Cyclin B2 overexpression promotes tumour growth by regulating jagged 1 in hepatocellular carcinoma.
Our previous study showed that Cyclin B2 (CCNB2) is closely related to the occurrence and progression of hepatocellular carcinoma (HCC). This study aimed to clarify the effect of CCNB2 gene silencing on tumorigenesis in nude mice and to detect the potential mechanism. The effect of CCNB2 on HCC was tested in vivo. The downstream target genes of CCNB2 were predicted by proteomics and confirmed by western blot assay. The regulatory functions of CCNB2 in the proliferation and migration of HCC cells were determined through functional recovery experiments. The expression of the downstream target genes of CCNB2 was detected by immunohistochemistry. Knockdown of CCNB2 decreased tumour formation rate and tumour volume and weight and inhibited tumour proliferation. A total of 130 differentially expressed proteins were detected by proteomics, and Jagged 1 (JAG1) was predicted as the potential downstream target of CCNB2. Western blot assay revealed that CCNB2 and JAG1 expression was significantly correlated in HCC cells. The results of functional recovery experiments suggested that CCNB2 knockdown weakened the proliferation and migration ability of HCC cells, while JAG1 overexpression restored this ability of HCC cells that was weakened by CCNB2 knockdown. Immunohistochemistry showed that JAG1 expression was higher in HCC tissues than in paracancerous tissues and was related to tumour size and number and tumour thrombus formation. The proliferation of HCC cells in vivo was inhibited by CCNB2 knockdown. CCNB2 may accelerate the proliferation and metastasis of HCC cells by increasing JAG1 expression.


Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1.
The majority of human rhinoviruses use intercellular adhesion molecule 1 (ICAM-1) as a cell surface receptor. Two soluble forms of ICAM-1, one corresponding to the entire extracellular portion [tICAM(453)] and one corresponding to the two N-terminal immunoglobulin-like domains [tICAM(185)], have been produced, and their effects on virus-receptor binding, virus infectivity, and virus integrity have been examined. Results from competitive binding experiments indicate that the virus binding site is largely contained within the two N-terminal domains of ICAM-1. Virus infectivity studies indicate that tICAM(185) prevents infection by direct competition for receptor binding sites on virus, while tICAM(453) prevents infection at concentrations 10-fold lower than that needed to inhibit binding and apparently acts at the entry or uncoating steps. Neutralization by both forms of soluble ICAM-1 requires continual presence of ICAM-1 during the infection and is largely reversible. Both forms of soluble ICAM-1 can alter rhinovirus to yield subviral noninfectious particles lacking the viral subunit VP4 and the RNA genome, thus mimicking virus uncoating in vivo, although this irreversible modification of rhinovirus is not the major mechanism of virus neutralization.


Association between omentin and echo parameters in patients with chronic heart failure.
Adipose-derived adipokines have been demonstrated to be associated with the development of experimental heart disease through chronic inflammation and cardiac cell apoptosis. Omentin is to be one of the novel adipokines. The aim of this study is to investigate the relationship between circulating omentin and cardiac dysfunction in patients with chronic heart failure (CHF). A total of 189 CHF patients were studied, determining serum omentin and echocardiographic parameters. All participants were divided into two experimental groups: the 111 patients who had a left ventricular ejection fraction (EF) ≥40% (EF-H) and the 78 patients exhibiting EF values <40% (EF-L). The EF-L group showed significantly higher circulating omentin levels compared to the EF-H group (210.8±67.2 vs. 155.3±45.3, P<0.001; Student's t-test). Overall, the data of the linear regression analysis revealed that serum omentin levels correlated positively with left atrial diameters (r=0.31, P=0.006), left ventricular end-systolic dimensions (r=0.42, P<0.001), and left ventricular end-diastolic dimensions (r=0.38, P=0.002) and negatively with left ventricular EF (r=-0.45, P=0.001; Spearmen's rank correlations coefficients for each). The multiple regression model included all variables at p<0.1 by the univariate analysis. A multiple logistic regression analysis demonstrated that high levels of patients' serum omentin were associated with cardiac dysfunction in patients with CHF (OR=1.22; 95% CI: 0.91-1.58; P=0.009). These findings suggested that elevated serum omentin levels were only very mildly related to the changes in cardiac volume and function in CHF patients. Further studies are then needed to assess the real clinical value of omentin in this setting.


Functionally Active Microheterogeneous Systems for Elastomer Fire- and Heat-Protective Materials.
Elastomeric materials are utilized for the short-term protection of products and structures operating under extreme conditions in the aerospace, marine, and oil and gas industries. This research aims to study the influence of functionally active structures on the physical, mechanical, thermophysical, and fire- and heat-protective characteristics of elastomer compositions. The physical and mechanical properties of elastomer samples were determined using Shimazu AG-Xplus, while morphological research into microheterogeneous systems and coke structures was carried out on a scanning electronic microscope, Versa 3D. Differential thermal and thermogravimetric analyses of the samples were conducted on derivatograph Q-1500D. The presence of aluminosilicate microspheres, carbon microfibers, and a phosphor-nitrogen-organic modifier as part of the aforementioned structures contributes to the appearance of a synergetic effect, which results in an increase in the heat-protective properties of a material due to the enhancement in coke strength and intensification of material carbonization processes. The results indicate an 8-17% increase in the heating time of the unheated surface of a sample and a decrease in its linear burning speed by 6-17% compared to known analogues. In conclusion, microspheres compensate for the negative impact of microfibers on the density and thermal conductivity of a composition.


Effect of axial ligand plane reorientation on electronic and electrochemical properties observed in the A67V mutant of rat cytochrome b5.
Mutational studies directed at evaluating the effect of the axial ligand plane orientation on electrochemical properties of cytochrome b5 have been performed. As described in the previous paper, structural consequences of one of these mutations, the A67V mutation, have been evaluated using NMR solution methods. The lack of large shifts relative to the wild-type protein in both the imidazole Ndelta nitrogen and proton resonances of the H63 imidazole ring indicates that the hydrogen bond between the carbonyl of F58 and the imidazole ring of H63 remains intact in this mutant. Effects of the imidazole plane reorientation on the Fe d-orbitals were evaluated on the basis of interpretation of EPR spectra, near-infrared bands associated with ligand-to-metal charge transfer transitions, reorientation of the anisotropy of the paramagnetic center determined by calculation of pseudocontact shifts, and the temperature dependence of the contact-shifted resonances. The dominant effect of the imidazole reorientation appears to have been a destabilization of the d(xz) orbital energy and a reorientation of the d(pi) orbitals. This is surprising in light of the -20 mV shift in the reduction potential of the mutant relative to the wild-type protein and indicates that a destabilization of d(yz)-orbital energy level of the reduced state dictates the observed change in reduction potential. Measured values for the reorganizational energy and heterogeneous electron transfer rates were indistinguishable for wild-type and mutant proteins. This is perhaps surprising, given significant differences in the pattern of electron delocalization into the porphyrin ring observed as significantly altered contact shift patterns. Mutational studies perturbing the H39 imidazole were also performed but with more limited success.


Computational screening, ensemble docking and pharmacophore analysis of potential gefitinib analogues against epidermal growth factor receptor.
The observable mutated isoforms of epidermal growth factor receptor (EGFR) are important considerable therapeutic benchmarks in moderating the non-small cell lung cancer (NSCLC). Recently, quinazoline-based ATP competitive inhibitors have been developed against the EGFR; however, these imply the mutation probabilities, which contribute to the discovery of high probable novel inhibitors for EGFR mutants. Therefore, SAR-based bioactivity analysis, molecular docking and computational toxicogenomics approaches were performed to identify and evaluate new analogs of gefitinib against the ligand-binding domain of the EGFR double-mutated model. From the diverse groups of molecular clustering and molecular screening strategies, top high-binding gefitinib-analogues were identified and studied against EGFR core cavity through three-phase ensemble docking approach. Resulted high possible leads showed good binding orientations than gefitinib (positive control) thus they were subjected to pharmacophore analysis that possesses possible molecular assets to tight binding with EGFR domain. Residues Ser720, Arg841 and Trp880 were observed as novel hot spots and involved in H-bonds, pi-stacking and π-cation interactions that contribute additional electrostatic potency to sustain stability and complexity of protein-ligand complexes, thus they have ability to profoundly adopted by pharmacophoric features. Furthermore, lead molecules have an inhibition percent probability, anticancer potency, toxic impacts, flexible pharmacokinetics, potential gene-chemical interactions towards EGFR were revealed by computational systems biology tools. Our multiple screening strategies confirmed that the druggable sub-pocket was crucial to strong EGFR-ligand binding. The essential pharmacophoric features of ligands provided viewpoints for new inhibitors envisaging, and predicted scaffolds could used as anticancer agents against selected EGFR mutated isoforms.


Impact of genetic and environmental determinants of taste with food preferences in older adults.
Individual differences in the ability to detect bitter tasting compounds, such as phenylthiocarbamide (PTC) or its derivative, 6-n-propylthiouracil (PROP) has long been recognized as a common genetic trait. This observation has been proposed to explain some of the variability in the dietary habits of a population. Several members of the TAS2R receptor gene family encode taste receptors on the tongue, and genetic polymorphisms of TAS2R38 have been associated with marked differences in the perception of PTC and PROP. An association between TAS2R38 genotype and food preferences has been found among children, but no associations have been reported among older adults. This, along with the decreased ability to taste certain foods with increasing age, suggests that environmental factors are more important than genetic influences in food preferences among the elderly. The elderly may be more inclined to try and accept novel foods because of diet-related attitudes and beliefs that are formulated throughout the years.


