Estimate of the cost of multiple sclerosis in Spain by literature review.
Multiple Sclerosis (MS) is a progressive disease leading to increasing disability and costs. A literature review was carried out to identify MS costs and to estimate its economic burden in Spain. Areas Covered: The public electronic databases PubMed, ScienceDirect and IBECS were consulted and a manual review of communications presented at related congresses was carried out. A total of 225 references were obtained, of which 43 were finally included in the study. Expert Commentary: Three major cost groups were identified: direct healthcare costs, direct non-healthcare costs and indirect costs. There is a direct relationship between disease progression and increased costs, mainly direct non-healthcare costs (greater need for informal care) and indirect costs (greater loss of productivity). The total cost associated with MS in Spain is €1,395 million per year, and that the mean annual cost per patient is €30,050. Beyond costs, a large impact on the quality of life of patients, with an annual loss of up to 13,000 quality-adjusted life years was also estimated. MS has a large economic impact on Spanish society and a significant impact on the quality of life of patients.


What Is Being Done to Increase Organ Donation?
The need for organs greatly outnumbers the amount of organs donated for transplantation. This is true for all countries around the world. Many organizations globally have been created to solve this problem. Spain has been very successful with its drive to increase organ donation. Educational campaigns are a great tool being utilized by all countries and the medical communities to promote a positive perception of organ donation. These campaigns include using the television industry, raising money for travel expenses, and education seminars. This article looks at the different groups and programs aimed at increasing organ donation.


Lyme borreliosis awareness.
A Lyme borreliosis information leaflet has been produced to promote awareness amongst the general public. It was designed to provide a framework for similar material throughout Europe and complements a questionnaire produced to measure awareness of Lyme borreliosis. This questionnaire can be used to determine the impact of educational campaigns using material such as the leaflet. Feasibility studies showed that the questionnaire successfully highlighted predictable differences between sample groups and also that the leaflet performed well in increasing knowledge in low-awareness groups.


Palmitic Acid and β-Hydroxybutyrate Induce Inflammatory Responses in Bovine Endometrial Cells by Activating Oxidative Stress-Mediated NF-κB Signaling.
Ketosis is a nutritional metabolic disease in dairy cows, and researches indicated that ketonic cows always accompany reproductive problems. When ketosis occurs, the levels of non-esterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA) in the blood increase significantly. Palmitic acid (PA) is a main component of saturated fatty acids composing NEFA. The aim of this study was to investigate whether high levels of PA and BHBA induce inflammatory responses and regulatory mechanisms in bovine endometrial cells (BEND). Using an enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blotting, we evaluated oxidative stress, pro-inflammatory factors, and the nuclear factor (NF)-κB pathway in cultured BEND cells treated with different concentrations of PA, BHBA, pyrrolidinedithiocarbamate (PDTC, an NF-κB pathway inhibitor), and N-acetylcysteine (NAC, an antioxidant). The content of malondialdehyde was significantly higher, the content of glutathione was lower, and antioxidant activity-glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity-was lower in treated cells compared with control cells. PA- and BHBA-induced oxidative stress activated the NF-κB signaling pathway and upregulated the release of pro-inflammatory factors. Moreover, PA- and BHBA-induced activation of NF-κB-mediated inflammatory responses was inhibited by PDTC and NAC. High concentrations of PA and BHBA induce inflammatory responses in BEND cells by activating oxidative stress-mediated NF-κB signaling.


HSV-1 infection of human corneal epithelial cells: receptor-mediated entry and trends of re-infection.
The human cornea is a primary target for herpes simplex virus-1 (HSV-1) infection. The goals of the study were to determine the cellular modalities of HSV-1 entry into human corneal epithelial (HCE) cells. Specific features of the study included identifying major entry receptors, assessing pH dependency, and determining trends of re-infection. A recombinant HSV-1 virus expressing beta-galactosidase was used to ascertain HSV-1 entry into HCE cells. Viral replication within cells was confirmed using a time point plaque assay. Lysosomotropic agents were used to test for pH dependency of entry. Flow cytometry and immunocytochemistry were used to determine expression of three cellular receptors--nectin-1, herpesvirus entry mediator (HVEM), and paired immunoglobulin-like 2 receptor alpha (PILR-a). The necessity of these receptors for viral entry was tested using antibody-blocking. Finally, trends of re-infection were investigated using viral entry assay and flow cytometry post-primary infection. Cultured HCE cells showed high susceptibility to HSV-1 entry and replication. Entry was demonstrated to be pH dependent as blocking vesicular acidification decreased entry. Entry receptors expressed on the cell membrane include nectin-1, HVEM, and PILR-α. Receptor-specific antibodies blocked entry receptors, reduced viral entry and indicated nectin-1 as the primary receptor used for entry. Cells re-infected with HSV-1 showed a decrease in entry, which was correlated to decreased levels of nectin-1 as demonstrated by flow cytometry. HSV-1 is capable of developing an infection in HCE cells using a pH dependent entry process that involves primarily nectin-1 but also the HVEM and PILR-α receptors. Re-infected cells show decreased levels of entry, correlated with a decreased level of nectin-1 receptor expression.


Proliferative kidney disease in rainbow trout (Oncorhynchus mykiss) under intensive breeding conditions: Pathogenesis and haematological and immune parameters.
Proliferative kidney disease (PKD) is an endoparasitic disease of salmonid fish caused by Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea). This study presents a comprehensive view on PKD development in rainbow trout (Oncorhynchus mykiss) reared at an intensive fish breeding facility, with focus on mortality, pathology/histopathology, haematological findings and immune functions. Diseased and reference fish were sampled monthly and time course of natural infection was followed up from the onset of clinical signs (September 2014) to full recovery (January 2015). PKD- associated cumulative mortality was 30% with a peak value in October, while immunohistochemical testing indicated a continuous significant decrease in T. bryosalmonae numbers from September to December; with no parasites detected in January. During peak clinical infection, a significant decrease in red blood cell counts, haematocrit values, haemoglobin concentration, along with a reduction in lymphocytes and a significant phagocyte elevation corresponding with an increase in phagocyte oxidative burst were measured in comparison to control animals. Complement activity and total immunoglobulin plasma concentrations were also elevated, though only during the initial monitoring period (September). Individuals surviving PKD, recovered and were able to fully regenerate both renal structure and haematopoietic parameters to normal levels. Changes in the red blood cell parameters indicate anaemia and a decreased oxygen transportation capacity during the clinical disease phase. Together with an increased oxygen demand at higher temperatures and decreased oxygen solubility this could lead to decompensation and elevated mortality. The stimulation of immune parameters, and especially oxidative phagocytic burst, is likely to have had a strong effect on both, regeneration and elimination of the pathogenic agent.


[New Method for Stable Expression of SFTS Virus-like Particles in CHO-K1 Cells].
To explore a new method for stable expression of virus-like particles (VLPs) of the severe fever with thrombocytopenia syndrome (SFTS) virus, an expression plasmid for the membrane glycoprotein (GP) and nucleocapsid protein (NP) of the SFTS virus was constructed by fusion of the two proteins via a serine residue, and a yellow fluorescence protein (YFP) gene was introduced into the plasmid as a reporter. CHO-K1 cells were transfected with this plasmid, and stable cell lines constructed using the limited dilution method. Cellular colonies were hand-picked based on YFP with the help of fluorescence microscopy and expanded without selection pressure. Stability of cell lines was evaluated by monitoring of fluctuation of the intensity of YFP for 40 passages. VLP production was characterized using an indirect fluorescence assay, immunoblotting, and electronic microscopy. We showed that GP and NP fusion proteins could be assembled into VLPs in vivo, and that VLPs had similar morphologies to virus particles. Selected cell lines were stable for YFP expression: no significant fluctuation was detected in 40 passages. These data demonstrated the effectiveness of this new method for expression of structural proteins of the SFTS virus and screening for stable cell lines. Our results could provide new concepts for the production of biopharmaceuticals.


Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells.
To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral microangiopathy in diabetic nude mice. Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immunohistopathy. In situ apoptosis was detected by using TdT-mediated dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally delivered to the adductor muscles. Mononuclear cells were also isolated and cultured in vitro for the detection and counting of endothelial progenitor cells(EPC). Rarefication of capillaries and arterioles, enhanced apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice. Prophylactic local delivery of M-PBMNC halted the progression of microvascular rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected the survival, migration and incorporation of transplanted M-PBMNC into the murine vasculature in vivo. In addition, more EPC were available from M-PBMNC than non-mobilized cells. These results suggested that the prophylactic local delivery of M-PBMNC may represent a novel approach for the treatment of microvascular complications in diabetics.


[CEOP regimen in the treatment for non-Hodgkin's lymphoma].
The aim of this study is to analyse the efficacy and toxicity of CEOP regimen in the treatment of non-Hodgkin's lymphoma (NHL). From January 1995 to December 2000, 121 patients with NHL were treated by CEOP regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analysed retrospectively. Of these 121 patients, 83 (68.6%) had B-cell NHL and 38(31.4%) peripheral T or NK-cell NHL; 55. 4% (67/121) had early disease (stage I or II), and 89.3% (108/121) had IPI score 0-2. The median age was 53 years (range: 7-79 yr). All patients were treated by CEOP regimen (totally, 471 cycles) with or without radiotherapy. The overall response (OR) rate in this series was 90.9% (110/121) with a complete remission (CR) rate of 71.9% (87/121); whereas the response rate of chemotherapy alone was 88.4% (107/121) with a CR rate of 67.8% (82/121). Major toxicity consisted of grade III-IV myelosuppression (11.9%), neutropenia (1.9%) and thrombocytopenia and anemia (1.1%). Alopecia was observed in 46.3%. However, cardiotoxicity was mild and reversible. Median follow-up duration in this series was 63 months (range: 2-116 months). The overall 1-, 3- and 5-year survival rate was 84.8%, 62.7% and 55.9%, respectively, with a median survival time of 85 months (2-118 months). Our data show that CEOP regimen combined with or without radiotherapy for the involved field is effective and well tolerated by the patients with non-Hodgkin's lymphoma.


