[Factors leading to delay in obtaining definitive diagnosis of suspicious lesions for breast cancer in a dedicated health unit in Rio de Janeiro].
To evaluate the factors leading to delays in obtaining definitive diagnosis of suspicious lesions for breast cancer. A cross-sectional, observational study was carried out with 104 women attending a cancer hospital with a diagnosis or suspected diagnosis of breast cancer. A semistructured questionnaire on the patients' demographic, clinical characteristics and the use of services was applied.Variables were compared using t-Student test, Mann-Whitney test, Pearson's chi2 test or Fisher's exact test, as appropriate. In order to identify the variables associated with delays in breast cancer diagnosis, the Odds Ratio (OR) were calculated together with their respective 95% confidence intervals (95%CI) and a logistic regression model was constructed. Age of patients was 54+/-12.6 years (mean+/-standard deviation). Most of the women were white (48.1%), married (63.5%), living in the city of Rio de Janeiro (57.7%) and poorly educated (60.6%). The median time between the first sign or symptom of the disease and first consultation was one month and the mean time between first consultation and confirmation of diagnosis was 6.5 months. In 51% of the women, diagnosis was late (stages II-IV). Symptomatic presentation and longer delay between symptom onset and the first evaluation and between symptom onset and the diagnosis were found to be significant factors (p<0.05) for delays in obtaining definitive diagnosis of suspicious lesions. The results of this study suggest that efforts must be made to reduce the time needed to get an appointment with a doctor and to confirm a diagnosis of suspicious lesions, as well as to educate physicians and the women themselves regarding the importance of breast symptoms and the value of prompt evaluation, diagnosis, and treatment.


Flow cytometry-based FRET identifies binding intensities in PPARγ1 protein-protein interactions in living cells.
PPARγ is a pharmacological target in inflammatory and metabolic diseases. Upon agonistic treatment or following antagonism, binding of co-factors is altered, which consequently affects PPARγ-dependent transactivation as well as its DNA-independent properties. Therefore, establishing techniques to characterize these interactions is an important issue in living cells. Methods: Using the FRET pair Clover/mRuby2, we set up a flow cytometry-based FRET assay by analyzing PPARγ1 binding to its heterodimerization partner RXRα. Analyses of PPARγ-reporter and co-localization studies by laser-scanning microscopy validated this system. Refining the system, we created a new readout to distinguish strong from weak interactions, focusing on PPARγ-binding to the co-repressor N-CoR2. Results: We observed high FRET in cells expressing Clover-PPARγ1 and mRuby2-RXRα, but no FRET when cells express a mRuby2-RXRα deletion mutant, lacking the PPARγ interaction domain. Focusing on the co-repressor N-CoR2, we identified in HEK293T cells the new splice variant N-CoR2-ΔID1-exon. Overexpressing this isoform tagged with mRuby2, revealed no binding to Clover-PPARγ1, nor in murine J774A.1 macrophages. In HEK293T cells, binding was even lower in comparison to N-CoR2 constructs in which domains established to mediate interaction with PPARγ binding are deleted. These data suggest a possible role of N-CoR2-ΔID1-exon as a dominant negative variant. Because binding to N-CoR2-mRuby2 was not altered following activation or antagonism of Clover-PPARγ1, we determined the effect of pharmacological treatment on FRET intensity. Therefore, we calculated flow cytometry-based FRET efficiencies based on our flow cytometry data. As with PPARγ antagonism, PPARγ agonist treatment did not prevent binding of N-CoR2. Conclusion: Our system allows the close determination of protein-protein interactions with a special focus on binding intensity, allowing this system to characterize the role of protein domains as well as the effect of pharmacological agents on protein-protein interactions.


Temperature-induced multi-species cohort effects in sympatric snakes.
In reptiles, reproductive maturity is often determined by size rather than age. Consequently, growth early in life may influence population dynamics through effects on generation time and survival to reproduction. Because reproductive phenology and pre- and post-natal growth are temperature dependent, environmental conditions may induce multi-species cohort effects on body size in sympatric reptiles. I present evidence of this using 10 years of neonatal size data for three sympatric viviparous snakes, Dekay's Brown snakes (Storeria dekayi), Red-bellied Snakes (S. occipitomaculata), and Common Garter snakes (Thamnophis sirtalis). End-of-season neonatal size varied in parallel across species such that snout-vent length was 36%-61% greater and mass was 65%-223% greater in years when gestating females could achieve higher April-May (vs. June-July or August-September) operative temperatures. Thus, temperature had a larger impact during follicular enlargement and ovulation than during gestation or post-natal growth. Multi-species cohort effects like these may affect population dynamics and the magnitude of these effects may increase with climate change.


The large subunit of replication factor C interacts with the histone deacetylase, HDAC1.
Replication factor C (RFC) is a pentameric complex of five distinct subunits that functions as a clamp loader, facilitating the loading of proliferating cell nuclear antigen (PCNA) onto DNA during replication and repair. More recently the large subunit of RFC, RFC (p140), has been found to interact with the retinoblastoma (Rb) tumor suppressor and the CCAAT/enhancer-binding protein alpha (C/EBP alpha) transcription factor. We now report that RFC (p140) associates with histone deacetylase activity and interacts with histone deacetylase 1 (HDAC1). This complex is functional and when targeted to promoters as a Gal4 fusion, RFC (p140) is a strong, deacetylase-dependent repressor of transcription. Further analysis revealed that RFC (p140) contains two distinct transcriptional repression domains. Moreover, both of these domains interact separately with HDAC1.


Liver unidentified bright object in a septic patient.
The typical sonographic appearance of liver hemangiomas is a well-demarcated hyperechoic mass with homogeneous echodensity. Focal liver lesions may change their ultrasound characteristics over time. We present a case of dynamic pattern of liver hemangiomas during a state of systemic inflammation.


Development of a high-throughput method to evaluate serum bactericidal activity using bacterial ATP measurement as survival readout.
Serum Bactericidal Activity (SBA) assay is the method of choice to evaluate the complement-mediated functional activity of both infection- and vaccine-induced antibodies. To perform a typical SBA assay, serial dilutions of sera are incubated with target bacterial strains and complement. The conventional SBA assay is based on plating on agar the SBA reaction mix and counting the surviving bacterial colony forming units (CFU) at each serum dilution. Even with automated colony counting, it is labor-intensive, time-consuming and not amenable for large-scale studies. Here, we have developed a luminescence-based SBA (L-SBA) method able to detect surviving bacteria by measuring their ATP. At the end of the SBA reaction, a single commercially available reagent is added to each well of the SBA plate, and the resulting luminescence signal is measured in a microplate reader. The signal obtained is proportional to the ATP present, which is directly proportional to the number of viable bacteria. Bactericidal activity is subsequently calculated. We demonstrated the applicability of L-SBA with multiple bacterial serovars, from 5 species: Citrobacter freundii, Salmonella enterica serovars Typhimurium and Enteritidis, Shigella flexneri serovars 2a and 3a, Shigella sonnei and Neisseria meningitidis. Serum bactericidal titers obtained by the luminescence readout method strongly correlate with the data obtained by the conventional agar plate-based assay, and the new assay is highly reproducible. L-SBA considerably shortens assay time, facilitates data acquisition and analysis and reduces the operator dependency, avoiding the plating and counting of CFUs. Our results demonstrate that L-SBA is a useful high-throughput bactericidal assay.


All-cause mortality and medication risk factors in schizophrenia: a prospective cohort study.
It is well established that persons with schizophrenia have high mortality rates. There is conflicting evidence that antipsychotic and perhaps other medications routinely used to treat schizophrenia contribute to mortality risk. A health insurer database was used to examine schizophrenia diagnosis and mortality in 2008. Information from the period 2006-2008 was used to analyze demographics and medication prescriptions. The risk set composed of patients with schizophrenia using an antipsychotic (n = 7415) and a group of randomly chosen control subjects (n = 97,726). The mortality risk for having a diagnosis of schizophrenia and using an antipsychotic versus the random control group was a hazard ratio (HR) of 2.6; 95% CI, 2.0-3.2. Over the 3-year period, age, receiving a first-generation antipsychotic, and the use of a mood stabilizer were associated with a higher risk of mortality: HR, 1.06; 95% CI, 1.04-1.08; HR, 2.36; 95% CI, 1.38-4.04; and HR, 8.42; 95% CI, 3.06-24.07, respectively. Patients with schizophrenia have higher mortality rates than normal controls. The type of antipsychotic and concomitant medication can affect mortality rates in schizophrenia.


A rare cause of recurrent acute pancreatitis.
Annular pancreas is a rare entity. It clinically presents with intestinal obstruction. We present a case of a young female with incomplete annular pancreas presented with recurrent acute pancreatitis.


Transport of a Fluorescent Analogue of Glucose (2-NBDG) versus Radiolabeled Sugars by Rumen Bacteria and Escherichia coli.
Fluorescent tracers have been used to measure solute transport, but transport kinetics have not been evaluated by comparison of radiolabeled tracers. Using Streptococcus equinus JB1 and other bacteria, the objective of this study was to determine if a fluorescent analogue of glucose (2-NBDG) would be transported with the same kinetics and transporters as [(14)C]glucose. We uniquely modified a technique for measuring transport of radiolabeled tracers so that transport of a fluorescent tracer (2-NBDG) could also be measured. Deploying this technique for S. equinus JB1, we could detect 2-NDBG transport quantitatively and within 2 s. We found the Vmax of 2-NBDG transport was 2.9-fold lower than that for [(14)C]glucose, and the Km was 9.9-fold lower. Experiments with transport mutants suggested a mannose phosphotransferase system (PTS) was responsible for 2-NBDG transport in S. equinus JB1 as well as Escherichia coli. Upon examination of strains from 12 species of rumen bacteria, only the five that possessed a mannose PTS were shown to transport 2-NBDG. Those five uniformly transported [(14)C]mannose and [(14)C]deoxyglucose (other glucose analogues at the C-2 position) at high velocities. Species that did not transport 2-NBDG at detectable velocities did not possess a mannose PTS, though they collectively possessed several other glucose transporters. These results, along with retrospective genomic analyses of previous 2-NBDG studies, suggest that only a few bacterial transporters may display high activity toward 2-NBDG. Fluorescent tracers have the potential to measure solute transport qualitatively, but their bulky fluorescent groups may restrict (i) activity of many transporters and (ii) use for quantitative measurement.


