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Although highly active antiretroviral therapy has improved the clinical course of patients with HIV, this population remains at a significantly increased risk for non-Hodgkin's lymphoma (NHL). Spinal cord compression is a rare presentation of NHL, regardless of the patient population. We encountered a patient with HIV-related NHL who presented with a thoracic spinal cord compression and had a complicated clinical course as a result of the atypical presentation. [ABSTRACT FROM AUTHOR]

Severe pain is highly prevalent, with rates of 40% to 70% in patients with advanced cancer, liver disease, heart failure, human immunodeficiency virus, and renal failure. Wide variations in pain assessment and reporting methods and the measurement of multiple symptoms should be addressed in future studies. Regarding psychological approaches, determining whether hypnotherapy or other individual psychotherapeutic interventions reduce pain and/or psychological distress in a palliative care population is difficult. Interest is increasing in the concept of demoralization syndromes and the role of posttraumatic stress disorder in modulating responses to pain at the end of life. We review evidence from multiple studies that the use of rehabilitative therapy improves functional status and pain control among patients with advanced cancer, and we raise the possibility that rehabilitation therapy will be helpful in patients with other advanced diseases. We summarize ongoing clinical trials of electronic order sets, clinical care pathways, and care management pathways to improve pain management in palliative care. Wagner's Chronic Illness Model provides a way of analyzing how healthcare systems can be changed to provide adequate and continuing pain management in palliative care. Much work remains to ensure that pain is recognized, treated, and monitored effectively. [ABSTRACT FROM AUTHOR]

The assessment and treatment of pain in persons with cognitive impairments pose unique challenges. Disorders affecting cognition include neurodegenerative, vascular, toxic, anoxic, and infectious processes. Persons with memory, language, and speech deficits and consciousness alterations are often unable to communicate clearly about their pain and discomfort. Past research has documented that persons with cognitive impairments, particularly dementia, are less likely to ask for and receive analgesics. This article provides an overview of the assessment, treatment, and management of pain in adults with cognitive impairments. We review types of cognitive impairment; recent work specific to best practices for pain management in patients with dementia, including assessment-tool development and pharmacological treatment; challenges in patients with delirium and in medical intensive care and palliative care settings; and directions for future research. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify independent predictors of clinically significant fatigue based upon a multidimensional model. A total of 180 cancer patients completed the Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), Memorial Symptom Assessment Scale Short Form (MSAS-SF), and the Zung Self-Rating Depression Scale (SDS). Additional data included Karnofsky Performance Status (KPS) score, laboratory tests, and demographic information. The BFI usual fatigue severity > or =3/10 was defined as clinically significant fatigue. Possible independent variables were identified from a biopsychosocial model of fatigue. Fisher's exact test was used to univariately assess the association of each variable with clinically significant fatigue. Multiple logistic regression analyses were used to identify independent predictors of fatigue within each dimension, and then across dimensions. Fatigue was present in 113 (62%) patients, and 80 (44.4%) patients had usual fatigue > or =3/10. The unidimensional independent predictors were use of analgesics (situation dimension); hemoglobin and serum sodium (biomedical dimension); feeling drowsy, dyspnea, pain and lack of appetite (physical symptom dimension); and feeling sad and feeling irritable (psychological symptom dimension). In a multidimensional model, dyspnea, pain, lack of appetite, feeling drowsy, feeling sad, and feeling irritable predicted fatigue independently with good calibration (Hosmer Lemeshow Chi Square=5.73, P=0.68) and discrimination (area under the receiver operating characteristic curve=0.88). Physical and psychological symptoms predict fatigue independently in the multidimensional model, and superseded laboratory data. These findings support a symptom-oriented approach to assessment of cancer-related fatigue. [ABSTRACT FROM AUTHOR]

To document quality-of-life (QOL), symptom distress and Karnofsky Performance Status (KPS) over time, 67 advanced cancer patients completed the Functional Assessment of Cancer Therapy (FACT-G) and Memorial Symptom Assessment Scale - Short Form (MSAS-SF) from the time of determination of no active anti-cancer treatment to death at 3-6 week intervals. The KPS was determined at each time point. Statistical analyses with mixed effects models were performed to examine the association between changes in QOL, symptom distress and KPS at selected time points in the advanced cancer trajectory. Median survival for the population was 115 days, and a median of 5 interviews was completed per patient. Slow steady changes in KPS, MSAS-SF and FACT-G QOL parameters started 6 months prior to death, with accelerated decline in the last 2 to 3 months and dramatic increase in psychological symptoms during the last month. Different domains changed at different rates at different selected time points. The correlation between changes in KPS, FACT-G parameters and MSAS-SF subscales at enrollment and near death suggests that when patients were stable, changes in KPS correlated significantly with changes in sum FACT-G QOL and physical well being, and with changes in the MSAS-SF subscales. However, when patients were near death, changes in KPS did not correlate with any other changes, and only emotional well being reflected changes in physical and psychological symptom distress. The sequence of changes, and how determinants of symptom distress and QOL change over time, may help clinicians assess the prognosis of terminally ill patients and plan appropriate interventions. [ABSTRACT FROM AUTHOR]