Gender dimorphisms in progenitor and stem cell function in cardiovascular disease.
Differences in cardiovascular disease outcomes between men and women have long been recognized and attributed, in part, to gender and sex steroids. Gender dimorphisms also exist with respect to the roles of progenitor and stem cells in post-ischemic myocardial and endothelial repair and regeneration. Understanding how these cells are influenced by donor gender and the recipient hormonal milieu may enable researchers to further account for the gender-related disparities in clinical outcomes as well as utilize the beneficial effects of these hormones to optimize transplanted cell function and survival. This review discusses (1) the cardiovascular effects of sex steroids (specifically estradiol and testosterone); (2) the therapeutic potentials of endothelial progenitor cells, mesenchymal stem cells, and embryonic stem cells; and (3) the direct effect of sex steroids on these cell types.


Evaluation of toluene degradation pathways by two-dimensional stable isotope fractionation.
Toluene degradation by several pure and mixed microbial cultures was investigated bytwo-dimensional compound specific isotope analysis (2D-CSIA). For most of the cultures, the respective toluene degradation pathway and toluene attacking enzymatic step was known. The slope of the linear regression for hydrogen (delta delta(2)H) vs. carbon (delta delta(13)C) discrimination (lamda = delta delta(2)H/ delta delta(13)C approximately epsilonH(bulk)/epsilonC(bulk)) was determined in order to characterize aerobic and anaerobic toluene degradation pathways. The highest lamda value was estimated for the monohydroxylation of the methyl group by Pseudomonas putida (lamda = 53 +/- 5). The lowest value was observed for Rhodococcus opacus (lamda = 2 +/- 2) due to its insignificant hydrogen fractionation, which indicates that a ring dioxygenase was responsible for the initial attack of toluene. The fungus Cladosprium sphaerospermum containing a cytochrome P450-dependent methyl monooxygenase grouped within these extreme values (lamda = 16 +/- 6). Lamda values for organisms attacking toluene under anoxic conditions by benzylsuccinate synthase were significantly different and ranged from lamda = 4 +/- 3 (Blastochloris sulfoviridis) to 31 +/- 11 (strain TRM1). Values were in the same range for organisms using nitrate (lamda = 11-14) or sulfate (lamda = 28-31) as electron acceptor, indicating that it might be possible to distinguish toluene degradation under different electron acceptor conditions by 2D-CSIA.


A novel partnership in psychiatric education.
The authors describe a unique institutional partnership between an adult psychiatry training program and a K-12 school that focuses on enriching educational opportunities and improving outcomes at both institutions. Beginning with reciprocal consultations, the partnership has expanded to involve the students and faculty at both institutions. Feedback has confirmed that both residents in the training program and teachers at the school consider the exchanges highly beneficial. A wide range of educational improvements has resulted. In the training program, these have included recurring exposure to and interactions with children and adolescents in normative educational environments and increased reflection about effective pedagogy. In the school, improvements have ranged from more rounded intervention strategies to teachers' increased sophistication about neurodevelopmental phenomena in a learning setting. Collaboration between an adult psychiatry training program and a K-12 school can provide significant benefits not otherwise available to both institutions. The authors believe this partnership model is valuable and might be replicated in other settings where adult and/or child training programs can establish similar relationships with a school.


The correlation between exposure to neighborhood violence and perpetration of moderate physical violence among Arab-Palestinian youth: Can it be moderated by parent-child support and gender?
In the current study, we examined the role of parent-child support as a protective factor that moderates the correlation between exposure to neighborhood violence and perpetration of moderate physical violence among 3,187 Arab-Palestinian adolescents who live in Israel (aged 12 to 18), from 21 different schools who were selected randomly. The probability sampling method was a nonproportional multistage stratified cluster sample. We also examined gender differences across this protective process. Participants completed a structured, anonymous self-report questionnaire. The findings of the study reveal that 47.3% of the adolescents had perpetrated moderate physical violence against others at least once during the month preceding the study. Moreover, exposure of adolescents to violence in their neighborhood correlated significantly and positively with perpetration of moderate physical violence. A moderation analysis was tested and found that this correlation was stronger among adolescents who had poor parent-child support than among those who had strong parent-child support. Furthermore, the findings reveal that the correlation of exposure to neighborhood violence with perpetration of moderate physical violence was not moderated by gender. However, parent-child support correlated strongly with lower levels of perpetration of moderate physical violence among males than females. The findings of the study highlight the critical role of parental factors in decreasing violent behaviors among adolescents (especially boys) as well as among adolescents who are at risk for exposure to violence in their neighborhoods. In light of the findings, we recommend that practitioners working with these adolescents include parents in intervention programs. (PsycINFO Database Record


Pelvic shape change in adult Japanese macaques and implications for childbirth at old age.
Pelvic morphology exhibits a particular sexual dimorphism in humans, which reflects obstetrical constraints due to the tight fit between neonates and mothers. Huseynov et al. [Proc. Natl. Acad. Sci. U.S.A. 113, 5227-5232 (2016)] showed that in humans, pelvic sexual dimorphism is greatest around the age of highest fertility, and it becomes less marked in association with menopause in females. They proposed that this reflects changes of obstetrical versus locomotor functional demands in females. It remains unknown whether such developmental adjustment of the pelvic morphology is unique to humans. Macaques exhibit human-like cephalopelvic proportions, but they lack menopause and usually maintain fertility throughout adulthood. Here, we track pelvic development in Japanese macaques from neonate to advanced ages using computed tomography-based data. We show that female pelvic morphology changes throughout adult life, reaching the obstetrically most favorable shape at advanced ages rather than around primiparity. We hypothesize that pelvic morphology in Japanese macaques is developmentally adjusted to childbirth at advanced ages, where obstetrical risks are potentially higher than at younger ages. Our data contribute to the growing evidence that the female primate pelvis changes its morphology during the whole lifespan, possibly adjusting for changing functional demands during adulthood.


Microwave coagulation therapy for urinary bladder tumors.
A new device has been developed for microwave coagulation of urinary bladder tumors. Twenty-one patients with urinary bladder tumors were treated by irradiation with microwave energy of 2,450 MHz. Results were obtained as follows: (1) microwave coagulation was performed in 21 patients with transitional cell carcinoma of the urinary bladder. Excluding 4 patients who subsequently received radical cystectomy, 17 patients showed a complete response, although 2 patients subsequently developed recurrences in different parts of the bladder within the following several months. Histological examination of the excised specimen revealed complete eradication of the tumor in 2 patients. In the remaining 2 patients with high-stage tumor (T4), viable tumor cells were noted in the urethra or vaginal wall. (2) Although neither technical difficulties nor severe complications were encountered, transient urinary frequency and calcification of the bladder wall were noted. The results of this study indicate that microwave coagulation may be used in the treatment of both superficial and invasive tumors.


Third-nerve palsy due to penetrating trauma.
Penetrating trauma is an unusual etiology of third-nerve palsy. Of 815 hospitalized patients with third-nerve palsies, 20 had such an etiology, with gunshot wounds being the usual cause.


Development of optimized epoxy graphite implant for the total hip joint.
Various metal implants are available for total hip joint replacements. There are problems associated with the micromovement of the implants with bone and/or with bone cement and about ten percent failure cases are reported. The mechanical properties of the metal implants do not match with that of human bone in the femur resulting in a stress distribution in the femur different from one without implant. Many researchers are working with different materials like alloy materials with lower modulus of elasticity, ceramic, etc. The study conducted at S.D.S.M. & T. biomechanics laboratory investigates the feasibility of using epoxy graphite as an implant material. The mechanical properties of the implant material are being optimized using experimental and analytical methods. The reflection polariscope method (photo stress method) was used to determine the micromovement of the implant and the bone, and stress distribution in the femur subjected to cyclic loading. A finite element method was used to optimize the mechanical properties of the implant to obtain a stress distribution closer to the one without implant. An epoxy graphite implant with optimized mechanical properties is being manufactured and tests are in progress.


The Effect of a Multicomponent Dual-Task Exercise on Cortical Thickness in Older Adults with Cognitive Decline: A Randomized Controlled Trial.
The aim of this study was to examine cortical thickness changes associated with a multicomponent exercise intervention combining physical exercise and cognitive training in older adults with cognitive decline. This study involved a secondary analysis of neuroimaging data from a randomized controlled trial with 280 older adults having cognitive decline who were randomly assigned to either a multicomponent exercise group (n = 140) that attended weekly 90-minute exercise and cognitive training sessions or a health education control group (n = 140). The cortical thickness and cognitive performance were assessed at the baseline and at trial completion (10 months). The cortical thickness in the frontal and temporal regions was determined using FreeSurfer software. Cognitive performance was evaluated using the Gerontology-Functional Assessment Tool (NCGG-FAT). The cortical thickness significantly increased in the middle temporal (p < 0.001) and temporal pole (p < 0.001) in the multicomponent exercise group compared with the control group. Cortical thickness changes were significantly associated with change in trail making test (TMT)-A, TMT-B, and story memory after a 10-month multicomponent exercise intervention. This study suggests that multicomponent exercise programs combining physical exercise and cognitive training have important implications for brain health, especially in providing protection from age-related cortical thinning.


Picosecond-time-scale fluctuations of proteins in glassy matrices: the role of viscosity.
Through elastic neutron scattering we investigated the fast dynamics of lysozyme in hydrated powder form or embedded in glycerol-water and glucose-water matrices. We calculated the relaxational contribution to the mean square displacements of protein hydrogen atoms. We found that the inverse of this quantity is linearly proportional to the logarithm of the viscosity of the solvent glassy matrix. This relationship suggests a close connection between the picosecond-time-scale dynamics of protein side chains and the solvent structural relaxation.


Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle.
The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.


Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer.
The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [68Ga]PSMA I&T. 240 patients who underwent a [68Ga]PSMA I&T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging. The overall detection rates of [68Ga]PSMA I&T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P < 0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [68Ga]PSMA I&T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease. [68Ga]PSMA I&T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study.


Allograft Versus Autograft in Anterior Cervical Discectomy and Fusion: A Propensity-Matched Analysis.
Objective To compare the 30-day complication rate associated with allograft versus autograft in anterior cervical discectomy and fusion (ACDF) and to determine preoperative factors that may influence complication rate. Methods The American College of Surgeons National Surgical Quality Improvement Program database was retrospectively queried from 2014 to 2017 for all procedures with CPT codes for ACDF (22551). Patients undergoing ACDF with either autograft or allograft were matched by propensity scores based on age, sex, body mass index, and comorbidities. The incidence of adverse events in the 30-day postoperative period was compared. Results A total of 21,588 patients met the inclusion and exclusion criteria. Following the 10:1 propensity match, 17,061 remained in the study (1,551 autograft and 15,510 allograft). The overall adverse event rate was 3.18%; 3.48% for autograft and 3.15% for allograft (P=0.494). Autograft had a significantly greater incidence of extended length of stay (>2 d) (LOS) (48.9% vs 34.8%; P<0.001). Multivariate analysis suggested that autograft selection was associated with extended LOS (OR 1.4; 95% CI 1.3-1.5). Conclusion The results of this study provide information regarding how graft selection can relate to extended hospital LOS and influence postoperative complications. Extended LOS may be associated with worse patient outcomes and increase the overall cost of care. Further study should be performed to determine which patients would benefit from autograft versus allograft with regards to long-term outcomes, in consideration of these increased short-term complications.


High precision control of laser energy for laser-matter interaction studies.
Precise, highly reproducible control of the laser energy is required for high confidence laser-matter interaction research such as in dynamic compression science and high energy density physics. The energy must be adjustable without affecting the pulse shape (time varying intensity) or beam smoothness. We have developed a convenient two-stage energy tuning method for a nominal 100 J, 351 nm (UV) laser. The energy is adjusted in 10 J (10%) increments by operating the laser at full energy and inserting a beam splitter in the laser output. As the splitter is located after the final frequency tripling optics, the UV pulse shape is unchanged. The energy is varied by substituting a splitter of different reflectivity. For finer 3 J (3%) increments, the infrared pulse is attenuated inside the laser before the final amplifier. This requires modest tuning to preserve the pulse shape. The demonstrated variation in shot-to-shot reproducibility is less than +/-2.5 J (5% of the full energy), irrespective of the laser output energy. These approaches can be adapted to most ∼100 J class lasers. We describe these techniques and show two examples where they have elucidated the underlying physics in laser shock compression experiments. One used only the beam splitters to establish the pressure for melting in iron. The other combined both techniques to finely increment the peak stress (∼2 GPa steps) in germanium to precisely determine the onset and completion of melting-including the melting kinetics. These unambiguous results would not be possible without the developments described here.


Reduced dose intensity FOLFOX-4 as first line palliative chemotherapy in elderly patients with advanced colorectal cancer.
To evaluate the toxicity and efficacy of a reduced dose intensity (mini-) FOLFOX-4 regimen as a first-line palliative chemotherapy in elderly patients (> or =70 yr of age) with advanced colorectal cancer, data from prospective databases at Seoul National University Bundang Hospital and Seoul Municipal Boramae Hospital were analyzed. A total of 20 patients were enrolled between January 2001 and August 2004, and were treated with oxaliplatin 65 mg/m2 on day 1, and with 2-hr infusions of leucovorin 150 mg/m2 followed by a 5-FU bolus (300 mg/m2) and 22-hr continuous infusions (450 mg/m2) for 2 consecutive days every 2 weeks until progression, unacceptable toxicity or patient refusal. Sixteen patients were evaluable for response with an overall response rate of 43.8%. Median progression-free survival was 4.8 months (95% CI: 3.0-6.7) and overall survival was 13.5 months (95% CI: 11.1-16.0). The main side effects were anemia and neutropenia, which were observed in 20.8% and 17.7%, respectively, of the total cycles administered. There were no grade 4 toxicities and only one patient suffered from febrile neutropenia. No grade 3 toxicities occurred except for anemia (5.2%) and vomiting (1.0%). In conclusion, the mini-FOLFOX-4 regimen was found to be well tolerated with acceptable toxicity, and to provide a benefit for elderly patients with colorectal cancer.


Global stability analysis of birhythmicity in a self-sustained oscillator.
We analyze the global stability properties of birhythmicity in a self-sustained system with random excitations. The model is a multi-limit-cycle variation in the van der Pol oscillator introduced to analyze enzymatic substrate reactions in brain waves. We show that the two frequencies are strongly influenced by the nonlinear coefficients alpha and beta. With a random excitation, such as a Gaussian white noise, the attractor's global stability is measured by the mean escape time tau from one limit cycle. An effective activation energy barrier is obtained by the slope of the linear part of the variation in the escape time tau versus the inverse noise intensity 1/D. We find that the trapping barriers of the two frequencies can be very different, thus leaving the system on the same attractor for an overwhelming time. However, we also find that the system is nearly symmetric in a narrow range of the parameters.


Effect of protein kinase C on cyclic 3',5'-adenosine monophosphate-dependent phosphodiesterase in hypertrophic cardiomyopathic hamster hearts.
"Cross-talk," or interaction between different signal transduction pathways, is known to exist in noncardiac cells, but it has not been demonstrated previously in mammalian hearts. We found that hypertrophic cardiomyopathic Syrian hamster (BIO 14.6, 6 months old) hearts were deficient in cyclic 3',5'-adenosine monophosphate (cAMP) [11.9 +/- 0.4 vs. 15.4 +/- 0.4 pmol/mg protein in age-matched control hamsters (BIO RB), n = 6, P = .0005] but not in cyclic 3',5'-guanosine monophosphate (1.23 +/- 0.10 vs. 1.34 +/- 0.18 pmol/mg protein in BIO RB, n = 6, P = N.S.). The reduction in cAMP was at least partly accounted for by an increase in the cytosolic phosphodiesterase (PDE) activity in BIO 14.6 hearts (1709 +/- 119 vs. 1341 +/- 113 pmol/min/mg protein in age-matched BIO RBs, n = 12, P = .006), suggesting that there is an increase in cAMP turnover in BIO 14.6 hearts. Protein kinase C (PKC) activities were also significantly elevated in BIO 14.6 hearts (77.9 +/- 2.1 vs. 54.6 +/- 3.3 pmol/min/mg protein in BIO RBs, n = 6, P < .001). Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 10 microM) produced significant potentiation in PDE activities in BIO 14.6 but not in BIO RB hearts, and the PMA-induced increase in PDE activity could be blocked by the PKC-specific pseudosubstrate inhibitor peptide PKC(19-31).(ABSTRACT TRUNCATED AT 250 WORDS)


Role of the coagulation system in tumor-cell-induced platelet aggregation and metastasis.
The ability of tumor cells to initiate coagulation and subsequent platelet aggregation is believed to facilitate the metastatic process. The mechanism by which tumor cells initiate thrombotic alterations is unclear. We have purified a plasma membrane protein platelet aggregating activity/procoagulant activity (PAA/PCA) from several rodent tumors which initiates the coagulation of homologous plasma and aggregation of homologous platelets by a mechanism independent of factor VII. This protein does not possess any proteinase activity; however, its activity is dependent upon the presence of factor X. In addition, PAA/PCA requires reconstitution with phospholipid for expression of activity. These results suggest that tumor cells express a unique protein which possesses procoagulant activity resulting in thrombin generation. Thrombin is responsible for subsequent tumor-cell-induced platelet aggregation.


Attentive mechanisms in visual search.
Selective attention can be employed to a restricted region in space or to specific objects. Many properties of this attentional window or spotlight are not well understood. In the present study, we examined the question whether the putative shape of the attentional spotlight can be determined by endogenous cueing within a visual search paradigm. Participants searched for a target among distractors, which were arranged within a vertical or horizontal rectangle. The shape of this rectangle was cued endogenously in a valid or invalid way. Response times (RTs) to correct identification of target orientation were recorded. In Experiment 1, the difference between valid and invalid RTs demonstrated that cueing resulted in elongated attentional areas. This was true only for a group of experienced psychophysical participants, whereas a group of inexperienced participants were not able to use cueing in this way. In Experiment 2, the line motion illusion was used to examine the spatial properties of the attended area. The results confirmed for both experienced and inexperienced participants that attention was confined to the cued elongated area only. We present converging evidence for an attentional spotlight whose shape can be adjusted flexibly by appropriate endogenous cueing.


Long-term nasotracheal intubation in an adult patient. A case of 174 days in spontaneous breathing.
A 67 year old female whole trachea was compressed by malignant thyroid tumour complained of severe dyspnoea. Tracheostomy was considered but was rejected because of the risk of massive bleeding. Nasotracheal intubation improved markedly her condition. The patient underwent radiation and chemotheraphy with the tube in place. By these treatment compression of the trachea was alleviated, and the nasotracheal tube was removed uneventfully on the 174th day of intubation. The management of long-term nasotracheal intubation is discussed and the literature is reviewed.


