Dietary modification in the treatment of schizophrenia spectrum disorders: A systematic review.

BackgroundSchizophrenia spectrum disorders impact functioning, reduce quality of life and increase the risk of physical illness and premature mortality. Nutritional intervention studies aimed at decreasing body weight have demonstrated efficacy in improving metabolic outcomes; however, few studies have explored the impact of interventions designed to modify diet on mental health outcomes.AimTo synthesize the existing experimental studies of adjunctive diet modification as an intervention in the treatment of psychotic disorders, analyze findings related to effectiveness and safety, highlight knowledge gaps and limitations, and set forward recommendations for future research studies.MethodsAn extensive a priori search strategy was developed and the databases Embase, Embase Classic, Ovid MEDLINE were searched. Screening and data extraction were completed in duplicate. Studies included in this analysis were experimental studies of an adjunctive dietary intervention (overall dietary pattern or education on dietary change) for treatment of schizophrenia spectrum disorders. No restrictions were placed on control groups or blinding. The studies were required to report a mental health outcome.ResultsTwenty-five clinical trials were identified, along with two additional protocols and two meta-analyses. Nineteen of the clinical trials reported improvement in one or more mental health domain including psychosis symptoms, cognition, and quality of life. A high level of heterogeneity was found with respect to patient population, intervention, and study design. All of the studies included lifestyle or psychosocial components in addition to dietary modification. The nutrition advice provided to participants was poorly described overall and compliance was not assessed. The studies that showed benefit tended to have a smaller sample size and were less likely to be randomized but were more likely to use a group delivery intervention.ConclusionFurther research assessing effectiveness and efficacy of clearly reported dietary interventions is warranted, especially those using rigorous methodology, modifying diet in isolation and assessing participant compliance

Applied Quantum Chemistry: Spectroscopic Detection and Characterization of the F\u3csub\u3e2\u3c/sub\u3eBS and Cl\u3csub\u3e2\u3c/sub\u3eBS Free Radicals in the Gas Phase

In this and previous work [D. J. Clouthier, J. Chem. Phys. 141, 244309 (2014)], the spectroscopic signatures of the X2BY (X = H, halogen, Y = O, S) free radicals have been predicted using high level ab initio theory. The theoretical results have been used to calculate the electronic absorption and single vibronic level (SVL) emission spectra of the radicals under typical jet-cooled conditions. Using these diagnostic predictions, the previously unknown F2BS and Cl2BS free radicals have been identified and characterized. The radicals were prepared in a free jet expansion by subjecting precursor mixtures of BF3 or BCl3 and CS2 vapor to an electric discharge at the exit of a pulsed molecular beam valve. The B̃2A1-X̃2B2 laser-induced fluorescence spectra were found within 150 cm-1 of their theoretically predicted positions with vibronic structure consistent with our Franck-Condon simulations. The B̃2A1 state emits down to the ground state and to the low-lying Ã2B1 excited state and the correspondence between the observed and theoretically derived SVL emission Franck-Condon profiles was used to positively identify the radicals and make assignments. Excited state Coriolis coupling effects complicate the emission spectra of both radicals. In addition, a forbidden component of the electronically allowed B̃-X̃ band system of Cl2BS is evident, as signaled by the activity in the b2 modes in the spectrum. Symmetry arguments indicate that this component gains intensity due to a vibronic interaction of the B̃2A1 state with a nearby electronic state of 2B2 symmetry

Apego como marco teórico para entender los trastornos de personalidad: Consideraciones psicoterapéuticas, neurocientíficas y de desarrollo

