Functional characterization of Clonorchis sinensis sodium-bile acid co-transporter (CsSBAT) as a steroid sulfate transporter.
Clonorchis sinensis (Cs) is a common trematode in Asian countries. Infection by Cs can result in many clinical symptoms. Here, a cDNA encoding a Cs apical sodium-dependent bile acid transporter (CsSBAT) was isolated from a Cs cDNA library, and functional characterization was performed using Xenopus laevis oocyte expression system. When expressed in Xenopus laevis oocytes, CsSBAT mediated the transport of radiolabeled estrone sulfate and dehydroepiandrosterone sulfate. No trans-uptake of carnitine, estradiol 17 β-D glucuronide, prostaglandin E2, p-aminohippuric acid, α-ketoglutaric acid, and tetraethylammonium was observed. CsSBAT-mediated estrone sulfate uptake was in a time- and sodium-dependent manner. CsSBAT showed no exchange properties in efflux experiments. Concentration-dependent results showed saturable kinetics consistent with the Michaelis-Menten equation. Nonlinear regression analyses yielded a Km value of 0.3 ± 0.04 μM for [3H]estrone sulfate. CsSBAT-mediated estrone sulfate uptake was strongly inhibited by sulfate conjugates but not glucuronide conjugates. These findings contribute to our understanding of CsSBAT transport properties and the cascade of estrogen metabolite movement in Cs.


[Sepsis: from systemic inflammatory response syndrome to organ dysfunction].
Based on their extensive experience and literature data, the author outlines difficulties in the morphological diagnosis of sepsis, by taking into account the current clinical classification. Occurring not only in sepsis and lacking clear morphological criteria, a systemic inflammatory response and organ dysfunction cannot be absolute signs of sepsis diagnosis. The author gives the morphological characteristics of the systemic inflammatory response, septic shock, and organ dysfunction.


Effects of high hydrostatic pressure on Campylobacter jejuni in poultry meat.
Campylobacter jejuni inactivation by high pressure processing (HPP) in poultry meat (chicken breast) was investigated. The pressure was created by high hydrostatic pressure piston-cylinder food processor. Contaminated with C. jejuni (108 CFU g-1) samples of ground poultry meat were hermetically sealed in a polyamide-polyethylene bags and exposed to HPP for 9 different combinations of pressure (200 MPa, 300 MPa and 400 MPa) and time (5 min, 10 min and 15 min). Quantitative bacteriological analysis was carried out in order to determine the number of surviving C. jejuni cells. The obtained results showed that C. jejuni is relatively sensitive to high pressure treatment as compared to other food-borne pathogens. The loss of C. jejuni viability increased in a dose- and time-dependent manner. On the basis of the results, D-values were calculated. For reduction C. jejuni in poultry meat by 6 log units (6D-values), considered as sufficient for consumer protection, the application of 300 MPa for 8.73 min, or 400 MPa for 4.37 min is needed. The linear regression equations, which has been calculated on the basis of this study, allows to determine the degree of C. jejuni reduction in poultry meat for any selected duration of pressurization in a given pressure range.


Cardiovascular risk factors in hypertensive patients born in Northern Africa and living in France.
Northern Africans constitute one of the largest immigrant groups in France; however, limited data are available on their cardiovascular risk factors. We carried out a retrospective cross-sectional study in a French hypertension unit, comparing 719 patients born in Northern Africa to 3558 controls born in Europe, individually matched for age and sex. Using a Bonferroni adjusted alpha-level=0.001, we found no significant difference between the groups for blood pressure levels, anti-hypertensive treatment, prevalence of target organ damage or the proportion of patients with secondary hypertension. However, patients of both sexes born in Northern Africa were less likely to take regular physical exercise than their controls. In addition, women born in Northern Africa were less often current or former smokers than their European counterparts (19.9% vs 30.5%, p < 0.001), but had a higher body mass index (28.5 vs 26.8 kg/m(2), p < 0.001) and a higher prevalence of diabetes (19.1% vs 8.9%, p < 0.001 after adjusting for BMI). These results suggest that targeted lifestyle interventions, including regular physical exercise, could be proposed to prevent weight gain and decrease the incidence of diabetes in hypertensive women born in Northern Africa and living in western countries.


Short-Term Therapeutic Adherence of Hospitalized Older Patients with Oropharyngeal Dysphagia after an Education Intervention: Analysis of Compliance Rates, Risk Factors and Associated Complications.
Oropharyngeal dysphagia (OD) is associated with adverse outcomes that require a multidisciplinary approach with different strategies. Our aim was to assess the adherence of older patients to dysphagia management recommendations during hospitalization, after a specific nurse guided dysphagia education intervention and to identify short term complications of OD and their relationship with short-term adherence. We carried out a prospective observational study in an acute and an orthogeriatric unit of a university hospital over ten months with a one-month follow-up. Four hundred and forty-seven patients (mean age 92 years, 70.7% women) were diagnosed with dysphagia using Volume-Viscosity Swallow Test (V-VST). Compensatory measures and individualized recommendations were explained in detail by trained nurse. Therapeutic adherence was directly observed during hospital admission, after an education intervention, and self-reported after one-month. We also recorded the following reported complications at one month, including respiratory infection, use of antibiotics, weight loss, transfers to the emergency department, or hospitalization). Postural measures and liquid volume were advised to all patients, followed by modified texture food (95.5%), fluid thickeners (32.7%), and delivery method (12.5%). The in-hospital compliance rate with all recommendations was 37.1% and one-month after hospital discharge was 76.4%. Both compliance rates were interrelated and were lower in patients with dementia, malnutrition, and safety signs. Higher compliance rates were observed for sitting feeding and food texture, and an increase in adherence after discharge in the liquid volume and use of thickeners. Multivariate logistic regression analysis showed that adherence to recommendations during the month after discharge was associated with lower short-term mortality and complications (i.e., respiratory infection, use of antibiotics, weight loss, transfers to the emergency department, or hospitalization). One-third of our participants followed recommendations during hospitalization and three-quarters one month after admission, with higher compliance for posture and food texture. Compliance should be routinely assessed and fostered in older patients with dysphagia.


Leukotriene B4 production in human atherosclerotic plaques.
We evaluated the hypothesis that leukotriene (LT) B4, a potent chemotactic and endothelium-permeabilizing autacoid, may be a factor in the progression of the atherosclerotic lesion. Human vascular fragments, freshly obtained at vascular surgery from saphenous veins, atrial appendages, normal aortas and atherosclerotic lesions (histologically classified as fibrous plaques, fatty plaques and complicated lesions) were incubated at 37 degree C with mechanical agitation, for various times ranging between 5 and 60 minutes, sequentially, with buffer (basal), ionophore A23187 (IONO), and arachidonic acid (AA). After each step medium was assayed for LTB4 production by radioimmunoassay. Incubations were also performed in a chamber allowing selective exposure of the endothelial surface to the medium. Basal production (15 minute incubation, ng/g, mean +/- SD) was lowest for fibrous plaques (0.9 +/- 0.2, n = 38) and saphenous veins (1.0 +/- 0.3, n = 32) and much higher (P less than 0.01) for fatty plaques (7.3 +/- 2.2, n = 35) and complicated lesions (5.3 +/- 3.0, n = 28). A virtual abolition of production was observed after boiling of the vascular fragment. Production was increased in the presence of AA and IONO (in atheromas: 11.5 +/- 4.2 AND 14.3 +/- 5.3, respectively, with 15 minutes incubation), and decreased after incubation with 5-lipooxigenase inhibitors. Peak of ionophore or arachidonic acid-stimulated production in kinetic studies was reached at 20 minutes. LTB4 production was able to reach the luminal surface in both basal and stimulated conditions. There was no relationship with concomitantly measured prostacyclin production (mainly endothelial), while a correlation was found between LTB4 levels and degree of white cell infiltration in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolated Rectal Metastases from Locally Advanced Carcinoma Prostate Detected by 18 F-PSMA-1007 PET/CT.
Rectal involvement by prostate carcinoma is rare and isolated rectal metastases are even rarer with only a few cases having been reported in the literature. In our knowledge, no case of isolated rectal metastases diagnosed on prostate specific membrane antigen positron emission tomography/computed tomography has been reported to date. We present a case of a 66-year-old patient who presented with rectal bleeding and passage of urine from anal region and was diagnosed with carcinoma prostate infiltrating the rectum along with solitary rectal metastases.


The paradox of metabolism in quiescent stem cells.
The shift between a proliferating and a nonproliferating state is associated with significant changes in metabolic needs. Proliferating cells tend to have higher metabolic rates, and their metabolic profiles facilitate biosynthesis, as compared to those of nondividing cells of the same sort. Recent studies have elucidated specific molecules that control metabolic changes while cells shift between proliferation and quiescence. Embryonic stem cells, which are rapidly proliferating, tend to have metabolic patterns that are similar to those of nonstem cells in a proliferative state. Moreover, although adult stem cells tend to be quiescent, their metabolic profiles have been reported in multiple organs to more closely resemble those of proliferating than those of nondividing cells in some respects. The findings raise questions about whether there are metabolic profiles that are required for stemness, and whether these profiles relate to the metabolic properties that may be required for quiescence. Here, we review the literature on how metabolism changes upon commitment to proliferation and compare the proliferating and nonproliferating metabolic states of differentiated cells and embryonic and adult stem cells.