A further study on capillary-like bile ductules proliferation in chronic active hepatitis.
64 cases of chronic active hepatitis (CAH) and 84 cases of non-CAH liver diseases were studied with keratin stain. The capillary-like bile ductules (CLBD) were proliferating and their morphology was identical to that with Type V collagen stain reported before. CLBD proliferation were more marked in CAH than in other liver diseases, and it was considered to be one of the characteristics of CAH and could be used for differential diagnosis. The ultrastructure of CLBD was specific in morphology. The HBV-DNA in CLBD shown by the technique of in situ hybridization suggested that HBV might infect the cells of CLBD.


Ongoing Crestal Bone Loss around Implants Subjected to Computer-Guided Flapless Surgery and Immediate Loading Using the All-on-4® Concept.
The All-on-4(®) concept is widely applied for full-arch rehabilitations, using two tilted and two axially loaded implants in order to overcome anatomical constraints. The aim of this study was to assess the survival and individual success of implants immediately loaded with an All-on-4 full-arch screw-retained prosthetic bridge in fully edentulous mandibles or maxillae over up to 3 years. In total, 20 patients with atrophic jaws (9 maxillae, 11 mandibles) were treated with computer-guided flapless surgery and immediately provided with a provisional bridge. The final prosthesis was delivered after 6 months. In total, 80 TiUnite(™) Brånemark implants were placed. Radiographs were taken after surgery and 1 and 3 years later. A 3-year survival rate of 100% was seen for all implants, both in lower and in upper jaw. None of the temporary or definite prostheses were lost over the follow-up period of 3 years. After 1 year, the mean bone loss was 1.13 mm (SD 0.94; range -0.1 to 3.8), and after 3 years, it was 1.61 mm (SD 1.40; range 0 to 5). The mean bone loss between the 1-year and 3-year follow-ups was 0.48 mm (SD 0.66; range -1.2 to 3.6). This difference was statistically significant (p < .001), indicative of ongoing bone loss. Twenty-six percent of the implants had bone loss above 1.5 mm after 1 year, but after 3 years, 30% of the implants had already lost more than 1.9 mm. The implant and prosthetic survival was 100%, and patients benefited from the All-on-4 treatment. However, unacceptable ongoing bone loss was seen in 49.2% of the patients; this may be a warning sign for future problems and needs clinical attention. Overloading and surgery-related aspects need to be investigated as potential explanations.


Tactical Knowledge, Decision-Making, and Brain Activation Among Volleyball Coaches of Varied Experience.
This study compared decision-making (DM) of experienced and novice volleyball coaches while measuring blood flow brain activation with functional near-infrared spectroscopy. We sampled 34 coaches (mean [ M] age of 32.5, standard deviation [ SD] = 9.4 years) divided into two experience groups: (a) novice ( M = 2.8, SD = 1.9 years) and (b) experienced (M = 19, SD = 7.2 years). We evaluated coaches' DM through their responses to video-based scenarios of attacks performed in the extremities of the net within the Declarative Tactical Knowledge Test in Volleyball. We found no significant DM differences between the two groups of coaches ( p = .063), though novice (vs. experienced) coaches showed greater blood flow of the prefrontal cortex when visualizing the game situations. While experienced coaches may have better prefrontal neural efficiency during DM in these situations, further research is needed to evaluate other cerebral areas; since blood flow is an indirect measure of neural efficiency, and activity in remaining cortical components was unknown in this study.


Highly efficient deep-blue phosphorescence from heptafluoropropyl-substituted iridium complexes.
New deep-blue iridium complexes, consisting of a heptafluoropropyl (HFP) substituent at the 3' position of 2',4''-difluorophenyl, have a deep HOMO level and decreased shoulder electronic transition and inhibit self-quenching due to the sterically hindered group without conjugation. An OLED using (HFP)2Ir(mpic) exhibited a maximum EQE of 21.4% with a CIE of (0.146, 0.165).


Intracytoplasmic collagen fibers observed in cartilage of the pathological conditions.
The young male rabbit ear cartilage after intravenous injection of chymopapain was studied by electron microscope. Fibrous long spacing (FLS)-like fibers were observed in the cytoplasm of the cartilage cells. These fibers were then compared with segment long spacing (SLS) fibers within the golgi vacuoles in the secondary well differentiated chondrosarcoma cells. These collagen fiber formation do not represent a normal collagen fiber formation, but it may be possible that the tropocollagen molecules are aggregated in the golgi vacuoles in a manner characteristic to FLS or SLS fiber by the close relationship with lysosome.


The associations among co-morbidity, cardiac geometries and mechanics in hospitalized heart failure with or without preserved ejection fraction.
The associations among chronic health conditions, ventricular geometric alterations or cardiac contractile mechanics in different phenotypes heart failure (HF) remain largely unexplored. We studied 438 consecutive hospitalized patients (mean age: 64.9 ± 16.6 years, 52.5% female) with or without clinical evidence of HF. We examined the associations among clinical co-morbidities, LV geometries and systolic mechanics in terms of global myocardial strains. Increasing clinical co-morbidities was associated with greater LV mass, worse longitudinal deformations and higher proportion of admission with HF diagnosis, which was more pronounced in HFpEF (from 6.4% to 40.7%, X2 < 0.001). The independent association between co-morbidity burden and longitudinal functional decay remained unchanged after adjusting for age and sex for all admissions and in HFpEF (Coef: 0.82 & 0.71, SE: 0.13 & 0.21, both p≤0.001). By using co-morbidity scores, the area under receiver operating characteristic curves (AUROC) in identifying HFpEF was 0.71 (95% CI: 0.65 to 0.77), 0.64 (95% CI: 0.58 to 0.71) for HFrEF and 0.72 for both (95% CI: 0.67 to 0.77). Co-morbidity burden superimposed on LV mass index and LV filling pressure (E/E') further expanded the AUROC significantly in diagnosing both types HF (c-statistics from 0.73 to 0.81, p for ΔAUROC: 0.0012). Chronic health conditions in the admission population were associated with unfavorable cardiac remodeling, impair cardiac contractile mechanics and further added significantly incremental value in HF diagnosis. Our data suggested the potentiality for better cardiac function by controlling baseline co-morbidities in hospitalized HF patients, especially HFpEF. CAD: coronary artery disease; CKD: chronic kidney disease; DT: deceleration time; eGFR: Estimated glomerular filtration rate; HF: heart failure; IVRT: iso-volumic relaxation time; LV: left ventricular; LVEF: left ventricular ejection fraction; RWT: relative wall thickness; TDI: Tissue Doppler imaging.


Connecting care for life.
Connecting care was one of the four reform themes that emerged during the deliberations of the National Health and Hospital Reform Commission (NHH RC). The 10 commissioners argued that the health care system needed to move to a model where people received or could access 'comprehensive care over all their lifetime'. Forty-one of the 123 recommendations (33%) are grouped under this theme, underlining the importance of developing pragmatic and workable solutions. The disjointed nature of the health care system is well known and a cause of much inefficiency and frustration. During the NHH RC consultations, consumers constantly emphasised the need for someone to help them 'navigate' through our complex system.


The influence of intra-arterial infusion of cisplatinum and bleomycin on the cell cycle in uterine cervical carcinoma.
We examine the influence of CDDP and BLM on the cell cycle in the patients with uterine cervical cancer. Specimens were obtained from 8 cases of local recurrent uterine cervical cancer which were treated with CDDP and BLM bolus infusions into bilateral internal iliac arteries. Except for two patients who showed no response according to the criteria of the National Cancer Institute (NCI), the other patients exhibited partial response (PR). The concentrations of BLM and CDDP were 0.83 +/- 0.05 microgram/g and 2.9 +/- 0.54 microgram/g in the tumor tissues 24 hours after treatment. The peak values of the drug concentrations in serum, which were observed at 30 min for both drugs, were 0.92 +/- 0.12 microgram/ml BLM and 1.02 +/- 0.65 microgram/ml CDDP and the concentrations of the drugs decreased rapidly in the serum. The higher levels of CDDP and BLM were retained in the tumor tissue 24 hours after treatment, than in serum. Changes in DNA content determined by flow cytometry, revealed that proliferation indices (PI) increased after treatment only in PR cases. The mean increase in the ratio was 0.10 +/- 0.015. The BrdU staining showed that cells in S phase increased in tumor tissues. Labeling indices increased from 0.10 +/- 0.04 to 0.18 +/- 0.05. These results suggested that cell synchronization was induced by CDDP and BLM in vivo. PI seemed a useful parameter for measuring drug sensitivity.


Endothelial dysfunction, distensibility and intima-media thickness and aetiology of stroke.
This study measured carotid artery distensibility, intima-media thickness (IMT) and flow-mediated dilatation (FMD) in patients with ischaemic stroke and evaluated if there was a relationship between these measurements and the presence of atrial fibrillation. Distensibility and IMT were measured in 89 patients with ischaemic stroke using ultrasonography; 44 patients had atrial fibrillation. Distensibility was determined using the Reneman equation. FMD was measured in a second group of 52 patients with ischaemic stroke; 20 patients had atrial fibrillation. Patients with atrial fibrillation had lower IMT values compared with patients without atrial fibrillation (0.67 versus 0.79 mm, respectively). Distensibility increased in patients with atrial fibrillation compared with patients without atrial fibrillation (0.19 versus 0.10 mm/100 mmHg, respectively). Patients with atrial fibrillation had significantly better FMD results than patients without atrial fibrillation (5.7% versus 3.2%, respectively). Measuring distensibility, IMT and FMD might be helpful in differentiating between stroke of embolic and thrombotic aetiology.


