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Background and purpose: The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin treatment on prevention of PD. This study analyzed the associations between pioglitazone, statins, and the incidence of PD in patients with diabetes mellitus (DM) in Taiwan. Methods: We used the National Health Insurance database from 1996 to 2013. DM and PD were diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used the propensity score‐matching method to match the study groups. Cox regression analyses were employed to calculate the relative risk of the incidence of PD. Results: There were 48 828 patients matched and categorized equally into the pioglitazone group and the non‐pioglitazone group. The number of PD patients in the pioglitazone group and the non‐pioglitazone group was 275 (1.1%) and 417 (1.7%), respectively. The pioglitazone group had a lower incidence of PD, with an adjusted hazard ratio (aHR) of 0.66 [95% confidence interval (CI): 0.57–0.78], and this benefit was dose‐dependent. Of note, as compared with either pioglitazone or statin treatment, our results first showed that the combination of pioglitazone and statins further lowered the risk of PD, with an aHR of 0.78 (95% CI: 0.64–0.94; P = 0.010). Conclusions: Our study results suggested that pioglitazone could be a promising agent for reducing the incidence of PD in patients with DM, and works synergistically with statins. [ABSTRACT FROM AUTHOR]

The alarming transmission rate of surgical site infections (SSI) in hospitals due to ineffective sterilization has encouraged researchers to search for a safe and easily available antibacterial agent. Common sterilization methods involving UV radiation and fumigants lead to hazardous effects on the environment and humans. These drawbacks have caused researchers to shift their attention towards visible light to activate certain materials to act as antibacterial agents. Thus, the present work reports optimization and antibacterial studies of sol‐gel coupled ultrasound synthesis of photo‐activated magnesium oxide (MgO) nanoparticles. The transmission electron microscope (TEM) and diffuse reflectance spectroscopy (DRS) analysis confirmed that smaller sized particles ranging from 13 nm‐25 nm are formed with narrower bandgap of 2.54 eV (1 eV = 1.602 × 10−19 J). The size reduction in the MgO nanoparticles narrowed their band gap, compared to previous results, which extends their absorptivity of light wavelength from UV (<400 nm) to the visible light region (400‐550 nm). The disc diffusion antibacterial analysis optimized using response surface methodology (RSM) revealed that a 0.01 mol/L MgO nanoparticle concentration of 531 μL dosages exhibited a maximum zone of inhibition (ZoI) of 54.1 mm against E. coli, which was achieved with a visible light distance of 5.7 cm. Similarly, a maximum ZoI of 61.3 mm for S. aureus was obtained with a visible light distance of 5 cm and MgO concentration and dosage of 0.01 mol/L and 401 μL. This study confirms the ability of MgO nanoparticle as an alternate and better antibacterial agent via photo‐activation for the first time. These photo‐activated MgO nanoparticles will be beneficial in the possible inhibition of bacterial growth in surgical equipment, lab coats, or even as antibacterial paints in hospitals. [ABSTRACT FROM AUTHOR]

Objectives: A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs LeFort 1 maxillary advancement surgery.Setting and Sample Population: The primary site for the clinical trial is Children's Hospital Los Angeles; the satellite test site is Seattle Children's Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion.Material and Methods: A total of 50 patients, ages 11-14, will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16-21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study.Results: Current recruitment of patients is on track to complete the study within the proposed recruitment period.Conclusion: This observational trial is collecting information that will examine dental, skeletal, financial and quality-of-life issues from both research cohorts. [ABSTRACT FROM AUTHOR]

Objective Bipolar disorder ( BP) frequently co-occurs with other psychiatric disorders. We examine whether course of anxiety disorders ( ANX), attention deficit hyperactivity disorder ( ADHD), disruptive behavior disorders ( DBD), and substance use disorders ( SUD) influence likelihood of recovery and recurrence of depression and mania in BP youth. Method Weekly ratings of psychiatric disorder intensity were obtained from 413 participants of the Course and Outcome of BP Youth project, followed for an average of 7.75 years. Multiple-event Cox proportional hazards regression analyses examined worsening of comorbid disorders as predictors of mood episode recovery and recurrence. Results Increased severity in ANX and SUD predicted longer time to recovery and less time to next depressive episode, and less time to next manic episode. Multivariate models with ANX and SUD found that significant effects of ANX remained, but SUD only predicted longer time to depression recovery. Increased severity of ADHD and DBD predicted shorter time to recurrence for depressive and manic episodes. Conclusion There are significant time-varying relationships between the course of comorbid disorders and episodicity of depression and mania in BP youth. Worsening of comorbid conditions may present as a precursor to mood episode recurrence or warn of mood episode protraction. [ABSTRACT FROM AUTHOR]