Intracranial stenting in patients with atherosclerotic stenosis associated with various aneurysms in the same diseased arterial segment.
Aneurysms are rarely associated with symptomatic intracranial stenosis. We report the results of recanalization by stent placement in patients with symptomatic severe intracranial stenosis associated with adjacent aneurysms. Of 139 patients who underwent intracranial stent placement during a 5-year period, 10 (7%) had symptomatic severe intracranial stenosis associated with adjacent aneurysms. Five were in the VA, 3 in the BA, and 2 in M1. The types of aneurysm were atherosclerotic fusiform (n = 5), ulcerative (n = 4), and saccular (n = 1). We analyzed angiographic findings based on biplane and 3D angiograms and assessed patient outcomes and complications after stent placement. The results were compared with those of a control group without aneurysms who underwent stent placement during the same study period. Aneurysm locations were post- (n = 6), in- (n = 2), and pre-stenotic (n = 2). After angioplasty with stent placement and/or aneurysm embolization, there were no lesion-related strokes or deaths during a median follow-up period of 25 months (range, 11-43 months). One patient had asymptomatic restenosis. The final mRS score was good (≤2) in all patients. There were no statistically significant differences in event or restenosis rates compared with the control group. Adjacent aneurysms were rarely associated with severe intracranial stenosis but were more common in the posterior circulation. Intracranial stent placement may be performed without additional stroke risk, regardless of the type and location of the aneurysm.


Freshman 15: valid theory or harmful myth?
The authors investigated whether the perception that freshmen gain 15 pounds during their 1st year of college is related to either actual or perceived weight gain. Forty-nine incoming freshmen at a small liberal arts college completed the study by filling out questionnaires and health data at the beginning and end of their 1st year on campus. The findings revealed no significant weight gain at the end of the year. The "Freshman 15" myth was found to play an important role in perpetuating negative attitudes toward weight. Freshmen who were concerned about gaining 15 pounds were more likely to think about their weight, have a poorer body image than others, and categorize themselves as being overweight.


Clinical accuracy of ExacTrac intracranial frameless stereotactic system.
In this paper, the authors assess the accuracy of the Brainlab ExacTrac system for frameless intracranial stereotactic treatments in clinical practice. They recorded couch angle and image fusion results (comprising lateral, longitudinal, and vertical shifts, and rotation corrections about these axes) for 109 stereotactic radiosurgery and 166 stereotactic radiotherapy patient treatments. Frameless stereotactic treatments involve iterative 6D image fusion corrections applied until the results conform to customizable pass criteria, theirs being 0.7 mm and 0.5° for each axis. The planning CT slice thickness was 1.25 mm. It has been reported in the literature that the CT slices' thickness impacts the accuracy of localization to bony anatomy. The principle of invariance with respect to patient orientation was used to determine spatial accuracy. The data for radiosurgery comprised 927 image pairs, of which 532 passed (pass ratio of 57.4%). The data for radiotherapy comprised 15983 image pairs, of which 10 050 passed (pass ratio of 62.9%). For stereotactic radiotherapy, the combined uncertainty of ExacTrac calibration, image fusion, and intrafraction motion was (95% confidence interval) 0.290-0.302 and 0.306-0.319 mm in the longitudinal and lateral axes, respectively. The combined uncertainty of image fusion and intrafraction motion in the anterior-posterior coordinates was 0.174-0.182 mm. For stereotactic radiosurgery, the equivalent ranges are 0.323-0.393, 0.337-0.409, and 0.231-0.281 mm. The overall spatial accuracy was 1.24 mm for stereotactic radiotherapy (SRT) and 1.35 mm for stereotactic radiosurgery (SRS). The ExacTrac intracranial frameless stereotactic system spatial accuracy is adequate for clinical practice, and with the same pass criteria, SRT is more accurate than SRS. They now use frameless stereotaxy exclusively at their center.


Prolonged seasonality of respiratory syncytial virus infection among preterm infants in a subtropical climate.
There is limited epidemiological data on the seasonality of respiratory syncytial virus (RSV) infection in subtropical climates, such as in Taiwan. This study aimed to assess RSV seasonality among children ≤24 months of age in Taiwan. We also assessed factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with RSV-associated hospitalization in preterm infants to confirm the appropriateness of the novel Taiwanese RSV prophylactic policy. From January 2000 to August 2010, 3572 children aged ≤24-months were admitted to Taipei Mackay Memorial Hospital due to RSV infection. The monthly RSV-associated hospitalization rate among children aged ≤24 months was retrospectively reviewed. Among these children, 378 were born preterm. The associations between GA, CA, and BPD and the incidence of RSV-associated hospitalization in the preterm infants were assessed. In children aged ≤24 months, the monthly distribution of RSV-associated hospitalization rates revealed a prolonged RSV season with a duration of 10 months. Infants with GAs ≤32 weeks and those who had BPD had the highest rates of RSV hospitalization (P<0.001). Preterm infants were most vulnerable to RSV infection within CA 9 months. Given that Taiwan has a prolonged (10-month) RSV season, the American Academy of Pediatrics' recommendations for RSV prophylaxis are not directly applicable. The current Taiwanese guidelines for RSV prophylaxis, which specify palivizumab injection (a total six doses until CA 8-9 months) for preterm infants (those born before 28(6/7) weeks GA or before 35(6/7) weeks GA with BPD), are appropriate. This prophylaxis strategy may be applicable to other countries/regions with subtropical climates.


Construction and overexpression in Escherichia coli of genetically engineered derivatives of penicillin-binding protein 2' of Staphylococcus epidermidis.
Removal of the putative amino-terminal membrane spanning region of penicillin-binding protein 2' (PBP-2') of Staphylococcus epidermidis WT55 was carried out by truncating the amino terminus-coding end of the mecA gene. PCR and site directed mutagenesis were used to introduce unique restriction sites at position 68 (HindIII) and at position 80 (NcoI) of the mecA gene, respectively. The coupling of the shortened coding regions to the trc promoter and gene fusion to the lacZ gene, aimed to facilitate subsequent protein purifications, resulted in strong expression in the cytoplasm of Escherichia coli and partial sequestration into insoluble protein granules. The truncated PBP-2' retained its penicillin-binding ability and also bound the monoclonal antibody directed against PBP-2' of Staphylococcus aureus.


The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity Via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts.
Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype. Extended periods of lactation protect against breast cancer development, but the mechanisms underlying this protection are unknown. We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways in triple negative breast cancer cells and patient samples. Finally, we used small molecular inhibitors to target relevant pathways and highlight these as potential candidates for the treatment of TN breast cancer. High levels of alpha-casein gene expression were predictive of good prognosis across 263 TNBC patient tumour samples. Alpha-casein over expression or exogenous addition reduces cancer stem cell (CSC) activity. HIF-1alpha was identified to be a key downstream target of alpha-casein, in both breast cancer cells and activated fibroblasts, and STAT transcription factors to be upstream of HIF-1alpha. Interestingly, HIF-1alpha is regulated by STAT3 in breast cancer cells, but STAT1 is the regulator of HIF-1alpha in activated fibroblasts. In analysis of 573 TNBC patient samples, alpha-casein expression, inversely correlated to HIF-1alpha, STAT3 and STAT1. STAT1 and STAT3 inhibitors target HIF-1alpha signalling in activated fibroblasts and MDA-MB-231 breast cancer cells respectively, and also abrogate CSC activities. Our findings provide an explanation for the protective effects of lactation in TNBC. Clinical data correlates high alpha-casein expression with increased recurrence-free survival in TNBC patients. Mechanistically, alpha-casein reduces breast cancer stem cell activity in vitro, and STAT3 and STAT1 were identified as regulators of pro-tumorigenic HIF-1alpha signalling in breast cancer cells and fibroblasts respectively.


[Morphological changes in sebaceous glands with aging in human males].
Using a computer stereographic analysis, the normal human forehead skin from 16 males of ages ranging from 7 to 77 years were investigated to known the morphological changes of the sebaceous glands with aging. The volume of sebaceous glands increased abruptly in teens, reaching maximum in the 20s; it was maintained at high levels even at middle ages and then began to decrease gradually in the 60s. The volume of sebaceous glands positively correlated with the number of the sebaceous cells but not with their sizes. Ultrastructually, in the large sebaceous glands, and peripheral cells were cuboidal, whereas they were flat in the small sebaceous glands. It is concluded that the sebaceous glands in males show no morphological change in relation to age between the 20s and 50s.


The induction and function study on dendritic cells derived from blasts from patients with acute myelogenous leukemia.
To investigate the induction method and function of dendritic cells (DC) derived from acute myelogenous leukemia (AML) blasts in vitro, cytokine-supplemented suspension cultures of leukemia blasts in 25 AML patients were performed. Mononuclear cells were cultured for 8 to 12 days using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), recombinant human interleukin-4 (rhIL-4) and recombinant human tumor necrosis factor-alpha (rhTNF-alpha). Morphology, phenotype, cytogenetics, and function of induced cells were studied. The results showed that after culture for 3 days, cells in 20/25 AML cases demonstrated an increase in size with dendritic morphology. After culture for 8 - 9 days, the percentage of such cells reached peak. When cultured for 12 days, the total number of cells and the number of cells with DC morphology decreased greatly. Phenotypic analyses of cells (11/20 cases) were measured by flow cytometry before and after culture. Before culture, cells did not express CD1a, CD80 and CD83, while expressed CD54, CD86 and HLA-DR with low frequency. After culture, cells upregulated CD1a, CD80, CD83, CD54, CD86 and HLA-DR significantly. A marked increase of the T-cell stimulatory capacity could be generated in Allo-MLRs. FISH confirmed the leukemic origin of generated cells. In conclusion, leukemia-derived DC can be generated from AML blasts using cytokine combination (GM-CSF, IL-4, and TNF-alpha) in vitro.