We measured pain outcomes in a cohort of patients with cancer pain in a general hematology/oncology setting at a Veterans Administration Medical center (VA). The outcomes included pain relief, pain severity, changes in pain severity, interference scores, symptom distress, quality of life (QOL), and satisfaction. Seventy-four (74) consecutive patients with worst cancer-related pain equal to or greater than 4/10 were recruited. Cancer pain diagnoses were made and the cancer pain management guidelines of the United States Agency for Health Care Policy and Research were followed. Patients were followed weekly using the Brief Pain Inventory (BPI), medication diary, satisfaction questionnaire, visual analogue quality of life scale (VASQOL) and record of side effects for 3 weeks. The Functional Assessment of Cancer Therapy (FACT-G) and Memorial Symptom Assessment Scale Short Form (MSAS-SF) were used at initial and final interviews. The mean initial worst pain severity was 8.3 (range 4-10) and mean pain relief was 40% (range 0-100). By week 1, the majority of patients achieved pain relief of >/=80%, with a corresponding decrease in worst pain severity and pain interference scores. Pain continued to decrease over three weeks. At week 3, there was a significant improvement in the MSAS-SF psychological symptom distress subscale (P = 0.02). The average number of opioid-related side effects was 5 and remained steady over time. Most patients felt "quite a bit" or "very much" satisfied at all weeks. There was a significant improvement in VASQOL (P < 0.005) and in FACTG SUMQOL scores (P = 0.007). This experience demonstrates that cancer pain management can result in measurable and significant changes in pain relief, pain severity, pain interference scores, psychological symptom distress, and QOL scores. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a Cancer Pain Prognostic Scale (CPPS) which could predict the likelihood of pain relief within 2 weeks for cancer patients with moderate to severe pain. Seventy-four (74) consecutive patients who presented with cancer-related pain were managed in accordance with the guidelines for pain management developed by the United States Agency for Health Care Policy and Research (AHCPR). Patients were followed weekly using the Brief Pain Inventory (BPI), and medications were recorded weekly for 3 weeks. Baseline scores from the Functional Assessment of Cancer Therapy (FACT-G), Mental Health Inventory (MHI), Karnofsky Performance Status (KPS), and Memorial Symptom Assessment Scale Short Form (MSAS-SF) at initial interview served as explanatory variables in a logistic regression model. Pain relief > or = 80% at the end of weeks 1 and 2 were used as outcomes in this model. From this analysis, we developed a predictive formula, the CPPS, which includes the worst pain severity, FACT-G emotional well being, daily opioid dose, and pain characteristics. The rule yields a numerical score that ranges from 0-17. Higher scores correspond to a higher probability of good pain relief. The CPPS has the potential to rapidly identify patients with poor pain prognosis. It can be used as a research tool to characterize pain in cancer patients. [ABSTRACT FROM AUTHOR]

To examine the relationship between different cancer pain management outcomes over time, 74 patients with the worst cancer related pain rated as four or greater on an 11-point numeric scale were followed weekly with the Brief Pain Inventory (BPI), and the satisfaction questionnaire and global visual analogue scale quality of life (VASQOL) for 3 weeks. Univariate and multivariate regression analyses were performed at weekly time points. The analyses indicated that pain outcomes can be categorized into separate QOL and satisfaction paths linked by the worst pain severity. In the QOL path, the worst pain severity predicted a pain interference score, which consistently predicted VASQOL. For the satisfaction path, independent predictors were pain relief at Week 1, and worst pain severity and changes in worst pain severity at Week 2. No variables predicted satisfaction at Week 3. The data suggest that satisfaction and quality of life may be independent outcomes of pain management. The timing of assessment may itself be important. [ABSTRACT FROM AUTHOR]

There are very few symptom assessment instruments in Chinese. We present the validity and reliability of the Memorial Symptom Assessment Scale Short Form (MSAS-SF) and the Condensed Form MSAS (CMSAS) in Chinese cancer patients. The Chinese version of the 32-item MSAS-SF, a self-report measure for assessing symptom distress and frequency in cancer patients, was administered to 256 Chinese patients with colorectal cancer at a clinical oncology outpatient unit. Highly prevalent symptoms included worrying (59%), dry mouth (54%), lack of energy (54%), feeling sad (48%), feeling irritable (48%), and pain (41%). Both the MSAS-SF and CMSAS demonstrated good validity and reliability. For the MSAS-SF subscales, Cronbach alphas ranged from 0.84 to 0.91, and for CMSAS subscales, from 0.79 to 0.87. Moderate-to-high correlations of MSAS-SF and CMSAS subscales with appropriate European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 subscales (0.42-0.71, Ps<0.001) indicated acceptable convergent validity. Low correlations with the Rosenberg Self-Esteem and Optimism Scale (0.22, P<0.001) indicated divergent validity. MSAS subscales varied as expected with other Chinese scales--the Chinese Health Questionnaire (CHQ) and the Life Orientation Scale. Construct validity of both MSAS versions was demonstrated by effective differentiation between clinically distinct patient groups (Karnofsky scores <80% vs. > or =80% [P<0.001]; no active treatment vs. active treatment [P<0.002-0.034]; CHQ-12 scores < or =4 vs. CHQ-12 scores >4 [P<0.001]). The Number of Symptoms subscale correlated appropriately with the EORTC QLQ-C30 function (-0.46 to -0.60, P<0.001) and symptom scales (0.31-0.64, P<0.001). The average time to complete the MSAS-SF was six minutes. The Chinese versions of the MSAS-SF and CMSAS are valid and practical measures. Further validation is needed for Chinese patients with other cancer types and with other symptom instruments. Copyright © 2008 U.S. Cancer Pain Relief Committee. [ABSTRACT FROM AUTHOR]

Purpose: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS., Patients and Methods: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972)., Results: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS., Conclusions: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race., (©2024 American Association for Cancer Research.)

