Increased Mortality in Patients Transferred to a Level 1 Trauma Center with Blunt and Penetrating Extremity Vascular Injuries.

BACKGROUND: Trauma care depends on a complex transfer system to ensure timely and adequate management at major trauma centers. Patient outcomes depend on the reliability of triage in local or community hospitals and access to tertiary or quaternary trauma institutions. Patients with polytrauma, extremity trauma, or vascular injuries require multidisciplinary management at trauma hospitals. Our study investigated outcomes in this population at a level one trauma center in San Bernardino County, the largest geographic county in the contiguous United States. METHODS: We conducted a retrospective review of all patients with extremity trauma who presented to a single level 1 trauma center over 10 years. The cohort was divided into following two groups: 1. transferred from another medical center for a higher level of care or 2. those who directly presented. Overall, 19,417 patients were identified, with 15,317 patients presenting directly and 3,830 patients transferred from an outside hospital. Extremity of vascular injuries was observed in 268 patients. Demographic data were ascertained, including the injury severity score, mechanism of injury, response level, arrival method, tertiary center emergency department disposition, and presence of vascular injury in the upper or lower extremities. Univariate and multivariate analyses were performed to assess patient mortality. RESULTS: A total of 268 patients with vascular injuries were analyzed, including 207 nontransferred and 61 transferred patients. In the univariate analysis, injury severity score means were compared at 11.4 in nontransferred patients versus 8.4 in transferred (P < 0.001), 50% of blunt injury in the nontransferred group, and 28% in the transferred group (P < 0.001); in-hospital mortality was 4% in nontransferred patients versus 28% in the transferred group (P < 0.001). Multivariate logistic regression demonstrated that mortality is 8 times more likely if a patient with vascular extremity injuries is transferred from an outside hospital. A 10% mortality rate was observed in patients without blood transfusion within 4 hr of arrival to the trauma center and 3% mortality in transferred patients transfused blood. CONCLUSIONS: Extremity trauma with vascular injury can be lethal if managed appropriately. Patients transferred to our level 1 trauma center had a substantial increase in mortality compared with nontransferred patients. Furthermore, the transfer distance was associated with increased mortality. Further research is required to address this vulnerable patient population.

The protein phosphatase-2A subunit PR130 is involved in the formation of cytotoxic protein aggregates in pancreatic ductal adenocarcinoma cells.

As a major source of cellular serine and threonine phosphatase activity, protein phosphatase-2A (PP2A) modulates signaling pathways in health and disease. PP2A complexes consist of catalytic, scaffolding, and B-type subunits. Seventeen PP2A B-type subunits direct PP2A complexes to selected substrates. It is ill-defined how PP2A B-type subunits determine the growth and drug responsiveness of tumor cells. Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis. We analyzed the responses of murine and human mesenchymal and epithelial PDAC cells to the specific PP2A inhibitor phendione. We assessed protein levels by immunoblot and proteomics and cell fate by flow cytometry, confocal microscopy, and genetic manipulation. We show that murine mesenchymal PDAC cells express significantly higher levels of the PP2A B-type subunit PR130 than epithelial PDAC cells. This overexpression of PR130 is associated with a dependency of such metastasis-prone cells on the catalytic activity of PP2A. Phendione induces apoptosis and an accumulation of cytotoxic protein aggregates in murine mesenchymal and human PDAC cells. These processes occur independently of the frequently mutated tumor suppressor p53. Proteomic analyses reveal that phendione upregulates the chaperone HSP70 in mesenchymal PDAC cells. Inhibition of HSP70 promotes phendione-induced apoptosis and phendione promotes a proteasomal degradation of PR130. Genetic elimination of PR130 sensitizes murine and human PDAC cells to phendione-induced apoptosis and protein aggregate formation. These data suggest that the PP2A-PR130 complex dephosphorylates and thereby prevents the aggregation of proteins in tumor cells.

A randomized controlled trial of a targeted support program for informal caregivers in adult psychiatry.

