A via receptor NMDA-óxido nítrico-GMP cíclico como alvo para o desenvolvimento de medicações antipsicóticas não-dopaminérgicas para a esquizofrenia

Schizophrenia is a devastating disorder that occurs in about 1% of the population worldwide. For over 30 years, it has been considered to be the result of dysfunctional brain dopaminergic pathways. However, dopaminergic antipsychotic drugs have proven effective for only some of the symptoms found in schizophrenia patients. Recent evidence suggests that dopaminergic abnormalities may be secondary to dysfunctions in multi-neurotransmitter systems modulating dopamine. One of the key neurotransmitters thought to be involved in schizophrenia is glutamate, and there is strong support for the involvement of a hypoactivity of N-methyl-D-aspartate (NMDA) glutamate receptors in the pathogenesis of schizophrenia. However, research with NMDA receptor agonists for the treatment of schizophrenia has produced inconsistent results, which may be due to the development of rapid tolerance to these compounds secondary to down-regulation of NMDA receptors. Perhaps the development of drugs that act on targets downstream NMDA receptors, such as nitric oxide (NO), could avoid the problem of the down-regulation of these receptors

Effect of powder metallurgy synthesis parameters for pure aluminium on resultant mechanical properties

In this work, pure aluminium powders of different average particle size were compacted, sintered into discs and tested for mechanical strength at different strain rates. The effects of average particle size (15, 19, and 35 μm), sintering rate (5 and 20 °C/min) and sample indentation test speed (0.5, 0.7, and 1.0 mm/min) were examined. A compaction pressure of 332 MPa with a holding time of six minutes was used to produce the green compacted discs. The consolidated green specimens were sintered with a holding time of 4 h, a temperature of 600 °C in an argon atmosphere. The resulting sintered samples contained higher than 85% density. The mechanical properties and microstructure were characterized using indentation strength measurement tests and SEM analysis respectively. After sintering, the aluminium grain structure was observed to be of uniform size within the fractured samples. The indentation test measurements showed that for the same sintering rate, the 35 μm powder particle size provided the highest radial and tangential strength while the 15 μm powder provided the lowest strengths. Another important finding from this work was the increase in sintered sample strength which was achieved using the lower sinter heating rate, 5 °C/min. This resulted in a tangential stress value of 365 MPa which was significantly higher than achieved, 244 MPa, using the faster sintering heating rate, 20 °C/min

Fit between humanitarian professionals and project requirements: hybrid group decision procedure to reduce uncertainty in decision-making

Choosing the right professional that has to meet indeterminate requirements is a critical aspect in humanitarian development and implementation projects. This paper proposes a hybrid evaluation methodology for some non-governmental organizations enabling them to select the most competent expert who can properly and adequately develop and implement humanitarian projects. This methodology accommodates various stakeholders’ perspectives in satisfying the unique requirements of humanitarian projects that are capable of handling a range of uncertain issues from both stakeholders and project requirements. The criteria weights are calculated using a two-step multi-criteria decision-making method: (1) Fuzzy Analytical Hierarchy Process for the evaluation of the decision maker weights coupled with (2) Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) to rank the alternatives which provide the ability to take into account both quantitative and qualitative evaluations. Sensitivity analysis have been developed and discussed by means of a real case of expert selection problem for a non-profit organisation. The results show that the approach allows a decrease in the uncertainty associated with decision-making, which proves that the approach provides robust solutions in terms of sensitivity analysis

THE CHALLENGES FACED BY SCHOOL COUNSELLORS IN THE REPORTING OF CHILD SEXUAL ABUSE

Identifying and reporting sexually abused children is one of the most important responsibilities of school counsellors. In this study, we aimed to determine the challenges of reporting child sexual abuse. We used a questionnaire form that was prepared by reviewing the literature about reporting sexual abuse. Participants were asked to state their level of knowledge of child sexual abuse, whether they had encountered such cases, whether they faced any challenges when notifying to authorities, and the possible solutions to problems encountered during this process. Of the school counsellors contacted, 40.9% of the participants stated that they encountered a claim of child sexual abuse at least once, but the majority of them (47.4%) could not report it to judicial authorities because of various reasons; such as being unsure whether the event was really happening, anticipating reactions towards them or school management, and fearing the school’s loss of reputation in the case of disclosure.  Article visualizations

A prenatally detected adrenal cyst treated by adrenal-sparing surgery: case report and review of the literature