The ongoing repercussions of the COVID-19 pandemic provide an unparalleled context to examine how distressing events are remembered. Prior theory and research suggest that (a) distress during lockdowns may fade and be remembered as less distressing, or remain salient and be remembered as more distressing, than initially experienced and (b) emotional suppression and cognitive reappraisal may predict these memory biases. We test these possibilities by assessing depressive symptoms and emotion regulation during two lockdowns: at the start of the pandemic (Lockdown 2020) and 17 months later (Lockdown 2021) in a sample of parents with young children ( N = 272). We assessed tracking accuracy, directional bias, and projection bias in memory of depressive symptoms in Lockdown 2020, and the moderating role of emotion regulation at the time of encoding (Lockdown 2020) and recall (Lockdown 2021). People experiencing more depressive symptoms later in the pandemic (2021) remembered the start of the pandemic (2020) to involve more depressive symptoms than initially experienced (projection bias). People engaging in greater emotional suppression at recall (2021) were less likely to project their current depressive symptoms onto memory of the prior lockdown (lower projection bias) and remembered feeling lower depressive symptoms than initially experienced (underestimation directional bias). By contrast, people engaging in cognitive reappraisal at recall (2021) remembered feeling greater depressive symptoms than they initially experienced (overestimation directional bias). These unexpected results indicate that emotion regulation may shape memory of emotion during real-life challenges differently than patterns observed in lab-based research and may reflect helpful coping with life events. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Sarcopenic obesity and muscle attenuation have been associated with survival in patients with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA); however, these relationships are unknown for patients with resectable PDA. This study examined the associations between skeletal muscle and adipose tissue as measured on baseline computed tomography (CT) and the overall survival (OS) of participants with resectable PDA in a secondary analysis of the Southwest Oncology Group S1505 clinical trial (identifier: NCT02562716)., Methods: The S1505 phase II clinical trial enrolled patients with resectable PDA who were randomized to receive modified FOLFIRINOX or gemcitabine and nab-paclitaxel as perioperative chemotherapy, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software, and measurements were recorded for skeletal muscle area and skeletal muscle density, visceral adipose tissue area (VATA) and density, and subcutaneous adipose tissue area and density. The relationships between CT metrics and OS were analyzed using Cox regression models, with adjustment for baseline participant characteristics., Results: Of 98 eligible participants with available baseline abdominal CT, 8 were excluded because of imaging quality (eg, orthopedic hardware), resulting in 90 evaluable cases: 51 men (57.0%; mean age, 63.2 years [SD, 8.5]; mean body mass index [BMI], 29.3 kg/m 2 [SD, 6.4]), 80 White (89.0%), 6 Black (7.0%), and 4 unknown race (4.0%). Sarcopenia was present in 32 participants (35.9%), and sarcopenic obesity was present in 10 participants (11.2%). Univariable analyses for the 6 variables of interest indicated that the standardized mean difference (hazard ratio [HR], 0.75; 95% CI, 0.57-0.98; P = .04) was statistically significantly associated with OS. In models adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity, VATA was statistically significantly associated with OS (HR, 1.58; 95% CI, 1.00-2.51; P = .05). No difference was observed in OS between participants according to sarcopenic obesity or sarcopenia categories. The median OS estimates were 25.1 months for participants without sarcopenic obesity, 18.6 months for participants with sarcopenic obesity, 23.6 months for participants without sarcopenia, and 27.9 months for participants with sarcopenia., Conclusion: This was the first study to systematically evaluate body composition parameters in a prospective multicenter trial of patients with resectable PDA who received perioperative chemotherapy. Visceral adipose tissue was associated with survival; however, there was no association between OS and sarcopenia or sarcopenic obesity. Further studies should evaluate these findings in more detail., (Copyright © 2023. Published by Elsevier Inc.)

The biopsychosocial model of challenge and threat emphasizes how individuals appraise stress. Close relationship theories emphasize the interpersonal context, communication, and outcomes that arise from stress. We integrate these approaches by examining the individual variability surrounding appraisals of sufficient (more challenge, less threat) or insufficient (more threat, less challenge) resources to cope with demands and examining how these appraisals are associated with couples' behavior and feelings toward each other. Across three studies, 459 romantic couples ( N  = 918), and various potentially stressful in-lab conversations (extra-dyadic problem, dislikes about each other, dependability, and relationship conflict), we found evidence that stress appraisals indicative of more challenge and less threat were associated with more approach- and less avoidance-oriented behaviors within interactions. These approach- and avoidance-oriented behaviors were associated with greater feelings of relationship security and well-being after the conversation. However, whose (actors or partners) appraisals and behaviors were associated with security and well-being varied across the three studies. This work provides theoretical and empirical evidence for an interpersonal emphasis on intraindividual stress appraisal processes through a dyadic and close relationships lens. Our integrative theoretical framework breaks away from the idea that stress is inherently "bad" or "maladaptive" to show that appraising stress as more manageable (more challenge, less threat) is associated with more relationship behaviors that approach incentives and less that avoid threats and enhance feelings of relationship security and well-being., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00235-3., Competing Interests: Conflict of InterestNot applicable., (© The Author(s) 2024.)

Feeling loved (loved, cared for, accepted, valued, understood) is inherently dyadic, yet most prior theoretical perspectives and investigations have focused on how actors feeling (un)loved shapes actors' outcomes. Adopting a dyadic perspective, the present research tested whether the established links between actors feeling unloved and destructive (critical, hostile) behavior depended on partners' feelings of being loved. Does feeling loved need to be mutual to reduce destructive behavior, or can partners feeling loved compensate for actors feeling unloved? In five dyadic observational studies, couples were recorded discussing conflicts, diverging preferences or relationship strengths, or interacting with their child (total N = 842 couples; 1,965 interactions). Participants reported how much they felt loved during each interaction and independent coders rated how much each person exhibited destructive behavior. Significant Actors' × Partners' Felt-Loved interactions revealed a strong-link/mutual felt-unloved pattern: partners' high felt-loved buffered the damaging effect of actors' low felt-loved on destructive behavior, resulting in actors' destructive behavior mostly occurring when both actors' and partners' felt-loved was low. This dyadic pattern also emerged in three supplemental daily sampling studies. Providing directional support for the strong-link/mutual felt-unloved pattern, in Studies 4 and 5 involving two or more sequential interactions, Actors' × Partners' Felt-Loved in one interaction predicted actors' destructive behavior within couples' subsequent conflict interactions. The results illustrate the dyadic nature of feeling loved: Partners feeling loved can protect against actors feeling unloved in challenging interactions. Assessing Actor × Partner effects should be equally valuable for advancing understanding of other fundamentally dyadic relationship processes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical scaffold into a bi-cyclic structure. Rapid screening of diverse bacteriophage libraries against SARS-CoV-2 Spike yielded unique Bicycle binders across the entire protein. Exploiting Bicycles' inherent chemical combinability, we converted early micromolar hits into nanomolar viral inhibitors through simple multimerization. We also show how combining Bicycles against different epitopes into a single biparatopic agent allows Spike from diverse variants of concern (VoC) to be targeted (Alpha, Beta, Delta and Omicron). Finally, we demonstrate in both male hACE2-transgenic mice and Syrian golden hamsters that both multimerized and biparatopic Bicycles reduce viraemia and prevent host inflammation. These results introduce Bicycles as a potential antiviral modality to tackle new and rapidly evolving viruses., (© 2023. The Author(s).)

