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Background: Ecological momentary assessment (EMA) involves completing multiple surveys over time in daily life, capturing in-the-moment experiences in real-world contexts. EMA use in psychosis studies has surged over several decades. To critically examine EMA use in psychosis research and assist future researchers in designing new EMA studies, this systematic review aimed to summarize the methodological approaches used for positive symptoms in psychosis populations and evaluate feasibility with a focus on completion rates., Methods: A systematic review of PubMed, PsycINFO, MEDLINE, Web of Science, EBSCOhost, and Embase databases using search terms related to EMA and psychosis was conducted. Excluding duplicate samples, a meta-analysis was conducted of EMA survey completion rates and meta-regression to examine predictors of completion., Results: Sixty-eight studies were included in the review. Characteristics and reporting of EMA methodologies were variable across studies. The meta-mean EMA survey completion computed from the 39 unique studies that reported a mean completion rate was 67.15% (95% CI = 62.3, 71.9), with an average of 86.25% of the sample meeting a one-third EMA completion criterion. No significant predictors of completion were found in the meta-regression. A variety of EMA items were used to measure psychotic experiences, of which few were validated., Conclusions: EMA methods have been widely applied in psychosis studies using a range of protocols. Completion rates are high, providing clear evidence of feasibility in psychosis populations. Recommendations for reporting in future studies are provided., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Peer workers support individuals experiencing mental health challenges by drawing on their shared lived experience. Peer support has become increasingly popular for young people with anxiety and depression, but the evidence base is unclear. This systematic review aimed to understand the effectiveness of peer support for youth depression and anxiety (either primary or comorbid), and to understand in which contexts, for whom, and why peer support works., Methods: A systematic search was conducted with the Orygen Evidence Finder, Embase, MEDLINE, and PsycInfo from January 1980 to July 2022. Controlled trials of interventions to improve mental health in young people (mean age 14-24), delivered by a peer worker with lived experienced of mental health challenges were included. Outcomes related to depression or anxiety were extracted and descriptive synthesis was undertaken due to the heterogeneity of studies. Study quality was rated using the Critical Appraisal Skills Programme; reporting adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Results: Nine randomised controlled trials with 2,003 participants were included, with seven undertaken in high income countries. One targeted depression and anxiety, two stigma-distress (any mental disorder), one first episode psychosis, four studies preventing eating disorders and one drug misuse. One study successfully reduced anxiety and depression, another reduced depression only, four reported reductions in negative affect, with the final three measuring, but not having a significant impact on depression. Study quality was rated as 'good' overall., Discussion: Despite the uptake of youth peer support globally, there is limited evidence from controlled trials of the effect of peer support-related interventions on anxiety and depression. There is some effect on negative affect, especially for university students. Further rigorously designed trials of peer delivered interventions for young people need to be conducted with a focus on understanding the mechanisms of action underpinning peer support., (© 2023. The Author(s).)

The asymmetric unit of the anhydrous title compound, 2Na(+)·C(4)H(4)O(6) (2-), contains two sodium cations and one tartrate anion. Each sodium ion is six coordinate, with bonding to six O atoms from both the carboxyl-ate and hydroxyl groups of the anion. A three-dimensional coordination network is formed with sodium ions stacking in layers along the c-axis direction. This network is supported by additional O-H⋯O hydrogen bonds.

Natural infection of humans with human T-cell lymphotropic virus type I (HTLV-I) and of old world nonhuman primates with the simian counterpart, STLV-I, is associated with development of neoplastic disease in a small percentage of individuals after long latent periods. HTLV-I is also the etiologic agent of a more rapidly progressive neurologic disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Macaques have been used experimentally in studies to evaluate HTLV-I candidate vaccines for efficacy, but no evidence of disease was observed. Here we report experimental infection of pig-tailed macaques with STLV-I(sm) and HTLV-I(ACH), both of which were associated with a disease syndrome characterized by rapid onset, hypothermia, lethargy, and death within hours to days. Other pathologic sequelae included diarrhea, rash, bladder dysfunction, weight loss, and, in one animal, arthropathy. Both retroviruses were detected in the central nervous systems of some animals, either by culture or by direct antigen capture for p19 Gag in cerebrospinal fluid. Although virus was recovered throughout infection from peripheral blood mononuclear cells (PBMC), all infected macaques maintained low antiviral antibody titers and stable proviral burdens, which generally ranged between 10 and 100 copies per 10(6) PBMC. However, of 13 macaques infected with HTLV-I(ACH) or STLV-I(sm), seven animals (54%) died between 35 weeks and 412 years after infection. This unexpected high mortality within a relatively short time suggests that infection of pig-tailed macaques might be a useful model for studying immune responses to and pathologic events resulting from HTLV-I infection., (Copyright 2002 Elsevier Science (USA))