In this paper we propose that John Bowlby\u27s attachment theory provides a theoretically coherent, empirically based, and clinically useful model for understanding personality pathology. This theoretical framework brings parsimony and breadth to the conceptualization of the etiology, maintenance, and treatment of personality disorders (PDs). Attachment theory can explain both the intrapersonal and interpersonal difficulties common in those with PDs and is consistent with findings from studies across multiple domains of knowledge, including evolutionary biology, ethology/comparative psychology, developmental psychology, experimental social-personality psychology, and neuroscience.PDs are characterized by significant interpersonal challenges. Recently, these challenges have been hypothesized to stem from underlying maladaptive attachment schemas. Our goal is to outline and elaborate on attachment theory as a foundation for the etiology and pathology of PDs and to highlight the implications of this theory for treatment. We begin with a brief review of attachment, describing its conceptualization and assessment in both children and adults in order to examine PD development. This theoretical foundation is supported by a body of empirical research, from which we present findings from neurobiological and developmental literatures linking attachment and PDs. We then examine the role of attachment in the psychotherapy process and in treatment outcome. Further, we outline research reporting changes in attachment patterns as a result of treatment. Finally, we summarize the implications of attachment theory for understanding PDs and present possible directions for future research.En este trabajo proponemos que la teoría de apego de John Bowlby ofrece un modelo teoréticamente coherente, empíricamente basado y clínicamente útil para entender la patología de personalidad. Este marco teorético trae parquedad y anchura a la conceptualización de la etiología, mantenimiento y tratamiento de trastornos de personalidad. La teoría de apego puede explicar las dificultades tanto intrapersonales como interpersonales comunes a las personas con trastornos de personalidad y es consistente con los descubrimientos de estudios de varios dominios del saber, incluyendo biología evolutiva, etiología/psicología comparada, psicología de desarrollo, psicología de personalidad y psicología social-personalidad experimental, y neurociencia. Trastornos de personalidad son caracterizados por los retos interpersonales significativos. Últimamente, se han hecho hipótesis que estos retos son el resultado de esquemas de apego mal adaptivos. Nuestro objetivo es explicar y elaborar la teoría de apego como la base para la etiología y patología de trastornos de personalidad y acentuar las implicaciones de esta teoría para el tratamiento. Empezamos con un pequeño análisis del apego, describiendo sus conceptualizaciones y evaluación tanto en niños como adultos para examinar el desarrollo de trastornos de personalidad. Este fundamento teórico está apoyado por la investigación empírica, de la que presentamos resultados de la literatura neurobiológica y de desarrollo relacionados con el apego y los trastornos de personalidad. Luego investigamos el papel que tiene el apego en los procesos de psicoterapia y en los resultados del tratamiento. Finalmente, resumimos las implicaciones de la teoría de apego para entender trastornos de personalidad y presentamos unas posibles direcciones para las futuras investigaciones

Doppler-Free Spectroscopy of Weak Transitions: An Analytical Model Applied to Formaldehyde

Experimental observation of Doppler-free signals for weak transitions can be greatly facilitated by an estimate for their expected amplitudes. We derive an analytical model which allows the Doppler-free amplitude to be estimated for small Doppler-free signals. Application of this model to formaldehyde allows the amplitude of experimentally observed Doppler-free signals to be reproduced to within the experimental error.Comment: 7 pages, 7 figures, 1 table, v2: many small improvements + corrected line assignmen

Evidence for the prepattern/cooption model of vertebrate jaw evolution

The appearance of jaws was a turning point in vertebrate evolution because it allowed primitive vertebrates to capture and process large, motile prey. The vertebrate jaw consists of separate dorsal and ventral skeletal elements connected by a joint. How this structure evolved from the unjointed gill bar of a jawless ancestor is an unresolved question in vertebrate evolution. To understand the developmental bases of this evolutionary transition, we examined the expression of 12 genes involved in vertebrate pharyngeal patterning in the modern jawless fish lamprey. We find nested expression of Dlx genes, as well as combinatorial expression of Msx, Hand and Gsc genes along the dorso-ventral (DV) axis of the lamprey pharynx, indicating gnathostome-type pharyngeal patterning evolved before the appearance of the jaw. In addition, we find that Bapx and Gdf5/6/7, key regulators of joint formation in gnathostomes, are not expressed in the lamprey first arch, whereas Barx, which is absent from the intermediate first arch in gnathostomes, marks this domain in lamprey. Taken together, these data support a new scenario for jaw evolution in which incorporation of Bapx and Gdf5/6/7 into a preexisting DV patterning program drove the evolution of the jaw by altering the identity of intermediate first-arch chondrocytes. We present this “Pre-pattern/Cooption” model as an alternative to current models linking the evolution of the jaw to the de novo appearance of sophisticated pharyngeal DV patterning

Three-dimensional scapular morphology is associated with rotator cuff tears and alters the abduction moment arm of the supraspinatus.

