Cornelia de Lange Syndrome mutations in SMC1A cause cohesion defects in yeast.

Cornelia de Lange Syndrome (CdLS) is a developmental disorder characterized by limb truncations, craniofacial abnormalities, and cognitive delays. CdLS is caused mainly by mutations in genes encoding subunits or regulators of the cohesin complex. Cohesin plays 2 distinct roles in chromosome dynamics as follows: it promotes looping, organization, and compaction of individual chromosomes, and it holds newly replicated sister chromatids together until cell division. CdLS-associated mutations result in altered gene expression likely by affecting chromosome architecture. Whether CdLS mutations cause phenotypes through impact on sister chromatid cohesion is less clear. Here, we show that CdLS-associated mutations introduced into the SMC1A gene of budding yeast had measurable impacts on sister chromatid cohesion, mitotic progression, and DNA damage sensitivity. These data suggest that sister chromatid cohesion-related defects may contribute to phenotypes seen in CdLS affected individuals.

The Reliability of Rating via Audio-Recording Using the Mindfulness-Based Interventions: Teaching Assessment Criteria.

Background: The Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is an important tool for assessing teacher skill and aspects of the fidelity of mindfulness-based interventions, but prior research on and implementation of the MBI:TAC has used video recordings, which can be difficult to obtain, share for assessments, and which increase privacy concerns for participants. Audio-only recordings might be a useful alternative, but their reliability is unknown. Objective: To assess evaluator perception of the rating process and inter-rater reliability of MBI:TAC ratings using audio-only recordings. Methods: We prepared audio-only files from video recordings of 21 previously rated Mindfulness-Based Stress Reduction teachers. Each audio recording was rated by 3 trained MBI:TAC assessors drawn from a pool of 12 who had previously participated in rating the video recordings. Teachers were rated by evaluators who had not viewed the video recording and did not know the teacher. We then conducted semi-structured interviews with evaluators. Results: On the 6 MBI:TAC domains, the intraclass correlation coefficients (ICCs) for audio recordings ranged from .53 to .69 using an average across 3 evaluators. Using a single rating resulted in lower ICCs (.27-.38). Bland-Altman plots showed audio ratings had little consistent bias compared to video recordings and agreed more closely for teachers with higher ratings. Qualitative analysis identified 3 themes: video recordings were particularly helpful when rating less skillful teachers, video recordings tended to provide a more complete picture for rating, and audio rating had some positive features. Conclusions: Inter-rater reliability of the MBI:TAC using audio-only recordings was adequate for many research and clinical purposes, and reliability is improved when using an average across several evaluators. Ratings using audio-only recordings may be more challenging when rating less experienced teachers.

Yoga for firefighters: Evaluation of a quality improvement program in California fire departments.

BACKGROUND: Firefighters experience high levels of physical and mental challenges. Yoga interventions have suggested benefits for firefighters. METHODS: This study reports results from a quality improvement assessment at fire departments with a 10-class yoga program. Main outcome is the total score on the Functional Movement Scale (FMS), an observer-based objective performance measure. A score of at least 14 [range 0-20] is considered as protective against injury. Secondary outcome is the score on the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire, a self-report measure for interoceptive bodily awareness as a parameter for a mechanism of action with yoga. We used descriptive statistics and regression analyses. RESULTS: Both total FMS and MAIA scores improved statistically significantly. The strongest performance improvement was seen in trunk stability. The mean FMS score improved from below 14 to 14 and higher indicating a decrease in the risk for injury. Changes in FMS and MAIA did not appear to be correlated. DISCUSSION: Despite the limitation of the study design, the findings support the potential benefits from a yoga program for firefighters.

Feasibility and acceptability of a Whole-Body hyperthermia (WBH) protocol.

BACKGROUND: Whole-body hyperthermia (WBH) has shown promise as a non-pharmacologic treatment for major depressive disorder (MDD) in prior trials that used a medical (infrared) hyperthermia device. Further evaluation of WBH as a treatment for MDD has, however, been stymied by regulatory challenges. OBJECTIVE: We examined whether a commercially available infrared sauna device without FDA-imposed limitations could produce the degree of core body temperature (101.3 °F) associated with reduced depressive symptoms in prior WBH studies. We also assessed the frequency of adverse events and the amount of time needed to achieve this core body temperature. We explored changes (pre-post WBH) in self-reported mood and affect. METHODS: Twenty-five healthy adults completed a single WBH session lasting up to 110 min in a commercially available sauna dome (Curve Sauna Dome). We assessed core body temperature rectally during WBH, and mood and affect at timepoints before and after WBH. RESULTS: All participants achieved the target core body temperature (101.3 °F). On average, it took participants 82.12 min (SD = 11.3) to achieve this temperature (range: 61-110 min), and WBH ended after a participant maintained 101.3 °F for two consecutive minutes. In exploratory analyses of changes in mood and affect, we found that participants evidenced reductions (t[24] = 2.03, M diff = 1.00, p=.054, 95% CI [-2.02,0.02]) in self-reported depression symptoms from 1 week pre- to 1 week post-WBH, and reductions (t[24]= -2.93, M diff= -1.72, p=.007, 95% CI [-2.93, -0.51]) in self-reported negative affect pre-post-WBH session. CONCLUSION: This novel WBH protocol holds promise in further assessing the utility of WBH in MDD treatment. TRIAL REGISTRATION: This trial was registered at clinicaltrivals.gov (NCT04249700).

