Simvastatin reduces caspase-3 activation and inflammatory markers induced by hypoxia-ischemia in the newborn rat.
The present study was undertaken to evaluate whether in a neonatal model of stroke a prophylactic neuroprotective treatment with simvastatin modulates hypoxia-ischemia-induced inflammatory and apoptotic signaling. Procaspase-3 and cleaved caspase-3 expression showed a peak at 24 h and returned to control values after 5 days. Caspase-3 activity followed the same pattern of caspase-3 proteolytic cleavage. In simvastatin-treated ischemic animals, the expression of these proteins and caspase-3 activity were significantly lower when compared to that of ischemic animals. alpha-Spectrin and protein kinase C-alpha (PKCalpha) cleavages were not affected by the treatment. Poly (ADP-ribose) polymerase fragmentation, caspase-1 activation, and IL-1beta and ICAM-1 mRNA expression were increased by hypoxia-ischemia and significantly reduced in simvastatin-treated animals. The results indicate that simvastatin-induced attenuation of hypoxia-ischemia brain injury in the newborn rat occurs through reduction of the inflammatory response, caspase-3 activation, and apoptotic cell death.


Three-year oral clodronate treatment does not impair mineralization of newly formed bone--a histomorphometric study.
Bisphosphonates have been used successfully in the treatment of malignant hypercalcemia and skeletal metastases. Recently, clodronate has been studied in adjuvant settings in primary breast cancer. However, long-term effect of adjuvant clodronate on bone histology has not been reported, whereas bone mineral density studies have been published. The aim of this study was to examine the effect and safety of long-term clodronate treatment on bone quality as measured by histomorphometric techniques from bone biopsies. A total of 299 patients with early stage breast cancer were randomized to receive adjuvant oral clodronate (1.6 g/day) or to a control group for 3 years. All patients had adjuvant treatment: premenopausal women had six cycles of chemotherapy and postmenopausal women had antiestrogen for 3 years. Trabecular bone quality was examined in transiliac bone biopsy specimens by using histomorphometric techniques in 28 clodronate treated and 35 control patients who were disease-free at 3 years and who allowed the biopsy specimen to be obtained. No statistically significant differences were found in the values of osteoid, mineral apposition rate, or mineralization lag time in bone biopsies between the clodronate and the control groups. Postmenopausal women who received two antiresorptive drugs, antiestrogen and clodronate, developed features of secondary hyperparathyroidism with increased eroded surface and osteoclast number. In premenopausal, women clodronate with adjuvant chemotherapy, which induced early menopause and rapid bone loss in most of the patients, seemed to conduct slight depression in bone formation. Three-year oral clodronate treatment does not impair mineralization of newly formed bone: however, clodronate with different adjuvant breast cancer treatments has a diverse impact on bone histomorphometry depending on the type of therapy.


Factors associated with health-related quality of life among Indian women in mining and agriculture.
Women facing social and economic disadvantage in stressed communities of developing countries are at greater risk due to health problems. This paper investigates the relationships between structural, health and psychosocial predictors among women in mining and agricultural communities. This paper is a report of a study of the predictors of the health-related quality of life among Indian women in mining and agricultural communities. A descriptive cross-sectional research design was used. The instruments used are SF-36 Health Survey and Coping Strategy Checklist. ANOVA, MANOVA and GLM were used in the analysis. The study was conducted between January-September 2008 with randomly selected women in a mining (145) and an agricultural community (133) in India. Women in the agricultural community had significantly increased Physical Health, Mental Health and SF36 scores compared with those in the mining community. Years of stay, education and employment were significant predictors among women in the agricultural community. 39% (33%) and 40% (26%) of the variance in Physical and Mental health respectively among women in agricultural and mining communities are predicted by the structural, health and psychosocial variables. Perceived health status should be recognised as an important assessment of Physical and Mental Health among women in rural stressed communities. Cognitive, emotional and behavioural coping strategies are significant predictors of health related quality of life. Implications. Nurses should use the SF-36 as a diagnostic tool for assessing health related quality of life among women and discuss coping strategies, so that these can target women's adaptive behaviour. This should be an essential part of the nursing process for facilitating adaptive process for improved health related quality of life.


Substance Use Disorders and Role of Complementary and Integrative Medicine/Functional Medicine.
Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.


Drug release from xyloglucan beads coated with Eudragit for oral drug delivery.
Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.


Detecting R-Loop Formation Using a Plasmid-Based In Vitro Transcription Assay.
R-loops are three-stranded nucleic acid structures that consist of a DNA-RNA hybrid and a displaced single-stranded DNA. Since it was first reported by Ronald Davis and colleagues over 40 years ago, the study of R-loops has become an increasingly expanded area of research. Numerous factors have been identified to modulate the dynamic formation and resolution of R-loops, which are critical for proper controls of gene expression and genome stability. Along the lines of these discoveries, various biochemical and cellular assays have been developed to detect R-loop changes in vitro and in vivo. In this chapter, we describe a protocol for measuring R-loop formation using a plasmid-based in vitro transcription assay. The R-loop formed is then detected and quantified by using gel mobility, antibody staining, and DNA-RNA immunoprecipitation (DRIP)-qPCR assays. Unlike the helicase assay that uses short R-loop substrates, this assay system introduces DNA topology and active transcription as additional variables that impact R-loop formation, thus, more closely recapitulating in vivo situations. Furthermore, this method can be adopted for investigation of cis-elements and trans-acting factors that influence R-loop formation.


miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor.
Influenza A virus (IAV) infections result in a large number of deaths and substantial economic losses each year. MicroRNAs repress gene expression and are involved in virus-host interactions. miR-29a is known to have anti-tumor and anti-fibrotic effects. However, the role of miR-29a in IAV infection is unclear. In the present study, we investigated the effect of miR-29a on IAV infection and the mechanisms by which it functions. IAV infection was found to cause decreased miR-29a expression in lung epithelial A549 cells and mouse lungs. Overexpression of miR-29a reduced IAV mRNA and protein levels and progeny virus production in HEK293 and A549 cells. Inhibition of IAV infection by miR-29a was observed with different strains of IAV, including A/PR/8/34, A/WSN/1933, and clinical isolates A/OK/3052/09 and A/OK/309/06 H3N2. Knockout of miR-29a using CRISPR/Cas9 resulted in an increase in viral mRNA and protein levels, confirming that miR-29a suppresses IAV infection. A 3' untranslated region (3'-UTR) reporter assay showed that miR-29a had binding sites in the 3'-UTR of the Wnt-Ca2+ signaling receptor frizzled 5 gene, and overexpression of miR-29a reduced the level of the endogenous frizzled 5 protein. Wnt5a treatment of HEK293 and A549 cells enhanced IAV infection. Our results suggest that miR-29a inhibits IAV infection, probably via the frizzled 5 receptor.


Non-steroidal anti-inflammatory drug-associated nephrotoxicity in Bartter syndrome.
We have followed four patients with Bartter syndrome for a mean of 25.4 years (range 21.5-28.8 years) after diagnosis. All patients received non-steroidal anti-inflammatory drugs (NSAID). In all patients, various degrees of renal dysfunction were noted to be temporally associated with NSAID therapy. In two patients, renal dysfunction resolved after discontinuing NSAID therapy, while maintaining other chronic medications such as potassium-sparing diuretics. Renal dysfunction persisted after NSAID withdrawal in two patients. We report these cases as a warning that NSAID should be considered an important cause of either reversible or irreversible renal dysfunction in Bartter syndrome.


Beach debris quantity and composition around the world: A bibliometric and systematic review.
Anthropogenic pollution of marine ecosystems caused by beach debris has become a serious environmental concern in the last few decades. Regarding the raising production of beach debris, the present work aimed to summarize the quantity and quality of beach debris reported from different beach areas of the world. Also, a bibliometric analysis was used to analyze research trends and upgrade knowledge in this research area. Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), the eligible papers reviewed regarding beach debris abundance along with their composition from 2010, which were extracted from the Scopus database. The results of the study showed that plastic items represented the dominant material (61.25%), followed by food (5.88%), wood (5.78%), metals (5.2%), and glass (5%). Further, the beaches studied were classified into three degrees, including highly polluted (31.5 items/m2), moderate polluted (3.47 items/m2), and low polluted (0.37 items/m2), based on the average abundance of debris.


Effect of cereal-legume chapati diets on absorption and retention of calcium.
Wheat chapati, wheat + Bengal gram (80:20 and 70:30) chapatis and casein diets, at 10 percent protein level, were fed to rats for 12 weeks to study the effect on calcium utilization. The supplementation of Bengal gram to wheat diets significantly improved the calcium absorption. The urinary calcium excretion in wheat + Bengal gram chapati diets was significantly less than that of wheat chapati diet fed group. The in vivo 45Ca absorption (CPM/100 microliters serum) was also less in wheat chapati group as compared to wheat + Bengal gram chapati diets fed groups. The supplementation of legumes to cereals improved the calcium utilization and it may be concluded that there will be no risk of occurrence of protein induced hypercalciuria.


