Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Early childhood trauma exposure and neurocognitive and emotional processes: Associations in young children in a partial hospital program.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program. Children who had experienced two or more categories of trauma had lower scores in episodic memory, global cognition, and inhibitory control as measured in a relational (but not computerized) task, when compared to children with less or no trauma. Interpersonal trauma was similarly associated with global cognition and relational inhibitory control. Family contextual factors did not moderate associations. Findings support examining inhibitory control in both relationally significant and decontextualized paradigms in early childhood, and underscore the importance of investigating multiple neurocognitive and emotional processes simultaneously to identify potential targets for early intervention.

Effect of Short versus Long Duration Naps on Blood Pressure during Simulated Night Shift Work: A Randomized Crossover Trial.

OBJECTIVE: Blunting of the sleep-related dip in blood pressure (BP) has been linked to numerous cardiovascular outcomes including myocardial infarction. Blunting of BP dipping occurs during night shift work and previous research suggest that a 60-min or longer on-shift nap is needed to restore normal/healthy BP dipping. We sought to determine the effect of different durations of napping on BP during and following simulated night shifts. We hypothesized that the greatest benefit in terms of restoration of normal BP dipping during night shift work would be observed during a longer duration nap versus a shorter nap opportunity. METHODS: We used a randomized crossover laboratory-based study design. Participants consented to complete three separate 72-hr conditions that included a 12-hr simulated night shift. Nap conditions included a 30-min and 2-hr nap compared to a no-nap condition. Ambulatory BP monitoring was assessed hourly and every 10-30 mins during in-lab naps. Blunted BP dipping during in-lab naps was the primary outcome. Goal enrollment of 25 (35 with attrition) provided 80% power to detect a mean difference of 5 mmHg in BP between nap conditions. RESULTS: Of the 58 screened, 28 were consented, and 26 completed all three 72-hr conditions. More than half (53.6%) were female. Mean age was 24.4 years (SD7.2). Most (85.7%) were certified as emergency medical technicians or paramedics. The mean percentage dip in systolic BP (SBP) and diastolic BP (DBP) did not differ between the 30-min and 2-hr nap conditions (p > 0.05), yet a greater proportion of participants experienced a 10-20% dip in SBP or DBP during the 2-hr nap versus the 30-min nap (p < 0.05). For every additional minute of total sleep during the 30-min nap, the percentage of SBP dip improved by 0.60%, and the percentage of DBP dip improved by 0.68% (p < 0.05). These improvements approximate to a 6% per minute relative advancement toward normal/healthy BP dipping. CONCLUSIONS: Restoration of a normal/healthy dip in BP is achievable during short and long duration nap opportunities during simulated night shift work. Our findings support the hypothesis that BP dipping is more common during longer 2-hr versus shorter 30-min naps. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04469803. Registered on 9 July 2020.

Are Short Duration Naps Better than Long Duration Naps for Mitigating Sleep Inertia? Brief Report of a Randomized Crossover Trial of Simulated Night Shift Work.

