The association of thyroid cancer and SA has been previously described in individual case reports. We are describing 4 patients with co-existence of papillary thyroid cancer (PTC) and SA who presented a diagnostic and management challenge.

METHODS

One patient (Patient 1) with known history of SA was referred for thyroid nodules and cervical adenopathies; Fine needle aspiration (FNA) showed PTC. At surgery, he was found to have non-necrotizing granulomatous inflammation (NNGI) in lymph nodes in addition to PTC. Another patient (Patient 2) with known history of PTC presented with a palpable LN. FNA showed NNGI. She was subsequently found to have diffuse lymphadenopathies from SA. A third patient (Patient 3) who was totally asymptomatic, without history of PTC or SA, presented with a right thyroid nodule and a right lateral neck adenopathy both of which were positive for PTC. Pathology showed extensive NNGI and PTC in 4 LNs. Subsequent work up revealed diffuse lymphadenopahies throughout the body on positron-emitting tomography/computed tomography with elevated serum angiotensin converting enzyme level. The last patient (Patient 4) who did not have any history of SA or PTC presented with systemic symptoms. Work up revealed a large goiter with substernal extension that required a thyroidectomy. At surgery, suspicious adenopathies were resected and were found to contain NNGI. The thyroid specimen contained PTC.

CONCLUSIONS

Clinicians should be wary of this association/co-existence of SA and PTC to avoid mismanagement of neck lymphadenopathies in patients with current or history of SA. Although 4% of thyroid cancers may induce a sarcoid reaction in the thyroid gland, SA as a disease may coexist with PTC although causality remains uncertain. Being aware of this association is important in the differential diagnosis of a thyroid mass and/or a LN in a patient with SA. Therefore, patients with known SA who are found to have cervical adenopathies or thyroid nodules should have a thorough work up.

BACKGROUND Sirtuin1 (SIRT1) participates in a wide variety of cellular processes, but the molecular mechanism remains largely unknown. miR-155 is an element of the inflammatory signaling pathway in atherosclerosis. Therefore, we tested the hypothesis that TNF-alpha stimulates miR-155 to target SIRT1 and thereby regulates endothelial senescence, and we also explored the function of miR-155 as a regulator of cardiovascular diseases. MATERIAL AND METHODS TNF-alpha was used to stimulate human umbilical vein endothelial cells (HUVECs), after which protein and gene expression were assessed via Western blotting and RT-qPCR. miR-155 targeting of SIRT1 was confirmed via luciferase reporter assays, while MTT and senescence-associated ß-galactosidase (SA-ß-gal) assays were used for quantifying cellular proliferation and senescence. RESULTS We found that miR-155 was upregulated in response to TNF-alpha treatment, in addition to inducing marked changes in SIRT1/FoxO-1/p21 pathway protein level. When we overexpressed miR-155 mimics, SIRT1 was markedly reduced, whereas miR-155 inhibition had the opposite effect in TNF-alpha-treated cells. We additionally confirmed that miR-155 was able to directly bind to SIRT1 3'-UTR, and that inhibition of miR-155 reduced the ability of TNF-alpha to induce senescence in HUVECs, thereby leading to their enhanced proliferation. Simvastatin was associated with suppression of miR-155 expression in HUVECs following TNF-alpha treatment, and with a corresponding reduction in TNF-alpha-induced senescence, whereas miR-155 overexpression had the opposite effect. CONCLUSIONS Our findings suggest that TNF-alpha upregulates miR-155, which then targets SIRT1, suppressing its expression and driving HUVEC apoptosis. Simvastatin disrupted this senescence mechanism via the miR-155/SIRT1/FoxO-1/p21 pathway signaling. Hence, miR-155 is a possible therapeutic approach to endothelial senescence in the development of cardiovascular diseases.

OBJECTIVE

Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA.

METHODS

We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC.

RESULTS

Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men (p < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE.

CONCLUSIONS

IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA.

Exposure to estrogen has long been associated with an increased risk of developing breast cancer. However, how estrogen signaling promotes breast carcinogenesis remains elusive. Senescence is known as an important protective response to oncogenic events. We aimed to elucidate the role of estrogen receptor alpha (ERα) on senescence in transformed human mammary epithelial cells and breast cancer cells. Our results show that ectopic expression of oncoprotein H-ras-V12 in immortalized human mammary epithelial cells (HMEC) significantly inhibited the phosphorylation of the retinoblastoma protein (Rb) and increased the activity of the senescence-associated beta-galactosidase (SA-β-Gal). These senescence-like phenotypes were reversed by ectopic expression of ERα. Similar inhibition of the H-ras-V12-induced SA-β-Gal activity by ERα was also observed in the human mammary epithelial MCF-10A cells. Co-expression of ERα and H-ras-V12 resulted in HMEC anchorage-independent growth in vitro and tumor formation in vivo. Furthermore, inhibition of ERα expression induced senescence-like phenotypes in ERα positive human breast cancer cells such as increased activity of SA-β-Gal, decreased phosphorylation of RB, and loss of mitogenic activity. Thus, the suppression of cellular senescence induced by oncogenic signals may be a major mechanism by which ERα promotes breast carcinogenesis.

