Understanding the influence of urban- or rural-living on cardiac patients' decisions about diet and physical activity: descriptive decision modeling.
It is challenging to assist people to attend to risk factors for coronary artery disease (CAD). There is potential for cultural elements associated with place of residence (i.e., urban- or rural-living) to have an effect on peoples' decision-making about managing CAD risk. To better understand patient's decision-making processes regarding having a heart-healthy diet and engaging in regular physical activity (major CAD risk factors), and the potential influence of urban- or rural-living. Based on a previous series of qualitative interviews with 42 cardiac patients (21 urban-living, 21 rural-living), hierarchical decision-models regarding eating a heart-healthy diet and engaging in regular physical activity were developed, and a survey based on the decision-models generated. The models were then tested for 'fit' with another group of 42 cardiac patients, and were revised to make them more parsimonious. The final models were tested with a novel group of 647 CAD patients from Alberta, Canada (327 urban-living, 320 rural-living). The primary analysis was focused on determining the extent to which patients completing the survey fell in the correct behavioral group. Thereafter individual nodes were examined to determine decision-making constructs that were different between urban- and rural-living patients. When tested, the models had overall accuracy of 93.5% for diet and 97.5% for physical activity. The most salient model nodes that led to differing behavioral outcomes reflected these constructs: perception of control over health; time, effort, or competing priorities; receipt of appropriate information; and appeal of the activity. This information is potentially useful to assist healthcare providers to: (1) understand patients' decisions regarding their cardiac risk factor modification behavior, and (2) better direct conversations about risk factor modification and educational activities.


Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization.
The objective was to identify the factors, if any, that may predict long-term results of CIN treatment and HPV clearance/persistence after locally excisional therapy. A series of 252 women with CIN lesions treated by conization were subjected to sequential HPV detection by repeated PCR during the prospective posttreatment follow-up. Factors predicting viral clearance during the follow-up (10.26 months) were elaborated using univariate and multivariate statistical techniques applied on epidemiological, clinical and biological data of the lesions. Sensitivity of the PAP test in detecting high-grade lesions was 93.9%, and specificity 27.3%. Odds ratio for having CIN 3/Stage IA1 squamous cervical cancer in the cone with HSIL PAP test was 5.69; 77.8 and 22.2% residual disease were found among PCR-positive and -negative cases, respectively. HPV DNA was negative in 74/252 (29.8%) samples at the first PCR. Multivariate logistic regression analysis showed that HPV 16 was an independent explanatory factor for high-grade CIN (P = 0.0001). HPV clearance increased to 63.5% at completion of the follow-up, corresponding to the monthly clearance rate of 5.27%. In Kaplan-Meier analysis, the highly significant (P = 0.0001) predictors of HPV clearance/persistence were age, lesion grade in the biopsy, lesion grade in the cone, volume of the cone, length of active sexual life, and involvement of endocervical margin (P = 0.0013). In chi-square tests, high-risk HPV type (P = 0.001) was such a predictor. In multivariate (Cox) model, the significant independent predictors of HPV clearance were involved endocervical margin (P = 0.001), lesion grade in the cone (P = 0.004), high-grade lesion in the colposcopic biopsy (P = 0.023), age (P = 0.029), and HSIL in PAP smear (P = 0.029). These data suggest that posttreatment follow-up should include both the PAP test and HPV detection techniques for early detection of any patients at increased risk for disease recurrence and progression, because of persistent oncogenic HPV types.


Clinical results of endocapsular phacoemulsification and complete in-the-bag intraocular lens fixation.
Endocapsular phacoemulsification was performed in the Hara Eye Hospital on 77 eyes of 69 patients between October 1984 and January 1986. The age of patients ranged from 52 to 86 years with an average of 71 years. In 71 of 77 eyes, a posterior chamber lens was inserted. The procedure was attempted in 243 eyes and was successfully performed in 77 of them (32%). The causes of failure in 166 eyes were anterior capsule rupture in 149 eyes (90%) and posterior capsule rupture in 27 eyes (16%). With the exception of one eye lost to follow-up, the results of these cases were satisfactory. A postoperative visual acuity of better than 20/20 was achieved in 45 eyes (58%), better than 20/40, in 70 eyes (91%). The main postoperative complications in 50 completely recorded eyes were anterior capsule opacity in 44 eyes (88%), severe iris atrophy because of intraoperative ultrasound in seven eyes (9%), and posterior capsule opacity causing visual disturbance in three eyes (4%).


Effects of chronic oral dosing with quinine sulphate in the rat.
Male Leeds strain rats were given 0.1% guinine sulphate in their drinking water for up to 15 months. A high mortality rate was obtained, but no tumours arose during the 20 month duration of the experiment. However, liver parenchymal changes were observed which appeared to be associated with chronic toxicity due to quinine and did not include hyperplasia.


Physician-Reported Barriers to Osteoporosis Screening: A Nationwide Survey.
Despite increased awareness, osteoporosis screening rates remain low. The objective of this survey study was to identify physician-reported barriers to osteoporosis screening. We conducted a survey of 600 physician members of the Endocrine Society, American Academy of Family Practice, and American Geriatrics Society. The respondents were asked to rate barriers to osteoporosis screening in their patients. We performed multivariable logistic regression analyses to determine correlates with the most commonly reported barriers. Of 566 response-eligible physicians, 359 completed the survey (response rate, 63%). The most commonly reported barriers to osteoporosis screening included patient nonadherence (63%), physician concern about cost (56%), clinic visit time constraints (51%), low on the priority list (45%), and patient concern about cost (43%). Patient nonadherence as a barrier was correlated with physicians in academic tertiary centers (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.06-5.13), whereas clinic visit time constraints were correlated with physicians in both community-based academic affiliates and academic tertiary care ([OR, 1.96; 95% CI, 1.10-3.50] and [OR, 2.48; 95% CI, 1.22-5.07], respectively). Geriatricians (OR, 0.40; 95% CI, 0.21-0.76) and physicians with >10 years in practice were less likely to report clinic visit time constraints as a barrier (11-20 years: OR, 0.41; 95% CI, 0.20-0.85; >20 years: OR, 0.32; 95% CI, 0.16-0.65). Physicians with more patient-facing time (3-5 compared with 0.5-2 d/wk) were more likely to place screening low on the priority list (OR, 2.66; 95% CI, 1.34-5.29). Understanding barriers to osteoporosis screening is vital in developing strategies to improve osteoporosis care.


Risk factors for heart, cerebrovascular, and kidney diseases: evaluation of potential side effects of medications to control hypertension, hyperglycemia, and hypercholesterolemia.
Heart disease (HD), cerebrovascular disease (CBD), and kidney disease (KD) are serious diseases worldwide. These diseases constitute the leading causes of death worldwide and are costly to treat. An analysis of risk factors is necessary to prevent these diseases. Risk factors were analyzed using data from 2,837,334, 2,864,874, and 2,870,262 medical checkups obtained from the JMDC Claims Database. The side effects of medications used to control hypertension (antihypertensive medications), hyperglycemia (antihyperglycemic medications), and hypercholesterolemia (cholesterol medications), including their interactions, were also evaluated. Logit models were used to calculate the odds ratios and confidence intervals. The sample period was from January 2005 to September 2019. Age and history of diseases were found to be very important factors, and the risk of having diseases could be almost doubled. Urine protein levels and recent large weight changes were also important factors for all three diseases and made the risks 10%-30% higher, except for KD. For KD, the risk was more than double for individuals with high urine protein levels. Negative side effects were observed with antihypertensive, antihyperglycemic, and cholesterol medications. In particular, when antihypertensive medications were used, the risks were almost doubled for HD and CBD. The risk would be triple for KD when individuals were taking antihypertensive medications. If they did not take antihypertensive medications and took other medications, these values were lower (20%-40% for HD, 50%-70% for CBD, and 60%-90% for KD). The interactions between the different types of medications were not very large. When antihypertensive and cholesterol medications were used simultaneously, the risk increased significantly in cases of HD and KD. It is very important for individuals with risk factors to improve their physical condition for the prevention of these diseases. Taking antihypertensive, antihyperglycemic, and cholesterol medications, especially antihypertensive medications, may be serious risk factors. Special care and additional studies are necessary to prescribe these medications, particularly antihypertensive medications. No experimental interventions were performed. As the dataset was comprised of the results of health checkups of workers in Japan, individuals aged 76 and above were not included. Since the dataset only contained information obtained in Japan and the Japanese are ethnically homogeneous, potential ethnic effects on the diseases were not evaluated.


Thin-layer chromatography-mass spectrometry using activated carbon, surface-assisted laser desorption/ionization.
The analysis of compounds separated by thin-layer chromatography (TLC) by surface-assisted laser desorption ionization (SALDI) mass spectrometry has been demonstrated. The compounds are analyzed from the surface of the intact TLC plate, and the preparation of the TLC plate is rapid and robust: the gel surface is covered with 2 microns activated carbon particles, and glycerol is added. Analytes diffuse from the interior of the gel to the surface where they are adsorbed onto the activated carbon. A nitrogen laser is used to desorb analyte ions from the carbon particles in a time-of-flight mass spectrometer. A wide range of organic compounds, including peptides, can be detected, either as protonated or as cationized molecules. Interference with "matrix peaks" is limited since background TLC-SALDI mass spectra typically show only a few intense peaks at low mass. The detection limit for bradykinin from a developed plate is approximately 25 ng (calculated for S/N = 3). The mass resolution (FWHM) varied from a high of about 500 to a low of about 100. This variability was likely due to surface charging. Methods to improve both mass resolution and sensitivity of TLC-SALDI are suggested.