Application of a mind-body tool in a rural population to improve post-operative outcomes in women with breast cancer: A pilot study.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women in the United States. While improvements in treatment have improved mortality, they can negatively impact quality of life (QOL). Mindfulness-based programs are low-cost interventions shown to improve QOL. The study aim was to evaluate a well-validated mind-body program - determining its feasibility, acceptability, and improvement in symptomatology in post-operative breast cancer patients in a rural setting. METHODS: We recruited patients during post-operative appointments following mastectomy or lumpectomy for breast cancer. Each participant completed 3 surveys before and after the intervention: (8 PROMIS-29, PROMIS -Global QOL, and MAAS (Mindfulness Attention Awareness Scale). The intervention was an 8-week course: "The Stress Management and Resiliency Training (SMART) - Relaxation Response and Resiliency Program (3RP)", which has been well-validated for the treatment of various clinical problems. Feasibility, acceptability, quantitative survey data, and demographics were analyzed. RESULTS: SMART-3RP was highly acceptable with greater than >80% completion rate. 23% of the invited participants enrolled, although over 70% of patients approached (34/48) expressed interest. The principal recruitment deterrent was scheduling. Sleep and anxiety/depression were improved in participants although not significantly due to small sample size. We also demonstrated improving trends in other QOL measures. CONCLUSIONS: This small pilot study proved feasibility, showed excellent acceptability, and demonstrated a benefit in post-operative breast cancer patients. Even with our small sample size, we found trends in improvement in certain QOL measures which emphasizes SMART-3RP's potential effectiveness. A large-scale randomized controlled trial is warranted.

Assessing Mental Health Concerns of Spanish-Speaking Dairy Farm Workers.

Background: Hispanic dairy farm workers have risk factors for mental health concerns. There is insufficient study of their mental health needs.Methods: We conducted focus groups at five farms. We quantified the burden of depressive symptoms with Patient Health Questionnaires (PHQ-2 and PHQ-9) during three seasons of mobile clinics on farm sites.Results: Focus groups revealed that sources of stress included working conditions, language barriers, fear of deportation, and distance from family. Depression screening found that the rate of mild depressive symptoms ranged from 0% to 3.2%. No individual scored higher than mild depression.Discussion: Rates of depressive symptoms were substantially lower than in the general US population, which may be explained by a population that self-selects for resilience. Our mixed qualitative and quantitative data acquisition provided us a more robust and comprehensive understanding of our population's mental health concerns than using one method alone.

Combined Modality Treatment With Brentuximab Vedotin and Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: A Case Report.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a rare form of non-Hodgkins lymphoma. Current frontline treatments for pcALCL include surgical resection, anthracycline-based chemotherapy, and/or radiation therapy (RT) depending on disease severity. While brentuximab vedotin (BV) has been used for refractory/relapsed cases, it recently received Food and Drug Administration (FDA) approval for use in combination with chemotherapy for peripheral T-cell lymphomas. In this case report, we utilized a combined modality therapy of RT and BV for a limited stage aggressive pcALCL presentation for which routine management is contraindicated. A 59-year-old man with a history of peripheral vascular disease (PVD) presented with an aggressive pcALCL involving the left inferior eyelid and small ipsilateral level II hypermetabolic lymph nodes at stage IIE. Due to the patient's history of PVD, the tumor's rapid growth, possible lymph node involvement, and eye proximity, BV was chosen as the initial chemotherapy treatment followed by RT. Complete metabolic resolution of the primary cutaneous lesion and lymphadenopathy was reached after BV treatment alone; complete clinical response of the primary tumor was reached following radiation therapy. Relapse occurred within 7 months. Salvage cyclophosphamide, vincristine, etoposide, and prednisone were not effective. Retreatment with BV + RT is currently being used to treat the new lesions. Our case illustrates that a combination of BV and RT can be a safe and effective initial treatment in patients with limited stage pcALCL who cannot tolerate anthracycline-based chemotherapy. Our patient had a complete response but ultimately relapsed; thus larger clinical trials are needed to better understand early-stage disease.

Collection of pregnancy outcome records following infertility-challenges and possible solutions.

