Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants.

INTRODUCTION: Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. OBJECTIVE: The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. METHODS: We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. RESULTS: In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. CONCLUSIONS: These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial.

Importance: Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. Objective: To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. Design, Setting, and Participants: Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. Interventions: Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). Main Outcomes and Measures: The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was -11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. Results: Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, -3.5% [1-sided 95% CI, -11.5% to ∞]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was -0.4% (63.9% vs 64.3%; [1-sided 95% CI, -6.9 to ∞]; P value for noninferiority = .004) at week 1, -0.7% (66.8% vs 67.6%; [1-sided 95% CI, -8.1 to ∞]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, -4.6 to ∞]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. Conclusions and Relevance: Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding. Trial Registration: ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008.

Investigate the efficacy of size exclusion chromatography for the isolation of extracellular vesicles from C. elegans.

Isolation of Extracellular Vesicles (EVs) has been done extensively in the past using ultracentrifugation, a recent shift has been observed towards precipitation, and exosome isolation kits. These methods often co-elute contaminants of similar size and density which makes their detection and downstream applications quite challenging. As well as the EV yield is also compromised in some methodologies due to aggregate formation. In recent reports, size-exclusion chromatography (SEC) is replacing density gradient-based ultracentrifugation as the gold standard of exosome isolation. It outperforms in yield, purity and does not account for any physical damage to the EVs. We have standardized the methodology for an efficient pure yield of homogenous exosomes of size even smaller than 75 nm in Caenorhabditis elegans homogenate. The paper entails the application and optimization of EV isolation by SEC based on previous studies by optimizing bed size and type of sepharose column employed. We propose that this method is economically feasible in comparison with currently available approaches. A comparative study was conducted to investigate the performance of CL-6B in relation to CL-2B and further, this was combined with ultracentrifugation for higher efficacy. The methodology could be introduced in a clinical setting due to its therapeutic potential and scope. The eluted EVs were studied by flow cytometry, nanotracking and characterized for size and morphology.

Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA).

PURPOSE: High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1 to G4 GI toxicities, quality of life (QOL), and patient satisfaction. Suppression of prostate-specific antigen (PSA) and signals for survival differences were also analyzed. METHODS AND MATERIALS: This was a single-center randomized trial in patients with intermediate- and high-risk localized prostate cancer who received HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE). The International Prostate Symptom Score (IPSS) was used to assess lower urinary tract symptoms. The International Index of Erectile Function scale (IIEF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) were used to assess erectile dysfunction and QOL at 0, 3, 9, and 12 months. RESULTS: Fifty patients were recruited to each arm, with 48 and 46 patients completing treatment and follow-up in each arm, 81.5% of whom had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after treatment commenced (45.7% and 42.2% in Arm A and B, respectively). Up to 11% of patients reported G1 urinary frequency at 12 months. Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain, and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point. Over 30% of patients had G1 flatulence at baseline, and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12 months (21.4% and 25.6% in Arm A and B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis, and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon except for G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P, and QOL scores between the arms. Median prostate-specific antigen (PSA) follow-up was 5 years. Seven patients had treatment failure in each arm. Disease Free Survival (DFS) was 93.3% and 90.7% at 5 years in Arm A and B, respectively, with median failure time of 60 and 48 months in Arm A and B, respectively. There were no statistically significant differences between arms. CONCLUSIONS: The sequencing of HDR-BT and EBRT did not affect the incidence of G3 or G4 toxicities, and no significant differences were seen in other patient-reported outcomes. Treatment was well tolerated with maintained QOL scores. Treatment failure was low in both arms in a high-risk cohort; however, a larger study with longer follow-up is underway to establish whether the difference in median time to failure between the 2 arms is a signal of superiority.

How negative and positive constructs and comorbid conditions contribute to disability in chronic orofacial pain.

BACKGROUND: Temporomandibular disorders (TMD) symptoms develop into chronic pain for some patients, but the reasons for this are unclear. Psychosocial factors and chronic overlapping pain conditions are believed to contribute to the development of pain-related disability. We examined the role of jaw function, negative and positive psychological factors and chronic overlapping pain conditions (COPCs) on pain-related disability whilst controlling for demographic variables. METHODS: We collected demographics, medical and psychosocial history and the Graded Chronic Pain Scale, a measure of pain intensity and pain interference from 400 participants with chronic TMD. Structural equation modelling was used to assess a model of COPCs and the latent variables of psychological unease (pain catastrophizing, somatic symptoms and negative affect), positive valence factors (optimism and positive affect), jaw function (chewing, opening and expression limitation) and pain-related disability (pain intensity and pain interference) whilst controlling for demographic variables. RESULTS: We achieved good fit of a parsimonious model (root-mean-square error of approximation = 0.063 [90% CI] [0.051-0.075]), comparative fit index = 0.942, standard root-mean-square residual = 0.067. Jaw function was the strongest latent variable predictor, followed by psychological unease and COPCs suggesting resources focused on improving joint function, psychosocial support and management of COPCs will improve pain-related disability in TMDs. CONCLUSIONS: These findings not only increase the body of knowledge related to TMD clinical phenotypes but also, have a translational impact in further supporting the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.