Three-dimensional sperm surface reconstruction: a novel approach to assessing sperm morphology.
To create a rapid, inexpensive, efficient, and reproducible real-time three-dimensional (3-D) analysis of viable spermatozoa. Previous studies have demonstrated that abnormal semen profiles are associated with a modest increase in the frequency of sperm chromosomal abnormalities, and that sperm with aberrations in the shape and contours of the head may be carriers of chromatinic defects. Although high-power magnification and enhanced video-generated magnification have been suggested, these techniques are inherently limited by the clarity of the image, the time required for the analysis, and the risk of variable head-positioning during imaging. In vitro experiment. University-affiliated infertility research laboratory. Anonymous sperm donors. Individual motile sperm were identified, analyzed at ×600 magnification, and a 10-second digital video was obtained. Image-tracking software captured serial photographs of sperm from recorded videos. Images were automatically extracted from each video frame using enhanced correlation coefficient maximization; the general shape of the sperm was extracted via space-carving. The reconstructed image was rotated to permit viewing from any direction, and the final image was rendered through interpolation. This technique yielded images that enable noninvasive, 3-D, real-time, in vitro assessment of sperm surface morphology. This proof-of-principle demonstrates that by keeping spermatozoa in a fluid environment, a 3-D sperm-surface reconstruction can be created. This technique can be automated, requires minimal computing power, and utilizes equipment already available in most embryology laboratories.


Quantum chemical computations, vibrational spectroscopic studies, NLO and NBO/NLMO analysis of o-chlorobenzohydrazide.
The molecular vibrations of o-chlorobenzohydrazide (OCBH) have been investigated in polycrystalline sample, at room temperature, by recording Fourier transform infrared (FT-IR) and FT-Raman spectroscopies. The complete vibrational assignment and analysis of the fundamental modes was carried out using the experimental data and quantum chemical studies. The observed vibrational data were compared with the wavenumbers derived theoretically for the optimized geometry of the compound from the HF and DFT/B3LYP calculations employing 6-311++G(d,p) basis set. The (1)H and (13)C NMR chemical shifts have been simulated. Thermodynamic properties have been calculated at different temperatures. HOMO-LUMO energy gap has been calculated. The intramolecular contacts have been interpreted using Natural Bond Orbital (NBO) and Natural Localized Molecular Orbital (NLMO) analysis.


Immunocytochemical demonstration of erythropoietin in hypoxic human hepatoma cultures.
The possibility of demonstrating erythropoietin at the light microscopic level was examined in homogenous cultures of the erythropoietin-producing human hepatoma cell lines HepG2 and Hep3B. Immunoperoxidase staining was applied in combination with several mono- and polyclonal antibodies. Sufficiently strong colour responses were obtained with all three polyclonal antibodies and with one of three monoclonal antibodies raised against recombinant human erythropoietin. The staining intensity was increased in hypoxic versus nonhypoxic hepatoma cultures. Intracellular erythropoietin immunoreactivity was confirmed by Western blot analysis of HepG2 extracts. The effect of oxygen supply on erythropoietin gene expression was confirmed by competitive polymerase chain reaction of erythropoietin mRNA and by radioimmunoassay of secreted erythropoietin.


Evaluation of MRI fat fraction in the liver and spine pre and post SPIO infusion.
This study evaluates the robustness of a magnetic resonance (MR) fat quantification method to changes in R2* caused by an intravenous infusion of superparamagnetic iron oxide (SPIO) contrast agent. The R2* and proton density fat fraction (PDFF) were measured in liver and spine in 14 subjects using an investigational sequence (IDEAL IQ) provided by the MR scanner vendor. Measurements were made before and after SPIO infusion. Results showed SPIO significantly increased R2* in both liver (p=8.8×10(-8)) and spine (p=1.3×10(-2)) but PDFFs were not significantly different in either the liver (p=5.5×10(-1)) or the spine (p=5.6×10(-1)). These results confirm that the IDEAL IQ method of fat quantification is robust to changes in R2*.


Macrophage depletion and manipulation of enhanced immune response in an animal model of bladder cancer.
In a transplantable model of bladder cancer the inhibition of tumor growth by polyinosinic:polycytidylic acid (poly(I:C], concomitant stimulation of natural killer cell activity, and inhibition of both effects by prior inoculation with anti-interferon antiserum have been previously observed. The possible role of macrophages in these interactions is explored. Depletion of peritoneal macrophages by silica at concentrations that did not markedly depress natural killer cell activity was found to inhibit the enhancement of natural killer cell activity by subsequent in vivo poly(I:C) inoculation. Inoculation with silica also seemed to abrogate the tumor inhibitory effect of poly(I:C) treatment. To determine whether effects of poly(I:C) on natural cytotoxicity and tumor growth were mediated through production of interferon, anti-interferon antiserum (alpha-IF) was inoculated prior to poly(I:C) therapy. Tumor growth appeared to be uneffected by this maneuver even though poly(I:C)-induced enhancement of natural cytotoxicity was inhibited. Taken together, both macrophages and interferon may play a pivotal role in the immune response in both a stimulatory and a suppressive capacity. Additional study on such influences may be important if in vivo manipulation of these regulatory effects is to be accomplished successfully.


Intraprofessional fieldwork education: occupational therapy and occupational therapist assistant students learning together.
In the past 10 years, the use of support personnel in Canada has generated significant interest from occupational therapists, professional associations, regulatory bodies, employers, educational institutions, and government agencies. The purpose of this study was to explore the impact of a combined collaborative fieldwork placement and weekly tutorial as a teaching strategy for intraprofessional education. Seven pairs of student occupational therapists and occupational therapist assistants were assigned to fieldwork placements. Tutorials were scheduled during the placements to discuss intraprofessional issues and provision of occupational therapy services in the clinical setting. Journaling and focus groups were used to collect data from students, tutors, and preceptors. Three key themes emerged from the data: (1) developing the relationship, (2) understanding roles, and (3) recognizing environmental influences on learning. Intraprofessional learning experiences prior to graduation can help prepare occupational therapy and occupational therapist assistant students for future collaborative practice.


The duration of excretion of viable bacilli in elderly patients on treatment for cavitating pulmonary tuberculosis.
To determine the period of excretion of viable tubercle bacilli in cavitating pulmonary tuberculosis in elderly patients while on treatment. 10 consecutive black hospital inpatients over the age of 65 years (6 men, 4 women) with positive acid-fast bacilli smears and Lowenstein-Jenssen culture-proven pulmonary tuberculosis and radiological cavitation had weekly smears and cultures until at least three smears or two cultures were negative. Supervised treatment comprising rifampicin, pyrazinamide, ethambutol and isoniazid. It look an average of 5.7 weeks (range 4-9 weeks) for the cultures and 8.2 weeks (range 4-14 weeks) for the smears to become negative. Patients with cavitating pulmonary tuberculosis continue to excrete viable tubercle bacilli for approximately 6 weeks despite supervised treatment. It is suggested that allowing such patients back into an environment where three are immunocompromised subjects (e.g. elderly people in retirement homes or HIV-positive subjects) is probably hazardous until the patients are culture or smear negative.


Cryopreserved bone marrow aspirate concentrate as a cell source for the colony-forming unit fibroblast assay.
The prevalence of connective tissue progenitor cells within a cell-based therapy is often quantified using the colony-forming unit fibroblast (CFU-F) assay. The present study investigates the feasibility of using cryopreserved bone marrow aspirate concentrate (BMAC) as an alternative cell source to fresh BMAC for CFU-F quantification. Freshly prepared and corresponding cryopreserved BMAC samples from patients receiving autologous cell therapy (n = 98) were analyzed using the CFU-F assay for comparison. Cultures were established by directly plating BMAC at low cell densities and maintained for a 2-week growth period. Colonies were enumerated to determine CFU-F frequency, and a subset of cultures was imaged and analyzed to quantify colony area and density. A nonlinear relationship was observed between plating density and CFU-F frequency over a wide range in plating densities (~30-fold). Cryopreserved BMAC yielded recoverable (77 ± 23%) and viable (73 ± 9%) nucleated cells upon thawing. After cryopreservation, CFU-F frequencies were found to be significantly lower (56.6 ± 34.8 vs. 50.3 ± 31.7 colonies per million nucleated cells). Yet the number of CFU-F in fresh and cryopreserved BMAC were strongly correlated (r = 0.87) and had similar area and densities. Further, moderate correlations were observed between the number of CFU-F and nucleated cells, and both the mean colony area and density were negatively correlated with patient age. Notably, no relationship was found between CFU-F frequency and age, regardless of whether fresh or cryopreserved BMAC was used. Freshly prepared and cryopreserved BMAC yielded correlated results when analyzed using the CFU-F assay. Our findings support the cryogenic storage of patient BMAC samples for retrospective CFU-F analyses, offering a potential alternative for characterizing BMAC and furthering our understanding of progenitor cells in relation to clinical outcome.


Indentation of an osteochondral repair: sensitivity to experimental variables and boundary conditions.
The sensitivity of the affects of indenter radius, defect depth, cartilage permeability and flow boundary conditions, on the indentation testing of a repairing osteochondral defect was investigated. Since the boundary condition on the flow across the cartilage repair-subchondral bone interface is not known, the effects of two different conditions were investigated: free-flow and no-flow. A poroelastic finite element model of an osteochondral defect at different stages of the repair process was developed using dimensions typical of the rabbit knee. Results showed when the radius of the indenter was much less than the thickness of the cartilage the sensitivity of the indentation displacement to flow boundary conditions decreased. Simulated indentation displacement was insensitive to bone regeneration up to 50% of the initial defect depth, which suggests that only the properties of the material in the upper-half of the defect are being evaluated. Small variations in permeability had little affect on the simulated indentation. In a fully repaired defect, the simulated indentation is independent of the boundary condition. However, while the defect is in the process of repair and the regenerated cartilage is deeper than the host, indentation is sensitive to the flow boundary condition. Based on these results, and feasible experimental conditions, we conclude that the boundary condition on the repair-subchondral bone interface must be known in all cases except when the defect approaches full repair, if accurate estimates of material properties are to be obtained from indentation.


Tissue-specific modulation of rat glucagon receptor mRNA by thyroid status.
The influence of thyroid status on glucagon receptor mRNA levels was investigated in rats using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Glucagon receptor mRNA was detected in liver, brown and white adipose tissues (BAT and WAT) and brain. In BAT and WAT, pharmacologically-induced moderate hypothyroidism resulted in a marked reduction in the relative abundance of glucagon receptor mRNA. Short-term treatment of hypothyroid rats with exogenous 3,3',5'-triiodo-L-thyronine (T3), resulting in a marked hyperthyroidism, reversed the phenomenon in BAT while the reversal was only partial in WAT. In the liver, there was no significant effect of mild hypothyroidism while there was a positive effect of hyperthyroidism. In brain, the relative tissue abundance of glucagon receptor mRNA was not affected by the large changes in plasma T3. The present results therefore indicate that thyroid status may modulate the relative abundance of glucagon receptor mRNA in a tissue-specific manner.