Adsorption of polycyclic aromatic hydrocarbons at the air-water interface and its role in atmospheric deposition by fog droplets.
This review addresses the significance of air-water interfacial adsorption in the fate and transport of polycyclic aromatic hydrocarbons (PAHs) in dispersed systems, such as fog droplets in the atmosphere and air bubbles in wastewater systems. The equilibrium (partition constants) and transport (mass accommodation coefficients) parameters in dispersed systems are discussed. Specific cases where the air-water interfacial adsorption makes a significant impact, such as uptake of naphthalene by fog droplets in a falling droplet reactor and of pyrene removal on air bubbles in a solvent sublation reactor, are discussed as illustrations. The consequence of the air-water interface in atmospheric wet deposition of PAHs by fog droplets is analyzed mathematically.


Susceptibility Analysis in Several Mouse Strains Reveals Robust T-Cell Responses After Mycoplasma pneumoniae Infection in DBA/2 Mice.
Mycoplasma pneumoniae (Mp) is a highly contagious respiratory pathogen responsible for human community-acquired pneumonia. The number of antibiotic-resistant Mp strains is increasing; therefore, to develop novel therapeutics, it is crucial to precisely understand the pathogenesis of mycoplasma pneumonia. Herein, we examined the susceptibility and response to Mp among eight inbred mouse strains. Following infection, the bacterial load in the bronchoalveolar lavage fluid (BALF) from DBA/2 mice was higher than that in the other tested strains such as BALB/c mice, which are frequently used in Mp research. In contrast, the numbers of CD45+ immune cells and neutrophils in BALF were comparable between BALB/c and DBA/2 mice, with lower numbers observed in C57BL/6J and CBA/N mice than in BALB/c mice. Among the tested strains, the BALF level of interleukin 12 subunit p40 was highest in DBA/2 mice; however, significant differences in other cytokines levels were not observed between BALB/c and DBA/2 mice. After Mp infection, Mp-specific Th1 and Th17 responses were significantly enhanced in DBA/2 mice when compared with BALB/c mice. Furthermore, prior infection with Mp increased the number of neutrophils in BALF after the reinfection of DBA/2 mice through an Mp-specific CD4+ T cell-dependent mechanism. Thus, DBA/2 may be an appropriate strain for evaluating Mp infection. Moreover, a comparison of responses revealed by various inbred mouse strains could be useful for elucidating the pathogenesis of Mycoplasma pneumonia.


Correlation between Biophysical Properties of Niosomes Elaborated with Chloroquine and Different Tensioactives and Their Transfection Efficiency.
Lipid nanocarriers, such as niosomes, are considered attractive candidates for non-viral gene delivery due to their suitable biocompatibility and high versatility. In this work, we studied the influence of incorporating chloroquine in niosomes biophysical performance, as well as the effect of non-ionic surfactant composition and protocol of incorporation in their biophysical performance. An exhaustive comparative evaluation of three niosome formulations differing in these parameters was performed, which included the analysis of their thermal stability, rheological behavior, mean particle size, dispersity, zeta potential, morphology, membrane packing capacity, affinity to bind DNA, ability to release and protect the genetic material, buffering capacity and ability to escape from artificially synthesized lysosomes. Finally, in vitro biological studies were, also, performed in order to determine the compatibility of the formulations with biological systems, their transfection efficiency and transgene expression. Results revealed that the incorporation of chloroquine in niosome formulations improved their biophysical properties and the transfection efficiency, while the substitution of one of the non-ionic surfactants and the phase of addition resulted in less biophysical variations. Of note, the present work provides several biophysical parameters and characterization strategies that could be used as gold standard for gene therapy nanosystems evaluation.


Evaluation of the anticancer potential of secondary metabolites from Pseudevernia furfuracea based on epidermal growth factor receptor inhibition.
UHPLC/ESI/MS/MS profiling followed by bioactivity guided isolation of Pseudevernia furfuracea (P. furfuracea) extract yielded two polyphenolic molecules, Methyl haematommate (PF-1) and Atraric acid (PF-2). These molecules were evaluated for bioactivity against five cancerous cell lines. The results revealed that atraric acid showed significant activity against ovarian cancer cell line (PA-1) having GI50 at 16.42 µg/mL and moderate activity against the breast cancer cell line (MCF-7), having GI50 at 64.35 µg/mL. The results were further supported by in silico molecular docking studies of atraric acid with the epidermal growth factor receptor (EGFR) tyrosine kinase protein. The study revealed that atraric acid has the capacity to act as a potential EGFR inhibitor via occupying the ATP binding pocket of EGFR and making favourable electrostatic interactions and van der Waals interaction with its key residues. Our results highlight P. furfuracea and its polyphenolic compound, atraric acid as a promising candidate for ovarian cancer management.


A service-learning project to eliminate barriers to oral care for children with special health care needs.
Children with special health care needs face many barriers to oral care and are at high risk for oral disease. School nurses are in a unique position to promote oral wellness in this vulnerable population. Collaboration between school nurses and dental hygiene faculty resulted in the formation of a partnership between a university-based dental hygiene program and two special education districts in rural southern Illinois. Senior dental hygiene students participated in a school-based service-learning project that provided dental examinations, preventive services, and education to children with special health care needs. Evidence-based behavioral interventions were used to teach children to comply with oral procedures. School nurses mentored dental hygiene students in behavior management of children. Dental exams were provided to 234 children from four special education schools with the majority receiving cleanings and fluoride.


Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India.
We undertook the present study to ascertain the contributing risk factors and explore the epidemiological and mycological characteristics of opportunistic candidemia among patients with hematological malignancies. Observational cross-sectional study in a tertiary care center. Consecutive patients with hematological malignancies reporting to the collaborating medical and pediatric units with a febrile episode were recruited and screened for candidemia by blood culture. Recovered Candida isolates were speciated and antifungal susceptibility testing was performed as per Clinical and Laboratory Standards Institute guideline (CLSI) guidelines M44-A. Further analysis was done for potential risk factors and compared between culture positive and negative patients. Of 150 patients recruited, the majority (n=27) were between 51 and 60 years and the male to female ratio was 1.63:1. Fifteen patients (10%) were culture positive. The culture positivity was significantly higher in acute lymphocytic leukemia (ALL) than in non-ALL patients (p=0.03). There was significant association of candidaemia with leucopenia, chemotherapeutic drugs, corticosteroids and presence of indwelling devices. Duration of disease (p=0.032) and duration of hospitalization (p=0.003) were significantly prolonged in culture positive patients. C. tropicalis was the commonest isolate (46.67%), with non- Candida albicans outnumbering C. albicans in all categories of hematological malignancies (2.75:1). All isolates of C. albicans were uniformly sensitive to all the azoles, but only 50% were sensitive to amphotericin B and none to nystatin and flucytosine. This observational study identifies ALL and chronic lymphocytic leukemia (CLL) as the forms of hematological malignancy predominantly associated with candidemia; specifies risk factors and chemotherapeutic agents predisposing patients towards its occurrence; reports a preponderance of C. tropicalis among the causative agents and finds voriconazole to be the most effective antifungal agent against the recovered isolates. This information could assist in tailoring prophylactic and therapeutic antifungal practices for this infection, according to local epidemiological and mycological characteristics.


Effect of vanadium on insulin sensitivity and appetite.
Vanadium, a potent nonselective inhibitor of protein tyrosine phosphatases, has been shown to mimic many of the metabolic actions of insulin both in vivo and in vitro. The mechanism(s) of the effect of vanadium on the decrease in appetite and body weight in Zucker fa/fa rats, an insulin-resistant model, is still unclear. Because insulin may inhibit hypothalamic neuropeptide Y (NPY), which is known to be related to appetite, and increase leptin secretion in adipose tissue, we studied the possibility that the changes in appetite produced by vanadium may be linked to altered NPY levels in the hypothalamus. We also examined effects of vanadium on leptin. Zucker lean and fatty rats were chronically treated with bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, in the drinking water. Plasma and adipose tissue leptin levels were measured by radioimmunoassay and immunoblotting, respectively. Hypothalamic NPY mRNA and peptide levels were measured using in situ hybridization and immunocytochemistry, respectively. BMOV treatment significantly reduced food intake, body fat, body weight, plasma insulin levels, and glucose levels in fatty Zucker rats. Fifteen minutes after insulin injection (5 U/kg, intravenous [IV]), circulating leptin levels (+100%) and adipose leptin levels (+60%) were elevated in BMOV-treated fatty rats, although these effects were not observed in untreated fatty rats. NPY mRNA levels in the arcuate nucleus (ARC) (-29%), NPY peptide levels in ARC (-31%), as well as in the paraventricular nucleus (PVN) (-37%) were decreased with BMOV treatment in these fatty rats. These data indicate that BMOV may increase insulin sensitivity in adipose tissue and decrease appetite and body fat by decreasing NPY levels in the hypothalamus. BMOV-induced reduction in appetite and weight gain along with normalized insulin levels in models of obesity, suggest its possible use as a therapeutic agent in obesity.


Recent Developments in NAFLD.
The aim of our Special Edition, entitled "Nonalcoholic Fatty Liver Disease/Metabolic Associated Fatty Liver Disease: New Insights", is to point out recent developments in the area of NAFLD pathogenesis and treatment [...].


Progress in reducing mortality among Wisconsin residents, 1980-2000: rates decline, but black-white disparities increase.
To assess progress towards 2 overarching public health goals--improvement in length of life and reducing health disparities. Age specific mortality rates in Wisconsin from 1980 to 2000 were obtained from the US Centers for Disease Control and Prevention WONDER database. Rates for each age group were gathered for the entire Wisconsin population and for black and white subgroups. Trends in mortality rates were plotted, change in mortality rates was estimated, and the number of "lives saved" annually from 1980-1984 to 1996-2000 was calculated. In addition, black vs white rate ratios were calculated at both the beginning and the end of the time period to determine trends in black-white mortality disparities. Mortality is decreasing in Wisconsin in every age group. The largest relative improvements in mortality rates occurred among infants <1 year (-30%), children 1-14 years (-27%), and adults 45-64 years (-23%). Comparatively little progress was seen among adults 25-44 years (-5%) and those 85 years and older (-0.5%). Black/white disparities increased in every age group. During 1996-2000, approximately 5000 fewer deaths occurred each year than expected based on mortality rates from 1980-1984. Despite progress towards increasing length of life, progress towards eliminating disparities was not seen over the 1980 to 2000 time period.