Paracentric inversion-associated t(8;21) variant in de novo acute myelogenous leukemia: characteristic patterns of conventional cytogenetics, FISH, and multicolor banding analysis.
Acute myelogenous leukemia (AML) with t(8;21)(q22;q22) demonstrates unique clinico-pathologic disease entity in patients with hematologic malignancies. The t(8;21), which results in fusion of the AML1 gene on 21q22 and the ETO gene on 8q22 on a molecular level, is one of the most common nonrandom chromosomal changes, and it is found in about 5-12% of patients with AML. Among these cases, complex variants involving chromosomes 8 and 21, as well as a third or fourth chromosome, account for approximately 6-10% of patients with an AML1/ETO chimeric gene, and about 100 variant cases with AML1/ETO fusion transcript have been reported in the literature. Here, we describe a rare case report of reciprocal paracentric inversion-associated t(8;21) variant in a 28-year old male patient with de novo AML. The abnormal results of conventional cytogenetics and interphase fluorescent in situ hybridization in this patient drove us to perform further studies and a literature review. This report emphasizes the value of "conventional" cytogenetics, as well as "newly developed" molecular cytogenetic methods in the diagnosis of rare complex t(8;21) variant in patients with AML.


Long-term anatomical and functional outcomes of idiopathic macular hole surgery. The yield of spectral-domain OCT combined with microperimetry.
To evaluate the correlations between anatomical and functional changes studied with microperimetry (MPM) and spectral-domain OCT (SD-OCT) in patients after successful repair of idiopathic macular hole (MH). Monocentric, retrospective, interventional study in 23 eyes of 23 patients who underwent successful surgery for MH defined as closure of the hole, at least 1 year before. Reported data were pre- and postoperative best-corrected visual acuity (BCVA), retinal sensitivity values on MPM, macular and foveal thicknesses, and retinal anatomic lesions on SD-OCT. Macular sensitivity (MS) and foveal sensitivity (FS) were lower and the number of lesions of the outer retinal layers was higher in patients with a poorer postoperative VA (P = 0.029, P = 0.011 and P = 0.003 respectively). Preoperative MH size was lower and MS and FS were better in patients with a preserved junction line between the inner and outer segments of photoreceptors (IS/OS) (P = 0.045, P = 0.001, and P = 0.001 respectively). Better postoperative VA was correlated with better preoperative VA (P = 0.012, r = 0.513). Postoperative VA was correlated with MS and FS (P = 0.032, r = 0.449, and P = 0.019, r = 0.483 respectively). Greater foveal thickness was associated with better postoperative VA (P = 0.020, r = 0.482). Postoperative outer retinal layer integrity is associated with better final retinal sensitivity. Further studies are warranted to assess the role of SD-OCT and microperimetry in the pre- and postoperative evaluation of idiopathic macular holes.


Removal of PAHs at high concentrations in a soil washing solution containing TX-100 via simultaneous sorption and biodegradation processes by immobilized degrading bacteria in PVA-SA hydrogel beads.
Soil washing process enhanced by surfactants is a promising technique in removing organic pollutants from soil. In this work, a simultaneous sorption and biodegradation technique was used to remove 16 PAHs from a soil washing solution (SWS) obtained by rinsing a heavily contaminated soil from a coking plant with Triton X-100 (TX-100). This was done by immobilizing a pyrene-degrading bacterial strain in polyvinyl alcohol-sodium alginate (PVA-SA) hydrogel beads. Removal performance of free bacteria, blank PVA-SA beads and beads with immobilized degrading bacteria at a low, medium and high initial concentration was evaluated. The recycling and removal performance of the used beads were also examined. Our findings showed that hydrogel beads with immobilized bacteria at a medium concentration can remove around 77% ∑16PAHs from SWS in 96 h. The beads can be recycled and reused to treat a new SWS; 32-55% ∑16PAHs was removed in 24 h. The bead provided protection for bacteria against the co-existing substances such as TX-100. The bacteria-immobilized beads are more efficient and sustainable than free bacteria and blank beads due to simultaneous sorption and biodegradation processes, thus providing a solid reference for possible industrial application of bacteria immobilization technique to deal with SWSs with complex composition.


Metal-ion catalyzed polymerization in the eutectic phase in water-ice: a possible approach to template-directed RNA polymerization.
The emergence of an RNA world requires among other processes the non-enzymatic, template-directed replication of genetic polymers such as RNA or related nucleic acids, possibly catalyzed by metal-ions. The absence of uridilate derivative polymerization on adenine containing templates has been the main issue preventing an efficient template-directed RNA polymerization. We report here the investigation of template-directed RNA polymerization in the eutectic phase in water-ice. In particular, it was found that activated uridilate monomers in the presence of metal-ion catalysts could efficiently elongate RNA hairpins whose 5'-overhangs served as the templating sequence. The same applies for every other pyrimidine and purine nucleobase. Moreover, the initial elongation rates were always higher in the presence of a template complementary to the nucleotide than in systems without proper base-pairing opportunities. These results suggest that a template-directed RNA polymerization catalyzed by metal-ions could be carried out under eutectic phase in water-ice conditions.


Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women: A Case-Control Study.
To identify a potential genetic basis for early failure after prolapse surgery. Case-control study (Canadian Task Force classification II). This study was carried out in 1 academic community medical center referral practice, and all patients had surgery at 1 of 2 hospitals. Ten women with early, multicompartment prolapse recurrence after robotic sacrocolpopexy compared with 40 control subjects with known success after the same procedure. Patients were treated with robotic sacrocolpopexy. DNA was isolated and initially genotyped on a single nucleotide polymorphism (SNP) array to direct more detailed exome analyses. Exome sequences were mapped to the Human Genome Reference Sequence (GRCh37), and variants were compared between groups and to participants in the 1000 Genomes Project. Statistical analyses were performed using a software package commonly used in genetics research. TaqMan assay was used for verification, and p values were adjusted using the false discovery rate. Demographics of groups were compared using χ(2), Mann-Whitney U, and t tests. A SNP [rs171821] located near the ZFYVE16 gene was associated with patients but not control subjects, and the false discovery rate-adjusted p value was .046 (odds ratio, 45.2; 95% confidence interval, 5.06-403). Exome analyses of this gene yielded another SNP [rs249038 (G/A)] in 6 of 10 patients and none of the control subjects (p = .02). This SNP causes a heterozygous missense mutation of glycine to serine predicted to be deleterious by the Protein Variation Effect Analyzer and was also very rare among participants in the 1000 Genomes Project (p < .001). Two SNPs located near the ZFYVE16 gene on chromosome 5 may have played a role in the early, multicompartment sacrocolpopexy failure experienced by our patients. (www.clinicaltrials.gov Identifier: NCT01614587).


Prevalence of recurrent symptoms and their association with epilepsy and febrile seizure in school-aged children: a community-based survey in Iceland.
We determined the prevalence of common recurrent symptoms in a community-based study of children and investigated whether these symptoms were associated with epilepsy and febrile seizure. A questionnaire was developed and sent to parents of all children attending school in the Reykjavik school district, grades 1-10. The questions assessed personality traits, headache, epilepsy, febrile seizure, and recurrent symptoms. Of the 13,044 questionnaires distributed, 10,578 were returned (81%). We analyzed the subset of 9679 (91%) questionnaires with complete information on relevant factors. The prevalence of epilepsy was 7.7/1000; febrile seizures were reported in 5.1% of children. Prevalence estimates of recurrent symptoms were similar to the published literature. In our cohort, recurrent dizzy spells and recurrent visual disturbances were associated with epilepsy after adjustment for age, migraine and febrile seizure. This association could reflect, only in part, the occurrence of auras in children with epilepsy.


Differential counts of B and T lymphocytes in the lymph nodes, circulating blood and spleen after inhalation of high concentrations of diesel exhaust.
Inhalation of diluted diesel engine exhaust results in the deposition of submicron carbonaceous particles in the respiratory airways. The particles are phagocytized by the pulmonary alveolar macrophages and cleared from the respiratory tract via the mucociliary escalator or through lymphatic channels. Lung clearance via lymphatics results in accumulation of particles in the regional lymph nodes. Differential counts of B and T lymphocytes were performed to determine whether the deposited carbon particles in the lymphatic tissue can alter the subpopulation composition of various lymphoid compartments. In contrast to the effect of materials such as heavy metals, halogenated hydrocarbons or cigarette smoke condensate, all of which have been shown to alter B and T cell differential counts of lymphoid compartments under various test conditions, assays of lymphocytes from tracheobronchial lymph nodes, spleen and blood from guinea pigs exposed to diluted diesel exhaust with a particulate concentration of 1500 micrograms m-3 for up to 8 weeks revealed no significant changes when compared with age-matched controls. Furthermore, cell viability as measured by trypan blue exclusion in the exposed groups was comparable to that of the age-matched controls. These data indicate that, within the range of tested conditions, the deposited diesel particles do not exert major effects on the parameters of the immune system that were measured.


Successful radiofrequency ablation therapy for intractable ventricular tachycardia with a ventricular assist device.
Refractory ventricular tachycardia (VT) can be a potentially life-threatening rhythm in the presence of non-ischemic dilated cardiomyopathy, particularly when it results in hemodynamic compromise. A 65-year-old man with non-ischemic cardiomyopathy was referred for multiple episodes of VT. A HeartMate left ventricular assist device (LVAD) was implanted to stabilize and control the VT. However, he had multiple episodes of VT and the frequency of ventricular arrhythmias did not improve after LVAD implantation. He required electrical cardioversion to treat each episode. On Day 41 post-operatively, radiofrequency ablation was performed. Two significant areas of scarring were identified and were successfully ablated. After ablation, he did not have significant sustained VT episodes and was discharged.