Background: The importance of informal caregivers for persons with severe mental illness has been demonstrated. However, this role may cause a high care burden that considerably affects caregiver health. The Ensemble program is a five-session brief individual intervention designed to support informal caregivers. This trial aimed to assess the efficacy of the program versus SAU (support as usual) for participants with a high care burden. Methods: A single-center randomized controlled trial including 149 participants was conducted. Caregivers in the intervention arm participated in the Ensemble program. The effects of the intervention were assessed using mixed models for repeated measures analysis of variance on improvements in informal caregivers' psychological health status, optimism levels, burden scores, and quality of life at three time points (T0 = pretest; T1 = posttest at 2 months, and T2 = follow-up at 4 months). Results: Analysis of the Global Psychological Index showed no significant effect at the two endpoints in favor of the Ensemble group. However, the Brief Symptom Inventory-Positive Symptom Distress Index was significantly lower at the two-month follow-up. A significant reduction in burden on the Zarit Burden Interview was observed post-intervention, along with an increase in optimism levels on the Life Orientation Test-Revised at follow-up in the Ensemble group. No significant differences were observed in quality of life. Clinical improvements in both psychological health status and burden levels were also identified. Conclusion: The Ensemble program offers an inclusive approach based on a recovery perspective that significantly reduces symptom distress and burden and increases optimism among informal caregivers.Clinical trial registration: https://clinicaltrials.gov/, NCT04020497.

The Impact of Computed Tomography Scans on the Management and Wait Times in Perianal Abscess Diagnoses.

Background Diagnosis and management of perianal abscesses (PAA) are based on history and clinical examination. Imaging is not indicated except in complicated cases, as determined by the surgical team. The monetary, ionizing radiation, and resource utilization costs of a computed tomography (CT) scan in the emergency room must be considered when used for diagnostic purposes of PAAs. Methods A retrospective analysis of 129 patients diagnosed with a diagnosis of PAA between 2015-2020 was performed. The primary endpoints included length of stay, CT performed, time from patient presentation to CT, and CT scan completion prior to surgical consultation. Data is reported as n (%) or median (IQR). Results Of the 129 patients diagnosed with PAA, 81 underwent CT, and 48 did not. General surgery was consulted in 88% of cases. There were no statistically significant differences in age (p=0.562), sex (p=0.531), or ethnicity (p=0.356). The median hospitalization time was two days when CT was performed (p=0.001). The median time elapsed from presentation to the emergency department and CT scan performed was 16 hours (p=0.001). CT scans were ordered before the surgical consultation in 65% of cases (p=0.001) and 17% after a surgical consultation was placed (p=0.009). Conclusion Performing CT scans prior to surgical evaluation for the diagnosis of PAA is not a responsible practice. The cost, resources, and radiation exposure must be considered. This study demonstrated that more CT scans are ordered prior to surgical consultation for PAA, resulting in a prolonged wait time in the emergency department.

Integration of a peer practitioner in a hospital unit for patients with psychotic disorders: an exploratory qualitative study.

Introduction: Studies on the integration of peer mental health practitioners (PMHP) in hospitals are sparse, despite significant benefits being reported for patients and professionals. The integration of PMHP requires the consideration of several parameters and a change in the culture of care. This study aims to understand the impact of the integration of a PMHP in a hospital unit caring for patients with psychiatric disorders. Methods: A qualitative content analysis of three focus groups with the interdisciplinarity team were conducted. A consulting PMHP was integrated into the entire research process. Results: Data analysis revealed five main themes: the importance of integration, benefits for patients linked to the identification process, benefits for the team and institution, potentials risks, and perspectives. Discussion: The study was conducted in a hospital setting with patients suffering from severe psychiatric disorders associated with behavioral disturbances. The benefits reported in the results outline the feasibility of PMHP integration in an acute psychiatric care setting. Nevertheless, further formalization of the PMHP role is required to minimize possible areas of tension between respective fields of activity of each professional.