Performance of high producing dairy cows with three different feeding systems combining pasture and total mixed rations.
Forty-five Holsteins cows in early to mid lactation were used to compare three feeding systems combining pasture and total mixed rations (TMR) on animal performance in a 21-wk repeated-measures experiment. The three treatments were: 1) pasture plus concentrate (PC), 2) pasture plus partial TMR (pTMR), and 3) TMR (non-pasture). Total dry matter intake, using chromic oxide as a marker, was 21.6, 25.2, and 26.7 kg/d for PC, pTMR, and TMR, respectively. Milk production was highest for TMR (38.1 kg/d), lowest on PC (28.5 kg/d), and intermediate for pTMR (32.0 kg/d). Cows on pTMR and TMR had higher milk fat and true protein percentages than cows on PC. Cows on PC gained less body weight and lost more body condition compared with cows on pTMR and TMR. Initial concentrations of plasma nonesterified fatty acids were higher on PC (302 microeq/L) than on pTMR (130 microeq/L) and TMR (225 microeq/L). Plasma and milk urea nitrogen were lower on both pTMR and TMR than on PC. Combining pasture and TMR resulted in higher milk production, milk fat and protein percentage, and maintenance in body condition score compared to pasture plus concentrate. The TMR feeding system resulted in the highest total dry matter intake and milk production.


Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice.
To investigate the effect of carvedilol on liver fibrosis and hepatic sinusoidal capillarization in mice with carbon tetrachloride (CCl4)-induced fibrosis. A liver fibrosis mouse model was induced by intraperitoneal CCl4 injection for 8 weeks. The mice were divided into five experimental groups: the normal group, the oil group, the CCl4 group, the CCl4+carvedilol (5 mg/kg/d) group, and the CCl4+carvedilol (10 mg/kg/d) group. The extent of liver fibrosis was evaluated by histopathological staining, and the changes in fenestrations of hepatic sinus endothelial cells were observed by scanning electron microscope (SEM). The expression of α-smooth muscle actin (α-SMA) and vascular endothelial markers was detected by immunohistochemistry and Western blot assays. The effect of carvedilol on cell apoptosis was studied via Terminal deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL) assay, and the serum levels of matrix metalloproteinase-8 (MMP-8), vascular endothelial growth factor (VEGF), and angiopoietin-2 were detected through a Luminex assay. Liver fibrosis in CCl4-treated mice was attenuated by reduced accumulation of collagen and the reaction of inflammation with carvedilol treatment. Carvedilol reduced the activation of hepatic stellate cells (HSCs) and increased the number of apoptotic cells. The expression of α-SMA, CD31, CD34 and VWF (von Willebrand factor) was significantly decreased after carvedilol treatment. In addition, the number of fenestrae in the hepatic sinusoid showed notable differences between the groups, and the serum levels of MMP-8, VEGF and angiopoietin-2 were increased in the mice with liver fibrosis and reduced by carvedilol treatment. The study demonstrated that carvedilol could prevent further development of liver fibrosis and hepatic sinusoidal capillarization in mice with CCl4-induced fibrosis.


Histology of the terminal ileum in coeliac disease.
The histological lesion of gluten sensitivity primarily affects the proximal small bowel. The purpose of this study was to assess whether there were features of gluten-sensitive enteropathy in biopsies taken from the terminal ileum during colonoscopy/ileoscopy. Specific and sensitive abnormalities might facilitate diagnosis of coeliac disease in patients undergoing colonoscopy as their initial procedure or help select those who should proceed to upper gastrointestinal endoscopy and duodenal biopsy. Terminal ileal biopsies, taken from 30 patients with duodenal villous atrophy consistent with coeliac disease and from 60 control patients with no evidence of coeliac or inflammatory bowel disease, were reviewed blindly and compared. Biopsies were assessed for the presence or absence of villous atrophy and crypt hyperplasia, and counts were made of intraepithelial lymphocytes (IELs). One patient only, in the coeliac group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher (P< 0.005) in the coeliac group than among controls (mean per 100 enterocytes 26 versus 10). An ileal IEL count > or =25 had a sensitivity for duodenal villous atrophy (VA) of 60% and specificity of 100%. Coeliac disease may affect the entire small bowel. Increased IEL density in the terminal ileum is associated with duodenal VA and should prompt a search for coeliac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of coeliac disease with confidence.


Mapping the Mechanical Properties of Hierarchical Supercrystalline Ceramic-Organic Nanocomposites.
Multiscale ceramic-organic supercrystalline nanocomposites with two levels of hierarchy have been developed via self-assembly with tailored content of the organic phase. These nanocomposites consist of organically functionalized ceramic nanoparticles forming supercrystalline micron-sized grains, which are in turn embedded in an organic-rich matrix. By applying an additional heat treatment step at mild temperatures (250-350 °C), the mechanical properties of the hierarchical nanocomposites are here enhanced. The heat treatment leads to partial removal and crosslinking of the organic phase, minimizing the volume occupied by the nanocomposites' soft phase and triggering the formation of covalent bonds through the organic ligands interfacing the ceramic nanoparticles. Elastic modulus and hardness up to 45 and 2.5 GPa are attained, while the hierarchical microstructure is preserved. The presence of an organic phase between the supercrystalline grains provides a toughening effect, by curbing indentation-induced cracks. A mapping of the nanocomposites' mechanical properties reveals the presence of multiple microstructural features and how they evolve with heat treatment temperature. A comparison with non-hierarchical, homogeneous supercrystalline nanocomposites with lower organic content confirms how the hierarchy-inducing organic excess results in toughening, while maintaining the beneficial effects of crosslinking on the materials' stiffness and hardness.


Scratch Properties of Clear Coat for Automotive Coating Comprising Molecular Necklace Crosslinkers with Silane Functional Groups for Various Environmental Factors.
Automotive coatings, which comprise multiple layers, i.e., primer, base coating, and clear coat layers, are exposed to various environmental conditions that pose various types of damages to them. In particular, the outer layer of the automotive coating, i.e., the clear coat, is affected significantly by such damages. Therefore, a reliable and durable clear coat must be developed to improve the appearance of automobiles. In this study, a new clear coat based on an acrylic-based clear coat modified using polyrotaxane crosslinkers, which are necklace-shaped supramolecules composed of ring-shaped host molecules, is developed and characterized. The effects of polyrotaxane and silane on the scratch properties and mechanisms of the clear coating are analyzed. It is observed that the critical loads of the clear coat from scratch tests can be improved by adding optimal molecular necklace crosslinkers comprising silane functional groups. The improvement in the scratch properties of the modified acrylic-based clear coat may be attributed to the crosslinking characteristics and dynamic molecular movements of the polyrotaxane. In addition, the effects of environmental factors on the scratch characteristics of the modified acrylic-based clear coat are investigated by addressing the scratch durability of the clear coat.


Melorheostosis in the upper extremity.
Melorheostosis is a rare mesodermal disease affecting the skeleton and adjacent soft tissues. Often it is incidentally detected on radiographs. In the standard radiology and orthopedics literature, melorheostosis is described as a "flowing hyperostosis, resembling dripping candle wax as an incidental radiographic finding." A 22-year-old man presented with a 2-year history of right-hand pain. Radiologic evaluation of the hand showed massive sclerotic changes in the first and second metacarpal and phalangeal bones on the right side. Further radiographic evaluation of the right upper extremity revealed the same sclerotic changes in the right scapula, humerus, radius, and scaphoid. Computed tomography (CT) scans showed a high attenuation undulating cortical hyperostosis with a "dripping candle wax appearance" involving the radial and/or dorsal aspects of humerus, radius, scaphoid, and first and second ray bones of the hand. Radionuclide triphasic bone scintigraphy showed diffuse homogenous radiotracer uptake within the entire right upper extremity involving the scapula, humerus, radius, scaphoid, and first and second metacarpals and phalangeal bones of the hand. The patient was followed conservatively, and 1-year follow-up revealed no change in the clinical, laboratory, or radiological findings. The diagnosis of melorheostosis was made on the basis of the characteristic distribution, location, and combined radiographic, CT, and radionuclide imaging features of the abnormalities. Conservative treatment was recommended for the patient. After 26 months of follow-up, despite the persistence of the radiologic findings, the patient is currently well, with no painful symptoms unless he performs forceful exercise.


Do preoperative statins reduce atrial fibrillation after coronary artery bypass grafting?
Recent studies have demonstrated that statins have pleiotropic effects, including anti-inflammatory effects and atrial fibrillation (AF) preventive effects. The objective of this study was to assess the efficacy of preoperative statin therapy in preventing AF after coronary artery bypass grafting (CABG). 221 patients underwent CABG in our hospital from 2004 to 2007. 14 patients with preoperative AF and 4 patients with concomitant valve surgery were excluded from this study. Patients were divided into two groups to examine the influence of statins: those with preoperative statin therapy (Statin group, n = 77) and those without it (Non-statin group, n = 126). In addition, patients were divided into two groups to determine the independent predictors for postoperative AF: those with postoperative AF (AF group, n = 54) and those without it (Non-AF group, n = 149). Patient data were collected and analyzed retrospectively. The overall incidence of postoperative AF was 26%. Postoperative AF was significantly lower in the Statin group compared with the Non-statin group (16% versus 33%, p = 0.005). Multivariate analysis demonstrated that independent predictors of AF development after CABG were preoperative statin therapy (odds ratio [OR] 0.327, 95% confidence interval [CI] 0.107 to 0.998, p = 0.05) and age (OR 1.058, 95% CI 1.004 to 1.116, p = 0.035). Our study indicated that preoperative statin therapy seems to reduce AF development after CABG.