Objective To determine the longitudinal impact of borderline personality disorder ( BPD) on the course and outcome of bipolar disorder ( BP) in a pediatric BP sample. Method Participants ( N = 271) and parents from the Course and Outcome of Bipolar Youth ( COBY) study were administered structured clinical interviews and self-reports on average every 8.7 months over a mean of 93 months starting at age 13.0 ± 3.1 years. The structured interview for DSM- IV personality disorders ( SIDP- IV) was administered at the first follow-up after age 18 to assess for symptoms of BPD. BPD operationalized at the disorder, factor, and symptom level, was examined as a predictor of poor clinical course of BP using all years of follow-up data. Results The number of BPD symptoms was significantly associated with poor clinical course of BP, above and beyond BP characteristics. Affective dysregulation was most strongly associated with poor course at the factor level; the individual symptoms most strongly associated with poor course were dissociation/stress-related paranoid ideation, impulsivity, and affective instability. Conclusion BPD severity adds significantly to the burden of BP illness and is significantly associated with a more chronic and severe course and outcome beyond what can be attributable to BP characteristics. [ABSTRACT FROM AUTHOR]

Structured Abstract Objectives This study tested whether or not gene expression in human marrow stromal fibroblast ( MSF) cells depends on light wavelength and energy density. Materials and Methods Primary cultures of isolated human bone marrow stem cells ( hBMSC) were exposed to visible red ( VR, 633 nm) and infrared ( IR, 830 nm) radiation wavelengths from a light emitting diode ( LED) over a range of energy densities (0.5, 1.0, 1.5, and 2.0 Joules/cm2) Cultured cells were assayed for cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content. mRNA was analyzed by microarray and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell type specific. Protein array analysis was used to further analyze key pathways identified by microarrays. Result Different wavelengths and energy densities produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF-beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF-beta protein arrays suggested switching from canonical to non-canonical TGF-beta pathways with increases to longer IR wavelengths. Microarrays suggest RANKL and MMP 10 followed IR energy density dose-response curves. Epithelial and mesenchymal cells respond differently to stimulation by light suggesting cell type-specific response is possible. Conclusions These studies demonstrate differential gene expression with different wavelengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the literature when wavelengths, energy densities and cell types differ. [ABSTRACT FROM AUTHOR]

Background Storage of platelet concentrates ( PCs) after Mirasol pathogen reduction technology ( PRT) treatment changes platelet ( PLT) surface marker expression and secretion of immunomodulatory factors. Given that PLTs are known to participate in immune function, PRT may alter the way PLTs interact with the immune cells of a recipient upon transfusion. As such, the aim of this study was to assess the effects of PRT treatment on the functional ability of PLTs to interact with peripheral blood mononuclear cells ( PBMNCs). Study Design and Methods Buffy coat-derived PCs were pooled and split to obtain matched pairs. One unit was treated using the Mirasol PRT system, while the control PC remained untreated. After 5 days of storage, either the PLTs or the PLT supernatants from the PCs were cocultured with PBMNCs, with or without lipopolysaccharide ( LPS). The immunomodulatory factors secreted into culture medium after coculture were examined. Results PRT-treated PLTs and PLT supernatant significantly increased the interleukin ( IL)-8 concentration, which was manifested only in the presence of LPS. Conversely, PRT-treated PLTs secreted less soluble P-selectin ( sCD62 P) upon coculture with PBMNCs. Conclusion PRT-treatment induced differential secretion of IL-8 and sCD62 P during coculture, which may be attributed to either bioactive substances present in PLT supernatant or as a result of cell-cell interactions. [ABSTRACT FROM AUTHOR]