Symptoms of Infarction in Women: Is There a Real Difference Compared to Men? A Systematic Review of the Literature with Meta-Analysis.
(1) Context: The management of acute coronary syndrome (ACS) is based on a rapid diagnosis. The aim of this study was to focus on the ACS symptoms differences according to gender, in order to contribute to the improvement of knowledge regarding the clinical presentation in women. (2) Methods: We searched for relevant literature in two electronic databases, and analyzed the symptom presentation for patients with suspected ACS. Fifteen prospective studies were included, with a total sample size of 10,730. (3) Results: During a suspected ACS, women present more dyspnea, arm pain, nausea and vomiting, fatigue, palpitations and pain at the shoulder than men, with RR (95%CI) of 1.13 [1.10; 1.17], 1.30 [1.05; 1.59], 1,40 [1.26; 1.56], 1.08 [1.01; 1.16], 1.67 [1.49; 1.86], 1.78 [1.02; 3.13], respectively. They are older by (95%CI) 4.15 [2.28; 6.03] years compared to men. The results are consistent in the analysis of the ACS confirmed subgroup. (4) Conclusions: We have shown that there is a gender-based symptomatic difference and a female presentation for ACS. The "typical" or "atypical" semiology of ACS symptoms should no longer be used.


Interferon and cytotoxic chemotherapy for the treatment of post-transplant lymphoproliferative disorder.
Interferon-alpha and cytotoxic chemotherapy may be effective treatment modalities for the post-transplant lymphoproliferative disorder. Interferon-alpha may result in a complete response in up to 40% of patients, while chemotherapy may be effective in 75% of those failing local surgical excision, a reduction in immunosuppression, and an antiviral agent. Interferon may be used early after diagnosis in patients with relatively slowly growing tumors. Chemotherapy should be selected for patients with bulky, rapidly growing malignancies. The toxicity of chemotherapy may be minimized by discontinuing maintenance immunosuppression during chemotherapy, administering GCSF, and providing antimicrobial prophylaxis. Rejection is minimized by the reintroduction of maintenance immunosuppression when the patient is no longer neutropenic.


Recent Advance of Nanomaterial-Mediated Tumor Therapies in the Past Five Years.
Cancer has posed a major threat to human life and health with a rapidly increasing number of patients. The complexity and refractory of tumors have brought great challenges to tumor treatment. In recent years, nanomaterials and nanotechnology have attracted more attention and greatly improved the efficiency of tumor therapies and significantly prolonged the survival period, whether for traditional tumor treatment methods such as radiotherapy, or emerging methods, such as phototherapy and immunotherapy, sonodynamic therapy, chemodynamic therapy and RNA interference therapeutics. Various monotherapies have obtained positive results, while combination therapies are further proposed to prevent incomplete eradication and recurrence of tumors, strengthen tumor killing efficacy with minimal side effects. In view of the complementary promotion effects between different therapies, it is vital to utilize nanomaterials as the link between monotherapies to achieve synergistic performance. Further development of nanomaterials with efficient tumor-killing effect and better biosafety is more in line with the needs of clinical treatment. In a word, the development of nanomaterials provides a promising way for tumor treatment, and here we will review the emerging nanomaterials towards radiotherapy, phototherapy and immunotherapy, and summarized the developed nanocarriers applied for the tumor combination therapies in the past 5 years, besides, the advances of some other novel therapies such as sonodynamic therapy, chemodynamic therapy, and RNA interference therapeutics have also been mentioned.


A nasal interleukin-12 DNA vaccine coexpressing Yersinia pestis F1-V fusion protein confers protection against pneumonic plague.
Previous studies have shown that mucosal application of interleukin-12 (IL-12) can stimulate elevated secretory immunoglobulin A (IgA) responses. Since possible exposure to plague is via Yersinia pestis-laden aerosols that results in pneumonic plague, arming both the mucosal and systemic immune systems may offer an added benefit for protective immunity. Two bicistronic plasmids were constructed that encoded the protective plague epitopes, capsular antigen (F1-Ag) and virulence antigen (V-Ag) as a F1-V fusion protein but differed in the amounts of IL-12 produced. When applied nasally, serum IgG and mucosal IgA anti-F1-Ag and anti-V-Ag titers were detectable beginning at week 6 after three weekly doses, and recombinant F1-Ag boosts were required to elevate the F1-Ag-specific antibody (Ab) titers. Following pneumonic challenge, the best efficacy was obtained in mice primed with IL-12(Low)/F1-V vaccine with 80% survival compared to mice immunized with IL-12(Low)/F1, IL-12(Low)/V, or IL-12(Low) vector DNA vaccines. Improved expression of IL-12 resulted in lost efficacy when using the IL-12(High)/F1-V DNA vaccine. Despite differences in the amount of IL-12 produced by the two F1-V DNA vaccines, Ab responses and Th cell responses to F1- and V-Ags were similar. These results show that IL-12 can be used as a molecular adjuvant to enhance protective immunity against pneumonic plague, but in a dose-dependent fashion.


Anti-inflammaging effects of Lactobacillus brevis OW38 in aged mice.
In the present study, lactic acid bacteria (LAB) strains were collected from kimchi and were screened to isolate strains that inhibit lipopolysaccharide (LPS) production by Escherichia coli and p16 expression and nuclear factor-kappa B (NF-κB) activation in LPS-stimulated macrophages. Oral administration of Lactobacillus brevis OW38 (1×109 cfu/mouse) to aged mice (male, 18 months old) for 8 weeks reduced the LPS level in colon fluid and blood. In addition, OW38 treatment also reduced the ratio of Firmicutes or Proteobacteria to Bacteroidetes, which was significantly higher in aged mice than in young mice. Treatment with OW38 in aged mice inhibited the expression of inflammatory markers, such as myeloperoxidase, tumour necrosis factor (TNF), and interleukin (IL)-1β, and inhibited NF-κB activation. Furthermore, it induced the expression of colonic tight junction proteins zonula occludens-1, occludin, and claudin-1. OW38 treatment also suppressed the expression of senescence markers p16, p53, and SAMHD1 in the colon and the hippocampus of aged mice. In addition, it significantly restored spontaneous alternation as well as the expression of brain-derived neurotrophic factor and doublecortin in aged mice compared to that in young mice (P<0.05). Based on these findings, we conclude that OW38 treatment may ameliorate aging-associated colitis and memory impairment by inhibiting gut microbiota LPS production, NF-κB activation, and p16 expression.


Sequential appearance of IL-1 and IL-6 activities in rat carrageenin-induced pleurisy.
IL-1 and IL-6 activities were measured in the pleural exudate of rats during carrageenin-induced pleurisy to examine the relationship of the local production of cytokines to the inflammatory reaction. Time courses of appearance of the cytokines and inflammatory parameters in the exudate were compared. IL-1 activity and exudate volume started to increase at 1 h after the carrageenin injection, and then slightly later IL-6 activity and leukocyte number began to increase. IL-1 showed peak activity of approximately 700 U at 3 h and IL-6, of 6000 U at 5 h in the exudate, whereas exudate volume and number of polymorphonuclear leukocytes continued to increase thereafter. Furthermore, IL-6 level in the plasma of the carrageenin-injected rats showed a peak at 4 h (30 U/ml), and when rhIL-1 alpha (100,000 U) was intrapleurally injected, the more rapid increase in plasma IL-6 level was demonstrated at 1 h (30 U/ml). This latter rise was neutralized with simultaneous injection of anti-rhIL-1 alpha antibody. These facts indicate the possibility that IL-1 produced in the exudate or injected could rapidly propagate a signal to induce IL-6 production in the circulation. It took several hours to transmit an inflammatory signal that stimulated the liver to synthesize the acute-phase protein, T-kininogen. The time lag from the peak induction of IL-1 to the T-kininogen-increase in the pleurisy corresponded well to the interval for T-kininogen-increase by exogenous rhIL-1 alpha injection. These results strongly suggest that the initial inflammatory stimulus induces sequentially IL-1, IL-6, and T-kininogen production in this carrageenin inflammation.


Evaluating the aggregate spatial structure of Canadian metropolitan areas.
"Few attempts have been made to develop and test a conceptual framework for the comparative analysis of urban spatial structure and growth. This paper offers one aggregate approach as well as a series of empirical tests based on Canada's 27 largest urban areas. Six composite indices are introduced: population densities, rates of change, intraurban population redistribution, mobility rates, incidence of low-income populations, and degree of social polarization. Regression analyses reveal that differences among urban areas in spatial patterning and structural change are consistent with the hypothesized effects of city size, age, transport usage, social heterogeneity, production base, and physical setting. Yet immense regional and intraurban diversity remains. No single model of urban structure is sufficient to capture this diversity." (SUMMARY IN FRE)


Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer?
The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except alpha(2)-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 microg/L (areas under the curve, 0.851 vs 0.838). Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.


[Analysis of clonal origin of concomitant chronic lymphocytic leukemia and multiple myeloma in a patient with advanced age].
Concomitant chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) is a rare disease. Studies on the clonal origin of both lymphocyte and plasma cell in this disease has been few. So far it has not been reported in China. The paper reports a case of 92-year old patient with concomitant CLL and MM and the research results on the origin of lymphocyte and plasma cell by analyzing the morphologic characteristics, monoclonal antibodies, immunoglobulin Ig or TCR gene rearrangement (GR), Ig single-strand conformation polymorphsm (SSCP) fingerprint mapping and heteroduplex formation. The Ig H GR segments same in size, single strand conformation and sequence characteristics have been obtained from both peripheral blood and bone marrow DNA, even though the cells of CLL and MM had different characteristics in morphology and different secretion of IgM lambda and IgA lambda. The results suggested that the malignant cells of both CLL and MM in this patient had common origin from the B-cell.