Use of Electronic Patient-Reported Outcomes in the Care of Patients with Kidney Failure.
This article in the "Exploring the Evidence" series provides nephrology nurses and clinicians with a description of what electronic patient-reported outcomes (ePROs) and patient-reported outcome measures (PROMs) entail, as well as an understanding of how they can be used in nephrology patient care. Specifically highlighted are some questions and issues that clinicians have raised in our various research studies that have explored ePRO use and integration in the movement toward person-centered kidney care (Schick-Makaroff, 2017; Schick-Makaroff and Molzahn, 2014, 2015, 2017; Schick-Makaroff, Tate et al., 2019).


Online Discussions About Tinnitus: What Can We Learn From Natural Language Processing of Reddit Posts?
This study was aimed at identifying key topics in online discussions about tinnitus by examining a large data set extracted from Reddit social media using a natural language processing technique. A corpus of 113,215 posts about tinnitus was extracted from Reddit's application programming interface. After cleaning the data for duplications and posts without any text information, the sample was reduced to 101,905 posts, which was subjected to cluster analysis using the open-source IRaMuTeQ software to identify main topics based on the co-occurrence of texts. These clusters were named by a panel of tinnitus experts (n = 9) by reading typical text segments within each cluster. The cluster analysis identified 16 unique clusters that belong to two topics, which were named "tinnitus causes and consequences" and "tinnitus management and coping." Based on their characteristics, the clusters were named: tinnitus timeline (10%), tinnitus perception (9.7%), medical triggers and modulators (8.8%), hearing research (8.8%), attention and silence (8.6%), social media posts about tinnitus (7.4%), hearing protection (7.3%), interaction with hearing health care providers (6.7%), mental health and coping (5.8%), music listening (5.7%), hope for a cure (5.6%), interactions with people without tinnitus (5.4%), dietary supplements and alternative therapies (3.2%), sleep (3.9%), dietary effects (1.7%), and writing about tinnitus and being thankful to online community (1.4%). Despite some limitations, tinnitus posts on Reddit provide rich real-world data to identify various issues and complaints that tinnitus patients and their significant others discuss in online communities. Some of the clusters identified here are novel (e.g., tinnitus timeline, interactions with people without tinnitus) and have not been much discussed in the tinnitus literature. The results suggest that individuals with tinnitus relay on social media for support and highlight the service delivery needs in providing social support through other means (e.g., support groups).


Novel microbial consortia facilitate metalliferous immobilization in non-ferrous metal(loid)s contaminated smelter soil: Efficiency and mechanisms.
Exposure to toxic metals from nonferrous metal(loid) smelter soils can pose serious threats to the surrounding ecosystems, crop production, and human health. Bioremediation using microorganisms is a promising strategy for treating metal(loid)-contaminated soils. Here, a native microbial consortium with sulfate-reducing function (SRB1) enriched from smelter soils can tolerate exposures to mixtures of heavy metal(loid)s (e.g., As and Pb) or various organic flotation reagents (e.g., ethylthionocarbamate). The addition of Fe2+ greatly increased As3+ immobilization compared to treatment without Fe2+, with the immobilization efficiencies of 81.0% and 58.9%, respectively. Scanning electronic microscopy-energy dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy confirmed that the As3+ immobilizing activity was related to the formation of arsenic sulfides (AsS, As4S4, and As2S3) and sorption/co-precipitation of pyrite (FeS2). High-throughput 16S rRNA gene sequencing of SRB1 suggests that members of Clostridium, Desulfosporosinus, and Desulfovibrio genera play an important role in maintaining and stabilizing As3+ immobilization activity. Metal(loid)s immobilizing activity of SRB1 was not observed at high and toxic total exposure concentrations (220-1181 mg As/kg or 63-222 mg Pb/kg). However, at lower concentrations, SRB1 treatment decreased bioavailable fractions of As (9.0%) and Pb (28.6%) compared to without treatment. Results indicate that enriched native SRB1 consortia exhibited metal(loid) transformation capacities under non-toxic concentrations of metal(loid)s for future bioremediation strategies to decrease mixed metal(loid)s exposure from smelter polluted soils.


Fabricational morphology of oblique ribs in bivalves.
The formation of oblique ribs of bivalve shells usually has been attributed to processes of reaction-diffusion of morphogens from cell to cell at the mantle margin or neural activation and lateral inhibition in the mantle. In particular, such ribs appear with high rates of lateral diffusion. Nevertheless, theoretical models fail to explain either partially or wholly some varieties of oblique ribs. After surveying the modes of formation of the shell and oblique ribs by the bivalve mantle and associated fabricational defects, I have determined that the mantle is able to develop an elaborate behavior in order to displace the rib in a particular direction during growth. The mantle margin is, therefore, not only the shell-secreting organ, but also the main morphogenetic unit. In particular, there are two main fabricational strategies. In forms with strict contact guidance (SCG) the mantle is able to project far enough beyond the shell margins so as to feel the already formed reliefs and to align new growth increments of the ribs in the appropriate directions. The shell margin is always strongly reflected. In bivalves with reduced contact guidance plus constant lateral shift (RCG), the margin is usually acute and the information about ribs available to the mantle is reduced. During rib construction the mantle extrudes slightly from the shell edge and then pushes laterally by muscular action; in this way, the new growth increment of the rib is displaced laterally on a small scale. The contact-guidance model is supported also by the homogeneous structure of the shell-secreting mantle. From the morphogenetic standpoint, oblique ribs are related to commarginal ones and both differ completely from other ribbing patterns of bivalves.


Angiogenesis determines blood flow, metabolism, growth rate, and ATPase kinetics of tumors growing in an irradiated bed: 31P and 2H nuclear magnetic resonance studies.
Experimental tumors growing in irradiated tissue have been used to study the biological differences characteristic of locally recurrent tumors. Since the hypoxic cell fraction of tumors growing in irradiated tissue is increased and growth rate is slowed, these tumors are assumed to be metabolically deprived with hypoperfusion. In this study, we directly measured the effect of tumor bed irradiation on blood flow, growth rate, rate of nucleoside triphosphate (NTP) turnover, and metabolic state using 31P and 2H nuclear magnetic resonance, and an intradermal assay for angiogenesis. (NTP turnover refers to ATP-synthetase mediated NTP turnover that is visible to 31P nuclear magnetic resonance using the technique of saturation transfer.) A decrease in the number of small blood vessels perfusing tumors in a preirradiated bed was found. Most of the decrease was due to a loss of vessels with diameters less than 0.04 mm. When tumors growing in preirradiated tissue reached approximately 100 mm3 in volume, a high frequency of gross and microscopic necrosis and hemorrhage was already observed in most tumors. Consistent with these observations, the phosphocreatine/inorganic phosphate and nucleoside triphosphate/inorganic phosphate ratios were significantly lower in the tumors growing in a preirradiated bed compared with tumors in a nonirradiated bed. The blood flow rate was similar to control for tumors less than 100 mm3 (45.8 versus 40.5 ml/100 g/min, P = not significant), but was significantly lower than control for tumors greater than 100 mm3 (40.4 versus 12.2 ml/100 g/min, P less than 0.01). The NTP turnover rates correlated (P less than 0.005, r = 0.66) with the volume doubling rate (1/tumor volume doubling time), but for tumors approximately 100 mm3 in size neither the volume doubling rate nor the NTP turnover rate of tumors growing in an irradiated bed was statistically lower than control [NTP turnover: 14 +/- 3%/s versus 9 +/- 2%/s; volume doubling rate: 0.47 +/- 0.07/day versus 0.33 +/- 0.04/day (mean +/- SE)]. A large intertumor variability of all metabolic parameters was observed.


Adding nebivolol to ongoing antihypertensive therapy improves blood pressure and response rates in patients with uncontrolled stage I-II hypertension.
This study assessed blood pressure (BP) reductions and response rates following addition of nebivolol to ongoing antihypertensive therapy in patients with uncontrolled stage I-II hypertension despite antihypertensive treatment. Patients with an average sitting diastolic BP (SiDBP) > or =90 and < or =109 mm Hg while taking an antihypertensive regimen were included in this double-blind, placebo-controlled, parallel-group study. The primary efficacy end point was reduction from baseline to week 12 in mean trough SiDBP. In total, 669 patients were randomized to once-daily nebivolol 5, 10 or 20 mg or placebo. Addition of nebivolol 5, 10 and 20 mg significantly reduced BP; placebo-subtracted least squares mean reductions in trough SiDBP were -3.3, -3.5 and -4.6 mm Hg, respectively (P<0.001) and -5.7, -3.7 and -6.2 mm Hg in trough sitting systolic BP (SiSBP), respectively (P< or =0.015). Adding nebivolol 5-20 mg resulted in significantly more responders (SiDBP <90 or > or =10 mm Hg reduction; range: 53.0-65.1 vs 41.3% with placebo; P< or =0.028) and significantly better control rates (SiSBP/SiDBP <140/90 mm Hg; range: 41.3-52.7 vs 29.3% with placebo; P< or =0.029). Nebivolol was well tolerated; the incidence of adverse events with nebivolol was similar to that with placebo (40.2 vs 38.9%, respectively; P=0.763). Addition of once-daily nebivolol to ongoing antihypertensive therapy provided significant additional BP reductions and better response rates in patients with uncontrolled hypertension and was well tolerated.


