Caveat emptor: Mental health specialty certifications and the public's preferences for clinical care.

Appropriate training and continuing education for mental health professionals are designed to ensure that clinicians provide effective and ethical care. Mental health consumers may depend upon these credentials to judge the level of a professional's competence, but whether these activities and credentials provide a valid indicator of knowledge and skills is subject to debate. The present study was designed to examine preferences for mental health clinicians among potential consumers and factors that may inform these preferences, specifically comparing preferences for doctoral-level mental health clinicians and masters-level clinicians with and without specialty certification for treating anxiety symptoms. Cross-sectional assessment with self-report surveys (clinician preferences, prior mental health diagnosis and treatment, demographic characteristics, generalized anxiety symptoms, mental health literacy, and mental health stigma) was administered in two samples: a college student sample (N = 224; 71.9% female; Mage = 19.1, SD = 1.5) and a sample of adults with chronic pain (N = 116; 74.1% female; Mage = 43.8, SD = 13.8). The present study found that across both samples, therapists with a specialty certification were preferred over those without such credentials within each profession, and that certification status trumped professional standing such that certified masters-level clinicians were rated more highly than noncertified PhD-level clinicians. These findings are indicative of a schism between how the field of clinical psychology conceptualizes itself and how it is seen by its consumers. Implications of our findings for mental health consumers, clinicians, and professional organizations are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Corrigendum Compounds Errors and Again Fails to Support the Specificity of Acupoint Tapping.

ABSTRACT: In a prior article (Spielmans, Rosen, Spence-Sing J Nerv Ment Dis 208:628-631, 2020), we demonstrated that Church, Stapleton, Yang, and Gallo's (J Nerv Ment Dis 206:783-793, 2018) meta-analytic finding that acupoint tapping had specific therapeutic benefit was highly flawed, both statistically and methodologically. Our analysis based on corrected effect sizes found no significant benefit for acupoint tapping at study endpoint. Church, Stapleton, Kip, and Gallo (J Nerv Ment Dis 208:632-635, 2020) issued a corrigendum in which they reported a new post hoc analysis using follow-up (rather than study endpoint) measures. Shifting to a post hoc outcome while pooling highly disparate follow-up endpoints is problematic; it ignored the nonsignificant result of the a priori analysis. Here, we clarify these issues and address Church, Stapleton, Kip, and Gallo's (J Nerv Ment Dis 208:632-635, 2020) often irrelevant or confusing responses to our methodological concerns. Considering this recent exchange of articles, and absent meaningful correction to the original incorrect findings, we remain concerned that emotional freedom technique proponents will continue to advance unfounded claims regarding the purported benefits of acupoint tapping.

Tapping Away at a Misleading Meta-analysis: No Evidence for Specificity of Acupoint Tapping.

Church et al.'s meta-analysis of three studies claimed to support the specificity of acupoint tapping as a therapeutic technique in the treatment of mental health problems. However, our critical analysis found substantial methodological problems and inaccurate statistical analyses, which render their results invalid. Specifically, 1) two included studies did not include participants with documented mental health problems; 2) two included studies did not specifically isolate the effect of acupoint tapping; 3) clear rationales for selected measures were not provided; 4) comparison groups were not bona fide therapies; 5) researcher and therapist allegiances were not controlled; and 6) selection of included studies may have been biased. Further, our attempt to replicate their results failed; we found that acupoint tapping fared no better than comparison groups: k = 3 studies, d = -0.38 (95% confidence interval, 0.10 to -0.87), p = 0.12. We conclude that the Church et al.'s meta-analysis actually found no specific mental health benefits for acupoint tapping.

Does Improvement of Low Serum Ferritin Improve Symptoms of Restless Legs Syndrome in a Cohort of Pediatric Patients?