Nosocomial central venous catheter-related infections in intensive care units.
To examine the recent microbiology of catheter-related infections (CRIs) in the intensive care unit (ICU) setting and to determine the association between selected factors and mortality among ICU patients diagnosed with a CRI, a retrospective review of all ICU patients determined to have a CRI between January 1992 and December 1994 was undertaken. A total of 108 patients with 111 episodes of CRIs were identified. The most common isolate was coagulase negative staphylococcus (37.9%), followed by Staphylococcus aureus (20.9%). Methicillin resistance was common in both CNS (93%), and S aureus (42%) isolates. Factors predictive for death in a multivariate analysis were as follows: male sex (relative risk (RR) 2.43, 95% confidence interval (CI) 1.0, 6.07), hypotension (RR 6.90, 95% CI 1.56, 12.2), American Society of Anesthesiologist physical status score greater than 3 (RR 4.36, 95% CI 1.56, 12.2), and underlying medical condition (RR 3.50, 95% CI 1.17, 10.5). This study demonstrated the increasing proportion of CRIs due to methicillin-resistant organisms in the ICU. Functional status and degree of illness were the strongest predictors for survival in this population.


PHENOTYPIC AND GENETIC EFFECTS OF HYBRIDIZATION IN DARWIN'S FINCHES.
Morphological consequences of hybridization were studied in a group of three interbreeding species of Darwin's finches on the small Galápagos island of Daphne Major in the inclusive years 1976 to 1992. Geospiza fortis bred with G. scandens and G. fuliginosa. Although interbreeding was always rare (< 5%), sufficient samples of measurements of hybrids and backcrosses were accumulated for analysis. Five beak and body dimensions and mass were measured, and from these two synthetic (principal-component) traits were constructed. All traits were heritable in two of the interbreeding species (G. fuliginosa were too rare to be analyzed) and in the combined samples of F, hybrids and backcrosses to G. fortis. In agreement with expectations from a model of polygenic inheritance, hybrid and backcross classes were generally phenotypically intermediate between the breeding groups that had produced them. Hybridization increased additive genetic and environmental variances, increased heritabilities to a moderate extent, and generally strengthened phenotypic and genetic correlations. New additive genetic variance introduced by hybridization is estimated to be two to three orders of magnitude greater than that introduced by mutation. Enhanced variation facilitates directional evolutionary change, subject to constraints arising from genetic correlations between characters. The Darwin's finch data suggest that these constraints become stronger when species with similar proportions hybridize, but some become weaker when the interbreeding species have different allometries. This latter effect of hybridization, together with an enhancement of genetic variation, facilitates evolutionary change in a new direction.


Dependence of intermittency scaling on threshold in chaotic systems.
Numerical and experimental investigations of intermittency in chaotic systems often lead to claims of universal classes based on the scaling of the average length of the laminar phase with parameter variation. We demonstrate that the scaling in general depends on the choice of the threshold used to define a proper laminar region in the phase space. For sufficiently large values of the threshold, the scaling exponent tends to converge but significant fluctuations can occur particularly for continuous-time systems. Insights into the dependence can be obtained using the idea of Poincaré recurrence.


Meiosis: the chromosomal foundation of reproduction.
Meiosis is the chromosomal foundation of reproduction, with errors in this important process leading to aneuploidy and/or infertility. In this review celebrating the 50th anniversary of the founding of the Society for the Study of Reproduction, the important chromosomal structures and dynamics contributing to genomic integrity across generations are highlighted. Critical unsolved biological problems are identified, and the advances that will lead to their ultimate resolution are predicted.


Improving outcomes for homeless people with alcohol disorders: a multi-program community-based approach.
Background: Relatively few community-based programs have been found to be helpful for homeless people with alcohol disorders, even though this group represents a high-risk, vulnerable population prone to poor outcomes.Aims: This study sought to implement and evaluate intensive community-based programs for homeless people with alcohol disorders.Method: The project worked closely with a homeless outreach team for referrals, and then provided two different, intensive substance abuse treatment approaches matched to the needs of two subgroups: homeless individuals with alcohol disorders without severe mental illness received community reinforcement approach (CRA) and case management services, while those with alcohol and severe mental illness were assigned to assertive community treatment and integrated dual disorders (ACT/IDDT) services. The study enrolled 322 homeless people with alcohol disorders and outcomes were assessed at six months and program discharge.Results: Participants improved significantly over the first six months in a number of outcome areas, including substance abuse, mental health, housing, employment and health; progress generally remained stable between six months and discharge.Conclusions: Community-based programs that coordinate with mobile outreach teams and then provide CRA and ACT/IDDT appear to be promising approaches for helping individuals with alcohol disorders out of homelessness and into recovery.


The effect of AC frequency on the electrowetting behavior of ionic liquids.
This paper presents a study of electrowetting of ionic liquids (ILs) under AC voltages, where nine different ILs (including mono-, di-, and tricationic varieties) with three different AC frequencies (60 Hz, 1 kHz, 10 kHz) were experimentally investigated. The main foci of this study are (i) an investigation of AC frequency dependence on the electrowetting of ILs; (ii) obtaining theoretical relationships between the relevant factors that explain the experimentally achieved frequency dependence; and (iii) a systematic comparison of electrowetting of ILs using AC vs DC voltage fields. The frequency of the AC voltage was found to be directly related to the apparent contact angle change (Deltatheta) of the ILs. This relationship was further analyzed and explained theoretically. The electrowetting properties of ILs under AC voltages were compared to that under DC voltages. All tested ILs showed greater apparent contact angle changes with AC voltage conditions than with DC voltage conditions. The effect of structure and charge density also was examined. Electrowetting reversibility under AC voltage conditions was studied for few ILs. Finally, the physical properties and AC electrowetting properties of ILs were measured and tabulated.


NLRs: Nucleotide-Binding Domain and Leucine-Rich-Repeat-Containing Proteins.
Eukaryotes have evolved strategies to detect microbial intrusion and instruct immune responses to limit damage from infection. Recognition of microbes and cellular damage relies on the detection of microbe-associated molecular patterns (MAMPs, also called PAMPS, or pathogen-associated molecular patterns) and so-called "danger signals" by various families of host pattern recognition receptors (PRRs). Members of the recently identified protein family of nucleotide-binding domain andleucine-rich-repeat-containing proteins (NLR), including Nod1, Nod2, NLRP3, and NLRC4, have been shown to detect specific microbial motifs and danger signals for regulating host inflammatory responses. Moreover, with the discovery that polymorphisms in NOD1, NOD2, NLRP1, and NLRP3 are associated with susceptibility to chronic inflammatory disorders, the view has emerged that NLRs act not only as sensors butalso can serve as signaling platforms for instructing and balancing host immune responses. In this chapter, we explore the functions of these intracellular innate immune receptors and examine their implication in inflammatory diseases.


Calcineurin and cardiac hypertrophy: where have we been? Where are we going?
The heart is a dynamic organ capable of adapting its size and architecture in response to alterations in workload associated with developmental maturation, physiological stimulation and pathological diseases. Such alterations in heart size typically result from the hypertrophic growth of individual myocytes, but not myocyte cellular proliferation. In recent years, a great deal of investigation has gone toward elucidating the molecular signalling machinery that underlies the hypertrophic response and manner in which increased cardiac load promotes alterations in gene expression. To this end, the Ca(2+)-calmodulin-activated phosphatase calcineurin has been proposed as a necessary component of the multi-pathway hypertrophy program in the heart. Despite initial controversy over this hypothesis due to disparate results from pharmacological inhibitory studies in animal models of hypertrophy, compelling data from genetic models with calcineurin inhibition now exist. This review will summarize many of these studies and will attempt to address a number of unanswered issues. In particular, specific downstream mediators of calcineurin signalling will be discussed, as well as the need to identify calcineurin's temporal activation profile, transcriptional targets and cross-communication with other reactive signalling pathways in the heart. Finally, we will present evidence suggesting that calcineurin, as a Ca(2+)-responsive enzyme, may function as an internal load sensor in cardiac myocytes, matching output demands to hypertrophic growth.


Neonatal bloodstream infections in a pediatric hospital in Vietnam: a cohort study.
Septicemia and bloodstream infections (BSIs) are major causes of neonatal morbidity and mortality in developing countries. We prospectively recorded all positive blood cultures (BSI) among neonates admitted consecutively to a tertiary pediatric hospital in Vietnam during a 12-month period. Among 5763 neonates, 2202 blood cultures were performed, of which 399 were positive in 385 neonates. Among these, 64 died, 62 in relation to septicemia. Of the BSI isolates, 56% was known pathogenic and 48% was gram-negative bacteria, most frequently Klebsiella spp. (n = 78), Acinetobacter spp. (n = 58) and Escherichia coli (n = 21). Only three Streptococcus spp. were identified, none group B. Resistance against antibiotics applied was common. The mortality was highest in neonates with gram-negative BSI compared with no confirmed BSI and gram-positive BSI (P < 0.01). In this setting, the majority of BSI were likely to have been transmitted from the environment. Improvement of hygienic precautions and systematic BSI surveillance are recommended.


Safety and efficacy of self-expandable Evolut R vs. balloon-expandable Sapien 3 valves for transcatheter aortic valve implantation: A systematic review and meta-analysis.
The aim of this study was to systematically search literature and conduct a meta-analysis comparing the clinical efficacy and safety of Evolut R and Sapien 3 valves for transcatheter aortic valve implantation (TAVI). The PubMed, Biomed Central, Scopus, Cochrane library and Google scholar databases were searched for articles published up to June, 2019. A total of 5 studies were included. In total, 795 patients underwent TAVI with Evolut R, while 665 patients received the Sapien 3 valve in the included studies. Overall device success with Evolut R was 95.7% and with Sapien 3 was 94.2%. Pooled data indicated no significant differences between the 2 valves (OR, 1.12; 95% CI, 0.66-1.89; P=0.68; I2=0%). No significant differences were observed in the incidence of none to mild paravalvular leakage between the 2 groups (OR, 1.71; 95% CI, 0.83-3.54; P=0.14; I2=0%). Both mean [random; mean difference (MD) = -3.96; 95% CI, -4.61 to -3.31; P<0.00001, I2=0%] and peak (random; MD = -6.85; 95% CI, -8.22 to -5.48; P<0.00001, I2=0%) aortic valve gradients were significantly lower with Evolut R. No significant differences were observed in the 30-day mortality (OR, 1.32; 95% CI, 0.45-3.87; P=0.62; I2=0%) or 30-day stroke outcomes (OR, 0.76; 95% CI, 0.32-1.81; P=0.54; I2=0%) between the 2 devices. On the whole, the findings of this study indicate that Evolut R and Sapien 3 valves may be comparable in terms of device success and short-term complications. The differences between the 2 devices for post-operative moderate to severe paravalvular leak and permanent pacemaker implantation remain unclear. There is thus a need for a large multi-center randomized controlled trial to provide stronger evidence on this subject.