Balloon catheter dilation for treatment of adults with partial nasolacrimal duct obstruction: a preliminary report.
The purpose of this study is to determine the efficacy and morbidity of balloon catheter dilation for treatment of partial acquired nasolacrimal duct obstruction in adults with epiphora. We performed balloon dacryocystoplasty prospectively on a series of 15 partial nasolacrimal duct obstructions in 13 adults with epiphora. Partial obstruction was diagnosed by a negative Jones-1 test and canalicular irrigation revealing simultaneous reflux through the opposing punctum and drainage into the nose. Balloon dacryocystoplasty was performed under local anesthesia using an antegrade insertion technique. Silicone intubation of the nasolacrimal system was performed immediately after balloon catheter dilation, and the tubes were removed 2 months postoperatively. Success was measured objectively and subjectively at follow-up examinations 2 months and 6 months after the procedure. At 2 months, 11 (73%) of 15 obstructions were open on irrigation, with subjective success (Munk, grade 0 or grade 1) reported in 13 (87%) of 15 obstructions. At 6 months, 11 (73%) of 15 obstructions were open on irrigation, with subjective success (Munk, grade 0 or grade 1) reported in 9 (60%) of 15 obstructions. Balloon dacryocystoplasty may be a satisfactory primary treatment for adults with acquired partial nasolacrimal duct obstruction who exhibit no clinical signs of chronic infection. Additional long-term observations following balloon dacryocystoplasty are required.


Dellon's anterior submuscular transposition of the ulnar nerve: Retrospective study of 82 operated patients with 11.5 years' follow-up.
Anterior submuscular transposition of the ulnar nerve described by Dellon can solve the dynamic component of cubital tunnel syndrome at the elbow. We carried out a retrospective, single-surgeon study. The McGowan scale as modified by Goldberg (MG) was used preoperatively and at the final assessment; the QuickDASH was completed at the final assessment. The cohort comprised of 82 patients (38 females, 44 males) with a mean age of 61.2 years (37-92). The preoperative MG grade was: stage I (52%), IIA (28%), IIB (16%), III (4%). Three postoperative complications (3.5%) were recorded: two hematomas that did not require surgical revision and one case of elbow stiffness that resolved with physical therapy. Mean follow-up was 11.1 years (11-12). We identified 5 cases of confirmed recurrences (5.9%), 7 of secondary deterioration (8.5%) and 3 of initially poor result (3.5%). Sixty-six patients (86%) considered themselves cured at the final assessment. The MG scale at the last follow-up was: stage 0 (85.5%), I (9%), IIA (5%), III (0%). The QuickDASH was 11.88 (11-16). Mean time to recurrence was 6.3 years (1.5-10). Dellon's anterior submuscular transposition can be considered a reliable procedure. Eighty-six percent of patients were cured and 6% recurrence rate was noted. However, this is a demanding procedure.


Improving balance by improving motor skills.
The effectiveness of a computer-assisted balance training was compared with a home based exercise program in healthy elderly subjects. Twenty-four physically active community dwelling elderly (median age 71 years) participated in the study. Balance was assessed by a summary performance score, measuring postural stability while standing, reaching, stepping and walking. Subjects of the computer-assisted balance training group could considerably improve their performance on the training device (p = 0.0078) as well as in the summary balance score (p = 0.0176). No improvement of balance was documented in the home-based exercise group. A superiority of the computer-assisted balance training exercise protocol over the home-based exercise group could not be documented (p = 0.3934). The study indicates that a computer-assisted balance training, focussing on one motor skill, can improve balance. It is suggested that a home-based exercise program is ineffective to improve balance in elderly persons, if there is no direct supervision.


Poly thymine stabilized copper nanoclusters as a fluorescence probe for melamine sensing.
In this work, poly-thymine stabilized copper nanoclusters have been used as a fluorescence probe for melamine sensing for the first time. Melamine can bind to thymine through hydrogen bond, which could dramatically enhance the fluorescence intensity of poly-thymine stabilized copper nanoclusters. The enhancement factors (I-I0)/I0 increase linearly with the lgCmelamine over the melamine concentration range of 0.1 µM to 6 µM. The detection limit of melamine is 95 nM, which is 200 times lower than the US Food and Drug Administration estimate melamine safety limit 20 µM. Melamine in milk was detected with good recovery, which suggested that this novel fluorescence probe has great potential in practical application.


The effects of liposome size and surface charge on liposome-mediated delivery of methotrexate-gamma-aspartate to cells in vitro.
We have studied the liposome-mediated delivery of methotrexate-gamma-aspartate to five cell lines. The sensitivity of the cells to encapsulated drug varies widely in accordance with their ability to take up the liposomes. CV1-P cells can be 150-times more sensitive to encapsulated methotrexate-gamma-aspartate than to free drug, while AKR/J SL2 cells are only twice as sensitive to the encapsulated drug. Negatively-charged liposomes are much more efficient for delivery than are neutral liposomes, and cholesterol is an essential component of the liposome membrane for optimal drug delivery. The optimal liposome size for drug delivery is 0.1 micron, although the amount of cell-associated lipid is the same for all liposome sizes. The effect of the encapsulated drug is inhibited by NH4Cl, suggesting an endocytic mechanism for delivery. The potency of the encapsulated drug is not affected by wide variations in the drug: lipid ratio.


The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α.
Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α. Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined. Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.


Dexamethsone suppresses bone formation via the osteoclast.
Glucocorticoids are central to treating inflammatory and immune disorders. These steroids, however, profoundly impact the skeleton, particularly when administered for prolonged periods. In fact, high-dose glucocorticoid therapy is almost universally associated with bone loss, prompting among the most common forms of crippling osteoporosis. Despite the frequency and severity of glucocorticoid-induced osteoporosis, its treatment is less than satisfactory, suggesting that its pathogenesis is incompletely understood. Net bone mass represents the relative activities of osteoblasts and osteoclasts and there is little question that glucocorticoids suppress the bone-forming cells, in vivo, via a process involving accelerated apoptosis (Weinstein 2001; Weinstein, Jilka, Parfitt, et al. 1998). Surprisingly, however, addition of glucocorticoids to cultures of osteoprogenitor cells actually increases their capacity to form mineralized bone nodules (Aubin 1999; Purpura, Aubin, and Zandstra 2004). This paradox raises the possibility that glucocorticoid suppression of bone formation, in vivo, reflects, at least in part, the steroid's targeting intermediary cells, which in turn inhibit the osteoblast. Bone remodeling is an ever-occuring event in mammals which is characterized by tethering of osteoclast and osteoblast function. The process is initiated by osteoclasts (OCs) resorbing a packet of bone, which in turn leads to osteoblasts being recruited to the site of resorption. This process establishes that osteoclastic bone resorption, in some manner, promotes osteoblastic bone formation at the same location. Consequently, pathologically or pharmacologically inhibited resorption eventuates in arrested osteoblast activity.


[The effects of erythromycin on the secretion of tumor necrosis factor-alpha and transforming growth factor-beta1 and expression of connexin 43 in human pleural mesothelial cells].
To investigate the effects of erythromycin on secretion of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)), and the level of connexin 43 in human pleural mesothelial cells (HPMC), and to explore the mechanism of pleurodesis. HPMC was incubated with erythromycin at concentrations of 100 mg/L or 25 mg/L. The levels of TNF-alpha and TGF-beta(1) in the supernatants were measured by ELISA method, and levels of connexin 43 were detected by Western blot. The secretion of TNF-alpha by HMPC increased after incubation with 100 mg/L erythromycin for 3 or 5 days, and the secretion of TGF-beta(1) increased markedly after incubation with lower or higher concentrations of erythromycin. The levels of connexin 43 in HPMC decreased after stimulation with 100 mg/L erythromycin, but no relationship was observed between the levels and the stimulation time. HPMC incubated with erythromycin showed increased secretion of TNF-alpha and TGF-beta(1), which may be one of the mechanisms for erythromycin pleurodesis. Erythromycin decreased the level of connexin 43 in HPMC, and this effect may be a response of the cells to the stimulus. A high concentration of erythromycin is suggested for clinical pleurodesis based on the results from this study.


Sport after total hip arthroplasty.
Up to now, sporting activity after total hip arthroplasty has been limited or terminated completely because of the risk of failure. In the case of younger patients, it is desirable to know whether this attitude is justified. Consequently, an analysis has been made of 110 patients (all male, average age at the time of the operation 55 years, 42 bilateral). Sport was practised in 78 and 56% of the cases prior to an after the operation respectively. The patients with intense sporting activity were examined and the findings compared with those who did not participate in a sporting activity after the operation. The incidence of replacement due to loosening is surprisingly higher among the group of patients with no sporting activity (14.3% to 1.6%). In the light of these findings, there is no need to prohibit sport in these cases. To allow for a gradual resumption of sport, guidelines have been elaborated on the basis of present-day knowledge of quantitative and qualitative hip strain. The short load peaks appearing as the heel touches the ground on walking or running will be attenuated by means of a viscoelastic heel pad.


Clinicopathological and immunological characterization of RNA m6 A methylation regulators in ovarian cancer.
N6 -methyladenosine (m6 A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m6 A regulators in ovarian cancer are still poorly understood. We integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m6 A regulators in ovarian cancer. We showed that alterations in the expression of m6 A regulators were related to the malignancy and poor prognosis of ovarian cancer. We found decreased YTHDC1 and increased RBM15 expressions were associated with ovarian cancer cell metastases and HNRNPC was a predictor of paclitaxel resistance. Moreover, dysregulated m6 A regulators were enriched in the activation of cancer-related pathways. Our results further demonstrated that the level of immune cell infiltration and the expression of various immune gene markers were closely associated with the expressions of specific m6 A regulators (RBM15B, ZC3H13, YTHDF1, and IGF2BP1). Our study establishes a new prognostic profile of ovarian cancer patients based on m6 A regulators, and highlights the potential roles of m6 A regulators in ovarian cancer development.