Persistent facial ulcerations with a unique clinical appearance: possible trigeminal trophic syndrome.
We reported a 53-year-old woman with a persistent facial ulcer which moved gradually from the right marginal portion of the nasal root to the right lateral canthus along the margin of the right lower eyelid. The ulcer healed spontaneously. A similar ulcer developed at the entrance of the right anterior naris. The clinical findings were suggestive of squamous cell carcinoma, deep mycosis, mycobacterial infection, or a related condition. However, no definitive diagnosis could be made from the clinicopathological findings or the laboratory examinations, including bacterial, mycobacterial, and fungal cultures. The characteristic location of the lesion, and course of the disease, however, suggested the diagnosis of trigeminal trophic syndrome.


An update on romiplostim for treatment of acute radiation syndrome.
Detonation of an improvised nuclear weapon, or a radiological dispersal device by terrorists, or an unintended radiological/nuclear accident in populated areas would result in a mass casualty scenario with radiation exposures of different severities. Such incidences are perceived as national security threats of major consequences. Acute radiation syndrome (ARS) is triggered by an exposure to a high dose of penetrating ionizing radiation during a short time window. In humans, moderate exposure to 2 to 4 Gy of ionizing radiation results in clinically manageable hematopoietic ARS (H-ARS), characterized by severe depletion of vital blood cells and bone marrow progenitors. Since 2015, the United States Food and Drug Administration (U.S. FDA) has approved four radiation medical countermeasures for H-ARS following the Animal Rule; namely, Neupogen, Neulasta, Leukine and Nplate (romiplostim). Here, we briefly present the treatment modalities for H-ARS. We have discussed the latest FDA-approved agent, romiplostim, as a treatment modality for H-ARS. The nature of this agent and the preclinical and clinical work that preceded its FDA approval as a radiation medical countermeasure are discussed, as are the development and use of related thrombopoietic agents for the treatment of radiation-exposed victims.


Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis.
Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol-chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.


Obesity and Cancer Screening according to Race and Gender.
The relationship between obesity and cancer screening varies by screening test, race, and gender. Most studies on cervical cancer screening found a negative association between increasing weight and screening, and this negative association was most consistent in white women. Recent literature on mammography reports no association with weight. However, some studies show a negative association in white, but not black, women. In contrast, obese/overweight men reported higher rates of prostate-specific antigen (PSA) testing. Comparison of prostate cancer screening, mammography, and Pap smears implies a gender difference in the relationship between screening behavior and weight. In colorectal cancer (CRC) screening, the relationship between weight and screening in men is inconsistent, while there is a trend towards lower CRC screening in higher weight women.


Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis).
During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50-70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70-90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator.


Retailers' knowledge of tobacco harm reduction following the introduction of a new brand of smokeless tobacco.
Tobacco retailers are potential public health partners for tobacco harm reduction (THR). THR is the substitution of highly reduced-risk nicotine products, such as smokeless tobacco (ST) or pharmaceutical nicotine, for cigarettes. The introduction of a Swedish-style ST product, du Maurier snus (dMS) (Imperial Tobacco Canada Limited), which was marketed as a THR product, provided a unique opportunity to assess retailers' knowledge. This study examined retailers' knowledge of THR and compliance with recommendations regarding tobacco sales to young adults. Male researchers, who may have looked younger than 18 years old, visited 60 stores in Edmonton that sold dMS. The researchers asked the retailers questions about dMS and its health risks relative to those from other tobacco products. They also attempted to purchase dMS to ascertain whether retailers would ask for identification to verify that they were at least 18 years old. Overall, the retailers were only moderately knowledgeable about THR and the differences between dMS and other tobacco products. About half of the retailers correctly indicated that snus is safer than cigarettes; half of whom knew it is safer because it is smoke-free. Fifty percent incorrectly believed that snus causes oral cancer. Less than fifty percent indicated that dMS differs from chewing tobacco because it is in pouches and is used without spitting or chewing (making it more promising for THR). Most (90%) of the retailers asked the researchers for identification when selling dMS. Tobacco retailers are potentially important sources of information about THR, particularly since there are restrictions on the promotion of all tobacco products (regardless of the actual health risks) in Canada. This study found that many retailers in Edmonton do not know the relative health risks of different tobacco products and are therefore unable to pass on accurate information to smokers.


The in vivo anti-plasmodial activity of haliclonacyclamine A, an alkaloid from the marine sponge, Haliclona sp.
The compound haliclonacyclamine A was isolated from the Haliclona sponge at Solomon Islands. It acts as a powerful in vitro and in vivo anti-plasmodial agent against the chloroquine-resistant Plasmodium falciparum strain FCB1and Plasmodium vinckei petteri-infected mice, respectively.


Response rates to HB vaccine in CKD stages 3-4 and hemodialysis patients.
Hepatitis-B virus (HBV) infection is a big problem in chronic kidney disease (CKD) population. We attempted to compare the response rate to HB vaccine in CKD stages3-4 patients with that in hemodialysis (CKD stage-5; HD patients) and medical staff. Three hundred and three participants were enrolled into the study to test the seroconversion rate after vaccination. Participants formed three groups: Group-A:HD patients, Group-B: diagnosed with CKD stages 3-4, and Group-C: healthy medical staff. CKD stages 3-4 participants were vaccinated from February to November 2010. HD patients were vaccinated at the time of initial HD. While the medical staffs were vaccinated at the time they started working at the hospital. Group-A, Group-B and Group-C received four 40μg (in 0,1,2 and 6 months), three 40μg (0, 1 and 6 months) and three 20μg (0, 1and 6 months) doses of HB vaccine, respectively. Three months after completion of the vaccination schedule, seroconversion and seroprotection rates in each group were investigated. Seroconversion rates were 44.3%, 89.7%, and 96.2% for groups A, B and C, respectively. CKD stages 3-4 patients showed higher response rate than dialysis patients [χ(2)(1):30.6, P <0.001]. But a significant difference in the seroconversion rate between CKD stages 3-4 patients and medical staffs was not observed [χ(2)(1):3.4, P = 0.064]. Multivariate analyses showed patients with more advanced CKD and who were older had less seroconversion rates [odds ratio: 0.09(95%CI: 0.04 - 0.25) and [odds ratio: 0.39(95% CI: 0.18-0.85)], respectively. But sex was not associated with seroconversion (P>0.05). Stages 3-4 patients with higher dosages of routine HB vaccine had higher seroconversion rate than HD patients. Future studies should evaluate the recommended dosage of HB vaccine among these patients.


Isolation, characterisation and crystallisation of a water-soluble fragment of the Rieske iron-sulfur protein of bovine heart mitochondrial bc1 complex.
A water-soluble fragment of the bc1 complex from bovine heart mitochondria was isolated containing the intact Rieske [2Fe-2S] cluster. The fragment consists of the last 129 amino acid residues of the Rieske iron-sulfur protein and has a molecular mass of 14592 Da including two iron atoms. The absorption, visible CD, and EPR spectra of the fragment are indistinguishable from those of the membrane-bound iron-sulfur protein. The redox potential as determined by EPR-monitored redox titration was + 306 mV. The far-ultraviolet CD spectrum is indicative of a protein with little regular secondary structure, while significant alpha-helix content was detected in the membrane anchor of the complete iron-sulfur protein. The fragment could be crystallized using poly(ethylene glycol) 6000 as precipitant. Needle-shaped single crystals have been grown by the hanging-drop vapor diffusion technique. These crystals belong to the space group P21 and diffract well beyond 0.2 nm resolution. Phase determination using the multiple-wavelength anomalous-scattering technique is underway.


Immunological aspects of HBs antigenemia in patients with hematological malignancies.
HBsAg positive sera of 70 patients with lymphoproliferative disorders were tested for hepatitis Be antigen (HBEAg) and antibodies to hepatitis B virus serum immunoglobulins: IgG, IgM and IgA were measured systematically in the whole group before and after acquisition of HBV infection. Sera of 37 patients with neoplastic disorders and of control group were also tested for antibodies to rubella virus (LRV). HBeAg was found in serum of 2 asymptomatic carriers of HBsAg, anti-HBs in serum of 2/70 patients who eliminated HBsAg from their serum within 3 months, anti-HBc were found in serum samples of all transient or persistent HBsAg positive patients. Substantial rise of IgG concentration was determined in the whole infected group irrespective of the clinical course. The percentage of patients without anti-RV was lower in HBsAg positive than in HBsAg negative patients. The differences in reactions to RV between cancer patients and control group were not significant. General impairment of humoral immunity or more specific defects are discussed as factors determining relative or absolute deficiency of anti-HBs and persistence of HBsAg in patients with lymphoproliferative disorders.


Meta-Learning Analysis of Ultrasonic Guided Waves for Coated Cortical Bone Characterization.
Due to its sensitivity to geometrical and mechanical properties of waveguides, ultrasonic guided waves (UGWs) propagating in cortical bones play an important role in the early diagnosis of osteoporosis. However, as impacts of overlaid soft tissues are complex, it remains challenging to retrieve bone properties accurately. Meta-learning, i.e., learning to learn, is capable of extracting transferable features from a few data and, thus, suitable to capture potential characteristics, leading to accurate bone assessment. In this study, we investigate the feasibility to apply the multichannel identification neural network (MCINN) to estimate the thickness and bulk velocities of coated cortical bone. It minimizes the effects of soft tissue by extracting specific features of UGW, which shares the same cortical properties, while the overlaid soft tissue varies. Distinguished from most reported methods, this work moves from the hand-design inversion scheme to data-driven assessment by automatically mapping features of UGW to the space of bone properties. The MCINN was trained and validated using simulated datasets produced by the finite-difference time-domain (FDTD) method and then applied to experimental data obtained from cortical bovine bone plates overlaid with soft tissue mimics. A good match was found between experimental trajectories and theoretical dispersion curves. The results demonstrated that the proposed method was feasible to assess the thickness of coated cortical bone plates.