Nonsurgical management of a rectovaginal fistula caused by a Gellhorn pessary.
Pessaries are generally thought to be a safe, well-tolerated treatment for pelvic organ prolapse. An 85-year-old woman had a Gellhorn pessary placed for pelvic organ prolapse. Although she was seen regularly for care, the pessary had not been removed for several years. She presented stating that she felt the pessary had shifted. On examination, the patient's pessary stem had eroded through the vagina into the rectum. The pessary was removed and the patient was treated with vaginal estradiol cream. One month later the fistula tract had resolved and the patient continued to desire a pessary to manage her pelvic organ prolapse. Pessaries require care and maintenance. Patients' desires for conservative management should be coupled with education and routine follow-up.


Role of family physicians in an urban hospital: Tracking changes between 1977, 1997, and 2014.
To investigate changes in family doctors' attitudes about and participation in hospital activities and inpatient care in an urban hospital family medicine department from 1977 to 1997 and 2014. Cross-sectional survey design. The Department of Family Medicine at St Joseph's Healthcare Hamilton in Ontario. Family physicians affiliated with the Department of Family Medicine at St Joseph's Healthcare Hamilton were surveyed in 2014. Data were compared with findings from similar surveys administered at this institution in 1977 and 1997. Family physicians' roles in hospital activities, attitudes toward the role of the family physician in the hospital setting, and the barriers to and facilitators of maintaining this role. A total of 93 physicians returned completed surveys (37.3% response rate). In 2014, half of the respondents provided some inpatient care. This patient care was largely supportive and newborn care (71.7% and 67.4%, respectively). In 2014, 47.3% believed the quality of care would suffer (compared with 92.1% in 1977 and 87.5% in 1997) if they were not involved in patient care in the hospital. There was also a considerable shift away from the 1977 and 1997 perception that the family physician had a role as patient advocate: 92.0% and 95.3%, respectively, compared with only 49.5% in the 2014 survey. Family physicians' hospital activities and attitudes continued to change from 1977 to 1997 and 2014 in this urban hospital setting. Most of the respondents had stopped providing direct inpatient care, with a few continuing to provide supportive care. Despite this, most respondents still see a role for the Department of Family Medicine within the hospital as a focus for identifying with their family physician community, a place to interact with other specialist colleagues, and a source of some continuing medical education.


Pulmonary Sarcoidosis Presenting with Miliary Opacities.
Lung lesions often appear in patients with sarcoidosis; however, miliary opacities are rare. We herein report the case of a 40-year-old woman with pulmonary sarcoidosis who presented with dyspnea on exertion. Subsequent computed tomography showed miliary opacities, and the presence of granulomas was confirmed by a transbronchial lung biopsy. Glucocorticoid therapy was initiated and the symptoms and miliary opacities rapidly improved. Although miliary sarcoidosis is uncommon, physicians should consider sarcoidosis in addition to tuberculosis, malignancy, and pneumoconiosis when presented with miliary opacities.


[Heart, heart-lung and lung transplantation, 1994 status].
In recent years, heart transplantation has become a clinically routine means of treating patients with terminal cardiac disease. One-year survival rates of more than 80%, and five-year rates of about 70% vindicate the clinical acceptance of this form of treatment. Combined heart and lung transplantation has been practiced for the past ten years. Following the introduction of unilateral and bilateral lung transplantation in 1985, the combined heart/lung approach is now rarely indicated. In the treatment of interstitial, but also pulmonary vascular, diseases, unilateral and bilateral lung transplantation has been increasingly employed. Currently, the one-year survival rate of single-lung transplantation is 70%, that of two-lung or heart-lung transplantation about 60%. The main complications of such procedures remain the high incidence of infection and graft rejection. The lack of availability of suitable donor organs continues to be the major factor limiting the number of transplantations performed.


Sensenbrenner Syndrome Presenting with Severe Anorexia, Failure to Thrive, Chronic Kidney Disease and Angel-Shaped Middle Phalanges in Two Siblings.
Sensenbrenner syndrome is a very rare autosomal recessive disorder caused by variants in genes involved in the functional development of primary cilia. Typical clinical manifestations include craniofacial and skeletal abnormalities, hence the alternative name cranioectodermal dysplasia. Chronic kidney disease due to progressive tubulointerstitial nephritis (nephronophthisis) has been described in these patients. The authors present 2siblings with severe anorexia, failure to thrive, chronic kidney disease, and angel-shaped middle phalanges. Two previously described variants p.(Leu641*) and p.(Asp841Val) were identified in the WDR35 gene which is most commonly affected in this condition. Analysis of all coding exons of the GDF5 gene was normal. This is the first report of Sensenbrenner syndrome presenting with severe anorexia and failure to thrive at early age. Angel-shaped middle phalanges in the absence of the GDF5 variant may represent an overlapping phenotypic manifestation of ciliopathy.


Droplet Motion Control on Dynamically Hydrophobic Patterned Surfaces as Multifunctional Liquid Manipulators.
In this letter, we introduce a novel liquid manipulation strategy to design dynamically hydrophobic and statically hydrophobic/hydrophilic patterned surfaces using an "omniphobicity"-based technique. The surfaces guide the sliding direction of a droplet in the presence of a statically hydrophilic area where the droplet does not stick on the transport path significantly enhancing the fluidic system transport efficiency. The concept of dynamically hydrophobic and statically hydrophobic/hydrophilic patterned surfaces in conjunction with omniphobic patterning techniques having surface multifunctionality, we believe, has potential not only for fluidic applications but also for future material engineering development.


Optical coherence tomography study of retinal changes in normal aging and after ischemia.
Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-month-, 1-year-, and 2-year-old mice and after experimental anterior ischemic optic neuropathy (AION). We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after a photochemical thrombosis model of AION. The scans were manually or automatically segmented. In normal aging, there was 1.3-μm thinning of the ganglion cell complex (GCC) between 3 months and 1 year (P < 0.0001) and no further thinning at 2 years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to that of the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three weeks after AION, there was 8.9-μm thinning of the GCC (circular scan; P < 0.0001), 50-μm thinning of the optic disc (posterior pole scan; P < 0.0001), and 17-μm thinning of the retina (posterior pole scan; P < 0.0001) in the 3-month-old group. Changes in the older eyes after AION were similar to those of the 3-month-old group. Optical coherence tomography imaging of a large number of eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. Measurement of the GCC was superior to total retinal thickness in quantifying age-related changes, and both circular and posterior pole scans were useful to track short-term changes after AION.


SUN2: A potential therapeutic target in cancer.
The incidence of cancer is increasing at an alarming rate despite recent advances in prevention strategies, diagnostics and therapeutics for various types of cancer. The identification of novel biomarkers to aid in prognosis and treatment for cancer is urgently required. Uncontrolled proliferation and dysregulated apoptosis are characteristics exhibited by cancer cells in the initiation of various types of cancer. Notably, aberrant expression of crucial oncogenes or cancer suppressors is a defining event in cancer occurrence. Research has demonstrated that SAD1/UNC84 domain protein-2 (SUN2) serves a suppressive role in breast cancer, atypical teratoid/rhabdoid tumors and lung cancer progression. Furthermore, SUN2 inhibits cancer cell proliferation, migration and promotes apoptosis. Recent reports have also shown that SUN2 serves prominent roles in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are critical for evading initiation of cancer. Additionally, increasing evidence has demonstrated that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in cancer cells. The focus of the present review is to provide an overview on the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a promising therapeutic target and novel predictive marker in various types of cancer.


The Effect of 4 Weeks Aerobic Exercise Training with Detraining Courses in Various Prevention Phases on BCl-2 and BAX Genes Expression and Proteins.
The aim of this study was to investigate the effect of aerobic exercise with detraining in different phases of prevention on BCL2 Associated X (BAX) and B-cell lymphoma 2 (BCl-2) gene expression and proteins. For this purpose, 32 female Balb-c mice (18-20 g) were purchased and randomly assigned to primordial prevention (A), primary prevention (B), secondary prevention (C), and control (D). A group performed aerobic exercise for 4 weeks, after 4T1 cells injection detrained for 8 weeks. Group B performed aerobic exercise for 4 weeks immediately after injecting 4T1 cells and then detrained for 4 weeks. In C group, the 4T1 cells were first injected and did not perform any activity for 4 weeks, followed by 4 weeks of aerobic exercise. Forty-eight hours after the last training session and detraining courses, after anesthesia, sacrificing, and tissue removal, were performed. Reverse transcription polymerase chain reaction (RT PCR) was used to measure gene expression and Western blot (WB) was used to measure protein content. One-way Analysis of variance (ANOVA) test was used to analyze data. The results showed that aerobic exercise in A, B, and C groups compared to D group reduced BCl-2 gene expression and protein and increased BAX gene expression and protein. Therefore, exercise can cause apoptosis in tumor cells by increasing pre-apoptotic factors and decreasing antiapoptotic factors in tumor cells, and consequently improving the disease status.