BACKGROUND

Obstructive Sleep Apnea (OSA) is associated with many cardiovascular and psychiatric diseases. Day-time sleepiness is a common consequence of sleep apnea and correlates with road-traffic accidents (RTA). Pakistan has a high prevalence of factors which predispose an individual to OSA and death from RTAs are a huge burden. However there is a dearth of prevalence studies in this regard. We aim to understand local relevance of the disease and estimate the prevalence of individuals high-risk for OSA.

METHODS

This cross-sectional survey was conducted among 450 individuals at Aga Khan University Hospital (AKUH), which is a tertiary care teaching hospital in Pakistan. We used the BQ as our measurement tool. Based on the responses, participants were grouped into high or low-risk for OSA.

RESULTS

Our study sample size was 418 with 63.2% males. Mean age of our study population was 30.4 SD+/-12.3 years; and mean BMI was 23.2 SD+/-5 kg/m2. Out of the total sample size 24.9% reported snoring and there were twice as many males who snored as compared to females. Forty-five individuals reported that they had nodded off to sleep while driving at least once in their lifetime. On the other hand, the highest proportion of high risk individuals 47.6% was found in the age group 60 or above. The overall prevalence of individuals who were high risk for sleep apnea was 10%.

CONCLUSIONS

A significant proportion of the population is at high-risk for OSA. Our study shows that despite low BMI and favorable craniofacial anatomy sleep apnea is still a locally relevant disease. Given the local relevance of OSAS, it is important to increase awareness among general population but more importantly among physicians of the developing countries, like Pakistan, about common clinical features and pertinent risk factors and complications of OSAS.

Ca(2+) serves as a second messenger in plant responses to different signals, and salicylic acid (SA) has been recognized as a signal mediating plant responses to many stresses. We recently found that SA treatment led to the cytoplasmic acidification of Salvia miltiorrhiza cells and alkalinization of extracellular medium. Here, we demonstrate that SA can rapidly induce Ca(2+) mobilization in protoplasts, but the induction can be blocked with a channel blocker of either plasma or organellar membranes. Following SA, A 23187, or 10 mmol/L Ca(2+) treatment, rosmarinic acid (RA) accumulation reached the highest level at 16 h, whereas the peak was found at 10 h if plasma membrane channel blockers were used. By contrast, the highest accumulation of RA occurred at 16 h when organellar channels were blocked, exhibiting the same tendency with SA-induced cells. In agreement with these observations, both phenylalanine ammonia-lyase (PAL) activity and its gene expression detected by real-time PCR also showed the same patterns. These results indicate that SA treatment firstly results in calcium release from internal stores, which in turn leads to PAL activity increase, RA accumulation, and a large amount of Ca(2+) influx from apoplast after 10 h of SA induction.

<p><div><b>PURPOSE</b></div>Tr<em>a</em>dition<em>a</em>l tre<em>a</em>tment regimens for <em>a</em>dv<em>a</em>nced prost<em>a</em>te c<em>a</em>ncer, especi<em>a</em>lly c<em>a</em>str<em>a</em>tion-resist<em>a</em>nt prost<em>a</em>te c<em>a</em>ncer, result in low surviv<em>a</em>l times with severe side effects. Therefore, new tre<em>a</em>tment options <em>a</em>re required. Vit<em>a</em>min C (VC) h<em>a</em>s been identified <em>a</em>s <em>a</em> promising <em>a</em>nti-c<em>a</em>ncer <em>a</em>gent of which the effects depend on the <em>a</em>ccumul<em>a</em>tion of H₂O₂ th<em>a</em>t is produced through <em>a</em>utoxid<em>a</em>tion. Sulf<em>a</em>s<em>a</em>l<em>a</em>zine (<em>SAS</em>), <em>a</em> cystine tr<em>a</em>nsporter (X_c^-) inhibitor, is known to suppress cellul<em>a</em>r glut<em>a</em>thione (GSH) biosynthesis. Here, we hypothesized th<em>a</em>t t<em>a</em>rgeting the X_c^- tr<em>a</em>nsporter vi<em>a</em> <em>SAS</em> m<em>a</em>y improve the <em>a</em>nti-c<em>a</em>ncer <em>a</em>ctivity of VC through regul<em>a</em>ting GSH biosynthesis, which in turn m<em>a</em>y result in the <em>a</em>ccumul<em>a</em>tion of re<em>a</em>ctive oxygen species (ROS).</p><Abstr<em>a</em>ctText>The <em>a</em>nti-c<em>a</em>ncer effect of VC <em>a</em>nd/or <em>SAS</em> on prost<em>a</em>te c<em>a</em>ncer cells w<em>a</em>s <em>a</em>ssessed using WST-8, colony form<em>a</em>tion <em>a</em>nd <em>a</em>nnexin V-FITC/PI FACS <em>a</em>ss<em>a</em>ys. Ch<em>a</em>nges in cellul<em>a</em>r ROS <em>a</em>nd GSH levels were determined to verify our hypothesis. Fin<em>a</em>lly, BALB/c nude mice be<em>a</em>ring prost<em>a</em>te c<em>a</em>ncer xenogr<em>a</em>fts were used to <em>a</em>ssess the <em>a</em>nti-c<em>a</em>ncer effects of single or combined VC <em>a</em>nd <em>SAS</em> ther<em>a</em>pies.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>We found th<em>a</em>t <em>SAS</em> could potenti<em>a</em>te the short- <em>a</em>nd long-term cytotoxicity of VC in prost<em>a</em>te c<em>a</em>ncer cells. We <em>a</em>lso found th<em>a</em>t the synergistic effect of <em>SAS</em> <em>a</em>nd VC led to signific<em>a</em>nt cellul<em>a</em>r GSH depletion, resulting in incre<em>a</em>sed ROS <em>a</em>ccumul<em>a</em>tion. This synergistic effect could be reversed by the <em>a</em>ntioxid<em>a</em>nt N-<em>a</em>cetyl-L-cysteine (NAC). The synergistic effect of <em>SAS</em> <em>a</em>nd VC w<em>a</em>s <em>a</em>lso noted in prost<em>a</em>te c<em>a</em>ncer xenogr<em>a</em>fts <em>a</em>nd correl<em>a</em>ted with immunohistochemistry results.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>Our results strongly indic<em>a</em>te th<em>a</em>t <em>SAS</em>, <em>a</em> rel<em>a</em>tively non-toxic drug th<em>a</em>t t<em>a</em>rgets cystine tr<em>a</em>nsporters, in combin<em>a</em>tion with VC m<em>a</em>y be superior to their single <em>a</em>pplic<em>a</em>tions in the tre<em>a</em>tment of prost<em>a</em>te c<em>a</em>ncer.</Abstr<em>a</em>ctText>