Late-passage SC-1 cells resistant to N- and B-tropic viruses but sensitive to NB-tropic viruses.
A late-passage derivative of SC-1 cells with stable relative resistance to N- and B-tropic viruses but with retained sensitivity to NB-tropic viruses has been identified. Dual resistance was seen with the XC plaque assay, as well as reverse transcriptase assay and radioimmunoassay for viral p30. Evidence was found for resistance in clonal derivatives. These findings suggest a possible instability in determinants of cellular resistance to endogenous retroviruses and may be useful in further analysis of resistance to retrovirus infection.


Clinical tolerance, parasitological efficacy and environmental effects of dehumidifiers in stable asthmatics sensitized to house dust mites.
Dehumidifiers (DH) are potentially effective appliances as coadjuvant therapy in the treatment of bronchial asthma caused by sensitization to house dust mites. The aims of this study were to analyze DH tolerance in asthmatic patients, to assess the parasitological effects and to analyze the environmental effects produced by the use of these appliances in the bedrooms of asthmatic patients sensitized to house dust mites. 10 stable asthmatic patients sensitized to house dust mites were studied. DH appliances (CD-300) were installed in their bedrooms. Each patient was given symptom scoring tables and a portable peak expiratory flow (P.E.F.) during a period of 5 months, 1 month before installing the DH and 4 months afterwards. To study the parasitological efficacy of the DHs, we analyzed dust samples from the bedrooms and determined the Der p I, Der f I and Der II allergens by means of a modified ELISA based on monoclonal antibodies. Dust samples were collected before installing the DHs and after they had been working for 2 and 4 months. Dry temperature and relative humidity measurements at three time intervals (7-9, 15-17 and 22-24 h) were carried out. The 1st measurement was done prior to installation of the DHs in the patients' bedrooms and the 2nd and 3rd were achieved 2 and 4 months respectively after the installation. Statistical analysis was done by comparison of paired means. No significant differences were detected in the patients' symptoms nor in the P.E.F. measurements in the course of the study. Decreases in the house dust mite allergens were observed in 4 bedrooms. A significant decrease in relative humidity in the bedrooms of mite asthma patients after use of dehumidifier appliances was observed (p < 0.01). Significant differences between the measurements of the bedrooms with and without DH were detected (p < 0.01). In summary, DHs were well tolerated by stable asthmatic patients, produced a significant decrease in the relative humidity level and showed some parasitological efficacy.


Ameliorative effect of vitamin C on chronic chlorpyrifos-induced erythrocyte osmotic fragility in Wistar rats.
Chronic exposure to chlorpyrifos (CPF) has been shown to cause increased lipoperoxidative changes in the erythrocyte membranes. The relationship between chronic CPF-induced lipoperoxidative changes and erythrocyte fragility has not been elucidated. The aim of the present study is to evaluate the role of lipoperoxidation on CPF-induced erythrocyte fragility and the ameliorative effect of vitamin C. Twenty animals divided at random into four groups of five animals each served as subject for this study. Rats in group I served as the control group and were given only soya oil at a dose of 2 mL/kg body weight (b.w.). Rats in group II were dosed with vitamin C (100 mg/kg b.w.) and then supplemented with soya oil (2 mL/kg b.w.), while those in group III were administered with CPF only at a dose of 10.6 mg/kg b.w. (~one-eighth of the previously determined median lethal dose [LD(50)]). Rats in group IV were pretreated with 100 mg/kg b.w. of vitamin C, and then dosed with CPF at a dose of 10.6 mg/kg b.w., 30 min later. The different treatment regimens were orally administered daily for a period of 17 weeks. Blood collected from the animals at the end of the test period were analyzed for erythrocyte osmotic fragility and malonaldehyde (MDA) concentration as an index of lipid peroxidation. The study showed that CPF caused significant increase in erythrocyte fragility and MDA concentration, which were ameliorated by pretreatment with vitamin C. In conclusion, the study showed that CPF-evoked erythrocyte fragility due to increased lipoperoxidative changes was ameliorated by pretreatment with vitamin C.


A simplified method for determining regurgitant fraction by Doppler echocardiography in patients with aortic regurgitation.
This study attempted to develop and validate a simple method for calculating aortic regurgitant fraction by use of pulsed wave Doppler echocardiography. Although several investigators have been able to determine aortic regurgitant fraction by Doppler echocardiography, the methods used require accurate determination of the cross-sectional areas of intracardiac sites at which the volumetric flow is calculated. Our concept was based on a constant relation that exists between the cross-sectional area of the left ventricular outflow tract and the mitral valve annulus in normal subjects. To verify this, we used Doppler echocardiography to measure the flow velocity integral of the left ventricular outflow tract and the mitral annulus in the apical view in 50 normal subjects (32 men, 18 women, mean age 34 years). Close correlation (r = 0.95) was observed between the flow velocity integral (FVI) of the outflow tract (OT) and that of the mitral annulus (MA): FVIMA/FVIOT = 0.77. Because mitral flow equals aortic flow in normal subjects, the ratio of the cross-sectional area of the mitral annulus to that of the outflow tract was 1/0.77. In patients with aortic regurgitation, the regurgitant fraction (RF) = (Aortic flow-Mitral flow)/Aortic flow = 1-Mitral flow/Aortic flow. Substituting 0.77 for the area component of flow, RF = 1-(1/0.77).(FVIMA/FVIOT). To evaluate the accuracy of this method, we compared the regurgitant fraction derived by Doppler echocardiography with that from catheterization findings in 20 patients with aortic regurgitation (an isolated lesion was found in 14). The regurgitant fraction by catheterization was the difference between total (angiographic) and forward (thermodilution) stroke volumes as a percent of total flow. Good correlation was observed between catheterization and Doppler regurgitant fraction (r = 0.88, SEE 9%, p < 0.01). Thus, regurgitant fraction can be estimated from Doppler echocardiography in patients with aortic regurgitation by a method that requires only measurements of the flow velocity integral from the mitral annulus and left ventricular outflow tract.


Adherence of oral streptococci to keratinized and nonkeratinized human oral epithelial cells.
The ability of Streptococcus mutans, Streptococcus sanguis, Streptococcus mitis, and Streptococcus salivarius to adhere to keratinized versus nonkeratinized human oral epithelial cells was compared. S. mitis and S. salivarius exhibited significantly greater adherence to keratinized cells than to nonkeratinized cells. S. mutans and S. sanguis adhered equally well to either epithelial cell type. It is concluded that keratinization of epithelial cells may be a significant factor in the adherence of certain oral streptococci to the oral mucosa.


[Survey of physical activity and doping in a sample of 6,915 students aged 14-18 years].
Promoting physical activity is one of the main goals of health-promotion policies. The period of adolescence is characterised by a high rate of abandonment of any physical activity. In this age range, moreover, the risk of assuming substances in order to improve muscular-mass or athletic results is concrete. This study quantifies the involvement in physical activities and substance assumption in a sample of 6915 students aged 14 to 18 years and living in 7 different areas, mostly in northern Italy. The survey's tool is an adapted and modified vision of the Youth Risk Behaviour Surveillance questionnaire, created by US Centers for Disease Control and Prevention (CDC). The study showed a high percentage of the sample not involved in any form of physical activity out of school (33.8%), more among girls (44.1%) than boys (21.2%). Between 14 and 18 years, a continuous reduction of involvement in physical activity is evident, while the percentage of totally physically inactive subjects rises from 30.1% to 43%. Finally, 5.6% in our sample admitted to have been using substances to improve muscular-mass or athletic results at least once in the past. According to this study, only a minority of the interviewed adolescents is involved in a regular physical activity. In males, using substances to improve physical strength showed to be rather diffused. Specific health promotion projects are suggested.


Automating Individualized Formative Feedback in Large Classes Based on a Directed Concept Graph.
Student learning outcomes within courses form the basis for course completion and time-to-graduation statistics, which are of great importance in education, particularly higher education. Budget pressures have led to large classes in which student-to-instructor interaction is very limited. Most of the current efforts to improve student progress in large classes, such as "learning analytics," (LA) focus on the aspects of student behavior that are found in the logs of Learning Management Systems (LMS), for example, frequency of signing in, time spent on each page, and grades. These are important, but are distant from providing help to the student making insufficient progress in a course. We describe a computer analytical methodology which includes a dissection of the concepts in the course, expressed as a directed graph, that are applied to test questions, and uses performance on these questions to provide formative feedback to each student in any course format: face-to-face, blended, flipped, or online. Each student receives individualized assistance in a scalable and affordable manner. It works with any class delivery technology, textbook, and learning management system.


Fluid Elasticity-Enhanced Insulator-Based Dielectrophoresis for Sheath-Free Particle Focusing in Very Dilute Polymer Solutions.
Focusing particles into a narrow stream is usually a necessary step in microfluidic flow cytometry and particle sorting. We demonstrate that the addition of a small amount of poly(ethylene oxide) (PEO) polymer into a buffer solution can reduce by almost 1 order of magnitude the threshold DC electric field for single-line dielectrophoretic focusing of particles in a constricted microchannel. The particle focusing effectiveness of this fluid elasticity-enhanced insulator-based dielectrophoresis (E-iDEP) in very dilute PEO solutions gets enhanced with the increase of the PEO molecular weight and particle size. These two trends are consistent with a theoretical analysis that accounts for the fluid elasticity effects on the electrokinetic and dielectrophoretic particle motions. Surprisingly, the particle-focusing effectiveness of E-iDEP is observed to first increase and then decrease with an increase in the PEO concentration.


Epigenetic regulation of cardiac myocyte differentiation.
Cardiac myocytes (CMs) proliferate robustly during fetal life but withdraw permanently from the cell cycle soon after birth and undergo terminal differentiation. This cell cycle exit is associated with the upregulation of a host of adult cardiac-specific genes. The vast majority of adult CMs (ACMs) do not reenter cell cycle even if subjected to mitogenic stimuli. The basis for this irreversible cell cycle exit is related to the stable silencing of cell cycle genes specifically involved in the progression of G2/M transition and cytokinesis. Studies have begun to clarify the molecular basis for this stable gene repression and have identified epigenetic and chromatin structural changes in this process. In this review, we summarize the current understanding of epigenetic regulation of CM cell cycle and cardiac-specific gene expression with a focus on histone modifications and the role of retinoblastoma family members.


