Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial.

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.

Single-Nuclei Multiome (ATAC + Gene Expression) Sequencing of a Primary Canine Osteosarcoma Elucidates Intra-Tumoral Heterogeneity and Characterizes the Tumor Microenvironment.

Osteosarcoma (OSA) is a highly aggressive bone tumor primarily affecting pediatric or adolescent humans and large-breed dogs. Canine OSA shares striking similarities with its human counterpart, making it an invaluable translational model for uncovering the disease's complexities and developing novel therapeutic strategies. Tumor heterogeneity, a hallmark of OSA, poses significant challenges to effective treatment due to the evolution of diverse cell populations that influence tumor growth, metastasis, and resistance to therapies. In this study, we apply single-nuclei multiome sequencing, encompassing ATAC (Assay for Transposase-Accessible Chromatin) and GEX (Gene Expression, or RNA) sequencing, to a treatment-naïve primary canine osteosarcoma. This comprehensive approach reveals the complexity of the tumor microenvironment by simultaneously capturing the transcriptomic and epigenomic profiles within the same nucleus. Furthermore, these results are analyzed in conjunction with bulk RNA sequencing and differential analysis of the same tumor and patient-matched normal bone. By delving into the intricacies of OSA at this unprecedented level of detail, we aim to unravel the underlying mechanisms driving intra-tumoral heterogeneity, opening new avenues for therapeutic interventions in both human and canine patients. This study pioneers an approach that is broadly applicable, while demonstrating significant heterogeneity in the context of a single individual's tumor.

The Effects of an Online Positive Psychology Course on Happiness, Health, and Well-Being.

This study investigated the effects of an 8-week online positive psychology course on happiness, health, and well-being. There were 65 undergraduate students in the course and a comparison group of 63 undergraduates taking other online psychology courses. The participants were assessed on positive mental health (e.g., happiness, positive emotions), negative mental health (e.g., anxiety, depression), general health, and personal characteristics (e.g., hope, resilience) during the first and last week of the courses. The anxiety and depression measures had cut-offs for clinically significant symptoms. The hypotheses were that the positive psychology students would have significant improvements on all measures and a reduction in the percent anxious and depressed relative to the comparison group. The hypotheses were supported with large effect sizes for positive and negative mental health (mean ds = 0.907 and - 0.779, respectively) and medium-to-large effects for general health and personal characteristics (d = 0.674 and mean ds = 0.590, respectively). There was a reduction from 49.2 to 23.1% percent anxious and from 18.6 to 6.2% percent depressed with no change in the comparison group. In addition, improvements in the online positive psychology course were compared with a previous study of a similar face-to-face positive psychology course (Smith et al., 2021) showing the effect sizes for improvements relative to the comparison groups were larger in the online vs. face-to-face course (mean ds = 0.878. vs. 0.593). Possible explanations for these differences are discussed along with the implications for maximizing the benefits of positive psychology courses in the future.

The age-invariant role of resilience resources in emotional symptomatology.

Objectives 1) To study the relationship between resilience resources (both social and individual) and emotional symptomatology (depression and anxiety symptoms), taking into account the potential indirect effects through perceived stress; 2) to investigate whether this network of relationships varies in different age groups. METHOD: A sample of 718 Brazilians completed self-reports on perceived stress, depressive and anxious symptomatology, social support and individual resilience. The sample comprised two age groups: a sample of adults aged 60 or older (n = 361; 38.78% men; Mage = 67.32 years, SDage = 5.76, range = 60-86), and a sample of younger adults (n = 357; 29.41% men; Mage = 41.37 years, SDage = 7.23, range = 18-59). Multigroup multiple indicator, multiple cause (MIMIC) modelling was used to test for the direct and indirect effects of resilience resources on emotional symptom development, considering the age groups. RESULTS: The relationship between individual resilience resources and depressive or anxiety symptomatology was found to take place exclusively through stressfulness appraisal. On the other hand, social resilience resources showed a direct and indirect effect on emotional symptoms. This pattern of relationships was found to be invariant across age groups. CONCLUSION: Our findings suggest that both individual and social resilience resources are negatively related to both depressive and anxiety symptoms in adults regardless of age, thus opening the way to future research analysing how interventions may build resilience resources to minimise the influence of stressful and traumatic events across the lifespan.

Professional Practice Guidelines for Personality Assessment.