Background: Exposing adult porcine pancreatic islets (PI) to xenoreactive natural antibodies (XNA) induces brisk inflammatory injury that involves activation of the complement system. Gene transfer of Bcl-2 has been shown to protect PI from apoptosis and necrosis in several models. In this study, we investigated the effect of Bcl-2 gene transfer on protection of PI from primate XNA and complement-mediated injury., Methods: The PI were isolated from adult female sows. Only islet preparations that exhibited >90% viability and purity were used. Fresh rhesus monkey serum served as the XNA source. Gene transfer of Bcl-2 was achieved with an adenoviral vector (AdBcl-2) at 500 particle forming units (pfu)/cell. The Bcl-2 expression was confirmed by Western blot technique. Untransfected and transfected PI were incubated in 50% fresh complete serum (CS) or heat-inactivated (HI) rhesus serum for 24 hours. The PI viability was analyzed with acridine orange and ethidium bromide staining. Antibody and complement-mediated cytotoxicity were tested by intracellular lactate dehydrogenase (LDH) release. The PI function was assessed in vitro by static incubation studies and in vivo after intraportal transplantation in diabetic severe combined immunodeficiency (SCID) mice., Results: The AdBcl-2 gene transfer resulted in Bcl-2 gene expression in >90% of PI cells. Following exposure to XNA, <15% of the untransfected cells were viable. Similar results were obtained in PI transfected with a similar recombinant adenovirus encoding the reporter gene E coli beta-galactosidase (AdLacZ), an irrelevant gene. A significant increase in LDH release was observed in control PI after exposure to CS compared with PI that overexpressed Bcl-2 (82.89% +/- 7.78% vs 34.31% +/- 5.4%, P <.005). Higher insulin release was observed in vitro in PI transfected with Bcl-2 compared with untransfected PI or islets transfected with AdLacZ (stimulation index of 0.9 +/- 0.31, 0.9 +/- 0.3 vs 2.67 +/- 0.4, respectively). Only PI treated with AdBcl-2 were able to achieve euglycemia after exposure to XNA and complement after transplantation., Conclusions: Transfer of the antiapoptotic and antinecrotic Bcl-2 gene into PI can reduce primate XNA and complement-mediated lysis. Cytoprotection of PI with Bcl-2 has potential to improve survival of PI xenotransplants.

Gender is a significant factor in determining the susceptibility to and severity of pulmonary diseases in both humans and animals. Murine respiratory mycoplasmosis (MRM), due to Mycoplasma pulmonis infection, is an excellent animal model for evaluation of the role of various host factors on the development of acute or chronic inflammatory lung diseases. MRM has many similarities to mycoplasma respiratory disease in humans. The purpose of the present study was to determine whether gender has a significant impact on lung disease due to M. pulmonis infection in mice. It was demonstrated that male mice consistently developed more severe disease in the lung parenchyma than did female mice. There was no gender difference in disease severity along the airways or any difference in mycoplasma numbers in lungs of male and female mice. Furthermore, surgical removal of reproductive organs reduced the severity of mycoplasma disease and the numbers of mycoplasma organisms recovered from lungs. Thus, gender plays a significant role in determining the severity of M. pulmonis disease. In fact, the gender of the host was a major factor in determining whether an acute or chronic inflammatory lung disease developed after infection with M. pulmonis.

During routine physical examination, a five-year-old male rhesus macaque (Macaca mulatta) was observed to have gaps in the right iris. Ophthalmic examination revealed inferior and superior iridodialysis with an anterior cortical cataract. The optic nerve head and fundus were normal. Uninvolved areas of the iris and anterior-chamber angle were normal on the basis of results of gonioscopy. Tonometry revealed normal intraocular pressure. The cause of the iridodialysis in this monkey's eye was not known. The animal had been housed individually since arrival due to requirements of the research protocol. Although the concomitant cataract supports a traumatic cause, there was no history of cranial or other ocular injuries. Trauma from fighting through the cage walls, self-trauma or falling inside the cage while under sedation cannot be ruled out. Multiple hematologic evaluations disclosed no abnormalities. This animal did not manifest behavioral abnormalities or any indication of pain. Therefore, treatment was not initiated. Intraocular pressure continues to be monitored at least semiannually.

Background: Pancreatic islet transplantation (PIT) is an attractive alternative for patients with type I diabetes mellitus. PIT is not yet an effective clinical reality due in part to the high incidence of rejection and early loss of functional islet mass. In addition, current immunosuppressive drugs have toxic effects on islets and increase the risk of morbidity and mortality. In the present study, the effects of PIT on glycemic parameters were assessed in spontaneously diabetic primates., Methods: Five insulinopenic nonhuman primates (three Macacca fascicularis, one Ceropithecus aethiops, and one Macacca mulatta) were studied. All required twice-daily treatment with 4-10 U of insulin. For immunosuppression, the animals received anti-CD3-immunotoxin (100 microg/kg(initially infused 2 hr before transplantation and again on day +1), cyclosporine (CsA) (20 mg/kg(i.v./2 hr before transplantation), cyclosporine microemulsion (Neoral) 60 mg/kg/b.i.d. on days +1 to +3 with dose adjusted by blood levels, and methylprednisolone (15 mg/kg day 0 to +3). Three recipients were given islets from a single donor (M mulatta). The islets were prepared by a semiautomated technique using Liberase. A mean of 13,136 islet equivalents/kg was infused into the portal vein. Two animals (M fascicularis and M mulatta) were used as a diabetic, nontransplanted control. Several metabolic parameters were evaluated., Results: All monkeys that underwent transplantation experienced reversal of diabetes mellitus with normalization of all diabetic glycemic parameters. In the nontransplanted primates given the same immunosuppression but no PIT, diabetic metabolic parameters were unchanged after 9 months of follow-up. In contrast, all three PIT recipients established fasting and nonfasting euglycemia within 1-2 weeks, and none required exogenous insulin after day 10. Normal intravenous glucose tolerance tests were observed at day 15, and no significant differences in the glucose disappearance rate (Kg) were observed at days 15, 45, 190, and 365 days after transplantation. The acute insulin response to glucose indicated no significant reduction of functional islet mass., Conclusions: PIT in severely insulinopenic type I diabetes mellitus primates resulted in restoration of normal glycemic parameters and durable islet mass. Operational tolerance was achieved with only 4 days of drug administration, sparing the animals from chronic exposure to potentially diabetogenic immunosuppressive drugs. These results offer an exciting new potential for type I diabetes mellitus treatment.

Introduction: Anti-CD3-immunotoxin (alpha-CD3-IT) promotes allograft tolerance in nonhuman primates owing to efficient depletion of sessile and circulating T cells. Common side effects of vascular leak syndrome, hepatotoxicity, and nephrotoxicity have limited tolerability of other immunotoxins. We report on preclinical studies of alpha-CD3-IT-related side effects., Methods: Normal rhesus monkeys received a kidney transplant and alpha-CD3-IT alone (on day -to +2) or in combination with brief peritransplant adjunctive immunosuppressive therapy. Some received donor CD34+ cells. Blood chemistries, complete blood count, weight, liver, and kidney biopsies were examined for immunotoxin-related changes. Five spontaneously diabetic primates also received alpha-CD3-IT, three of whom had a pancreas islet transplant., Results: The main side effect of alpha-CD3-IT, vascular leak syndrome, was entirely prevented by adjunctive immunosuppressive therapy. Renal and liver function tests and biopsies revealed a lack of nephrotoxicity and hepatotoxicity. All had transient weight loss (14+/-5%). Without infusion of donor CD34+ cells, 97% had full weight recovery. Of those given donor CD34+ cells, 50% were euthanized for wasting., Conclusions: Side effects of alpha-CD3-IT are manageable and should not prevent therapeutic application.

Objective: Bone morphogenetic proteins can serve as adjuncts to autologous bone to achieve bony fusion, and recombinant BMPs such as osteogenic protein-1 (OP-1) have the potential to replace autologous bone altogether as fusion substrate. However, relatively little is known about the safety of OP-1 for spinal fusion procedures. This study examined the effects of OP-1 intentionally placed in the subarachnoid space following thecal sac decompression, and used as graft substrate in a canine dorsolateral lumbar spine fusion model., Methods: Lumbar decompression with dorsolateral fusion was performed on 30 canines. The dura was opened to simulate an intraoperative rent and OP-1 was placed in the subarachnoid space and in the fusion bed. Animals were sacrificed after 16 weeks and the spines were examined manually, radiographically and pathologically., Results: All animals treated with OP-1 developed new bone in the subarachnoid space. This bone compressed the spinal cord, but no clinical or pathological features of neurotoxicity were noted. Mild spinal stenosis was noted at the site of dural decompression in the OP-1 treated animals. Over 80% of animals treated with OP-1 developed fusion as assessed by palpation (52% by CT criteria), while only 25% of control animals fused., Conclusions: Recombinant human OP-1 is effective at promoting fusion in a canine dorsolateral lumbar spine fusion model. However, bone growth can occur over exposed, decompressed dura, and it can form in the subdural and subarachnoid spaces. The use of OP-1 as an adjunct to spinal fusion appears to have merit, but its use must be carefully controlled to avoid unwanted bone formation and subsequent neural compression.

Background: Isolated pancreatic islet transplantation (IPITx) is an attractive alternative for treatment of insulin-dependent diabetes mellitus (IDDM). However, IPITx has been difficult to implement clinically because islets frequently fail to function, have a high incidence of rejection, and are susceptible to autoimmune recurrence and damage by chronic immunosuppressive therapy. Tolerance induction may be a rational approach to resolve several of these limitations. Because anti-CD3 immunotoxin (IT) has been successful in promoting stable primate kidney transplant tolerance in our experience, we considered that tolerance induction with IT might be duplicated in IPITx., Materials and Methods: Three monkeys with spontaneous IDDM (two Macaca fascicularis and one Ceropithecus aethiops) were treated with xenogeneic pancreatic islets (Macaca mulatta). Intrahepatic islet transplantation was performed at a mean of 13136+/-3860 islet equivalents/kg. Islet xenograft acceptance was accomplished by tolerance induction with two injections of IT given on day 0 at 2 hr before transplantation and on day +1, respectively. IT treatment was supplemented with cyclosporine and steroids administered on days 0 through 4. No additional immunosuppression was given thereafter. Two additional control macaques with spontaneous IDDM received the immunosuppressive protocol without islet infusion., Results: All recipients were restored to stable euglycemia, off exogenous insulin, within 1-2 weeks after transplantation. Glucose tolerance, C-peptide, and glycosylated hemoglobin tests confirmed the restoration of normal glucose homeostasis after islet transplantation. All three islet recipients have remained euglycemic at 410, 255, and 100 days of follow-up despite recovery of peripheral T cells to normal levels. In contrast, none of the controls presented changes in the diabetic status 4 and 8 months after treatment., Conclusions: These results represent the first demonstration in nonhuman primates of stable, long-term acceptance of nonencapsulated xenogeneic islets off all immunosuppression, suggesting operational tolerance. The findings have potential implications for islet transplantation as well as improved and more cost-effective therapy for IDDM.

Background: Tolerance is gaining momentum as an approach to reduce lifelong immunosuppressive therapy while improving transplant longevity. Anti-CD3 immunotoxin (IT), FN18-CRM9, has potential to induce tolerance owing to its exceptional ability to deplete sessile lymph node T cells. However, if initiated at the time of transplantation, alpha-CD3-IT alone elicits a proinflammatory cytokine response, precluding establishment of tolerance., Methods: Four groups of rhesus monkeys received kidney allografts and immunosuppression. Three groups received alpha-CD3-IT alone or alpha-CD3-IT supplemented with 15-deoxyspergualin (DSG) and/or methylprednisolone (MP). One group received alpha-CD3-monoclonal antibody with DSG and MP. Cytokines were measured by enzyme-linked immunosorbent assay., Results: Supplementing peritransplant alpha-CD3-IT treatment with a brief course of DSG and MP promoted rejection-free kidney allograft acceptance in 75% of macaques followed for up to 550 days. Among those given alpha-CD3-IT alone or with MP, none were long-term survivors. Tolerance developed after alpha-CD3-IT, DSG, and MP treatment, but not when the unconjugated a-CD3 monoclonal antibody was substituted for IT. Systemic production of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha induced after peritransplant alpha-CD3-IT was prevented only in animals given DSG. Despite high levels of interleukin (IL)-12 in the first month after transplant, tolerant recipients exhibited IL-12 resistance, as evidenced by baseline plasma levels of IFN-gamma but elevated IL-4. DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B., Conclusions: In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12.