Follow-up Analysis of Serum TNF-Related Apoptosis-Inducing Ligand Protein and mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Ischemic Stroke.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which is TNF receptor superfamily member, contributes to several diseases pathogenesis. The aim of this research was to investigate the relevance of serum TRAIL protein levels and mRNA expression in peripheral blood mononuclear cells (PBMC) of patients with stroke through 6 months follow-up. We enrolled patients with first-ever acute ischemic stroke (n = 95) and healthy controls (n = 95) in this study. Follow-up blood samples were collected from patients at day 7, 28, and 180 after the onset. The stroke severity was evaluated by National Institutes of Health Stroke Scale score. TRAIL protein levels were quantified by using ELISA kits and TRAIL mRNA expression by quantitative real-time PCR. Our study showed that stroke patients have statistically significant lower levels of serum TRAIL protein (p < 0.0001) and elevated TRAIL mRNA expression (p < 0.0001) in PBMC at the disease onset. Our follow-up study revealed that TRAIL protein levels were increased while mRNA expression levels were downregulated in later periods. Overall, our findings suggest that serum TRAIL levels and mRNA expression in PBMC could reliably serve as a predictor of stroke outcome. Additionally, our study supports that TRAIL plays a role in pathogenesis and progression of ischemic stroke.


Multiple cutaneous granular cell tumors: a case report and review of the literature.
Granular cell tumors are benign neoplasms derived from Schwann cells. Their clinical presentation ranges from large verrucose nodules, as in our patient, to small, nonspecific, subcutaneous papules. Approximately half of granular cell tumors develop in the head-and-neck region, most commonly on the tongue. Multiple granular cell tumors are not a sign of malignancy and may be more common than generally reported.


Cytokine production and DNA synthesis by human peripheral lymphocytes in response to palmitic, stearic, oleic, and linoleic acid.
Effects of palmitic, stearic, oleic, and linoleic acid on mitogen-induced DNA synthesis, on production of IL-1 beta, IL-2, IFN-gamma, and TNF-alpha, and on IL-2R expression were determined in human peripheral lymphocytes. Free fatty acids (FFA) were added over a wide range of concentrations to cells cultured under serum free conditions with fatty acid free albumin. DNA synthesis was stimulated by low and inhibited by high FFA concentrations. Physiological concentrations were stimulatory, except for linoleic acid. Cytokine production became affected by all FFA tested. Palmitic acid enhanced the release of IFN-gamma at concentrations that diminished TNF-alpha production. Saturated fatty acids were significantly more potent than unsaturated fatty acids in affecting cytokine production. IFN-gamma secretion was significantly more stimulated or inhibited by the various FFA compared with the other cytokines. IL-2R expression correlated with the production of IL-2. When tested in combination, stimulatory as well as inhibitory effects of the individual FFA became attenuated. It is suggested that palmitic, stearic, oleic, and linoleic acid are physiological regulators of DNA synthesis and cytokine release in human peripheral lymphocytes. Modulation of FFA ratios may be an effective means for the fine tuning of the immune system. As secretory mechanisms of cytokines appear to exhibit substrate specificity for FFA, the release of individual cytokines may be selectively influenced by FFA.


C. elegans sirtuin SIR-2.4 and its mammalian homolog SIRT6 in stress response.
Stress is a significant life event. The immediate response to stress is critical for survival. In organisms ranging from the unicellular Saccharomyces cerevisiae to protozoa (Trypanosoma brucei) and metazoan (such as Caenorhabditis elegans, Homo sapiens) stress response leads to the formation of cytoplasmic RNA-protein complexes referred to as stress granules (SGs). SGs regulate cell survival during stress by the sequestration of the signaling molecules implicated in apoptosis. They are a transient place of messenger ribonucleoproteins (mRNPs) remodeling for storage, degradation, or reinitiation of translation during stress and recovery from stress. Recently, we have identified chromatin factor, the sirtuin C. elegans SIR-2.4 variant and its mammalian homolog SIRT6 as a regulator of SGs formation. SIRT6 is highly conserved NAD(+)-dependent lysine deacetylase and ADP-ribosyltransferase impacting longevity, metabolism, and cancer. We observed that the cellular formation of SGs by SIRT6 or SIR-2.4 was linked with the cell viability or C. elegans survival and was dependent on SIRT6 enzymatic activity. Here, we discuss how SIR-2.4/SIRT6 influences SGs formation and stress response. We suggest possible mechanisms for such an unanticipated function of a chromatin regulatory factor SIRT6 in assembly of stress granules and cellular stress resistance.


Are trends in billing for high-intensity emergency care explained by changes in services provided in the emergency department? An observational study among US Medicare beneficiaries.
There has been concern that an increase in billing for high-intensity emergency care is due to changes in coding practices facilitated by electronic health records. We sought to characterise the trends in billing for high-intensity emergency care among Medicare beneficiaries and to examine the degree to which trends in high-intensity billing are explained by changes in patient characteristics and services provided in the emergency department (ED). Observational study using traditional Medicare claims to identify ED visits at non-federal acute care hospitals for elderly beneficiaries in 2006, 2009 and 2012. Billing intensity was defined by emergency physician evaluation and management (E&M) codes. We tested for overall trends in high-intensity billing (E&M codes 99285, 99291 and 99292) and in services provided over time using linear regression models, adjusting for patient characteristics. Additionally, we tested for time trends in rates of admission to the hospital and to the intensive care unit (ICU). Next, we classified outpatient visits into 39 diagnosis categories and analysed the change in proportion of high-intensity visits versus the change in number of services. Finally, we quantified the extent to which trends in high-intensity billing are explained by changes in patient demographics and services provided in the ED using multivariable modelling. High-intensity visits grew from 45.8% of 671 103 visits in 2006 to 57.8% of 629 010 visits in 2012 (2.0% absolute increase per year; 95% CI 1.97% to 2.03%) as did the mean number of services provided for admitted (1.28 to 1.41; +0.02 increase in procedures per year; 95% CI 0.018 to 0.021) and discharged ED patients (7.1 to 8.6; +0.25 increase in services per year; 95% CI 0.245 to 0.255). There was a reduction in hospital admission rate from 40.1% to 35.9% (-0.68% per year; 95% CI -0.71% to -0.65%; P<0.001), while the ICU rate of admission rose from 11.7% to 12.3% (+0.11% per year; 95% CI 0.09% to 0.12%; P<0.001). When we stratified by diagnosis category, there was a moderate correlation between change in visits billed as high intensity and the change in mean number of services provided per visit (r=0.38; 95% CI 0.07 to 0.63). Trends in patient characteristics and services provided accounted moderately for the trend in practice intensity for outpatient visits (pseudo R2 of 0.47) but very little for inpatient visits (0.051) and visits overall (0.148). Increases in services provided in the ED moderately account for the trends in billing for high-intensity emergency care for outpatient visits.


Effects of maxillary protraction for early correction of class III malocclusion.
This prospective study investigated the skeletal, dental, and soft-tissue effects of a mini maxillary protractor appliance in class III subjects with maxillary retrusion and mandibular protrusion and compared these changes with those of untreated, well matched control sample with normal occlusions. Twenty patients with class III malocclusion (mean age 11.1 ± 0.8 years) and 20 subjects with normal occlusion (mean age 10.9 ± 0.4 years) were included to this study. The class III subjects were treated with the mini maxillary protractor appliance, and the others were used as control subjects. Paired t-test and Student's t-test were used to determine the within- and between-group differences, respectively. In the study group, the maxilla moved forward (SNA, 2.0 degrees and A-Y, 2.4mm) (P < 0.001) with a slight rotation of palatal and occlusal planes (SN-PP, -0.8 degree and SN-OP, -0.7 degree) (P > 0.05). The mandible displaced backwards and downwards (SNB, -1.1 degrees; SND, -0.9 degree; B-Y, -0.9 mm and Pog-Y, -0.3mm; P < 0.001). These movements in the maxilla and mandible caused a significant improvement in intermaxillary sagittal relationship (ANB, 3.0 degrees; Convexity, 6.3 degrees; Wits, 4.6mm; P < 0.001). The maxillary incisors moved forward (2.2 degrees) while the mandibular ones backward (-1.9 degrees). The improvement in overjet was 5.0mm, and 66.1 per cent of this change (3.3mm) was skeletal (A-Y; 2.4mm and B-Y; -0.9 mm), and the remaining (1.7 mm) dentoalveolar (U1-NA; 0.9 mm and L1-NB; -0.8mm). The change in Ls-E measurement was more in the study group (2.1mm), and the difference between the groups was statistically significant (P < 0.001).


[Prenatal diagnosis of a case of Pallister-Killian syndrome].
To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.


Optimizing the fluidized bed bioreactor as an external bioartificial liver.
Our team previously designed and validated a new bioartificial liver (BAL) called Suppliver based on a Prismaflex™ device, including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes. To ensure correct fluidization within the bioreactor, the beads need to become heavier with the addition of inert glass microspheres. In this study, we assessed the impact of this additional component on the bead production process, bed fluidization, mass transfer and the mechanical properties of the beads, as well as cell viability and basic metabolic function. A concentration of 20 mg (1% v/v) of microspheres for 15-20 million cells per milliliter of alginate solution appears to be the best configuration. The filling ratio for the beads in the bioreactors can reach 60%. Four 250-mL bioreactors represent approximately 15% of the hepatocytes in a liver, which is a reasonable target for extracorporeal liver supply. Increasing bead density clearly maintained the performances of the fluidized bed with plasma of different compositions, without any risk of release out of the bioreactor. A 1% (v/v)-concentration of microspheres in alginate solution did not result in any alteration of the mechanical or biological behavior. This concentration can thus be applied to the production of large-scale encapsulated biomass for further use of the Suppliver setup in human scale preclinical studies.