This review will apply a multidisciplinary approach to GI symptoms with attention to symptom assessment (instruments and qualitative aspects), differential diagnosis, and recent findings relevant to management of symptoms and underlying diseases. We conclude that further development of supportive interventions for GI symptoms for both patient and caregivers has the potential to reduce distress from GI symptoms, and anticipate better symptom control with advances in scientific knowledge and improvement of the evidence base., (Published by Elsevier Inc.)

Interpersonal power involves how much actors can influence partners (actor power) and how much partners can influence actors (partner power). Yet, most theories and investigations of power conflate the effects of actor and partner power, creating a fundamental ambiguity in the literature regarding how power shapes social behavior. We demonstrate that actor and partner power are distinct and have differential effects on social behavior. Six studies (total N = 1,787) tested whether actor and partner power independently predicted behavioral inhibition (expressive suppression) and communal behavior (prioritization of partners' needs) within close relationships, including during couples' daily life (Study 1), lab-based social interactions (Studies 1-5; 1,012 dyadic interactions), and general responses during conflict (Studies 5 and 6). Actor power was negatively associated with behavioral inhibition, indicating that actors' low power prompts self-focused inhibition to prevent negative outcomes that low power actors are unable to control. Partner power was positively associated with actors' communal behavior, indicating that high partner power prompts other-focused behavior that prioritizes partners' needs and goals. These differential effects of actor and partner power replicated in work-based relationships with bosses/managers (Study 6). Unexpectedly, partner power was negatively associated with actors' behavioral inhibition within close relationships, consistent with a desire to prevent negative outcomes for low power partners. We present a framework that integrates the approach-inhibition and agentic-communal theories of power to account for the differential effects of actor and partner power. We describe the implications of this framework for understanding the effects of power in both close and hierarchical relationships. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

In the current research, we apply a dyadic perspective of expressive suppression (ES) to test whether ES represents a weak link, such that either actors' or partners' ES is sufficient to undermine relationship satisfaction. Our primary aim was to test this weak-link pattern by modeling Actor × Partner ES interactions on relationship satisfaction. To maximize power, we conducted integrative data analyses across four existing dyadic samples (N = 427 couples) that included self-reports of habitual ES and relationship satisfaction. Our second aim was to examine the role of conflict resolution ability as one potential mechanism for the ES weak-link pattern on satisfaction. These integrative data analyses involved two dyadic samples (N = 242 couples) that included self-reports of conflict resolution ability. Significant Actor × Partner ES interactions revealed a weak-link pattern: greater actors' or partners' ES was associated with lower relationship satisfaction. Accordingly, actors' lower ES was associated with higher satisfaction only when partners' ES was also low. This ES weak-link pattern also emerged for conflict resolution ability, which provided evidence that reduced conflict resolution ability is one interpersonal process that contributes to the weak-link pattern on satisfaction. ES likely operates as a weak link because actors' or partners' ES interferes with the coordination, cooperation, and connection needed to manage relationship challenges and sustain healthy relationships. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Have the demands of the COVID-19 pandemic risked declines in parents' health and family functioning, or have most parents been resilient and shown no changes in health and family functioning? Assessing average risk versus resilience requires examining how families have fared across the pandemic, beyond the initial months examined in prior investigations. The current research examines changes in parents' health and functioning over the first 1.5 years of the pandemic. Parents ( N = 272) who had completed general pre-pandemic assessments completed reassessments of psychological/physical health, couple/family functioning, and parenting within two mandatory lockdowns in New Zealand: at the beginning of the pandemic (26 March-28 April 2020) and 17 months later (18 August-21 September 2021). Parents exhibited average declines in psychological/physical health (greater depressive symptoms; reduced well-being, energy and physical health) and in couple/family functioning (reduced commitment and family cohesion; greater problem severity and family chaos). By contrast, there were no average differences in parent-child relationship quality and parenting practices across lockdowns. Declines in health and couple/family functioning occurred irrespective of pre-pandemic health and functioning, but partner support buffered declines in couple/family functioning. The results emphasize that attending to the challenges parents and couples face in the home will be important to mitigate and recover from the impact of the pandemic on parents' and children's well-being., (© The Author(s) 2022.)

