Mental health and social support among public safety personnel.

BACKGROUND: Social support may be a protective factor for the mental health of public safety personnel (PSP), who are frequently exposed to potentially psychologically traumatic events and report substantial post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) symptoms. Research examining perceived social support and its association with PTSD and MDD in different PSP categories (e.g. firefighters, paramedics) is limited. AIMS: To examine differences in perceived social support across PSP and determine whether perceived social support is associated with differences in rates of MDD and PTSD. METHODS: We asked Canadian PSP, including correctional workers and officers, public safety communications officials, firefighters, paramedics, municipal and provincial police officers, and Royal Canadian Mounted Police (RCMP) officers, to complete an online anonymous survey that assessed socio-demographic information (e.g. occupation, sex, marital status, service years), social supports and symptoms of mental disorders, including PTSD and MDD. Analyses included ANOVA and logistic regression models. RESULTS: Perceived social support differed by PSP occupation. RCMP officers reported lower social support than all other PSP except paramedics. For most PSP categories, PSP who reported greater social support were less likely to screen positive for PTSD (adjusted odds ratios [AORs]: 0.90-0.93). Across all PSP categories, greater perceived social support was associated with a decreased likelihood of screening positive for MDD (AORs: 0.85-0.91). CONCLUSIONS: Perceived social support differs across some PSP categories and predicts PTSD and MDD diagnostic status. Studies involving diagnostic clinical interviews, longitudinal designs and social support interventions are needed to replicate and extend our results.

Mental disorders, suicidal ideation, plans and attempts among Canadian police.

BACKGROUND: Recent investigations have demonstrated a significant prevalence of mental health disorders, including post-traumatic stress disorder (PTSD), and suicidal ideation, plans and attempts among Canadian public safety personnel, including police officers. What remains unknown is the relationship between mental disorders and suicide among sworn police officers, and the prevalence of both among civilian police workers. AIMS: To examine the relationship between suicidal ideation, plans and attempts and positive mental health screens for depression, anxiety, panic disorder, alcohol abuse and PTSD among Canadian sworn and civilian police employees. METHODS: Participants completed an online survey that included self-report screening tools for depression, anxiety, panic disorder, alcohol abuse and PTSD. Respondents were also asked if they ever contemplated, planned or attempted suicide. Between-group (Royal Canadian Mounted Police [RCMP], provincial/municipal police and civilians) differences on mental health screening tools were calculated using Kruskal-Wallis analyses. The relationship between mental disorders and suicidal ideation, plans and attempts was evaluated with a series of logistic regressions. RESULTS: There were 4236 civilian and sworn officer participants in the study. RCMP officers reported more suicidal ideation than other police and scored highest on measures of PTSD, depression, anxiety, stress and panic disorder, which were significantly associated with suicidal ideation and plans but not attempts. Relative to provincial and municipal police, civilians reported more suicide attempts and scored higher on measures of anxiety. CONCLUSIONS: The results identify a strong relationship between mental health disorders and increased risk for suicidal ideation, plans and attempts among sworn and civilian Canadian police employees.

Co-morbidities in elderly patients with hip fracture: recommendations of the ISFR-IOF hip fracture outcomes working group.

INTRODUCTION: Hip fractures are the second leading cause of hospitalization in the aged and by 2041, epidemiologists forecast an increase in economic cost to $2.4 billion. The hip patient population often presents with comorbidities causing these patients to receive less aggressive medical treatment and have a low quality of life. We believe that physical function is a patient-important outcome for many medical and surgical interventions. The functional co-morbidity index (FCI), unlike prior co-morbidity indices, was developed with physical function as an outcome instead of being designed for administrative purposes or to predict mortality. Our objective was to evaluate the perceptions of practitioners in hip fracture care about the impact of comorbidities on physical function as primary outcome. METHODS: We piloted and then distributed a self-administered survey to members of the International Society for Fracture Repair hip fracture outcomes working group. For each of the 18 diagnoses included in the FCI index, we asked in our survey whether the presence of the co-morbidity and whether the severity of the co-morbidity was perceived to impact physical function in patients following a hip fracture. RESULTS: Seventeen out of 20 respondents completed the questionnaire. The presence and severity of arthritis was 'strongly' believed to predict physical function in those with hip fracture (69 and 85.7 %, respectively). Respondents 'agreed' (range 53-73 %) that 10/18 diagnoses would predict changes in physical function following hip fracture treatment. Whereas, 63 % of the practitioners'strongly disagreed' that diabetes types I and II would change physical function scores. Furthermore, dementia was listed as an additional diagnosis that would affect physical function. CONCLUSION: The FCI may provide a useful instrument to predict functional outcome after hip fracture; however, the index may need to be modified for this specific population.