Individual Dimensions of Pain Catastrophizing Do Not Mediate the Effect of Sociodemographic and Psychological Factors on Chronic Orofacial Pain Severity, Interference, and Jaw Limitation: A Structural Equation Modeling Approach.

Pain catastrophization (PC), involving rumination, magnification, and helplessness, can be viewed as a coping strategy associated with chronic pain. PC is considered a driving force in mediating pain-related outcomes, but it is still unclear whether PC mediates the relationship between psychological and sociodemographic factors with chronic pain when considered in a single model. Using baseline data from a parent study, this study examined the effect of positive and negative psychological and sociodemographic factors on pain severity, interference, and jaw limitation mediated by the PC dimensions in a sample of 397 temporomandibular disorder (TMD) participants using structural equation modeling (SEM). SEM revealed that pain severity regressed on age, sex, education, and income; interference regressed on positive and negative psychological factors, education, and income; and jaw limitation regressed on age. The PC dimensions did not individually mediate these relationships. Although they jointly mediated the relationships between negative psychological factors and pain severity and between age and pain interference, the effect size was small, suggesting that PC is not a critical factor in mediating TMD pain outcomes. Reducing negative cognitions, not just PC, may be of greatest benefit to the most vulnerable TMD populations. PERSPECTIVE: This study examines sociodemographic and psychological factors that affect orofacial pain, finding that the pain catastrophizing dimensions do not mediate these relationships. Understanding which factors most strongly affect pain outcomes will help identify targets for intervention to produce the greatest benefit for the most vulnerable persons suffering from pain.

Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice.

Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here, we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

The coping skills and quality of life among rape survivors - A descriptive study from Kerala.

Background: Rape is one of the most heinous of acts. It constitutes a major violation of an individual's basic rights and intensely impacts their mental and physical health. Coping skills used to deal with the trauma could provide information on their quality of life (QOL). Objectives: To assess the coping skills and QOL of rape survivors and to explore its association with their coping skills. Materials and Methods: Data were collected through a questionnaire, and coping skills were assessed using the Brief COPE scale and QOL using the World Health Organization quality of life questionnaire (WHOQOL-BREF). Results were analyzed using the Kruskal-Wallis H test and Spearman rank correlation. Results: Adaptive coping skills such as use of instrumental support, active coping, use of emotional support, self-distraction, and acceptance had higher COPE mean scores. QOL in the domain of physical health (mean = 52.71) had the highest mean score, followed by the domains of environment (mean = 51.35) and psychological health (mean = 48.37). Use of coping skills like active coping, use of emotional support, use of instrumental support, positive reframing, and acceptance had a significant positive correlation with the QOL in the domains of physical health and environment. Active coping and positive reframing were positively correlated with the QOL in the domain of psychological health, while positive reframing and humor were positively correlated with the social relationships domain. Conclusion: Those who employed adaptive coping skills (active coping, use of emotional support, use of instrumental support, positive reframing, acceptance) showed significantly better QOL than those with maladaptive skills.

Cortisol Reactivity and Observed Parenting among Mothers of Children with and without ADHD.

OBJECTIVE: Neurobiological models suggest links between maternal cortisol reactivity and parenting; however, no studies have examined cortisol reactivity and parenting in mothers of school-age children with ADHD. METHOD: We examined the relationship between observed parenting and maternal cortisol reactivity in two laboratory contexts: the Trier Social Stress Task (TSST) and parenting-child interaction (PCI). Mothers of children with (N = 24) and without (N = 36) ADHD participated. RESULTS: During the TSST, greater cortisol output and increase were associated with decreased positive and increased negative parenting. However, during the PCI, cortisol output was associated with increased self-reported and observed positive parenting, and decreased observed negative parenting. Cortisol change during the PCI was associated with decreased observed positive parenting and increased self-reported negative parenting. Among mothers of children with ADHD, cortisol output during the PCI was negatively associated with negative, inconsistent parenting. Change in cortisol predicted more inconsistent discipline and corporal punishment. CONCLUSION: Findings contribute to an integrative biological, psychological, and cognitive process model of parenting in families of children with ADHD.

Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

BACKGROUND: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival. PATIENTS AND METHOD: SCORAD is a randomised trial of 686 patients comparing a single dose of 8 Gy radiotherapy with 20 Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). A multivariable Cox regression for overall survival (OS) and a logistic regression for ambulatory status at 8 weeks were performed in the training set using baseline factors and a backward selection regression to identify a parsimonious model with p ≤ 0.10. Receiver Operating Characteristic (ROC) analysis evaluated model prognostic performance in the validation set. Validation of the final survival model was performed in a separate registry dataset (n = 348). RESULTS: The survival Cox model identified male gender, lung, gastrointestinal, and other types of cancer, compression at C1-T12, presence of non-skeletal metastases and poor ambulatory status all significantly associated with worse OS (all p < 0.05). The ROC AUC for the selected model was 75% (95%CI: 69-81) in the SCORAD validation set and 68% (95%CI: 62-74) in the external validation registry data. The logistic model for ambulatory outcome identified primary tumour breast or prostate, ambulatory status grade 1 or 2, bladder function normal and prior chemotherapy all significantly associated with increased odds of ambulation at 8 weeks (all p < 0.05). The ROC AUC for the selected model was 72.3% (95% CI 62.6-82.0) in the validation set. CONCLUSIONS: Primary breast or prostate cancer, and good ambulatory status at presentation, are favourable prognostic factors for both survival and ambulation after treatment.

Audiovisual cues and perceptual learning of spectrally distorted speech.

Two experiments investigate the effectiveness of audiovisual (AV) speech cues (cues derived from both seeing and hearing a talker speak) in facilitating perceptual learning of spectrally distorted speech. Speech was distorted through an eight channel noise-vocoder which shifted the spectral envelope of the speech signal to simulate the properties of a cochlear implant with a 6 mm place mismatch: Experiment I found that participants showed significantly greater improvement in perceiving noise-vocoded speech when training gave AV cues than when it gave auditory cues alone. Experiment 2 compared training with AV cues with training which gave written feedback. These two methods did not significantly differ in the pattern of training they produced. Suggestions are made about the types of circumstances in which the two training methods might be found to differ in facilitating auditory perceptual learning of speech.

Pain experience and mood disorders during the lockdown of the COVID-19 pandemic in the United States: an opportunistic study.

INTRODUCTION: The unknown and uncontrollable situation of the coronavirus disease 2019 (COVID-19) pandemic may have triggered changes in pain, anxiety, and depression along with a perception of nonspecific COVID-19 symptoms. OBJECTIVES: We determined how anxiety, depression, and pain outcomes varied during the "Stay-at-Home" order compared with the prepandemic period and whether nonspecific COVID-19 symptoms would occur. METHODS: We conducted an online survey to opportunistically reassess clinical anxiety, depression, pain intensity, and pain interference while controlling for somatic symptom severity during the prepandemic and Stay-at-Home order period. During the Stay-at-Home period, anxiety, depression, pain intensity, and pain interference were reassessed. Coping strategies were assessed as a critical factor influencing pain behaviors. In addition, we explored the occurrence of nonspecific COVID-19 symptoms with an ad hoc survey referencing the Centers for Disease Control and Prevention publicly available COVID-19 symptoms. RESULTS: We observed a significant increase in depression and anxiety levels during the Stay-at-Home period. Coping strategy changes (eg, increased exercise) were linked to lower pain severity and interference which improved overall. Participants who self-reported nonspecific COVID-19 symptoms had higher prepandemic depression. Among the 72 participants not diagnosed with COVID-19, 70.8% of the participants experienced symptoms resembling those associated with COVID-19. CONCLUSION: We suggest the parallel between pain outcome improvement and worsening anxiety and depression during the Stay-at-Home order might reflect a shift in symptoms, indicating that those patients with underlying mood disorders may require more help than they did before the pandemic.

The Unique Effects of Maternal ADHD Symptoms and Emotion Dysregulation on Parenting Behavior.