Perceived stress undermines emotional wellbeing, and poorer emotional wellbeing may intensify perceived stress. The current studies examined whether biased memories contribute to the possible reciprocal links between perceived stress and depressive symptoms. Two longitudinal studies compared the stress people perceived for several weeks (Study 1, N = 308) or during a conflict interaction (Study 2, N = 261) with memories of perceived stress gathered in subsequent weeks. People with low depressive symptoms remembered their past as involving less perceived stress than they initially experienced (positive bias). By contrast, people with average or higher levels of depressive symptoms remembered their past as involving exactly as much perceived stress as initially experienced (depressive realism) or, at very high levels of depressive symptoms, more perceived stress than initially experienced (negative bias). These memory biases had important implications. Accounting for initial levels of perceived stress, more negative memories of perceived stress predicted greater weekly depressed mood (Study 1) and greater depressive symptoms across time (Study 2). Evaluating whether life has involved as much perceived stress as now remembered may help facilitate emotional wellbeing in the face of rising perceived stress and depressive symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that the protonated PTSCs are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: Although gastric cancer is one of the most common tumors worldwide, there is little knowledge about symptom clusters and quality of life (QoL) in this population., Objectives: The objectives were to identify the symptom clusters in gastric cancer patients receiving chemotherapy, and explore their effects on QoL., Methods: Gastric cancer patients receiving chemotherapy were recruited. Data were collected using the Memorial Symptom Assessment Scale Short Form, the Functional Assessment of Cancer Therapy-Gastric and the self-designed General Information Evaluation Form. The symptom clusters were extracted through the exploratory factor analysis. The influencing factors of symptom clusters and their effects on QoL were identified using multiple linear regression analysis., Results: A total of 322 participants were enrolled from three medical centers. Five factors were identified in this exploratory factor analysis based on symptom prevalence, namely fatigue related symptom cluster, epithelial symptom cluster, neurologic symptom cluster, malnutrition related symptom cluster and psychological symptom cluster (χ 2  = 31.470, P < 0.05). The affecting factors across symptom clusters and QoL subscales were relatively stable, but also different. Generally, fatigue related symptom cluster, malnutrition related symptom cluster and psychological symptom cluster demonstrated significantly negative effects on all aspects of QoL except social well being., Conclusion: Five symptom clusters were identified in gastric cancer patients receiving chemotherapy in mainland China. The symptom clusters negatively contributed to the variance in all aspects of QoL except social well being. Further studies should examine interventions for symptom clusters, their influencing factors, and their effects on improving QoL., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Mesenchymal stem cells (MSCs) can become dysfunctional in patients with hematological disorders. An unanswered question is whether age-linked disruption of the bone marrow (BM) microenvironment is secondary to hematological dysfunction or vice versa. We therefore studied MSC function in patients with different hematological disorders and found decreased MHC-II except from one sample with acute myeloid leukemia (AML). The patients' MSCs were able to exert veto properties except for AML MSCs. While the expression of MHC-II appeared to be irrelevant to the immune licensing of MSCs, AML MSCs lost their ability to differentiate upon contact and rather, continued to proliferate, forming foci-like structures. We performed a retrospective study that indicated a significant increase in MSCs, based on phenotype, for patients with BM fibrosis. This suggests a role for MSCs in patients transitioning to leukemia. NFĸB was important to MSC function and was shown to be a potential target to sensitize leukemic CD34+/CD38- cells to azacitidine. This correlated with their lack of allogeneic stimulation. This study identified NFĸB as a potential target for combination therapy to treat leukemia stem cells and showed that understanding MSC biology and immune response could be key in determining how the aging BM might support leukemia. More importantly, we show how MSCs might be involved in transitioning the high risk patient with hematological disorder to AML., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current research examined whether men's hostile sexism was a risk factor for family-based aggression during a nationwide COVID-19 lockdown in which families were confined to the home for 5 weeks. Parents who had reported on their sexist attitudes and aggressive behavior toward intimate partners and children prior to the COVID-19 pandemic completed assessments of aggressive behavior toward their partners and children during the lockdown (N = 362 parents of which 310 were drawn from the same family). Accounting for pre-lockdown levels of aggression, men who more strongly endorsed hostile sexism reported greater aggressive behavior toward their intimate partners and their children during the lockdown. The contextual factors that help explain these longitudinal associations differed across targets of family-based aggression. Men's hostile sexism predicted greater aggression toward intimate partners when men experienced low power during couples' interactions, whereas men's hostile sexism predicted greater aggressive parenting when men reported lower partner-child relationship quality. Novel effects also emerged for benevolent sexism. Men's higher benevolent sexism predicted lower aggressive parenting, and women's higher benevolent sexism predicted greater aggressive behavior toward partners, irrespective of power and relationship quality. The current study provides the first longitudinal demonstration that men's hostile sexism predicts residual changes in aggression toward both intimate partners and children. Such aggressive behavior will intensify the health, well-being, and developmental costs of the pandemic, highlighting the importance of targeting power-related gender role beliefs when screening for aggression risk and delivering therapeutic and education interventions as families face the unprecedented challenges of COVID-19. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The current research tests the links between emotion regulation and psychological and physical health during the COVID-19 pandemic. In Study 1, parents ( N = 365) who had reported on their psychological and physical health prior to the pandemic completed the same health assessments along with their use of emotion regulation strategies when confined in the home with their school-aged children during a nationwide lockdown. In Study 2, individuals ( N = 1,607) from a nationally representative panel study completed similar measures of psychological and physical health and use of emotion regulation strategies one-year prior to the lockdown and then again during the lockdown. Accounting for prepandemic psychological health, greater rumination and emotional suppression were independently associated with poorer psychological health (greater depressive symptoms and psychological distress, lower emotional and personal well-being), even when controlling for the emotional challenges of the pandemic (emotion control difficulties, perceived support; Studies 1 and 2) and a range of demographic covariates (Study 2). Greater rumination was also associated with greater fatigue in both studies, but greater rumination and emotional suppression were only independently associated with poorer perceptions of physical health in Study 2. The results for cognitive reappraisal were mixed; positive associations with personal well-being and general health only emerged in Study 2. The results provide evidence that key models in affective science help explain differences in psychological and physical health within the throes of a real-world demanding context and thus offer targets to help facilitate health and resilience during the pandemic (and other crises). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The COVID-19 pandemic is placing demands on parents that may amplify the risk of parents' distress and poor parenting. Leveraging a prepandemic study in New Zealand, the current research tested whether parents' psychological distress during a mandated lockdown predicts relative residual changes in poorer parenting and whether partner support and cooperative coparenting buffer this potentially detrimental effect. Participants included 362 parents; 310 were from the same family (155 dyads). Parents had completed assessments of psychological distress and parenting prior to the pandemic and then reported on their distress, parenting, partner support, and cooperative coparenting during a nationwide COVID-19 lockdown. Parents' distress during the lockdown predicted relative residual increases in harsh parenting, but this effect was buffered by partner support. Parents' distress also predicted residual decreases in warm/responsive parenting and parent-child relationship quality, but these effects were buffered by cooperative coparenting. Partner support and cooperative coparenting are important targets for future research and interventions to help parents navigate challenging family contexts, including COVID-19 lockdowns. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. Here, we show that ferritin-like Dps from hyperthermophilic Sulfolobus islandicus, covalently coupled with SARS-CoV-2 antigens via the SpyCatcher system, forms stable multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) elicited a higher antibody titre and an enhanced neutralising antibody response compared to monomeric RBD. A single immunisation with RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold., (© 2021 MRC Laboratory of Molecular Biology. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA hypomethylating agents such as decitabine and azacitidine are used as therapeutic treatments and have shown to promote expression of genes involved in tumor suppression, apoptosis, and immune response. Another anti-cancer drug, the proteasome inhibitor bortezomib, is used as a chemotherapeutic treatment for multiple myeloma (MM). Phase III clinical trials of decitabine and azacitidine used alone and in combination with other chemotherapeutics demonstrated their capacity to treat hematological malignancies and prolong the survival of MDS and AML patients. Although phase III clinical trials examining bortezomib's role in MDS and AML patients are limited, its underlying mechanisms in MM highlight its potential as a chemotherapeutic for such malignancies. Further research is needed to better understand how the epigenetic mechanisms mediated by these chemotherapeutic agents and their targeted gene networks are associated with the development and progression of MDS into AML. This review discusses the mechanisms by which decitabine, azacitidine, and bortezomib alter epigenetic programs and their results from phase III clinical trials.

Purpose: Symptom monitoring is attracting attention as a way to improve adherence to cancer therapy, reduce treatment-related toxicities, and possibly improve overall survival. How reporting thresholds affect symptom alert generation and clinical outcomes is poorly understood., Patients and Methods: We analyzed data from 38 US health care institutions collected for the prospective Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E2Z02 Symptom Outcomes and Practice Patterns study. Participants were outpatients receiving chemotherapy for breast (n = 642), colorectal (n = 486), or lung cancer (n = 340) who rated symptom severity using the MD Anderson Symptom Inventory at 2 assessment points 1 month apart. Percentages of patients with pain, dyspnea, fatigue, or distress at different thresholds (score of 4-7 on a 0-10 scale) were compared. The percentage of patients whose performance status had worsened at follow-up was used to estimate risk for missing clinically important symptom data by using higher severity thresholds., Results: At the guideline-recommended threshold of ≥ 4, suprathreshold rates were 60% for any of the 4 symptoms at the initial survey; performance status worsened at follow-up for 27% of all patients with any symptom rated ≥ 4 at the initiate survey. When the threshold was increased to ≥ 7, approximately half of patients (51%) with worsened performance status were not identified., Conclusion: The burden to clinicians from an alert threshold of ≥ 4 (per many current guidelines) would be substantial. However, setting higher alert thresholds may miss a large percentage of patients who need clinical intervention. These results may inform resource planning when implementing electronic symptom screening at an institutional or practice level., Competing Interests: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Partners' negative emotions communicate social information necessary for individuals to respond appropriately to important relational events. Yet, there is inconsistent evidence regarding whether partners' emotional expression enhances accurate perceptions of partners' emotions. The current studies make methodological and theoretical extensions to the extant literature by directly assessing whether partners' emotional expression during relationship interactions predicts 2 types of accuracy relevant to the theorized interpersonal functions of negative emotions: tracking accuracy and directional bias. In Studies 1 and 2, both members of recruited couples reported on their own negative emotions, disclosure of emotions, and perceptions of their partners' negative emotions during relationship interactions at the end of each day for 21 days. In Study 3, couples engaged in an emotionally relevant discussion in the laboratory. Participants immediately reviewed their discussions and rated their own negative emotions and perceptions of their partners' negative emotions within each 30-s segment of the discussion. Independent coders rated the degree to which each person expressed their emotions during the discussion. In all three studies, partners' greater emotional expression predicted perceivers more accurately tracking partners' negative emotions (greater tracking accuracy). High levels of partners' emotional expression also predicted perceivers overestimating partners' negative emotions (greater directional bias). This expression-perception pattern should support the interpersonal function of negative emotions by orienting perceivers to important emotional events that would be costly to overlook. The results, considered in the context of prior research, highlight the importance of matching methodological approaches with the theoretical processes under investigation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Thyroglobulin (TG) is the protein precursor of thyroid hormones, which are essential for growth, development and the control of metabolism in vertebrates 1,2 . Hormone synthesis from TG occurs in the thyroid gland via the iodination and coupling of pairs of tyrosines, and is completed by TG proteolysis 3 . Tyrosine proximity within TG is thought to enable the coupling reaction but hormonogenic tyrosines have not been clearly identified, and the lack of a three-dimensional structure of TG has prevented mechanistic understanding 4 . Here we present the structure of full-length human thyroglobulin at a resolution of approximately 3.5 Å, determined by cryo-electron microscopy. We identified all of the hormonogenic tyrosine pairs in the structure, and verified them using site-directed mutagenesis and in vitro hormone-production assays using human TG expressed in HEK293T cells. Our analysis revealed that the proximity, flexibility and solvent exposure of the tyrosines are the key characteristics of hormonogenic sites. We transferred the reaction sites from TG to an engineered tyrosine donor-acceptor pair in the unrelated bacterial maltose-binding protein (MBP), which yielded hormone production with an efficiency comparable to that of TG. Our study provides a framework to further understand the production and regulation of thyroid hormones.