Hyperfractionation decreases the deleterious effects of conventional radiation fractionation on vertebral growth in animals.
Craniospinal axis irradiation in the treatment of pediatric tumors is associated with serious long-term sequelae including decreased bone growth (short sitting stature). In this study, an animal model was used to determine the effects of smaller incremental doses of radiation on bone growth. Sprague-Dawley weanling rats were given 25 Gy to the spine in 8 to 9 days, with fraction sizes ranging from 1.0 to 1.8 Gy. The animals receiving smaller doses per fraction (1.0 or 1.25 Gy) showed significantly more growth of the vertebral bodies in the treated fields than animals given larger incremental doses (1.5 or 1.8 Gy). These findings indicate a protective effect on bone growth for hyperfractionated irradiation of vertebral bodies.


Ion-exchange voltammetry and electrocatalytic sensing capabilities of cytochrome c at polyestersulfonated ionomer coated glassy carbon electrodes.
The incorporation and electrochemical behaviour of cytochrome c (Cyt C) at glassy carbon electrodes modified with the polyestersulfonated ionomer Eastman AQ 55 are examined. The presence of the polyelectrolytic coating allows the preconcentration of the protein within the polymer and the observation of the direct electrochemistry of Cyt C at the modified electrode without addition of promoters or mediators in the solutions. The dependence of voltammetric signals on typical parameters such as solution pH and nature or concentration of the supporting electrolyte supports the ion-exchange nature of the incorporation process. The relevant role of the permselectivity of the polymeric modifier is highlighted also by the study of electrocatalytic processes which take place at the modified electrode loaded with Cyt C. No electrocatalytic effect is observed when the electrogenerated dication (ferricenylmethyl)trimethylammonium is present as possible oxidant. On the contrary, electrocatalytic current enhancements are observed for anionic substrates such as Fe(CN)(6)(3-) (oxidant) and ascorbate (reductant). Catalytic currents increase with the substrate concentration, with higher sensitivity for Fe(CN)(6)(3-). Due to ionic repulsion, the reaction with anions occurs at the polymer-solution interface. In the case of chemically unstable substrates, such as superoxide anion, ionic repulsion slow down the approach rate of the substrate so that spontaneous decomposition can prevail over the reaction with Cyt C incorporated in the coating.


Spermatogenesis as a tool for staging gonad development in the gonochoric appendicularian Oikopleura dioica Fol 1872.
Oikopleura dioica, the only gonochoric species among appendicularians, has a spematozoon with a mid-piece and a conspicuous acrosome that, during fertilisation, undergoes a reaction forming an acrosomal process. To provide more insight into the spermatogenesis of a holoplanktonic tunicate species that completes its life cycle in three to five days, changes in the testis during individual growth have been examined. Spermatogenesis has been subdivided into seven stages based on ultrastructural features during the formation and organisation of the male gonad and the relationships between its macroscopic anatomy and the events of sperm differentiation. Gametes undergo highly synchronised differentiation due to the presence of widespread syncytial structures. Both meiosis and spermiogenesis are brief, and the passage from spermatocytes to spermatids involves a progressive segregation of the germ cells from the syncytial mass with the formation of large cytoplasmic bridges and volume reduction for nucleus compacting and cytoplasmic material changing. The nucleus is small and penetrated anteriorly by a complex acrosome and posteriorly by the distal centriole and part of the flagellum. In spermatids, the single, large mitochondrion appears laterally to the nucleus, and finally, in spermatozoa, it migrates into the mid-piece, wrapping the proximal portion of the axoneme. Because this mitochondrial position is reached only in the late phases of spermatogenesis, it suggests that appendicularians have derived oligopyrenic sperms in which the small nucleus results from adaptation to the assembly of numerous spermatozoa inside the narrow space of the testis compacted in the genital cavity. The formulation of a staging system of gonad development in a model tunicate species known for having the most compacted genome in chordates led to a comparison of histological observations with recent molecular data, improving the characterisation of its biology and life cycle in light of evolutionary implications.


Flow-injection chemiluminescence sensor for determination of isoniazid in urine sample based on molecularly imprinted polymer.
In this paper, molecularly imprinted polymer (MIP) of isoniazid is synthesized through thermal radical copolymerization of metharylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) in the presence of isoniazid template molecules. A novel flow injection chemiluminescence sensor for isoniazid determination is developed by packing the isoniazid-MIP into the flow cell as recognition elements. Isoniazid could be selectively adsorbed by the MIPs and the adsorbed isoniazid was sensed by its great enhancing effect on the weak CL reaction between luminol and periodate which were mixed in the flow cell. The enhanced CL intensity is linear in the range 2x10(-9) to 2x10(-7) g/mL and the detection limit is 7x10(-10) g/mL (3sigma) isoniazid with a relative standard deviation 2.8% (n=9) for 8x10(-8) g/mL. The sensor is reversible and reusable. It has a great improvement in sensitivity and selectivity for CL analysis. As a result, the sensor has been successfully applied to determination of isoniazid in human urine. At the same time, the binding characteristic of the polymer to isoniazid was evaluated by batch method and the dynamic method, respectively.


Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.
Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.


Responsive microgels-based colloidosomes constructed from all-aqueous pH-switchable coacervate droplets.
Colloidosomes made of stimuli-responsive microgels offer the opportunity to design polymeric capsules with a hierarchical and tunable pore distribution. Coacervates stabilized by a microgel monolayer represent a unique strategy to build colloidosomes from all-aqueous emulsion drops, while exploiting the sequestration and dissolution properties of the coacervates. Methacrylated poly(N-isopropylacrylamide) (pNIPAM) microgels are used to stabilize coacervates made of an ampholyte polymer at a pH close to its isoelectric point. They are further cross-linked under UV-irradiation. The resulting assemblies are studied by means of confocal microscopy. Their permeability towards dextrans and nanoparticles is studied before and after dissolution of the coacervate. PNIPAM microgels are found to stabilize the coacervates by adsorbing at their surface. Inter cross-linking the microgels results in the formation of an elastic colloidosome that persists after the coacervate dissolution and withstands surface deformations up to about 200%. The coacervate is exploited as a sequestrating core to entrap a water-soluble payload, which can be further released upon coacervate dissolution, while the membrane exhibits a size-selecting permeability. The membrane properties can also be switched by the volume phase transition of the microgels. Coacervate-embedded colloidosomes open new perspectives in the area of encapsulation/extraction and controlled transport of water-soluble/dispersed species.


Radical reactions with 2-bromobenzylidene group, a protecting/radical-translocating group for the 1,6-radical hydrogen transfer reaction.
[Structure: see text] The 2-bromobenzylidene group, designed as a novel protecting/radical-translocating (PRT) group, proved to be effective for an unusual 1,6-hydrogen transfer reaction. Using this PRT group, 4-branched ribose derivatives were stereoselectively prepared.


Diagnostic challenges of adult asthma.
Bronchial asthma is a common disorder that affects about 300 million people worldwide. Its signs and symptoms however, can be present in other pulmonary and/or airway diseases and therefore a careful workup of patients with respiratory symptoms that might be due to asthma is required to a) keep a broad differential diagnosis, especially in cases that do not respond well to standard antiasthmatic therapy and b) attempt to subphenotype patients within the syndrome of asthma to diagnose e.g. precipitating factors, inflammatory subtypes and comorbidities. The syndrome of asthma contains a number of different phenotypes that offer the possibility of personalized medicine based on the respective asthma phenotype. There are attempts to combine asthma and COPD in newly postulated overlap syndromes which this review discourages to do but instead, based on new and old information concerning asthma phenotyping, suggests to rule in comorbidities and rule out a number of other diseases that can mimick asthma clinically. Bronchial asthma, although one of the most common respiratory diseases, can be mimicked by a number of other pulmonary and airway diseases, and especially patients with so called severe or treatment refractory asthma should receive a detailed diagnostic workup with a rather broad differential diagnosis.


Gastric plexiform fibromyxoma, an uncommon mesenchymal tumor.
Plexiform fibromyxoma (PF) is an uncommon primary tumor of the gastrointestinal tract, with a mesenchymal origin and a benign behavior. Herein, we report a case and provide a literature review. A 41-year-old male patient underwent surgery in our unit for a PF at the gastric antrum, after being admitted due to vomiting and weight loss. As illustrated by our case, the mean age at presentation is around 40 years, the antrum is the most common location and abdominal pain the most widely reported manifestation. None of the reviewed cases involved regional or distant spread.


Clinical manifestations of malfunctioning sympathetic mechanisms in tetraplegia.
Patients who are tetraplegic with cervical spinal cord transection do not appear to have cerebral control over the sympathetic nervous system. Soon after transection they are often in a state of spinal shock during which even isolated spinal cord sympathetic activity is absent. This affects, in particular, the cardiovascular system and other homeostatic mechanisms which are dependent on appropriate regulation of the vasculature, such as thermoregulation. After a few weeks isolated spinal cord activity returns but the absence of control absence of control by the brain results in sympathetic malfunction of various systems. Inappropriate inactivity therefore occurs during postural change and causes orthostatic hypotension, while over-activity, which results in the syndrome of autonomic dysreflexia and hypertension, occurs if spinal sympathetic reflexes are activated. Examples are provided of clinical effects of sympathetic malfunction in tetraplegics in relation to circulatory, thermoregulatory, pupillary, genital, gastrointestinal and urinary tract function.


