Daniel J. Martin

Relation of the therapeutic alliance with outcome and other variables: A meta-analytic review.

To identify underlying patterns in the alliance literature, an empirical review of the many existing studies that relate alliance to outcome was conducted. After an exhaustive literature review, the data from 79 studies (58 published, 21 unpublished) were aggregated using meta-analytic procedures. The results of the meta-analysis indicate that the overall relation of therapeutic alliance with outcome is moderate, but consistent, regardless of many of the variables that have been posited to influence this relationship. For patient, therapist, and observer ratings, the various alliance scales have adequate reliability. Across most alliance scales, there seems to be no difference in the ability of raters to predict outcome. Moreover, the relation of alliance and outcome does not appear to be influenced by other moderator variables, such as the type of outcome measure used in the study, the type of outcome rater, the time of alliance assessment, the type of alliance rater, the type of treatment provided, or the publication status of the study.

Microglia from Creutzfeldt-Jakob Disease-Infected Brains Are Infectious and Show Specific mRNA Activation Profiles

ABSTRACT Neurons are often assumed to be the principal sites for replication of the infectious agents causing Creutzfeldt-Jakob disease (CJD), scrapie, and bovine spongiform encephalopathy because they express high levels of normal and pathological prion protein (PrP). However, isolated brain cell types have not been evaluated for either infection or gene expression. Microglia purified from CJD-infected mice showed infectivity comparable to that of starting brain homogenate but expressed ∼50-fold less PrP. CJD-infected microglia also displayed morphological changes indicative of cellular activation. To determine the molecular pathways of activation, we evaluated pertinent transcripts, including those linked to inflammation. Semiquantitative reverse transcription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation, the cytokine interleukin-1β, and the chemokine B-lymphocyte chemoattractant. The profile of microglial changes induced by the CJD agent differed substantially from activation induced by bacterial lipopolysaccharide or by β-amyloid, a structure comparable to pathological PrP. These microglial studies emphasize migratory hematopoietic cells in the dispersion, and possibly replication, of the CJD agent. The low PrP levels in these highly infectious and activated cells further support the concept that pathological PrP is the result of infection rather than the infectious agent itself. Because microglia develop a specific pattern of responses to the CJD agent, microglial markers may be exploited in the diagnosis of these spongiform encephalopathies.

Blood borne transit of CJD from brain to gut at early stages of infection

BackgroundIn Creutzfeldt-Jakob disease (CJD) and other related transmissible spongiform encephalopathies it is critical to understand the various pathways by which the infectious agent spreads to different organs.MethodsWe injected a CJD agent into mice, either intracerebrally (ic) or intraperitoneally (ip) and monitored the progressive appearance of abnormal PrP in peripheral tissues over time.ResultsAbnormal PrP was detected in lymphoreticular tissues of the gastrointestinal tract as early as 28 to 32 days after infection by both routes. This change persisted until the terminal stages of disease. In contrast, abnormal PrP was not detected in brain or spinal cord until 80 to 120 days after ic inoculation, or until 170 days after ip inoculation.ConclusionsBrain lacks significant lymphatic drainage, and has little infectivity before 40 days, even after ic inoculation. Thus the infectious inoculum must spread to the gut by a vascular route, a direction opposite to that generally assumed. This interpretation is consistent with previous studies demonstrating white blood cell infectivity as well as perivascular PrP accumulations in CJD. Notably, enteric infection at early as well as later stages of disease, and regardless of the route of agent entry, implicates potential environmental spread by fecal matter.

Oxygen Reduction by Homogeneous Molecular Catalysts and Electrocatalysts

The oxygen reduction reaction (ORR) is a key component of biological processes and energy technologies. This Review provides a comprehensive report of soluble molecular catalysts and electrocatalysts for the ORR. The precise synthetic control and relative ease of mechanistic study for homogeneous molecular catalysts, as compared to heterogeneous materials or surface-adsorbed species, enables a detailed understanding of the individual steps of ORR catalysis. Thus, the Review places particular emphasis on ORR mechanism and thermodynamics. First, the thermochemistry of oxygen reduction and the factors influencing ORR efficiency are described to contextualize the discussion of catalytic studies that follows. Reports of ORR catalysis are presented in terms of their mechanism, with separate sections for catalysis proceeding via initial outer- and inner-sphere electron transfer to O2. The rates and selectivities (for production of H2O2 vs H2O) of these catalysts are provided, along with suggested methods for accurately comparing catalysts of different metals and ligand scaffolds that were examined under different experimental conditions.

Decreased respiratory sinus arrhythmia in individuals with deceptive intent.

In detecting deception, the Cognitive Load hypothesis states that lying requires more cognitive resources compared to truth telling. Further, increases in cognitive load are predicted to decrease respiratory sinus arrhythmia (RSA). We evaluated the impact of cognitive tasks and the intent to deceive on RSA in 40 male, native Arabic-speaking participants quasi-randomized into truthful (n=14) or deceptive (n=26) groups. Participants donned an ambulatory physiologic recording device and completed cognitive testing after receiving translated instructions about their role in an impending mock crime. The results show that a decrease in RSA recorded during the cognitive testing was greater in individuals who were about to commit a deceptive act.

Rational Design of Mononuclear Iron Porphyrins for Facile and Selective 4e–/4H+ O2 Reduction: Activation of O–O Bond by 2nd Sphere Hydrogen Bonding

Facile and selective 4e-/4H+ electrochemical reduction of O2 to H2O in aqueous medium has been a sought-after goal for several decades. Elegant but synthetically demanding cytochrome c oxidase mimics have demonstrated selective 4e-/4H+ electrochemical O2 reduction to H2O is possible with rate constants as fast as 105 M-1 s-1 under heterogeneous conditions in aqueous media. Over the past few years, in situ mechanistic investigations on iron porphyrin complexes adsorbed on electrodes have revealed that the rate and selectivity of this multielectron and multiproton process is governed by the reactivity of a ferric hydroperoxide intermediate. The barrier of O-O bond cleavage determines the overall rate of O2 reduction and the site of protonation determines the selectivity. In this report, a series of mononuclear iron porphyrin complexes are rationally designed to achieve efficient O-O bond activation and site-selective proton transfer to effect facile and selective electrochemical reduction of O2 to water. Indeed, these crystallographically characterized complexes accomplish facile and selective reduction of O2 with rate constants >107 M-1 s-1 while retaining >95% selectivity when adsorbed on electrode surfaces (EPG) in water. These oxygen reduction reaction rate constants are 2 orders of magnitude faster than all known heme/Cu complexes and these complexes retain >90% selectivity even under rate determining electron transfer conditions that generally can only be achieved by installing additional redox active groups in the catalyst.