Cross talk between beta-adrenergic and bradykinin B(2) receptors results in cooperative regulation of cyclic AMP accumulation and mitogen-activated protein kinase activity.

Costimulation of G protein-coupled receptors (GPCRs) may result in cross talk interactions between their downstream signaling pathways. Stimulation of GPCRs may also lead to cross talk regulation of receptor tyrosine kinase signaling and thereby to activation of mitogen-activated protein kinase (MAPK). In COS-7 cells, we investigated the interactions between two particular mitogenic receptor pathways, the endogenously expressed beta-adrenergic receptor (beta-AR) and the transiently transfected human bradykinin (BK) B(2) receptor (B(2)R). When beta-AR and B(2)R are costimulated, we found two different cross talk mechanisms. First, the predominantly G(q) protein-coupled B(2)R is enabled to activate a G(i) protein and, subsequently, type II adenylate cyclase. This results in augmentation of beta-AR-mediated cyclic AMP (cAMP) accumulation by BK, which alone is unable to increase the cAMP level. Second, independently of BK-induced superactivation of the cAMP system, costimulation of beta-AR leads to protein kinase A-mediated blockade of phospholipase C activation by BK. Thereby, the pathway from B(2)R to MAPK, which essentially involves protein kinase C activation, is selectively switched off. The MAPK activation in response to isoproterenol was not affected due to costimulation. Furthermore, in the presence of isoproterenol, BK lost its ability to stimulate DNA synthesis in COS-7 cells. Thus, our findings might establish a novel paradigm: cooperation between simultaneously activated mitogenic pathways may prevent multiple stimulation of MAPK activity and increased cell growth.

Regional access to acute ischemic stroke intervention.

BACKGROUND AND PURPOSE: Benefit-risk ratios from recombinant tissue plasminogen activator (rtPA) therapy for acute ischemic stroke demonstrate lack of efficacy if intravenous administration is commenced beyond 3 hours of symptom onset. We undertook to enhance therapeutic effectiveness by ensuring equitable access to rtPA for patients affected by acute ischemic stroke within a 20 000 km(2) population referral base served by a tertiary facility. METHODS: Representatives of all provider groups involved in emergency medical services developed a Regional Acute Stroke Protocol (RASP), a coordinated regional system response by dispatch personnel, paramedics, physicians, community service providers, emergency and inpatient staff in community hospitals, and the tertiary facility acute stroke team. RESULTS: As of July 26, 1999, all ambulance services in Southeastern Ontario began bypassing the closest hospital to deliver patients meeting the criteria for the RASP to the Kingston General Hospital. At 12 months, approximately 403 ischemic strokes have occurred in the region, the RASP has been activated 191 times, and 42 patients have received rtPA. CONCLUSIONS: We conclude that (1) acute stroke patients in Southeastern Ontario have improved access to interventions for stroke care; (2) geography of the region is not a barrier to access to interventions for patients with acute stroke; and (3) acute ischemic stroke patients treated with rtPA account for 5% of all acute strokes and 10% of all ischemic strokes in this region.

Defining the location and function of domains of McrB by deletion mutagenesis.

The GTP-dependent restriction endonuclease McrBC of E. coli K12, which recognizes cytosine-methylated DNA, consists of two protein subunits, McrB and McrC. We have investigated the structural assignment and interdependence of the McrB subunit functions, namely (i) specific DNA recognition and (ii) GTP binding and hydrolysis. Extending earlier work, we have produced McrB variants comprising N- and C-terminal fragments. The variants McrB1-162 and McrB1-170 are still capable of specific DNA binding. McrB169-465 shows GTP binding and hydrolysis characteristics indistinguishable from full-length McrB as well as wild-type like interaction with McrC. Thus, DNA and GTP binding are spatially separated on the McrB molecule, and the respective domains function quite independently.