Estimation of CD3, CD4, and CD8 in Iraqi patients with alopecia areata and alopecia universalis.
Alopecia areata is considered to be an autoimmune disease characterized by T-cell response and production of cytokines around the anagen stage. The aim of this study was to assess T cells in blood using immune biomarkers (CD3, CD4, and CD8) in patients with AA and AU compared with healthy individuals. This study was carried out at private clinic and in the Department of Dermatology in Al Karama Teaching Hospital. The study groups included 58 patients from different geographic areas in Iraq, with ages ranging from 5 to 48 years from the end of August 2019 to the January 2020; AA patient group included 19, AU patient group included, 11 and control group included 30 with no scalp or body lesions in their disease history. All patients were clinically diagnosed to detect clinical types of disease in the scalp, in the body, and any hair-bearing area. Venous blood samples were collected from all participants where CD3 T cell, CD4 T cell, and CD8 T cell in whole blood were estimated by flow cytometry technique. The present study has found the males are more susceptible to infection than the females in both types of disease. There was no significant difference (p > 0.05) detected for immune biomarkers (CD3, CD4, and CD8) in blood between patient groups in comparison with healthy individuals, but there was a significant decrease (p ≤ 0.05) in immune biomarkers (CD8, CD3) according to stress status in AU and in CD8 T cell between patient groups. CD4/CD8 ratio increased in alopecia patients. In current study, There was no significant difference detected for biomarkers (CD3, CD4, and CD8) in blood between patient groups and healthy control, but significantly decrease in CD8 T cell and CD3T cell according to stress in AU, and in CD8T cell between patient groups according to stress This research may have proven one of the theories. Study of CD markers receptors and B cell receptors these will help for future studies.


Biphasic regulation of the NADPH oxidase by HGF/c-Met signaling pathway in primary mouse hepatocytes.
Redox signaling is emerging as an essential mechanism in the regulation of biological activities of the cell. The HGF/c-Met signaling pathway has been implicated as a key regulator of the cellular redox homeostasis and oxidative stress. We previously demonstrated that genetic deletion of c-Met in hepatocytes disrupts redox homeostasis by a mechanism involving NADPH oxidase. Here, we were focused to address the mechanism of NADPH oxidase regulation by HGF/c-Met signaling in primary mouse hepatocytes and its relevance. HGF induced a biphasic mechanism of NADPH oxidase regulation. The first phase employed the rapid increase in production of ROS as signaling effectors to activate the Nrf2-mediated protective response resulting in up-regulation of the antioxidant proteins, such as NAD(P)H quinone oxidoreductase and γ-glutamylcysteine synthetase. The second phase operated under a prolonged HGF exposure, caused a suppression of the NADPH oxidase components, including NOX2, NOX4, p22 and p67, and was able to abrogate the TGFβ-induced ROS production and improve cell viability. In conclusion, HGF/c-Met induces a Nrf2-mediated protective response by a double mechanism driven by NADPH oxidase.


User Experience of Intraoral Scanners in Dentistry: Transnational Questionnaire Study.
Intraoral scanners (IOS) are continuing to gain popularity in clinical dentistry, replacing the traditional impression-taking and related technology. Despite their increasing importance, there are few data on the utility and usage of IOS amongst dentists. This study investigates the user experience of IOS technology as well as the perceived quality of a variety of IOS used by dental clinicians worldwide. An online survey of 1072 dentists was conducted to elicit data on the number of individual IOS used, their accessibility, the maintenance fees, and the programmes used. The first part of the questionnaire included demographic data and related questions, whilst the second part focussed on the specific IOS used by the respondents and the satisfaction with their scanners. We surveyed 1072 respondents from 109 different countries. More than three-quarters of the survey cohort (78.8%) use IOS in their daily work, whilst 21.17% do not. The average number of scanners owned by the respondents was 1.5 (±0.9), and in total, the cohort used 36 different types of IOS. More than one-third (38.6%) of the respondents used computer-aided design (CAD) software as well. As for the frequency of IOS usage, 51.5% used the system on a daily basis, 28.2% did so 2 to 3 times a week, and 10.0% did so once a week. Overall, the top 3 IOS used by the cohort were Medit i700 followed by wireless Medit i700 and Dentsply Sirona Primescan. This study describes, for the first time, the IOS user experience in an international cohort. More than 75% of the respondents used IOS on a daily basis in their practice, whilst Medit and Dentsply Sirona brands were the most popular scanners amongst the group. It appears that digital impression-taking technology is universal, and digital workflow in dentistry will continue to grow.


Amikacin in the treatment of gram-negative pneumonia.
A clinical efficacy study of amikacin in the treatment of 15 adults with nonbacteremic, gram-negative bacillary pneumonia is presented. All patients had serious underlying illnesses (11 organic heart disease, five chronic obstructive pulmonary disease, one cancer); 11 had undergone major surgical procedures. All had required respiratory assistance during their hospitalization and all had recently received other antibiotics. Thirteen of 15 patients showed clinical improvement with amikacin therapy; the pathogen was also eradicated in 10 of the 13. The mean minimum inhibitory concentration of amikacin for the 17 isolated pathogens was 3.13 microng/ml. The mean peak serum concentration of amikacin was 17.7 microng/ml. No evidence of ototoxicity or nephrotoxicity was seen. Seventy-three case reports submitted to the manufacturer by multiple investigators of patients with gram-negative pneumonia, treated with amikacin, are also reviewed. All isolated pathogens were sensitive to both amikacin and gentamicin. Fifty-four (74%) of these patients showed improvement with amikacin therapy.


Monoisoamyl dimercaptosuccinic acid induced changes in pregnant female rats during late gestation and lactation.
Monoisoamyl dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelating agent and an analogue of a conventional metal chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA) has recently been gaining recognition to be more effective chelating agent than DMSA in mobilizing lead, mercury and arsenic. However, very little information is available on the toxicological properties of this chelator. In the present study, MiADMSA was administered to pregnant female rats from day 14 of gestation to day 21 of lactation at different doses through oral (p.o.) and intraperitoneal (i.p.) routes to examine the toxicity in the pups and dams. Results suggested that MiADMSA had no effect on period of gestation, litter-size, sex ratio, and viability and lactation. No skeletal defects were observed following the administration of the chelator. However, MiADMSA administration produced few signs of oxidative stress in dams particularly at the higher doses (100 and 200mg/kg) as evident from increased thiobarbituric acid reactive substances (TBARS) in RBCs and decrease in the delta-aminolevulinic acid dehydratase (ALAD) activity. Administration of MiADMSA also caused some alterations in the essential metal concentration in the soft tissues especially tissue copper loss in lactating mothers and pups, which would be of some concern. Apart from copper, changes were also observed in the tissue zinc concentrations in mothers and pups following MiADMSA administration. The study thus suggests that the chelator is relatively safe during late gestation and it does not cause any major alteration in the mothers and the developing pups. However, detailed studies with MiADMSA, post-toxic metal exposure in pregnant animals may provide useful information.


Effect of sex hormones on the fate of methylmercury and on glutathione metabolism in mice.
To investigate the mechanisms for the sex-related difference in the in vivo fate of methylmercury (MeHg), the effects of hormonal manipulation on the distribution and urinary excretion of the mercurial moiety (Hg) of injected MeHg and on hepato-renal metabolism of glutathione were studied in C57BL/6N mice. Twenty-four hours after oral administration of MeHg, urinary Hg levels were significantly higher in males than in females. Tissue Hg levels of males were higher in the kidney, but lower in the brain, liver and plasma than those of females. The fate of injected MeHg in castrated males was similar to that in normal females except for its brain levels. This feminization of the mercurial behavior in the castrated males was restored by treating with testosterone propionate (TP). When control mice were treated with TP, urinary excretion of Hg increased in both sexes, whereas renal Hg level increased only in females. Administration of estradiol benzoate (EB) to males decreased the renal accumulation and urinary excretion of Hg, whereas its hepatic levels increased. However, no significant change in the fate of MeHg was found in females pretreated with EB. Castration of females slightly decreased the urinary excretion of Hg. Thus, tissue distribution and urinary excretion of the administered MeHg seem to be subject to sex hormone control. Since MeHg has a high affinity for GSH, effects of hormonal manipulation on the metabolism of hepato-renal glutathione were also investigated. A significant sex-related difference in glutathione levels was found in plasma but not in the kidney, liver and erythrocytes. The half-lives of glutathione in the liver and kidney were significantly shorter in males than in females as determined by treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis. This difference was also modulated by the hormonal treatment. Since half-lives of GSH in the liver and kidney predominantly reflect the rate of its efflux from these tissues, the results suggest that GSH metabolism and/or secretory transport may be regulated by sex hormones. These and other observations suggest that the fate of MeHg may be modulated by way of regulating the inter-organ metabolism and transport of glutathione and its derivatives.