The current paper conveys guidelines for personality assessment developed by a work group formed by the Society for Personality Assessment (SPA), which are intended to serve as an aid for best practices specific to personality assessment for professionals, and a source of information for consumers and policy makers. The guidelines were developed after a careful and systematic review of the literature on personality assessment and examination of practice patterns, and were refined through multiple rounds of input from stakeholders including members of SPA and other professionals routinely conducting personality assessment. The guidelines address the scope of personality assessment and current practice trends, minimum education and training qualifications, ethical practices, diversity considerations, assessment procedures, and appropriate applications. By following these guidelines and other established professional standards, psychologists can help ensure that they practice ethically, competently, with appropriate attention to diversity, and to the highest standards of the profession. These guidelines can function as a resource for educators and supervisors of personality assessment. Additionally, the guidelines will serve as a benchmark for best practices in personality assessment and, as such, represent a first step in what is hoped to be an evolution of ever improving personality assessment standards of practice.

In vitro functional genetic modification of canine adenovirus type 2 genome by CRISPR/Cas9.

Genetically modified oncolytic adenoviruses have been proposed as a vehicle for cancer therapy. However, several concerns, such as toxicity to normal cells and organs, lack of suitable cell surface receptors to allow viral entry to the desired cell type(s), and activation of both innate and adaptive immune systems in patients, restrict the successful clinical application of adenoviral-mediated cancer gene therapy. Successful virotherapy will require efficient transductional and transcriptional targeting to enhance therapeutic efficacy by ensuring targeted adenoviral infection, replication, and/or therapeutic transgene expression. Targeted modification of viral components, such as viral capsid, fiber knob, and the insertion of transgenes for expression, are prerequisites for the necessary transductional and transcriptional targeting of adenovirus. However, the conventional approach to modify the adenoviral genome is complex, time consuming, and expensive. It is dependent on the presence of unique restriction enzyme sites that may or may not be present in the target location. Clustered regularly interspaced short palindromic repeat (CRISPR) along with the RNA-guided nuclease Cas9 (CRISPR/Cas9) is one of the most powerful tools that has been adopted for precise genome editing in a variety of cells and organisms. However, the ability of the CRISPR/Cas9 system to precisely and efficiently make genetic modification, as well as introduce gene replacements, in adenoviral genomes, remains essentially unknown. Herein the ability of in vitro CRISPR/CAS9-mediated editing of the canine adenovirus type 2 (CAV2) genome to promote targeted modification of the viral genome was assessed. To demonstrate the feasibility of this goal, CRISPR/Cas9 has been used to successfully insert the RFP (red fluorescent protein) reporter construct into the CAV2 genome. Initial results demonstrated high efficiency and accuracy for in vitro CRISPR-mediated editing of the large CAV2 genome. Furthermore, this application was expanded, using multiple guide RNAs, to conduct gene replacement in the CAV2 genome by substituting a portion of the E3 gene with a construct designed to express a single chain antibody to canine PD-1. Thus, this work provides a significantly improved and efficient method for targeted editing of adenoviruses to generate altered and potentially therapeutic viral genomes in the shortest possible time.

Brief Resilience Scale (BRS) Portuguese Version: validity and metrics for the older adult population.

OBJECTIVE: This study aims to analyze the psychometric properties of the new Brazilian-Portuguese version of the Brief Resilience Scale (B-BRS) in older adults. METHOD: A sample of 1251 participants (54.20% women; M = 68.02 years, SD = 6.52) completed the B-BRS and seven scales on successful aging and mental health. Confirmatory factor analysis was used to study the B-BRS dimensionality. Convergent and divergent validity was analyzed by means of examining the relationships of B-BRS with scales on successful aging and mental health. RESULTS: The results supported the unidimensionality of the B-BRS after controlling for wording method, as well as satisfactory reliability (ω = .79). B-BRS structure remained invariant across education level and income groups. B-BRS scores positively correlated with successful aging factors and negatively with psychopathology symptoms. CONCLUSION: To conclude, our findings provide some evidence on the reliability and validity of the B-BRS, as well as its validation for use in the senior population.

Mindfulness and Meditative Movement Interventions for Men Living With Cancer: A Meta-analysis.

