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Question: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach., Study Selection and Analysis: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis., Findings: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias., Conclusions: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response., Prospero Registration Number: CRD42017069090., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.)

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis., Methods and Findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials., Conclusions: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objective of this study was to test if the Personality Inventory for DSM-5 (PID-5) is an adequate instrument to evaluate psychiatric inpatients' pathological personality traits., Methods: Inpatients (n = 130; mean age: 38.5 years; 62.3% female; 63.9% single) answered the PID-5 after clinical improvement of their psychiatric symptoms. The mean scores of the DSM-5 personality domains, facets and profiles, and ICD-11 domain traits were compared with the mean scores of a Brazilian normative sample (n = 656). We investigated the diagnostic performance of the scales to identify individuals with and without psychopathology., Results: The final sample included mainly diagnoses of mood disorders. Except for Antagonism and Disinhibition, all DSM-5 personality domains and most facets as well as almost all DSM-5 personality disorder profiles (except Narcissist) and ICD-11 trait domains (except Detachment and Dissociality) of the inpatients presented high differences compared with the normative sample. In general, the PID-5 scales presented a high negative predictive value and a low positive predictive value to identify individuals with severe psychopathology., Discussion: This study found high scores of pathological personality traits in a sample of Brazilian psychiatric inpatients. The PID-5 may be a promising instrument to measure pathological personality traits among psychiatric inpatients. Methodological and sample size limitations may have influenced the results. © 2018 John Wiley & Sons, Ltd., (© 2018 John Wiley & Sons, Ltd.)

Introduction: User satisfaction assessment in mental health services is an important indicator of treatment quality. The objective of this study was to evaluate treatment satisfaction in a sample of inpatients with mental disorders and the associations between levels of satisfaction and clinical/sociodemographic variables., Methods: This exploratory study investigated 227 psychiatric inpatients who answered the Patient Satisfaction with Mental Health Services Scale (SATIS-BR) and the Perception of Change Scale (EMP). SATIS scores were analyzed according to associations with clinical and sociodemographic data. Pearson correlations were used to correlate SATIS scores with other variables., Results: We found a high degree of satisfaction with care at the psychiatric inpatient unit assessed. In general, patients rated maximum satisfaction for most items. The highest satisfaction scores were associated with patients receiving treatment through the Brazilian Unified Health System (SUS) and with less education. SATIS showed a moderate positive correlation with EMP. The worst evaluated dimension was physical facilities and comfort of the ward., Conclusion: Patients treated via SUS may be more satisfied than patients with private health insurance when treated in the same facility. The evaluation of treatment satisfaction can be used to reorganize services at psychiatric inpatient units.

Background: The constraints imposed by minimal access surgery have driven the need for enabling technologies for thermal vessel occlusion or "tissue welding." The objective of this study was to determine the values of, and interaction between, tissue temperature, apposition force, and clamp time for optimum tissue welding., Methods: A dedicated experimental device with heated occluding jaws was used for ex vivo experiments on harvested sheep carotid vessels. The device allowed individual variation of temperature (60, 70, 80, and 90 °C), compression force (20, 40, 60, and 80 N) and clamp time (5, 10, 15 s). Weld strength was measured by burst pressure., Results: The best seal quality was obtained at a temperature of 90 °C (p = 0.03), a compression force between 60 and 80 N (p = 0.03), and clamp time of 10 s (p = 0.058). The individual effects of temperature, compression force, and clamp time were all significant at p < 0.001. Although all three were considered to have large effects, clamp time had a reduced effect, relative to temperature and compression force., Conclusions: Temperature, compression force, and clamp time influence the quality of thermal welding, but the interaction between temperature and apposition force appears to be more dominant.

Unlabelled: Postpartum depression (PPD) is the most common psychiatric complication observed in women after they give birth. Some women are particularly sensitive to hormonal changes, starting in early menarche, thus increasing their vulnerability to psychological stressing agents that are triggered by environmental and physiological factors throughout their lives. Decreased serum brain-derived neurotrophic factor (BDNF) levels have been associated to different neuropsychiatric conditions and BDNF has been considered as a candidate marker for such dysfunctions. The goal of this study was to compare the levels of BDNF between mothers who suffer from PPD and healthy control mothers as well as to searching for associations between BDNF levels and the severity of PPD. This is a case-control study including 36 mothers with PPD and 36 healthy control mothers. PPD was defined according to the Beck Depression Inventory (BDI). Serum BDNF was assayed with the sandwich ELISA method., Results: Serum levels of BDNF were significantly lower in women with PPD than in control mothers (P ≤ 0.03). A significant negative correlation between BDI score and serum BDNF levels was observed (P ≤ 0.02 and r = -0.29). Our study demonstrated that low BDNF levels are associated with PPD. This result point out to the potential usage of BDNF in the screening of PPD, which could promote early treatment and, therefore, reduce the burden to the PPD women and to the health system.