A neonatal case of left adrenal cyst detected in utero and successfully treated by adrenal-sparing surgery is presented and discussed with review of the literature. Incidentally discovered prenatal adrenal masses present a diagnostic dilemma. Benign and malignant conditions can present as a fetal suprarenal mass. There is a wide spectrum of management modalities ranging from followup by serial sonographic scanning during pregnancy to early primary excision of the mass. We report a neonate with prenatal diagnosis of a cystic mass arising from the left adrenal gland. Postnatal excision of the mass without adrenalectomy was carried out. Frozen sections of the mass and a biopsy of the left adrenal gland confirmed the benign nature of the cyst and normal adrenal tissue. The uniloculated cyst was reported as a pseudocyst. After surgery, the recovery was uneventful, and the patient was discharged 4 days postoperatively in good condition. On the basis of this case and review of the literature, we may conclude that early primary surgical excision is recommended for either diagnosis or treatment if the results of prenatal or postnatal imaging studies are unreliable for the precise diagnosis of suprarenal mass. Adrenal-sparing surgery is recommended if pathological evaluation of frozen sections has confirmed the benign nature of the mass.Keywords: adrenal-sparing surgery, neonates, prenatal diagnosis, suprarenal cys

Surfaces of Revolution with Constant Gaussian Curvature in Four-Space

In this paper, we show that the constant property of the Gaussian curvature of surfaces of revolution in both $\mathbb R^4$ and $\mathbb R_1^4$ depend only on the radius of rotation. We then give necessary and sufficient conditions for the Gaussian curvature of the general rotational surfaces whose meridians lie in two dimensional planes in $\mathbb R^4$ to be constant, and define the parametrization of the meridians when both the Gaussian curvature is constant and the rates of rotation are equal.Comment: 8 paper

Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic cell development from common dendritic cell progenitors

Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c(+) MHCII- precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking. Analysis of CDP genealogies revealed a stepwise differentiation of CDPs into pDCs in a part of the CDP colonies. This developmental pathway involved an early CD11c(+) SiglecH(-) pre-DC stage and a Siglec H+ CCR9(low) precursor stage, which was followed rapidly by upregulation of CCR9 indicating final pDC differentiation. In the majority of the remaining CDP pedigrees however the Siglec H+ CCR9(low) precursor state was maintained for several generations. Thus, although a fraction of CDPs transits through precursor stages rapidly to give rise to a first wave of pDCs, the majority of CDP progeny differentiate more slowly and give rise to longer lived precursor cells which are poised to differentiate on demand

Comparison of iron-reduced and iron-supplemented semisynthetic diets in T cell transfer colitis

Clinical observations in inflammatory bowel disease patients and experimental studies in rodents suggest that iron in the intestinal lumen derived from iron-rich food or oral iron supplementation could exacerbate inflammation and that iron depletion from the diet could be protective. To test the hypothesis that dietary iron reduction is protective against colitis development, the impact of iron reduction in the diet below 10 mg/kg on the course of CD4+ CD62L+ T cell transfer colitis was investigated in adult C57BL/6 mice. Weight loss as well as clinical and histological signs of inflammation were comparable between mice pretreated with semisynthetic diets with either < 10mg/kg iron content or supplemented with 180 mg/kg iron in the form of ferrous sulfate or hemin. Accumulation and activation of Ly6C(high) monocytes, changes in dendritic cell subset composition and induction of proinflammatory Th1/Th17 cells in the inflamed colon were not affected by the iron content of the diets. Thus, dietary iron reduction did not protect adult mice against severe intestinal inflammation in T cell transfer induced colitis

An investigation into aripiprazole's partial D(2) agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. Objectives: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole’s prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole’s unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. Method: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. Results: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d’) and speeded reaction times. In contrast to aripiprazole’s neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d’ and additionally had reduced errors of commission compared with placebo. Conclusion: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone’s serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade

Domain-Size-Dependent Residual Stress Governs the Phase-Transition and Photoluminescence Behavior of Methylammonium Lead Iodide

Methylammonium lead iodide (MAPbI3) perovskite has garnered significant interest as a versatile material for optoelectronic applications. The temperature-dependent photoluminescence (TDPL) and phase-transition behaviors revealed in previous studies have become standard indicators of defects, stability, charge carrier dynamics, and device performance. However, published reports abound with examples of irregular photoluminescence and phase-transition phenomena that are difficult to reconcile, posing major challenges in the correlation of those properties with the actual material state or with the subsequent device performance. In this paper, a unifying explanation for the seemingly inconsistent TDPL and phase-transition (orthorhombic-to-tetragonal) characteristics observed for MAPbI3 is presented. By investigating MAPbI3 perovskites with varying crystalline states, ranging from polycrystal to highly oriented crystal as well as single-crystals, key features in the TDPL and phase-transition behaviors are identified that are related to the extent of crystal domain-size-dependent residual stress and stem from the considerable volume difference (ΔV&nbsp;≈ 4.5%) between the primitive unit cells of the orthorhombic (at 80 K) and tetragonal phases (at 300 K) of MAPbI3. This fundamental connection is essential for understanding the photophysics and material processing of soft perovskites