The effects of cannabinoid administration on sleep: a systematic review of human studies.
This paper reviews the literature regarding the effects of cannabinoid administration on sleep in humans. A literature search using a set of cannabinoid and sleep-related terms was conducted across eight electronic databases. Human studies that involved the administration of cannabinoids and at least one quantitative sleep-related measure were included. Review papers, opinion pieces, letters or editorials, case studies (final N < 7), published abstracts, posters, and non-English papers were excluded. Thirty-nine publications were included in the review. Findings were mixed and showed various effects of cannabinoid administration on several aspects of sleep. Methodological issues in the majority of studies to date, however, preclude any definitive conclusion.


Hepatic Plexus Nerve Block for Microwave Ablation of Hepatic Tumors.
Seven patients underwent microwave ablation of hepatic tumors; during ablation, a hepatic nerve plexus block was used for pain control. The mean visual analog scale (VAS) score for pain (scale, 0-10) was 0.3 ± 0.5 (SD) at baseline and 2.5 ± 1.4, 2.6 ± 1.4, and 2.3 ± 0.9 at 1, 5, and 10 minutes during ablation. Two patients reported a VAS score of 4 or greater during ablation, which improved in both patients to a VAS score of 3 after one rescue sedation dose. The remaining patients required no additional sedation. No major complication occurred. No patient required conversion to general anesthesia.


Dog-Assisted Therapy vs Relaxation for Children and Adolescents with Fetal Alcohol Spectrum Disorder: A Randomized Controlled Study.
The rationale of this study was to evaluate the efficacy of Dog-assisted Therapy (DAT) in children and adolescents with Fetal Alcohol Spectrum Disorder (FASD). We conducted a randomized controlled trial in a cohort of 71 children and adolescents with FASD. Participants were randomly assigned either to DAT group (n = 38) or Relaxation Group (control group) (n = 33). Results revealed that participants who were assigned to the DAT group experienced significantly reduced externalizing symptoms (CBCL Externalizing Inattention: t (69) = 2.81, p = .007; d = 0.7); CBCL Opposition: t (69) = 2.54, p = .013; d = 0.6), reduced internalizing symptoms (CBCL Social problems: t (69) = 3.21, p = .002; d = 0.8) as well as improvements on social skills (SSIS-P Problem behavior: t (68) = 2.55, p = .013; d = 0.6), and quality of life (KidScreen Autonomy and Parents: t (51) = - 2.03, p = .047; d = 0.5) compared to the relaxation control group. The relaxation control group obtained significant differences between the pre- and post-treatment evaluation, diminishing withdraw symptoms (t (32) = 3.03, p = .005; d = 0.2). Results suggest that DAT and relaxation may be promising adjunctive treatments for children and adolescents with FASD.Clinical trial registration information: http://clinicaltrials.gov/ ; NCT04038164.


Macrofaunal control of microbial community structure in continental margin sediments.
Through a process called "bioturbation," burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but geochemically and sedimentologically divergent, continental margin sites are highly similar but differ clearly from those in nonbioturbated surface and underlying subsurface sediments. Solid- and solute-phase geochemical analyses combined with modeled bioturbation activities reveal that dissolved O2 introduction by burrow ventilation is the major driver of archaeal community structure. By contrast, solid-phase reworking, which regulates the distribution of fresh, algal organic matter, is the main control of bacterial community structure. In nonbioturbated surface sediments and in subsurface sediments, bacterial and archaeal communities are more divergent between locations and appear mainly driven by site-specific differences in organic carbon sources.


Immunologic evaluation of children with homozygous beta-thalassemia treated with desferrioxamine.
In 15 children with thalassemia major (age 4-17 years) a detailed analysis of different immune functions was performed: phagocyte function, specific cellular immunity, humoral defense system. All patients had been subjected to a desferrioxamine therapy and a high transfusion regimen. Examination of neutrophil function included adherence, random migration, chemotaxis, killing of Escherichi coli and production of superoxide radical; these neutrophil functions were shown to be normal. In addition, lymphocyte proliferation in response to different lectins (phytohemagglutinin, concanavalin A, pokeweed mitogen) was identical in patients and controls. However, the number of circulating T-lymphocytes, helper T-cells and B-lymphocytes was increased in some patients. This phenomenon probably reflects an unspecific stimulation of the antibody-producing cells by repeated blood transfusions.


A disease with a sweet tooth: exploring the Warburg effect in Alzheimer's disease.
After more than 80 years from the revolutionary discoveries of Otto Warburg, who observed high glucose dependency, with increased glycolysis and lactate production regardless of oxygen availability in most cancer cells, the 'Warburg effect' returns to the fore in neuronal cells affected by Alzheimer's disease (AD). Indeed, it seems that, in the mild phase of AD, neuronal cells "prefer" to use the energetically inefficient method of burning glucose by glycolysis, as in cancer, proving to become resistant to β-amyloid (Aβ)-dependent apoptosis. However, in the late phase, while most AD brain cells die in response to Aβ toxicity, only small populations of neurons, exhibiting increased glucose uptake and glycolytic flux, are able to survive as they are resistant to Aβ. Here we draw an overview on the metabolic shift for glucose utilization from oxidative phosphorylation to glycolysis, focusing on the hypothesis that, as extreme attempt to oppose the impending death, mitochondria-whose dysfunction and central role in Aβ toxicity is an AD hallmark-are sent into quiescence, this likely contributing to activate mechanisms of resistance to Aβ-dependent apoptosis. Finally, the attempt turns out fruitless since the loss of the adaptive advantage afforded by elevated aerobic glycolysis exacerbates the pathophysiological processes associated with AD, making the brain susceptible to Aβ-induced neurotoxicity and leading to cell death and dementia. The understanding of how certain nerve cells become resistant to Aβ toxicity, while the majority dies, is an attractive challenge toward the identification of novel possible targets for AD therapy.


A validated HPLC method with fluorescence detection for the glucuronides of Combretastatin A1 in human plasma, and studies on their cis-trans isomerisation.
Two monoglucuronides (CA1G1 and CA1G2) of the catecholic cis-stilbene Combretastatin A1 (CA1, OXi4500), have been identified in a clinical trial of the bisphosphate prodrug of OXi4500, OXi4503. A validated assay for the two glucuronides in human plasma using HPLC with fluorescence detection after post-column photolysis is described. The assay was linear over the range 25 nM (CA1G1) or 50 nM (CA1G2) - 5000 nM, R(2)≥ 0.996. The intra-day precision for CA1G1 was better than 8.7% RSD (19.4% at the LLOQ), and the inter-day precision was better than 5.5% RSD (7.6% at the LLOQ). The intra- and inter-day accuracies were better than ± 12.6% relative error (14.8% at the LLOQ) and 4.8% (5.4% at the LLOQ) respectively. For CA1G2, the intra-day precision was better than 5.7% RSD (7.5% at the LLOQ), and the inter-day precision was better than 4.8% RSD (11.9% at the LLOQ). The intra- and inter-day accuracies were better than ± 10.1% relative error (12.6% at the LLOQ) and 2.2% (3.8% at the LLOQ) respectively. Recovery from plasma was measured at three concentrations (125, 625 and 2500nM). Mean recovery of CA1G1 was 94.5% and ranged from 94.4 to 99.2%. Mean recovery of CA1G2 was 90.7%, range 88-92%. During the validation process, one of the isomers was unexpectedly found to be unstable. CA1G1, substituted ortho to the stilbene, was relatively stable, but the meta-substituted CA1G2 readily converted from the cis-stilbene conformation to the trans isomer. This was catalysed by acid and heavy metals, and could be inhibited by antioxidants such as ascorbic acid. Isomerisation could also be induced by one-electron oxidation processes such as horseradish peroxidase and azide radicals.


Pure topographical disorientation: a definition and anatomical basis.
Four patients showing the syndrome of "topographical disorientation" are reported. Patients became unable to find their way, especially in unfamiliar surroundings, following a single lesion in the territory of the right posterior cerebral artery, as evidenced on CT-scan. Associated disturbances included: left hemianopia, mild face recognition problems, and various degree of impairment in face-learning and visual maze-learning tasks. Language, visuo-perceptive and constructional abilities, object and picture recognition were intact. Memory tests only showed a mild, generally non-significant, impairment of visual memory. As inferred from the lesion located in the 4 patients, this syndrome seems to be strongly related to damage to the right parahippocampal gyrus, a structure that thus appears crucial for specifically storing and/or retrieving visual information necessary to achieve orientation in the locomotor environment.


Machine Learning-Based Human Posture Identification from Point Cloud Data Acquisitioned by FMCW Millimetre-Wave Radar.
Human posture recognition technology is widely used in the fields of healthcare, human-computer interaction, and sports. The use of a Frequency-Modulated Continuous Wave (FMCW) millimetre-wave (MMW) radar sensor in measuring human posture characteristics data is of great significance because of its robust and strong recognition capabilities. This paper demonstrates how human posture characteristics data are measured, classified, and identified using FMCW techniques. First of all, the characteristics data of human posture is measured with the MMW radar sensors. Secondly, the point cloud data for human posture is generated, considering both the dynamic and static features of the reflected signal from the human body, which not only greatly reduces the environmental noise but also strengthens the reflection of the detected target. Lastly, six different machine learning models are applied for posture classification based on the generated point cloud data. To comparatively evaluate the proper model for point cloud data classification procedure-in addition to using the traditional index-the Kappa index was introduced to eliminate the effect due to the uncontrollable imbalance of the sampling data. These results support our conclusion that among the six machine learning algorithms implemented in this paper, the multi-layer perceptron (MLP) method is regarded as the most promising classifier.