It is unknown whether spinal cord motion has a significant effect on cerebrospinal fluid (CSF) pressure and therefore the importance of including fluid structure interaction (FSI) in computational fluid dynamics models (CFD) of the spinal subarachnoid space (SAS) is unclear. This study aims to determine the effects of FSI on CSF pressure and spinal cord motion in a normal and in a stenosis model of the SAS. A three-dimensional patient specific model of the SAS and spinal cord were constructed from MR anatomical images and CSF flow rate measurements obtained from a healthy human being. The area of SAS at spinal level T4 was constricted by 20% to represent the stenosis model. FSI simulations in both models were performed by running ANSYS CFX and ANSYS Mechanical in tandem. Results from this study show that the effect of FSI on CSF pressure is only about 1% in both the normal and stenosis models and therefore show that FSI has a negligible effect on CSF pressure.

The specific radioactivity (SA) of 125I-lysine vasopressin (LVP) was determined by analyzing the binding B (cpm/tube) of variable amounts of tracer T (cpm/tube) to a constant amount of an LVP antibody, in the presence of known quantities L (mol/tube) of LVP standards. The parameters of the equations B = f(F) and B/F = g(T), describing B as a function of free F (cpm/tube) tracer or the ratios B/F as a function of T, were first calculated by nonlinear regression analysis of the results obtained with tracer alone. Then the dependent variables B or B/F were measured in the presence of LVP and analyzed with the same equations by substituting the independent variables F or T with (F + alpha FL) and (T + alpha L), respectively, where alpha (cpm/mol) represents a measure of the SA and FL (FL = L.F/T), free LVP, respectively. The SA was thus treated as an unknown parameter to be calculated by nonlinear regression. This method was compared with the traditional interpolation of the SA from the self-displacement and standard curves. Tracer and ligand were found to have the same affinity for the binding sites, since the set of equations B = f(F + alpha FL) and B/F = g(T + alpha L), describing the binding of the tracer in the presence of LVP and equations B = f(F) and B/F = g(T) to which these equations reduce in the absence of LVP (L = 0), had identical binding parameters. To be valid, any method based on self-displacement requires that the tracer and standards have the same affinity for the binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Are the immune cell profiles and the cytokine concentrations in follicular fluid (FF) and serum at the preovulatory stage different in conventional exogenous gonadotrophin stimulated IVF (c-IVF) compared with natural cycle IVF (NC-IVF)?

The cell counts of CD45+ leucocytes and T cell subpopulations and the cytokine concentrations in FF and serum are different in c-IVF compared to NC-IVF.

FF-derived cells are heterogeneous. Immune cells are involved in intra-ovarian processes and cytokines are required for normal follicular development. Gonadotrophins stimulate the regulatory intrafollicular system and influence the local distribution of immune cells and the intrafollicular release of cytokines. Administration of exogenous gonadotrophins may have a significant effect on this local regulatory system, which then in turn could influence oocyte quality.

The study included 105 patients, 69 undergoing c-IVF and 36 undergoing NC-IVF. c-IVF was performed by exogenous ovarian stimulation with hMG and GnRH antagonists.

FF samples were collected from the first dominant follicle in c-IVF without pooling and from single leading preovulatory follicles in NC-IVF. Three different approaches were used to analyze FF samples: (i) microscopic investigation of CD45+ leucocytes, (ii) fluorescence-activated cell sorting to determine CD19+ B cells and CD3+ T cells including T cell subpopulations (CD4+, CD8+), and (iii) evaluation of tumour necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukins (IL)-2, -6, -8, -10 and vascular endothelial growth factor (VEGF) levels in matched FF and serum samples using the Bio-Plex® platform.

