Regulatory effects of biophysical strain on rat TMJ discs

Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair.     

The superimmunity gene sim of bacteriophage P1 causes superinfection exclusion

Previous work has shown that the sim gene of bacteriophage P1, if cloned into a multicopy vector, confers immunity against P1 infection to cells. We show that a 1.85-kb DNA fragment from the sim region of P1 (in the multicopy plasmid pMK4) expresses immunity and encodes three proteins with molecular weights of about 25, 24, and 15 kDa. Deletion of 650 bp from the sim region abolished synthesis of all three proteins and of the sim phenotype. Expression of sim did not prevent adsorption of P1 to cells. Successful transfection with linear P1 DNA suggests that the recombinational circularization of P1 DNA is not inhibited in the presence of sim. Plasmid pMK4 and a P1 prophage can be stably maintained in the cell indicating that replication of the prophage is not disturbed by sim. The prophage can be induced in the presence of sim. This shows that the sim phenotype is not caused by preventing lytic replication or phage maturation. In cells with pMK4 there is no expression of genes from infecting phages and transduction frequency is drastically reduced. We suggest that sim functions as a superinfection exclusion system by preventing transfer of DNA from the adsorbed phages into the cytoplasm.     

The association between psychopathology of first-episode psychosis patients within the schizophrenia spectrum and previous offending

Patients with schizophrenia have been shown to have an increased risk of criminality. The aim was to describe possible psychopathological differences between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis. In a multi-centre study, 16 psychiatric treatment centres included and rated 477 patients with first-episode psychosis over a 2-year period on socio-demography, the Positive and Negative Syndrome Scale, OPerational CRITeria checklist, Global Assessment of Functioning, Premorbid Adjustment Scale and Self-report Insight Scale for psychosis. Data were linked with data concerning criminal and psychiatric history. No key characteristics were found to assist the early detection of criminal persons before first psychiatric hospital contact for a psychotic incident. However, when adjusted for sex, age, abuse, living conditions, marital status, employment status and education, a primarily positive symptomatology was associated with a prior criminal career. The premorbid level of functioning and several function parameters were also significantly associated with criminal history. There are significant differences in psychopathology between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis, and a better screening procedure in the judicial system could detect these individuals earlier and make adequate treatment possible.     

Four-Year Follow-Up of a Randomized Controlled Trial of Triple P Group for Parent and Child Outcomes

Approximately 15–20 % of children experience behavioral and/or emotional difficulties. Evidence-based treatment will likely not be sufficient to reduce the prevalence of these difficulties in children and adolescents. Effective prevention programs are therefore also needed to enable families access to support at multiple points across the lifecourse. The aim of the current investigation was to evaluate the 4-year efficacy of the group-based Triple P (Positive Parenting Program) as a prevention program administered universally. Seventeen preschools were randomly assigned to Triple P (n?=?11 preschools, 186 families) or a no parenting intervention control group (n?=?6 preschools, 94 families). Long-term efficacy was analyzed with hierarchical linear models using maternal and paternal self-report measures. Mothers and fathers from the intervention preschool group reported significant reductions in dysfunctional parenting behavior (d?=?0.24 and 0.19, respectively). Mothers also reported a less steep decline from pre- to post-intervention in positive parenting behavior, which was maintained 4 years later (d?=?0.38). Fathers from intervention preschools reported a delayed less steep decline in positive parenting during the follow-up (d?=?0.33). In addition, mothers from intervention preschools reported immediate improvement in child behavior problems during the program while mothers from control preschools did not report this immediate change. However, with mothers from intervention preschools reporting more child behavior problems at baseline, the effect disappeared by the fourth year (d?=?0.19). The results support the long-term efficacy of the Triple P-group program as a universal prevention intervention for changing parenting behavior while there was little evidence for maintenance of change in behavior problems.     

Release patterns of pregnancy‐associated plasma protein A in patients with acute coronary syndromes assessed by an optimized monoclonal antibody assay

Objective. Pregnancy‐associated plasma protein A (PAPP‐A) is expressed in eroded and ruptured atheromatous plaques, and circulating levels are elevated in acute coronary syndromes (ACS). Our objective was to investigate release patterns of PAPP‐A in ACS and whether they differ among different types of ACS. Methods. In 40 patients, PAPP‐A concentrations were measured in serially collected samples assessed by a novel ELISA technique. The patients were grouped according to type of ACS. Results. Release patterns for ST elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) showed a single substantial PAPP‐A increase shortly after pPCI, followed by an abrupt return to normal levels without secondary peaks. STEMI, high‐risk and low‐risk non‐ST elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients without pPCI showed highly variable patterns with primary peaks followed by secondary PAPP‐A increases. All patients with elevated PAPP‐A levels reached the upper reference level within 24?h. There was a significant difference in median peak levels between STEMI (23.2?mIU/L) and low‐risk ACS patients (6.35?mIU/L) (p = 0.004) and between high‐risk (median = 15.3?mIU/L) and low‐risk ACS patients (p = 0.01). Among high‐risk ACS patients, NSTEMI patients had significantly higher peak levels than UAP patients (p = 0.003). Conclusion. PAPP‐A serum levels increase above normal values within 24?h after onset of symptoms in ACS. There are significant differences in PAPP‐A peak levels and release patterns across the spectrum of ACS patients.     

Modified immunoenriched (32)P-HPLC assay for the detection of O(4)-ethylthymidine in human biomonitoring studies

Increased excretion of ethylated DNA bases has been reported in the urine of cigarette smokers. To study DNA ethylation in the target organs of smokers, an immunoenriched (32)P-postlabeling assay for O(4)-ethylthymidine (O(4)-etT) was developed. O(4)-etT-3'-monophosphate (O(4)-etT-3'P) was synthesized, purified, and characterized by LC-MS, ESI-MS, and NMR. DNA was enzymatically digested to 2'-deoxynucleoside-3'-monophosphate followed by immunoprecipitation of O(4)-etT-3'P using specific monoclonal antibodies. The immunoconjugate was washed by filtration, and O(4)-etT-3'P was recovered by ethanol treatment. The enriched O(4)-etT-3'P was labeled with [gamma-(32)P]ATP in the presence of T4-polynucleotide kinase at pH 6.8 to yield its 5'-labeled monophosphate and was subsequently resolved on RP-HPLC and detected with online detection of radioactivity. Adduct recovery was >80%, and the detection limit was approximately 500 amol. To further validate the method, O(4)-etT levels were determined in calf thymus DNA treated with N-ethyl-N-nitrosourea, and a dose-dependent formation of O(4)-etT was observed. Furthermore, O(4)-etT was found to be present in the cells obtained from the lower respiratory tract by sputum induction of two out of four smokers but not in three nonsmokers. O(4)-etT is a poorly repaired promutagenic DNA lesion; thus, it could be of potential use for biomonitoring smoking-related DNA damage. Our improved assay was found to be sufficiently sensitive and specific to detect O(4)-etT in surrogate cells from cigarette smoke exposed humans.