THAP11 Functions as a Tumor Suppressor in Gastric Cancer through Regulating c-Myc Signaling Pathways.
We aim to investigate the role of THAP11 (thanatos-associated protein11) in gastric cancer and its regulation mechanisms. THAP11 expression was analyzed in 51 pairs of GC tissues and the corresponding paracancerous tissues by qRT-PCR and Western blot. After THAP11 was overexpressed or knocked-down, cell proliferation, cell cycle, and apoptosis were detected in MKN-45 cells. We found that THAP11 was significantly downregulated in GC tissues and GC cell lines. Functionally, THAP11 overexpression markedly inhibited cell growth, induced G1/G0 cell-cycle arrest, and promoted cell apoptosis of MKN-45 cells, while silencing of THAP11 led to increased cell growth, increased DNA synthesis, and inhibited apoptosis. In addition, THAP11 negatively regulated the expression of c-Myc, decreased cyclinD1 protein, and increased p27 and p21 protein levels. We also found cell growth suppression induced by THAP11 was rescued by c-Myc overexpression, further confirming that THAP11 suppresses gastric cancer cell growth via the c-Myc pathway. THAP11 acts as a cell growth suppressor and exerts its role possibly through negatively regulating c-Myc pathway in gastric cancer.


Enucleation in a tertiary eye care centre in India: prevalence, current indications and clinicopathological correlation.
Enucleation is a standard surgical treatment modality for many end-stage eye diseases. Indications for enucleation vary with changing trends in disease management. Few studies have addressed the issue of the frequency and indications of enucleation of eyes in India. We aimed to determine the frequency and the current clinical indications for enucleation in patients at a tertiary eye care centre in India, and attempted a clinicopathological correlation. Medical records of patients undergoing enucleation at a tertiary eye care centre over a period of 3 1/2 years (January 1995 to July 1998) were reviewed to obtain patients' demographic data and socio-economic status. The clinical indications and predisposing factors were assessed. The formalin-fixed, paraffin-embedded sections of all enucleated eyes were re-evaluated and histopathological findings were correlated with the clinical diagnosis. The prevalence of enucleation was calculated, and age adjustments were done using the Indian population data from 1998 mid-year statistics. Enucleation of the eye was performed in 150 patients (151 eyes) out of 88,991 new ophthalmic cases, constituting 0.17% of the cases seen in the hospital, and amounting to a prevalence of 0.33% (95% CI, 0.27-0.40). Males outnumbered females in a ratio of 1.85:1 (98 males, 53 females). The median age was 8 years (mean 16.8 +/- 18.3 years). Children below 15 years of age constituted 85.2% (95% CI, 81.2-89.21%) of cases that underwent enucleation. Clinical indications for enucleation included tumours in 74 (49%); staphyloma in 38 (25%); acute injury in 20 (13%); absolute glaucoma in 9 (6%); painful blind eye in 5 (3%); phthisis bulbi in 1 (1%); and others in 4 (3%). Of the 74 cases with a clinical diagnosis of tumour, histopathology revealed retinoblastoma in 55 (74%) cases, melanoma in 6 (8%) and ocular surface tumours in 4 (6%). Clinico-pathological correlation was 100% in cases with a definite clinical diagnosis of retinoblastoma and melanoma. Nine blind eyes (6%) in which an intraocular tumour was one of the differential diagnoses, were negative for a tumour on histopathology. Staphyloma was more prevalent in the low socio-economic group (p = 0.0004), with a history of childhood trauma in 34% cases. The prevalence of enucleation in the population reporting to this tertiary eye care centre was 33 per 10,000 population over the study period of 3 1/2 years. Major indications for enucleation were tumours, staphyloma and trauma (88% of all cases). Increased frequency in the young was due to the high proportion of retinoblastoma and staphyloma. Childhood trauma, inflammation and malnutrition may together play a role in the pathogenesis of staphyloma. Awareness at the level of primary health care providers, paediatricians and general practitioners should be promoted to identify the disease process at an early stage and facilitate early intervention measures that could result in eye and vision salvage.


Cytokine quantification and association with cervical length in a prospective cohort of pregnant women.
Preterm birth is a leading cause of infant morbidity and mortality; its multifactorial causes are an obstacle to understanding etiology and pathogenesis. The importance of cytokines and inflammation in its etiology and association with the short cervix is nowadays well-proven. To date, there are no reliable biological or biochemical markers to predict preterm birth; even though the length of the cervix has high specificity, its sensitivity with the cervix below 2.5 cm is low. We study the association of plasma cytokine levels and cervical length in search of predictors of preterm birth. We evaluated a total of 1400 pregnant women carrying a single fetus between 20 and 25 weeks of gestation, and 1370 of them after childbirth in a nested case-control study of a prenatal cohort. Eligible pregnant women were interviewed and submitted to obstetric morphological and transvaginal ultrasound with cervical length measurement, gynecological examination, and blood collection. Preterm birth occurred in 133 women, 129 included in the study, and a control group randomly selected at a 2:1 ratio. A total of 41 cytokines with a higher probability of being associated with preterm birth or being of significance during labor were determined. Cytokine and cervical length analysis by multivariate analysis of the conditional interference tree revealed that growth-related oncogene values of less than 2293 pg/mL were significantly associated with a cervical length of less than 2.5 cm. As well as a cervical length shorter than 2.5 cm, growth-related oncogene levels of less than 2293 pg/ml may be associated with an increased risk of PB. Analysis based on the association of biomarkers and of the interaction between cytokines is a promising pathway in search of a predictor of preterm birth.


Monitoring of potential cytotoxic and inhibitory effects of titanium dioxide using on-line and non-invasive cell-based impedance spectroscopy.
Titanium dioxide (TiO2) nanoparticles (NPs) with different sizes and structures were probed for plausible cytotoxicity using electric cell-substrate impedance sensing (ECIS), a non-invasive and on-line procedure for continuous monitoring of cytotoxicity. For insect cells (Spodoptera frugiperda Sf9), the ECIS50 values, i.e., the concentration required to achieve 50% inhibition of the response, differed depending on the size and shape of the TiO2 nanostructure. The lowest ECIS50 value (158 ppm) was observed for the needle shaped rutile TiO2 (10 nm×40 nm, 15.5 nm nominal particle size), followed by 211 ppm for P-25 (34.1 nm, 80% anatase and 20% rutile), 302 ppm for MTI5 (5.9 nm, 99% anatase) and 417 ppm for Hombitan LW-S bulk TiO2 (169.5 nm, 99% anatase). Exposure of TiO2 NPs to UV light at 254 nm or 365 nm exhibited no significant effect on the ECIS50 value due to the aggregation of TiO2 NPs with diminishing photocatalytic activities. Chinese hamster lung fibroblast V79 cells, exhibited no significant cytotoxicity/inhibition up to 400 ppm with P25, MTI5 and bulk TiO2. However, a noticeable inhibitory effect was observed (ECIS50 value of 251 ppm) with rutile TiO2 as cell spreading on the electrode surface was prevented.


Comparative pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of 3 different formulations of epoprostenol sodium for injection in healthy men.
Epoprostenol sodium for injection is approved for the treatment of severe cases of primary pulmonary arterial hypertension. Currently, there are 3 approved formulations of this drug containing the same active ingredient (epoprostenol sodium) but differing with regard to excipients. When compared with epoprostenol sodium formulated with glycine-mannitol (epoprostenol GM), 2 new formulations of epoprostenol sodium, one formulated with arginine-mannitol (epoprostenol AM) and one formulated with arginine-sucrose (epoprostenol AS), have improved stability after reconstitution and dilution. The biocomparability of epoprostenol AM and epoprostenol GM, with regard to pharmacokinetic (PK), pharmacodynamic (PD), safety, and tolerability profiles, has been shown previously. This study compared PK, PD, safety, and tolerability profiles of the 3 different formulations of epoprostenol sodium for injection. This was a prospective, single-center, open-label, 2-period, 2-treatment, randomized, crossover, ascending dose study in 2 parts. Twenty healthy men in part 1 and 20 different individuals in part 2 received epoprostenol AM and epoprostenol AS and epoprostenol GM and epoprostenol AS, respectively, in a crossover fashion, as sequential IV infusions of 2, 4, 6, and 8 ng/kg/min for 2 hours each. In each part, the PK profile of epoprostenol was characterized via analysis of the concentration-time profiles of its 2 primary metabolites: 6-keto-prostacyclin F1α and 6,15-diketo-13,14-dihydro-prostacyclin F1α. The effect of the formulations was assessed using the 90% CI of the geometric mean ratio calculated for the exposure PK parameters. The PD variables cardiac output, cardiac index, and heart rate were assessed using echocardiography. Adverse events were recorded through the study. The plasma concentration versus time curves of epoprostenol AM and epoprostenol AS in part 1 and epoprostenol GM and epoprostenol AS in part 2 were similar in shape and almost superimposable. For each study part, the 90% CIs of ratios of geometric means for AUC0-∞ of the assessed epoprostenol formulations were within the range for bioequivalence (0.8-1.25). The increases in cardiac output, cardiac index, and heart rate resulting from infusion with epoprostenol sodium were comparable between all formulations, with maximum values attained after 8 hours. Almost all study participants reported at least one treatment-emergent adverse event, the most common being headache, which was reported in 80% to 85% of study participants. Overall, the PK, PD, safety, and tolerability profiles of the 3 formulations of epoprostenol sodium for injection are comparable and meet the criteria of bioequivalence. Australian New Zealand Clinical Trials Registry identifier: ACTRN12612001086853.


[Effect of low pH values on the chemical composition of a chemostat culture of Bacillus megaterium].
Inhibition of the growth of Bacillus megaterium was studied in the conditions of chemostat. Inhibition of the growth by hydrogen ions had almost no effect on the content of DNA, RNA, protein and polysaccharides, but the protein-synthesizing activity of RNA changed. The content of polyphosphates, of high and low molecular weight, depended on pH; the relationship was of a non-linear character. The total content of lipids increased with the concentration of hydrogen ions.


