Treatment Outcome in Patients Receiving Assertive Community Treatment

In an observational study of severely mentally ill patients treated in assertive community treatment (ACT) teams, we investigated how treatment outcome was associated with demographic factors, clinical factors, and motivation for treatment. To determine psychosocial outcome, patients were routinely assessed using the Health of the Nation Outcome Scales (HoNOS). Trends over time were analyzed using a mixed model with repeated measures. The HoNOS total score was modeled as a function of treatment duration and patient-dependent covariates. Data comprised 637 assessments of 139 patients; mean duration of follow-up was 27.4 months (SD = 5.4). Substance abuse, higher age, problems with motivation, and lower educational level were associated with higher HoNOS total scores (i.e., worse outcome). To improve treatment outcome, we recommend better implementation of ACT, and also the implementation of additional programs targeting subgroups which seem to benefit less from ACT

Expression and Purification of Recombinant Hemoglobin in Escherichia coli

Recombinant DNA technologies have played a pivotal role in the elucidation of structure-function relationships in hemoglobin (Hb) and other globin proteins. Here we describe the development of a plasmid expression system to synthesize recombinant Hbs in Escherichia coli, and we describe a protocol for expressing Hbs with low intrinsic solubilities. Since the α- and β-chain Hbs of different species span a broad range of solubilities, experimental protocols that have been optimized for expressing recombinant human HbA may often prove unsuitable for the recombinant expression of wildtype and mutant Hbs of other species.As a test case for our expression system, we produced recombinant Hbs of the deer mouse (Peromyscus maniculatus), a species that has been the subject of research on mechanisms of Hb adaptation to hypoxia. By experimentally assessing the combined effects of induction temperature, induction time and E. coli expression strain on the solubility of recombinant deer mouse Hbs, we identified combinations of expression conditions that greatly enhanced the yield of recombinant protein and which also increased the efficiency of post-translational modifications.Our protocol should prove useful for the experimental study of recombinant Hbs in many non-human animals. One of the chief advantages of our protocol is that we can express soluble recombinant Hb without co-expressing molecular chaperones, and without the need for additional reconstitution or heme-incorporation steps. Moreover, our plasmid construct contains a combination of unique restriction sites that allows us to produce recombinant Hbs with different α- and β-chain subunit combinations by means of cassette mutagenesis

Insight dimensions and cognitive function in psychosis: a longitudinal study

BACKGROUND: It has been reported that lack of insight is significantly associated with cognitive disturbance in schizophrenia. This study examines the longitudinal relationships between insight dimensions and cognitive performance in psychosis. METHODS: Participants were 75 consecutively admitted inpatients with schizophrenia, affective disorder with psychotic symptoms or schizoaffective disorder. Assessments were conducted at two time points during the study: at the time of hospital discharge after an acute psychotic episode and at a follow-up time that occurred more than 6 months after discharge. A multidimensional approach of insight was chosen and three instruments for its assessment were used: the Scale to Assess Unawareness of Mental Disorder (SUMD), three items concerning insight on the Assessment and Documentation in Psychopathology (AMDP) system and the Insight and Treatment Attitudes Questionnaire. The neuropsychological battery included a wide range of tests that assessed global cognitive function, attention, memory, and executive functions. RESULTS: After conducting adequate statistical correction to avoid Type I bias, insight dimensions and cognitive performance were not found to be significantly associated at cross-sectional and longitudinal assessments. In addition, baseline cognitive performance did not explain changes in insight dimensions at follow-up. Similar results were found in the subset of patients with schizophrenia (n = 37). The possibility of a Type II error might have increased due to sample attrition at follow-up. CONCLUSION: These results suggest that lack of insight dimensions and cognitive functioning may be unrelated phenomena in psychosis

A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls (P = 0.0009, OR = 7.2) and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls (P = 0.028, OR = 2.5). Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents (P = 0.037, OR = 6). Probands were more likely to carry an additional large copy-number variant when compared to matched controls (10 of 42 cases, P = 5.7 x 10(-5), OR = 6.6). The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease

A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: A longitudinal cohort study