STUDY OBJECTIVES: To determine whether an oral iron supplement improves restless leg/restless sleep symptoms in a pediatric population. METHODS: In a cohort study, 47 patients (age 5-18 years) exhibiting restless legs/restless sleep symptoms and low serum ferritin levels (< 50 ng/mL) were given a daily oral iron supplement (ferrous sulfate + vitamin C) and re-evaluated 8 weeks later. A diagnosis of definite Restless Legs Syndrome (RLS) was determined based on criteria established by the International RLS Study Group. Using Wilcoxon signed-rank tests and Spearman rho, the change and association between the measures of Pediatric Restless Legs Syndrome Severity Scale and serum ferritin levels were also examined. RESULTS: Overall, the median change and distribution of ferritin was statistically significantly different after 8 weeks of treatment (40.0 versus 23.0 ng/mL, P < .0001). Median RLS score was also statistically significantly lower from baseline to follow-up (4.0 versus 6.0, P = .0283). Sixteen patients met criteria for definite RLS; however, the change in RLS score was not determined to be significant in our population (9.5 versus 7.0, P = .0558), despite significant change in ferritin (25.0 versus 42.5 ng/mL, P < .0001). In addition, no correlation was observed between change in RLS score and ferritin level (rho = -.39, P = .1362). CONCLUSIONS: In preliminary findings, we found a modest, yet nonsignificant improvement in children exhibiting restless sleep and RLS symptomatology, despite significant improvement in ferritin levels. Though not statistically significant, the findings can lend to the suggested benefit of iron supplementation in patients with RLS; however, clinical judgment and further research is necessary. CITATION: Rosen GM, Morrissette S, Larson A, Stading P, Barnes TL. Does improvement of low serum ferritin improve symptoms of restless legs syndrome in a cohort of pediatric patients? J Clin Sleep Med. 2019;15(8):1149-1154.

Use of a Probiotic to Enhance Iron Absorption in a Randomized Trial of Pediatric Patients Presenting with Iron Deficiency.

OBJECTIVE: To evaluate the efficacy of low dose ferrous sulfate for the treatment of iron deficiency and if the probiotic Lactobacillus plantarum 299v (LP299v) enhances treatment. STUDY DESIGN: This randomized, double-blinded, controlled trial of the treatment of iron deficiency in children compared the use of low-dose ferrous sulfate (1-3 mg/kg/day), with or without probiotic (LP299v). RESULTS: Serum ferritin level increased in all children from a baseline of 23.7 ng/mL to 45.4 ng/mL after 6-8 weeks of treatment. There was no significant difference in the increase in serum ferritin in children taking the probiotic LP299v compared with controls (23.2 vs 20.0 ng/mL, respectively). Additionally, an increase in ferritin level was not significantly associated with probiotic use when controlling for other factors, including child weight and dosing. Overall, the treatments were well-tolerated, with mild side effects. CONCLUSIONS: Treatment with low-dose ferrous sulfate is well-tolerated and effective in correcting iron deficiency in children. However, the probiotic LP299v did not enhance treatment. Further attention should examine the dose-response effect in children, including an alternate day dosing schedule. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01617044.

Demonstration of a Tritiated Nitroxide Nuclear Battery.

Unattended, compact, terrestrial and space sensors require sources that have high energy and power densities to continuously operate for 3 to 99 years depending on application. Currently, chemical sources cannot fully satisfy these applications, especially in solid state form. Betavoltaic (ßV) nuclear batteries using ß--emitting radioisotopes possess energy densities 1000 times greater than conventional chemical sources. Their power density is a function of ß- flux saturation point relative to the planar (2D) configuration, ß- emission range, and the semiconductor converter, the betavoltaic (ßV) cell, properties. The figure of merit is the beta (ß-)-flux surface power density ( [Formula: see text] in µWn per cm2 footprint), where an optimal portion of incident beta particles penetrates the surrounding semiconductor depletion region. Tritiated nitroxides are favorable radioisotope sources with the potential to have the highest specific activity (Am in Ci/g) and [Formula: see text] for an organic compound in solid form. The goal of this research is to demonstrate a tritiated nitroxide nuclear battery using the planar (2D) coupling configuration. The reproducible tritiation procedure produced stable product with a Am of approximately 635 Ci/g, which was 70% of the theoretical Am. For the nuclear battery demonstration, the tritiated nitroxide, dissolved in methanol, was deposited on a 4H-SiC ßV and InGaP photovoltaic (PV) cell using a dispensing apparatus and micropipette. Both devices' characteristics were measured beforehand using a controlled electron beam source to approximate the surface radioactivity from the deposited radioisotope. The maximum power point (MPP) of the 4H-SiC and InGaP were 7.77 nW/cm2 and 1.63 nW/cm2 with 100 mCi and 67 mCi, respectively. The power and total efficiency were lower than expected due to partial solvent evaporation and droplet thickness. Numerical models using MCNP6 Monte Carlo code were used to simulate an optimal nuclear battery prototype. The models' accuracy was confirmed with the device calibration curves and a previous metal tritide model based on empirical results. Based on optimal model results, the tritiated nitroxide saturation layer thickness (D0.99) and [Formula: see text] (D0.99) were 10 µm and 558 nW/cm2, respectively, using a 4H-SiC.