[Thrombolytic treatment for acute myocardial infarction in menstruating women].
A 44-year-old woman was admitted to the intensive cardiac care unit due to an extensive anterior myocardial infarction of acute onset. Because she was menstruating, thrombolytic treatment was relatively contraindicated. On primary coronary angioplasty, an occluding clot was found in her proximal, left anterior coronary artery. Despite menstrual bleeding, 500,000 IU/10 min of urokinase was infused into the artery. After restoration of blood flow, angioplasty was performed and a 90% residual stenosis was found in the artery. She was then fully heparinized for 5 days and concomitantly given aspirin, 100 mg/day. There were no complications, nor was menstrual bleeding excessive. She was discharged in good clinical and hemodynamic status after 10 days of hospitalization. Based on our experience, and reinforced by an additional 23 cases reported by others, we suggest that thrombolytic treatment should not be withheld even in menstruating women, when access to primary, coronary angioplasty is not available.


The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-alpha, IL-1beta and IFN-gamma.
It is becoming widely accepted that the inflammatory response is involved in neurodegenerative disease. In this context, we have developed an animal model of dopaminergic system degeneration by the intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation. To address the importance of the inflammatory response in the LPS-induced degeneration of nigral dopaminergic neurones, we carried out two different kinds of studies: (i) the possible protective effect of an anti-inflammatory compound, and (ii) the effect of the intranigral injection of inflammatory cytokines (TNF-alpha, IL-1beta and IFN-gamma) on dopaminergic neurones viability. Present results show that dexamethasone, a potent anti-inflammatory drug that interferes with many of the features characterizing pro-inflammatory glial activation, prevented the loss of catecholamine content, Tyrosine hydroxylase (TH) activity and TH immunostaining induced by LPS-injection and also the bulk activation of microglia/macrophages. Surprisingly, injection of the pro-inflammatory cytokines failed to reproduce the LPS effect. Taken together, our results suggest that inflammatory response is implicated in LPS-induced neurodegeneration. This damage may be due, at least in part, to a cascade of events independent of that described for TNF-alpha/IL-1 beta/IFN-gamma.


Simultaneous analysis of gamma-hydroxybutyric acid, gamma-butyrolactone, and 1,4-butanediol by micellar electrokinetic chromatography.
A micellar electrokinetic chromatography (MEKC) method was optimised for simultaneous analysis of gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (BD). Best conditions for separation and baseline stability were achieved using a carrier electrolyte comprising 30.0mM sodium barbital and 150.0mM sodium dodecyl sulphate (SDS) at pH 10.2. Calibration functions were linear, giving correlation coefficients (r(2)) >0.998 for the three target compounds. Limits of detection (LOD) defined as three times the noise, were 5.1mg/l, 0.34 and 0.25g/l for GHB, GBL and BD, respectively. The repeatability of migration times and peak areas, expressed as the R.S.D. (n = 9) was better than 0.41 and 3.05%, respectively. Some casework samples were analysed using the optimised conditions.


The direct and indirect effects of motor competence on adolescents' mental health through health-related physical fitness.
Mental health is an important public health issue and up to one in five youth experience mental health problems. The primary purpose of this study was to examine the relationship among motor competence, health-related physical fitness and mental health outcomes in adolescents. A secondary goal was to test the direct and indirect effects of motor competence on adolescents' mental health through health-related physical fitness. Participants were 279 adolescents (Mage = 12.49, SD = 0.89) recruited in the south-west region of the US Motor competence including volleyball, soccer, and ultimate Frisbee, were assessed using PE Metrics™. FITNESSGRAM® test battery was used to assess health-related physical fitness components. Students completed a survey measuring their depressive symptoms and health-related quality of life. Motor competence was significantly associated with components of health-related physical fitness (r ranged from -0.15 to 0.38). The robust fit of the model supports the significant indirect effect of motor competence on mental health outcomes through health-related physical fitness (χ2/df = 39.92/25; CFI = 0.97; RMSEA = 0.046; 90% CI [0.02, 0.07]). The hypothesized conceptual model tested in this study provides insights into the potential interaction of motor competence and health-related physical fitness with adolescents' mental health.


OUHP: an optimized universal hairpin primer system for cost-effective and high-throughput RT-qPCR-based quantification of microRNA (miRNA) expression.
MicroRNAs (miRNAs or miRs) are single-stranded, ∼22-nucleotide noncoding RNAs that regulate many cellular processes. While numerous miRNA quantification technologies are available, a recent analysis of 12 commercial platforms revealed high variations in reproducibility, sensitivity, accuracy, specificity and concordance within and/or between platforms. Here, we developed a universal hairpin primer (UHP) system that negates the use of miRNA-specific hairpin primers (MsHPs) for quantitative reverse transcription PCR (RT-qPCR)-based miRNA quantification. Specifically, we analyzed four UHPs that share the same hairpin structure but are anchored with two, three, four and six degenerate nucleotides at 3'-ends (namely UHP2, UHP3, UHP4 and UHP6), and found that the four UHPs yielded robust RT products and quantified miRNAs with high efficiency. UHP-based RT-qPCR miRNA quantification was not affected by long transcripts. By analyzing 14 miRNAs, we demonstrated that UHP4 closely mimicked MsHPs in miRNA quantification. Fine-tuning experiments identified an optimized UHP (OUHP) mix with a molar composition of UHP2:UHP4:UHP6 = 8:1:1, which closely recapitulated MsHPs in miRNA quantification. Using synthetic LET7 isomiRs, we demonstrated that the OUHP-based qPCR system exhibited high specificity and sensitivity. Collectively, our results demonstrate that the OUHP system can serve as a reliable and cost-effective surrogate of MsHPs for RT-qPCR-based miRNA quantification for basic research and precision medicine.


[Value of multi-slice spiral CT portal venography in prediction of esophagogastric variceal bleeding].
To assess the clinical value of multi-slice spiral CT portal venography in prediction of esophagogastric variceal bleeding. The relation was detected between esophagogastric variceal bleeding and the location of left gastric vein orifice on portal system. Also the correlation was studied between the severity of esophageal varices endoscopically and the diameter of portal vein with multi-slice spiral CT portal venography. Sixty-nine patients with esophagogastric varices confirmed by both endoscopy and 16-detector row CT portal venography due to cirrhosis were enrolled. Excellent image quality of portal collateral vessels with CTPV was obtained in all patients. The portal and left gastric veins were visualized both with CTPV 69/69 (100%). Esophageal and gastric varices were visualized with CTPV 62/69 (89.9%) and 50/69 (72.5%) respectively. The left gastric vein orifice was located on the portal vein in 42 cases. There was correlation between esophagogastric variceal hemorrhage and the location of left gastric vein orifice (Chi(2) = 4.406, P < 0.05). But no relation was found between the severity of esophageal varices and the diameter of portal vein (P > 0.05). CTPV can not only provide important and accurate information of collateral circulation in patients with portal hypertension, but also measure the diameter of collateral blood vessel. There is a higher probability of esophagogastric variceal bleeding for the patients with left gastric vein orifice on portal vein. The combined approaches of CTPV and endoscopy can not only diagnose the severity of esophagogastric varices, but also predict the risk of esophagogastric variceal bleeding.


Screening for depression in African-Caribbean elders.
There are increasing numbers of older African-Caribbeans in the UK. Primary care staff often feel less confident about diagnosing depression in this group. Screening instruments may assist in making diagnoses in cross-cultural consultations. We aimed to determine the sensitivity and specificity of screening instruments for depression in older African-Caribbean people in Manchester, UK. We carried out a two-stage study to compare three screening instruments for depression (Geriatric Depression Scale, Brief Assessment Schedule Depression Cards, Caribbean Culture Specific Screen), with a computerized diagnostic interview for mental health disorders in older adults (Geriatric Mental State). The study was set in inner-city Manchester. The subjects were community-resident African-Caribbeans aged 60 years and over; 227 subjects were approached. Of the 160 people screened, 130 agreed to diagnostic interview. The main outcome measures were Spearman correlation coefficients; these were calculated between each screening instrument and the diagnostic interview. Receiver-operating characteristic (ROC) curve analysis was used to determine appropriate sensitivity and specificity for each instrument. The results for the largest subgroup, the Jamaicans (n = 96/130), demonstrated highly significant correlations between screening instruments and diagnostic interview (P < 0.001). Each instrument had a high sensitivity: Brief Assessment Schedule depression cards (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 82.1% (95% CI 74.0-90.3)), Caribbean Culture Specific Screen (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 74.1% (95% CI 64.8-83.4)), and Geriatric Depression Scale (cut-off > or =4; sensitivity 100% (95% CI 97.1-100), specificity 69.1% (95% CI 59.6-79.2)). These screening instruments demonstrate high sensitivity levels, if an appropriate cut-off point is used. The culture-specific instrument did not perform better than the traditional instruments. Health professionals should approach the consultation in a culturally sensitive manner and use the validated instrument they are most familiar with.


Effects of Wood Smoke Constituents on Mucin Gene Expression in Mice and Human Airway Epithelial Cells and on Nasal Epithelia of Subjects with a Susceptibility Gene Variant in Tp53.
Exposure to wood smoke (WS) increases the risk for chronic bronchitis more than exposure to cigarette smoke (CS), but the underlying mechanisms are unclear. The effect of WS and CS on mucous cell hyperplasia in mice and in human primary airway epithelial cells (AECs) was compared with replicate the findings in human cohorts. Responsible WS constituents were identified to better delineate the pathway involved, and the role of a tumor protein p53 (Tp53) gene polymorphism was investigated. Mice and primary human AECs were exposed to WS or CS and the signaling receptor and pathway were identified using short hairpin structures, small molecule inhibitors, and Western analyses. Mass spectrometric analysis was used to identify active WS constituents. The role of a gene variant in Tp53 that modifies proline to arginine was examined using nasal brushings from study participants in the Lovelace Smokers Cohort, primary human AECs, and mice with a modified Tp53 gene. WS at 25-fold lower concentration than CS increased mucin expression more efficiently in mice and in human AECs in a p53 pathway-dependent manner. Study participants who were homozygous for p53 arginine compared with the proline variant showed higher mucin 5AC (MUC5AC) mRNA levels in nasal brushings if they reported WS exposure. The WS constituent, oxalate, increased MUC5AC levels similar to the whole WS extract, especially in primary human AECs homozygous for p53 arginine, and in mice with a modified Tp53 gene. Further, the anion exchange protein, SLC26A9, when reduced, enhanced WS- and oxalate-induced mucin expression. The potency of WS compared with CS in inducing mucin expression may explain the increased risk for chronic bronchitis in participants exposed to WS. Identification of the responsible compounds could help estimate the risk of pollutants in causing chronic bronchitis in susceptible individuals and provide strategies to improve management of lung diseases. https://doi.org/10.1289/EHP9446.