The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Cytoskeletal actin dynamics is essential for T cell activation. Here, we show evidence that the binding kinetics of the antigen engaging the T cell receptor influences the nanoscale actin organization and mechanics of the immune synapse. Using an engineered T cell system expressing a specific T cell receptor and stimulated by a range of antigens, we found that the peak force experienced by the T cell receptor during activation was independent of the unbinding kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the synapse revealed a striking dependence on the antigen unbinding kinetics. These findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalize the force experienced by the T cell receptor in an antigen-specific manner. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to adjust the lengthscale and timescale of T cell receptor signaling., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Activation of immune cells relies on a dynamic actin cytoskeleton. Despite detailed knowledge of molecular actin assembly, the exact processes governing actin organization during activation remain elusive. Using advanced microscopy, we here show that Rat Basophilic Leukemia (RBL) cells, a model mast cell line, employ an orchestrated series of reorganization events within the cortical actin network during activation. In response to IgE antigen-stimulation of FCε receptors (FCεR) at the RBL cell surface, we observed symmetry breaking of the F-actin network and subsequent rapid disassembly of the actin cortex. This was followed by a reassembly process that may be driven by the coordinated transformation of distinct nanoscale F-actin architectures, reminiscent of self-organizing actin patterns. Actin patterns co-localized with zones of Arp2/3 nucleation, while network reassembly was accompanied by myosin-II activity. Strikingly, cortical actin disassembly coincided with zones of granule secretion, suggesting that cytoskeletal actin patterns contribute to orchestrate RBL cell activation., Competing Interests: The authors declare no competing interests.

Structural, biochemical and biophysical studies of eukaryotic soluble and membrane proteins require their production in milligram quantities. Although large-scale protein expression strategies based on transient or stable transfection of mammalian cells are well established, they are associated with high consumable costs, limited transfection efficiency or long and tedious selection of clonal cell lines. Lentiviral transduction is an efficient method for the delivery of transgenes to mammalian cells and unifies the ease of use and speed of transient transfection with the robust expression of stable cell lines. In this protocol, we describe the design and step-by-step application of a lentiviral plasmid suite, termed pHR-CMV-TetO 2 , for the constitutive or inducible large-scale production of soluble and membrane proteins in HEK293 cell lines. Optional features include bicistronic co-expression of fluorescent marker proteins for enrichment of co-transduced cells using cell sorting and of biotin ligase for in vivo biotinylation. We demonstrate the efficacy of the method for a set of soluble proteins and for the G-protein-coupled receptor (GPCR) Smoothened (SMO). We further compare this method with baculovirus transduction of mammalian cells (BacMam), using the type-A γ-aminobutyric acid receptor (GABA A R) β3 homopentamer as a test case. The protocols described here are optimized for simplicity, speed and affordability; lead to a stable polyclonal cell line and milligram-scale amounts of protein in 3-4 weeks; and routinely achieve an approximately three- to tenfold improvement in protein production yield per cell as compared to transient transduction or transfection.

The current research extends prior research linking negative emotions and emotion regulation tendencies to memory by investigating whether (a) naturally occurring negative emotions during routine weekly life are associated with more negatively biased memories of prior emotional experiences-a bias called projection; (b) tendencies to regulate emotions via expressive suppression are associated with greater projection bias in memory of negative emotions; and (c) greater projection bias in memory is associated with poorer future well-being. Participants (N = 308) completed a questionnaire assessing their general tendencies to engage in expressive suppression. Then, every week for 7 weeks, participants reported on (a) the negative emotions they experienced across the current week (e.g., "This week, I felt 'sad'"), (b) their memories of the negative emotions they experienced the prior week (e.g., "Last week, I felt 'sad'"), and (c) their well-being. First, participants demonstrated significant projection bias in memory: Greater negative emotions in a given week were associated with remembering emotions in the prior week more negatively than those prior emotions were originally reported. Second, projection bias in memory of negative emotions was greater for individuals who reported greater tendencies to regulate emotions via expressive suppression. Third, greater projection bias in memory of negative emotions was associated with reductions in well-being across weeks. These 3 novel findings indicate that (a) current negative emotions bias memory of past emotions, (b) this memory bias is magnified for people who habitually use expressive suppression to regulate emotions, and (c) this memory bias may undermine well-being over time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Context: Comprehensive symptom assessment is crucial for symptom management. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) has been validated for symptom assessment in cancer patients, but there is no simplified Chinese version., Objectives: To present the validation procedures and results for the simplified Chinese version of the Memorial Symptom Assessment Scale-Short Form (MSAS-SF-SC) among cancer patients in mainland China., Methods: The MSAS-SF was translated and culturally adapted into simplified Chinese. About 359 cancer patients completed the MSAS-SF-SC, the Chinese Functional Assessment of Cancer Therapy-General, the Chinese Brief Fatigue Inventory, the Chinese Hospital Anxiety and Depression Scale, and the Chinese Medical Outcomes Study Social Support Survey. Reliability was assessed by internal consistency and test-retest coefficients. Convergent and divergent validity were analyzed by Pearson's correlation coefficients between MSAS-SF-SC subscales and the other instruments. Known-groups validity used Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site., Results: The MSAS-SF-SC was reliable with Cronbach's alpha coefficients for subscales ranging from 0.782 to 0.874 and test-retest coefficients ranging from 0.819 to 0.872. MSAS-SF-SC subscales correlated with corresponding Chinese Functional Assessment of Cancer Therapy-General subscales (-0.557 to -0.680; P < 0.001), Chinese Brief Fatigue Inventory (0.620; P < 0.001), and Chinese Hospital Anxiety and Depression Scale (0.663; P < 0.001) indicating convergent validity. MSAS-SF-SC subscales showed low or no correlations with the Chinese Medical Outcomes Study Social Support Survey (-0.146 to -0.165; P < 0.01), indicating divergent validity. MSAS-SF-SC subscales showed appropriate differences by Eastern Cooperative Oncology Group-Performance Status, hemoglobin level, and primary site., Conclusion: The MSAS-SF-SC demonstrated good psychometric properties and is culturally adapted. The instrument could be a valuable tool for Chinese health care professionals and researchers., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The Memorial Symptom Assessment Scale Short Form (MSAS-SF) is a widely used symptom assessment instrument. Patients who self-complete the MSAS-SF have difficulty following the two-part response format, resulting in incorrectly completed responses. We describe modifications to the response format to improve useability, and rational scoring rules for incorrectly completed items., Methods: The modified MSAS-SF was completed by 311 women in our Peer and Nurse support Trial to Assist women in Gynaecological Oncology; the PeNTAGOn study. Descriptive statistics were used to summarise completion of the modified MSAS-SF, and provide symptom statistics before and after applying the rational scoring rules. Spearman's correlations with the Functional Assessment for Cancer Therapy-General (FACT-G) and Hospital Anxiety and Depression Scale (HADS) were assessed., Results: Correct completion of the modified MSAS-SF items ranged from 91.5 to 98.7%. The rational scoring rules increased the percentage of useable responses on average 4% across all symptoms. MSAS-SF item statistics were similar with and without the scoring rules. The pattern of correlations with FACT-G and HADS was compatible with prior research., Conclusion: The modified MSAS-SF was useable for self-completion and responses demonstrated validity. The rational scoring rules can minimise loss of data from incorrectly completed responses. Further investigation is recommended.