Objective: Separate literatures have examined the associations between maternal ADHD symptoms and parenting and maternal emotion regulation (ER) and parenting. This study examined the effects of both maternal ADHD symptoms and ER on parenting. Method: This cross-sectional study used a multi-method evaluation of parenting behavior to examine the independent and interactive effects of maternal ADHD symptoms and ER on self-reported and observed parenting among 79 demographically diverse families of 5- to 10-year-old children. Results: There were significant main effects of maternal ER difficulties on negative parenting and of maternal ADHD symptoms on harsh responses to children's negative emotions. Maternal ADHD symptoms and ER were not significantly associated with positive parenting behavior. No interaction effects were observed. Conclusion: Maternal ADHD symptoms and emotion dysregulation may uniquely contribute to parenting difficulties. Maternal ADHD symptoms were associated with difficulties responding to children's negative emotions, whereas maternal ER was associated with difficulties with discipline practices.

Analysis of chromosome dynamics and chromosomal proteins in Drosophila spermatocytes.

A wide variety of techniques have been utilized to determine the localization of various proteins from premeiotic through meiotic stages in Drosophila males. Live imaging has been instrumental in monitoring chromosome pairing and the localization of fusion proteins. Immunofluorescence has been a widely utilized technique to examine the localization and colocalization of the many proteins involved in meiosis. Recently, an immuno-FISH protocol was developed to observe the co-localization of DNA probes and proteins. In this chapter, detailed protocols outlining these three types of experiments are presented.

Helping nursing homes "at risk" for quality problems: a statewide evaluation.

The Quality Improvement Program for Missouri (QIPMO), a state school of nursing project to improve quality of care and resident outcomes in nursing homes, has a special focus to help nursing homes identified as "at risk" for quality concerns. In fiscal year 2006, 92 of 492 Medicaid-certified facilities were identified as "at risk" using quality indicators (QIs) derived from Minimum Data Set (MDS) data. Sixty of the 92 facilities accepted offered on-site clinical consultations by gerontological expert nurses with graduate nursing education. Content of consultations include quality improvement, MDS, care planning, evidence-based practice, and effective teamwork. The 60 "at-risk" facilities improved scores 4%-41% for 5 QIs: pressure ulcers (overall and high risk), weight loss, bedfast residents, and falls; other facilities in the state did not. Estimated cost savings (based on prior cost research) for 444 residents who avoided developing these clinical problems in participating "at-risk" facilities was more than $1.5 million for fiscal year 2006. These are similar to estimated savings of $1.6 million for fiscal year 2005 when 439 residents in "at-risk" facilities avoided clinical problems. Estimated savings exceed the total program cost by more than $1 million annually. QI improvements demonstrate the clinical effectiveness of on-site clinical consultation by gerontological expert nurses with graduate nursing education.

Population Management: A Tool to Improve Timely Care in Pediatric and Young Adult Patients with Inflammatory Bowel Disease.

BACKGROUND: Maintenance of health leads to better outcomes in patients with chronic illness. ImproveCareNow, an international inflammatory bowel disease (IBD) quality improvement (QI) network, recommends maintenance-of-health visits twice a year. We identified a gap in care, with only 64% of IBD patients having documented visits within 200 days. Therefore, we sought to improve our follow-up rate to a goal of 80%. METHODS: Using population management (PM) reports, we identified patient-, data-, and treatment-related reasons for no documented visit within 200 days. We used the Pareto chart, key drivers, and process flow mapping and implemented changes using Plan-Do-Study-Act (PDSA) cycles to improve follow-up visit rates. Outcomes were presented using a control run chart with pre- and post- intervention data. RESULTS: The most common reasons for no visits were patient nonadherence with appointments (50%) and relocation/transition to an adult provider (25%). The median percentage of documented visits within 200 days increased from 64% to 83% (p < 0.0001), and this increase has been sustained for one year. CONCLUSIONS: Using the PM tool and focused QI interventions improved data quality and the percentage of patients with a documented visit within 200 days. The process is simple and can be applied to patients with other chronic illnesses.

Meiotic pairing and disjunction of mini-X chromosomes in drosophila is mediated by 240-bp rDNA repeats and the homolog conjunction proteins SNM and MNM.

In most eukaryotes, segregation of homologous chromosomes during meiosis is dependent on crossovers that occur while the homologs are intimately paired during early prophase. Crossovers generate homolog connectors known as chiasmata that are stabilized by cohesion between sister-chromatid arms. In Drosophila males, homologs pair and segregate without recombining or forming chiasmata. Stable pairing of homologs is dependent on two proteins, SNM and MNM, that associate with chromosomes throughout meiosis I until their removal at anaphase I. SNM and MNM localize to the rDNA region of the X-Y pair, which contains 240-bp repeats that have previously been shown to function as cis-acting chromosome pairing/segregation sites. Here we show that heterochromatic mini-X chromosomes lacking native rDNA but carrying transgenic 240-bp repeat arrays segregate preferentially from full-length sex chromosomes and from each other. Mini-X pairs do not form autonomous bivalents but do associate at high frequency with the X-Y bivalent to form trivalents and quadrivalents. Both disjunction of mini-X pairs and multivalent formation are dependent on the presence of SNM and MNM. These results imply that 240-bp repeats function to mediate association of sex chromosomes with SNM and MNM.