Potential of Natural Fiber Reinforced Polymer Composites in Sandwich Structures: A Review on Its Mechanical Properties.
The interest in using natural fiber reinforced composites is now at its highest. Numerous studies have been conducted due to their positive benefits related to environmental issues. Even though they have limitations for some load requirements, this drawback has been countered through fiber treatment and hybridization. Sandwich structure, on the other hand, is a combination of two or more individual components with different properties, which when joined together can result in better performance. Sandwich structures have been used in a wide range of industrial material applications. They are known to be lightweight and good at absorbing energy, providing superior strength and stiffness-to-weight ratios, and offering opportunities, through design integration, to remove some components from the core element. Today, many industries use composite sandwich structures in a range of components. Through good design of the core structure, one can maximize the strength properties, with a low density. However, the application of natural fiber composites in sandwich structures is still minimal. Therefore, this paper reviewed the possibility of using a natural fiber composite in sandwich structure applications. It addressed the mechanical properties and energy-absorbing characteristics of natural fiber-based sandwich structures tested under various compression loads. The results and potential areas of improvement to fit into a wide range of engineering applications were discussed.


Mycoplasmal respiratory infections in small animals: 17 cases (1988-1999).
Seventeen cases (i.e., 14 dogs and three cats) were identified as having Mycoplasma spp. as the sole bacterial isolate cultured from airway washings in 224 cases evaluated for lower respiratory disease that was present in each case. Primary diagnoses included pneumonia (35.3%), airway collapse (35.3%), and bronchitis (29.4%). Fourteen cases had follow-up information available. Of these cases, eight showed resolution or improvement with antimycoplasmal drugs. Mycoplasma spp. is recognized as a primary cause of respiratory disease in several species, including humans. The relationship between Mycoplasma spp. and respiratory disease detected in some of these cases suggests some Mycoplasma spp. may act as primary pathogens in dogs and cats.


The effect of chronic stress on hepatic and gastric lipid peroxidation in long-term depletion of glutathione in rats.
The effect of chronic stress (immobilization and cold) on hepatic and gastric thiobarbituric acid reactive substances (TBARS) and vitamin C levels were investigated in rats having long-term depletion of glutathione (GSH) by applying buthionine sulfoximine (BSO). GSH and vitamin C levels decreased and TBARS levels increased in the liver and stomach of rats subjected to stress. Long-term BSO administration along with stress caused no additional changes in these parameters. These results may indicate that long-term glutathione depletion did not potentiate stress-induced hepatic and gastric lipid peroxidation.


Segmentation of focal cortical dysplasia lesions on MRI using level set evolution.
Focal cortical dysplasia (FCD) is the most frequent malformation of cortical development in patients with medically intractable epilepsy. On MRI, FCD lesions are not easily differentiable from the normal cortex and defining their spatial extent is challenging. In this paper, we introduce a method to segment FCD lesions on T1-weighted MRI. It relies on two successive three-dimensional deformable models, whose evolutions are based on the level set framework. The first deformable model is driven by probability maps obtained from three MRI features: cortical thickness, relative intensity and gradient. These features correspond to the visual characteristics of FCD and allow discriminating lesions and normal tissues. In a second stage, the previous result is expanded towards the underlying and overlying cortical boundaries, throughout the whole cortical section. The method was quantitatively evaluated by comparison with manually traced labels in 18 patients with FCD. The automated segmentations achieved a strong agreement with the manuals labels, demonstrating the applicability of the method to assist the delineation of FCD lesions on MRI. This new approach may become a useful tool for the presurgical evaluation of patients with intractable epilepsy related to cortical dysplasia.


Brachial plexus palsy: an in utero injury?
Acquired brachial plexus injury historically has been linked with excessive lateral traction applied to the fetal head, usually in association with shoulder dystocia. Recent reports in the obstetric literature, however, have suggested that in utero forces may underlie a significant portion of these injuries. Brachial plexus palsies may therefore precede the delivery itself and may occur independent of the actions of the accoucheur. Thus we propose that the long-held notions of a traction-mediated pathophysiologic mechanism for all brachial plexus injuries warrant critical reappraisal.


Pathophysiology of intestinal uptake and absorption of antigens in food allergy.
An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier, the infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms that act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. These defenses include a unique local immunologic system adapted to function in the complicated milieu of the intestine as well as other nonimmunologic processes such as a gastric barrier, intestinal surface secretions, peristaltic movement, etc, all of which help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, especially for premature and "small-for-date" infants, this elaborate local defense system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, nature has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system: human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes, but many other substances that can interfere with bacterial colonization and prevent antigen penetration.


Impact of public preventive programmes on oral quality of life of 11 to 12-yr-old school students.
The objective was to analyze the impact of preventive programmes on oral quality of life in school students aged 11-12 yrs. In the school year 1996/97, a quasi-experimental study was initiated in Granada province with four groups of students aged 6-7 yrs: Sealant + Fluoride (sealants on first permanent molars applied in the health centre for a 3-yr active programme, and fluoride varnish applied every four months for 3 yrs, n=65), Sealant (only sealants, n=80), Fluoride (only fluoride varnish, n=107) and Control group (n=59). All students were examined every 6 months at school during the 3-yr active programme and received an oral health report after each examination. At 5.5 yrs (school year 2002/03), after 2.5 yrs with no programme, students were again examined and completed a questionnaire on oral quality of life scored from -6 (minimum) to +6 (maximum). Oral quality of life values (+/- standard deviation) were: 3.31+/-0.30 (Sealant + Fluoride), 3.11+/-0.27 (Sealant), 3.18+/-0.23 (Fluoride) and 2.95+/-0.32 (Control), with no statistically significant differences among them. Fissure sealant and fluoride varnish programmes had no significant influence on oral quality of life after a 5.5- yr follow-up (3 yrs of active programme plus 2.5 yrs of discontinuation).


Preparation and characterization of a monoclonal antibody against the protein LIGHT.
LIGHT (which is homologous to lymphotoxins, shows inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes [Genome Database designation, TNFSF14]), a newly identified member of the TNF superfamily, is up-regulated upon activation of T-cells. LIGHT plays an important role in the T-cell-mediated tumor and graft-versus-host disease via LIGHT/HVEM/LT beta R signaling. To prepare specific monoclonal antibody (MAb) against murine LIGHT, a fragment containing the extracellular domain of LIGHT was inserted into prokaryotic expression vector pET-32a(+). The his-tagged fusion protein was expressed in BL21(DE3) in the form of inclusion bodies. The fusion protein was purified and refolded on-column using immobilized mental affinity chromatography. Rat MAb against murine LIGHT was obtained with hybridoma technique and specific ELISA screening. Western blotting and flow cytometry assays showed that MAb 4C11 had specific binding ability with LIGHT protein in eukaryotic cells. Lymphocyte proliferation assays indicated that this MAb could co-stimulate the proliferation of T-cells. Thus, this MAb may be the basis for detection of LIGHT protein in tissue or cell and be beneficial for the study of LIGHT/HVEM/LT beta R pathway.


Extreme violence--homicide; an analysis of 265 cases from the offices of JMO Colombo and Ragama--a study from Sri Lanka.
Violence in a society can be categorized into many areas such as interpersonal violence, domestic violence, violence against children, violence of human rights, violence due to wars etc. The most extreme form of violence is killing of another human. To study whether the underlying reasons (motives) for killing has a relationship to the methods employed for killing. A retrospective descriptive study based on autopsy reports, magistrate orders and case notes attached was carried out on all the cases examined at the office of the JMO Colombo and Ragama from July 2005 to June 2006. The data were analyzed using SPSS statistical package. Out of 265 autopsy examinations alleged to be homicides, 39% of deaths were related to terrorist acts while previous enmity was recorded in 35% of cases. The commonest method of homicide was firearms (31%) while explosives recorded the second highest (28%). Blunt force and sharp force trauma were the reasons for 23% and 14% of homicides respectively. Almost all the deaths related to war was caused by firearms and bombs (96%) where as 47% of previous enmity deaths were caused by firearms. Firearms were never used in homicides of sudden provocation or drunken brawls. The increased use of firearms was not only seen in terrorism related homicides, but also in homicides related to previous enmity. Further research is needed in this area as to why it occurs despite having a tight firearm policy in Sri Lanka.


Cannabis and cannabinoids: pharmacology and therapeutic potential.
Cannabis (also known as marijuana) is the most frequently used psychoactive substance in the world. The role of cannabis in medicine is rapidly evolving, and advances in the understanding of its pharmacology have led to numerous proposed uses of these drugs. Cannabis contains Δ9-tetrahydrocannabinol and cannabidiol as the primary constituents responsible for pharmacological activity. It is now known that there are at least two types of cannabinoid receptors. CB1 receptors are found mainly in the CNS, and their primary role is to inhibit the release of neurotransmitters. CB2 receptors' leading role is to modulate cytokine release and immune cell migration. Colocalisation of cannabinoid receptors with other types of nervous system receptors allows them to interact with many other transmitters such as dopamine, noradrenaline, acetylcholine, gamma-aminobutyric acid, serotonin, and glutamic and aspartic acids. The rapidly expanding understanding regarding cannabinoids led to initial attempts to treat selected diseases with cannabinoid receptor agonists and antagonists. The most promising of these was the potential possibility of treating diseases for which current therapy is unsatisfactory, such as neurological diseases including multiple sclerosis, spastic muscular tension, extrapyramidal system diseases, neurodegenerative diseases and cerebral ischaemia. Attempts to treat psychiatric diseases (e.g. psychoses, neuroses, mood disorders, and alcohol dependence syndrome) with cannabinoids are much less advanced. Cannabis and cannabinoids can be widely used to treat several diseases or alleviate symptoms, but their efficacy for specific indications is not always apparent. Further exploration is needed to understand whether the enhanced sensitivity to the cognitive effects of Δ9-THC depends on brain cannabinoid receptor dysfunction, and how these changes contribute to the cognitive deterioration and core pathophysiology symptoms associated with schizophrenia or other neurological and somatoform disorders.