FF obtained from c-IVF contained proportionally more CD45+ leucocytes (P = 0.0384), but fewer CD8+ cytotoxic T cells than FF from NC-IVF. CD3+ T lymphocytes were the most common type of lymphocytes, and the number thereof was comparable in the two study groups. In c-IVF, serum VEGF levels were higher (P = 0.007) than in NC-IVF while FF contained marginally decreased concentrations of IL-8 in c-IVF in comparison to NC-IVF. The cytokine concentration gradient between FF and serum in c-IVF was 10-fold for IL-8 and 8-fold for VEGF and thereby markedly lower than in NC-IVF, where the differences were 32-fold and 30-fold, respectively. Strong positive correlations were determined between FF- IL-10 and FF- VEGF in c-IVF (r = 0.85, P < 0.0001) and in NC-IVF (r = 0.81, P < 0.0001).

N/A.

The ovulation of NC-IVF follicles was induced by the exogenous administration of hCG, which means that the environment did not fully correspond to the physiological situation.

The differences in the immune profile and the cytokine concentrations in c-IVF and NC-IVF follicles support the hypothesis that conventional ovarian stimulation affects indirectly and heterogeneously the intrafollicular milieu, and thereby possibly affects the oocyte quality and the IVF outcome. However, further studies are needed to confirm our findings and to refine stimulation protocols in the context of optimizing the intrafollicular environment during oocyte maturation.

The study was supported by a research grant from IBSA Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. The authors are clinically involved in low dose mono-follicular stimulation and IVF-therapies, using gonadotrophins from all gonadotrophins distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH.

(<em>A</em>bstractText>This pilot study aimed to investigate the effects of incorporating vibrotactile sensory augmentation (<em>SA</em>) on balance performance among people with unilateral vestibular disorders (UVD).</<em>A</em>bstractText>(<em>A</em>bstractText>Eight participants with UVD were recruited. Participants completed 18 balance training sessions across six weeks in a clinical setting. Four participants (68.1±7.5 yrs) were randomized to the experimental group (EG) and received trunk-based vibrotactile <em>SA</em> while performing the balance exercises, and four participants (63.1±11.3 yrs) were assigned to the control group (CG); CG participants completed the balance training without <em>SA</em>. Clinical and kinematic balance performance measures were collected before training; midway through training; and one week, one month, and six months after training.</<em>A</em>bstractText>(<em>A</em>bstractText><em>A</em>ll participants, regardless of group, demonstrated improvements in a subset of the clinical or balance metrics immediately following completion of the balance training protocol. The EG showed significantly greater improvements than the CG for the <em>A</em>ctivities-specific Balance Confidence Scale and postural stability during the two standing balance exercises with head movements. The EG also had larger improvements than the CG for the Sensory Organization Test (SOT), Mini Balance Evaluations Systems Test, Gait Speed Test, Dynamic Gait Index, Functional Gait <em>A</em>ssessment, and vestibular reliance metric calculated based on the SOT.</<em>A</em>bstractText>(<em>A</em>bstractText>Incorporating vibrotactile <em>SA</em> into vestibular rehabilitation programs may lead to additional benefits that may be retained up to six months after training, compared to training without vibrotactile <em>SA</em>. <em>A</em> larger study is warranted to demonstrate statistical significance between the groups.</<em>A</em>bstractText>

Tocopherols are lipid-soluble antioxidants synthesized in plastids of higher plants and other photosynthetic organisms. The four known tocopherols alpha-, beta-, gamma- and delta-tocopherol differ in number and position of methyl groups on their chromanol head group. In unstressed Arabidopsis thaliana leaves, alpha-tocopherol constitutes the main tocopherol form, whereas seeds predominantly contain gamma-tocopherol. Here, we show that inoculation of Arabidopsis leaves with the bacterial pathogen Pseudomonas syringae induces expression of genes involved in early steps of tocopherol biosynthesis, and triggers strong accumulation of gamma-tocopherol, moderate production of delta-tocopherol, and generation of the benzoquinol precursors of tocopherols. The pathogen-inducible biosynthesis of tocopherols is promoted by the immune regulators ENHANCED DISEASE SUSCEPTIBILITY1 and PHYTOALEXIN-DEFICIENT4. In addition, tocopherols accumulate in response to bacterial flagellin and reactive oxygen species. By assessing the content and composition of tocopherol forms in naïve and inoculated plants of wild-type and tocopherol biosynthetic pathway mutants, we provide biochemical insights into the pathogen-inducible tocopherol pathway. Notably, vte2 mutant plants, which are compromised in both tocopherol and benzoquinol precursor accumulation, exhibit increased susceptibility towards compatible P. syringae and possess heightened levels of markers of lipid peroxidation after bacterial infection. The deficiency of tri-unsaturated fatty acids in vte2-1 fad3-2 fad7-2 fad8 quadruple mutants prevents increased lipid peroxidation in the vte2 background and restores pathogen resistance to wild-type levels. Therefore, the tocopherol biosynthetic pathway positively influences SA biosynthesis and guarantees effective basal resistance of Arabidopsis against compatible P. syringae bacteria, possibly by protecting leaves from the pathogen-induced oxidation of trienoic fatty acid-containing lipids.