Women involvement in the informal caregiving field: A perspective review.

The patient recovery process of individual with mental health disorder is reinforced if they are connected with their community and supported by relatives. The literature has shown that caregivers are important, although their roles can lead to alterations in their own health; and women are the most involved in this role. The present review investigated women's involvement in the informal caregiver scientific field. A literature review indicated gender differences; researchers who are women are more interested in this field than men. Even with a good representation of women in this scientific field, the results showed a statistically significant gender difference for the first and second authors, whereas there was no significant gender difference among the last authors. More efforts must be made to recognize the importance of women's involvement in research because they raise a specific important field. Family caregivers are key players in the healthcare system, but to date, there has been little recognition of their enormous contribution. Our results also indicated the informal caregiver role is filled more by women than by men, which creates social inequalities in many domains, especially in opportunities at the professional level. Tailored interventions are required to address the specific needs and issues of family caregivers. A better redistribution of unpaid work, such as informal caregiving, compared to paid work must be made to respect gender in social existence.

The epigenetic modifier HDAC2 and the checkpoint kinase ATM determine the responses of microsatellite instable colorectal cancer cells to 5-fluorouracil.

The epigenetic modifier histone deacetylase-2 (HDAC2) is frequently dysregulated in colon cancer cells. Microsatellite instability (MSI), an unfaithful replication of DNA at nucleotide repeats, occurs in about 15% of human colon tumors. MSI promotes a genetic frameshift and consequently a loss of HDAC2 in up to 43% of these tumors. We show that long-term and short-term cultures of colorectal cancers with MSI contain subpopulations of cells lacking HDAC2. These can be isolated as single cell-derived, proliferating populations. Xenografted patient-derived colon cancer tissues with MSI also show variable patterns of HDAC2 expression in mice. HDAC2-positive and HDAC2-negative RKO cells respond similarly to pharmacological inhibitors of the class I HDACs HDAC1/HDAC2/HDAC3. In contrast to this similarity, HDAC2-negative and HDAC2-positive RKO cells undergo differential cell cycle arrest and apoptosis induction in response to the frequently used chemotherapeutic 5-fluorouracil, which becomes incorporated into and damages RNA and DNA. 5-fluorouracil causes an enrichment of HDAC2-negative RKO cells in vitro and in a subset of primary colorectal tumors in mice. 5-fluorouracil induces the phosphorylation of KAP1, a target of the checkpoint kinase ataxia-telangiectasia mutated (ATM), stronger in HDAC2-negative cells than in their HDAC2-positive counterparts. Pharmacological inhibition of ATM sensitizes RKO cells to cytotoxic effects of 5-fluorouracil. These findings demonstrate that HDAC2 and ATM modulate the responses of colorectal cancer cells towards 5-FU.

Bronchopulmonary Fistula Development in an Elderly Male With COVID-19 Infection.

COVID-19 pneumonia can cause a wide range of complications including pneumothorax and empyema. However, in severe cases, it can lead to bronchopulmonary fistula (BPF) formation and a persistent air leak due to a connection between the pleural space and the bronchial tree. We report the case of a 77-year-old man with a history of hypertension, who presented to the emergency department for evaluation of dyspnea. Admission labs were significant for a positive rapid antigen SARS-Cov-2 test and elevated troponin I. A chest x-ray demonstrated patchy interstitial opacification and ground glass appearance bilaterally. Within the first 24 hours of presentation, the patient developed a right-sided spontaneous pneumothorax and had a 14 French pigtail catheter placed. The patient subsequently developed a persistent air leak after chest tube placement and required video-assisted thoracoscopic surgery (VATS) with talc pleurodesis and a 32 French chest tube placement. In this unique case, we describe an elderly patient's experience of bronchopulmonary fistula formation as a complication of COVID-19 pneumonia and the successful management of this complication with VATS.

Development of Early Abdominal Compartment Syndrome Leading to Emergent Decompressive Laparotomy in Full-Thickness Burn Injury.