The GTP-binding domain of McrB: more than just a variation on a common theme?

The methylation-dependent restriction endonuclease McrBC from Escherichia coli K12 cleaves DNA containing two R(m)C dinucleotides separated by about 40 to 2000 base-pairs. McrBC is unique in that cleavage is totally dependent on GTP hydrolysis. McrB is the GTP binding and hydrolyzing subunit, whereas MrC stimulates its GTP hydrolysis. The C-terminal part of McrB contains the sequences characteristic for GTP-binding proteins, consisting of the GxxxxGK(S/T) motif (position 201-208), followed by the DxxG motif (position 300-303). The third motif (NKxD) is present only in a non-canonical form (NTAD 333-336). Here we report a mutational analysis of the putative GTP-binding domain of McrB. Amino acid substitutions were initially performed in the three proposed GTP-binding motifs. Whereas substitutions in motif 1 (P203V) and 2 (D300N) show the expected, albeit modest effects, mutation in the motif 3 is at variance with the expectations. Unlike the corresponding EF-Tu and ras -p21 variants, the D336N mutation in McrB does not change the nucleotide specificity from GTP to XTP, but results in a lack of GTPase stimulation by McrC. The finding that McrB is not a typical G protein motivated us to perform a search for similar sequences in DNA databases. Eight microbial sequences were found, mainly from unfinished sequencing projects, with highly conserved sequence blocks within a presumptive GTP-binding domain. From the five sequences showing the highest homology, 17 invariant charged or polar residues outside the classical three GTP-binding motifs were identified and subsequently exchanged to alanine. Several mutations specifically affect GTP affinity and/or GTPase activity. Our data allow us to conclude that McrB is not a typical member of the superfamily of GTP-binding proteins, but defines a new subfamily within the superfamily of GTP-binding proteins, together with similar prokaryotic proteins of as yet unidentified function.

Does the restriction endonuclease EcoRV employ a two-metal-Ion mechanism for DNA cleavage?

Two models for the catalytic mechanism of the restriction endonuclease EcoRV exist which differ in the number and function of metal ions proposed to be directly involved in catalysis. In one model, two metal ions bound by Glu45, Asp74, and Asp90 are assumed to have a direct catalytic function; in the other, only one metal ion bound by Asp74 and Asp90. We show here that in the presence of Mn2+, the catalytic activity of an EcoRV-E45A mutant is only slightly reduced (1.8-fold) as compared to wild type EcoRV and that the single-turnover rate constant of DNA cleavage by E45A is reduced only 39-fold, whereas the D74A and D90A mutants are catalytically inactive under all conditions. These findings make an important catalytic function of Glu45, like binding of an essential divalent metal ion, unlikely. In addition, we have analyzed the dependence of the DNA cleavage rate by EcoRV and EcoRV mutants on the concentration of Mg2+ and Mn2+. We found for the wild type enzyme a sigmoidal dependence of the rate of DNA cleavage on the concentration of Mg2+ or Mn2+, indicative of at least two metal ions involved in DNA binding and catalysis. This, however, does not mean that EcoRV follows a two-metal-ion mechanism in DNA cleavage, because also for the E45A mutant a sigmoidal dependence of the rate of DNA cleavage on the Mg2+ concentration was found, making metal ion binding to the E45/D74 site unlikely. In contrast, the Y219C mutant shows a hyperbolic dependence. In agreement with results obtained earlier, these findings demonstrate binding of a Mg2+ ion at a site influenced by Tyr219, an amino acid residue that is far away from the active site. Metal binding at this site does not have a catalytic role but rather supports specific DNA binding. We conclude that on the basis of our data a two-metal-ion mechanism of DNA cleavage is unlikely for EcoRV and that the complex metal ion effects observed are due to metal ion binding at sites that are not directly involved in catalysis.