Challenges in profiling Australian scuba divers through surveys.
This study aimed to compare the results from three Australian scuba diver surveys. As the surveys differed in recruitment methods, the expectation was that respondents would differ in some important characteristics. Anonymous, online, cross-sectional surveys of the demographics, health, diving practices and outcomes were distributed to: (1) Divers Alert Network Asia-Pacific (DAN AP) members; (2) Professional Association of Diving Instructors (PADI) Asia-Pacific members; and (3) divers who had received any PADI non-leadership certification within the previous four years. Only data from divers resident in Australia were analysed. A total of 2,275 responses were received from current Australian residents, comprising 1,119 of 4,235 (26.4%) DAN members; 350 of 2,600 (13.5%) PADI members; and 806 of 37,000 (2.2%) PADI divers. DAN and PADI members had similar diving careers (medians 14 and 15 years, respectively). PADI members had undertaken more dives (median 800) than DAN members (330) and PADI divers (28). A total of 692 respondents reported suffering from diabetes or a cardiovascular, respiratory, neurological or psychological condition and included 34% of the DAN members and 28% of each of the PADI cohorts. Eighty-four divers had been treated for decompression illness (approximately 5% of DAN and PADI member groups and 1% of the PADI divers). Eighty-seven of 1,156 (7.5%) PADI respondents reported a perceived life-threatening incident while diving. Despite low response rates, this study indicates clear differences in the characteristics of the divers in the three cohorts. Therefore, a survey of a single cohort may represent that diving population alone and the findings may be misleading. This bias needs to be clearly understood and any survey findings interpreted accordingly.


Long noncoding RNA SNHG16 acts as an oncogene in Wilms' tumor through sponging miR-200a-3p.
Recently, the role of long noncoding RNA (lncRNAs) in tumor progression has attracted much attention. The aim of this study was to investigate the role of lncRNA SNHG16 in the development of Wilms' tumor, and to explore the underlying mechanism. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect SNHG16 expression in Wilms' tumor patients' tissues. Function assays, including wound healing assay, and transwell assay, were conducted to detect the changes of biological behaviors in Wilms' tumor cells due to gain or loss of SNHG16. Besides, the luciferase reporter gene assay was performed to explore the underlying mechanism. The expression level of SNHG16 was significantly up-regulated in Wilms' tumor tissues when compared with adjacent tissues. Cell migration and invasion abilities were significantly repressed via down-regulation of SNHG16. However, opposite results were obtained after up-regulation of SNHG16 in vitro. After the down-regulation of SNHG16, the expression of miR-200a-3p increased significantly. However, the expression of miR-200a-3p was remarkably reduced via up-regulation of SNHG16 in vitro. Furthermore, SNHG16 acted as a competing endogenous RNA via sponging miR-200a-3p in Wilms' tumor. SNHG16 induced the metastasis of Wilms' tumor via sponging miR-200a-3p. Our findings might provide a new prospect for the diagnosis and therapy of Wilms' tumor.


The performance of taxonomic and trait-based approaches in the assessment of dusky flounder parasite communities as indicators of chemical pollution.
We assessed the performance of taxonomic and several functional trait-based approaches in the assessment of spatial and temporal patterns of dusky flounder (Syacium papillosum) parasite assemblages along the Yucatan shelf to determine their potential as bioindicators of marine chemical pollution. Fish specimens were collected throughout three research cruises that took place in 2015, 2016 and 2018. In addition to the traditional taxonomic approach, four trait-based approaches were performed including community-weighted means (CWM), functional trait niche (FTN), functional groups (FGs), and Rao's functional diversity (FD). Significant spatial and temporal variations in parasite communities were detected using the taxonomic approach. In general, these variations were also reflected in the four trait-based approaches performed, indicating that changes in taxa composition and abundance also resulted in functional composition shifts. Resemblance matrices of both taxonomic and functional trait approaches were significantly correlated. Variations in taxonomic and trait-based composition using the four approaches were significantly correlated with depth, and at least one chemical pollutant variable. Feeding mode, transmission, life stage and attachment structure displayed spatial variability and significant correlations with predictor variables, which indicates that this set of attributes functions as a good surrogate for assessing variations in the functional composition of flatfish parasite communities in relation to pollution. FTN and CWM were the approaches that best detected spatio-temporal variation. CWM and FD were best suited for detecting pollution gradients. These results reveal the feasibility of using trait-based approaches to assess marine parasite communities as bioindicators of chemical pollution. Functional traits of marine metazoan parasites are as good indicators of the effect of oil pollution as taxonomic diversity. This may be a time-saving and cost-effective approach to performing environmental assessments.


Cascade time scales for energy and helicity in homogeneous isotropic turbulence.
We extend the Kolmogorov phenomenology for the scaling of energy spectra in high-Reynolds-number turbulence, to explicitly include the effect of helicity. There exists a time scale tau(H) for helicity transfer in homogeneous, isotropic turbulence with helicity. We arrive at this time scale using the phenomenological arguments used by Kraichnan to derive the time scale tau(E) for energy transfer [J. Fluid Mech. 47, 525 (1971)]]. We show that in general tau(H) may not be neglected compared to tau(E), even for rather low relative helicity. We then deduce an inertial range joint cascade of energy and helicity in which the dynamics are dominated by tau(E) in the low wave numbers with both energy and helicity spectra scaling as k(-5/3); and by tau(H) at larger wave numbers with spectra scaling as k(-4/3). We demonstrate how, within this phenomenology, the commonly observed "bottleneck" in the energy spectrum might be explained. We derive a wave number k(h) which is less than the Kolmogorov dissipation wave number, at which both energy and helicity cascades terminate due to dissipation effects. Data from direct numerical simulations are used to check our predictions.


N-dodecanoyl-homoserine lactone influences the levels of thiol and proteins related to oxidation-reduction process in Salmonella.
Quorum sensing is a cell-cell communication mechanism mediated by chemical signals that leads to differential gene expression in response to high population density. Salmonella is unable to synthesize the autoinducer-1 (AI-1), N-acyl homoserine lactone (AHL), but is able to recognize AHLs produced by other microorganisms through SdiA protein. This study aimed to evaluate the fatty acid and protein profiles of Salmonella enterica serovar Enteritidis PT4 578 throughout time of cultivation in the presence of AHL. The presence of N-dodecanoyl-homoserine lactone (C12-HSL) altered the fatty acid and protein profiles of Salmonella cultivated during 4, 6, 7, 12 and 36 h in anaerobic condition. The profiles of Salmonella Enteritidis at logarithmic phase of growth (4 h of cultivation), in the presence of C12-HSL, were similar to those of cells at late stationary phase (36 h). In addition, there was less variation in both protein and fatty acid profiles along growth, suggesting that this quorum sensing signal anticipated a stationary phase response. The presence of C12-HSL increased the abundance of thiol related proteins such as Tpx, Q7CR42, Q8ZP25, YfgD, AhpC, NfsB, YdhD and TrxA, as well as the levels of free cellular thiol after 6 h of cultivation, suggesting that these cells have greater potential to resist oxidative stress. Additionally, the LuxS protein which synthesizes the AI-2 signaling molecule was differentially abundant in the presence of C12-HSL. The NfsB protein had its abundance increased in the presence of C12-HSL at all evaluated times, which is a suggestion that the cells may be susceptible to the action of nitrofurans or that AHLs present some toxicity. Overall, the presence of C12-HSL altered important pathways related to oxidative stress and stationary phase response in Salmonella.


Projection status of calbindin- and parvalbumin-immunoreactive neurons in the superficial layers of the rat's superior colliculus.
Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 +/- 2.2% (mean +/- standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 +/- 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 +/- 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 +/- 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 +/- 2.5%) or the SO (9.2 +/- 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.


Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi.
Sharing cancer gene variant and relevant clinical data could accelerate progress in cancer genomics. However, data sharing is currently impeded by issues related to financial sustainability, equity, incentives, privacy and security, and data quality. Evidence-based policy options to facilitate data sharing in these domains, and ultimately improve interpretation of cancer-associated genomic variants, are therefore needed. We conducted a modified policy Delphi with expert stakeholders that involved generating, evaluating, and ranking potential policy options to address these issues, with a focus on the US context. We found policy options in the financial sustainability domain were highly ranked, particularly stable funding for trusted entities. However, some Delphi panelists noted that the culture of public research funding has favored short-term grants. Panelists favored policy options focused on action by funders, which had the highest overall total scores that combined effectiveness and feasibility ratings and priority ranking within domains. Panelists also endorsed some policy options connected to actors such as journals, but they were more skeptical of policy options connected to legislative actors and data resources. These findings are critical inputs for policy makers as they consider policies to enable sharing of cancer gene variant data to improve health.


Agarose-based 3D Cell Confinement Assay to Study Nuclear Mechanobiology.
Cells in living tissues are exposed to substantial mechanical forces and constraints imposed by neighboring cells, the extracellular matrix, and external factors. Mechanical forces and physical confinement can drive various cellular responses, including changes in gene expression, cell growth, differentiation, and migration, all of which have important implications in physiological and pathological processes, such as immune cell migration or cancer metastasis. Previous studies have shown that nuclear deformation induced by 3D confinement promotes cell contractility but can also cause DNA damage and changes in chromatin organization, thereby motivating further studies in nuclear mechanobiology. In this protocol, we present a custom-developed, easy-to-use, robust, and low-cost approach to induce precisely defined physical confinement on cells using agarose pads with micropillars and externally applied weights. We validated the device by confirming nuclear deformation, changes in nuclear area, and cell viability after confinement. The device is suitable for short- and long-term confinement studies and compatible with imaging of both live and fixed samples, thus presenting a versatile approach to studying the impact of 3D cell confinement and nuclear deformation on cellular function. This article contains detailed protocols for the fabrication and use of the confinement device, including live cell imaging and labeling of fixed cells for subsequent analysis. These protocols can be amended for specific applications. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Design and fabrication of the confinement device wafer Basic Protocol 2: Cell confinement assay Support Protocol 1: Fixation and staining of cells after confinement Support protocol 2: Live/dead staining of cells during confinement.