Evolution of the human cold/menthol receptor, TRPM8.
Genes showing versatile functions or subjected to fast expansion and contraction during the adaptation of species to specific ecological conditions, like sensory receptors for odors, pheromones and tastes, are characterized by a great plasticity through evolution. One of the most fascinating sensory receptors in the family of TRP channels, the cold and menthol receptor TRPM8, has received significant attention in the literature. Recent studies have reported the existence of TRPM8 channel isoforms encoded by alternative mRNAs transcribed from alternative promoters and processed by alternative splicing. Since the first draft of the human genome was accomplished in 2000, alternative transcription, alternative splicing and alternative translation have appeared as major sources of gene product diversity and are thought to participate in the generation of complexity in higher organisms. In this study, we investigate whether alternative transcription has been a driving force in the evolution of the human forms of the cold receptor TRPM8. We identified 33 TRPM8 alternative mRNAs (24 new sequences) and their associated protein isoforms in human tissues. Using comparative genomics, we described the evolution of the human TRPM8 sequences in eight ancestors since the origin of Amniota, and estimated in which ancestors the new TRPM8 variants originated. In order to validate the estimated origins of this receptor, we performed experimental validations of predicted exons in mouse tissues. Our results suggest a first diversification event of the cold receptor in the Boreoeutheria ancestor, and a subsequent divergence at the origin of Simiiformes.


Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy.
Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.


[Sulfasalazine: side effects and duration of therapy in patients with rheumatoid arthritis].
Sulphasalazine (SSZ) is now recognised to be a useful agent in the management of rheumatoid arthritis (RA). We studied SSZ toxicity (2 g/die) and duration of therapy in 102 patients with RA. Adverse events occurred in 25.4% of all patients. In all patients the reactions subsided on either discontinuation of the drug or decrease of the dose. Gastrointestinal was the most common. At 5 years of follow-up the percentage of patients treated with SSZ still on drug was 29%, the inefficacy was 40% of the total drop-out.


Activity of the enzyme adenosine deaminase in serum, erythrocytes and lymphocytes of rats infected with Trypanosoma evansi.
In Trypanosoma evansi infections changes in the haemogram are commonly observed, and the enzyme adenosine deaminase (ADA) plays an important role in the production and differentiation of blood cells. Thus, the aim of this study was to evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats infected with T. evansi compared to non-infected rats. Thirty adult rats were used, divided into 3 uniform groups. The animals in groups A and B were infected intraperitoneally with 2 x 10⁶ trypomastigotes/rat. Rodents from group C (control group), were not-infected. Blood collection was performed on days 4 and 20 post-infection (p.i.) in order to obtain acute and chronic infection stages of disease. The blood was used to assess the activity of ADA. In the blood, reduced haematocrit and increased lymphocytes were correlated with ADA activity in erythrocytes and lymphocytes. We observed reduction of ADA activity in serum and erythrocytes in rats infected with T. evansi compared to non-infected rats (P < 0.05). ADA activity in lymphocytes was decreased after 4 days, when the parasitaemia was high and increased after 20 days, when the number of circulating parasites was low. In conclusion, our results showed that the ADA activity was altered in serum, lymphocytes and erythrocytes of rats, concomitantly with haematological parameters, in experimental infection by T. evansi.


Thermal requirements and effect of temperature and prey on the development of the predator Harmonia axyridis.
Thermal requirements (lower temperature threshold and thermal constant) for the development of each developmental stage of the predator Harmonia axyridis (Pallas) were studied on Aphis fabae Scopoli and Dysaphis crataegi (Kaltenbach) under controlled laboratory conditions. The effect of temperature (15, 20, 25, and 30°C) and prey species was examined on pre-imaginal developmental duration and life cycle (pre-oviposition period included) of the predator. Our results suggest comparable thermal requirements for the development of H. axyridis on the particular prey and when compared with other aphid species. The total preimaginal development of H. axyridis, at 15, 20, and 30°C, and its life cycle, at 15 and 30°C, are shorter on D. crataegi than on A. fabae.


An application of nonlinear mixed-effects modeling to pharmacokinetic data exhibiting nonlinear and time-dependent behavior.
A population pharmacokinetic (PK) analysis was performed on plasma concentrations of GW468816 observed in dogs after 10, 25, and 50 mg/kg/day repeated intravenous administration. A two-compartment model was fitted to the concentration-time data using the NONMEM program. Dose and time dependency of PK parameters was investigated. Selection of the best model was performed using a stepwise approach. A Michaelis-Menten elimination process was used to describe the PK dose dependency, whereas an interoccasion variability on V(m) (the maximum elimination rate of the Michaelis-Menten elimination process) was initially used to describe the time dependency of the PKs, and the final model included an exponential function to account for time variance on V(m). The K(m) value of the final model was 29.6 microg/mL, whereas V(m) was estimated to vary with time from 4.97 microg/h/kg at day 1 to a maximum mean value of 9.64 microg/h/kg at day 14. This approach can be applied to either rich or sparse data leading to estimates of individual parameters by using Bayesian feedback. The overall information obtained can be used to interpret toxicological and pharmacological endpoints and integrated with further in vitro-in vivo studies to supply a comprehensive PK behavior before the first time in human studies.


Preliminary evaluation of pancreatic islets in rats with experimental uremia and after thyroparathyroidectomy.
Hormonal disorders are the permanent symptoms of renal failure. They concern all known hormones and can be due to quantitative changes of the secretory activity and disturbances of endocrine cell functions. The aim of this study was to establish whether experimental thyroparathyroidectomy in uremic animals causes detectable histomorphological changes in endocrine cells of pancreatic islets. Thyroparathyroidectomy was performed in rats 30 days after nephrectomy. Fragments of pancreatic tissue were collected 14 days after the operation. Paraffin sections were stained with H+E and by silver salt impregnation. Immunohistochemical reactions were conducted using antibodies against calcitoningene-related peptide (CGRP), synaptophysin (SPh), somatostatin (ST), neuron-specific enolase (NSE), and chromogranin (CgA). It was shown that endocrine cells of pancreatic islets in thyroparathyroidectomized rats show intensified immunoreactivity to SPh and ST as compared to the control group of animals. Immunocytochemical reactions for NSE, CgA, and CGRP were negative.


[Renal malakoplakia: prognostic aspects].
We report the changes in imaging findings over a 5 year period of a patient with unilateral malakoplakia involving renal parenchyma and pelvis. The imaging findings of malakoplakia will be reviewed.


The Prevalence of Helicobacter pylori Infection Decreases with Older Age in Atrophic Gastritis.
The clinical pathological characteristics of 3969 adult patients with chronic atrophic gastritis were retrospectively studied. The positivity of intestinal metaplasia and dysplasia in atrophic gastric specimens increased with age; however, H. pylori positivity and inflammatory activity decreased significantly with increased age. H. pylori infection was present in 21.01% of chronic atrophic gastritis patients, and 92.33% of the subjects with H. pylori infection were found to have simultaneous inflammatory activity. The intestinal metaplasia and dysplasia positivity markedly increased as the degree of gastric atrophy increased. In conclusion, the incidence of H. pylori infection decreased with age and correlated significantly with inflammatory activity in atrophic gastritis patients. The intestinal metaplasia and dysplasia positivity notably increased as the degree of gastric atrophy increased. Large population-based prospective studies are needed to better understand the progression of CAG.


Strength Profile of Hip Abductor and Adductor Muscles in Youth Elite Soccer Players.
The main objective of this study was to provide an extensive isokinetic profile of the hip joint in youth soccer players, where the literature is limited. Additionally, this study investigated the effect of age on isokinetic peak torque values of hip abductor and adductor muscles and on reciprocal muscle group torque ratios in youth soccer players at different angular velocities (30 vs. 90o/s) and muscle actions (concentric vs. eccentric). Sixty young elite male soccer players were assigned into three equal groups (n = 20): children, young adolescents and older adolescents, and performed five maximal concentric and eccentric hip-abductions and adductions at 30o/s and 90o/s. The results showed a significant increase (p < 0.05) in peak torque values from childhood to adolescence, with the exception of young adolescents vs. older adolescents where no differences were observed. The reciprocal ratios were not affected by age, but improved with an increase in angular velocity with the exception of the CON/ECC ratio that was higher at 30o/s. The data presented in this study provide an extensive isokinetic profile of hip abductor and adductor muscle strength in youth soccer players to assist both coaches and sports medicine professionals in strength monitoring and training.


The value of CT-based radiomics in early assessment of chemotherapeutic effect in patients with advanced lung adenocarcinoma: a preliminary study.
Computed tomography (CT) is the preferred method for evaluating the therapeutic effect of lung cancer. Radiomics parameters can provide a lot of supplementary information for clinical diagnosis and treatment. To investigate the value of radiomics features of CT imaging to predict and evaluate the early efficacy of chemotherapy in patients with advanced lung adenocarcinoma. A total of 101 patients with advanced lung adenocarcinoma were enrolled. Patients were classified into a response group and non-response group according to RECIST 1.1 standard. All patients underwent chest CT examination before and after two cycles of chemotherapy. A total of 293 radiomics features were calculated. The features between response group and non-response group were compared before and after chemotherapy. The diagnostic efficacy was evaluated using the receiver operating characteristic curve. The six pre-chemotherapy radiomics features were selected, with area under the curve (AUC), sensitivity, and specificity at 0.720, 68.3%, and 69.0% in the training group and 0.573, 50.0%, and 76.9% in the test group, respectively. The eleven post-chemotherapy radiomics features were selected, with AUC, sensitivity, specificity at 0.789, 75.6%, and 75.9% in the training group and 0.718, 61.1%, and 76.9% in the test group, respectively. The prognostic value of △f8, △f16, %f8, and %f16 were higher than the other features with AUCs of 0.787, 0.837, 0.763, and 0.877, respectively. Radiomics is expected to provide more valuable information for evaluating the chemotherapy efficacy of lung adenocarcinoma.