Development of tritiated nitroxide for nuclear battery.

Beta radioisotope energy sources, such as tritium (3H), have shown significant potential in satisfying the needs of a sensor-driven world. The limitations of current beta sources include: (i) low beta-flux power, (ii) intrinsic isotope leakage and (iii) beta self-absorption. The figure of merit is the beta-flux power (dPß/dS in µWn/cm2), where an optimal portion of incident beta particles penetrates the semiconductor depletion region. Thus, the goal of this research was to identify a compound to contain a beta emitter that can permit beta-flux power of at least 0.73 µWn/cm2 from one side, where it can be used for both planar and textured semiconductor structures. Nitroxides were chosen because of previous demonstrated deuteration, ease of synthesis, diversity of structure, and pliability. As a proof-of-principle, nitroxide [1] was prepared and tritiated with a specific activity of 103Ci/g. The corresponding tritiated nitroxide in toluene was found to have no measurable 3H2 outgassing after 27 days, thus it was considered stable. After 256 days in solution, analysis of the compound showed only 2% tritium loss, whereas in solid form, there was approximately 50% of tritium loss after 21 days. To compare with the performance of a typical metal tritide carrier, the standard MCNPX Monte Carlo code was used to calculate the beta-flux power of tritiated nitroxide and titanium tritide (0.2 µWn/cm2 and 0.70 µWn/cm2), respectively. The difference between numerical and empirical results of titanium tritide was 4%, showing the model validity. For the tritiated nitroxide to be comparable to titanium tritide in a planar configuration (2-D), the gravimetric density (3H weighted percentage) would need to be at least 9%.

Imaging thiol redox status in murine tumors in vivo with rapid-scan electron paramagnetic resonance.

Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of 2H,15N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with l-buthionine sulfoximine (BSO) markedly altered the kinetic images.

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent.

OBJECTIVE: To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. MATERIALS AND METHODS: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 µM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. RESULTS: At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. CONCLUSION: The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically.

Designing Molecular Probes To Prolong Intracellular Retention: Application to Nitroxide Spin Probes.

Targeted delivery of molecular probes into cells enables cellular imaging through optical and magnetic modalities. Probe molecules that are well retained by cells can accumulate to higher intracellular concentrations, and thus increase the signal-to-noise ratio of, and widen the temporal window for, imaging. Here we synthesize a paramagnetic spin probe bearing six ionic functional groups and show that it has long intracellular half-life (>12 h) and exceptional biostability in living cells. We demonstrate that judicious incorporation of ionic substituents on probe molecules systematically increases intracellular retention time, and should therefore be beneficial to imaging experiments.

Has DSM-5 saved PTSD from itself?

In 2007, Robert Spitzer considered validity challenges to the diagnosis of post-traumatic stress disorder (PTSD), a construct that originated when he was Chair of DSM-III. Spitzer suggested changes for DSM-5, then in its planning stages, for the purpose of 'Saving PTSD from itself'. With years gone by, it can be asked if DSM-5 followed Spitzer's recommendations to advance our understanding of post-traumatic disorder.

In vivo EPR oximetry using an isotopically-substituted nitroxide: Potential for quantitative measurement of tissue oxygen.