Role of the mod(mdg4) common region in homolog segregation in Drosophila male meiosis.

Homologous chromosomes must pair and establish stable connections during prophase I of meiosis to segregate reliably from each other at anaphase I. In most organisms, the stable connections, called chiasmata, arise from crossovers. In Drosophila males, homologs pair and segregate without crossing over. Chiasmata are replaced by a homolog conjunction complex that includes the Stromalin in Meiosis (SNM) and Modifier of Mdg4 in Meiosis (MNM) proteins. MNM is one of 31 alternative splice products of mod(mdg4), all of which share a common 402-amino-acid N terminus and differ at their C termini. Previous data demonstrated that an MNM-specific exon is required for homolog conjunction, but did not address whether the N-terminal common region, which includes a BTB domain that can mediate coalescence of protein-DNA complexes, is also required. Here we describe a mutation in the common region of mod(mdg4), Z3-3401, that causes qualitatively similar phenotypes as the MNM-specific alleles but disrupts X-Y segregation much more drastically than autosomal segregation. The mutant MNM protein in Z3-3401 is expressed throughout prophase I in spermatocytes but the protein is confined to the cytoplasm, suggesting that the Z3-3401 mutation disrupts a signal required for nuclear localization or retention. Z3-3401 fails to complement a large battery of lethal and semilethal alleles in the common region for meiotic nondisjunction, including an allele containing an amino acid substitution at a conserved residue in the BTB/POZ domain, consistent with a general requirement for the mod(mdg4) common region in homolog segregation.

Maternal Executive Functioning and Scaffolding in Families of Children with and without Parent-Reported ADHD.

Parental scaffolding robustly predicts child developmental outcomes, including improved self-regulation and peer relationships and fewer externalizing behaviors. However, few studies have examined parental characteristics associated with a parent's ability to scaffold. Executive functioning (EF) may be an important individual difference factor associated with maternal scaffolding that has yet to be examined empirically. Scaffolding may be particularly important for children with attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorder (DBD) symptoms due to their core difficulties with inattention, disorganization, EF, and self-regulation, their need for greater parental structure, and higher-than-average rates of parental EF deficits. Yet, little research has examined child ADHD in relation to parental scaffolding. This cross-sectional study examined: (1) the association between maternal EF (as measured by the Hotel Test, Barkley's Deficits in Executive Functioning Scale, and Digit Span) and observed scaffolding, (2) the association between parent-reported child ADHD/DBD symptoms and scaffolding, and (3) the interaction between child ADHD/DBD symptoms and maternal EF in predicting scaffolding. In a sample of 84 mothers and their 5-10 year-old biological children (62% male) with and without parent-reported ADHD, we found that maternal EF, as measured by Digit Span and the Hotel Test, predicted observed maternal scaffolding. However, child ADHD/DBD symptoms did not significantly predict maternal scaffolding controlling for child age, maternal education, and maternal EF, nor did the interaction of maternal EF and parent-reported child ADHD/DBD symptoms. Working memory and task shifting may be key components of parental EF that could be targeted in interventions to improve parental scaffolding.

Diffuse uterine leiomyomatosis with uterine rupture and benign metastatic lesions of the bone.

BACKGROUND: We report a case of diffuse uterine leiomyomatosis in pregnancy complicated by uterine rupture and dissemination to the bone. CASE: A 35-year-old nulliparous woman with a history of uterine leiomyoma presented at term with fetal demise. Failed induction of labor and hemodynamic instability due to uterine rupture resulted in a cesarean hysterectomy. A free-air series performed postoperatively to confirm paralytic ileus revealed multiple lytic bone lesions. The diagnosis of diffuse uterine leiomyomatosis with metastasis was made on histology of the resected uterus and fine-needle aspiration biopsy of the bone. She was managed conservatively, and the lesions are now regressing. CONCLUSION: Diffuse uterine leiomyomatosis should be considered in pregnant women with a history of uterine fibroids and peripartum hemorrhage.