A decision support system for assisting fine needle aspiration diagnosis of thyroid malignancy.
To assist diagnosis of thyroid malignancy, implementing a decision support system (DSS) using fine needle aspiration biopsy (FNAB) data. The set of 2,035 thyroid smears contained 1,886 smears of nonmalignancy (class 1) and 150 smears of malignancy (class 2) verified histologically. For each smear, 67 medical features were considered by the expert, forming 2,036 feature vectors, which were fed into a DSS for discriminating between malignant and nonmalignant smears. The DSS comprised a feature selection and classification module using a combination of three classifiers, the artificial neural network, the support vector machines, and the k-nearest neighbor, under the majority vote procedure. The overall classification accuracy of the DSS was 98.6%, marginally better than the FNAB (97.3%). The DSS had lower sensitivity (89.1%) and better specificity (99.4%) compared to the FNAB. Regarding the smears characterized as "suspicious" by FNAB, a significant improvement of overall accuracy was obtained by the proposed DSS system (84.6%) compared to the FNAB (50.0%). The proposed DSS provides significant improvement compared to FNAB regarding discrimination of smears characterized by an expert as "suspicious," reducing the number of patients undergoing surgical procedures.


[Anti-mitochondrial M2 antibody-positive myositis preceded by heart failure and cardiac conduction disturbance. A case report].
A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.


i-Motif formation and spontaneous deletions in human cells.
Concatemers of d(TCCC) that were first detected through their association with deletions at the RACK7 locus, are widespread throughout the human genome. Circular dichroism spectra show that d(GGGA)n sequences form G-quadruplexes when n > 3, while i-motif structures form at d(TCCC)n sequences at neutral pH when n ≥ 7 in vitro. In the PC3 cell line, deletions are observed only when the d(TCCC)n variant is long enough to form significant levels of unresolved i-motif structure at neutral pH. The presence of an unresolved i-motif at a representative d(TCCC)n element at RACK7 was suggested by experiments showing that that the region containing the d(TCCC)9 element was susceptible to bisulfite attack in native DNA and that d(TCCC)9 oligo formed an i-motif structure at neutral pH. This in turn suggested that that the i-motif present at this site in native DNA must be susceptible to bisulfite mediated deamination even though it is a closed structure. Bisulfite deamination of the i-motif structure in the model oligodeoxynucleotide was confirmed using mass spectrometry analysis. We conclude that while G-quadruplex formation may contribute to spontaneous mutation at these sites, deletions actually require the potential for i-motif to form and remain unresolved at neutral pH.


Left ventricular volume, mass, and function following surgical correction of chronic aortic regurgitation.
Following surgical correction of chronic aortic regurgitation, left ventricular (LV) volume falls to normal or near normal in most patients; this change generally occurs within the first week after surgery. During the ensuing six months, a significant regression of LV hypertrophy occurs, but most patients do not achieve a normal LV mass. The systolic ejection fraction may increase while the LV end-diastolic pressure almost uniformly falls to normal. Postoperative studies of LV volume mass and function should be aimed at identifying those patients which do not undergo these favorable changes so that medical therapy can be directed at this high risk group.


SCFAs: The Enigma of Weak Electrolyte Transport in the Colon.
Short-chain fatty acids are the predominant luminal anions in the colon (>75 mM) and thus create a rather unique environment for transporting epithelium. The colon absorbs short-chain fatty acids, either by diffusion of the protonated species across the apical membrane or by an anion exchange process with bicarbonate. Additionally, short-chain fatty acids modulate Na absorption, Cl secretion, intracellular pH, and cell volume.


Direct Iterative Reconstruction of Computed Tomography Trajectories Reconstruction from limited number of projections with DIRECTT.
X-ray computed tomography has many applications in materials science and non-destructive testing. While the standard filtered back-projection reconstruction of the radiographic datasets is fast and simple, it typically fails in returning accurate results from missing or inconsistent projections. Among the alternative techniques that have been proposed to handle such data is the Direct Iterative REconstruction of Computed Tomography Trajectories (DIRECTT) algorithm. We describe a new approach to the algorithm, which significantly decreases the computational time while achieving a better reconstruction quality than that of other established algorithms.


Correlation of tacrolimus levels in peripheral blood mononuclear cells with histological staging of rejection after liver transplantation: preliminary results of a prospective study.
Therapeutic drug monitoring of tacrolimus (TAC) is characterized by a complex relationship between trough blood TAC concentrations and therapeutic efficacy. This prospective study evaluates the predictive value of intrahepatic, peripheral blood mononuclear cells (PBMCs) and blood TAC concentrations during the early postliver transplantation (LT) period. In a cohort of 90 adult liver recipients under TAC-based monotherapy, liver biopsies were performed at day 7 post-LT, and PBMCs TAC concentrations were measured at day 1, 3, 5, and 7 post-LT. Both intrahepatic and PBMCs TAC concentrations were determined. All biopsies were graded following the Banff scoring. Intrahepatic, and day 3, 5, 7 PBMCs concentrations correlated very well with day 7 liver Banff rejection scores (P < 0.05). Clinical rejection was characterized by significantly lower mean TAC PBMCs concentrations at day 5 and 7 (P < 0.05) and tended to be associated to lower mean intrahepatic TAC concentrations at day 7 (P = 0.059). Intrahepatic TAC concentrations at day 7 significantly correlated with TAC PBMCs concentrations from day 5 post-LT (P < 0.05). TAC PBMCs concentrations might be reliable markers of immunosuppression efficacy during the early phase after LT. This finding could represent an additional tool to individualize more precisely early immunosuppressive schemes after liver transplantation.


Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component.
To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.


Cryptosporidium and Giardia in dam water on sheep farms - An important source of transmission?
Cryptosporidium and Giardia infections can negatively impact livestock health and reduce productivity, and some species and genotypes infecting livestock have zoonotic potential. Infection occurs via the faecal-oral route. Waterborne infections are a recognised source of infection for humans, but the role of livestock drinking water as a source of infection in livestock has not been described. This study aimed to determine whether contaminated drinking water supplies, such as farm dams, are a likely transmission source for Cryptosporidium and Giardia infections for extensively managed sheep. Dam water samples (n = 47) were collected during autumn, winter and spring from 12 farm dams located on six different farms in south west Western Australia, and faecal samples (n = 349) were collected from sheep with access to these dams. All samples were initially screened for Cryptosporidium spp. at the 18S locus and Giardia spp. at the gdh gene using qPCR, and oocyst numbers were determined directly from the qPCR data using DNA standards calibrated by droplet digital PCR. Cryptosporidium-positive sheep faecal samples were typed and subtyped by sequence analysis of 18S and gp60 loci, respectively. Giardia-specific PCR and Sanger sequencing targeting tpi and gdh loci were performed on Giardia- positive sheep faecal samples to characterise Giardia duodenalis assemblages. To identify Cryptosporidium and Giardia spp. in dam water samples, next-generation sequencing analysis of 18S and gdh amplicons were performed, respectively. Two species of Cryptosporidium (Cryptosporidium xiaoi and Cryptospordium ubiquitum (subtype family XIIa)) were detected in 38/345 sheep faecal samples, and in water from 9/12 farm dams during the study period, with C. xiaoi the species most frequently detected in both faeces and dam water overall. Giardia duodenalis assemblages AI, AII and E were detected in 36/348 faecal samples and water from 10/12 farm dams. For dam water samples where oo/cysts were detected by qPCR, Cryptosporidium oocyst concentration ranged from 518-2429 oocysts/L (n = 14), and Giardia cyst concentration ranged from 102 to 1077 cysts/L (n = 17). Cryptosporidium and Giardia with zoonotic potential were detected in farm dam water, including C. ubiquitum, C. hominis, C. parvum, C. cuniculus, C. xiaoi, and G. duodenalis assemblages A, B and E. The findings suggest that dam water can be contaminated with Cryptosporidium species and G. duodenalis assemblages that may infect sheep and with zoonotic potential, and farm dam water may represent one source of transmission for infections.


National Trends in the Repair of Isolated Superior Labral Tear from Anterior to Posterior in Korea.
The optimal treatment for superior labral tear from anterior to posterior (SLAP) lesions is controversial. Thus, we aimed to investigate the national surgical trends in isolated SLAP repair in Korea. We analyzed a nationwide database from the Korean Health Insurance Review and Assessment Service from 2008 to 2017. We investigated the trends in SLAP repair by time, sex, age, and the type of health care institution. From 2008 to 2017, 27,850 isolated SLAP repairs were identified. Age-adjusted incidence rate of isolated SLAP repair increased by 692% from 1.07/100,000 in 2008 to 8.48/100,000 in 2012 (P = 0.005). However, the incidence rate declined significantly after 2012 (P = 0.032) and was 5.28/100,000 in 2017. Sex-specific incidence rate of isolated SLAP repair was 2.3 times higher in men than in women. The decline since 2012 was most evident in patients aged ≥ 40 years (P = 0.01); however, the incidence rates of isolated SLAP repair during the study period were similar between patients aged ≥ 40 years and those aged < 40 years. Moreover, hospitals with 30-100 beds had the greatest change in the number of isolated SLAP repair cases. In Korea, the incidence of isolated SLAP repair increased dramatically until 2012; since then, it has declined. Although the decrease in isolated SLAP repair later in the study was evident in those aged ≥ 40 years, the incidence rate was still relatively high in patients aged ≥ 40 years.