BACKGROUND: Mindfulness-based interventions, Tai Chi/Qigong, and Yoga (defined here as meditative cancer interventions [MCIs]) have demonstrated small to medium effects on psychosocial outcomes in female breast cancer patients. However, no summary exists of how effective these interventions are for men with cancer. PURPOSE: A meta-analysis was performed to determine the effectiveness of MCIs on psychosocial outcomes (e.g., quality of life, depression, and posttraumatic growth) for men with cancer. METHODS: A literature search yielded 17 randomized controlled trials (N = 666) meeting study inclusion criteria. The authors were contacted to request data for male participants in the study when not reported. RESULTS: With the removal of one outlier, there was a small effect found in favor of MCIs across all psychosocial outcomes immediately postintervention (g = .23, 95% confidence interval [CI] 0.02 to 0.44). Studies using a usual care control arm demonstrated a small effect in favor of MCIs (g = .26, 95% CI 0.10 to 0.42). However, there was insufficient evidence of a superior effect for MCIs when compared to an active control group, including attention control. Few studies examined both short-term and long-term outcomes. CONCLUSIONS: There is evidence for MCIs improving psychosocial outcomes in male cancer survivors. However, this effect is not demonstrated when limited to studies that used active controls. The effect size found in this meta-analysis is smaller than those reported in MCI studies of mixed gender and female cancer patient populations. More rigorously designed randomized trials are needed that include active control groups, which control for attention, and long-term follow-up. There may be unique challenges for addressing the psychosocial needs of male cancer patients that future interventions should consider.

Hope-related goal cognitions and daily experiences of fatigue, pain, and functional concern among lung cancer patients.

PURPOSE: Cross-sectional research suggests that thinking about multiple ways to reach goals (hope pathways) and the belief that one can reach them (hope agency) may be adaptive for lung cancer patients. We examined the between-person and within-person associations among aspects of hope agency and pathways thinking, daily fatigue, pain, and functional concerns (e.g., sense of independence, usefulness) among lung cancer patients during active treatment. METHODS: Data from a daily diary study were used to examine relations among hope agency, hope pathways, fatigue, pain, and functional concern in 50 patients with advanced lung cancer. Participants were accrued from one outpatient cancer center and completed the study between 2014 and 2015. RESULTS: Adjusting for covariates and the previous day's symptoms or concern, patients who engaged in higher pathways thinking reported lower daily symptoms, whereas those who engaged in higher agency thinking reported less functional concern. Within-person increases in pathways thinking were associated with less daily fatigue, pain, and functional concern; within-person increases in agency thinking were associated with less daily fatigue and pain. Models examining symptoms and concerns as predictors of hope suggested within-person increases in functional concern and fatigue and pain were related to lower agency and pathways thinking the same day. Patients with higher fatigue and pain did not report lower agency or pathways thinking, but patients with more functional concern did. CONCLUSIONS: Increases in hope pathways thinking may be associated with lower symptoms and better functioning in lung cancer patients. This suggests that it is important to determine the efficacy of interventions that emphasize the pathways the component of hope.

Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation.

Cognitive deficits are commonly reported by patients following treatment with chemotherapeutic agents. Anthracycline-containing chemotherapy regimens are associated with cognitive impairment and reductions in neuronal connectivity in cancer survivors, and doxorubicin (Dox) is a commonly used anthracycline. Although it has been reported that Dox distribution to the central nervous system (CNS) is limited, considerable Dox concentrations are observed in the brain with co-administration of certain medications. Additionally, pro-inflammatory cytokines, which are overproduced in cancer or in response to chemotherapy, can reduce the integrity of the blood-brain barrier (BBB). Therefore, the aim of this study was to evaluate the acute neurotoxic effects of Dox on hippocampal neurons. In this study, we utilized a hippocampal cell line (H19-7/IGF-IR) along with rodent hippocampal slices to evaluate the acute neurotoxic effects of Dox. Hippocampal slices were used to measure long-term potentiation (LTP), and expression of proteins was determined by immunoblotting. Cellular assays for mitochondrial complex activity and lipid peroxidation were also utilized. We observed reduction in LTP in hippocampal slices with Dox. In addition, lipid peroxidation was increased as measured by thiobarbituric acid reactive substances content indicating oxidative stress. Caspase-3 expression was increased indicating an increased propensity for cell death. Finally, the phosphorylation of signaling molecules which modulate LTP including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt were increased. This data indicates that acute Dox exposure dose-dependently impairs synaptic processes associated with hippocampal neurotransmission, induces apoptosis, and increases lipid peroxidation leading to neurotoxicity.

A Randomized Controlled Trial of the Safety and Immunogenicity of Tetanus, Diphtheria, and Acellular Pertussis Vaccine Immunization During Pregnancy and Subsequent Infant Immune Response.

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.

Risk of seizures after immunization in children with epilepsy: a risk interval analysis.