This cross-sectional study explored the impact of stress, social anxiety, and social class on Internet addiction among adolescents. The subjects-1,634 middle school students-were investigated using the Chinese Perceived Stress Scale (CPSS), the Social Anxiety Scale for Adolescents (SAS-A) Chinese Short Form, the Chinese Internet Addiction Scale (CIAS), and the Questionnaire of Family Social-economic Status. The results show that 12% of the adolescents investigated showed signs of Internet addiction. With the increase of grade, the tendency of Internet addiction and the number of addicts gradually increased. It also showed that Internet addiction is positively correlated with stress and social anxiety and negatively correlated with social class. Social anxiety partially mediates the impact of stress on Internet addiction and social class indirectly influences Internet addiction by moderating the relationship between stress and social anxiety. In conclusion, there is a mediated-moderation effect between stress and adolescent Internet addiction This means that adolescents from different social classes have different types of anxiety when they feel the stress, which influences their choices concerning internet use.

We have reported that infusion of trioctanoin in conscious dogs had little effect on leucine oxidation but decreased the rate of appearance (Ra) and interconversion of leucine and its alpha-keto acid, alpha-ketoisocaproate (KIC). To verify that these conclusions were independent of the leucine tracers and isotope models employed, the studies were repeated using [1-14C]leucine and [4,5-3H]KIC rather than [1-14C]KIC and [4,5-3H]leucine. In the present study, leucine oxidation calculated using the plasma [14C]leucine or [14C]KIC specific activities (SA) increased nearly twofold (P less than 0.001) during trioctanoin infusion in direct contrast to our previous results. When the data from either study were analyzed using the plasma SA of the leucine moiety reciprocal to the infused tracer as a potential indicator of the intracellular leucine SA, similar conclusions were obtained from either study: trioctanoin infusion in conscious dogs appears to increase whole-body leucine oxidation and does not decrease proteolysis. These studies challenge the validity of previously used isotope models of leucine metabolism and suggest that the plasma KIC SA during infusion of labeled leucine may most accurately reflect changes in whole-body leucine metabolism.

BACKGROUND

Quantification of drug induced parkinsonism (DIP) for study purposes is difficult. The most often used Simpson Angus Scale (SAS) lacks proper clinimetric evaluation. The newer Schedule for Assessment of Drug-Induced Movement Disorders (SADIMoD) shows good clinimetric characteristics, but has not been used in published clinical studies, probably due to the complexity of the scale.

OBJECTIVE

To evaluate internal consistency and inter-rater reliability of the SAS and the correlation ot f the SAS with the parkinsonism subscale of the SADIMoD in elderly.

METHODS

Fifteen elderly diagnosed with DIP were recruited. The patients were assessed three times with the SAS by three independent investigators. The resident also performed the SADIMoD. Internal consistency was measured by Cronbach's alpha-coefficient, inter-rater variability was examined with weighted kappa values and percentage of agreement and correlation to SADIMoD by Spearman's correlation coefficient.

RESULTS

SAS demonstrated good internal consistency reliability (Cronbach's alpha coefficients 0.83). Inter-rater reliability for sum score was good. For individual items slight agreement on the item salivation and moderate to very good agreement on remaining items calculated by weighted kappa values was reached. We found 87-100% agreement on the individual items with acceptance of 1 point difference between raters. The SAS demonstrated acceptable correlation with the SADIMoD parkinsonism subscale scores (Spearman's rho = 0.66; p < 0.01).

CONCLUSIONS

The SAS appears to be a valid and by different instructed health care professionals easy to perform research tool to evaluate DIP.

The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

This study investigated the behaviour exhibited by 17 neuropathic pain patients (almost half of whom had documented neurological injury) with diffuse pain and extraterritorial sensory, sudomotor and vasomotor abnormalities, under the influence of intravenous administration of saline-controlled sodium amytal (SA), a medium action barbiturate. After SA (but not after normal saline) infusion, there was a dramatic and selective reduction of allodynia (touch-evoked pain) in all patients displaying this phenomenon, while pin prick and cold hypo- or hyperalgesia, as well as algometric pressure thresholds of the symptomatic limb (as a measurement of deep pain) were minimally changed in most patients. Spontaneous subjective pain was reduced substantially but not totally. The patients were able (once allodynia was eliminated) to recognize a deep-seated pain of which they were unaware before, evoked by firm but gentle palpation of the limb. Sympathetic blocks and A-fibre ischemic blocks in several patients and spinal stimulation in one patient produced effects identical to those observed during SA administration. The deep pain component was maintained despite elimination of allodynia even under stages of sleep induced by SA, at which time the patients would withdraw only the symptomatic limb upon firm but gentle palpation. We argue that neuropathic pain patients have two separate pain components, a cutaneous one (touch-evoked pain or allodynia) mediated by large fibres as a product of central sensitization, and a deep pain component mediated via nociceptors, which can be easily discriminated during systemic administration of SA.