Evaluating the introduction of a pilot client attachment scheme in mental health nursing education.
Client attachment (CA) allows student nurses to gain clinical experience through forming therapeutic attachments with individual clients, rather than through a series of location-based placements. This paper describes a pilot project that evaluated CA with pre-registration student mental health nurses. Using semi-structured interviews, the researchers identified the students', their supervisor's, and their clients' experiences of CA. Most participants agreed that students were able to learn relevant and appropriate clinical skills, and to consolidate experience-increasing motivation, autonomy, organizational skills, and confidence.


Ogilvie's Syndrome Secondary to Narcotics Complicated by Colonic Perforation.
Ogilvie's syndrome is a condition characterized by colonic dilation in the absence of mechanical obstruction. This case report presents a patient who was immobile and hospitalized for several months following a motor vehicle accident that left the patient paralyzed, who subsequently developed Ogilvie's syndrome. The aim of this study is to briefly discuss the clinical presentation, diagnostic workup, and management of Ogilvie's syndrome. This article also discusses the impact of narcotics and the possible association with Ogilvie's syndrome in this patient.


Artificial feeding of Black infants.
Analysis of milk formula feeds in a community where infant malnutrition is common, showed that overdilution of feeds is less frequent than expected. Many feeds were too concentrated. Modified and 'humanised' milks were more often and more seriously too strong than unmodified milks. An inadequate number and volume of milk feeds per day was probably more important in causing malnutrition than the strength of the feeds.


Development of an Activatable Fluorescent Probe for Prostate Cancer Imaging.
Technology to visualize small prostate cancers is urgently needed because of the difficulty of discriminating prostate cancer from normal tissue with the naked eye, and a fluorescence imaging method would be advantageous. Here, we describe the design and synthesis of a fluorogenic probe (Ac-KQLR-HMRG) that is activated by hepsin and matriptase (proteases over-expressed in prostate cancer). Ac-KQLR-HMRG exhibited significant turn-on fluorogenicity in the presence of hepsin (180-fold) and matriptase (80-fold) and allowed specific fluorescence imaging of various prostate cancer cell line in vitro. In addition, the probe enabled rapid imaging (within 1-10 min) of small prostate cancer nodules in mouse models of disseminated peritoneal tumor and orthotopic tumor.


Development and characterization of bovine x human hybrid cell lines that efficiently support the replication of both wild-type bovine and human adenoviruses and those with E1 deleted.
The 293 cell line that was generated by transforming human embryonic kidney cells with human adenovirus type 5 (HAV5) early region 1 (E1) sequences is an excellent host for generating and growing HAV5 recombinants with E1 deleted, but it does not support the replication of bovine adenovirus type 3 (BAV3). Madin-Darby bovine kidney (MDBK), an established bovine cell line, is an excellent host for growing and plaquing BAV3. For the purpose of combining the unique characteristics of these two cell lines (293 and MDBK), we generated a number of bovine x human hybrid (BHH) cell lines. Comparison of three BHH hybrid clones-BHH3, BHH8, and BHH2C-with 293-Puro (puromycin-resistant 293 cells) and MDBK-Neo (G418-resistant MDBK cells) cell lines for total cellular DNA content, species-specific surface markers, isoenzyme analysis, and karyotyping indicate that they are hybrid in nature. BHH clones constitutively expressed the E1 proteins (E1A, E1B-21kDa, and E1B-55kDa) of HAV5 and efficiently supported the replication of both wild-type and replication-incompetent bovine or human adenoviruses. Transient gene expression experiments with a plasmid encoding the bacterial beta-galactosidase gene demonstrated that BHH cell hybrids seem to have better transfection efficiencies than either of the parental cell lines. These cell lines will be useful for isolating and growing replication-competent human or bovine adenovirus recombinants with E1 deleted and for the study of cellular or viral factors important for viral replication. The development of somatic cell hybrids appears to be a simple way of combining some of the desirable characteristics present separately in two parental cell lines.


An Integrative Computational Approach to Evaluate Genetic Markers for Chronic Lymphocytic Leukemia.
Recent studies reported hundreds of genes linked to chronic lymphocytic leukemia (CLL). However, many of these candidate genes were lack of replication and results were not always consistent. Here, we proposed a computational workflow to curate and evaluate CLL-related genes. The method integrates large-scale literature knowledge data, gene expression data, and related pathways/network information for quantitative marker evaluation. Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using our approach, a scalable CLL genetic database was developed including CLL-related genes, pathways, diseases and information of supporting references. The CLL case/control classification supported the effectiveness of the four proposed metrics, which successfully identified nine well-studied CLL genes (i.e., TNF, BCL2, TP53, VEGFA, P2RX7, AKT1, SYK, IL4, and MDM2) and highlighted two newly reported CLL genes (i.e., PDGFRA and CSF1R). The computational biology approach and the CLL database developed in this study provide a valuable resource that may facilitate the understanding of the genetic profile of CLL.


Update in inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a common disease in Australia and frequently encountered in primary care. Major developments in investigation and management have taken place. This article aims to review some recent breakthroughs in IBD investigation and management. Diagnosis involves a changing combination of enhanced traditional techniques with new diagnostic tools, typically blood and stool testing with improved endoscopy and new radiological tests. Management has seen the introduction of new powerful biologic therapies, greater understanding in the way we use older therapies, and a focus on preventing complications such as malignancy or infection. Treatment philosophy now attempts to alter the natural history of the disease and prevent long term complications. The importance of associated, previously overlooked factors is being increasingly recognised. Only by taking a long term, patient centred multidisciplinary approach will an optimal outlook for the majority of patients with IBD be achieved.


A study on Notch signaling in human breast cancer.
Breast cancer is one of the leading causes of cancer death in women. The Notch family of proteins plays crucial roles in determining cell fates such as proliferation, differentiation and apoptosis. A role for Notch signaling in human breast cancer has been suggested by the development of adenocarcinomas in the murine mammary gland. However, it is not clear currently whether Notch signaling is frequently expressed and activated in breast cancers. Here we show that Notch signaling is overexpressed and highly activated in breast cancers. More significantly, the attenuation of Notch signaling by gamma-secretase inhibitor can inhibit the proliferation of breast cancer cells by both causing cell cycle arrest and apoptosis. Thus, targeting Notch signaling may be of therapeutic value in breast cancers.


Technological Advances in Spine Care.
Spinal medicine is one of the most rapidly evolving specialities of surgery and of medicine. The more critical and life saving specialties seem to have evolved first. General surgery, of course, existed for decades before the vascular and cardiac surgeon evolved in the 1950s and 1960s. Hand surgery and total joint surgery was in its heyday by the early 1970s. Spine surgery did not become a recognised specialty by the Academy of Orthopedic Surgery until almost 1990.


Effect of denture cleaning on abrasion resistance and surface topography of polymerized CAD CAM acrylic resin denture base.
The application of computer-aided design computer-aided manufacturing (CAD CAM) technology in the fabrication of complete dentures, offers numerous advantages as it provides optimum fit and eliminates polymerization shrinkage of the acrylic base. Additionally, the porosity and surface roughness of CAD CAM resins is less compared to conventionally processed resins which leads to a decrease in the adhesion of bacteria on the denture base, which is associated with many conditions including halitosis and aspiration pneumonia in elderly denture wearers. To evaluate the influence of tooth brushing with dentifrices on CAD CAM resin blocks in terms of abrasion resistance, surface roughness and scanning electron photomicrography. This experimental study was carried out at the Faculty of Dentistry of King Abdulaziz University during 2016. A total of 40 rectangular shaped polymerized CAD CAM resin samples were subjected to 40.000 and 60.000 brushing strokes under a 200-gram vertical load simulating three years of tooth brushing strokes using commercially available denture cleaning dentifrice. Data were analyzed by SPSS version 20, using descriptive statistics and ANOVA. ANOVA test revealed a statistical significant weight loss of CAD CAM acrylic resin denture base specimens following 40.000 and 60.000 brushing strokes as well as a statistical significant change (p=0.0.5) in the surface roughness following brushing. The CAD CAM resin samples SEM baseline imaging revealed a relatively smooth homogenous surface, but following 40,000 and 60,000 brushing strokes, imaging displayed the presence of small scratches on the surface. CAD CAM resin displayed a homogenous surface initially with low surface roughness that was significantly affected following simulating three years of manual brushing, but despite the significant weight loss, the findings are within the clinically acceptable limits.


Delay-Aware Energy-Efficient Routing towards a Path-Fixed Mobile Sink in Industrial Wireless Sensor Networks.
Wireless sensor networks (WSNs) involve more mobile elements with their widespread development in industries. Exploiting mobility present in WSNs for data collection can effectively improve the network performance. However, when the sink (i.e., data collector) path is fixed and the movement is uncontrollable, existing schemes fail to guarantee delay requirements while achieving high energy efficiency. This paper proposes a delay-aware energy-efficient routing algorithm for WSNs with a path-fixed mobile sink, named DERM, which can strike a desirable balance between the delivery latency and energy conservation. We characterize the object of DERM as realizing the energy-optimal anycast to time-varying destination regions, and introduce a location-based forwarding technique tailored for this problem. To reduce the control overhead, a lightweight sink location calibration method is devised, which cooperates with the rough estimation based on the mobility pattern to determine the sink location. We also design a fault-tolerant mechanism called track routing to tackle location errors for ensuring reliable and on-time data delivery. We comprehensively evaluate DERM by comparing it with two canonical routing schemes and a baseline solution presented in this work. Extensive evaluation results demonstrate that DERM can provide considerable energy savings while meeting the delay constraint and maintaining a high delivery ratio.