BACKGROUND: In children with epilepsy, fever and infection can trigger seizures. Immunization can also induce inflammation and fever, which could theoretically trigger a seizure. The risk of seizure after immunization in children with pre-existing epilepsy is not known. The study objective was to determine the risk of medically attended seizure after immunization in children with epilepsy < 7 years of age. METHODS: We conducted a retrospective study of children < 7 years of age with epilepsy in Nova Scotia, Canada from 2010 to 2014. Hospitalizations, emergency visits, unscheduled clinic visits, and telephone calls for seizures were extracted from medical records. Immunization records were obtained from family physicians and Public Health with informed consent. We conducted a risk interval analysis to estimate the relative risk (RR) of seizure during risk periods 0-14, 0-2, and 5-14 days post-immunization versus a control period 21-83 days post-immunization. RESULTS: There were 302 children with epilepsy who were eligible for the study. Immunization records were retrieved on 147 patients (49%), of whom 80 (54%) had one or more immunizations between the epilepsy diagnosis date and age 7 years. These 80 children had 161 immunization visits and 197 medically attended seizures. Children with immunizations had more seizures than either those with no immunizations or those with no records (mean 2.5 versus 0.7 versus 0.9, p < 0.001). The risk of medically attended seizure was not increased 0-14 days after any vaccine (RR = 1.1, 95% confidence interval (CI): 0.5-2.8) or 0-2 days after inactivated vaccines (RR = 0.9, 95% CI: 0.1-7.1) versus 21-83 days post-immunization. No seizure events occurred 5-14 days after live vaccines. CONCLUSIONS: Children with epilepsy do not appear to be at increased risk of medically attended seizure following immunization. These findings suggest that immunization is safe in children with epilepsy, with benefits outweighing risks.

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication.

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops' progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval.

Transoceanic drift and the domestication of African bottle gourds in the Americas.

Bottle gourd (Lagenaria siceraria) was one of the first domesticated plants, and the only one with a global distribution during pre-Columbian times. Although native to Africa, bottle gourd was in use by humans in east Asia, possibly as early as 11,000 y ago (BP) and in the Americas by 10,000 BP. Despite its utilitarian importance to diverse human populations, it remains unresolved how the bottle gourd came to be so widely distributed, and in particular how and when it arrived in the New World. A previous study using ancient DNA concluded that Paleoindians transported already domesticated gourds to the Americas from Asia when colonizing the New World [Erickson et al. (2005) Proc Natl Acad Sci USA 102(51):18315-18320]. However, this scenario requires the propagation of tropical-adapted bottle gourds across the Arctic. Here, we isolate 86,000 base pairs of plastid DNA from a geographically broad sample of archaeological and living bottle gourds. In contrast to the earlier results, we find that all pre-Columbian bottle gourds are most closely related to African gourds, not Asian gourds. Ocean-current drift modeling shows that wild African gourds could have simply floated across the Atlantic during the Late Pleistocene. Once they arrived in the New World, naturalized gourd populations likely became established in the Neotropics via dispersal by megafaunal mammals. These wild populations were domesticated in several distinct New World locales, most likely near established centers of food crop domestication.

Incisional Hernia After Peritoneal Dialysis Catheter Placement in a Patient on Sirolimus.

Hernias and peritoneal dialysis (PD) catheter leaks are frequent complications in patients on PD. Transplant recipients have multiple risk factors for delayed wound healing, such as use of corticosteroids and sirolimus, and the presence of uremia and diabetes mellitus. We report a rare occurrence of incisional hernia attributable to internal wound dehiscence after PD catheter placement in a patient on sirolimus.A 34-year-old Latino American man was started on PD training 4 weeks after placement of a PD catheter. Soon after completing training, he developed a large soft bulge close to the PD catheter, with expansile cough impulse suggestive of an incisional hernia filled with peritoneal dialysate. The size of the bulge would decrease after the dialysate was drained. No external leak of dialysate was evident along the exit site.Because of the size of the hernia and the history of it filling soon after dialysis exchange, the feeling was that wound dehiscence had occurred from the peritoneal side, resulting in a large incisional hernia. Because of the large size of the hernia within few weeks of starting PD, sirolimus was suspected to have induced poor wound healing, contributing to formation of the hernia.Sirolimus was stopped, and the patient underwent PD catheter removal and repair of the hernia. A new PD catheter was placed on the opposite side of the abdomen 10 days later. After another 6 weeks, the patient was started on PD. He has been doing well for the 15 months since then, with no recurrence of the hernia. Because he still had residual renal function, he continued to receive low-dose prednisone and mycophenolate sodium. At 10 months after PD start, he stopped the mycophenolate sodium on his own, and we did not resume it. He is still on low-dose prednisone.In end-stage renal disease resulting from failing renal transplantation or from calcineurin inhibitor nephropathy in solid-organ transplantation, sirolimus is a risk factor for wound dehiscence, development of incisional hernia, and peritoneal dialysate leak.Practical tips: Sirolimus should be stopped several days before PD catheter placement. Sirolimus should also be stopped if a PD catheter leak is detected or if incisional hernia develops soon after initiation of PD. Sirolimus should be held till surgical repair of the hernia and removal and replacement of the catheter.