[Clinical impact of gamma-glutamyl transpeptidase messenger RNA subtypes on early diagnosis of hepatocellular carcinoma].
It has been reported that hepatocellular carcinoma (HCC) expresses gamma-glutamyl transpeptidase (GGT) with unique carbohydrate moieties compared with normal liver GGT enzymes, this unique GGT was used as a marker for the diagnosis of HCC. However, the genomic changes in GGT relating to the development of HCC are not known. This study was designed to explore the relationship between alteration in GGTmRNA subtypes and the development of HCC, and to seek a new method for early diagnosis of HCC. Three GGTmRNA subtypes (F, H, P) were determined bu using RT-PCR in normal liver tissues, diseased liver tissues without HCC, cancerous and noncancerous tissues from the livers with HCC, noncancerous tissues from secondary carcinoma of liver and peripheral blood of all cases. The main subtype of GGTmRNA was type F in normal liver tissues, liver tissues from noncancerous liver diseases and paracancerous tissues from secondary carcinoma of liver. The prevalence of subtype H was significantly higher in cancerous tissues, adjacent paracancerous and distal cancerous tissues from the livers with HCC than that in tissues from normal livers and noncancerous liver diseases (P < 0.05). The prevalence of subtype F in cancerous tissues was significantly lower than that in tissues from normal livers and noncancerous liver diseases (P < 0.05). Among 26 patients with HCC, GGTmRNA-H in peripheral blood was found in 12 cases. In 10 HCC patients with negative AFP, GGTmRNA-H in peripheral blood was found in 5 cases. The changes of GGTmRNA subtypes are closely related to the development of HCC, and the analysis of GGT genes might be a sensitive assay to monitor the hepatic cell canceration.


Challenges of Clinical Management of Adolescent and Young Adults With Bone and Soft Tissue Sarcoma.
Clinical management of adolescents and young adults with bone and soft tissue sarcomas is quite challenging, mainly because of different chemotherapy approaches adopted by pediatric and adult oncologists and tumor-associated factors related to this peculiar age group. Overcoming these barriers is essential for adolescent and young adult patients, whose survival and long-term physical effects are worse than their pediatric counterparts. Nowadays, constant efforts from international collaborations between pediatric and adult oncologists of sarcoma groups have optioned in converging toward a common therapeutic strategy, while improving quality of treatment, as well as research advances dedicated to this at-risk age group of patients with sarcomas.


Externally mode-matched cavity quantum electrodynamics with charge-tunable quantum dots.
We present coherent reflection spectroscopy on a charge and dc Stark tunable quantum dot embedded in a high-quality and externally mode-matched microcavity. The addition of an exciton to a single-electron-charged quantum dot forms a trion that interacts with the microcavity just below the strong-coupling regime of cavity quantum electrodynamics. Such an integrated, monolithic system is a crucial step towards the implementation of scalable hybrid quantum-information schemes that are based on an efficient interaction between a single photon and a confined electron spin.


Pelvic hydatid disease as an example of pelvic masses of uncertain aetiology.
We describe two new cases of pelvic hydatid cysts, one with a clinical profile of local compression and the other one asymptomatic. The first case is a 75 year-old man who reported difficulty in defecating and urinating. An ultrasound revealed a large pelvic cystic mass displacing the bladder and rectosigmoid region. Computed tomography showed images compatible with hydatid disease and a hydatid liver cyst. The patient underwent a surgical procedure, with the pelvic cyst being partially excised. The other case of pelvic hydatid disease was asymptomatic, and was discovered by chance while examining a 75 year-old man for a prostatic adenoma. Because he was asymptomatic, we opted for observation. The pathology confirmed the diagnosis in the first case and radiological findings confirmed the second. Both patients are now asymptomatic. Hydatid disease must be considered in the differential diagnosis of any cystic masses in the pelvic organs, especially in countries where the disease is endemic. Although there are no serological tests which are 100% specific, there are some radiological procedures which can help to confirm the disease. Surgery is the treatment of choice.


The Racial and Ethnic Microaggressions Scale (REMS): construction, reliability, and validity.
Racial microaggressions are subtle statements and behaviors that unconsciously communicate denigrating messages to people of color. In recent years, a theoretical taxonomy and subsequent qualitative studies have introduced the types of microaggressions that people of color experience. In the present study, college- and Internet-based samples of African Americans, Latina/os, Asian Americans, and multiracial participants (N = 661) were used to develop and validate the Racial and Ethnic Microaggression Scale (REMS). In Study 1, an exploratory principal-components analyses (n = 443) yielded a 6-factor model: (a) Assumptions of Inferiority, (b) Second-Class Citizen and Assumptions of Criminality, (c) Microinvalidations, (d) Exoticization/Assumptions of Similarity, (e) Environmental Microaggressions, and (f) Workplace and School Microaggressions, with a Cronbach's alpha of .912 for the overall model and subscales ranging from .783 to .873. In Study 2, a confirmatory factor analysis (n = 218) supported the 6-factor model with a Cronbach's alpha of .892. Further analyses indicate that the REMS is a valid measure of racial microaggressions, as evidenced by high correlations with existing measures of racism and participants' feedback. Future research directions and implications for practice are discussed.


The complete chloroplast genome of Ananas comosus var. erectifolius (L.B. Smith) Coppens & Leal.
Ananas comosus var. erectifolius (L.B. Smith) Coppens & Leal, a tropical plant from Bromeliaceae family, has immense applications, especially for fiber production of excellent quality. The lack of available chloroplast (cp) genome information limits its breeding and application. Here, we assembled its complete cp genome using Illumina high-throughput sequencing technology. The cp genome size is 159,983 bp, with 37.4% GC content, including a large single copy region (LSC) of 87,787 bp, a small single copy region (SSC) of 18,606 bp, and a pair of inverted repeat regions (IRs) of 26,795 bp. It encodes 89 protein-coding, 38 tRNA and 8 rRNA genes. Phylogenetic analysis showed that A. comosus var. erectifolius was close to Ananas comosus. The complete cp genome sequences could provide valuable information for variety breeding and genetic analysis of agronomic and economic traits in A. comosus var. erectifolius.


A comparison of the periodontal ligament injection using 2% lidocaine with 1:100,000 epinephrine and saline in human mandibular premolars.
The purpose of this study is to evaluate, with the electric pulp tester, the anesthetic efficacy of the periodontal ligament injection using 2% lidocaine with 1:100,000 epinephrine and saline in human mandibular premolars. The periodontal ligament injection using 2% lidocaine with 1:100,000 epinephrine was found to be an effective technique for anesthetizing mandibular first premolars. However, the duration of profound pulpal anesthesia was approximately 10 minutes. The periodontal ligament injection using sterile saline was not an effective technique for anesthesia. Teeth mesial and distal to the injected tooth may also become anesthetized with this injection technique. The initial needle penetration and injection of the anesthetic solution in clinically healthy teeth were only mildly discomforting. No increase in tooth mobility was observed 45 minutes after the periodontal ligament injection. No clinically observable pulpal or periodontal damage was seen at 3 weeks after the injection.


N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.
Although stroke is very often the cause of death worldwide, the burden of ischemic and hemorrhagic stroke varies between regions and over time regarding differences in prognosis, prevalence of risk factors, and treatment strategies. Excitotoxicity, oxidative stress, dysfunction of the blood-brain barrier, neuroinflammation, and lysosomal membrane permeabilization, sequentially lead to the progressive death of neurons. In this process, protein kinases-related checkpoints tightly regulate N-methyl-D-aspartate (NMDA) receptor signaling pathways. One of the major hallmarks of cerebral ischemia is excitotoxicity, characterized by overactivation of glutamate receptors leading to intracellular Ca2+ overload and ultimately neuronal death. Thus, reduced expression of postsynaptic density-95 protein and increased protein S-nitrosylation in neurons is responsible for neuronal vulnerability in cerebral ischemia. In this chapter death-associated protein kinases, cyclin-dependent kinase 5, endoplasmic reticulum stress-induced protein kinases, hyperhomocysteinemia-related NMDA receptor overactivation, ephrin-B-dependent amplification of NMDA-evoked neuronal excitotoxicity and lysosomocentric hypothesis have been discussed.Consequently, ample evidences have demonstrated that enhancing extrasynaptic NMDA receptor activity triggers cell death after stroke. In this context, considering the dual roles of NMDA receptors in both promoting neuronal survival and mediating neuronal damage, selective augmentation of NR2A-containing NMDA receptor activation in the presence of NR2B antagonist may constitute a promising therapy for stroke.