The CGRP receptor can couple via pertussis toxin sensitive and insensitive G proteins.
Swiss 3T3 cell lines were constructed co-expressing receptor activity modifying protein (RAMP) 1 with the calcitonin receptor-like receptor (CRLR), and showed 125I-calcitonin-gene-related peptide (CGRP) 1 binding indicative of a type I CGRP receptor. Application of CGRP1 led to an increase in cAMP, which in 2/5 cell lines was augmented following pertussis toxin (PTX) pre-treatment. In Xenopus oocytes, expression of RAMP1, which potentiates an endogenous CGRP receptor, led to constitutive activation of co-expressed GIRK potassium channels. This potassium current was increased following CGRP application or co-expression of CRLR, but decreased by PTX or co-expression of transducin. We conclude that the CGRP receptor can signal to both PTX sensitive and insensitive G proteins.


15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications.
Rebamipide, a gastro-protective drug, was developed in Japan for the treatment of peptic ulcer disease. It was proven superior to the former same category drug cetraxate in a randomized, controlled, double-blind, comparative clinical study in 1989. Rebamipide's mechanisms of actions are different from anti-secretory drugs; it accelerates and improves the quality of ulcer healing and reduces ulcer recurrence rate. Numerous studies have been conducted to explain the mechanisms responsible for these actions, 37 papers were published by 1998. Major properties of rebamipide include: stimulation of prostaglandin and mucus glycoprotein synthesis, inhibition of reactive oxygen species, inflammatory cytokines and chemokines, and inhibition of neutrophils activation. Since 1998, 107 papers were published, clarifying further effects of rebamipide on cyclooxygenase-2, prostaglandin E receptors, growth factors (i.e., HGF, EGF, and VEGF), heat-shock proteins, nitric oxide, adhesion molecules, neutrophils, and Helicobacter pylori- and NSAID-related pathology. Moreover, inhibitory action of rebamipide on gastric cancer growth has also been shown. In this issue we reviewed recent advances in understanding of rebamipide's mechanism of action and its newest clinical applications.


Density functional theory and 3D-RISM-KH molecular theory of solvation studies of CO2 reduction on Cu-, Cu2O-, Fe-, and Fe3O4-based nanocatalysts.
Using OpenMX quantum chemistry software for self-consistent field calculations of electronic structure with geometry optimization and 3D-RISM-KH molecular theory of solvation for 3D site distribution functions and solvation free energy, we modeled the reduction of CO2+H2 in ambient aqueous electrolyte solution of 1.0-M KH2PO4 into (i) formic acid HCOOH and (ii) CO H2O on the surfaces of Cu-, Fe-, Cu2O-, and Fe3O4-based nanocatalysts. It is applicable to its further reduction to hydrocarbons. The optimized geometries and free energies were obtained for the pathways of adsorption of the reactants from the solution, successive reduction on the surfaces of the nanocatalysts, and then release back to the solution bulk.


Emergence of clonal chromosomal alterations during the mesenchymal stromal cell cultivation.
Use of human mesenchymal stromal cells (MSCs) is a promising strategy for cell therapy in injured tissues recovery. However, MSCs acquire genetic changes when cultivated in vitro that make them more susceptible to undergo neoplastic transformation. Therefore, genomic integrity of stem cells should be monitored carefully for the use in basic research and clinical trials, including karyotype analysis to confirm the absence of genetic instability. Here, we report a case of a male 67-year-old patient selected to join the study: "Autologous transplantation of mesenchymal cells for treatment of severe and refractory ischemic cardiomyopathy". He underwent nephrectomy for malignant tumor on the right kidney. Cytogenetic analysis on a bone marrow sample showed a normal karyotype: 46,XY[20]. However, the MSC at second passage showed a hyperdiploid clone, with clonal trisomies of chromosomes 4, 5, 10 and X. In order to investigate more, another sample from the same patient was used for a second cultivation and, at third passage, these cells showed a clonal translocation t(9;18)(p24;q11). The recurrent aberrations in MSC may indicate the beginning of a spontaneous transformation in culture, so, these cells were not used for cell therapy. Several analyses were performed at the Center for Cell Technology (152 samples), however this was the only case to show clonal cytogenetic abnormalities. Interestingly, two distinct clonal alterations were seen in two parallel cell cultivations from the same patient, suggesting a propensity for genetic instability. This highlights the need to evaluate these cells on a case-by-case basis, especially in patients with a history of cancer. Although there is controversy about the use of cells with cytogenetic abnormality for therapy, because their tumorigenic doubtful potential, we decided against the use of these cells for regenerative medicine. Here, we report a case of a male 67-year-old patient selected to join the study: "Autologous transplantation of mesenchymal cells for treatment of severe and refractory ischemic cardiomyopathy". He underwent nephrectomy for malignant tumor on the right kidney. Cytogenetic analysis on a bone marrow sample showed a normal karyotype: 46,XY[20]. However, the MSC at second passage showed a hyperdiploid clone, with clonal trisomies of chromosomes 4, 5, 10 and X. In order to investigate more, another sample from the same patient was used for a second cultivation and, at third passage, these cells showed a clonal translocation t(9;18)(p24;q11). The recurrent aberrations in MSC may indicate the beginning of a spontaneous transformation in culture, so, these cells were not used for cell therapy. Several analyses were performed at the Center for Cell Technology(152 samples), however this was the only case to show clonal cytogenetic abnormalities. Interestingly, two distinct clonal alterations were seen in two parallel cell cultivations from the same patient, suggesting a propensity for genetic instability. This highlights the need to evaluate these cells on a case-by-case basis, especially in patients with a history of cancer. Although there is controversy about the use of cells with cytogenetic abnormality for therapy, because their tumorigenic doubtful potential, we decided against the use of these cells forregenerative medicine.


Ushikulides A and B, immunosuppressants produced by a strain of Streptomyces sp.
Novel immunosuppressants, ushikulides A and B, were isolated from the culture broth of Streptomyces sp. IUK-102. Ushikulides A and B both have the same molecular formula, determined as C40H68O10. The structures of both compounds were elucidated to be novel 22-membered macrolides. Both compounds showed immunosuppressive activity for murine splenocyte proliferation in vitro.


Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery.
This paper explores the potential of polyethylene glycol enclatherated pectin-mucin (PEG-encl-PEC:MUC) submicron matrices (SMMs) as an intravaginal drug delivery system capable of delivering an anti-HIV-1 agent (zidovudine; AZT) over a prolonged duration. A three factor and three level (3(3)) Box-Behnken statistical design was employed to optimize the SMMs. Optimized PEG-encl-PEC:MUC SMMs prepared as a stable W/O emulsion (determined by the degree of reversible colloidal phenomena) were spherical with a mean particle size of 270.6 ± 5.533 nm and mean zeta potential of -34.4 ± 0.539 mV. The microencapsulation of AZT and the hydrogen bonding mediated shielding of AZT by SMMs was confirmed by Fourier Transform Infrared (FTIR) analysis. The thermochemical (differential scanning calorimetry and thermogravimetric analysis) data proposed that Ca(2+)-based macromolecular ionic crosslinking as well as the intermolecular interactions may be responsible for the thermal stability of the delivery system. The partially amorphous nature of drug-loaded SMMs, as confirmed by X-ray diffraction patterns, further strengthened the matricization of AZT into the pectin-mucin matrix. In vitro drug release studies from the SMMs showed approximately 91% zidovudine release in simulated vaginal fluid (SVF) and 94% in phosphate buffered saline (PBS) in 24h. The mean dissolution time (MDT) of zidovudine from the SMMs was 5.974 h. The attainment of required dimensional structure and drug release profiles from SMMs highlights the potential of their inclusion into a secondary carrier system for extended and controlled intravaginal stay.


Stable human T-lymphotropic virus type I carrier rates for 7 years among a teenaged blood donor cohort of 1986 in Kumamoto, Japan.
The human T-lymphotropic virus type I (HTLV-I) carrier rates for blood donors in Kumamoto, Kyushu, Japan for 8 years, 1986-1993, are currently available. The data show that 16-19-year-olds in 1986 and 20-29-year-olds in 1993 represent nearly the same cohort, because the median age in both groups is 24.5 years in 1993. Therefore, comparison of the HTLV-I positive rate for the two groups gives an estimate of the change in the rate over 7 years within the cohort. In males, 265 of 22,143 donors (1.20%) were seropositive for HTLV-I among 16-19-year-olds in 1986, and 214 were seropositive among 20,076 (1.07%) donors in 20-29-year-olds in 1993. In females, 203 were seropositive among 20,677 (0.98%) donors in 16-19-year-olds in 1986, and there 154 were seropositive among 18,660 (0.83%) donors in 20-29-year-olds in 1993. Thus, the seropositive rates declined in both sexes. However, the average annual rate of immigration to Kumamoto Prefecture was 2.37%. If seropositive rates for 20-29-year-olds in 1993 are adjusted for the dilution effect due to immigration (under the assumption that all immigrants were HTLV-I negative), the adjusted carrier rate for males is 1.26% and that for females is 0.98%. The adjusted carrier rates for both sexes are almost the same as those for 16-19-year-olds in 1986. This indicates that horizontal transmission was negligible for those in the cohort who were in their early reproductive period. Using all 8 year carrier rates for 16-19-year-olds and 20-29-year-olds, chronological changes of 20-29-year-olds, in the near future was estimated. The best goodness of fit model indicated that the HTLV-I carrier rate will decline exponentially, and that the rate will decrease by 50% approximately every 10 years for both sexes. It is probable that in recent years south-west Japan has lost the conditions that are favorable for HTLV-I endemicity and the virus will be virtually non-endemic within a few generations.


Activity of acyl-CoA: cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase in subfractions of hepatic microsomes enriched with cholesterol.
The influence of membrane cholesterol on the activities of acyl-CoA: cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase was examined in three microsomal subfractions (RNA-rich, RNA-poor, and smooth) that had been enriched with cholesterol by incubation with mixed lipoproteins from hypercholesterolemic rabbit serum. Acyl-CoA: cholesterol acyltransferase activity was significantly stimulated in the three subfractions, particularly in the RNA-rich microsomal component. 3-Hydroxy-3-methylglutaryl-CoA reductase, on the other hand, was suppressed (30%) in only one (RNA-poor) of the three microsomal subfractions, despite a 1.4-fold increase in the concentration of membrane cholesterol. An attempt was made to distinguish between an effect based exclusively on an increase in available cholesterol substrate and an activation of acyl-CoA: cholesterol acyltransferase in RNA-rich microsomes enriched with cholesterol. An experimental design was devised so that substrate cholesterol was provided in the form of heated smooth microsomes and acyl-CoA: cholesterol acyltransferase was provided as a separate preparation in the form of RNA-rich microsomes. Appropriate controls were carried out to test for transfer of cholesteryl ester between the two sets of particles. The results suggested that cholesterol enhanced acyl-CoA: cholesterol acyltransferase activity by serving both as a substrate and as a non-substrate modulator.