Burn injuries carry an increased risk of intra-abdominal hypertension and are an independent risk factor for abdominal compartment syndrome (ACS). ACS is most commonly due to large volume resuscitation. The added concern of ACS can complicate resuscitative efforts. Early monitoring for ACS (intra-abdominal pressure > 20 mm Hg with associated new-onset organ dysfunction) and performing prudent decompressive laparotomies are important factors to keep in mind when treating large surface area burn patients. This case report describes the hospitalization of a 60-year-old male who presented with 45% full-thickness (FT) total body surface area (TBSA) and inhalation injury. On arrival to the emergency department (ED), he had received a total of 6 L of intravenous lactate Ringers, and vasopressors were initiated due to hypotension. During the tertiary examination it was noted that there was increased difficulty ventilating the patient, and his abdomen was becoming increasingly distended and tense. His intra-abdominal pressure was measured in the ED and found to be elevated at 32 mm Hg. The findings were suggestive of ACS and a decompressive laparotomy was performed in the ED. Upon entering the abdominal cavity, the abdominal contents extruded through the incision and diffuse venous congestion and gastric distention were noted. Items commonly found in operating rooms (Top-Draper® warmer drape, Kerlix rolls, Jackson-Pratt suction drains, and 3M® Ioban sterile antimicrobial incise drape) were utilized to maintain an open abdomen where abdominal contents could easily be observed and to prevent delay in performing a decompressive laparotomy. Here we describe a patient with 45% FT TBSA and inhalation injuries requiring an emergent decompressive laparotomy for ACS after only 6 L of lactate Ringers were administered. This highlights the importance of early monitoring for ACS and the ease of performing a decompressive laparotomy with commonly found items in the ED and operating rooms.

An Evaluation of an Online Training Platform for Teaching Positive Emotions for People With Schizophrenia.

BACKGROUND: The dissemination of new interventions in clinical practice remains challenging. E-learning may provide wide access in various settings and allow tailored learning trajectories and an adapted training pace. This study evaluates an online platform to train professionals to lead the Positive Emotion Program for Schizophrenia (PEPS) for patients with anhedonia. This study aims to test the reception provided by clinicians to the platform and its perceived usefulness and investigate whether e-PEPS training improves knowledge about the facilitation of PEPS. MATERIALS AND METHODS: Participants were recruited through advertisements. All participants provided their informed consent on a registration form and completed two pre-test questionnaires, a knowledge test on negative symptoms in schizophrenia, learning strategies and the partnership relationship, and a test on the ability to savor pleasant moments. After the training, they completed the same questionnaire and an evaluation form of the training and its application in personal and professional life. RESULTS: Two-hundred and ten participants were registered to participate into the study, 185 received the access to the platform, and 101 participants completed the training and the post-test assessments. Satisfaction with training was high. The results showed that the participants significantly improved their knowledge about PEPS and increased the skills taught in their personal repertoire after the training. The training allows most clinicians to plan to lead a PEPS group in the year following training. DISCUSSION: As a result of this study, training has been improved and is now freely available to all interested clinicians.

Class 1 Histone Deacetylases and Ataxia-Telangiectasia Mutated Kinase Control the Survival of Murine Pancreatic Cancer Cells upon dNTP Depletion.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a dismal prognosis. Here, we show how an inhibition of de novo dNTP synthesis by the ribonucleotide reductase (RNR) inhibitor hydroxyurea and an inhibition of epigenetic modifiers of the histone deacetylase (HDAC) family affect short-term cultured primary murine PDAC cells. We used clinically relevant doses of hydroxyurea and the class 1 HDAC inhibitor entinostat. We analyzed the cells by flow cytometry and immunoblot. Regarding the induction of apoptosis and DNA replication stress, hydroxyurea and the novel RNR inhibitor COH29 are superior to the topoisomerase-1 inhibitor irinotecan which is used to treat PDAC. Entinostat promotes the induction of DNA replication stress by hydroxyurea. This is associated with an increase in the PP2A subunit PR130/PPP2R3A and a reduction of the ribonucleotide reductase subunit RRM2 and the DNA repair protein RAD51. We further show that class 1 HDAC activity promotes the hydroxyurea-induced activation of the checkpoint kinase ataxia-telangiectasia mutated (ATM). Unlike in other cell systems, ATM is pro-apoptotic in hydroxyurea-treated murine PDAC cells. These data reveal novel insights into a cytotoxic, ATM-regulated, and HDAC-dependent replication stress program in PDAC cells.