Biophysical and biochemical characterization of a hyperthermostable and Ca2+ -independent alpha-Amylase of an extreme thermophile Geobacillus thermoleovorans.
alpha-Amylases reported from various microbial sources have been shown to be moderately thermostable and Ca2+ dependent. The bacterial strain used in this investigation is an extremely thermophilic bacterium Geobacillus thermoleovorans that produces a novel alpha-amylase (26 kDa; alpha-amylase gt), which is hyperthermostable (Topt 100 degrees C) and does not require Ca2+ for its activity/stability. These special features of alpha-amylase gt make it applicable in starch saccharification process. The structural aspects of alpha-amylase gt are, therefore, of significant interest to understand its structure-function relationship. The circular dichroism spectroscopic data revealed the native alpha-amylase gt to contain 25% alpha-helix, 21% beta-sheet, and 54% random coils. The addition of urea, at high concentration (8 M), appeared to expose the buried Trp residues of the native alpha-amylase gt to the aqueous environment and thus showed low fluorophore. Fluorescence-quenching experiments using KI, CsCl, N-bromosuccinimide, and acrylamide revealed interesting features of the tryptophan microenvironment. Analysis of Ksv and fa values of KI, CsCl, and acrylamide suggested the overall Trp microenvironment in alpha-amylase to be slightly electropositive. Fluorescence-quenching studies with acrylamide revealed the occurrence of both collisional as well as static quenching processes. There was no change in the alpha-helix content or the enzyme activity with an increase in temperature (60-100 degrees C) that suggested a critical role of the alpha-helix content in maintaining the catalytic activity.


Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple-system atrophy: a systematic review and a meta-analysis.
This study was designed to review the diagnostic performance of iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between Parkinson's disease (PD) and multiple-system atrophy (MSA). A comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and MSA was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and MSA were selected. Pooled sensitivity and specificity of MIBG scintigraphy were presented with a 95% confidence interval (CI). The area under the ROC curve was calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and MSA. Ultimately, we identified 12 studies comprising a total of 1226 patients (593 patients with PD, 117 patients with other Lewy body disease, 129 patients with MSA, and 387 patients with other diseases). The pooled sensitivity of MIBG scintigraphy to detect PD was 89% (95% CI: 86-91%); the pooled specificity of MIBG scintigraphy to discriminate between PD and MSA was 77% (95% CI: 68-84%). The area under the ROC curve was 0.93. MIBG scintigraphy is an accurate test for PD detection and differential diagnosis between PD and MSA; this method shows high sensitivity and adequate specificity in this field. Nevertheless, possible causes of false negative and false positive findings should be considered when interpreting the scintigraphic results.


Microbial use for azo dye degradation-a strategy for dye bioremediation.
Azo dyes are aromatic compounds with one to many -N=N- groups as well as the leading class of synthetic dyes utilised in commercial solicitations. Azo dyes, released in the environment through textile effluents, have hazardous effects on the aquatic as well as human life. Their persistence and discharge into the environment are becoming a global concern; thus, the remediation of these contaminants has acquired great attention. The current review comprehensively discusses some of the main aspects of biodegradation of azo dyes. A variety of physicochemical approaches has already been utilised for treatment of textile effluents counting filtration, coagulation and chemical flocculation. Though these conventional techniques are effective, yet they are lavish and also comprise formation of concentrated sludge that makes a secondary disposal problem. In this regard, microbial usage is an effective, economical, bio-friendly and ecologically benign approach.


Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus.
Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10(-5)) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P = .86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10(-14)) for IFNL4-TT/TT and 1.44 (P = .03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.


Effects of vibration therapy on neuromuscular efficiency & features of the EMG signal based on endurance test.
Vibration Therapy (VT) stimulate the muscle spindles, which in turn enhances its afferent activities. The present study was designed to investigate the effect of VT at 23 and 35 Hz on muscle performance. The EMG features (six time-domain (TD) and four frequency-domain (FD)) and a new formula for computing neuromuscular performance were used as dependent variables to evaluate the effect of VT. The EMG recording was performed at 50% MVC during grip endurance test before and after VT. The EMG features were extracted out of raw EMG signals acquired from four forearm muscles, viz., flexor digitorum superficialis (FDS); flexor carpi ulnaris (FCU); extensor carpi radialis brevis (ECRB); and extensor carpi ulnaris (ECU) in supine position. Fatigue assessments were evaluated based on the pattern of TD and FD features. Statistical analysis showed a significant difference in the effect of vibration exposure frequency on IEMG (p < 0.001), MAV (p = 0.041), SSI (p = 0.032), and WL (p < 0.001) of FCU muscle. In addition, the greatest increase in neuromuscular efficiency (NME) was observed in the performance of ECRB after 35 Hz of VT and ECU muscles after 23 Hz of VT. The features of EMG signals could be used for fatigue analysis. However, the slope based on the median frequency regression line may be the best feature for fatigue assessment.


Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension.
Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by -7% and the upright plasma NE level by -24%. Supine plasma NE also fell (-24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by -6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL - cholesterol fraction.


Breast cancer larger than 2.5 cm with tumor-free radioisotope-hot sentinel nodes has higher risk of non-hot axillary lymph node metastasis.
Sentinel lymph node biopsy (SLNB) is the standard axillary staging approach for early breast cancer with clinically negative axillary involvement. Adequate SLNB should include the removal of not only radioactive tracer-labeled lymph nodes (hot nodes or SLNs) but also suspicious unlabeled nodes (non-hot nodes or non-SLNs). However, the biopsy of non-hot nodes is highly dependent on the surgeons' experiences. This article aims to facilitate the surgeon's decision making by elucidating parameters that correlate with non-hot node metastasis. From 2013 to 2016, clinically node-negative (cN0) breast cancer patients receiving axillary SLNB using single Tc-99m tracer method at our institute were recruited. Patients were excluded if they had received prior neoadjuvant chemotherapy. Among them, cases that have at least one non-isotope-hot node biopsied were retrospectively reviewed with a particular focus on patients with pathologically negative isotope-hot SLNs. The correlation of clinicopathological data with metastasis to axillary lymph nodes and sentinel lymph nodes was analyzed with the Chi-squared test, Fisher's exact test, and multivariate logistic regression. Receiver operating curve (ROC) was applied for continuous variables that predicted non-hot node metastasis; relapse-free survival (RFS) and locoregional relapse-free survival (LRRFS) were compared by Kaplan-Meier analysis. In 632 isotope-hot SLN negative patients, T stage showed a correlation with non-isotope-hot SLN metastasis (p = 0.035, odds ratio (OR) 9.65). Tumors larger than 2.5 cm best predict non-isotope-hot SLN metastasis (area under curve (AUC) = 0.71). With a median follow up of 41.80 months, locoregional relapse-free survival was significantly worse in cases with non-hot node metastasis (66.2% vs. 69.0%, p = 0.001). In the setting of SLNB using single radioisotope tracer, non-hot node metastasis in cases with negative hot SLN still carries a higher locoregional recurrence rate (13.3%). For early breast cancer larger than 2.5 cm, removal of suspicious non-hot nodes should be included for a precision therapy.


Pharmacological activation of plasma-membrane KATP channels reduces reoxygenation-induced Ca(2+) overload in cardiac myocytes via modulation of the diastolic membrane potential.
1. The opening of cardiac plasma-membrane ATP-sensitive K(+) channels (pmK(ATP)) can protect the heart against ischaemia/reperfusion injury. We recently demonstrated that the resting membrane potential (E(m)) of ventricular myocytes strongly modulates reoxygenation-induced Ca(2+) overload. This led to the hypothesis that activation of pmK(ATP) can influence the extent of chemically induced hypoxia (CIH)/reoxygenation Ca(2+) overload via hyperpolarization of the diastolic membrane potential of ventricular myocytes. 2. The membrane potential (E(m)) of isolated rat myocytes was determined using the perforated patch-clamp technique and DiBac(4)(3) imaging. Intracellular Ca(2+) ([Ca(2+)](i)) was monitored using FURA-2 imaging. 3. CIH/reoxygenation caused a significant depolarization of E(m) and a substantial increase in [Ca(2+)](i). The K(ATP) opener pinacidil (100 microm) and the pmK(ATP) opener P-1075 (100 microm) hyperpolarized the E(m) of normoxic myocytes. Pinacidil (100 microm) and P-1075 (10 and 100 microm), applied during reoxygenation, hyperpolarized E(m) and prevented reoxygenation-induced increases in [Ca(2+)](i). 4. Myocyte hypercontracture and death increased in parallel with an E(m) depolarization of 10-15 mV and increases in [Ca(2+)](i). Under these conditions, the selective pmK(ATP) channel inhibitor HMR 1098 further depolarized myocyte membrane potential and increased hypercontracture. 5. In conclusion, activation of pmK(ATP) channels can prevent CIH/reoxygenation-induced Ca(2+) overload via a mechanism that is dependent on hyperpolarization of diastolic membrane potential. Hyperpolarization toward normal resting membrane potential favours the Ca(2+) extrusion mode of Na(+)/Ca(2+) exchange.