Porous χ- Al2 O3 is a new material for fabricating coated inkjet printing paper. Paper coated with χ- Al2 O3 powders has excellent water fastness. This study investigated the dye-fixing ability of χ- Al2 O3 powders through measurements of adsorption isotherms. The variations in zeta potential, pore volume, pore size distribution, and specific surface area of χ- Al2 O3 powders during the dye-fixing process were also examined. The results show that χ- Al2 O3 powders have a strong affinity to dye colorants. The adsorption isotherm is classified as HA-type and the adsorption data fit the Langmuir model. In addition to the positive-charged surface of χ- Al2 O3 provides cationic sites for fixing dye colorants via electrostatic interaction, the porous structure on the surface of χ- Al2 O3 particles plays an indispensable role in trapping the colorant. [ABSTRACT FROM AUTHOR]

K. Bhaskar, G. A. Hobbs, S-H. Yen and G. Lee (2010) Neuropathology and Applied Neurobiology 36, 462–477 Tyrosine phosphorylation of tau accompanies disease progression in transgenic mouse models of tauopathy Aim: Tau protein is a prominent component of paired helical filaments in Alzheimer's disease (AD) and other tauopathies. While the abnormal phosphorylation of tau on serine and threonine has been well established in the disease process, its phosphorylation on tyrosine has only recently been described. We previously showed that the Src family non-receptor tyrosine kinases (SFKs) Fyn and Src phosphorylate tau on Tyr18 and that phospho-Tyr18-tau was present in AD brain. In this study, we have investigated the appearance of phospho-Tyr18-tau, activated SFK and proliferating cell nuclear antigen (PCNA) during disease progression in a mouse model of human tauopathy. Methods: We have used JNPL3, which expresses human tau with P301L mutation, and antibodies specific for phospho-Tyr18-tau (9G3), ser/thr phosphorylated tau (AT8), activated SFK and PCNA. Antibody staining was viewed by either epifluorescence or confocal microscopy. Results: Phospho-Tyr18-tau appeared concurrently with AT8-reactive tau as early as 4 months in JNPL3. Some 9G3-positive cells also contained activated SFKs and PCNA. We also investigated the triple transgenic mouse model of AD and found that unlike the JNPL3 model, the appearance of 9G3 reactivity did not coincide with AT8 in the hippocampus, suggesting that the presence of APP/presenilin influences tau phosphorylation. Also, Thioflavin S-positive plaques were 9G3-negative, suggesting that phospho-Tyr18-tau is absent from the dystrophic neurites of the mouse triple transgenic brain. Conclusions: Our results provide evidence for the association of tyrosine-phosphorylated tau with mechanisms of neuropathogenesis and indicate that SFK activation and cell cycle activation are also involved in JNPL3. [ABSTRACT FROM AUTHOR]

Objective: To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. Method: Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow-up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. Results: NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. Conclusion: NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment. [ABSTRACT FROM AUTHOR]

Objective: It is commonly believed that some features of borderline personality disorder (BPD) improve as individuals reach their late 30s and 40s. This study examined age-related change in borderline criteria and functional impairment, testing the hypothesis that older age would be associated with relatively more improvement than younger age. Method: A total of 216 male and female participants with BPD were followed prospectively with yearly assessments over 6 years. Results: Participants showed similar rates of improvement in borderline features regardless of age. A significant age by study year interaction showed functioning in older subjects to reverse direction and begin to decline in the latter part of the follow-up, in contrast to younger subjects who maintained or continued improvement over the 6 years. Despite the decline, functioning for the older subjects was comparable with or slightly better at year 6 than at year 1. Conclusion: Improvement in borderline features is not specific to the late 30s and 40s. There may be a reversal of improvement in functioning in some borderline patients in this older-age range. [ABSTRACT FROM AUTHOR]