Age-dependent integrity of the meiotic spindle assembly checkpoint in females requires Aurora kinase B.

A hallmark of advanced maternal age is a significant increase in meiotic chromosome segregation errors, resulting in early miscarriages and congenital disorders. These errors most frequently occur during meiosis I (MI). The spindle assembly checkpoint (SAC) prevents chromosome segregation errors by arresting the cell cycle until proper chromosome alignment is achieved. Unlike in mitosis, the SAC in oocytes is desensitized, allowing chromosome segregation in the presence of improperly aligned chromosomes. Whether SAC integrity further deteriorates with advancing maternal age, and if this decline contributes to increased segregation errors remains a fundamental question. In somatic cells, activation of the SAC depends upon Aurora kinase B (AURKB), which functions to monitor kinetochore-microtubule attachments and recruit SAC regulator proteins. In mice, oocyte-specific deletion of AURKB (Aurkb cKO) results in an increased production of aneuploid metaphase II-arrested eggs and premature age-related infertility. Here, we aimed to understand the cause of the short reproductive lifespan and hypothesized that SAC integrity was compromised. In comparing oocytes from young and sexually mature Aurkb cKO females, we found that SAC integrity becomes compromised rapidly with maternal age. We show that the increased desensitization of the SAC is driven by reduced expression of MAD2, ZW10 and Securin proteins, key contributors to the SAC response pathway. The reduced expression of these proteins is the result of altered protein homeostasis, likely caused by the accumulation of reactive oxygen species. Taken together, our results demonstrate a novel function for AURKB in preserving the female reproductive lifespan possibly by protecting oocytes from oxidative stress.

Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives.

With the prevalence of eye diseases, such as cataracts, retinal degenerative diseases, and glaucoma, different treatments including lens replacement, vitrectomy, and stem cell transplantation have been developed; however, they are not without their respective shortcomings. For example, current methods to seal corneal incisions induced by cataract surgery, such as suturing and stromal hydration, are less than ideal due to the potential for surgically induced astigmatism or wound leakage. Vitrectomy performed on patients with diabetic retinopathy requires an artificial vitreous substitute, with current offerings having many shortcomings such as retinal toxicity. The use of stem cells has also been investigated in retinal degenerative diseases; however, an optimal delivery system is required for successful transplantation. The incorporation of hydrogels into ocular therapy has been a critical focus in overcoming the limitations of current treatments. Previous reviews have extensively documented the use of hydrogels in drug delivery; thus, the goal of this review is to discuss recent advances in hydrogel technology in surgical applications, including dendrimer and gelatin-based hydrogels for ocular adhesives and a variety of different polymers for vitreous substitutes, as well as recent advances in hydrogel-based retinal pigment epithelium (RPE) and retinal progenitor cell (RPC) delivery to the retina.

Oxaliplatin-Induced Senescence in Colorectal Cancer Cells Depends on p14ARF-Mediated Sustained p53 Activation.