Evaluating the Threshold Score for Classification of Systemic Lupus Erythematosus Using the EULAR/ACR Criteria.
To evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE. We conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (-LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and -LRs < 0.1 provide evidence to rule in or rule out SLE. A total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a -LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; -LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the -LR (threshold score 10: -LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: -LR 0.05, 95% CI 0.04-0.06). The EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities.


CD36 in Alzheimer's Disease: An Overview of Molecular Mechanisms and Therapeutic Targeting.
CD36 is a membrane protein with wide distribution in the human body, is enriched in the monocyte-macrophage system and endothelial cells, and is involved in the cellular uptake of long chain fatty acids (LCFA) and oxidized low-density lipoproteins. It is also a scavenger receptor, binding hydrophobic amyloid fibrils found in the Alzheimer's disease (AD) brain. In neurobiology research, it has been mostly studied in relationship with chronic ischemia and stroke, but it was also related to amyloid clearance by microglial phagocytosis. In AD animal models, amyloid binding to CD36 has been consistently correlated with a pro-inflammatory response. Therapeutic approaches have two main focuses: CD36 blockade with monoclonal antibodies or small molecules, which is beneficial in terms of the inflammatory milieu, and upregulation of CD36 for increased amyloid clearance. The balance of the two approaches, centered on microglia, is poorly understood. Furthermore, CD36 evaluation in AD clinical studies is still at a very early stage and there is a gap in the knowledge regarding the impact of LCFA on AD progression and CD36 expression and genetic phenotype. This review summarizes the role played by CD36 in the pathogenic amyloid cascade and explore the translatability of preclinical data towards clinical research.


Discriminating aspects of global metabolism of neonatal cardiomyocytes from wild type and KO-CSRP3 rats using proton magnetic resonance spectroscopy of culture media samples.
Knockout of multifunction gene cysteine- and glycine-rich protein 3 (CSRP3) in cardiomyocytes (CMs) of mice leads to heart dilation, severely affecting its functions. In humans, CSRP3 mutations are associated with hypertrophic (HCM) and dilated cardiomyopathy (DCM). The absence of the CSRP3 expression produces unknown effects on in vitro neonatal CMs' metabolism. The metabolome changes in culture media conditioned by CSRP3 knockout (KO-CSRP3), and wild type (WT) neonatal cardiomyocytes were investigated under untreated or after metabolic challenging conditions produced by isoproterenol (ISO) stimulation, by in vitro high-resolution proton magnetic resonance spectroscopy (1H-MRS)-based metabolomics. Metabolic differences between neonatal KO-CSRP3 and WT rats' CMs were identified. After 72 h of culture, ISO administration was associated with increased CMs' energy requirements and increased levels of threonine, alanine, and 3-hydroxybutyrate in both neonatal KO-CSRP3 and WT CMs conditioned media. When compared with KO-CSRP3, culture media derived from WT cells presented higher lactate concentrations either under basal or ISO-stimulated conditions. The higher activity of ketogenic biochemical pathways met the elevated energy requirements of the contractile cells. Both cells are considered phenotypically indistinguishable in the neonatal period of animal lives, but the observed metabolic stress responses of KO-CSRP3 and WT CMs to ISO were different. KO-CSRP3 CMs produced less lactate than WT CMs in both basal and stimulated conditions. Mainly, ISO-stimulated conditions produced evidence for lactate overload within KO-CSRP3 CMs, while WT CMs succeeded to manage the metabolic stress. Thus, 1H-MRS-based metabolomics was suitable to identify early inefficient energetic metabolism in neonatal KO-CSRP3 CMs. These results may reflect an apparent lower lactate transport and consumption, in association with protein catabolism.


Evolutionary origins of genomic adaptations in an invasive copepod.
The ability of populations to expand their geographical ranges, whether as invaders, agricultural strains or climate migrants, is currently one of the most serious global problems. However, fundamental mechanisms remain poorly understood regarding factors that enable certain populations, such as biological invaders, to rapidly transition to novel habitats. According to one hypothesis, environmental fluctuations in the native range could promote successful invasions by imposing balancing selection on key traits and maintaining the genetic variation that enables rapid adaptation in novel habitats. Here we test the genomic predictions of this hypothesis by performing whole-genome sequencing of multiple independent invasive freshwater and native saline populations of the copepod Eurytemora affinis complex. We found that invasive populations have repeatedly responded to selection through the parallel use of the same single-nucleotide polymorphisms and genomic loci, to a much greater degree than expected. These same loci were enriched for signatures of long-term balancing selection in the native ranges, with 15-47% of loci exhibiting significant signatures of balancing selection. The strong association between parallel evolution in the invaded range and balancing selection in the native range supports the hypothesis that fluctuating habitats can promote invasive success and that balancing selection might serve as a widespread and important mechanism that enables rapid adaptation in nature.


Proteasomal degradation of WT proinsulin in pancreatic beta cells.
Preproinsulin entry into the endoplasmic reticulum yields proinsulin, and its subsequent delivery to the distal secretory pathway leads to processing, storage, and secretion of mature insulin. Multiple groups have reported that treatment of pancreatic beta cell lines, rodent pancreatic islets, or human islets with proteasome inhibitors leads to diminished proinsulin and insulin protein levels, diminished glucose-stimulated insulin secretion, and changes in beta-cell gene expression that ultimately lead to beta-cell death. However, these studies have mostly examined treatment times far beyond that needed to achieve acute proteasomal inhibition. Here, we report that although proteasomal inhibition immediately downregulates new proinsulin biosynthesis, it nevertheless acutely increases beta-cell proinsulin levels in pancreatic beta cell lines, rodent pancreatic islets, and human islets, indicating rescue of a pool of recently synthesized WT INS gene product that would otherwise be routed to proteasomal disposal. Our pharmacological evidence suggests that this disposal most likely reflects ongoing endoplasmic reticulum-associated protein degradation. However, we found that within 60 min after proteasomal inhibition, intracellular proinsulin levels begin to fall in conjunction with increased phosphorylation of eukaryotic initiation factor 2 alpha, which can be inhibited by blocking the general control nonderepressible 2 kinase. Together, these data demonstrate that a meaningful subfraction of newly synthesized INS gene product undergoes rapid proteasomal disposal. We propose that free amino acids derived from proteasomal proteolysis may potentially participate in suppressing general control nonderepressible 2 kinase activity to maintain ongoing proinsulin biosynthesis.


Cerebrospinal fluid B-cell activating factor levels as a novel biomarker in patients with neurosarcoidosis.
Neurosarcoidosis (NS) is a severe complication of sarcoidosis. Patients with NS often have poor outcomes. To improve both the quality of life and prognosis in patients with NS, accurate and reliable methods for early diagnosis and determining the efficacy of treatment are needed. This study aims to investigate B-cell-activating factor of the tumor necrosis factor family (BAFF) in cerebrospinal fluid (CSF) and elucidate the relationship between CSF BAFF levels and various parameters of NS. We studied 20 patients with NS and 14 control subjects. We measured CSF BAFF levels in all subjects and investigated the relationship with clinical findings, serum and CSF measures, and magnetic resonance imaging (MRI) findings. CSF BAFF levels were significantly increased in patients with NS compared with controls (median 0.089 vs 0.04 ng/mL, p = 0.0005). CSF BAFF values were correlated with CSF findings-cell count, protein, angiotensin-converting enzyme, lysozyme, soluble interleukin-2 receptor, and immunoglobulin G-but not with serum parameters. CSF BAFF levels were especially higher in patients with abnormal intraparenchymal lesions of the brain and abnormal spinal MRI findings. CSF BAFF levels decreased significantly after immunosuppressive therapy. CSF BAFF may aid the quantitative evaluation of NS and may serve as a biomarker for this disease.


Monoclonal antibody-induced inhibition of platelet function: effects on hemostasis and vascular graft thrombosis in baboons.
The usefulness of antiplatelet agents in vascular graft recipients remains controversial because of uncertainties regarding drug mechanisms of action and dose-duration effects. In our study, a well-characterized murine monoclonal antibody (LJ-CP8, 10 mg/kg) was infused into baboons to assess the hemostatic consequences and antithrombotic effectiveness of blocking the platelet glycoprotein IIb-IIIa receptor for fibrinogen and other adhesive glycoproteins. Five treated animals and six control animals were evaluated with serial measurements of platelet count, bleeding time, and platelet aggregation ex vivo (in response to adenosine diphosphate and collagen). Indium 111-labeled platelet deposition onto femoral vascular grafts (4 mm inner diameter Gore-Tex) implanted immediately after antibody infusion was measured by quantitative gamma camera imaging. Although the antibody did not alter circulating platelet counts, bleeding times were immediately prolonged to more than 30 minutes (vs. 4.8 +/- 0.4 minutes pretreatment) with only partial normalization by 48 hours (8.3 +/- 1.0 minutes, p less than 0.05). Platelet aggregation in response to both collagen and adenosine diphosphate was abolished immediately and remained impaired for 48 hours. Despite the profound inhibition of platelet function, graft platelet deposition was equivalent postoperatively in both the treated and untreated groups (p greater than 0.5), averaging approximately 5 x 10(9) platelets per graft. Graft-associated indium 111-labeled platelet activity increased over 48 hours and was not reduced by the antibody treatment (p greater than 0.5 at all times). All grafts were removed at 8 days; only one graft from a treated animal was found patent.(ABSTRACT TRUNCATED AT 250 WORDS)


KLF8 involves in TGF-beta-induced EMT and promotes invasion and migration in gastric cancer cells.
Krüppel-like factor 8 (KLF8), a downstream transcription factor of transforming growth factor-β1 (TGF-β1), has a role in tumorigenesis, tumor progress and epithelial-to-mesenchymal transition (EMT) induction. Recent studies mainly focused on its role in breast cancer and hepatocellular carcinoma; however, little is studied in gastric cancer. Here, we aim to explore whether KLF8 is involved in TGF-β1-induced EMT in gastric cancer cells. Western blot and real-time PCR assays were used to detect the expression of KLF8, E-cadherin and vimentin in gastric cancer cell line SGC7901 treated with or without TGF-β1. The lentivirus-mediated RNA interference technique was used to knock down the expression of KLF8 in gastric cancer cell line SGC7901. In vitro, the ability of cell migration and invasion were measured by transwell and wound healing assays; the cell motility was detected by high content screening assay. TGF-β1 could induce EMT via down-regulating E-cadherin and up-regulating vimentin expression in gastric cancer cells. Further study found that TGF-β1 could induce KLF8 expression at the protein and mRNA levels in gastric cancer cells (P < 0.05). Western blot and real-time PCR assays found that small interference RNA (siRNA)-mediated KLF8 silence blocked TGF-β1-induced EMT-like transformation and subsequently reversed the loss of E-cadherin and gain of vimentin. In vitro, inhibition of KLF8 decreased TGF-β1-prompted cell migration, invasion and motility. KLF8, a transcription factor, is involved in TGF-β1-induced EMT in gastric cancer cells and may be a novel therapeutic target for the treatment of gastric cancer.


Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long-acting release in healthy volunteers: a single-center Phase I study.
This study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PKs) of different doses of a long-acting release (LAR) formulation of pasireotide in healthy subjects. Single-center, open-label, randomized Phase I study. Twelve healthy male subjects received a single s.c. dose of pasireotide 300 μg followed by a washout period of 7 days (or at least 5 days), before receiving an i.m. injection of pasireotide -LAR 40 mg (n=5) or 60 mg (n=7). Assessments included adverse events (AEs), PKs, and glucose, insulin, glucagon, and HbA1c levels. Pasireotide LAR showed an extended-release profile over 1 month with two concentration peaks observed 1 and around 20 days after injection. The area under curve exposure of pasireotide LAR was dose proportional when the dose levels were compared, and the bioavailability of the LAR relative to the s.c. formulation was complete. Administration of pasireotide LAR resulted in an increase in fasting and postprandial glucose levels; however, an attenuation of the hyperglycemic effect was observed after 15 days. The most frequently reported AEs were mild-to-moderate diarrhea, abdominal pain, and flatulence. Only gastrointestinal AEs and injection site reactions were suspected to be drug related. Pasireotide LAR was generally well tolerated with mostly mild AEs at doses up to 60 mg and showed a dose-proportional, extended-release profile in healthy subjects. Based on the favorable results of this study, further clinical development of pasireotide LAR is under way, which will give insight into the PKs, efficacy, and safety of pasireotide LAR in patient populations.


[Treatment follow-up of transsexual patients. A catamnestic study].
In a retrospective study, 33 transsexual patients, 22 male-to-female transsexual (MF-TS), and 11 female-to-male transsexuals (FM-TS), were interviewed 53-121 months after their first referral to the psychiatric department of a university hospital. Social integration proved to be satisfactory and relatively stable. Twenty-five patients had gone through surgical sex reassignment, while 29 were currently undergoing hormonal treatment. Regarding the course of treatment, the FM-TS were a more homogeneous group than the MF-TS group. Overall, physical and psychosocial well-being was satisfactory. Psychometric measures yielded remarkably normal values, with some pathological findings regarding personality traits. In the majority of patients, self- and observer-rating appraisals of gender-specific physical appearance were equally positive. The results suggest a three-step procedure for the treatment of transsexual patients, as is practiced in other centers within German speaking continental Europe.


Is contralateral carotid artery occlusion a risk factor for carotid endarterectomy?
Occlusion of the contralateral internal carotid artery (ICA) is considered to have a significant impact on the outcome of carotid endarterectomy (CEA). The purpose of this study was to review one center's experience concerning CEA opposite an occluded ICA, to see whether results differed from those obtained in patients with patent contralateral ICA in terms of relevant neurologic complication rate (RNCR, fatal + disabling stroke), stroke-free rate, and survival rate. From January 1997 to December 2002, 1,381 patients underwent a total of 1,445 CEAs at the Department of Vascular Surgery of Padua University. Patients were divided into two groups: group A included 144 patients with occlusion of the contralateral ICA and group B consisted of 1,237 patients with a patent contralateral ICA. There was no postoperative mortality in patients of group A, while in group B, two patients died as a result of myocardial infarction and cardiac failure and one died as a direct result of perioperative stroke. Postoperative disabling strokes occurred in one (0.7%) patient in group A and 10 (0.8%) patients in group B (p > 0.5). At 72 months, there were no statistical differences between the two groups in terms of RNCR, stroke-free rate, and late death. Our results show that contralateral carotid occlusion does not reduce the safety of CEA. The efficacy in terms of RNCR, stroke-free rate, and late survival is no different in patients with contralateral carotid occlusion.


Targeting health visitor care: lessons from Starting Well.
UK child health promotion guidelines expect health visitors to assess family needs before new babies are aged 4 months and offer targeted care on that basis thereafter. Data from an intensive family support programme were used to assess how accurately family needs can be predicted at this stage. A population based cohort of 1202 families with new babies receiving an intensive health visiting programme. Analysis of routinely recorded data. Starting Well project, Glasgow, UK. Health visitor rating of family needs. Families receiving high visiting rates or referred to social work services. Of 302 families rated high need, only 143 (47%) were identified by age 4 months. Visiting rates in the first year for those initially rated high need were nearly double those for the remainder, but around two thirds of those with high contact rates/referred to social work were not initially rated high need. Six family characteristics (no income, baby born preterm, multiple pregnancy, South Asian, prior social work/criminal justice involvement, either parent in care as a child) were identified as the commonest/strongest predictors of contact rates; 1003 (83%) families had one such characteristics and/or lived in a highly deprived area, including 228 (93%) of those with high contact rates and 157 (96%) of those referred to social work. Most families at risk will not be identified on an individual basis in the early weeks. Most families in deprived areas need continued input if the most vulnerable families are to be reliably identified.


Responses of bacterial and archaeal communities to nitrate stimulation after oil pollution in mangrove sediment revealed by Illumina sequencing.
This study aimed to investigate microbial responses to nitrate stimulation in oiled mangrove mesocosm. Both supplementary oil and nitrate changed the water and sediment chemical properties contributing to the shift of microbial communities. Denitrifying genes nirS and nirK were increased several times by the interaction of oil spiking and nitrate addition. Bacterial chao1 was reduced by oil spiking and further by nitrate stimulation, whereas archaeal chao1 was only inhibited by oil pollution on early time. Sampling depth explained most of variation and significantly impacted bacterial and archaeal communities, while oil pollution only significantly impacted bacterial communities (p<0.05). Despite explaining less variation, nitrate addition coupled with oil spiking enhanced the growth of hydrocarbon degraders in mangrove. The findings demonstrate the impacts of environmental factors and their interactions in shaping microbial communities during nitrate stimulation. Our study suggests introducing genera Desulfotignum and Marinobacter into oiled mangrove for bioaugmentation.


Association between religious practice and risk of depression in older people in the subacute setting.
To identify the association between religious practice and risk of depression in older people admitted to a subacute hospital. A cross-sectional survey was conducted with 100 patients aged ≥65 years with Mini-Mental State Examination (MMSE) scores ≥24 consecutively admitted to a subacute hospital. Religious practice was measured using the Duke University Religion Index and risk of depression using the 15-item Geriatric Depression Scale (GDS). Geriatric Depression Scale was significantly correlated with intrinsic religiosity (r = -0.21, P = 0.04) and cognition (r = -0.22, P = 0.03). This cross-sectional study of older people in a subacute setting found depression scores were negatively and independently associated with both intrinsic religiosity and cognition. In conjunction with cognitive assessment, health professionals working with older people may consider taking a spiritual history as part of holistic care.


Z-335, a new thromboxane A(2) receptor antagonist, prevents arterial thrombosis induced by ferric chloride in rats.
We examined the antithrombotic effect of Z-335 ((+/-)-sodium [2-(4-chlorophenylsulfonylaminomethyl)indan-5-yl]acetate monohydrate), an orally active thromboxane A(2) receptor (TP-receptor) antagonist that ameliorates experimental gangrene, using a rat arterial thrombosis model. The thrombi were induced by topical application of 50% ferric chloride solution to the rats abdominal artery. Z-335 (0.3-3 mg/kg, p.o.) inhibited thrombus formation in a dose-dependent manner. The antithrombotic effect of Z-335 (1 and 3 mg/kg, p.o.) was almost equivalent with that of cilostazol (100 mg/kg, p.o.), a selective phosphodiesterase type III inhibitor. The effect of Z-335 (3 mg/kg, p.o.), but not cilostazol, persisted for 16 h. Z-335, but not cilostazol, inhibited platelet aggregation induced by U-46619 (a TP-receptor agonist, 9, 11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha)) for 16 h in rat whole blood. Histopathological examination also revealed that Z-335 prevented ferric chloride-induced thrombus formation. These results suggest that Z-335 may prevent ferric chloride-induced arterial thrombosis through its antiplatelet action by blocking TP-receptor activation.