OBJECTIVE

The purpose of this study was to investigate the early tissue response around three one-piece implant systems with different transmucosal designs.

METHODS

Three one-piece dental implant systems with different profiles and surface roughnesses on the transmucosal portion were examined in the current study. The transmucosal portions were flared and machined (FM), concave and machined with microgrooves (CMG), or straight and anodic oxidized (SA). A total of 30 implants (10 of each type) were placed in computer-generated randomized order in the mandibular residual ridges of five beagle dogs. Six months later, all animals were sacrificed and histologic sections were prepared to measure epithelial tissue height, connective tissue contact, and the amount of bone resorption. One-way analysis of variance and the Bonferroni post hoc test were used for statistical evaluation (alpha = 95%).

RESULTS

After a 6-month nonfunctional loading period, all 30 implants were clinically immobile. Slight swelling and redness of the peri-implant soft tissue were noticed around most of the implant abutments. Histometric analysis showed that the FM implants had a longer epithelial tissue height than the CMG implants. The CMG implants showed the greatest amount of connective tissue attachment among the three groups and the least amount of marginal bone resorption. The CMG and SA implants showed bone growth above the initial reference point at 10 and 7 measurement sites, respectively, whereas no bone overgrowth was noted around the FM implants.

CONCLUSIONS

Based on this study conducted in five beagle dogs, a concave transmucosal profile with a microgrooved surface was associated with longer connective tissue attachments and less bone resorption versus implants that were flared with a machined surface or straight with an anodic oxidized surface in the early healing phase. Int J Oral Maxillofac Implants 2010;25:309-314.

OBJECTIVE

To develop a short, 4-item arthritis severity questionnaire that is simple to score, clinically useful and meaningful, and suitable for use in primary care, where osteoarthritis (OA) is the primary prevalent arthritis illness.

METHODS

Data and items from the Medical Outcomes Study Short Form 36 (SF-36), the Western Ontario McMaster Osteoarthritis Index (WOMAC(c)), and visual analog scales (VAS) for pain and patient global severity were studied in 16,519 patients with arthritis. The Short Arthritis Assessment Scale (SAS) was developed by performing multivariable analyses that involved individually adding/subtracting items in differing regression models. The candidate items and scales were then studied by Rasch analysis, and tested for effect size, sensitivity to change, and reliability. The resultant scale was validated using data from a recent OA clinical trial.

RESULTS

The VAS pain and VAS global severity scales and 2 items from the WOMAC in the VAS format, difficulty going down stairs and difficulty shopping, were found to be the best predictors of change in health status. The 4-item SAS was reliable (Cronbach's alpha = 0.87), demonstrated good test-retest reliability (Lin's concordance coefficient = 0.85), was unidimensional, and was strongly correlated with other important clinical measures, indicating good construct validity. Using data from a recent randomized clinical trial in OA, the SAS performed better than the WOMAC pain scale and the SF-36 physical component score in detecting change, and at least as well as the clinical trial VAS pain scale.

CONCLUSIONS

The SAS is a 4-item arthritis severity questionnaire that can be easily administered in primary care for patients with OA, but is suitable for use across all arthritis illnesses. Scoring is simple, requiring only the addition of four 10-point scales, and interpretation is straightforward. The SAS may have a role in rapid assessment of the arthritis patient in primary care practice.