What governs the charge transfer in DNA? The role of DNA conformation and environment.
Charge transfer in DNA has received much attention in the last few years due to its role in oxidative damage and repair in DNA and also due to possible applications of DNA in nanoelectronics. Despite intense experimental and theoretical efforts, the mechanism underlying long-range hole transport is still unresolved. This is in particular due to the sensitive dependence of charge transfer on the complex structure and dynamics of DNA and the interaction with the solvent, which could not be addressed adequately in the modeling approaches up to now. In this work, we study the factors governing hole transfer in detail, using a DFT-based fragment-orbital method, which allows to compute the charge transfer parameters along multinanosecond molecular dynamics simulations. Environmental effects are captured using a hybrid quantum mechanics-molecular mechanics (QM/MM) coupling scheme. This methodology allows to analyze several factors responsible for charge transfer in DNA in detail. The fluctuation of counterions, strongly counterbalanced by the surrounding water, leads to large oscillations of onsite energies, which govern the energetics of hole propagation along the DNA strand. In contrast, the electronic couplings depend only on DNA conformation and are not affected by the solvent. In particular, the onsite energies are strongly correlated between neighboring nucleobases, indicating that a conformational-gating type of mechanism may be induced by the collective environmental degrees of freedom.


Dynamic changes in blood flow and oxygen consumption in the portal-drained viscera of growing pigs receiving acute administration of (L)-arginine.
This study tested the hypothesis that an increase in arginine concentration in the portal vein may affect blood flow and oxygen consumption in the portal-drained viscera (PDV) of swine. Eight barrows (70 kg body weight) were surgically fitted with chronic catheters in the portal vein, ileal vein, and carotid artery. Thirteen days after the surgery, pigs that had been fasted for 12 h were randomly allocated to receive administration of either L-alanine (103 mg/kg body weight, isonitrogenous control) or L-arginine-HCl (61 mg/kg body weight) via the portal vein. Portal vein blood flow (PVBF) was measured with infusion of p-aminohippuric acid into the ileal vein, and blood samples were simultaneously obtained every 0.5 h for 4 h. Compared with the control, arginine infusion increased PVBF at 30-90 min after infusion but decreased PDV oxygen consumption at 60-150 min after infusion (P < 0.05). Plasma concentrations of glutamate at infusion times of 180-240 min and of arginine at infusion times of 60-240 min in arginine-infused pigs were higher than those for the control group (P < 0.05). Plasma concentrations of insulin and glucagon at the infusion times of 30-90 min were higher and of free fatty acids at the infusion times of 60-120 min were lower than those for the control pigs (P < 0.05). These results indicate that increasing arginine concentration in the portal vein enhances PDV blood flow, reduces PDV oxygen consumption, and beneficially alters the metabolic profile in swine, an established animal model for studying human nutrition and metabolism.


The HIV protease inhibitor ritonavir blocks osteoclastogenesis and function by impairing RANKL-induced signaling.
Highly active antiretroviral therapy (HAART), which includes HIV protease inhibitors (PIs), has been associated with bone demineralization. To determine if this complication reflects accelerated resorptive activity, we studied the impact of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and function. Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number. Ritonavir given in vivo completely blunts parathyroid hormone-induced osteoclastogenesis in mice, which confirms that the drug is bone sparing. In keeping with its antiresorptive properties, ritonavir impairs receptor activator of nuclear factor kappaB ligand-induced (RANKL-induced) activation of NF-kappaB and Akt signaling pathways, both critical to osteoclast formation and function. In particular, ritonavir is found to inhibit RANKL-induced Akt signaling by disrupting the recruitment of TNF receptor-associated factor 6/c-Src complex to lipid rafts. Thus, ritonavir may represent a bone-sparing PI capable of preventing development of osteopenia in patients currently on HAART.


Comparison of nipple projection with the modified double-opposing tab and star flaps.
This study compared nipple projection after nipple reconstruction (following breast mound reconstruction) with either the modified double-opposing tab flap or the star flap. Areolar reconstruction and pigmentation of the nipple were achieved with tattooing. Nipple projection for 153 nipples was measured at least 6 months after the reconstruction, when projection was believed to have become stable. Mean follow-up was 2.27 years. In the 106 nipples reconstructed with modified double-opposing tab flaps, the mean projection was 2.4292 mm, while in the 47 nipples reconstructed with star flaps, the mean projection was 1.9681 mm (p = 0.021). We conclude that although both methods are effective, the modified double-opposing tab flap has slightly more projection after approximately 2 years. It is not known, however, whether this is because of reduced flap atrophy or longer initial projection by the modified double-opposing tab flap; further studies are ongoing.


Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse.
This study investigated the participation of MAPK in the resumption of meiosis [germinal vesicle breakdown (GVB)] in oocytes and cumulus expansion using oocyte-cumulus cell complexes (OCC) from Mos-null mice (Mos(tm1Ev)/Mos(tm1Ev), hereafter Mos(-/-)). MAPK activity was not detected in Mos(-/-) oocytes whether they matured in vivo or in vitro, with or without gonadotropin stimulation. Therefore, there are no pathways independent of MOS that activate MAPK during gonadotropin-induced maturation. In contrast, MAPK activity was always detected coincident with GVB in Mos(+/+) oocytes. Moreover, MAPK activity was detected in cumulus cells before gonadotropin-induced GVB in OCC regardless of genotype. A specific inhibitor (U0126) of MEK, a MAPKK required for MAPK activity, inhibited gonadotropin-induced GVB in OCC of both Mos(+/+) and Mos(-/-) mice. Activation of MAPK was downstream of elevation of cAMP. U0126 also inhibited cumulus expansion stimulated by FSH, epidermal growth factor, 8-bromo-cAMP, and recombinant growth differentiation factor-9. It is concluded that under the in vitro conditions used here, gonadotropin-induced GVB requires the participation of MAPK activity in the cumulus cells, but not in the oocyte. Moreover, the induction of cumulus expansion also requires the participation of MAPK, and this action is downstream of both elevation of cAMP and growth differentiation factor-9.


Chronic Regulatory Focus and Work-Family Conflict among Chinese Workers.
Survey data from 226 service employees were used to test the hypothesized moderating role of chronic self-regulatory focus on the relationships between work-family conflict (WFC) and challenge/hindrance strain. A follow-up scenario-based experiment (N = 93 executives) confirmed the results of the hypothesized model. Results from the two studies together demonstrated the moderating role of self-regulatory processes: chronic promotion-focused individuals perceived WFC as a challenge-type strain, while chronic prevention-focused individuals viewed WFC as a hindrance-type strain. Individuals use self-regulation strategically: in work domains, they regulate themselves so that family does not interfere with work. Individuals' stress perceptions differ depending on the two dimensions of WFC as they regard interferences from (WIF) as a personal challenge, perhaps affording them an opportunity to balance work and life and to refine their abilities, but interferences from family to work (FIW) act as a barrier preventing them from achieving career success. When two-way interactions between WIF/FIW and chronic promotion/prevention foci were taken into consideration, the WIF/FIW main effects on challenge/hindrance stress became insignificant, suggesting that chronic self-regulation fully moderated the relationship. The results extend the current work-family research by incorporating self-regulatory processes as an important moderating variable, suggesting new research directions. The findings can help human resource management establish policies and benefit programs that take individual differences into account.


CDC's 60th anniversary: director's perspective--James O. Mason, M.D., Dr.P.H., 1983-1989.
The growing momentum toward expanding CDC's responsibilities beyond infectious diseases gained strength during the 1980s. Tremendous advances in controlling infectious diseases had dramatically reduced illness and death from many long-standing health threats. In addition, the detrimental effects of chronic and other noncommunicable diseases on the nation's health were rapidly increasing. Programs to address cancer, heart disease, diabetes, and other leading killers became central to CDC's focus. Yet, for much of this decade, a newly emerging infectious disease would demand the skills and talents of persons across the agency. These new responsibilities led to additional funding, programs, staff, and partnerships for the growing agency, while introducing a host of new challenges.


FDA: keynote address, PDA/FDA conference.
In the beginning of my presentation, I alluded to the breadth of issues and change facing FDA and, in particular, the office of regulatory affairs. I hope you now have a feel for the changing times that you face with the FDA. I hope that FDA's persistence and investigative thoroughness inspires a greater concern for compliance by industry officials. FDA's reliance in "voluntary compliance," and the public's protection afforded by it, are dependent on industry's appreciation of the alternatives to voluntary compliance.


Direct measurement of the depletion interaction in binary solutions of polyelectrolytes.
Direct measurements of a depletion interaction between silica surfaces immersed in binary mixtures of non-adsorbing sodium poly(styrene sulfonate) have been made with an atomic force microscope. Variations in the secondary minimum depletion interaction as a function of binary mixture composition were recorded for a number of polymer molecular weights. The position and depth of the minimum in the force data was seen to depend on both the binary mixture composition and the choice of polymer molecular weights used in the mixture. For binary mixtures containing a low molecular weight polymer at a concentration near to or below the chain overlap concentration (C*) the position and depth of the minimum was seen to depend strongly on the properties of this low molecular weight component. This is consistent with previous theory predictions that depletion interactions in binary polymer mixtures will be controlled by the smaller component which can reside within the depletion layer of the higher molecular weight component.


Attenuation of RNA viruses by redirecting their evolution in sequence space.
RNA viruses pose serious threats to human health. Their success relies on their capacity to generate genetic variability and, consequently, on their adaptive potential. We describe a strategy to attenuate RNA viruses by altering their evolutionary potential. We rationally altered the genomes of Coxsackie B3 and influenza A viruses to redirect their evolutionary trajectories towards detrimental regions in sequence space. Specifically, viral genomes were engineered to harbour more serine and leucine codons with nonsense mutation targets: codons that could generate Stop mutations after a single nucleotide substitution. Indeed, these viruses generated more Stop mutations both in vitro and in vivo, accompanied by significant losses in viral fitness. In vivo, the viruses were attenuated, generated high levels of neutralizing antibodies and protected against lethal challenge. Our study demonstrates that cornering viruses in 'risky' areas of sequence space may be implemented as a broad-spectrum vaccine strategy against RNA viruses.


[Laser trabeculopuncture. II. Screen electron mascroscopic findings].
Laser trabeculopuncture was performed on preparations of human anterior chamber angle obtained from cadaver eyes. It was possible repeatedly to make about 50 mum large openings leading from anterior chamber to Schlemm canal. It was necessary to use short exposure times of maximum 200 msec and laser efficiency of at least 1,500 mW at the origin. The results were studied with a scanning electron microscope.