Distribution of virulence genes related to adhesins and toxins in shiga toxin-producing Escherichia coli strains isolated from healthy cattle and diarrheal patients in Japan.
Shiga toxin-producing Escherichia coli (STEC) isolated from Japan were investigated for the distribution of virulence genes. A total of 232 STEC strains including 171 from cattle and 61 from human were examined for the occurrence of genes responsible for bacterial adhesions to intestine, e.g., eae (intimin, E. coli attaching and effacing), saa (STEC autoagglutinating adhesin), iha (irgA homologue adhesin), efa1 (E. coli factor for adherence), lpfA(O113) (long polar fimbriae), and ehaA (EHEC autotransporter) by colony hybridization assay. Similarly, the presence of toxigenic cdt (cytolethal distending toxin), and subAB (subtilase cytotoxin) genes were also checked. Among cattle isolates, 170, 163, 161, 155, 112 and 84 were positive for lpfA(O113) (99%), ehaA (95%), iha (94%), saa (91%), subAB (65%), and cdt-V (49%), respectively, while 2 were positive for eae (1.2%) and efa1 (1.2%) each. In case of human isolates, 60, 59, 58 and 58 were positive for ehaA (98%), iha (97%), efa1 (95%), and eae (95%), respectively, while 11, 2, 2, and 1 were positive for lpfA(O113) (18%), saa (3.3%), cdt-V (3.3%), and subAB (1.6%), respectively. Therefore, in human STEC isolates efa1 and eae whereas in cattle isolates saa, lpfA(O113), cdt-V and subAB were prevalent. These data indicate differential occurrence of some pathogenic genes in human and cattle originated STEC strains in Japan.


Endogenous activation of glucokinase by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is glucose dependent.
Glucokinase (GK) plays a crucial role as glucose sensor in glucose-induced insulin secretion in pancreatic β-cells. The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) acts as an endogenous GK activator. Therefore, the goal of this study was the analysis of GK-PFK-2/FBPase-2 complex formation and its effect on metabolic stimulus-secretion coupling in β-cells in dependence upon glucose. The interaction between GK and PFK-2/FBPase-2 was analyzed in insulin-secreting MIN6 cells with a new fluorescence-based mammalian two-hybrid system. In contrast to the commonly used mammalian two-hybrid systems that require sampling before detection, the system used allows monitoring of the effects of environmental changes on protein-protein interactions on the single-cell level. Increasing the glucose concentration in the cell culture medium from 3 to 10 and 25 mmol/liter amplified the interaction between the enzymes stepwise. Importantly, in line with these results, overexpression of PFK-2/FBPase-2 in MIN6 cells evoked only at 10 and 25 mmol/liter, an increase in insulin secretion. Furthermore, a PFK-2/FBPase-2 mutant with an abolished GK-binding motif neither showed a glucose-dependent GK binding nor was able to increase insulin secretion. The results obtained with the mammalian two-hybrid system could be confirmed by fluorescence resonance energy transfer experiments in COS cells. Furthermore, the established interaction between GK and the liver GRP served in all experiments as a control. Thus, this study clearly showed that binding and activation of GK by PFK-2/FBPase-2 in β-cells is promoted by glucose, resulting in an enhancement of insulin secretion at stimulatory glucose concentrations, without affecting basal insulin secretion.


Fine-needle aspiration cytology of Warthin-like mucoepidermoid carcinoma: A case report with cytological review.
Warthin-like mucoepidermoid carcinoma (MEC) is a novel and rare subtype of MEC and is characterized histopathologically by the presence of abundant lymphocytic infiltration and cystic changes. A small number of cytological reports of this MEC variant is currently available. The present study reported on the sixth cytological case of Warthin-like MEC, reviewed the cytological features of the tumour and discussed the cytological differential diagnosis. A 16-year-old Japanese female presented with a painful mass in the left parotid gland. Fine-needle aspiration for cytological examination of the parotid gland tumour was performed, followed by partial parotidectomy. Cytological examination revealed sheet-like and folded epithelial cell clusters in a mucinous background accompanying abundant lymphocytic infiltration. Epithelial clusters comprised round cells with mildly enlarged round to oval nuclei, polygonal cells with relatively rich cytoplasm and slightly enlarged round to oval nuclei. Certain polygonal cells contained intracytoplasmic mucin. Histopathological examination of the resected parotid gland tumour indicated multiple cystic lesions with abundant lymphocytic infiltration accompanying lymphoid follicle formation. The cysts were lined by intermediate cells with occasional mucinous cells. Fluorescence in situ hybridization using the surgically resected specimen indicated mastermind-like transcriptional coactivator 2 (MAML2) rearrangement, a characteristic of Warthin-like MEC. Consequently, the patient was diagnosed with Warthin-like MEC. The literature review revealed that the characteristic cytological features of Warthin-like MEC are the presence of intermediate cells and lack of oncocytic cells in the mucinous material under an abundant lymphocytic background. Clinicopathological features may help with a differential diagnosis, particularly from Warthin's tumour, and detection of MAML2 rearrangement is able to improve the accuracy of diagnosis.


[PM2.5 Source Apportionment Based on a Variety of New Receptor Models].
In order to understand the applicability of various new receptor models, four receptor models, including the positive matrix factorization/multilinear engine 2-species ratio (PMF/ME2-SR), partial target transformation-positive matrix factorization (PTT-PMF), positive matrix factorization (PMF), and chemical mass balance (CMB), were used to analyze and verify the atmospheric fine particulate matter (PM2.5) data of a typical city in northern China. It was found that coal combustion (25%-26%), dust (19%-21%), secondary nitrate (17%-19%), secondary sulfate (16%), vehicle emissions (13%-15%), biomass burning (4%-7%), and steel (1%-2%) had a contribution to PM2.5. By comparing the source profiles and source contributions obtained by different models and calculating the coefficient of differences (CD) and average absolute error (AAE) of each source, we found that although the source apportionment results of the four models were in good agreement (the average CD value was between 0.6 and 0.7), there were still slight differences in the identification of some components in each source. Compared with the traditional model (PMF), the PMF/ME2-SR model can better identify sources with similar source profile characteristics, which is due to the component ratios of sources that are introduced. For example, the CD and AAE of dust sources were 15% and 54% lower than those of PMF, respectively. The PTT-PMF model takes the measured primary source profiles and virtual secondary source profiles as a constraint target, and the calculated CD and AAE of secondary sulfate were 0.25 and 17%, respectively, which were 55% and 23% lower than PMF. The PTT-PMF model can obtain more "pure" secondary sources and identify the pollution sources that are not identified by other models, which has more advantages in the refined identification of sources.


Microdialysis of cat pons reveals enhanced acetylcholine release during state-dependent respiratory depression.
Microinjection of cholinergic agonists and acetylcholinesterase inhibitors into the medial pontine reticular formation (mPRF) causes a state that is polygraphically similar to rapid-eye-movement (REM) sleep. Respiratory studies of intact unanesthetized cats during this cholinergically induced REM sleep-like state have shown that the same cholinoceptive pontine reticular regions that mediate REM sleep can also cause state-dependent respiratory depression. The present study investigated the hypothesis that acetylcholine (ACh) release in the mPRF is increased during the respiratory depression that accompanies the cholinergically induced REM sleep-like state. Cats were implanted for polygraphic recording of sleep and wakefulness and with guide tubes aimed for placing a microinjector in one mPRF and a microdialysis probe in the contralateral mPRF. ACh release was measured with high-performance liquid chromatography and electrochemical detection. Compared with waking levels, ACh was significantly increased and respiratory frequency was significantly decreased during the carbachol-induced REM sleep-like state. These results support the hypothesis that endogenous cholinergic neurotransmission in brain regions known to regulate REM sleep can also cause state-dependent changes in respiratory control.


Biodegradable mesoporous bioactive glass nanospheres for drug delivery and bone tissue regeneration.
Bioactive inorganic materials are attractive for hard tissue regeneration, and they are used as delivery vehicles for pharmaceutical molecules, scaffolds and components for bio-composites. We demonstrated mesoporous bioactive glass (BG) nanospheres that exhibited the capacity to deliver pharmaceutical molecules. Mesoporous BG nanospheres with variable Ca to Si ratios were synthesized using sol-gel chemistry. By controlling the hydrolysis and condensation conditions, the diameter of the mesoporous BG nanospheres was changed from 300 nm to 1500 nm. The porous structure and surface area of the BG nanospheres were shown to be dependent on their composition. The surface area of the BG nanospheres decreased from 400 ± 2 m(2) g(-1) to 56 ± 0.1 m(2) g(-1) when the Ca/Si ratio increased from 5 to 50 at.%. When the mesoporous BG nanospheres were loaded with ibuprofen (IBU), they exhibited a sustained release profile in simulated body fluid (SBF). In the meantime, the IBU-loaded BG nanospheres degraded in SBF, and induced apatite layer formation on the surface as a result of their good bioactivity. When the BG nanospheres were used as a composite filler to poly (ε-caprolactone) (PCL), they were shown to be effective at improving the in vitro bioactivity of PCL microspheres.


Synergistic effects of the combined treatment of U251 and T98G glioma cells with an anti‑tubulin tetrahydrothieno[2,3‑c]pyridine derivative and a peptide nucleic acid targeting miR‑221‑3p.
In the development of novel and more effective anticancer approaches, combined treatments appear to be of great interest, based on the possibility of obtaining relevant biological or therapeutic effects using lower concentrations of single drugs. Combination therapy may prove to be of utmost significance in the management of glioblastoma (GBM), a lethal malignancy that accounts for 42% of cancer cases of the central nervous system, with a median survival rate of 15 months. As regards novel therapeutic approaches, the authors have recently demonstrated that peptide nucleic acids (PNAs) that target microRNA (miRNA/miR)‑221 are very active in inducing the apoptosis of glioma cells. Furthermore, in a recent study, the authors described two novel series of tubulin polymerization inhibitors based on the 4,5,6,7‑tetrahydrothieno[2,3‑c]pyridine and 4,5,6,7‑tetrahydrobenzo[b]thiophene scaffold, which exerted a potent anti‑proliferative effect on a variety of tumor cell lines. The present study aimed to verify the activity on glioblastoma cancer cell lines of one of the most active compounds tested, corresponding to 2‑(3', 4', 5'‑trimethoxyanilino)‑3‑cyano/alkoxycarbonyl‑6‑substituted‑4 5,6,7‑tetrahydrothiene[2,3‑c] pyridine (compound 3b), used in combination with an anti‑miR‑221‑3p PNA, already demonstrated to be able to induce high levels of apoptosis. To the best of our knowledge, the results obtained herein demonstrate for the first time a 'combination therapy' performed by the combined use of a PNA targeting miR‑221 and the tetrahydrothiene[2,3‑c]pyridine derivative 3b, supporting the concept that the combined treatment of GBM cells with a PNA against a specific upregulated oncomiRNA (in the present study a PNA targeting miR‑221‑3p was used) and anti‑tubulin agents (in the present study derivative 3b was used) is an encouraging strategy which may be used to enhance the efficacy of anticancer therapies and at the same time, to reduce side‑effects.