<Abstr<em>a</em>ctText>Limited d<em>a</em>t<em>a</em> exist on the incidence of hip fr<em>a</em>ctures in South Afric<em>a</em> (<em>SA</em>). We report gender <em>a</em>nd ethnic specific incidence r<em>a</em>tes of hip fr<em>a</em>ctures in <em>SA</em>.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>In <em>a</em> multicentre prospective study, conducted in geogr<em>a</em>phic<em>a</em>lly defined municip<em>a</em>lities of three provinces in <em>SA</em>, <em>a</em> structured questionn<em>a</em>ire w<em>a</em>s <em>a</em>dministered to <em>a</em>ll subjects <em>a</em>ged 40 ye<em>a</em>rs <em>a</em>nd over, presenting with <em>a</em> new <em>a</em>tr<em>a</em>um<em>a</em>tic hip fr<em>a</em>cture, from 1 April 2017 to 31 M<em>a</em>rch 2018. Gender <em>a</em>nd ethnic specific incidence r<em>a</em>tes (IR) of hip fr<em>a</em>ctures were c<em>a</em>lcul<em>a</em>ted using popul<em>a</em>tion st<em>a</em>tistics from St<em>a</em>tistics <em>SA</em>.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>Of the 2767 subjects enrolled, 1914 (69·2%) were women <em>a</em>nd 853 (30·8%) were men. The m<em>a</em>jority of subjects were from the White popul<em>a</em>tion (40·9%) followed by those from the Afric<em>a</em>n (26·4%), Coloured (18·7%) <em>a</em>nd Indi<em>a</em>n (13·9%) popul<em>a</em>tions. Men with hip fr<em>a</em>ctures were signific<em>a</em>ntly younger th<em>a</em>n women in the tot<em>a</em>l group (69 [IQR 59-79] versus 77 ye<em>a</em>rs [IQR 68-84], p < 0·001) <em>a</em>nd in e<em>a</em>ch ethnic group. White subjects were signific<em>a</em>ntly older (p < 0·0001) <em>a</em>nd Afric<em>a</em>ns signific<em>a</em>ntly younger (p < 0·0001) th<em>a</em>n the other ethnic groups. In women, the highest IR w<em>a</em>s noted in the White popul<em>a</em>tion (176·0 per 100,000), followed by th<em>a</em>t in the Indi<em>a</em>n (147·7 per 100,000), Coloured (73·2 per 100,000) <em>a</em>nd Afric<em>a</em>n popul<em>a</em>tions (43·6 per 100,000). A simil<em>a</em>r p<em>a</em>ttern w<em>a</em>s seen in men <em>a</em>lbeit <em>a</em>t lower r<em>a</em>tes, with the highest r<em>a</em>te in White men <em>a</em>t 76·5 per 100,000. In the tot<em>a</em>l study popul<em>a</em>tion <em>a</em>nd the Afric<em>a</em>n popul<em>a</em>tion, the IR w<em>a</em>s higher in men comp<em>a</em>red to women in subjects under 60 ye<em>a</em>rs. In the White popul<em>a</em>tion, the IR w<em>a</em>s higher in men comp<em>a</em>red to women in the 40-44 ye<em>a</em>rs <em>a</em>ge group. While in the Coloured <em>a</em>nd Indi<em>a</em>n popul<em>a</em>tions the IR w<em>a</em>s higher in men comp<em>a</em>red to women in the 40-49 ye<em>a</em>rs <em>a</em>nd 45-54 ye<em>a</em>rs <em>a</em>ge groups, respectively. There w<em>a</em>s <em>a</em>n incre<em>a</em>se in the rel<em>a</em>tive risk r<em>a</em>tios with <em>a</em>ge in the tot<em>a</em>l study popul<em>a</em>tion, <em>a</em>nd in <em>a</em>ll ethnic groups in both women <em>a</em>nd men.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>Hip fr<em>a</em>ctures occur in <em>a</em>ll ethnic groups in South Afric<em>a</em> with higher IRs in the White <em>a</em>nd Indi<em>a</em>n popul<em>a</em>tions comp<em>a</em>red to the Coloured <em>a</em>nd Afric<em>a</em>n popul<em>a</em>tions. Consistent with the published liter<em>a</em>ture, the over<em>a</em>ll hip fr<em>a</em>cture IR w<em>a</em>s higher in women th<em>a</em>n in men, except in the younger <em>a</em>ge groups, <em>a</em>nd incre<em>a</em>sed with <em>a</em>ge.</Abstr<em>a</em>ctText><Abstr<em>a</em>ctText>South Afric<em>a</em>n Medic<em>a</em>l Rese<em>a</em>rch Council <em>a</em>nd the University of Kw<em>a</em>Zulu-N<em>a</em>t<em>a</em>l Competitive Rese<em>a</em>rch Gr<em>a</em>nt.</Abstr<em>a</em>ctText>

Pigs may play an important role in the evolution and ecology of influenza A virus. The tracheal epithelium of pigs contain both SA alpha 2,6 Gal and SA alpha 2,3 Gal receptors and can be infected with swine, human and avian viruses, therefore, pigs have been considered as an intermediate host for the adaptation of avian influenza viruses to humans or as mixing vessels for the generation of genetically reassortant viruses. Evolution patterns among swine influenza viruses including evolution of host adaptation, antigenic drift and genetic reassortment, and the latter is the main one. Unlike human influenza viruses, swine viruses have different epizootiological patterns in different areas of world, which is enzootic and geographic dependence. Currently, three predominant subtypes of influenza virus are prevalent in pig populations worldwide: H1N1, H3N2, and H1N2, and these include classical swine H1N1, avian-like H1N1, human-like H3N2, reassortant H3N2 and various genotype H1N2 viruses. In Europe, North America and China, influenza A viruses circulating in pigs are distinct in the genetic characteristics and genetic sources. Since 1979, three subtypes, avian-like H1N1, reassortant H1N2 and H3N2 viruses, have been co-circulating in European swine. Before 1998, classical H1N1 viruses were the exclusive cause of swine influenza in North America. However, after that, three triple-reassortant H1N2, H3N2 and H1N1 viruses with genes of human, swine and avian virus began to emerge in pigs. Genetically, the pandemic viruses emerging in human, so called influenza A (H1N1) viruses, contain genes from both Europe and North American SIV lineages. SIV is not the same as Europe and the United States in the prevalence and genetic background in China, mainly classical swine H1N1 and human-like H3N2 type virus. However, in recent years, SIV from Europe and North America have been introduced into Chinese pig herds, so more attention should be given on the evolutionary of SIV in China. Worldwide, more than 50 cases of SIV infection in human have been documented since the 1970s, which indicate that SIV is also an important zoonosis, and the potential of SIV as human pandemic virus or genes donator. In view of SIV in the importance of ecology, as well as a potential threat to human public health, it is recommended to start as soon as possible regular surveillance, paying close attention to its prevalence and molecular evolution. At the same time, we should establish the surveillance network of the whole influenza virus (including human and animal influenza virus) in China, ecologically mastering the prevalence and evolution of influenza viruses, which is of great significance for the protection of animal health and the prevention of human pandemic.