Variations in brain oxygen (O2) concentration can have profound effects on brain physiology. Thus, the ability to quantitate local O2 concentrations noninvasively in vivo could significantly enhance understanding of several brain pathologies. However, quantitative O2 mapping in the brain has proven difficult. The electron paramagnetic resonance (EPR) spectra of nitroxides are sensitive to molecular O2 and can be used to estimate O2 concentrations in aqueous media. We recently synthesized labile-ester-containing nitroxides, such as 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (nitroxide 4), which accumulate in cerebral tissue after in situ hydrolysis, and thus enable spatial mapping of O2 concentrations in the mouse brain by EPR imaging. In an effort to improve O2 quantitation, we prepared 3-acetoxymethoxycarbonyl-2,2,5,5-tetra((2)H3)methyl-1-(3,4,4-(2)H3,1-(15)N)pyrrolidinyloxyl (nitroxide 2), which proved to be a more sensitive probe than its normo-isotopic version for quantifying O2 in aqueous solutions of various O2 concentrations. We now demonstrate that this isotopically substituted nitroxide is ∼2-fold more sensitive in vivo than the normo-isotopic nitroxide 4. Moreover, in vitro and in vivo EPR spectral-spatial imaging results with nitroxide 2 demonstrate significant improvement in resolution, reconstruction and spectral response to local O2 concentrations in cerebral tissue. Thus, isotopic-substituted nitroxides, such as 2, are excellent sensors for in vivo O2 quantitation in tissues, such as the brain.

Reassessing the "traditional background hypothesis" for elevated MMPI and MMPI-2 Lie-scale scores.

The Lie (L) scale of the Minnesota Multiphasic Personality Inventory (MMPI) is widely regarded as a measure of conscious attempts to deny common human foibles and to present oneself in an unrealistically positive light. At the same time, the current MMPI-2 manual states that "traditional" and religious backgrounds can account for elevated L scale scores as high as 65T-79T, thereby tempering impression management interpretations for faith-based individuals. To assess the validity of the traditional background hypothesis, we reviewed 11 published studies that employed the original MMPI with religious samples and found that only 1 obtained an elevated mean L score. We then conducted a meta-analysis of 12 published MMPI-2 studies in which we compared L scores of religious samples to the test normative group. The meta-analysis revealed large between-study heterogeneity (I2 = 87.1), L scale scores for religious samples that were somewhat higher but did not approach the upper limits specified in the MMPI-2 manual, and an overall moderate effect size (d¯ = 0.54, p < .001; 95% confidence interval [0.37, 0.70]). Our analyses indicated that religious-group membership accounts, on average, for elevations on L of about 5 t-score points. Whether these scores reflect conscious "fake good" impression management or religious-based virtuousness remains unanswered. (PsycINFO Database Record

Disulfide-Linked Dinitroxides for Monitoring Cellular Thiol Redox Status through Electron Paramagnetic Resonance Spectroscopy.

Intracellular thiol-disulfide redox balance is crucial to cell health, and may be a key determinant of a cancer's response to chemotherapy and radiation therapy. The ability to assess intracellular thiol-disulfide balance may thus be useful not only in predicting responsiveness of cancers to therapy, but in assessing predisposition to disease. Assays of thiols in biology have relied on colorimetry or fluorimetry, both of which require UV-visible photons, which do not penetrate the body. Low-frequency electron paramagnetic resonance imaging (EPRI) is an emerging magnetic imaging technique that uses radio waves, which penetrate the body well. Therefore, in combination with tailored imaging agents, EPRI affords the opportunity to image physiology within the body. In this study, we have prepared water-soluble and membrane-permeant disulfide-linked dinitroxides, at natural isotopic abundance, and with D,(15)N-substitution. Thiols such as glutathione cleave the disulfides, with simple bimolecular kinetics, to yield the monomeric nitroxide species, with distinctive changes in the EPR spectrum. Using the D,(15)N-substituted disulfide-dinitroxide and EPR spectroscopy, we have obtained quantitative estimates of accessible intracellular thiol in cultured human lymphocytes. Our estimates are in good agreement with published measurements. This suggests that in vivo EPRI of thiol-disulfide balance is feasible. Finally, we discuss the constraints on the design of probe molecules that would be useful for in vivo EPRI of thiol redox status.

Potential role of autophagy in the bactericidal activity of human PMNs for Bacillus anthracis.