A Z-axis recumbent rotating device for use in parabolic flight.
A prototype apparatus for exposing persons to rotation about their Z-axis in parabolic flight is described. Although it resembles Earth-horizontal axis devices, added features are its strength and portability, and the fiber glass "couch" with adjustable elements providing support and restraint. Even under ground-based conditions, this device provides unique opportunities for investigations involving not only canalicular and macular mechanoreceptors, but also touch, pressure, and kinesthetic receptor systems.


Influence of Porosity of Sulfide-Based Artificial Solid Electrolyte Interphases on Their Performance with Liquid and Solid Electrolytes in Li and Na Metal Batteries.
Realization of all-solid-state batteries combined with metallic Li/Na is still hindered due to the unstable interface between the alkali metal and solid electrolytes, especially for highly promising thiophosphate materials. Artificial and uniform solid-electrolyte interphases (SEIs), serving as thin ion-conducting films, have been considered as a strategy to overcome the issues of such reactive interfaces. Here, we synthesized sulfide-based artificial SEIs (LixSy and NaxSy) on Li and Na by solid/gas reaction between the alkali metal and S vapor. The synthesized films are carefully characterized with various chemical/electrochemical techniques. We show that these artificial SEIs are not beneficial from an application point of view since they either contribute to additional resistances (Li) or do not prevent reactions at the alkali metal/electrolyte interface (Na). We show that NaxSy is more porous than LixSy, supported by (i) its rough morphology observed by focused ion beam-scanning electron microscopy, (ii) the rapid decrease of Rinterface (interfacial resistance) in NaxSy-covered-Na symmetric cells with liquid electrolyte upon aging under open-circuit potential, and (iii) the increase of Rinterface in NaxSy-covered-Na solid-state symmetric cells with Na3PS4 electrolyte. The porous SEI allows the penetration of liquid electrolyte or alkali metal creep through its pores, resulting in a continuous chemical reaction. Hence, porosity of SEIs in general should be carefully taken into account in the application of batteries containing both liquid electrolyte and solid electrolyte.


A Preliminary Report Showing Spinosad and Fluralaner Are Able to Incapacitate Cimex lectularius L., the Common Bed Bug.
Cimex lectularius L., the common bed bug, is a hematophagous human ectoparasite. The veterinary drugs, spinosad and fluralaner, were studied for their ability to incapacitate C. lectularius when administered in a blood meal using an artificial feeding system under laboratory conditions. Tested drug doses were based on the reported peak blood levels in animals given the drugs. Spinosad at doses 1,000 ng/mL or higher resulted in 75% or greater bed bug incapacitation (defined as death or immobility). Fluralaner at doses 500 ng/mL or higher had 100% bed bug incapacitation. Both drugs were significantly more effective than controls at these doses (P < 0.001).


[Seminal vesicle cyst: about a case].
We report the case of a patient with symptomatic seminal vesicle cyst on the right side. Imaging examinations (pelvic and endorectal ultrasound, abdominal-pelvic tomodensitometry and MRI) were perdormed and the patient underwent surgical removal of the cyst. In light of this case study, epidemiology, diagnosis and treatment options are discussed.


Nintedanib-Induced Renal Thrombotic Microangiopathy.
Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.


Clinical studies on hemorrhagic fever with renal syndrome found in Nagoya City University Medical School.
This study refers to the clinical features of 11 cases of hemorrhagic fever with renal syndrome (HFRS) which was prevalent in Nagoya City University Medical School. The clinical course was divided into two parts: the febrile stage and the polyuria stage. Symptoms such as lumbago, muscular pain, general malaise and anorexia disappeared along with a fall of fever. The incubation period of this disease was estimated to be about three weeks. Polyuria, proteinuria, gastric complication and impairment of liver function seemed to be some of clinical features of this disease. There was no HFRS patient with severe renal failure in our cases. The presence of disseminated intravascular coagulation (DIC) was confirmed in 3 of these 11 cases. Therefore, it was suggested that hemorrhagic tendency of this disease might be attributed to DIC. From our experiences, the most important factor for the treatment of the severe case was the earliest detection whether they were complicated by DIC or not. If they were suspected of DIC, it could be necessary to start treatment for DIC as soon as possible. Prophylactic measures for HFRS in our animal facility could contribute to the prevention of this disease.


tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine.
Targeted sequencing of discrete gene sets is a cost effective strategy to screen subjects for monogenic forms of disease. One method to achieve this pairs microfluidic PCR with next generation sequencing. The PCR step of this pipeline creates challenges in accurate variant calling. This includes that most reads targeting a specific exon are duplicates that have been amplified from the PCR step. To reduce false positive variant calls from these experiments, previous studies have used threshold-based filtering of alternative allele depth ratio and manual inspection of the alignments. However even after manual inspection and filtering, many variants fail to be validated via Sanger sequencing. To improve the accuracy of variant calling from these experiments, we are challenged to design a variant filtering strategy that sufficiently models microfluidic PCR-specific issues. We developed an open source variant filtering pipeline, targeted sequencing support vector machine ("tarSVM"), that uses a Support Vector Machine (SVM) and a new score the normalized allele dosage test to identify high quality variants from microfluidic PCR data. tarSVM maximizes training knowledge by selecting variants that are likely true and likely false variants by incorporating knowledge from the 1000 Genomes and the Exome Aggregation Consortium projects. tarSVM improves on previous approaches by synthesizing variant features from the Genome Analysis Toolkit and allele dosage information. We compared the accuracy of tarSVM versus existing variant quality filtering strategies on two cohorts (n = 474 and n = 1152), and validated our method on a third cohort (n = 75). In the first cohort, our method achieved 84.5 % accuracy of predicting whether or not a variant would be validated with Sanger sequencing versus 78.8 % for the second most accurate method. In the second cohort, our method had an accuracy of 73.3 %, versus 61.5 % for the second best method. Finally, our method had a false discovery rate of 5 % for the validation cohort. tarSVM increases the accuracy of variant calling when using microfluidic PCR based targeted sequencing approaches. This results in higher confidence downstream analyses, and ultimately reduces the costs Sanger validation. Our approach is less labor intensive than existing approaches, and is available as an open source pipeline for read trimming, aligning, variant calling, and variant quality filtering on GitHub at https://github.com/christopher-gillies/TargetSpecificGATKSequencingPipeline .


In vitro reassembly of basal body components.
Singlet microtubules and structures that have the morphology and dimensions of the basal body cartwheel complex self-assemble in extracts derived from Tetrahymena basal bodies.


Expression of αvβ6 integrin and collagen fibre in oral squamous cell carcinoma: association with clinical outcomes and prognostic implications.
This study aims to investigate the expression and significance of the αvβ6 integrin, collagen fibres and matrix metalloproteinases (MMP)-3 in oral squamous cell carcinoma (OSCC) and to analyse the possible regulatory relationships between αvβ6, collagen fibres and MMP-3. A series of 80 patients (mean age 56.4 years) diagnosed with OSCC were enrolled. Associations between αvβ6, MMP-3, collagen fibre expression levels and clinicopathological parameters were evaluated using the Fisher exact test. Survival analysis was performed with Kaplan-Meier curves. Spearman rank correlation was used to analyse interactions between αvβ6, MMP-3 and collagen fibres. αvβ6 and MMP-3 were strongly expressed in human OSCC, especially at the peripheral borders of invasive tumour islands, and collagen fibres were generally disrupted and degraded in the same areas. The expression intensity of αvβ6 was associated with the differentiation state of cells. β6 mRNA was expressed in almost all cancer cells. In carcinomas, αvβ6 and MMP-3 expression were correlated with the distribution of collagen fibres. Tumour cells highly expressing αvβ6 have a strong capability for invasion and migration, due to concomitant protease production and the destruction and remodelling of collagen fibres. Increased αvβ6 integrin and MMP-3 expression and collagen fibre changes in human OSCCs are related to unfavourable clinical prognostic factors and decreased survival.


Adjuvant chemotherapy with epirubicin and carmofur after radical resection of hepatocellular carcinoma: a prospective randomized study.
The intrahepatic recurrence rate is extremely high, even after radical resection of hepatocellular carcinoma (HCC). One report showed intra-arterial administration of epirubicin to be effective in the treatment of nonresectable HCC. We evaluated the effect of postoperative adjuvant chemotherapy including this drug. Fifty-seven patients who had undergone radical resection of HCC were entered in this study. Using the sealed-envelope method, 27 patients were assigned to a group undergoing resection only and 29 patients to a group also receiving adjuvant chemotherapy after resection. The protocol of the chemotherapy was intra-arterial administration of epirubicin (40 mg/m2) at 1 month after resection followed by intravenous administration of epirubicin (40 mg/m2) every 3 months for 2 years. In addition, 1-hexylcarbamoyl-5-fluorouracil (HCFU; carmofur), 300 mg/d, was administered orally every day, beginning from 1 month after the resection and continuing (in principle) for 24 months. The clinicopathologic backgrounds were well randomized between the two groups. The chemotherapy protocol was performed completely in only five patients (7.2%). Twenty-four (82.8%) patients had to cease the protocol due to various reasons: change to a new therapy after recurrence of HCC in 19 cases (79.2%), severe side effects of the chemotherapy in three cases (12.5%), liver failure in one case (4.2%), and a postoperative complication in one case (4.2%). The mean total doses were 128 +/- 114 mg for epirubicin and 144 +/- 84 g for HCFU. The cumulative overall and disease-free survival rates for 5 years were not significantly different between the two groups. The results of this prospective randomized study suggest that this adjuvant chemotherapy protocol with epirubicin and HCFU after radical resection of HCC was not effective.


Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation.
Regulation of stem cell self-renewal versus differentiation is critical for embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts divide asymmetrically to self-renew, and are a model system for studying stem cell self-renewal. Here we identify three mutations showing increased brain neuroblast numbers that map to the aurora-A gene, which encodes a conserved kinase implicated in human cancer. Clonal analysis and time-lapse imaging in aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic self-renewal). This phenotype is due to two independent neuroblast defects: abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to align the mitotic spindle with the cortical polarity axis. numb mutant clones have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that disrupt spindle alignment but not cortical polarity have increased neuroblasts. We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal.


Mucosal thickening adjacent to gastric malignancy: association with epidermal growth factor.
A high false negative rate from endoscopic forceps biopsy is well-known in gastric carcinoma. The initial aim of the present study was to determine whether possible thickening of adjacent nontumorous mucosa by nonspecific or specific trophic factors could contribute to this observation; 167 gastrectomy specimens (77 carcinomas, 14 lymphomas, 76 gastric ulcers) were examined and mucosal thickness measured. Mean thickness of uninvolved mucosa near carcinoma (1.4 +/- 0.08 mm, mean +/- SEM) and near lymphoma (1.5 +/- 0.1 mm) was in each case significantly greater than mucosal thickness near ulcer (1.14 +/- 0.05 mm) or at a distance in the same specimen (P less than 0.01 for each comparison). A subset of specimens representing 20% of carcinomas, showed marked mucosal thickening (2.01 +/- 0.05 mm) above the control mean. Immunohistochemical evaluation for intratumoral epidermal growth factor content (EGF) correlated with mucosal thickness in all groups examined (R = 0.67). Immunostaining for EGF receptor showed similar patterns of expression to those of EGF. EGF and EGF receptor contents were also correlated with depth of invasion when possible. In conclusion, the mucosal thickening adjacent to gastric malignancy may well contribute to the insensitivity of endoscopic forceps biopsy. More importantly, the higher tumor EGF and EGF-receptor contents seen in these lesions may prove to be a useful marker of biologic behavior and predictor of prognosis in these tumors.


Association between pro-inflammatory cytokine interleukin-33 and periodontal disease in the elderly: A retrospective study.
Senescence is a multifactorial process that in humans may be accompanied by inflammation and immune dysfunction in the oral cavity. Notably, periodontal disease, considered one of the most common inflammatory disorders in the oral cavity, has also been linked to the onset of other chronic inflammatory diseases common in the elderly. Thus, investigating immunity and inflammation during senescence may not only illuminate the pathophysiology of periodontal disease, but also identify new therapeutic targets. To this end, we retrospectively and systematically reviewed studies of immune molecules associated with periodontal disease. These studies were identified in PubMed from three independent searches based on distinct sets of search terms. The data highlight the need to further investigate inflammatory molecules involved in chronic periodontal disease in the elderly, but strongly suggest that interleukin (IL)-33 is involved. Indeed, various genetic and environmental factors appear to contribute to pathogenesis via IL-33. The IL-33 axis may be promising therapeutic target in elderly patients.


From negative to positive and back again: polarized affective and relational experience in borderline personality disorder.
A core feature of borderline personality disorder (BPD) is the tendency to evaluate one's experience with extreme polarity (i.e., feeling all good or all bad; Beck, Freeman, & Davis, 2004; Kernberg, 1975; Linehan, 1993). In this investigation, we examined the polarity of within-person reports of experience in individuals with BPD and healthy adults over the course of a 21-day, experience-sampling diary. We applied multilevel modeling techniques (Rafaeli, Rogers, & Ravelle, 2007) to capture the within-person covariance of momentary reports of negative and positive features of experience, either affective or relational. Our data indicated significantly greater polarity in reports of affective and relational experiences in BPD that increased during heightened interpersonal stress. We also examined the association of affective and relational polarity to reports of impulsive behaviors (e.g., self-injury, substance use, etc.) and found evidence that increased polarity in reports of affective (in low-stress contexts) and relational experiences (in high-stress contexts) predicted increased rate of reports of impulsive behaviors. Together, these data present strong evidence for the role of polarized experiences in BPD, and have implications for the treatment of individuals with this disorder.


[The effect of colostral immunity on the active formation of antibodies in pigs after the administration of inactivated vaccine against Aujeszky's disease].
In a large herd of pigs where a trial was performed to cure the animals from Aujeszky's disease (AD) by applying to all animals an inactivated vaccine, a post-vaccination antibody response was studied in piglets coming from the sows that were vaccinated several times. When the piglets were vaccinated at the age of eight weeks (the average virus-neutralizing titer (VNT) of colostral antibodies was 1:11.4) and revaccinated at the age of 11 weeks, 73% of the forty-five animals (examined at the age of 17 weeks) did not have any virus-neutralizing (VN) antibodies in the blood serum. After the third vaccination dose (at the age of 17 weeks), 11% of piglets did not have any VN antibodies if they were examined at the age of 22 weeks (the average antibody VNT was 1:15.3). Applying the ELISA procedure, the antibodies were demonstrated in the sera of all piglets after three vaccination doses. Shifting the time intervals of vaccination (at the age of 8, 13 and 19 weeks), the VN antibodies were found out after three vaccination doses in the sera of all piglets examined at the age of 23 weeks (the average VNT was 1:56.4). After three vaccination doses at the age of 12, 17 and 23 weeks, the VN antibodies were also demonstrated in all piglets at the age of 27 weeks (the average VNT was 1:208).


Magnetic Lateral Ladder for Unidirectional Transport of Microrobots: Design Principles and Potential Applications of Cells-on-Chip.
Functionalized microrobots, which are directionally manipulated in a controlled and precise manner for specific tasks, face challenges. However, magnetic field-based controls constrain all microrobots to move in a coordinated manner, limiting their functions and independent behaviors. This article presents a design principle for achieving unidirectional microrobot transport using an asymmetric magnetic texture in the shape of a lateral ladder, which the authors call the "railway track." An asymmetric magnetic energy distribution along the axis allows for the continuous movement of microrobots in a fixed direction regardless of the direction of the magnetic field rotation. The authors demonstrated precise control and simple utilization of this method. Specifically, by placing magnetic textures with different directionalities, an integrated cell/particle collector can collect microrobots distributed in a large area and move them along a complex trajectory to a predetermined location. The authors can leverage the versatile capabilities offered by this texture concept, including hierarchical isolation, switchable collection, programmable pairing, selective drug-response test, and local fluid mixing for target objects. The results demonstrate the importance of microrobot directionality in achieving complex individual control. This novel concept represents significant advancement over conventional magnetic field-based control technology and paves the way for further research in biofunctionalized microrobotics.


Different sensitivities of photosystem II in green algae and cyanobacteria to phenylurea and phenol-type herbicides: effect on electron donor side.
The effects of short-term treatment with phenylurea (DCMU, isoproturon) and phenol-type (ioxynil) herbicides on the green alga Chlorella kessleri and the cyanobacterium Synechocystis salina with different organizations of photosystem II (PSII) were investigated using pulse amplitude modulated (PAM) chlorophyll fluorescence and photosynthetic oxygen evolution measured by polarographic oxygen electrodes (Clark-type and Joliot-type). The photosynthetic oxygen evolution showed stronger inhibition than the PSII photochemistry. The effects of the studied herbicides on both algal and cyanobacterial cells decreased in the following order: DCMU>isoproturon>ioxynil. Furthermore, we observed that the number of blocked PSII centers increased significantly after DCMU treatment (204-250 times) and slightly after ioxynil treatment (19-35 times) in comparison with the control cells. This study suggests that the herbicides affect not only the acceptor side but also the donor side of PSII by modifications of the Mn cluster of the oxygen-evolving complex. We propose that one of the reasons for the different PSII inhibitions caused by herbicides is their influence, in different extents, on the kinetic parameters of the oxygen-evolving reactions (the initial S0-S1 state distribution, the number of blocked centers SB, the turnover time of Si states, misses and double hits). The relationship between the herbicide-induced inhibition and the changes in the kinetic parameters is discussed.


Dietary Diversity and Anthropometric Status of Mother-Child Pairs from Enset (False Banana) Staple Areas: A Panel Evidence from Southern Ethiopia.
A sizable cross-sectional studies demonstrated a low dietary diversity in Southern Ethiopia. However, its seasonal trend has not been well studied in areas where nutrient-poor enset (false banana (Ensete ventricosum)) foods are major staple. Moreover, there is scarcity of information on seasonal nature of anthropometric status of mother-child pairs (MCP) from the same areas in Southern Ethiopia. Therefore, the present study aimed to investigate the dietary diversity and anthropometric status of MCP in postharvest dry and lean wet seasons and identify factors associated with anthropometric status. The dietary intake and anthropometric data were collected from 578 households (578 mothers and 578 children) January-June 2017. The study compared data of the two seasons using McNemar's test for dichotomous, Wilcoxon signed-rank test for non-normally distributed, and paired samples t-test for normally distributed continuous data. Logistic regression was conducted to identify risk factors for malnutrition. In addition, Spearman's Rho test was used to determine correlations between maternal and child variables. Over 94% of the mothers did not fulfil the minimum diet diversity score in both seasons. The meal frequency and pulses/legumes intake significantly declined in lean wet season; however, dark green leaves consumption increased. Meat, poultry, and fish consumption dropped to almost zero in the lean wet season. The dietary diversity and anthropometric status of the MCP were correlated. Weight-for-age (WAZ) and weight-for-height (WHZ) of children significantly declined in the lean wet season. In the same way, maternal mid upper arm circumference (MUAC), body weight, and body mass index (BMI) dropped (p < 0.001) in this season. Being pregnant and a lactating mother, poverty, and the ability to make decisions independently predicted maternal undernutrition (low MUAC). On the other hand, maternal undernutrition and education were associated with child underweight. The results demonstrated that the dietary diversity of MCP is low in both postharvest dry and lean wet seasons. This suggests the need for continuous nutrition intervention to improve the dietary diversity. In addition, the anthropometric status of MCP declines in lean wet season. This may provide some clue for policy targeting on improving nutritional status of mothers and children in rural Southern Ethiopia.