Senescence is an important consequence of cytostatic drug-based tumor therapy. Here we analyzed to which degree the anticancer drug oxaliplatin induces cell death, cell cycle arrest, and senescence in colorectal cancer (CRC) cells and elucidated the role of p53. Oxaliplatin treatment resulted in the G2-phase arrest in all CRC lines tested (HCT116p53+/+, HCT116p53-/-, LoVo, SW48 and SW480). Immunoblot analysis showed that within the p53-competent lines p53 and p21CIP1 are activated at early times upon oxaliplatin treatment. However, at later times, only LoVo cells showed sustained activation of the p53/p21CIP1 pathway, accompanied by a strong induction of senescence as measured by senescence-associated ß-Gal staining and induction of senescence-associated secretory phenotype (SASP) factors. Opposite to LoVo, the p53/p21CIP1 response and senescence induction was much weaker in the p53-proficient SW48 and SW480 cells, which was due to deficiency for p14ARF. Thus, among lines studied only LoVo express p14ARF protein and siRNA-mediated knockdown of p14ARF significantly reduced sustained p53/p21CIP1 activation and senescence. Vice versa, ectopic p14ARF expression enhanced oxaliplatin-induced senescence in SW48 and SW480 cells. Our data show that oxaliplatin-induced senescence in CRC cells is dependent on p53 proficiency; however, a significant induction can only be observed upon p14ARF-mediated p53 stabilization.

Differential requirements for the CENP-O complex reveal parallel PLK1 kinetochore recruitment pathways.

Similar to other core biological processes, the vast majority of cell division components are essential for viability across human cell lines. However, recent genome-wide screens have identified a number of proteins that exhibit cell line-specific essentiality. Defining the behaviors of these proteins is critical to our understanding of complex biological processes. Here, we harness differential essentiality to reveal the contributions of the four-subunit centromere-localized CENP-O complex, whose precise function has been difficult to define. Our results support a model in which the CENP-O complex and BUB1 act in parallel pathways to recruit a threshold level of PLK1 to mitotic kinetochores, ensuring accurate chromosome segregation. We demonstrate that targeted changes to either pathway sensitizes cells to the loss of the other component, resulting in cell-state dependent requirements. This approach also highlights the advantage of comparing phenotypes across diverse cell lines to define critical functional contributions and behaviors that could be exploited for the targeted treatment of disease.

Trends in pneumonectomy for treatment of small-cell lung cancer.

BACKGROUND: According to practice guidelines, patients with clinical stage T1-2 node-negative small-cell lung cancer are candidates for surgical resection. However, the role of pneumonectomy in small-cell lung cancer patients is not well understood. The objective of this study was to assess the extent to which pneumonectomy is used and to evaluate the survival implications for small-cell lung cancer patients who underwent pneumonectomy. METHODS: A total of 106 small-cell lung cancer patients who underwent pneumonectomy between 2006 and 2016 and met the study criteria were identified in the National Cancer Database. Demographics and treatment regimens are described, and overall survival was assessed using Kaplan-Meier and log-rank tests. RESULTS: The most common treatment was surgery with adjuvant chemotherapy, followed by surgery only and surgery with neoadjuvant therapy. The 5-year overall survival for the entire cohort after pneumonectomy was 23%. In subgroup analysis, the 5-year overall survival was 30% for guideline-concordant clinical stage I patients and 28% for clinical stage II/III patients who underwent pneumonectomy. There was no statistical difference in survival according to pathologic N disease. Patients with a right-sided pneumonectomy had higher mortality than patients with a left-sided pneumonectomy. CONCLUSIONS: This study suggests a role for pneumonectomy in clinical stage I and potentially some clinical stage II and III small-cell lung cancer patients. Right-sided pneumonectomy is associated with higher mortality and should be approached with caution. Despite declining trends over the past decades, pneumonectomy is still an effective treatment that is able to achieve acceptable survival outcomes.

Impact of Positive Emotion Regulation Training on Negative Symptoms and Social Functioning in Schizophrenia: A Field Test.