Assessment Intervention Using the Rey-Osterrieth Complex Figure Test: A Clinical Illustration.

Therapeutic assessment (TA) aims to affect change in a client, in part, through an in vivo intervention using any number of assessment methods during a planned assessment intervention session (AIS). To date, neuropsychological tests have not been widely used in AIS. We suggest that the Rey-Osterrieth Complex Figure Test (RCFT) can be a helpful tool, especially when the assessment questions pertain to cognitive functioning, owing to its complexity and the fact that it taps several different cognitive functions. To illustrate this, we present the case of Mr. B, a 45-year-old man with a childhood history of neglect and abuse who was struggling with mood and cognitive complaints in the context of identifying a satisfying career. His performance on the RCFT had illuminated his cognitive style, and an AIS was built around observing and changing his approach to problem solving in the context of a supportive relationship. Based on the intervention, he was able to reassess his narrative of cognitive dysfunction, address his problems in organization, and practice using another person for support in problem solving.

Poor versus rich children with epilepsy have the same clinical course and remission rates but a less favorable social outcome: A population-based study with 25 years of follow-up.

OBJECTIVE: To explore the influence of several estimates of family socioeconomic status on the long-term clinical course and social outcomes of children with epilepsy. METHODS: The Nova Scotia childhood epilepsy cohort is population based and includes all children in this Canadian province who developed epilepsy between 1977 and 1985. Eligible patients had ≥10 years of follow-up. Children with childhood absence epilepsy were excluded. Total family income at seizure onset was assessed at seizure onset and classified as "poor" (first quintile), "adequate" (second to third quintiles), and "well-off" (fourth to fifth quintiles). We also assessed parental education and home ownership. Social outcome was assessed in those with normal intelligence who were ≥18 years of age at the end of follow-up using a semistructured interview that explored eight adverse effects. RESULTS: Of 584 patients, 421 (72%) were included. Average follow-up was 26 ± 5.6 years. Overall 137 families (33%) had "poor" income, 159 (38%) had "adequate income," and 125 (30%) were "well-off." Terminal remission of epilepsy occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off (p = ns). Intractable epilepsy, status epilepticus, number of antiepileptic drugs (AEDs) used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Home ownership did not predict remission. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes including failure to graduate from high school, unemployment, personal poverty, inadvertent pregnancy, and psychiatric diagnoses. SIGNIFICANCE: In Nova Scotia with universal health care, coming from a poor or more affluent family does not seem to affect the clinical course or long-term seizure outcome of childhood epilepsy. Unfortunately children from poor families are less likely to have a good social outcome.

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs.

BACKGROUND: Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal. RESULTS: Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma. CONCLUSIONS: Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

Context Matters: Commentary on Papers by Aschieri, Chudzik, Evans, and Fantini.

This article discusses articles by Aschieri, Chudzik, Evans, and Fantini (this issue) that address cultural considerations in Therapeutic Assessment (TA). The importance of the cultural context in which a TA is conducted is highlighted. Among the themes highlighted are the conceptualization of psychology, and more specifically psychological assessment, as a culture in and of itself and the importance of shame (Aschieri), the way the cultural values influence the practice of assessment (Chudzik), the importance of understanding the meaning of one's experience within their culture (Evans), and the role of subcultural differences (Fantini). The role of culture is seen as an important variable across these articles that explore varied conceptualizations and influences on assessment psychology. Cultural sensitivity and responsivity is seen as a crucial factor in the avoidance of misalliances. The articles in this special section are viewed as important contributions to the TA literature and demonstrate how the TA paradigm can help assessors overcome potential cultural influences that could affect the benefit of a psychological assessment.

Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells.

Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR) and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate is generally poor due to chemoresistance. Here, we sought to determine whether stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant, respectively. SDA, at its non-toxic concentrations, significantly promoted the antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp) function. This was confirmed in HEK293 cells stably expressing P-gp as well as by increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its chemosensitizing concentrations did not affect the viability of healthy dog peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study identifies a novel dietary fatty acid that may be used as a dietary supplement in combination with chemotherapy to promote the antitumor efficacy of the chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma.