and MgCl₂ concentration. The RT-PCR detected all known ephemeroviruses and several other closely related insect-transmitted rhabdoviruses, including FUKAV. Viruses could be identified by subsequent sequencing and phylogenetic analysis of the amplicons. BEFV could be detected using tissue culture isolates or cattle blood to a sensitivity of 500 RNA copies per reaction. This test will be useful for establishing the identity of the causative agent of bovine ephemeral fever from field samples and cultured isolates.


Quenched fluorescent substrate-based peptidase assays.
The use of specific quenched fluorescent substrates (QFS) provides a rapid and sensitive method to measure peptidase activity, and is readily adaptable to high-throughput screening of potential peptidase inhibitors. In this chapter, we discuss general considerations for the development of QFS assays, and describe in detail an assay protocol for the mammalian metallopeptidase, endothelin-converting enzyme.


Inhibitory effect of mouse interferon on the growth of an embryonal carcinoma in mice.
Embryonal carcinoma cells (F9) were resistant to the inhibitory effects of interferon (IFN) on viral multiplication and cell division in vitro. Nevertheless, daily administration of IFN resulted in a marked inhibition of the growth of this carcinoma injected intraperitoneally (ip) and increased mouse survival time. An incidental finding was that daily IFN treatment increased the serum level of alpha-fetoprotein in normal 129 mice.


Fourier analysis of the shape of normal and transformed epithelial cells derived from human transitional epithelium.
The aim of this paper is to show the possibility of objective mathematical description of changes occurring in the shape of cells in the process of transformation. The evaluation of the changes in cell shape of the chosen cell lines differing in transformation grade was performed by the use of Fourier analysis of the shape. Any two-dimensional contour can be described with specific accuracy in a mathematical manner using the closed form Fourier series of cosines. The components forming the analysed shape, called harmonics, are independent and uncorrelated measures of their contribution to the total shape. The shape of each cell can be represented by the spectrum of harmonic amplitudes. To quote the paper by Healy-Williams and Williams (1981): "The observed shape is partitioned into series, where gross shape, as elongation or triangularity, is measured by the harmonic amplitudes of the lower harmonic order and increasingly fine scaled surface sculpture is measured at higher orders". The statistically evaluated results allow the objective comparison of the cell shapes of several compared cell lines differing in transformation grades. Malignant transformation is supposed to be a multistep process. The different grades of transformation could be defined by several parameters as changes in the morphology of the cells, their ability to compete with fibroblasts, their life span, their angiogenic potency, their invasiveness in vitro and their tumorigenicity in nude mice. In this paper several human urothelial cell lines of normal and tumor origin differing in their transformation grade (TGr I-III) were compared by the use of Fourier analysis of their shape. TGr I cultures have finite life span but do not need intermittent collagenase treatment to prevent fibroblast overgrowth. TGr II cultures acquire infinite growth potential, here defined as capacity to survive at least 70 passages. They are neither tumorigenic nor invasive. TGr III cultures show infinite growth transformation, increased angiogenicity and ability to invade normal host tissue in vitro. They produce progressively growing tumors in nude mice. The following human uroepithelial cell lines differing in the degree of transformation were studied and compared by statistical evaluation of the harmonic amplitudes describing mathematically the cell shape: Two cell lines derived from human transitional cell carcinoma (TCC): 1. Hu 1703S classified as TGr I, 2. Hu 1703He classified as TGr III. It was found that these two cell lines differ in all harmonics. Two cell lines derived from morphological normal human bladder epithelium: 3. HCV-29 classified as TGr II.(ABSTRACT TRUNCATED AT 400 WORDS)


Erratum: Erratum: Breviscapine prevents downregulation of renal water and sodium transport proteins in response to unilateral ureteral obstruction.
[This corrects the article DOI: 10.22038/IJBMS.2016.6943.].


Species-dependent sensitivity to contaminants: an approach using primary hepatocyte cultures with three marine fish species.
There is limited knowledge about the sensitivity of different fish species to environmental pollutants. Such information is pivotal in risk assessment and to understand why some species appear to be more tolerant to contaminants than others. The aim of the current study was to evaluate whether primary hepatocyte cultures of three marine fish species could be established in the field and whether their sensitivity to selected contaminants would differ. Primary hepatocyte cultures of three marine fish species (plaice, long rough dab, Atlantic cod) were established and exposed for 24 h to copper (20-2500 mg L⁻¹) and statins (1-200 mg L⁻¹). Endpoints were esterase activity, metabolic activity and reduced glutathione (GSH) content, all using fluorescent probes. Flatfish hepatocytes were more susceptible to copper and statin exposure than hepatocytes from cod. This study has shown that species-dependent differences in contaminant sensitivity can be investigated using primary hepatocyte cultures.


Medial Patellofemoral Complex Reconstruction Techniques Are Not Equivalent at Lower Flexion in the Setting of Patella Alta: A Biomechanical Comparison.
To (1) determine the effect of severe patella alta on lateral patellar displacement after medial patellofemoral ligament (MPFL) reconstruction and medial quadriceps tendon-femoral ligament (MQTFL) reconstruction and (2) determine whether lateral displacement significantly differs between MPFL and MQTFL reconstructions in the setting of severe patella alta (Caton-Deschamps Index [CDI] of 1.6). Eight cadaveric specimens were included. High-tensile strength suture was used to create a model of adjustable patellar height. Patellar height was set using fluoroscopy to CDI ratios of 1.0 (normal) and 1.6 (alta). Specimens underwent testing (1) with MPFL reconstruction, (2) with MQTFL reconstruction, and (3) in a medial patellofemoral complex (MPFC)-deficient control state, in randomized order, at both CDI settings: 1.0 and 1.6. Lateral patellar translation was measured at 0°, 10°, 20°, 30°, 45°, 60°, and 90° of knee flexion with 10 N of laterally directed load. At a CDI of 1.6, MPFL reconstruction showed significantly lower lateral displacement than MQTFL reconstruction at 0° and 20°. When compared with MPFC-deficient controls at a CDI of 1.6, MPFL reconstruction showed significantly lower displacement at 0° and 20° whereas MQTFL reconstruction was not significantly different at any degree of flexion. In the setting of severe patella alta (CDI of 1.6), MPFL reconstruction results in less lateral patellar displacement than MQTFL reconstruction at 0° and 20° of knee flexion. At higher flexion angles (≥30°), there is no difference between the 2 reconstruction techniques and the CDI no longer has an effect. At a CDI of 1.0, MPFL reconstruction shows lower displacement than MQTFL reconstruction in full extension only. Surgeons performing MPFC reconstruction should evaluate patients for patella alta and consider patellar height when deciding on the reconstruction technique. This study suggests that MQTFL reconstruction may be less stable than MPFL reconstruction in the setting of patella alta, without other known pathoanatomic factors, at early knee flexion angles. Patellar height should be considered when choosing the appropriate reconstruction technique in the absence of a distalization procedure.


[Loco-regional anesthesia in remote medical units: II.--Anesthesia of the upper limb: plexic blocks (author's transl)].
The anesthetic block of the upper limb plexus may be realized by either sus-cladications and possible complications.


Uptake of different species of iodine by water spinach and its effect to growth.
A hydroponic experiment has been carried out to study the influence of iodine species [iodide (I(-)), iodate (IO(-)(3)), and iodoacetic acid (CH(2)ICOO(-))] and concentrations on iodine uptake by water spinach. Results show that low levels of iodine in the nutrient solution can effectively stimulate the growth of biomass of water spinach. When iodine levels in the nutrient solution are from 0 to 1.0 mg/l, increases in iodine levels can linearly augment iodine uptake rate by the leafy vegetables from all three species of iodine, and the uptake effects are in the following order: CH(2)ICOO(-) >I(-)>IO(-)(3). In addition, linear correlation was observed between iodine content in the roots and shoots of water spinach, and their proportion is 1:1. By uptake of I(-), vitamin C (Vit C) content in water spinach increased, whereas uptake of IO(-)(3) and CH(2)ICOO(-) decreased water spinach Vit C content. Furthermore, through uptake of I(-) and IO(-)(3). The nitrate content in water spinach was increased by different degrees.


Gender biases in Spanish rheumatology: Perception and facts.
To identify perceptions of gender bias in Spanish rheumatology and to quantify the involvement of both sexes in all areas of the specialty. A survey was sent to all members of the SER on participation and perception of biases and of their own competencies, and actual data on participation in governing bodies, congresses, committees, and Spanish rheumatology departments in the last 5 years were reviewed. The survey was answered by 95 rheumatologists, 4.8% of SER members (14 men and 81 women), both groups being similar in terms of age, academic level, and position and work centre. No differences were detected in the distribution of work and non-work tasks between sexes, nor in invitations to positions of power in the last five years, nor in the perception of capacity to occupy the different positions of power, which was high for both sexes. Male respondents more frequently consider that activities such as participating in a scientific committee or giving a conference are not empowering. A third of both sexes consider that the SER should review its processes with a gender perspective but less than a third believe that this should be done by quotas. The reality of the last 5 years is that 1) there is a male to female ratio of 3:2 on SER boards of directors and in this period there has been no female president or treasurer; 2) in the scientific committees of the congresses men predominate (2:1) although slightly less in the local organizing committee; 3) there are more male speakers and moderators than women (very striking in satellite symposia, 4: 1); 4) 9 out of 10 editors-in-chief are men; 5) in academic positions there are 3 men for every 2 women, 9 to 1 in professorships or emeritus positions; although more women supervise residents; and 6) there are more women (60%) than men (40%) in Spanish rheumatology departments, although 75% of department chiefs are men. Although not perceived by either the men or the women, there are biases in the involvement of women in important and leadership positions in the specialty.


Left atrial volume changes are an early marker of end-organ damage in essential hypertension: A multidisciplinary approach to an old problem.
Left atrial (LA) volume has been shown to be a predictor of adverse cardiovascular outcomes. The aim of this study was to evaluate the relation between LA phasic volumes and hypertensive end-organ damage (EOD), by using real time three-dimensional echocardiography (RT3DE) in patients with essential hypertension (HT). The study included 95 essential hypertensive patients (60 ± 10 years, 37 males). The patients were divided into three according to the presence of EOD, namely microalbuminuria and retinal vascular changes detected by direct ophthalmoscopy. The first group had no EOD. The second group (EOD+ group) had either microalbuminuria or retinal vascular changes while the third group (EOD++ group) had both renal and retinal damage. The three groups did not differ with regard to age, sex, or metabolic profile. In RT3DE measurements, there were significant differences in LA phasic volumes (LA maximal volume index, LA minimal volume index, LA pre-atrial contraction volume index, LA total stroke volume index, and LA active stroke volume index, P < .001) among the groups. Moreover, patients with more extended EOD had significantly worse LA reservoir and conduit functions. In the logistic regression analysis, the LA active stroke volume index was an independent predictor of EOD (82% sensitivity and 92% specificity, area under the curve = 0.96, P < .001). RT3DE measured LA phasic volumes and mechanical functions are associated with hypertensive EOD, which might serve as a surrogate endpoint for determining cardiovascular mortality and morbidity rates in patients with essential HT.


Change in Nox4 expression is accompanied by changes in myogenic marker expression in differentiating C2C12 myoblasts.
Myoblast differentiation is mediated by a cascade of changes in gene expression including transcription factors such as myogenin. Subsequent to myoblast differentiation, there is an increase in expression of the transmembrane protein NADPH oxidase (Nox). Nox is one of the primary factors for the generation of reactive oxygen species (ROS) in myogenic (C2C12) cells. Recently, ROS have been shown to be important regulators of several intracellular signaling pathways, and the full extent of their regulatory roles is yet to be discovered. In the present study, qRT PCR analysis demonstrated that Nox4 isoform is primarily expressed in differentiating C2C12 cells and contributes to the generation of ROS in C2C12 myoblast during differentiation. Over-expression and silencing of Nox4 expression during myoblast differentiation was accompanied by a reduction in intracellular ROS concentrations and an alteration in the expression patterns of Myf5, Pax7, MyoD1, and myogenin. This modulation was found to be associated with ERK1/2 phosphorylation. In both over-expression and reduced expression of Nox4, we found significant reductions in ERK1/2 phosphorylation. This indicates that cellular differentiation may be affected by Nox4-mediated endogenous ROS generation. These data suggest a new opportunity to study the temporal expression of Nox4 in the generation of ROS accompanying changes in myogenic differentiation.


Well-differentiated lymphocytic lymphoma with peripheral blood involvement, osteolytic bone lesions, and hypercalcemia. A case report and review of the literature.
It is rare for small lymphocytic B-cell malignancies to be associated with osteolytic bone lesions and/or hypercalcemia. The authors present an unusual case of well-differentiated lymphocytic lymphoma (DWDL) in a 70-year-old man who had osteolytic bone lesions and subsequently developed severe refractory hypercalcemia. The possible etiologic mechanisms responsible for these findings are discussed, and a brief review of the literature is presented.


Serum ghrelin levels in children with primary protein-energy malnutrition.
Ghrelin, an appetite-stimulating peptide, increases in cachectic conditions. It probably reflects peripheral nutritional status and influences nutrient intake and growth. The aim of the present study was to determine serum ghrelin levels in children with primary protein-energy malnutrition (PEM) and to find if any correlation exists between serum ghrelin levels and the clinical presentation of those patients. Twenty-eight children with primary PEM and 10 healthy children were included. Serum fasting ghrelin levels were measured using radioimmunoassay. Mean serum ghrelin level of healthy children and those with PEM were 107.7 +/- 40.1 pg/mL and 141.6 +/- 123.8 pg/mL, respectively (P < 0.001). Ghrelin levels were independent of age and sex (P > 0.05). Ghrelin was negatively correlated with body mass index in healthy children (P < 0.01), but not in those with PEM (P > 0.05). Mean serum ghrelin level of children with moderate malnutrition was higher than that of children with severe malnutrition (199.2 +/- 154.1 pg/mL vs 98.4 +/- 74.3 pg/mL, P < 0.05). Mean serum ghrelin levels of patients with kwashiorkor, marasmic kwashiorkor, and marasmus were 127.9 +/- 97.8 pg/mL, 138.7 +/- 95.8 pg/mL, and 162.3 +/- 185.0 pg/mL, respectively (P > 0.05). Serum ghrelin level is higher in patients with PEM, especially in those with marasmus, compared to healthy children. Although this observation suggests that ghrelin helps to fight malnutrition in children, it is obvious that further studies are needed to clarify the exact pathogenetic mechanism regarding this condition.


T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity.
Hematopoietic cell transplantation (HCT) has become standard-of-care for an increasing number of inborn errors of immunity (IEI). This report is the first to compare transplant outcomes according to T-cell-replete (ie, T-replete) HLA-matched grafts using alemtuzumab (n = 117) and T-cell-depleted (ie, T-depleted) HLA-mismatched grafts using T-cell receptor-αβ (TCRαβ)/CD19 depletion (n = 47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, peripheral blood stem cell (PBSC) in 85 (73%), and cord blood in 7 (6%). TCRαβ/CD19 depletion was performed on PBSCs from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year overall survival (OS) and event-free survival for the entire cohort were 85% (77%-90%) and 79% (69%-86%), respectively. Analysis according to age at transplant revealed a comparable 3-year OS between T-replete grafts (88%; 76%-94%) and T-depleted grafts (87%; 64%-96%) in younger patients (aged <5 years at HCT). For older patients (aged >5 years), the OS was significantly lower in T-depleted grafts (55%; 23%-78%) compared with T-replete grafts (87%; 68%-95%) (P = .03). Grade III to IV acute graft-versus-host disease was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete cord blood, and 2% of T-depleted PBSC (P = .73). Higher incidence of viremia (P < .001) and delayed CD3 reconstitution (P = .003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCRαβ/CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft.