Bacillus anthracis, the causative agent of anthrax, is acquired by mammalian hosts from the environment, as quiescent endospores. These endospores must germinate inside host cells, forming vegetative bacilli, before they can express the virulence factors that enable them to evade host defenses and disseminate throughout the body. While the role of macrophages and dendritic cells in this initial interaction has been established, the role of polymorphonuclear leukocytes (PMNs) has not been adequately defined. We discovered that while B. anthracis 34F2 Sterne endospores germinate poorly within non-activated human PMNs, these phagocytes exhibit rapid microbicidal activity toward the outgrown vegetative bacilli, independent of superoxide and nitric oxide. These findings suggest that a non-free radical pathway kills B. anthracis bacilli. We also find in PMNs an autophagic mechanism of bacterial killing based on the rapid induction of LC-3 conversion, beclin-1 expression, sequestosome 1 (SQSTM1) degradation and inhibition of bactericidal activity by the inhibitor, 3-methyladenine. These findings extend to PMNs an autophagic bactericidal mechanism previously described for other phagocytes.

Imaging disulfide dinitroxides at 250 MHz to monitor thiol redox status.

Measurement of thiol-disulfide redox status is crucial for characterization of tumor physiology. The electron paramagnetic resonance (EPR) spectra of disulfide-linked dinitroxides are readily distinguished from those of the corresponding monoradicals that are formed by cleavage of the disulfide linkage by free thiols. EPR spectra can thus be used to monitor the rate of cleavage and the thiol redox status. EPR spectra of (1)H,(14)N- and (2)H,(15)N-disulfide dinitroxides and the corresponding monoradicals resulting from cleavage by glutathione have been characterized at 250 MHz, 1.04 GHz, and 9 GHz and imaged by rapid-scan EPR at 250 MHz.

Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: A role for mitoBKCa channels.

Carbon monoxide (CO), a product of heme degradation by heme oxygenases, plays an important role in vascular homeostasis. Recent evidence indicates that mitochondria are among a number of molecular targets that mediate the cellular actions of CO. In the present study we characterized the effects of CO released from CORM-401 on mitochondrial respiration and glycolysis in intact human endothelial cells using electron paramagnetic resonance (EPR) oximetry and the Seahorse XF technology. We found that CORM-401 (10-100µM) induced a persistent increase in the oxygen consumption rate (OCR) that was accompanied by inhibition of glycolysis (extracellular acidification rate, ECAR) and a decrease in ATP-turnover. Furthermore, CORM-401 increased proton leak, diminished mitochondrial reserve capacity and enhanced non-mitochondrial respiration. Inactive CORM-401 (iCORM-401) neither induced mitochondrial uncoupling nor inhibited glycolysis, supporting a direct role of CO in the endothelial metabolic response induced by CORM-401. Interestingly, blockade of mitochondrial large-conductance calcium-regulated potassium ion channels (mitoBKCa) with paxilline abolished the increase in OCR promoted by CORM-401 without affecting ECAR; patch-clamp experiments confirmed that CO derived from CORM-401 activated mitoBKCa channels present in mitochondria. Conversely, stabilization of glycolysis by MG132 prevented CORM-401-mediated decrease in ECAR but did not modify the OCR response. In summary, we demonstrated in intact endothelial cells that CO induces a two-component metabolic response: uncoupling of mitochondrial respiration dependent on the activation of mitoBKCa channels and inhibition of glycolysis independent of mitoBKCa channels.

Improved sensitivity for imaging spin trapped hydroxyl radical at 250 MHz.

Radicals, including hydroxyl, superoxide, and nitric oxide, play key signaling roles in vivo. Reaction of these free radicals with a spin trap affords more stable paramagnetic nitroxides, but concentrations in vivo still are so low that detection by electron paramagnetic resonance (EPR) is challenging. Three innovative enabling technologies have been combined to substantially improve sensitivity for imaging spin-trapped radicals at 250 MHz. 1) Spin-trapped adducts of BMPO have lifetimes that are long enough to make imaging by EPR at 250 MHz feasible. 2) The signal-to-noise ratio of rapid-scan EPR is substantially higher than for conventional continuous-wave EPR. 3) An improved algorithm permits image reconstruction with a spectral dimension that encompasses the full 50 G spectrum of the BMPO-OH spin adduct without requiring the wide sweeps that would be needed for filtered backprojection. A 2D spectral-spatial image is shown for a phantom containing ca. 5 µM BMPO-OH.