Characteristics and formation of typical winter haze in Handan, one of the most polluted cities in China.
Handan, a city within the North China Plain (NCP) region, is a typical city influenced by regional particulate matter (PM) pollution. One-year hourly semi-continuous observation was carried out in 2015 in Handan with the aim of identifying the chemical composition and variations in PM2.5. Moreover, the concentration of aerosol precursors, meteorological factors, and secondary transformations are considered. The results demonstrate that the annual average PM2.5 concentration in Handan is 122.35μgm-3, approximately 3.5 times higher than the Chinese National Ambient Air Quality Standard (NAAQS) (35μgm-3), and only 12days were below the guideline. As expected, PM concentrations are highest in winter, especially in December. In addition, we measure the concentrations of five species commonly found in PM, nitrate, sulfate, ammonium, inorganic carbon, and organic carbon. Of these, nitrate and sulfate account for the largest proportion of PM2.5; during periods when the PM2.5 concentration was below 400μgm-3, nitrate dominates, while above this concentration, sulfate dominate. This is likely related to the nitrogen and sulfur oxidation ratios, which are in turn, especially the sulfur oxidation ratio, driven by high relative humidity (>60%). In addition, haze events are driven by other meteorological conditions, wind speed and direction, where low wind speeds from the south and southwest enable pollutant accumulation, which are infrequently interspersed with brief periods with high wind speeds that promote pollutant dispersal. Even though Handan is among the ten most polluted cities in China with regard to air pollution, few studies beyond model simulations have analyzed air pollutant concentrations in this city. Therefore, this study makes a significant contribution to understanding air pollution in Handan, which can further be used to improve our understanding of regional pollution in the highly populated North China Plain. These results have implications for the creation of policies and legislation, as well as other pollution control measures.


[Laryngeal cancer at the "Arnau de Vilanova" Hospital in Lleida].
Cancer of the larynx in the province of Lérida and its west border affects men (52:1). The majority are engaged in rural activities, ranging in age between 50-70 years. Supraglottic site showed predominance. At first examination in 73 per cent of the cases no palpable cervical nodes could be detected. Almost all the cases belong to the epidermoid carcinoma type (98 per cent).


Expression of the Polycomb-Group protein BMI1 and correlation with p16 in astrocytomas an immunohistochemical study on 80 cases.
A number of studies on the putative relation between Polycomb-Group (PcG) proteins overexpression and carcinogenesis have been published recently. BMI1, the prototype PcG gene, is critically involved in cell cycle control and differentiation, and despite the regulatory role demonstrated in central nervous system (CNS) development, its implication in brain tumorigenesis is scarcely known. Moreover, to the best of our knowledge, large studies on human brain tumors tissue are lacking. To gain a new insight, we tested 80 primary brain astrocytomas for BMI1 expression using immunohistochemistry and established a correlation with the expression of p16, a negatively regulated target of BMI1 function. Fifty-four cases (72.5%) were BMI1 + /p16-, and 22 cases (27.5%) were BMI1 + /p16+. Slight non-significant differences were noted in the expression profile between grades II, III, and IV astrocytomas. However, when the 22 BMI1 + /p16+ tumors were examined cytologically, a substantial proportion contained a significant gemistocytic component, which is thought to be an adverse prognostic factor or to display a high degree of anaplasia, suggesting a common molecular mechanism of BMI1/p16 pathway disruption, which may have prognostic implications.


High-Intensity Physical Activity with High Serum Vitamin D Levels is Associated with a Low Prevalence of Osteopenia and Osteoporosis: A Population-Based Study.
We found that combination of high-intensity PA and high 25(OH)D levels was associated with low prevalence of osteoporosis/osteopenia. In addition, the prevalence of osteoporosis was lower in the low PA with high 25(OH)D levels than in the moderate or high PA with low 25(OH)D levels. The aim of this study was to explore the association of physical activity (PA) and serum 25-hydroxyvitamin D (25[OH]D) levels with osteopenia/osteoporosis. The Korean National Health and Nutrition Examination Survey data from 2008 to 2011 were used in this study. Data from 6868 individuals were selected. Each individual's level of PA was classified as 'low', 'moderate', or 'high'. Serum 25(OH)D levels were classified as 'low' or 'high'. Accordingly, the combined PA and 25(OH)D groups were divided into 6 groups. Bone mineral density (BMD) was classified as 'normal (T score ≥ - 1.0)', 'osteopenia (- 2.5 < T score < - 1.0)' or 'osteoporosis (T score ≤ - 2.5)'. Crude and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated using multinomial logistic regression models. The AORs (95% CIs) for osteopenia were 0.64 (0.50-0.83) in the high PA with high 25(OH)D group and 0.69 (0.53-0.88) in the moderate PA with high 25(OH)D group. The AORs (95% CIs) for osteoporosis were increased in the groups in ascending order as follows: high PA with high 25(OH)D (0.40 [0.28-0.57]) < moderate PA with high 25(OH)D (0.47 [0.33-0.66]) < low PA with high 25(OH)D (0.59 [0.42-0.83]) < high PA with low 25(OH)D (0.70 [0.49-1.00]) < moderate PA with low 25(OH)D (0.76 [0.53-1.07]) < low PA with low 25(OH)D. This result was consistent in males but not evident in females. We suggest that the combination of high-intensity PA and high 25(OH)D levels is positively associated with high BMD.


Treatment of large impacted proximal ureteral stones: randomized comparison of minimally invasive percutaneous antegrade ureterolithotripsy versus retrograde ureterolithotripsy.
To provide appropriate evidence for treatment planning of patients with an impacted proximal ureteral stones ≥1.5 cm in size, by analyzing the therapeutic outcomes for those undergoing minimally invasive percutaneous antegrade ureterolithotripsy and retrograde ureterolithotripsy. From September 2010 to November 2011, eligible patients with impacted proximal ureteral stones ≥1.5 cm in size referred to our institute were considered for this study. The closed envelope method was used to randomize the enrolled patients to mini-PCNL (30) or retrograde ureterolithotripsy (29). The efficiency quotient (EQ) was calculated to specifically address the efficiency for both the techniques. All preoperative and postoperative data for both groups were recorded. The initial stone-free rate was 93.3% in the mini-PCNL group and 41.4% in the URSL group (p < 0.001). However, the overall stone-free rate at the 1-month follow-up visit after initial treatment was 100% in the mini-PCNL group and 89.7% in the URSL group (p = 0.07). The EQs for the mini-PCNL and URSL groups were 0.83 and 0.50, respectively. Our study shows that mini-PCNL removal of large impacted proximal ureteral calculi can achieve higher stone-free rates and safe.


Total synthesis of 6'-hydroxyjusticidin A.
The first total synthesis of 6'-hydroxyjusticidin A, isolated from Justicia procumbens L. with good inhibitory activity against cancer cells, has been accomplished. The structure was confirmed by ¹H NMR, ¹³C NMR, and HR-ESI-MS. The key steps involved a Diels-Alder cycloaddition reaction and a reduction in NaBH₄.


[Early onset of anti- erythropoietin antibody-mediated pure red cell aplasia after commencement of subcutaneous administration of epoetin-β].
We report a 73-year-old Japanese man with early onset pure red cell aplasia (PRCA) caused by subcutaneous administration of recombinant epoetin-β. Two months after the start of epoetin therapy, he developed PRCA. Anti-erythropoietin (EPO) antibody, detected in the patient's serum by enzyme immunoassay and radioimmunoprecipitation method, inhibited EPO-dependent growth of AS-E2 cells in vitro. Treatment with prednisone (1 mg/kg) significantly reduced antibody levels 3 months later. It is important to have an awareness of antibody-mediated PRCA. Our case shows that subcutaneous epoetin administration produces this complication in the early period of therapy.


Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: a 21-year longitudinal study.
The prognostic value of common and frequently associated diabetic microvascular complications (MVC), namely chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN), peripheral neuropathy (DPN), and retinopathy (DR), is well established. However, the impact of their different combinations on long-term mortality has not been adequately assessed. We retrospectively analyzed 21-year longitudinal data from 303 patients with long-standing type 1 (T1D) or type 2 diabetes (T2D), who were thoroughly characterized at baseline for the presence of MVC using 99mTc-DTPA dynamic renal scintigraphy, overnight urine collection, cardiovascular autonomic tests, monofilament testing, and dilated fundus oculi examination. After a 5,244 person-years follow-up, a total of 133 (43.9%) deaths occurred. The presence of CKD and CAN, regardless of other MVC, increased the adjusted all-cause mortality risk by 117% (HR 2.17 [1.45-3.26]) and 54% (HR 1.54 [1.01-2.36]), respectively. Concomitant CKD&CAN at baseline were associated with the highest mortality risk (HR 5.08 [2.52-10.26]), followed by CKD&DR (HR 2.95 [1.63-5.32]), and CAN&DR (HR 2.07 [1.11-3.85]). Compared with patients free from MVC, the mortality risk was only numerically higher in those with any isolated MVC (HR 1.52 [0.87-2.67]), while increased by 203% (HR 3.03 [1.62-5.68]) and 692% (HR 7.92 [2.93-21.37]) in patients with two and three concomitant MVC, respectively. Our study demonstrates the long-term, synergistic, negative effects of single and concomitant diabetic MVC on all-cause mortality, which should encourage comprehensive screenings for MCV in both T1D and T2D to improve risk stratification and treatment.


Extraction and analysis of fungal spore biomarkers in atmospheric bioaerosol by HPLC-MS-MS and GC-MS.
Airborne microorganisms, as bacteria and fungi, are ubiquitous components of the atmospheric aerosol particles. In this paper, we report a method for the simultaneous extraction, purification, separation, identification and quantification of ergosterol, mannitol and arabitol as biomarkers of fungal spores in bioaerosol particles. After sampling by a low volume sampler, filters were spiked with mannitol-(13)C and dehydrocholesterol as internal standards. Samples were then extracted by accelerated solvent extraction using pure ethanol. The extract was then passed through an amino cartridge and divided in two parts: the apolar fraction, released from the cartridge, was subjected to liquid liquid extraction (by n-hexane), while polar compounds, retained by the cartridge, were eluted by a mixture of methanol-water. The two fractions were joined and analyzed by HPLC equipped with two different columns in series, and coupled to a triple-quadrupole mass spectrometer with Atmospheric Pressure Chemical Ionization source. In addition, the same fractions were analyzed, after derivatization, by GC-MS. The results obtained by the two techniques were finally compared, showing good agreement between them. Last, the contents of the three biomarkers have been estimated in three atmospheric samples collected in a suburban/rural site and, using literature conversion factors, correlated to fungal biomass.