Context: Symptoms of patients with cancer need to be evaluated with a standard instrument. The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is a symptom assessment tool that has been validated in many languages., Objectives: The aim of the present study was to validate the Korean-version Memorial Symptom Assessment Scale-Short Form (MSAS-SF) in patients with gynecologic cancer., Methods: We translated the MSAS-SF into Korean, and 175 gynecologic cancer inpatients completed the MSAS-SF, Functional Assessment Cancer Therapy-General (FACT-G), and gathered demographic and clinical data and Karnofsky Performance Status (KPS). Reliability was assessed for internal consistency with Cronbach's alpha coefficient. Pearson's correlation coefficient was calculated between the MSAS-SF and FACT-G subscales for convergent validity. T-test analysis was used to compare differences in MSAS-SF subscales by cancer stage and KPS for discriminant validity., Results: The Cronbach's alpha coefficients for the MSAS-SF subscales ranged from 0.80 to 0.91. The Korean-version MSAS-SF subscales showed convergent validity with FACT-G subscales. The correlation coefficients were -0.640 (P < 0.001) and -0.628 (P < 0.001) for global distress index and total MSAS score with FACT-G total score. The scores of MSAS-SF subscales showed appropriate differences by cancer stage and KPS., Conclusion: The Korean-version MSAS-SF is a valid tool for the reliable assessment of patients with gynecologic cancer in Korea., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The discovery of genetic variants influencing sleep patterns can shed light on the physiological processes underlying sleep. As part of a large clinical sequencing project, WGS500, we sequenced a family in which the two male children had severe developmental delay and a dramatically disturbed sleep-wake cycle, with very long wake and sleep durations, reaching up to 106-h awake and 48-h asleep. The most likely causal variant identified was a novel missense variant in the X-linked GRIA3 gene, which has been implicated in intellectual disability. GRIA3 encodes GluA3, a subunit of AMPA-type ionotropic glutamate receptors (AMPARs). The mutation (A653T) falls within the highly conserved transmembrane domain of the ion channel gate, immediately adjacent to the analogous residue in the Grid2 (glutamate receptor) gene, which is mutated in the mouse neurobehavioral mutant, Lurcher. In vitro, the GRIA3(A653T) mutation stabilizes the channel in a closed conformation, in contrast to Lurcher. We introduced the orthologous mutation into a mouse strain by CRISPR-Cas9 mutagenesis and found that hemizygous mutants displayed significant differences in the structure of their activity and sleep compared to wild-type littermates. Typically, mice are polyphasic, exhibiting multiple sleep bouts of sleep several minutes long within a 24-h period. The Gria3A653T mouse showed significantly fewer brief bouts of activity and sleep than the wild-types. Furthermore, Gria3A653T mice showed enhanced period lengthening under constant light compared to wild-type mice, suggesting an increased sensitivity to light. Our results suggest a role for GluA3 channel activity in the regulation of sleep behavior in both mice and humans., (© The Author 2017. Published by Oxford University Press.)

The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ. Pentraxin then accumulates AMPA receptors on the postsynaptic terminal forming functional synapses. Our findings reveal a signaling pathway that regulates synaptic activity during central nervous system development and demonstrates a role for astrocytes as organizers of active synaptic connections by coordinating both pre and post synaptic neurons. As mutations in glypicans are associated with neurological disorders, such as autism and schizophrenia, this signaling cascade offers new avenues to modulate synaptic function in disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) versus elderly (> age 65) MM patients utilizing the Nationwide Inpatient Sample. Over a 3-year period (2008 to 2010), 2209 patients with MM were admitted to US hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74.7%) younger than age 65 and 559 patients (25.3%) 65 or older. Overall, in-hospital mortality in MM patients after auto-HSCT was rare (1.5%) and there was no significant difference in mortality between elderly and younger patients. Elderly patients did have a significantly increased mean length of stay (18.6 days + 10.8 days [SD] versus 16.8 days + 7.2 days [SD], P < .001) and mean total hospital charges ($161,117 + $105,008 [SD] versus $151,192 + $78,342 [SD] , P = .018) compared with younger patients. Elderly patients were significantly more likely than younger patients to develop major in-hospital post-transplantation complications such as severe sepsis (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.40 to 5.21; P = .003), septic shock (OR, 3.10; 95% CI, 1.43 to 6.71; P = .004), pneumonia (OR, 1.62; 95% CI, 1.06 to 2.46; P = .024), acute respiratory failure (OR, 3.44; 95% CI, 1.70 to 6.96; P = .001), endotracheal intubation requiring prolonged mechanical ventilation (OR, 2.19; 95% CI, 1.06 to 4.55; P = .035), acute renal failure (OR, 2.14; 95% CI, 1.38 to 3.33; P = .001), and cardiac arrhythmias (OR, 2.06; 95% CI, 1.52 to 2.79; P <.001). These data may help guide informed consent discussions and provide a focus for future studies to reduce treatment-related morbidity in elderly MM patients undergoing auto-HSCT., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.)