Peroxiporins Are Induced upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines.
Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.


Advances in the treatment of varicella-zoster virus infections.
Varicella-zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs subsequent to primary infection, while herpes zoster (usually associated with aging and immunosuppression) appears as a consequence of reactivation of latent virus. The major complication of shingles is postherpetic neuralgia. Vaccination strategies to prevent varicella or shingles and the current status of antivirals against VZV will be discussed in this chapter. Varivax®, a live-attenuated vaccine, is available for pediatric varicella. Zostavax® is used to boost VZV-specific cell-mediated immunity in adults older than 50 years, which results in a decrease in the burden of herpes zoster and pain related to postherpetic neuralgia. Regardless of the availability of a vaccine, new antiviral agents are necessary for treatment of VZV infections. Current drugs approved for therapy of VZV infections include nucleoside analogues that target the viral DNA polymerase and depend on the viral thymidine kinase for their activation. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analogue FV-100, the helicase-primase inhibitor ASP2151, and valomaciclovir (prodrug of the acyclic guanosine derivative H2G). Different candidate VZV drugs have been described in recent years. New anti-VZV drugs should be as safe as and more effective than current gold standards for the treatment of VZV, that is, acyclovir and its prodrug valacyclovir.


Supported gold catalysts: new properties offered by nanometer and sub-nanometer structures.
Nano-sized gold particles on solid supports offer unexpected catalytic properties, with new discoveries emerging rapidly for oxidation, hydrogenation, coupling, and other reactions. Oxidation of H2 to give H2O2 catalyzed by metal oxide-supported gold nanoclusters (reported in Chem. Commun. in 2002 by the group of Hutchings) offers promise for large-scale application. Catalysis by gold has become a vibrant, expanding field marked by continuing surprises, but fundamental understanding of how these catalysts work is emerging only slowly.


A simplified conceptual model of the human cervical spine for evaluating force transmission in upright static posture.
To develop a simplified graphical model appropriate for the evaluation of proposed theoretical force transmission mechanisms in the upright static cervical spine. The model is used to demonstrate in a visual format the underlying mechanical principles contributing to an optimal mechanical configuration of the cervical spine in upright posture. The model is also used to explore the relative mechanical efficiency of 2 different force transmission methods. A graphical model was developed to illustrate relevant force vectors acting on the head and neck in upright posture. This model was used to calculate theoretical static loading on the structures of the neck under various loading conditions resulting from specific configurations of passive elements and active supportive muscle effort. From the information gained from the model, a theorized optimal mechanical configuration and theorized role of various components of the cervical spine in static upright posture is presented. The model is used to test the mechanical validity of a concurrent force system with intersegmental muscle force rather than the parallel force system presented in the literature. The alternate models are examined in relation to their predictions and theoretical implications with respect to force transmission in the cervical spine. A simplified model has been developed that facilitates the graphical representation of forces involved in maintaining static upright posture in the human cervical spine. The model is used to explore the optimal spinal configuration of the major mechanical components of the neck.


Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients.
The authors report two cases of ejaculatory dysfunction induced by fluoxetine. Cyproheptadine, an antihistaminic and antiserotonergic drug, restored sexual function in each case. Possible mechanisms of fluoxetine-induced anorgasmia are presented and treatment options are reviewed.


Activation of the TRPV1 Thermoreceptor Induced by Modulated or Unmodulated 1800 MHz Radiofrequency Field Exposure.
The existence of effects of radiofrequency field exposure at environmental levels on living tissues and organisms remains controversial, in particular regarding potential "nonthermal" effects produced in the absence of temperature elevation. Therefore, we investigated whether TRPV1, one of the most studied thermosensitive channels, can be activated by the heat produced by radiofrequency fields and by some specific nonthermal interaction with the fields. We have recently shown that TRPV1 activation can be assessed in real-time on live cells using the bioluminescence resonance energy transfer technique. Taking advantage of this innovative assay, we monitored TRPV1 thermal and chemical modes of activation under radiofrequency exposure at 1800 MHz using different signals (CW, GSM, UMTS, LTE, Wi-Fi and WiMAX) at specific absorption rates between 8 and 32 W/kg. We showed that, as expected, TRPV1 channels were activated by the heat produced by radiofrequency field exposure of transiently-transfected HEK293T cells, but found no evidence of TRPV1 activation in the absence of temperature elevation under radiofrequency field exposure. There was no evidence either that, at fixed temperature, radiofrequency exposure altered the maximal efficacy of the agonist Capsaicin to activate TRPV1.


Acute respiratory distress syndrome following cutaneous exposure to Lysol: a case report.
Lysol (mixed cresols) is a brand of popular detergent commonly used to disinfect toilets and floors in Taiwan. We report a patient with acute respiratory failure immediately following chemical burns caused by skin contact with Lysol solution. On admission, chest radiography showed bilateral diffuse pulmonary infiltrates and an arterial blood gas analysis disclosed hypoxemia refractory to a high concentration of oxygen by inhalation. Under the impression of acute respiratory distress syndrome, our patient was admitted to the intensive care unit for respiratory care. Poor clinical improvement was noted, despite aggressive respiratory therapy. High-dose steroid therapy (hydrocortisone 30 mg/kg/day) was administered from the seventh day after mechanical ventilation began and the ratio of arterial partial pressure of oxygen to fractional concentration of oxygen in inspired gas improved thereafter. The amount of steroid was gradually tapered to the maintenance dose and the patient was successfully weaned from the ventilator after a 93-day course of mechanical ventilation.


[Effect on different concentrations of exogenous hormones on baicalin in Scutellaria baicalensis callus].
To determine the content of baicalin in Scutellaria baicalensis callus induced by different doncentrations of exogenous hormones. HPLC system was adopted to determine baicalin in S. baicalensis callus. Chromatographic conditions: ODS column was adopted, with methanol-water-phosphate (47: 53: 0.2) as the mobile phase. The flow velocity was 1 mL x min(-1), the detective wavelength was 280 nm, and the temperature of column was room temperature. S. baicalensis callus induced by 6-BA 1.0 mg x L(-1) + NAA 0.5 mg x L(-1) showed the highest baicalin content, up to 49.78 mg x g(-1). The experiment is such a simple, rapid and stable method for determining the baicalin content that it can be used for determining the baicalin content in S. baicalensis callus.


Changes in neurobiological parameters in the hippocampus after exposure to trimethyltin.
The effects of trimethyltin (TMT) on neurotransmitters, morphological changes and physiological activity of the hippocampus were studied. A single injection of TMT (8 mg/kg) decreased the high affinity uptake of glutamate (HA-Glu), which is a marker for glutamergic nerve terminals, after 7 days. The maximal reduction of HA-Glu was 42% and was obtained on postinjection day 21. Glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT), markers for GABAergic and cholinergic structures, were not affected. The electrical activity of the hippocampus recorded through chronically implanted electrodes was altered by day three postinjection. The amplitude of the hippocampal electrographic record gradually decreased and the EEG ceased to be correlated with the rats' behavioral state. Fink-Heimer staining showed degenerating neurons within the subiculum, CA1, ventral CA3 and CA4 hippocampal subfields. TMT (3 mg/kg) injected once a week for three weeks decreased the HA-Glu significantly 21 days after the first injection. The HA-Glu was reduced by a maximum of 68%. The activity of ChAT was slightly increased only at day 35 postinjection while the GAD activity was not significantly reduced over a 21 day period beginning on day 14. Fink-Heimer staining showed degeneration of nerve cells within the CA1, ventral CA3 and CA4 hippocampal subfields. Both injection schedules produced degenerating neurons in the entorhinal cortex. The neurons of the dorsal CA3 region and the granule cells of the dentate gyrus were not lesioned by either TMT injection. The relationship between the behavioral, physiological and neurochemical changes induced by TMT will be discussed.


[Reproducibility of centric relation of the patient with severe dental attrition for oral rehabilitation].
Standards for determining mandibular position, especially the centric relation (CR), are in controversy because of anatomical, neurophysiological factors and research methods or instrument. The purpose of this study was to reevaluate the reproducibility of centric relation of the patients with severe dental attrition for oral rehabilitation. Reproducibility of the centric relation of 6 patients with severe occlusal attrition was investigated by using D5A Denar fully adjustable articulator and the Pantronic recording system. 1. In supine position, anterior-posterior(AP) displacement of centric relation (CR) was 0.14 mm and superior-inferior(SI) displacements of CR were between 0.11 mm-0.12 mm. 2. In upright position, anterior-posterior displacement of CR was 0.35 mm and superior-inferior changes of CR were between 0.13 mm-0.20 mm. The CR is the most stable and reproducible position of mandibule in normal stomatological system and is useful as a reference position in occlusal treatment and functional rehabilitation.


The paroxysmal dyskinesias.
The clinical, pathophysiological and genetic features of some of the paroxysmal movement disorders are reviewed. Paroxysmal kinesigenic choreoathetosis/dyskinesias (PKC/PKD) is a condition in which brief and frequent dyskinetic attacks are provoked by sudden movement. PKC is more common in men and can be idiopathic (commonly familial) or due to a variety of causes. The pathophysiology of PKC is uncertain but it could be an ion-channel disorder. Antiepileptic drugs particularly carbamazepine are very helpful in a large proportion of cases. Paroxysmal exercise induced dystonia (PED) is a rare disorder manifesting as episodes of dystonia mostly affecting the feet induced by continuous exercise like walking or running. Although the initial cases were familial, there is a higher proportion of sporadic cases. The pathophysiology of PED is unknown and antiepileptic drugs are generally unhelpful. In paroxysmal dystonic choreoathetosis/non-kinesigenic dyskinesias (PDC/PNKD) the attacks are of long duration and induced by variety of factors including coffee, tea, alcohol and fatigue but not by sudden movement. PDC can be idiopathic (familial or sporadic) or symptomatic due to a variety of causes. The gene for familial PDC has been linked in 2 families to chromosome 2 q close to a cluster of ion channel genes again suggesting that this disorder may also be a channelopathy. Other paroxysmal disorders include paroxysmal nocturnal dyskinesia, a form of frontal lobe epilepsy in some cases which may be familial with autosomal dominant inheritance (ADNFLE). The gene for ADNFLE in one family has been found to be a mutation in the neuronal acetylcholine receptor gene (CHRNA4) on chromosome 20q. Tonic spasms in multiple sclerosis and Sandiffers syndrome producing intermittent torticollis in infants and children are other paroxysmal movement disorders.


Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer.
We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. In this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. Of 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non-squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. Addition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non-small-cell lung cancer, particularly squamous cell carcinoma.


Fibromodulin-deficient mice reveal dual functions for fibromodulin in regulating dental tissue and alveolar bone formation.
The extracellular matrix of newborn, 7- and 21-day-old fibromodulin-deficient (Fmod KO) mice was compared with age-matched wild-type (WT) mice. Western blotting of proteins from 21-day-old WT mice revealed that the molecular weight of Fmod is smaller in dental tissues (approx. 40 kDa) compared to alveolar bone extracts (approx. 52 kDa). Dentin matrix protein1 (DMP1) was slightly increased in Fmod KO versus WT tooth extracts. After chondroitinase ABC digestion, dentin sialophosphoprotein (DSPP) appeared as 2 strong bands (approx. 150 and 70 kDa) in incisors from 21-day-old Fmod KO mice, whereas the smaller-sized species of DSPP was nearly absent in WT molars and no difference was detected between WT and KO mice in molars. Dentin mineralization was altered in newborn and 7-day-old KO mice, but seemed normal in 21-day-old KO mice. DMP1 and DSPP may be involved in compensatory mechanisms. The enamel had a twisted appearance and looked porous at day 21 in KO incisor, and the outer aprismatic layer was missing in the molar. Alveolar bone formation was enhanced in Fmod KO mice at days 0 and 7, whereas no difference was detected at day 21. We conclude that Fmod may control dental tissue formation and early maturation, where it acts mostly as an inhibitor in alveolar bone accumulation, excerpting its effects only at early developing stages. These dual functions may be related to the different forms of Fmod found in bone versus teeth.


Role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in septic rats.
The aim of the present study was to investigate the role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in lipopolysaccharide (LPS)-induced septic rats. Male specific pyrogen-free Wistar rats were deprived food for 24 h before the experiment. Intravenous LPS (3 mg/kg dissolved in sterilized saline) was given to rats 12 h after food removal. Control rats received sterilized saline only. Under diethylether-anesthesia, the pylorus and esophageal sphincters of rats were ligated. Vagotomy also was performed. The stomachs were then irrigated for 3 h with physiological acid solutions containing 0-150 mM HCl plus adequate amount of NaCl. Increases in various ulcerogenic parameters, such as gastric acid back-diffusion, mucosal histamine concentration, luminal hemoglobin (Hb) content and stomach ulcer, were dependent on the concentration of acid solutions irrigated in stomachs of those LPS rats. Gastric vascular permeability also was increased in an acid concentration-related manner. In those LPS rats, high correlation was found between extents of acid back-diffusion and mucosal ulceration. Increased vascular permeability also closely related to the luminal Hb content. Moreover, these ulcerogenic parameters were dose-dependently ameliorated by intraperitoneal ketotifen and ranitidine. Diamine oxidase also was effective in inhibition, but exogenous histamine on the contrary, produced exacerbation of these ulcerogenic parameters. In conclusion, histamine plays a pivotal role in modulating gastric acid back-diffusion and vascular permeability that are greatly associated with hemorrhagic ulcer in septic rats.


Innovative Approach for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Pilot Study With the Hilotherm Device, the Poliambulanza Hospital Experience.
Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of taxanes, with no effective prevention or treatment available and a highly negative impact on patient quality of life. The aim of this study is to asses that the constant application of cooled cuffs on the hands and feet prevent and mitigate CIPN. Patients with breast, gynecologic, and pancreatic cancer who received weekly paclitaxel (PTX), PTX/carboplatin, and nab-paclitaxel (nab-PTX)/gemcitabine for any indication at the therapeutic scheduled dosage were included in this prospective study. Hilotherm Chemo care device forms a closed-loop system with cuffs and tubes through which a coolant flows at a temperature of 10 °C. CIPN was monitored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (edition 3.0), and the tolerability and side effects were scored by using the Common Terminology Criteria for Adverse Events (T4.03 2017). To date, we have enrolled 64 patients. Of these, 54 (84%) completed all cooling cycles. Continuous cooling was well tolerated by all patients. No patients had grade >2 CIPN or had serious or lasting adverse events as a result of Hilotherapy. The median time to CIPN onset was 77 days for the entire population. Hilotherapy has good effectiveness and tolerability and seems to be able to prevent or reduce the symptoms of CIPN. We are still recruiting patients to obtain more data and to collect data at 3 months after the end of chemotherapy. Prospective studies seem to be warranted.


Macaque V1 neurons can signal 'illusory' contours.
We describe here a new view of primary visual cortex (V1) based on measurements of neural responses in V1 to patterns called 'illusory contours' (Fig. 1a, b). Detection of an object's boundary contours is a fundamental visual task. Boundary contours are defined by discontinuities not only in luminance and colour, but also in texture, disparity and motion. Two theoretical approaches can account for illusory contour perception. The cognitive approach emphasizes top-down processes. An alternative emphasizes bottom-up processing. This latter view is supported by (1) stimulus constraints for illusory contour perception and (2) the discovery by von der Heydt and Peterhans of neurons in extrastriate visual area V2 (but not in V1) of macaque monkeys that respond to illusory contours. Using stimuli different from those used previously, we found illusory contour responses in about half the neurons studied in V1 of macaque monkeys. Therefore, there are neurons as early as V1 with the computational power to detect illusory contours and to help distinguish figure from ground.


[Effects of low-dose total body irradiation (TBI) on tumor-bearing rats].
To investigate the anti-tumor effects of low-dose total body irradiation (TBI) histologically, 5 x 10(5) KDH-8 cells were implanted into the right legs of WKAH rats. According to the treatment policies, rats were divided into four groups: non-treated, TBI alone, local irradiation (LI) following TBI, and LI alone. The total dose of TBI was 0.2 Gy, that of LI 10 Gy or 0.2 Gy. Local irradiation of 0.2 Gy had no suppressive effect on the growth of implanted tumor and/or metastasis. In the 10 Gy LI group, growth of the implanted tumor was totally suppressed, and histological findings (H-E staining) showed that there were few viable cells, few tissue-infiltrating cells, and severe fibrotic changes in the tumor tissue. In the TBI group, tumor growth was suppressed during only 7 days after TBI. However, abundant tumor infiltrating cells appeared 24 hours after TBI. Total body irradiation did not enhance the suppressive effect of LI on tumor growth. Metastases of the lung and abdominal lymph nodes were significantly suppressed by TBI. In the TBI group, using the lung-shield with 5 cm lead block, the suppression of lung metastasis was the same as that in the non-shield TBI group. These results suggested that a low dose of TBI brings about anti-tumor effects through a host immune response, unlike those produced by high-dose irradiation.


[Atmospheric and respiratory contamination by waste water aerosols].
A study was undertaken of the particle size of aerosols, emitted by a treatment plant for urban waste water, by counting the total flora, using and Andersen apparatus. Evidence of significant bacterial contamination was obtained on the perimeter of the installations. Calculations were made on the data obtained using a method to show the number of viable particles deposited at different levels within the pulmonary tree. During the working day approximately 10(4) viable particles, representing 1.5 x 10(6) organisms, products of the common flora of activated sludge were inhaled. Only a small fraction enters the pulmonary acini; the greater part are swallowed or excreted via the nose or on coughing.


Structure of an antimutagen from Carmona retusa leaves.
An antimutagenic compound was isolated from the leaves of Carmona retusa (Vahl) Masam. Its structure has been elucidated by spectral analysis to be 4-hydroxy-7,8,11,12,15,7',8',11',12',15'-decahydro-beta, psi-carotene. The results of the Micronucleus Test, an in vivo method, showed that the isolated antimutagenic compound reduced by approximately 68.4% the number of micronucleated polychromatic erythrocytes induced by tetracycline, a known mutagen.


Carbon-Encapsulated Ni3 Se4 /CoSe2 Heterostructured Nanospheres: Sodium/Potassium-Ion Storage Anode with Prominent Electrochemical Properties.
Heterogeneous structures are used as energy storage devices because of their ability to accelerate charge transfer, which greatly contributes to the rate capability of devices. However, the construction of heterostructures with conspicuous electrochemical properties remains a huge challenge. In this study, a design of heterostructured Ni3 Se4 /CoSe2 nanospheres encapsulated by a carbon shell (Ni3 Se4 /CoSe2 @C) synthesized through facile hydrothermal and annealing methods is presented. The Ni3 Se4 /CoSe2 @C exhibits excellent cyclic performance with a capacity of 420 mA h g-1 at 0.5 A g-1 after 100 cycles for Na-storage and 330.1 mA h g-1 at 0.1 A g-1 after 200 cycles for K-storage. The excellent cyclic performance can be attributed to the carbon coating that maintains the structural stability and enhances electrical conductivity, and significantly, the heterostructures that promote ion/electron transport. The sodium storage mechanism of the Ni3 Se4 /CoSe2 @C is revealed by ex situ X-ray powder diffraction, ex situ high-resolution transmission electron microscopy, and in situ electrochemical impedance spectra analyses. The first principles density functional theory calculation is performed to prove that the heterostructure on the Ni3 Se4 /CoSe2 interface can induce an electric field and thus improve the electrochemical reaction kinetics. This study provides an effective approach for constructing heterostructured composites for high-performance alkaline batteries.