Background: The poor efficacy of drug or psychological treatments on the primary negative symptoms of schizophrenia has led to the development of new interventions. The Positive Emotions Program for Schizophrenia (PEPS) is an emotion regulation strategy training that aims to intensify positive emotions and develop positive performance beliefs. A randomized controlled trial showed that PEPS is effective in reducing the composite score of the reduction of experience syndrome (anhedonia and apathy). The present study is designed to evaluate its feasibility in natural conditions to measure external validity of PEPS. Materials and Methods: Twenty-one participants recruited through the French national network of expert centers followed eight sessions of PEPS and were assessed pre- and posttest with the Scale for Assessment of Negative Symptoms (SANS) and the Personal and Social Performance (PSP). The scales of the SANS were divided into a composite score of the reduction of the ability to experience and a composite score of the reduction of expression. Results: All participants followed the 8 sessions of PEPS, and both composite scores were significantly and clinically improved at posttest. Social functioning assessed with the PSP was also improved. Conclusions: This field test shows that participation in PEPS is accompanied by a reduction of negative symptoms and an improvement of social functioning. Both negative syndromes, reduction of expression and reduction of experience, are improved. Participants are younger than those in previous studies, which may explain this unexpected result. However, this calls for a controlled study with younger participants.

The relationship between self-stigma and depression among people with schizophrenia-spectrum disorders: A longitudinal study.

Harmful consequences of self-stigma in schizophrenia are well established in the literature, but its relationship with symptomatology remains unclear. Self-stigma describes the process by which some patients eventually accept, adhere to and apply to themselves the stereotypes associated with schizophrenia. This study aims to describe self-stigma experienced by people with schizophrenia in French-speaking Switzerland and to examine the relationship between self-stigma and depression. This was a longitudinal study including 80 participants. Correlation and regression analyses were used to examine the relationship between self-stigma and depression over three points of time. Correlations between Stigma Scale subdimensions and sociodemographic variables indicated that age and duration of illness were associated with the discrimination subscale. Self-stigma was strongly correlated with depression over time, whereby higher scores of self-stigma were associated with higher depression. More precisely, the more the patient felt discriminated against and the less he or she perceived the positive aspects of his or her illness, the greater the symptoms of depression. This study highlights the severity of self-stigma endorsed by people with schizophrenia in French-speaking Switzerland. The results provide new knowledge about self-stigma and its potential impact on depressive symptoms. Implementation of self-stigma assessment in clinical practice will allow distinctions to be made between the impact of self-stigma and the consequences of schizophrenia to recommend appropriate intervention.

Improving Pleasure and Motivation in Schizophrenia: A Randomized Controlled Clinical Trial.

BACKGROUND: Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU. METHODS: Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2). RESULTS: The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up. CONCLUSIONS: PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).

Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis.

Errors in chromosome segregation during female meiosis I occur frequently, and aneuploid embryos account for 1/3 of all miscarriages in humans [1]. Unlike mitotic cells that require two Aurora kinase (AURK) homologs to help prevent aneuploidy (AURKA and AURKB), mammalian germ cells also require a third (AURKC) [2, 3]. AURKA is the spindle-pole-associated homolog, and AURKB/C are the chromosome-localized homologs. In mitosis, AURKB has essential roles as the catalytic subunit of the chromosomal passenger complex (CPC), regulating chromosome alignment, kinetochore-microtubule attachments, cohesion, the spindle assembly checkpoint, and cytokinesis [4, 5]. In mouse oocyte meiosis, AURKC takes over as the predominant CPC kinase [6], although the requirement for AURKB remains elusive [7]. In the absence of AURKC, AURKB compensates, making defining potential non-overlapping functions difficult [6, 8]. To investigate the role(s) of AURKB and AURKC in oocytes, we analyzed oocyte-specific Aurkb and Aurkc single- and double-knockout (KO) mice. Surprisingly, we find that double KO female mice are fertile. We demonstrate that, in the absence of AURKC, AURKA localizes to chromosomes in a CPC-dependent manner. These data suggest that AURKC prevents AURKA from localizing to chromosomes by competing for CPC binding. This competition is important for adequate spindle length to support meiosis I. We also describe a unique requirement for AURKB to negatively regulate AURKC to prevent aneuploidy. Together, our work reveals oocyte-specific roles for the AURKs in regulating each other's localization and activity. This inter-kinase regulation is critical to support wild-type levels of fecundity in female mice.