Pure versus guided mirror exposure to reduce body dissatisfaction: a preliminary study with university women.
While effectiveness of mirror exposure to reduce body dissatisfaction has been demonstrated, the exposure was almost always combined with other interventions. The aim of the study was to evaluate the effectiveness of a pure mirror exposure intervention compared with a guided mirror exposure (participants are guided to describe their body shape in a non-evaluative manner) and an imagery exposure intervention (participants are guided to describe their body through mental representation). Thirty-one women with high body dissatisfaction received five sessions of treatment under one of the three conditions. All interventions reduced body dissatisfaction, but only the mirror exposures successfully reduced the frequency of negative thoughts and feelings of ugliness. Pure mirror exposure was more effective than guided exposure for reducing body discomfort within and between sessions. Pure mirror exposure, based on the traditional extinction paradigm, led to strong emotional activation followed by a fast decrease in emotional reactivity.


Improving reverse osmosis concentrate treatment and nutrients conversion to Chlorella vulgaris bioenergy assisted with granular activated carbon.
Landfill leachate (LL), especially the reverse osmosis concentrate (ROC), is a societal burden due to high toxicity but may have intrinsic values attributing to copious nutrients and organics. ROC bioremediation by microalgae has attracted much attentions benefiting from its extra advantage of bioenergy production. However, efficient microalgae cultivation with ROC is still a challenging task attributing to notorious ROC characteristics, like high chromaticity and toxicity. To alleviate these negative influences, a technique integrating granular activated carbon (GAC) pretreatment and microalgae bioremediation was proposed, with which nitrogen and phosphorus removal efficiencies achieved 100% along with an optimized microalgal biomass concentration of 1.44 g/L and lipid yield of 482.4 mg/L. Furthermore, a total volumetric energy yield of 33.6 kJ/L was acquired, which was conducive to realize energy valorization. The visualization evidence of three-dimensional fluorescence spectroscopy revealed chromaticity degradation mechanism of ROC as humic acids reduction and transfer to family of soluble microbial by-products. Meanwhile, contributions of GAC adsorption and microalgae assimilation on nutrients removal were analyzed. Together, this work provides a promising method and valuable information for ROC bioremediation with microalgae.


Multiple effects of interferon on myogenesis in chicken myoblast cultures.
Effects of chicken interferon on the differentiation of chicken skeletal muscle in vitro were examined. Continuous treatment of chicken myoblast culture with 200 IU/ml of interferon (10 IU/mg protein) resulted in significant inhibition of cell fusion and subsequent myotube formation. However, treatment of myoblast culture with 2 to 200 IU/ml of interferon increased activities of creatine kinase and myokinase in 4- or 6-day cultured muscle cells in a dose-dependent fashion. The effect of interferon on myokinase was less than on creatine kinase. Three-fold increase in creatine kinase activity induced by interferon was not accompanied by the accelerated transition of creatine kinase isozyme from BB- to MM-type. On the other hand, accumulation of acetylcholinesterase in interferon-treated cells at day 6 was suppressed to nearly half the level of control cells. Rates of actin and myosin synthesis in 4-day cultures estimated by pulse-labelling with [35S]methionine were also suppressed to 85% of control cultures. However, a proportion of 35S-labelled actin and myosin in labelled proteins associated with glycerinated cells was not changed by interferon treatment. These results indicate that partially purified interferon has multiple effects on the process of the myogenic differentiation of chicken myoblast in vitro.


Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver.
We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver. Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well-differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non-neoplastic biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas. The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.


The role of Candida infections as an adverse effect upon head and neck cancer patients undergoing therapeutic radiation and the effect of antimycotic treatment.
Oral, pharyngeal and esophageal infections caused by Candida species occur very frequently when it comes to radiation therapy for head and neck cancer. In clinical terms oral candidosis is most often characterized by pseudomembranes or erythema. The erythematous form of oral candidosis has in particular to be distinguished from radiation mucositis. Candidosis of the oral and gastrointestinal tract often causes interruption of therapeutic radiation. Ketoconazole treatment is able to reduce the period of time during which the patient cannot be treated by radiation. Oral ketoconazole given at a daily dose of 200 mg is moreover superior to topical nystatin. To date, however, it is not yet clear if patients who have head and neck cancer in whom radiation therapy has to be started would profit from the prophylactic application of ketoconazole from start on.


Safe landing for global polio eradication: a perspective.
After over two decades of immense efforts, the global polio eradication initiative may be approaching its final phase. With leadership from WHO, great efforts of national programs and support from its collaborators, combined with the recent use of mono and bivalent oral polio vaccines, success may be at hand. For a "safe landing" of this global program, it is important once more to recall the key role of routine vaccination as the foundation on which mass vaccination campaigns can be successful. Continued effective routine vaccination programs are essential to reduce the ill effects of high population density in formerly endemic countries. Considering the large number of subclinical poliovirus infections, failing to reduce the number of unvaccinated persons per km(2) could severely impact the final stage of eradication. Here the authors, from their personal perspectives, discuss how the current program will be viewed from 2012 onwards. The authors will highlight the epidemiological importance of circulating vaccine-derived poliovirus, the problem of biosecurity as well as the use of inactivated polio vaccine and how each of these may affect the post eradication era and how research into each of these must continue to ensure success.


Lactobacillus acidophilus strain L-92 induces apoptosis of antigen-stimulated T cells by modulating dendritic cell function.
Beneficial effects of lactobacilli have been reported for patients with allergic diseases and intestinal disorders such as inflammatory bowel disease. However, it is not fully understood how such bacteria influence the immunologic response. For this purpose, we investigated the effect of Lactobacillus acidophilus strain L-92 (L-92) on antigen-stimulated T cell responses in vitro and in vivo. In vitro, L-92 decreased the proliferation of CD4(+) T cells stimulated with antigen, and also induced apoptosis of antigen-stimulated T cells. On the other hand, interferon (IFN)-gamma secretion from naïve T cells was increased while interleukin (IL)-4 secretion was decreased by L-92. Co-culture with L-92 induced apoptosis of differentiated Th1 and Th2 cells. The degree of apoptosis induction was higher in Th2 cells. Moreover, L-92 up-regulated the expression of B7-H1 and down-regulated that of B7-H2 on dendritic cells (DCs), and DCs exposed to L-92 also induced apoptosis of antigen-stimulated T cells. Finally, orally administered L-92 induced apoptosis of OVA-specific TCR Tg T cells. These results indicate that L-92 attenuates the CD4(+) T cell response by inducing DC-mediated apoptosis and that it might exert beneficial effects in patients with diseases resulting from a hyper-response of CD4(+) T cells.


Effectiveness of normal saline solution, dextran 40 or dextran 75, and aprotinin (Trasylol) on renal blood flow preservation during acute canine pancreatitis.
A decrease in renal blood flow is believed to be important in the genesis of the acute renal failure of acute pancreatitis. In some instances, this decrease is undoubtedly due to hypovolemia, whereas in other instances, a circulating vasotoxic agent, possibly trypsin, has been incriminated. Using a canine model of pancreatitis induced by retrograde injection of bile along the pancreatic duct, the effects on renal blood flow of correcting the hypovolemia or administering aprotinin (a trypsin inhibitor) were studied using externally applied flow probes. Correcting the hypovolemia with N saline solution had no effect; the renal blood flow continued to decrease (p less than 0.05). When dextran 40 or dextran 75 was employed, the decrease in renal blood flow was prevented. After the administration of aprotinin, the renal blood flow actually increased (p less than 0.025) compared with preadministration values. It appears that aprotinin may have played a role in preventing this serious complication of pancreatitis.


Age-related changes in enzyme activities, protein content and lipid composition of rat kidney brush-border membrane.
Age-related changes in enzyme activities, protein electrophoretic patterns and lipid composition of kidney-brush-border membranes were studied in 10-20- and 30-month-old male and female Wistar rats. Polyacrylamide gel electrophoresis of membrane proteins revealed very little changes with increasing age, whether males or females were considered. The Km of three hydrolases - maltase, L-aminopeptidase and alkaline phosphatase - were not affected by age while the Vmax of maltase and alkaline phosphatase, but not of L-aminopeptidase, decreased from 10 to 30 months. The phospholipid to protein ratio which remained constant between 10 and 20 months, rose in both sexes from 20 to 30 months. In males, the cholesterol content of the membrane increased faster than that of phospholipid and the cholesterol over phospholipid ratio was then greater at 30 months than at 10 months, while in females this ratio remained unchanged in the course of aging. The fatty acid composition of the brush-border remained more or less constant with age in female rat whereas in the male, a 10% decrease in the proportion of arachidonic acid from 10 to 30 months was responsible for a lower unsaturation index.


Smart waterborne composite coating with passive/active protective performances using nanocontainers based on metal organic frameworks derived layered double hydroxides.
Functional surfaces and coatings with excellent anticorrosion performances are of great significance for numerous engineering applications. However, developing waterborne coatings with long-term anticorrosion properties remains challenging. In this study, we developed a multifunctional nanocontainer for a waterborne coating matrix, using zeolitic imidazolate framework (ZIF)-derived layered double hydroxides (LDHs) as the gatekeepers for benzotriazole (BTA)-encapsulated mesoporous silica nanoparticles (MSNs-BTA). The LDHs outer layer and the ZIF intermediate layer endowed the MSNs-BTA@ZIF-LDHs nanocontainer with excellent compatibility, dispersion, and pH-responsive controllable release properties in the waterborne coating matrix. The waterborne epoxy composite coatings showed excellent passive and active anticorrosion performances, well-characterized by electrochemical impedance spectroscopy (EIS), permeation experiments, neutral salt spray (NSS) tests, and the scanning vibrating electrode technique (SVET). This excellent corrosion protection performance can be attributed to two factors: before corrosion, the MSNs-BTA@ZIF-LDHs served as passive nanofillers against corrosive media, significantly improving the barrier properties of the composite coatings; after the occurrence of corrosion, the MSNs-BTA@ZIF-LDHs acted as pH-responsive nanocontainers and released pre-loaded BTA corrosion inhibitors, preventing further damage to the exposed metal substrate. This study provides new insights into the development of multifunctional anticorrosion surfaces and coatings for various engineering applications.


Rapid nerve recovery following decompression--a case of post-traumatic axonamonosis.
We report a humeral fracture associated with complete radial nerve palsy, where immediate nerve recovery followed decompression. This uncommon type of nerve lesion is referred to as axonamonosis and is not included in the traditional Seddon nerve injury classification.