BACKGROUND: Numerous studies have reported an association between rotator cuff injury and two-dimensional measures of scapular morphology. However, the mechanical underpinnings explaining how these shape features affect glenohumeral joint function and lead to injury are poorly understood. We hypothesized that three-dimensional features of scapular morphology differentiate asymptomatic shoulders from those with rotator cuff tears, and that these features would alter the mechanical advantage of the supraspinatus. METHODS: Twenty-four individuals with supraspinatus tears and twenty-seven age-matched controls were recruited. A statistical shape analysis identified scapular features distinguishing symptomatic patients from asymptomatic controls. We examined the effect of injury-associated morphology on mechanics by developing a morphable model driven by six degree-of-freedom biplanar videoradiography data. We used the model to simulate abduction for a range of shapes and computed the supraspinatus moment arm. FINDINGS: Rotator cuff injury was associated with a cranial orientation of the glenoid and scapular spine (P = .011, d = 0.75) and/or decreased subacromial space (P = .001, d = 0.94). The shape analysis also identified previously undocumented features associated with superior inclination and subacromial narrowing. In our computational model, warping the scapula from a cranial to a lateral orientation increased the supraspinatus moment arm at 20° of abduction and decreased the moment arm at 160° of abduction. INTERPRETATIONS: Three-dimensional analysis of scapular morphology indicates a stronger relationship between morphology and cuff tears than two-dimensional measures. Insight into how morphological features affect rotator cuff mechanics may improve patient-specific strategies for prevention and treatment of cuff tears

Auriculocondylar syndrome 2 results from the dominant-negative action of PLCB4 variants.

Auriculocondylar syndrome 2 (ARCND2) is a rare autosomal dominant craniofacial malformation syndrome linked to multiple genetic variants in the coding sequence of phospholipase C β4 (PLCB4). PLCB4 is a direct signaling effector of the endothelin receptor type A (EDNRA)-Gq/11 pathway, which establishes the identity of neural crest cells (NCCs) that form lower jaw and middle ear structures. However, the functional consequences of PLCB4 variants on EDNRA signaling is not known. Here, we show, using multiple signaling reporter assays, that known PLCB4 variants resulting from missense mutations exert a dominant-negative interference over EDNRA signaling. In addition, using CRISPR/Cas9, we find that F0 mouse embryos modeling one PLCB4 variant have facial defects recapitulating those observed in hypomorphic Ednra mouse models, including a bone that we identify as an atavistic change in the posterior palate/oral cavity. Remarkably, we have identified a similar osseous phenotype in a child with ARCND2. Our results identify the disease mechanism of ARCND2, demonstrate that the PLCB4 variants cause craniofacial differences and illustrate how minor changes in signaling within NCCs may have driven evolutionary changes in jaw structure and function. This article has an associated First Person interview with the first author of the paper

GLUE-IT and PEDEL-AA: new programmes for analyzing protein diversity in randomized libraries

There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries generated by a number of these protocols. Our programmes suggested some empirical guidelines for library design; however, no information was provided regarding library diversity at the protein (rather than DNA) level. We have now updated our web server, enabling analysis of translated libraries constructed by site-saturation mutagenesis and error-prone PCR (epPCR). We introduce GLUE-Including Translation (GLUE-IT), which finds the expected amino acid completeness of libraries in which up to six codons have been independently varied (according to any user-specified randomization scheme). We provide two tools for assisting with experimental design: CodonCalculator, for assessing amino acids corresponding to given randomized codons; and AA-Calculator, for finding degenerate codons that encode user-specified sets of amino acids. We also present PEDEL-AA, which calculates amino acid statistics for libraries generated by epPCR. Input includes the parent sequence, overall mutation rate, library size, indel rates and a nucleotide mutation matrix. Output includes amino acid completeness and diversity statistics, and the number and length distribution of sequences truncated by premature termination codons. The web interfaces are available at http://guinevere.otago.ac.nz/stats.html

Nkx2.5 regulates Endothelin Converting Enzyme-1 during pharyngeal arch patterning

In gnathostomes, dorsoventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediates this process is Endothelin-1 (EDN1). Loss of EDN1 binding to the Endothelin-A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate-limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme-1 (ECE1). However, surprisingly little is known about how Ece1 transcription is induced or regulated. We show here that Nkx2.5 is required for proper craniofacial development in zebrafish and acts in part by upregulating ece1 expression. Disruption of nkx2.5 in zebrafish embryos results in defects in both ventral and dorsal pharyngeal arch-derived elements, with changes in ventral arch gene expression consistent with a disruption in Ednra signaling. ece1 mRNA rescues the nkx2.5 morphant phenotype, indicating that Nkx2.5 functions through modulating Ece1 expression or function. These studies illustrate a new function for Nkx2.5 in embryonic development and provide new avenues with which to pursue potential mechanisms underlying human facial disorders