Background: In this study, we investigated whether an abnormal hypothalamic-pituitary-adrenal (HPA) axis response to psychosocial stress at 18 years of age is associated with musculoskeletal (MS) pain alone and MS pain combined with increased pain sensitivity at 22 years of age. Methods: The study sample included 805 participants from the Western Australian Pregnancy Cohort (Raine) Study who participated in the Trier Social Stress Test (TSST) at age 18 years. Number of pain sites, pain duration, pain intensity and pain frequency were assessed at age 22 to measure severity of MS pain. Cold and pressure pain thresholds were determined at age 22. Group-based trajectory modeling was applied to establish cortisol response patterns based on the TSST. Logistic regression was used to study the association of TSST patterns with MS pain alone and MS pain combined with increased cold or pressure pain sensitivity, adjusted for relevant confounding factors. All analyses were stratified by sex. Results: The mean (standard deviation) age during the TSST was 18.3 (0.3) years, and during MS pain assessment it was 22.2 (0.6). Forty-five percent of the participants were female. Three cortisol response patterns were identified, with cluster 1 (34 % of females, 21 % of males) reflecting hyporesponse, cluster 2 (47 %, 54 %) reflecting intermediate response and cluster 3 (18 %, 24 %) reflecting hyperresponse of the HPA axis. MS pain was reported by 42 % of females and 33 % of males at age 22 years. Compared with females in cluster 2, females in cluster 1 had an increased likelihood of having any MS pain (odds ratio 2.3, 95 % confidence interval 1.0-5.0) and more severe MS pain (2.8, 1.1-6.8) if their cold pain threshold was above the median. In addition, females in cluster 1 had an increased likelihood (3.5, 1.3-9.7) of having more severe MS pain if their pressure pain threshold was below the median. No statistically significant associations were observed in males. Conclusions: This study suggests that a hyporesponsive HPA axis at age 18 years is associated with MS pain at 22 years in young females with increased pain sensitivity

ProSAAS-Derived Peptides are Colocalized with Neuropeptide Y and Function as Neuropeptides in the Regulation of Food Intake

ProSAAS is the precursor of a number of peptides that have been proposed to function as neuropeptides. Because proSAAS mRNA is highly expressed in the arcuate nucleus of the hypothalamus, we examined the cellular localization of several proSAAS-derived peptides in the mouse hypothalamus and found that they generally colocalized with neuropeptide Y (NPY), but not α-melanocyte stimulating hormone. However, unlike proNPY mRNA, which is upregulated by food deprivation in the mediobasal hypothalamus, neither proSAAS mRNA nor proSAAS-derived peptides were significantly altered by 1–2 days of food deprivation in wild-type mice. Furthermore, while proSAAS mRNA levels in the mediobasal hypothalamus were significantly lower in Cpefat/fat mice as compared to wild-type littermates, proNPY mRNA levels in the mediobasal hypothalamus and in other subregions of the hypothalamus were not significantly different between wild-type and Cpefat/fat mice. Intracerebroventricular injections of antibodies to two proSAAS-derived peptides (big LEN and PEN) significantly reduced food intake in fasted mice, while injections of antibodies to two other proSAAS-derived peptides (little LEN and little SAAS) did not. Whole-cell patch clamp recordings of parvocellular neurons in the hypothalamic paraventricular nucleus, a target of arcuate NPY projections, showed that big LEN produced a rapid and reversible inhibition of synaptic glutamate release that was spike independent and abolished by blocking postsynaptic G protein activity, suggesting the involvement of a postsynaptic G protein-coupled receptor and the release of a retrograde synaptic messenger. Taken together with previous studies, these findings support a role for proSAAS-derived peptides such as big LEN as neuropeptides regulating food intake

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems

Cortical Thinning in Patients with Recent Onset Post-Traumatic Stress Disorder after a Single Prolonged Trauma Exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD

Cigarette Smoking and Cognitive Function in Chinese Male Schizophrenia: A Case-Control study

Schizophrenic patients have higher smoking rates than the general population. Studies show that smoking may be a form of self-medication in an attempt to alleviate cognitive deficits in schizophrenic patients of European background. This study examined the relationships between smoking and cognitive deficits in Chinese schizophrenic patients, which have previously received little systemic study. We recruited 580 male chronic patients meeting DSM-IV criteria for schizophrenia and 175 male control subjects who were matched on age and education. The subjects completed a detailed cigarette smoking questionnaire, the Fagerstrom Test for Nicotine Dependence (FTND), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). All five RBANS subscales except for the Visuospatial/Constructional index showed significantly lower cognitive performance for schizophrenics than normal controls. The schizophrenic smokers scored lower than the schizophrenic non-smokers on the RBANS total score and the Visuospatial/Constructional and Immediate Memory indices. Similarly, the control smokers scored lower than the control non-smokers on the RBANS total score and the Immediate Memory index . Also, the schizophrenic smokers consistently performed the poorest on the cognitive domains of the RBANS. Among the schizophrenic patients, smokers displayed significantly fewer negative symptoms than non-smokers. Using multivariate regression analysis the following variables were independently associated with the RBANS total score: years of education, PANSS negative symptom score, age at schizophrenia onset, and number of hospitalizations. Our results show that smoking is associated with significant cognitive impairment in both schizophrenic patients and normal controls, but the smokers with schizophrenia had a reduced level of negative symptoms, suggesting that the benefits of smoking for those with schizophrenia may be limited to certain aspects of a given clinical phenotype