Pitfalls in anaphylaxis diagnosis and management at a university emergency department.
Some previous reports revealed suboptimal management of anaphylaxis (ANX) in the emergency department (ED). To evaluate the recorded diagnosis and management of patients who presented with ANX at our university hospital ED and to assess how the management correlated with the severity of the case and the training level of the ED staff. A descriptive study that involved reviewing the electronic medical records of patients who presented with ANX at the ED during a period of 4 years. When reviewing 1341 charts of potential cases, 60 met the criteria for ANX, but only 23% were correctly coded. Inaccurate coding was noted in 77%, mainly as an "allergic reaction." Systemic corticosteroids were administered in the ED to 85% of the patients and H1-antihistamines to 73%; only 20% received epinephrine. Ten patients required hospital admission, and, on discharge, only four patients (40%) were given epinephrine autoinjector prescriptions. Of the 50 who were discharged home, 48% were given epinephrine autoinjector prescriptions and 16% were given a referral for allergy evaluation. The observed low rates of appropriate diagnostic coding of ANX, of epinephrine administration, epinephrine autoinjector prescribing at discharge, and referral for allergy evaluation call for more education on these issues. Some of these pitfalls can be partly attributed to the setting in a university ED where health providers are usually busy in rendering urgent care.


Concertina browsers: a formative evaluation of user preference.
Evidence suggests that concertina browsers - browsers with the facility to expand and contract sections of information - are important in providing the reader with an enhanced cognition of small to medium amounts of information. These systems have been shown to be useful for visually disabled users surfing the World Wide Web (Web), and with the development of the Mobile Web, there has been renewed interest in their use. This is due to the similarities of reduced or constrained vision found to exist between visually impaired users and the users of mobile devices. The cognition of information fragments is key to the user experience and the reduction of 'information overload'; as such we are concerned with assisting designers of concertina browsers in providing an enhanced user experience by ascertaining user preference through a formative evaluation of concertina summaries. This aspect of browsing is important because in all concertina systems there is a distinct cognition speed/depth trade-off. Here we investigate a number of these concertina summarization techniques against each other. We describe a formative evaluation which concludes that users prefer concertina summarization of Web documents starting from 6.25% slices of both the top and bottom and expanding from the top in 2% steps to a target maximum of 18.50% (being 12.25% from the top and 6.25% from the bottom). These preferences were found to be representative of documents of less than 600 words of content, and included the preference to not fragment an individual sentence even if that meant slightly increasing the target: Starting, maximum, and step percentage slices.


Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury.
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury. We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement. However, the neural regeneration efficiency of induced neural stem cells remains limited. In this study, we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells. We found that H19 was the most downregulated neurogenesis-associated lncRNA in induced neural stem cells compared with induced pluripotent stem cells. Additionally, we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons. We predicted the target genes of H19 and discovered that H19 directly interacts with miR-325-3p, which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells. Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation, and miR-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition. Furthermore, H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells. Notably, silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice. Our results reveal that H19 regulates the neurogenesis of induced neural stem cells. H19 inhibition may promote the neural differentiation of induced neural stem cells, which is closely associated with neurological recovery following closed head injury.


Acute Monocular Blindness Due to Orbital Compartment Syndrome Following Pterional Craniotomy.
We present a case of orbital compartment syndrome (OCS) leading to monocular irreversible blindness following a pterional craniotomy for clipping of an anterior communicating artery aneurysm. OCS is an uncommon but vision-threatening entity requiring urgent decompression to reduce the risk of permanent visual loss. Iatrogenic orbital roof defects are a common finding following pterional craniotomies. However, complications related to these defects are rarely reported. A 65-year-old female who underwent an anterior communicating artery clipping via a pterional approach 4 days before developed proptosis, ocular movement paresis, and irreversible visual impairment following an orthopedic surgery. Computed tomography images revealed an intraorbital cerebrospinal fluid (CSF) collection, which was evacuated via an acute recraniotomy. The next day, proptosis and intraorbital CSF collection on computed tomography images reoccurred and an oral and maxillofacial surgeon evacuated the collection via a blepharoplasty incision and blunt dissection. In addition, the patient was treated with acetazolamide and an external lumbar CSF drainage during 12 days. Hereafter, the CSF collection did not reoccur. Unfortunately, monocular blindness was persistent. We hypothesize the CSF collection occurred due to the combination of a postoperative orbital roof defect and a temporarily increased intracranial pressure during the orthopedic surgery. We plead for more awareness of this severe complication after pterional surgeries and emphasize the importance of 1) strict ophthalmologic examination after pterional craniotomies in case of intracranial pressure increasing events, 2) immediate consultation of an oral and maxillofacial surgeon, and 3) consideration of CSF-draining interventions since symptoms are severely invalidating and irreversible within a couple of hours.


[Studies on synthesis and analgesic activities of bifentanyl derivatives].
In order to look for potent analgesic compounds and to study the relationships between structures and activities, twenty bifentanyl derivatives were synthesized and their analgesic activities were tested. The structures of the compounds were confirmed by spectral analysis and elemental analysis. Compounds IIa and IIb showed strong analgesic activities in preliminary pharmacological test. Further pharmacological examinations are in progress.


Intermediate Phenotype between ADULT Syndrome and EEC Syndrome Caused by R243Q Mutation in TP63.
A patient who had ectrodactyly, dry skin, exfoliative dermatitis, and hypodontia with peg-shaped teeth, but not cleft lip and palate, is described. Ectrodactyly with a tooth anomaly is recognized in both acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome. These 2 syndromes are caused by heterozygous mutations in the transcriptional factor gene p63. Mutation analysis of p63 gene showed a heterozygous mutation c.728G>A, p.Arg243Gln (previously referred to as R204Q) in the patient, but not in his parents. Therefore, this was a sporadic case of the p63 mutation-associated disorder. Although the mutation has been mostly reported in EEC syndrome patients, the present case did not have cleft lip and palate. Furthermore, the present case did not exhibit freckling or some of the other ectodermal dysplasia phenotypes typical of ADULT syndrome. The concept of ELA syndrome proposed by Prontera in 2011 resolves the problem confronted in diagnosing the present case. ELA syndrome is an acronym of EEC/limb-mammary syndrome/ADULT syndromes, and these 3 syndromes are united into a unique entity. This system can classify p63 mutation-associated disorders simply without interfering with treatment.


Tuning the Morphology of Li2O2 by Noble and 3d metals: A Planar Model Electrode Study for Li-O2 Battery.
In this work, a planar model electrode method has been used to investigate the structure-activity relationship of multiple noble and 3d metal catalysts for the cathode reaction of Li-O2 battery. The result shows that the battery performance (discharge/charge overpotential) strongly depends not only on the type of catalysts but also on the morphology of the discharge product (Li2O2). Specifically, according to electrochemical characterization and scanning electron microscopy (SEM) observation, noble metals (Pd, Pt, Ru, Ir, and Au) show excellent battery performance (smaller discharge/charge overpotential), with wormlike Li2O2 particles with size less than 200 nm on their surfaces. On the other hand, 3d metals (Fe, Co, Ni, and Mn) offered poor battery performance (larger discharge/charge overpotential), with much larger Li2O2 particles (1 μm to a few microns) on their surfaces after discharging. Further research shows that a "volcano plot" is found by correlating the discharging/charging plateau voltage with the adsorption energy of LiO2 on different metals. The metals with better battery performance and worm-like-shaped Li2O2 are closer to the top of the "volcano", indicating adsorption energy of LiO2 is one of the key characters for the catalyst to reach a good performance for the oxygen electrode of Li-O2 battery, and it has a strong influence on the morphology of the discharge product on the electrode surface.


Combating Obesity With Thermogenic Fat: Current Challenges and Advancements.
Brown fat and beige fat are known as thermogenic fat due to their contribution to non-shivering thermogenesis in mammals following cold stimulation. Beige fat is unique due to its origin and its development in white fat. Subsequently, both brown fat and beige fat have become viable targets to combat obesity. Over the last few decades, most therapeutic strategies have been focused on the canonical pathway of thermogenic fat activation via the β3-adrenergic receptor (AR). Notwithstanding, administering β3-AR agonists often leads to side effects including hypertension and particularly cardiovascular disease. It is thus imperative to search for alternative therapeutic approaches to combat obesity. In this review, we discuss the current challenges in the field with respect to stimulating brown/beige fat thermogenesis. Additionally, we include a summary of other newly discovered pathways, including non-AR signaling- and non-UCP1-dependent mechanisms, which could be potential targets for the treatment of obesity and its related metabolic diseases.


Productive, thermoregulatory, and hormonal responses of dairy goats supplemented with selenium-enriched yeast in the Brazilian semi-arid region.
The aim of this study was to evaluate the effect of adding selenium-enriched yeast (SE) in the diet of dairy goats during 60 days of lactation and its effect on productive, thermoregulatory, and hormonal responses of animals managed in a semi-arid region. Sixteen Saanen × Toggenburg crossbred goats were used in a completely randomized design. Goats were weighed, and their milk yield was monitored weekly. Before the animals entered the treatments and at every 20-day milk producing, blood samples were collected to determine the SE levels. At 20, 40, and days of the lactation cycle, individual milk samples were collected to determine composition, casein, urea nitrogen, and selenium content. Measurements of respiratory rate (RR), rectal temperature (RT), coat surface temperature (CST), and epidermal temperature (ET) were performed weekly during the experimental period in two shifts, one in the morning (9 am) and the other in the afternoon (3 pm). No difference (P > 0.05) was detected for body weight, milk yield, composition, selenium concentration, and urea nitrogen. Lower RR and ET (P < 0.05) were observed for animals that received SE supplementation. Thyroid hormone concentrations were similar between treatments (P > 0.05). The positive results of the SE supplementation were concentrated in thermoregulatory responses, and there was no effect on productive, hormonal responses, and plasmatic concentration of selenium in the milk. The SE supplementation for dairy goats managed in a Brazilian semi-arid region was able to promote reduction of RR and coat temperatures.


Adult marrow-derived very small embryonic-like stem cells and tissue engineering.
A population of CXCR4(+) lin(-) CD45(-) cells that express SSEA, Oct-4 and Nanog has been identified in adult bone marrow. These cells are very small and display several features typical for primary embryonic stem cells such as: i) a large nuclei surrounded by a narrow rim of cytoplasm; ii) open-type chromatin (euchromatin); and iii) high telomerase activity. These cells were named very small embryonic-like stem cells (VSEL-SC). The authors hypothesized that they are direct descendants of the germ lineage. Germ lineage, in order to pass genes on to the next generation, has to create soma and thus becomes a 'mother lineage' for all somatic cell lineages present in the adult body. Germ potential is established after conception in a totipotent zygote and retained subsequently during development in blastomers of morula, cells form the inner cell mass of blastocyst, epiblast and population of primordial germ cells. The authors envision that VSEL-SC are epiblast-derived pluripotent stem cells and could potentially become a less-controversial source of stem cells for regeneration.


Water in hydrated orthorhombic lysozyme crystal: Insight from atomistic simulations.
Biologically important water in orthorhombic lysozyme crystal is investigated using atomistic simulations. A distinct hydration shell surrounding lysozyme molecules is found from the number distribution of water molecules. While the number of water molecules in the hydration shell increases, the percentage decreases as the hydration level rises. Adsorption of water in the lysozyme crystal shows type-IV behavior. At low hydration levels, water molecules primarily intercalate the minor pores and cavity in the crystal due to the strong affinity between protein and water. At high hydration levels, the major pores are filled with liquidlike water as capillary condensation occurs. A type-H4 hysteresis loop is observed in the adsorption and desorption isotherms. The locations of the water molecules identified from simulation match fairly well with the experimentally determined crystallographic hydration sites. As observed in experiment, water exhibits anomalous subdiffusion because of the geometric restrictions and interactions of protein. With increasing hydration level, this anomaly is reduced and the diffusion of water tends to progressively approach normal Brownian diffusion. The flexibility of protein framework slightly enhances water mobility, but this enhancement decreases with increasing hydration level.


The Impact of Estrogen Receptor in Arterial and Lymphatic Vascular Diseases.
The lower incidence of cardiovascular diseases in pre-menopausal women compared to men is well-known documented. This protection has been largely attributed to the protective effect of estrogens, which exert many beneficial effects against arterial diseases, including vasodilatation, acceleration of healing in response to arterial injury, arterial collateral growth and atheroprotection. More recently, with the visualization of the lymphatic vessels, the impact of estrogens on lymphedema and lymphatic diseases started to be elucidated. These estrogenic effects are mediated not only by the classic nuclear/genomic actions via the specific estrogen receptor (ER) α and β, but also by rapid extra-nuclear membrane-initiated steroid signaling (MISS). The ERs are expressed by endothelial, lymphatic and smooth muscle cells in the different vessels. In this review, we will summarize the complex vascular effects of estrogens and selective estrogen receptor modulators (SERMs) that have been described using different transgenic mouse models with selective loss of ERα function and numerous animal models of vascular and lymphatic diseases.


[A case-control study on risk factors for nosocomial infection of epilepsy in hospitalized children].
To determine the incidence and risk factors for nosocomial infection in child epilepsy. A retrospective study was conducted among all (292 cases) hospitalized children epilepsy patients in First Affiliated Hospital of Fujian Medical University from 1996 to 2000 in Fuzhou city. With all patients with nosocomial infection as cases and all patients without nosocomial infection as controls, a case-control study on risk factors for nosocomial infection was carried out. Available data were analyzed by one-way Chi-square test and unconditional logistic multiple regression model. One hundred fourteen cases of nosocomial infection were identified among 292 cases with epilepsy with an incidence of 39.0% (114/292). The one-way Chi-square test showed that nosocomial infection was significantly associated with age below 3 years (OR = 2.55, P < 0.01), length of hospitalization over 14 days (OR = 4.75, P < 0.01), low intelligence (OR = 3.13, P < 0.01), receiving antibiotic unreasonably (OR = 3.51, P < 0.01), using gastrogarage (OR = 3.12, P < 0.01), other invasive operation (OR = 1.85, P < 0.05) dyskinesia or palsy (OR = 3.51, P < 0.01), and urinary nitrogen beyond normal range (OR = 5.00, P < 0.05), etc. Unconditional logistic multiple regression analysis revealed that the length of hospitalization over 14 days (OR = 4.30, OR 95% CI: 2.48 - 7.46, P < 0.01), taking antibiotic unreasonably (OR = 2.74, OR 95% CI: 1.30 - 5.77, P < 0.01), using gastrogarage (OR = 3.04, OR 95% CI: 1.28 - 7.18, P < 0.05), and low intelligence (OR = 2.32, OR 95% CI: 1.34 - 4.01, P < 0.01) were independent risk factors for nosocomial infection. The tendency chi-square test showed that the longer stay in the hospital with more kinds of antibiotic used and more gastrogarage they used, the greater the risk of nosocomial infection was. Data suggested that occurrence of the nosocomial infection of children epilepsy patients was correlated with the length of hospitalization over 14 days, unreasonable using antibiotic, using gastrogarage and low intelligence.


[Treatment of esophageal cancer in elderly patients].
During the last 30 years, the median survival time and 5-year survival rate of esophageal cancer have improved significantly. In recent years, two major factors have greatly contributed to improve the outcomes of treatment for esophageal cancer in Japan. One is the establishment of endoscopic diagnosis and treatment of superficial esophageal cancer, and another is the establishment of a standard surgical procedure, subtotal esophagectomy with dissection of three field lymph nodes. In an aging society like Japan, with the increased incidence, the diagnosis and treatment of esophageal cancer will become increasingly important in the future. The effectiveness and risk of surgical treatment, chemotherapy, radiotherapy and combination therapy for elderly patients with esophageal cancer will also become important. However, the average life expectancy has reached 79 years for Japanese men, and various evidence from clinical research on patients less than 75 years old is not longer sufficient. Care of elderly patients with esophageal cancer has relied on past experience. Now, clinical studies on elderly esophageal cancer must be improved.


[Ultrastructure of the secretory cells of the pancreatic islets in human fetuses].
An electron microscopic study of pancreatic islets of human fetuses 16--28 weeks old discovered four types of secretory cells -- B, A, D and type IV, which has not yet been given a generally accepted name. These cells contain small secretory granules more dense than granules D. In three cases endocrine elements with "mixed" granulation (D--A) were noted. The formation of insulin- and glucagon-containing granules in the ergastoplasm and Golgi complex was observed. The hormone secretion is realized by emyocitosis.


Supportive-expressive interventions in working through treatment termination.
Supportive-expressive (SE) psychodynamic treatment has been receiving much empirical support. It is based on conceptualizing and working through the patients' Core Conflictual Relationship Theme, which includes their main wish (W) in the context of an interpersonal relationship, an actual or anticipated subjective response from the other (RO) in relation to the W, and the subsequent emotional and behavioral response from the self (RS) to the RO. Studies suggest that the RO and RS components show the greatest change as a result of effective SE treatment. Clinical experience, however, suggests that in the last phase of treatment, when termination is anticipated, at least some patients regress to their original RS. This process is part of a separation conflict, which includes unconsciously renouncing their RS gains. In the present article we make recommendations regarding the timing and manner of initiating the termination discussion (the "clock-like reminder" and the "symbolic listening to termination cues"), integrating both supportive and expressive techniques. The article contains practice-based guidelines on how to work through the potential RS regression. We pay specific attention to what to do and not to do in the very last session and use examples from the pilot phase of a randomized controlled trial to demonstrate each recommended technique. Lastly, we suggest paths for future research to examine the proposed framework for working through termination. (PsycINFO Database Record


Protection of guinea pigs from primary and recurrent herpes simplex virus (HSV) type 2 cutaneous disease with vaccinia virus recombinants expressing HSV glycoprotein D.
Vaccinia virus recombinants containing herpes simplex virus (HSV) type 1 (VP176) or type 2 (VP221) glycoprotein D (gD) genes were studied for their protective potential in the guinea pig model of recurrent HSV type 2 disease. Cells infected with these recombinants synthesized at least one protein (precursor, mature form, or both) that was precipitated with monoclonal antibody to HSV type-common determinants on gD. These determinants were detected on the surface of cells infected with the recombinants at 2 hr after infection. VP176 immunization protected against primary (P much less than .001) and recurrent (P much less than .001) cutaneous HSV type 2 lesions and ganglionic latency (62% protection). VP221 immunization protected against recurrent disease (P less than .05), although HSV type 2 ganglionic infection was established. Protection, first observed at two weeks after immunization, apparently did not involve HSV-specific neutralizing antibody because seroconversion was detected at 35-45 days after immunization. Protection was correlated with HSV-specific lymphoproliferation and the elaboration of lymphokines that enhance natural killer cell cytolysis.