Vitamin E reduces platelet adhesion to human endothelial cells in vitro.
Although it has been reported that vitamin E (alpha-tocopherol) can reduce platelet adhesiveness and aggregation in vivo, the mechanism is still unknown. Therefore, the aim of the present study was to determine whether incubations of platelet-rich plasma (PRP) with vitamin E influence platelet adhesion to cultured endothelial cells. To exclude blood plasma involvement, also washed platelets were pretreated with alpha-tocopherol. Vitamin E (0.5-1.0 mM) was added to PRP or washed platelets. Endothelial cells in monolayer were incubated with thrombin-activated platelets (1 or 2 U/ml). After 1 hr of incubation, non-adhered platelets were removed and counted. Treating of PRP with alpha-tocopherol inhibited platelet adhesion to endothelial cell monolayer. This effect was dose dependent on concentrations of alpha-tocopherol and thrombin. In our experiments PRP was treated with alpha-tocopherol and endothelial cell monolayer was used as test surface. These findings agree with previous observations on the adhesivity of platelets to synthetic surfaces after dietary vitamin E in healthy volunteers. When washed platelets were incubated with alpha-tocopherol, no significant reduction of adhesion was detectable. As preincubation of washed platelets with alpha-tocopherol does not inhibit platelet adhesion, it may be supposed that the effect of vitamin E does not occur in a directly cellular mechanism. The data suggest that alpha-tocopherol may reduce platelet adhesiveness probably after incorporation by plasma lipoproteins.


[A second "reserve" epicardial catheter in unipolar electrosystolic stimulation via the epigastrium (author's transl)].
At the time of implantation of a unipolar epicardial pacemaker via an epigastric approach, it is suggested that two wires inserted into two different areas should be used. This method is useful in the treatment of wire fractures, exteriorisation of the box, increases in threshold and infections following numerous box changes which the young individual may need.


Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin.
Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin.


Correction to: Cardiac Magnetic Resonance Imaging in Pulmonary Arterial Hypertension: Ready for Clinical Practice and Guidelines?
The original version of this article contains error in the text.


Molecular cloning of pig ZPBP2 and mRNA expression of ZPBP1 and ZPBP2 in reproductive tracts of boars.
Zona pellucida binding proteins (ZPBPs) are important receptors of zona pellucida on sperm and play an essential role in sperm-egg interaction. In the present study, the full-length coding regions of transcript variant 1 and 2 of ZPBP2 were cloned in the pig. ZPBP1 gene expression was specifically present in testes of boar reproductive tracts; while ZPBP2 mRNA was detected with highly in testes, moderate in seminal vesicles and low in caudal epididymes. We also examined the expression profile of porcine ZPBP1 and ZPBP2 in testes and seminal vesicles at different developmental stages. The results revealed that ZPBP1 mRNA was not detectable until day 70 and kept relative stable from days 70 to 105, then increased sharply from days 105 to 160 during sexual maturity (P<0.01). ZPBP2 mRNA was detected with relative low level until day 70 and but increased significantly from days 70 to 105 (P<0.01), and increased further from days 105 to 160 during sexual maturity (P<0.01). The data indicated that testes are the main origin of ZPBPs and the expression of ZPBPs are parallel with reproduction development.


Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: a proof-of-concept, observational study.
To evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients. We enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation. LCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45-60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six. This pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.


Visual prostheses for the blind.
After more than 40 years of research, visual prostheses are moving from the laboratory into the clinic. These devices are designed to provide prosthetic vision to the blind by stimulating localized neural populations in one of the retinotopically organized structures of the visual pathway - typically the retina or visual cortex. The long gestation of this research reflects the many significant technical challenges encountered including surgical access, mechanical stability, hardware miniaturization, hermetic encapsulation, high-density electrode arrays, and signal processing. This review provides an introduction to the pathophysiology of blindness; an overview of existing visual prostheses, their advantages and drawbacks; the perceptual effects evoked by electrical stimulation; as well as the role played by plasticity and training in clinical outcomes.


Rapid separation and characterization of cocaine and cocaine cutting agents by differential mobility spectrometry-mass spectrometry.
Forensic drug laboratories are inundated with cases requiring time-consuming GC- or LC-based chromatographic separations of submitted samples. High-throughput analytical methods would be of great practical utility within forensic drug analysis. Recently developed ion-mobility-based separation methods combined with mass spectrometry can often be used without chromatography, suppress chemical interferents of similar mass, and operate in seconds. We have evaluated differential mobility spectrometry-mass spectrometry (DMS-MS) for performance on adulterated cocaine mixtures. The DMS interface is only a few centimeters in length, operates in seconds, and can be adapted to any MS system using atmospheric pressure ionization. Drug cutting agents, typical targets such as cocaine, and drug metabolites are rapidly separated by the DMS ion prefilter. Tests demonstrated characterization of complex mixtures, such as isolation of levamisole, an adulterant with alarming side effects, from a 13-component mixture. DMS-MS holds great potential for the analysis of drug samples submitted for forensic analysis.


Effects of Untreated Periodontitis on Osseointegration of Dental Implants in a Beagle Dog Model.
There have been previous studies on the relationship between periodontitis and peri-implantitis, but limited information is available on how periodontitis affects osseointegration and wound healing of newly placed dental implants adjacent to natural teeth. The objective of the present experiment is to evaluate healing around dental implants adjacent to teeth with untreated experimental periodontitis. The study included six male beagle dogs. Scaling and plaque control procedures were performed on three dogs (control group). In the other three dogs (experimental group), retraction cords and ligature wires were placed subgingivally around all premolars and the first molars. Induced experimental periodontitis was confirmed after 3 months. Each control or experimental group was divided into two subgroups depending on the timing of implant placement (immediate/delayed). Twelve dental implants (two implants for each dog) were placed immediately, and the other 12 dental implants (two implants for each dog) were placed 2 months after extraction. The animals were sacrificed 2 months after implant placement. Histologic and histometric analyses were performed. Four implants (three from the immediate placement group and one from the delayed placement group) failed in the experimental group. There were significant differences in the percentage of bone-to-implant contact and marginal bone volume density between the control and experimental groups. Both parameters were significantly lower in the experimental group than in the control group (P <0.05). There was a tendency toward more marginal bone loss in the experimental group than the control group. Immediate placement of implants is associated with a higher failure rate compared with delayed placement. Untreated experimental periodontitis was correlated with compromised osseointegration in the implants with delayed placement.


Structural features of two heteroxylan polysaccharide fractions from wheat bran with anti-complementary and antioxidant activities.
Wheat bran is a rich source of bioactive substances ascribed to its arabinoxylan component. Two water-soluble arabinoxylans were sequentially extracted from wheat bran. WB1, released during enzymatic digestion of starch and protein, contained medium-branched arabinoxylan (A/X=0.88) consisting of 3-O-substituted (22%), di-substituted (19.8%) and 58% unsubstituted Xylp residues. It was slightly contaminated with (1→3,1→4)-β-glucan and arabinogalactan, and free of protein. WB2 extracted with 0.5% NaOH contained ∼95% arabinoxylan (A/X=1.09). WB2 and two 5% NaOH-extracted arabinoxylans were rich in protein and phenolic compounds. All radical-scavenging assays indicated a relation with the protein and total phenolics contents. The protein-free WB1 displayed the highest hydroxyl radical scavenging effect indicating the distinct role of phenolic acids. The immunomodulatory activity of WB1 was somewhat lower, whereas, that of WB2 higher in comparison to the immunogenic polysaccharide PMII. The arabinoxylans have the potential as immuno-enhancing and antioxidant additives in functional foods.


Hexadecylphosphocholine interaction with lipid monolayers.
The phospholipid analogue miltefosine or hexadecylphosphocholine (HePC) is a drug of high interest in the treatment for fatal visceral leishmaniasis (VL) due to Leishmania donovani particularly because of its activity by oral route. In this study, the interaction of HePC with a monolayer of beta-palmitoyl-gamma-oleyl-phosphatidylcholine (POPC) as membrane model or sterol (ergosterol or cholesterol) was investigated. At a constant pressure of 25 mN/m, the adsorption kinetics of HePC into the monolayers showed that HePC molecules are inserted into the monolayer of lipids as monomers until the critical micellar concentration (CMC). At HePC concentrations superior to the CMC, the micelles of HePC are deployed at the interface as groups of monomers into the POPC or sterol monolayer. The study of mixture of HePC/(POPC or sterol), spread at the air-water interface, shows that a simple miscibility between HePC and POPC is observed, whereas a high condensation appears between HePC and sterols showing a high affinity between HePC and sterols. In addition, HePC does not act as detergent disturbing membrane integrity.


A randomized guinea pig study on external cell growth factors after fractional ultrapulsed CO(2) laser therapy.
The Fractional Ultrapulsed CO2 laser has been successfully used in treating fine wrinkles, acne scars, and photoaged skin. However, the downtime typically lasts a week or more. The purpose of this study was to observe the efficacy of external cell growth factors after Fractional Ultrapulsed CO2 laser therapy. The back skin of 20 male guinea pigs were divided into four regions after hair removal, then these four regions were irradiated with Fractional Ultrapulsed CO2 laser, respectively. These 80 incised wounds were randomly divided into three therapeutic groups and a control group. The general condition of the wound healing was observed grossly. The determination of physiological functions was done and biopsies were harvested at different time points to compare the change of skin flexibility and fibroblasts number. The wound healing time of therapeutic groups shortened when compared with the control group. The flexibility of skin and the number of fibroblasts were also more than the control group. The effects of combined application of rhEGF and rb-bFGF therapeutic group were most conspicuous. Combined application of rhEGF with rb-bFGF could be more beneficial to the wound after Fractional Ultrapulsed CO2 laser therapy. It could accelerate the wound healing and increase the flexibility of wound skin, so the significance was important to direct clinical application.