Inorganic polyphosphate (poly P) is a polymer of phosphate residues that has been shown to act as modulator of some vertebrate cathepsins. In the egg yolk granules of Rhodnius prolixus, a cathepsin D is the main protease involved in yolk mobilization and is dependent on an activation by acid phosphatases. In this study, we showed a possible role of poly P stored inside yolk granules on the inhibition of cathepsin D and arrest of yolk mobilization during early embryogenesis of these insects. Enzymatic assays detected poly P stores inside the eggs of R. prolixus. We observed that micromolar poly P concentrations inhibited cathepsin D proteolytic activity using both synthetic peptides and homogenates of egg yolk as substrates. Poly P was a substrate for Rhodnius acid phosphatase and also a strong competitive inhibitor of a pNPPase activity. Fusion events have been suggested as important steps towards acid phosphatase transport to yolk granules. We observed that poly P levels in those compartments were reduced after in vitro fusion assays and that the remaining poly P did not have the same cathepsin D inhibition activity after fusion. Our results are consistent with the hypothesis that poly P is a cathepsin D inhibitor and a substrate for acid phosphatase inside yolk granules. It is possible that, once activated, acid phosphatase might degrade poly P, allowing cathepsin D to initiate yolk proteolysis. We, therefore, suggest that degradation of poly P might represent a new step toward yolk mobilization during embryogenesis of R. prolixus.

Neuromyelitis optica (NMO), an uncommon central nervous system (CNS) demyelinating disease, produces transverse myelitis and severe optic neuritis. IgG-NMO autoantibody, a specific immunoglobulin binding aquaporin-4 water channel protein, confirms that NMO is a different entity to multiple sclerosis. Parallel to cytokine down-regulations found in serum of relapsing-NMO (rNMO) patients, it has been reported that IgG-NMO may also confer a worse course of the disease in r-NMO Caribbean patients. In this study, we were interested in exploring the influence of IgG-NMO autoantibody on S100beta levels and clinical parameters from serum of r-NMO patients. Serum samples from 24 rNMO patients and 10 controls were evaluated. The reduction of S100beta observed in r-NMO patients was not significant compared to controls; and no differences were present regarding IgG-NMO immunoreactivity. At the same time, a significant correlation was also observed between IgG-NMO autoantibody serum detection and EDSS (Expanded Disability Status Scale) in rNMO. These results corroborate a differential regulation of IgG-NMO autoantibodies on the S100beta glial marker and on the disability present in rNMO patients., (Copyright 2010 S. Karger AG, Basel.)

Acidocalcisomes are acidic organelles containing large amounts of polyphosphate (poly P), a number of cations, and a variety of cation pumps in their limiting membrane. The vacuolar proton-pyrophosphatase (V-H(+)-PPase), a unique electrogenic proton-pump that couples pyrophosphate (PPi) hydrolysis to the active transport of protons across membranes, is commonly present in membranes of acidocalcisomes. In the course of insect oogenesis, a large amount of yolk protein is incorporated by the oocytes and stored in organelles called yolk granules (YGs). During embryogenesis, the content of these granules is degraded by acid hydrolases. These enzymes are activated by the acidification of the YG by a mechanism that is mediated by proton-pumps present in their membranes. In this work, we describe an H(+)-PPase activity in membrane fractions of oocytes and eggs of the domestic cockroach Periplaneta americana. The enzyme activity was optimum at pH around 7.0, and was dependent on Mg(2+) and inhibited by NaF, as well as by IDP and Ca(2+). Immunolocalization of the yolk preparation using antibodies against a conserved sequence of V-H(+)-PPases showed labeling of small vesicles, which also showed the presence of high concentrations of phosphorus, calcium and other elements, as revealed by electron probe X-ray microanalysis. In addition, poly P content was detected in ovaries and eggs and localized inside the yolk granules and the small vesicles. Altogether, our results provide evidence that numerous small vesicles of the eggs of P. americana present acidocalcisome-like characteristics. In addition, the possible role of these organelles during embryogenesis of this insect is discussed.

We report the cloning, expression, purification, and characterization of the Trypanosoma cruzi exopolyphosphatase (TcPPX). The product of this gene (TcPPX), has 383 amino acids and a molecular mass of 43.1 kDa. TcPPX differs from most exopolyphosphatases in its preference for short-chain polyphosphate (poly P). Heterologous expression of TcPPX in Escherichia coli produced a functional enzyme that had a neutral optimum pH and was dramatically inhibited by low concentrations of Zn2+, high concentrations of basic amino acids (lysine and arginine), and heparin. TcPPX is a processive enzyme and does not hydrolyze ATP, pyrophosphate, or p-nitrophenyl phosphate, although it hydrolyzes guanosine 5'-tetraphosphate very efficiently. Overexpression of TcPPX resulted in a dramatic decrease in total short-chain poly P and partial decrease in long-chain poly P. This was accompanied by a delayed regulatory volume decrease after hyposmotic stress. These results support the role of poly P in T. cruzi osmoregulation.

The H+-PPase activity was characterized in membrane fractions of ovary and eggs of Rhodnius prolixus. This activity is totally dependent on Mg2+, independent of K+ and strongly inhibited by NaF, IDP and Ca2+. The membrane proteins of eggs were analyzed by western blot using antibodies to the H+-PPase from Arabidopsis thaliana. The immunostain was associated with a single 65-kDa polypeptide. This polypeptide was immunolocalized in yolk granule membranes by optical and transmission electron microscopy. We describe the acidification of yolk granules in the presence of PPi and ATP. This acidification is inhibited in the presence of NAF, Ca2+ and antibodies against H+-PPase. These data show for the first time in animal cells that acidification of yolk granules involves an H+-PPase as well as H+-ATPase.