Ralevski E, Sanislow CA, Grilo CM, Skodol AE, Gunderson JG, Tracie Shea M, Yen S, Bender DS, Zanarini MC, McGlashan TH. Avoidant personality disorder and social phobia: distinct enough to be separate disorders? Acta Psychiatr Scand 2005: 1–7. © 2005 Blackwell Munksgaard. Existing evidence from anxiety disorder research indicates that social phobics (SP) with avoidant personality disorder (AVPD) experience more anxiety and show more impairment than patients with SP alone. The purpose of this study was to examine whether in patients diagnosed with AVPD, the co-occurrence of SP adds to its severity. We hypothesized that the addition of SP will not add to the severity of AVPD alone. Two groups of patients (AVPD = 224; AVPD/SP = 101) were compared at baseline and 2 years later on multiple demographic and clinical variables. Patients with AVPD and an additional diagnosis of SP differed little from patients with AVPD alone. These findings suggest that AVPD and SP may be alternative conceptualizations of the same disorder. [ABSTRACT FROM AUTHOR]

Pagano ME, Skodol AE, Stout RL, Shea MT, Yen S, Grilo CM, Sanislow CA, Bender DS, McGlashan TH, Zanarini MC, Gunderson JG. Stressful life events as predictors of functioning: findings from the Collaborative Longitudinal Personality Disorders Study.Acta Psychiatr Scand 2004: 110: 421–429.© Blackwell Munksgaard 2004.Although much attention has been given to the effects of adverse childhood experiences on the development of personality disorders (PDs), we know far less about how recent life events influence the ongoing course of functioning. We examined the extent to which PD subjects differ in rates of life events and the extent to which life events impact psychosocial functioning.A total of 633 subjects were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS), a multi-site study of four personality disorders– schizotypal (STPD), borderline (BPD), avoidant (AVPD), obsessive-compulsive (OCPD)– and a comparison group of major depressive disorders (MDD)without PD.Borderline personality disorder subjects reported significantly more total negative life events than other PDs or subjects with MDD. Negative events, especially interpersonal events, predicted decreased psychosocial functioning over time.Our findings indicate higher rates of negative events in subjects with more severe PDs and suggest that negative life events adversely impact multiple areas of psychosocial functioning. [ABSTRACT FROM AUTHOR]

Grilo CM, Skodol AE, Gunderson JG, Sanislow CA, Stout RL, Shea MT, Morey LC, Zanarini MC, Bender DS, Yen S, McGlashan TH. Longitudinal diagnostic efficiency of DSM-IV criteria for obsessive–compulsive personality disorder: a 2-year prospective study. Acta Psychiatr Scand 2004: 110: 64–68. © Blackwell Munksgaard 2004. To examine the longitudinal diagnostic efficiency of the DSM-IV criteria for obsessive–compulsive personality disorder (OCPD). At baseline, criteria and diagnoses were determined using diagnostic interviews, and blinded assessments were performed 24 months later with 550 participants. Diagnostic efficiency indices (conditional probabilities, total predictive power, and kappa) were calculated for each criterion determined at baseline, using the independent OCPD diagnosis at follow-up as the standard. Longitudinal diagnostic efficiencies for the OCPD criteria varied; findings suggested the overall predictive utility of ‘preoccupied with details’, ‘rigid and stubborn’, and ‘reluctant to delegate’. These findings suggest the predictive validity of three cognitive-interpersonal OCPD criteria. [ABSTRACT FROM AUTHOR]

Family-based studies of genetic association and linkage play a key role in mapping susceptibility genes of complex human diseases. Recent admixture between genetically differentiated populations can result in high levels of linkage disequilibrium even at far apart loci. This has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. Here the authors describe an alternative approach for admixture mapping. The genome is divided into several non-overlapping intervals and the information of the markers in the same interval is integrated— the ‘ interval transmission/disequilibrium test’ (ITDT). This method requires information in the form of the marker allele frequencies in the founding populations. However, computer simulations show that the performances of ITDT are hardly affected by imprecise allele-frequency information. Simulations also show that an interval-by-interval scan using ITDT perform much better than a conventional marker-by-marker scan using TDT, even under conditions where the admixture process occurred over many generations and the individuals in the admixed populations show considerable variation in admixture proportion. Hence the ITDT is a promising new genomewide scan method. [ABSTRACT FROM AUTHOR]