We studied the location of alpha-tocopherol (alpha-Toc) in the liposome membranes, and the dynamics of its radical scavenging and recycling by ascorbic acid. The quenching efficiency of alpha-Toc fluorescence by acrylamide, a water soluble quencher with a very low capacity to penetrate through phospholipid bilayers, was very low in dimyristoyl-phosphatidylcholine (DMPC) liposomes with and without charges, but relatively high in sodium dodecylsulphate (SDS) or tetradecyl-trimethylammonium bromide (TTAB) micelles. These findings indicate the low exposure of the chromanol at the surface of the liposome membranes. alpha-Toc was oxidized by positively charged Fe3+ more slowly in DMPC liposomes negatively charged with dicetylphosphate (DCP) (1st order rate constant, 1.41 x 10(-3) sec-1) than in negatively charged SDS micelles (7.14 x 10(-1) sec-1). Assuming that 100% of the OH-groups of alpha-Toc are at the membrane surface of the SDS micelles, as the oxidation rate of alpha-Toc in liposomes is 0.32 microM sec-1, which is about 150 times slower than that in micelles (49.3 microM sec-1), only 0.65% of the OH-groups of alpha-Toc are probably present at the membrane surface of the liposomes. The fluorescence of alpha-Toc was most effectively quenched by interaction with the spin group of the probe 5-(N-oxyl-4,4'-dimethyloxazolidin-2-yl) stearic acid (5-NS), indicating that its OH-group was located in a position corresponding to an inner 5-methylene carbon under the membrane surface. Ascorbic acid (AsA) was rapidly oxidized by 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN) when it was ionically trapped at the positively charged membrane surface of egg yolk phosphatidylcholine (egg PC) liposomes with stearylamine (SA), but was scarcely oxidized in negatively charged egg PC-DCP liposomes because it was present in the bulk water phase. These findings suggest that lipid peroxy-radicals move from the hydrophobic region to near the membrane surface, where they are trapped by alpha-Toc. The electron spin resonance (ESR) spectra of 5-NS and 16-NS labeled in DMPC or DMPC-DCP liposomes were not changed by the addition of AsA in the buffer solution of pH 7.0, indicating that negatively charged AsA could not penetrate into neutrally or negatively charged membranes. alpha-Toc inhibited AMVN-induced lipid peroxidation and AsA extended its inhibition period, but glutathione (GSH) did not affect this inhibition period.(ABSTRACT TRUNCATED AT 400 WORDS)

To provide evidence for the oxidative effect of nickel (Ni) treatment on blood, lipid peroxidation (LPO) and hydroxyl radical (*OH) generation were examined in human plasma. Nickel chloride induced LPO in plasma of human blood in vitro in a concentration-dependent (0-10 mM) and time-dependent (0-2 h) manner. The *OH production in plasma was quantified by measurement of conversion of salicylic acid (SA) into its hydroxylated products, 2,3- and 2,5-dihydroxybenzoate (DHB). The concentrations of 2,3- and 2,5-DHB in plasma increased in a concentration-dependent manner after Ni treatment for 1 h. Furthermore, a decreasing trend in alpha-tocopherol levels in plasma was observed after Ni treatment. Concurrent incubation with gluthathione (GSH), catechin (CTCH), and mannitol decreased lipid peroxidation and reduced *OH formation induced by Ni, but exacerbation of the decrease of alpha-tocopherol in plasma occurred with catechin.

Acidic glycolipid of ganglio-(containing sialic acid) and sialyl-lactofucosyl-type, SA-Lex (containing sialic acid and fucose) are developmentally regulated and appear to be ubiquitous on neuronal and cancer cell surfaces of animals. Two glycolipid: beta-galactosyltransferases, GalT-3 and GalT-4, were characterized in embryonic chicken brain (ECB). Based on substrate competition experiments, these two activities were believed to be due to expression of two gene products. A cDNA fragments (about 600 bp) encoding the catalytic domain of the GalT-4 (UDP-Gal:LcOse3Cer beta1,4galactosyltransferase) from ECB and human Colo-204 were isolated. These cDNAs were expressed as a soluble glutathione-S-transferase fusion protein (48 kDa) in Escherichia coli. Interactions between GlcNAc-, UDP-hexanolamine-, and alpha-lactalbumin were studied with the purified fusion protein (recombinant and truncated). Functionally it was similar to that of native GalT-4 purified (40000-fold) from 11-day-old ECB. GalT-3 (UDP-Gal:GM2beta1,3galactosyltransferase) was purified from 19-day-old ECB, and a polyclonal antibody was produced against the peptide backbone for immunoscreening of a lambdaZAP ECB cDNA expression library. Each of the GalT-3 peptides (62 and 65 kDa was analyzed by protein fingerprinting analysis indicating a similar peptide mapping pattern.