The presence of smooth muscle cells in the rat ovary.
Using a histochemical procedure for the demonstration of glycogen phosphorylase, smooth muscle cells have been demonstrated in the rat ovary around follicles, corpora lutea, atretic follicles and between groups of interstitial cells.


Analysis of the immune response of human dendritic cells to Mycobacterium tuberculosis by quantitative proteomics.
The cellular immune response for Mycobacterium tuberculosis (M. tuberculosis) infection remained incompletely understood. To uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed M. tuberculosis (HKTB) treatment. Organic solvent-assisted trypsin digestion coupled with stable-isotope labeling and LC-MS/MS analysis was applied to quantitatively analyze the membrane protein expression of THP-1 derived dendritic cells. We evaluated proteins that were upregulated in response to HKTB treatment, and applied STRING website database to analyze the correlations between these proteins. Of the investigated proteins, aminopeptidase N (CD13) was found to be largely expressed after HKTB treatment. By using confocal microscopy and flow cytometry, we found that membranous CD13 expression was upregulated and was capable of binding to live mycobacteria. Treatment dendritic cell with anti-CD13 antibody during M. tuberculosis infection enhanced the ability of T cell activation. Via proteomics data and STRING analysis, we demonstrated that the highly-expressed CD13 is also associated with proteins involved in the antigen presenting process, especially with CD1 proteins. Increasing expression of CD13 on dendritic cells while M. tuberculosis infection and enhancement of T cell activation after CD13 treated with anti-CD13 antibody indicates CD13 positively involved in the pathogenesis of M. tuberculosis.


Projecting the effect of climate change on residential property damages caused by extreme weather events.
New Zealand's public insurer for natural hazards, the Earthquake Commission (EQC), provides residential insurance for some weather-related damage. Climate change and the expected increase in intensity and frequency of extreme weather-related events are likely to translate into higher damages and thus an additional financial liability for the EQC. We project future insured damages from extreme precipitation events associated with future projected climatic change. We first estimate the empirical relationship between extreme precipitation events and the EQC's weather-related insurance claims based on a complete dataset of all claims from 2000 to 2017. We then use this estimated relationship, together with climate projections based on future greenhouse gases concentration scenarios from six different dynamically downscaled Regional Climate Models, to predict the impact of future extreme precipitation events on EQC liabilities for different time horizons up to the year 2100. Our results show predicted adverse impacts that vary over time and space. The percent change between projected and past damages-the climate change signal-ranges between an increase of 7%-8% in liabilities for the period 2020 to 2040, and between 9% and 25% higher for the period 2080 to 2100. We also provide detail caveats as towhy these quantities might be mis-estimated. The projected increase in the public insurer's liabilities could also be used to inform private insurers, regulators, and policymakers who are assessing the future performance of both the public and private insurers that cover weatherrelated.


Laparoscopic cytoreductive nephrectomy and adrenalectomy for metachronous RCC metastases-Case report.
We report the case of a 69 y.o. man with a left solitary kidney presenting 3 tumoral masses and suspicion of a left adrenal nodular tumor. 48 months previously, the patient underwent laparoscopic right radical nephrectomy and adrenalectomy for a clear cell renal carcinoma, with a tumor free adrenal gland. 3D laparoscopic transperitoneal left cytoreductive nephrectomy and left adrenalectomy were performed within 23 min warm ischemia with no need of post operatory hemodialysis. The pathology exam reported metachronous metastases on left adrenal gland and on a left multifocal tumoral solitary kidney from the contralateral clear cell renal carcinoma prior diagnosed and treated at this patient. Cytoreductive nephrectomy on a solitary kidney brings technical challenges for the laparoscopic approach, especially when the tumor presents as multifocal lesions. Contralateral metachronous metastases and adrenal involvement in case of renal carcinoma are scarcely presented in the literature. The "en bloc" excision of the tumoral masses optimized warm ischemia time and improved the technical approach, even if the endophytic presentation imposed difficulty.