Transgenic mice (JNPL3), which develop neurofibrillary degeneration and express four-repeat human tau with P301L missense mutation, were characterized biochemically to determine whether the development of aggregated tau from soluble tau involves an intermediate stage. Homogenates from mice of different ages were separated into buffer-soluble (S1), sarkosyl- and salt-extractable (S2) and sarkosyl-insoluble pellet (P3) fractions, and analyzed for human tau distribution, phosphorylation and filament formation. S1 and S2 fractions contained 50-60-kDa tau whereas the S2 fraction also had 64-kDa tau. The level of tau in the P3 fraction increased in an age-dependent manner and correlated positively with the soluble tau concentration. The P3 fraction from 2.5-6.5-month-old mice contained 64- and 50-60-kDa tau, whereas that from 8.5-month and older transgenic animals contained mostly 64-kDa and higher molecular weight tau. The S2 and P3 fractions contained comparable amounts of 64-kDa tau. The 64-kDa tau was predominantly human, and phosphorylated at multiple sites: Thr181, Ser202/Thr205, Thr212, Thr231, Ser262, Ser396/Ser404, Ser409 and Ser422. Most of these sites were phosphorylated to a lesser extent in S2 than in P3 fractions. Tau polymers were detected in P3 fractions from 3-month and older female JNPL3 mice, but not in non-transgenic controls. The results suggest that tau in S2 represents an intermediate from which insoluble tau is derived, and that phosphorylation may play a role in filament formation and/or stabilization. [ABSTRACT FROM AUTHOR]

Introduction: There have been very limited and inconsistent attempts at combining the cultured epidermal autograft (CEA) with the neodermis of artificial skin (Integra). The reasons for this remain unknown. The basement membrane proteins of conventional CEA sheets are easily damaged by the dispase treatment during the harvesting of the CEA from the culture flask. The damage of the basement membrane proteins may affect the anchorage of CEA onto the neodermis of Integra. A new Composite Biocompatible Skin Graft (CBSG) was recently developed. Methods: Composite biocompatible skin graft consists of autologous keratinocytes cultivated on a pliable hyaluronate-derived membrane (Laserskin) which has been pre-seeded with allogenic dermal fibroblasts. Basement membrane proteins of CBSG are protected from the dispase treatment because the keratinocytes are directly seeded onto Laserskin. The engraftment of CBSG was evaluated on 20 wounds of 10 rats. Integra was grafted on two freshly excised full-thickness wounds (3 cm in diameter) in the dorsum of each animal. A polypropylene ring was applied to each wound to prevent the migration of epithelium from the edges. Composite Biocompatible Skin Graft was used to cover the neodermis of Integra after the silicone membrane was removed 14-21 days postgrafting. Results: Fourteen (70%) of 20 skin biopsies taken at day 21 from the centre of the grafted wounds revealed regenerated epithelium. Conclusion: A feasible delivery system of cultured keratinocytes onto the neodermis of Integra is demonstrated in this animal ­experiment. [ABSTRACT FROM AUTHOR]

Summary The effect of octopamine on β3 -adrenoceptors has been studied in isolated adipocytes of Wistar rats using uptake of [14 C]-deoxy-D-glucose as the indicator. Octopamine (0.1–1 nmol 1-1 ) induced a concentration-dependent decrease of [14 C]-deoxy-D-glucose uptake into the adipocytes and this inhibition was not influenced by halperidol at concentrations sufficient to block dopaminergic receptors. Pindolol and propranolol reversed this inhibition of octopamine in a concentration-dependent manner. The effect of octopamine was reduced in the presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. A direct effect of octopamine on β3 -adrenoceptors was proved using the application of antibodies. In the presence of an antibody for β3 -adrenoceptors, the actions of octopamine were concentration-dependantly reduced in a manner similar to the decrease of BRL37344-induced inhibitions. The same degree of diminished activities for octopamine as that of BRL37344, the well-known specific agonist of β3 -adrenoceptors, was also obtained in isoprenline-desensitized adipocytes. Insulin-stimulated uptake of [14 C]-deoxy-D-glucose into adipocytes was not modified by isoprenaline induced desensitization. These results suggest that octopamine can activate β3 -adrenoceptors to lower the glucose uptake through an increase of cAMP in rat white adipocytes. [ABSTRACT FROM AUTHOR]