PURPOSE: The aim of this study is to report challenges encountered when conducting inter-institutional data collection of obstetric (prenatal and postpartum) and delivery outcomes for research purposes and to propose solutions for enhanced efficiency. METHODS: Data were collected from women who consented to collection of obstetric and delivery records for an observational study of pregnancy and delivery outcomes following infertility treatment. We analyzed key issues relevant to improving efficiency of obstetric and delivery data collection via quantification of effort (such as number of calls and faxes) required to obtain records from different types of obstetric clinics and hospitals before and after utilization of a revised authorization. RESULTS: At time of analysis, records were successfully collected from 320 of the 451 participants who had delivered. The 320 participants received obstetric care at 63 institutions and delivered at 27 hospitals, with 168 (52.5 %) delivering at institutions other than home facility. At time of consent (8 weeks gestation), 155 of 320 (48.5 %) correctly predicted where they would receive obstetric care and 176 (55 %) where they would delivery. Most facilities (nearly 90 %) rejected our original authorization, but most (90 %) accepted the revised authorization described in this manuscript. CONCLUSIONS: Collecting records is time-consuming but important as over 50 % of our participants received care outside of the home facility. To efficiently collect outside records, we recommend that researchers interested in maternal and neonatal outcomes consider the guidelines outlined in this manuscript. This report also provides strong evidence of the need to develop data sharing through electronic health records for research purposes.

Spanish- and English-Speaking Pregnant Women's Views on cfDNA and Other Prenatal Screening: Practical and Ethical Reflections.

The rapid clinical implementation of cell-free DNA (cfDNA) screening, a non-invasive method of prenatal genetic screening, has outpaced research on its social and ethical implications. This study is the first to compare the ethical and practical views of Spanish- and English-speaking pregnant women in the United States about cfDNA screening. Semi-structured interviews were conducted with diverse Spanish- and English-speaking women who had received prenatal care at a large academic medical center. Of the 24 interviewees, ten were Latinas who were interviewed in Spanish; English-language interviews were conducted with seven non-Hispanic Asian and seven non-Hispanic White women. Participants held positive opinions concerning the accuracy of cfDNA screening and often noted that it would enhance preparedness. Participants also expressed concerns about the possibility of inaccurate results and the potentially negative effects of cfDNA screening on the experience of pregnancy. Differences emerged between Spanish and English speakers in their portrayals of their relationships with prenatal health care providers, the extent to which they questioned providers' advice, their ethical concerns, and their informational needs. We emphasize the importance of customizing prenatal test counseling to the needs of the individual patient, providing educationally appropriate counseling and literature, and mitigating potential language barriers.

Symptom dimensions and functional impairment in early psychosis: more to the story than just negative symptoms.

Functional impairment is a defining feature of psychotic disorders and usually appears well before their onset. Negative symptoms play a prominent role in the impaired functioning of individuals with schizophrenia and those at clinical-high-risk (CHR) for psychosis. Despite high rates of depression and anxiety in early psychosis, few studies have examined the contribution of these symptoms to functioning in the putative 'prodrome.' In the current study, we tested the hypotheses that 1) worse negative and disorganized, but not positive, symptoms would be significantly related to impaired social and role functioning in two cohorts of CHR individuals (combined N=98) and a separate sample of individuals with recent-onset (RO) psychotic disorders (N=88); and 2) worse anxiety and depression would be significantly related to impaired functioning in both samples, above and beyond the contributions of negative and disorganized symptoms. Findings largely supported our hypotheses that more severe negative and disorganized symptoms were related to poorer social and role functioning in both samples. Anxiety and depression severity were significantly related to poorer functioning in both samples. In addition, depression, but not anxiety, predicted poorer global and social functioning above and beyond that explained by negative symptoms in the CHR sample. These results suggest the need for phase-specific treatment in early psychosis, with a focus on symptom dimensions to improve functional outcomes for CHR individuals.

Psychometric properties of the Sutter-Eyberg Student Behavior Inventory with rural middle school and high school children.

This study examined the psychometric properties of the Sutter-Eyberg Student Behavior Inventory (SESBI) in a rural sample of children and adolescents. Thirty-eight 5th- through 12th-grade teachers completed the SESBI on 726 children in their classrooms. High Cronbach's alphas supported the reliability of the SESBI scales in this population. Higher SESBI scores were obtained by boys than girls and by African American students than Caucasian students, more so at lower grades. Teacher's race did not affect SESBI scores. In contrast to children with developmental delay, children with learning disabilities obtained higher scores than others on the SESBI Intensity scale but not on the Problem scale. This suggests that teachers of children with learning disabilities recognize the higher frequency of problem behaviors in their students but do not consider these behaviors to be problems for themselves. On both SESBI scales, children with developmental delay were not distinguishable from peers without developmental delays.