OBJECTIVE: We sought to test the effects of different duration naps on post-nap cognitive performance during simulated night shifts. METHODS: We used a randomized laboratory-based crossover trial design with simulated 12-hr night shifts and each participant completing three conditions of 72 hrs each (Clinicaltrials.gov; registration # NCT04469803). The three conditions tested included no-nap, a 30-min nap opportunity, and a 2-hr nap opportunity. Naps occurred at 02:00 hrs. Cognitive performance was assessed with the Brief 3-min Psychomotor Vigilance Test (PVT-B). Four PVT-B measures include: reaction time (RT in milliseconds (ms)), lapses (RT > 355 ms), false starts (reactions before stimulus or RT <100 ms), and speed (1,000/RT). The PVT-B was performed at the start of the simulated night shift (19:00), end of shift (07:00), pre-nap (02:00), and at 0 mins, 10 mins, 20 mins, and 30 mins following the 30-min and 2-hr nap conditions. Simultaneously, participants reported subjective ratings of fatigue and other constructs. RESULTS: Twenty-eight (15 female), mostly certified emergency medical technicians or paramedics, consented to participate. For all three conditions, looking within condition, PVT-B lapse performance at the end of the 12-hr simulated night shift (at 07:00) was poorer compared to shift start (p < 0.05). Performance on PVT-B speed, RT, and false starts were poorer at shift end than shift start for the no-nap and 30-min nap conditions (p < 0.05), but not for the 2-hr nap condition (p > 0.05). Compared to pre-nap measures, performance on the PVT-B assessed at 0 mins post-nap showed significant performance declines for lapses and speed for both the 30-min and 2-hr nap conditions (p < 0.05), but not at 10, 20, or 30 mins post-nap. After waking from the 2-hr on-shift nap opportunity (at 0 mins), participants rated sleepiness, difficulty with concentration, and alertness poorer than pre-nap (p < 0.05). Participants in the 30-min nap condition rated alertness poorer immediately after the nap (at 0 mins) compared to pre-nap (p < 0.05). CONCLUSIONS: While sleep inertia was detectable immediately following short 30-min and long 2-hr nap opportunities during simulated night shift work, deficits in cognitive performance and subjective ratings quickly dissipated and were not detectable at 10-30 mins post-nap.

Ambulatory blood pressure monitoring among emergency medical services night shift workers.

OBJECTIVES: Higher 24-hour blood pressure (BP) and blunted BP dipping during sleep and night-time hours are associated with adverse health outcomes. Night shift work may affect 24-hour BP and dipping patterns, but empirical data in emergency medical services (EMS) clinician shift workers are sparse. We implemented ambulatory blood pressure monitoring (ABPM) in EMS workers to characterise BP during night shift work versus a non-workday, and sleep versus wake. METHODS: Participants worked night shifts. Hourly ABPM and wrist actigraphy (to measure sleep) were collected during two 24-hour periods, one scheduled night shift and one non-workday. Blunted BP dipping was defined as a BP decrease of <10%. RESULTS: Of 56 participants, 53 (53.6% female, mean age 26.5 (SD 7.5) years) completed the study. During daytime sleep on a workday, 49.1% of participants had blunted systolic BP (SBP) or diastolic BP (DBP) dipping. During night-time sleep on a non-workday, 25% had blunted SBP dipping and 3.9% blunted DBP dipping. Blunted SBP or DBP dipping occurred among all participants who did not nap during the night shift or who napped <60 min. Blunted SBP dipping occurred in only 14.3% of participants who napped 60-120 min. CONCLUSIONS: During night shift work, the BP dipping of EMS shift workers is blunted; however, most who nap for 60 min or longer experience a healthy dip in BP. The potential health consequences of these observations in EMS clinicians warrant further study.

Predictors of Partial Hospital Readmission for Young Children with Oppositional Defiant Disorder.

This study aimed to: (1) examine rates of readmission among young children with oppositional defiant disorder (ODD) following discharge from a psychiatric partial hospital treatment program, and (2) examine child factors (i.e., age, sex, co-occurring diagnoses, suicidality) and family factors (i.e., parental depression, stress) as prospective predictors of readmission. Participants were 261 children (ages 3-7 years) who entered the study at the time of their initial program admission and who met DSM-IV criteria for ODD. Of these 261 children, 61 (23%) were subsequently readmitted, with most readmissions occurring within 1 year. Cox regression survival analyses demonstrated that younger child age, child suicidal thoughts and behavior, and child PTSD diagnosis were associated with decreased time to readmission. Findings suggest that young children with ODD who present with co-occurring suicidality or PTSD are at risk for readmission following partial hospitalization, with implications for treatment and aftercare planning.

Temper Loss and Persistent Irritability in Preschoolers: Implications for Diagnosing Disruptive Mood Dysregulation Disorder in Early Childhood.

Disruptive Mood Dysregulation Disorder (DMDD) is a new and controversial child psychiatric disorder characterized by persistent irritability and frequent temper loss. Among the controversies surrounding DMDD is whether the age of onset criterion-that DMDD may not be diagnosed before age 6 years-is justified. This study examined DMDD symptoms and associated patterns of psychiatric comorbidity, behavioral, and family functioning in a sample of 139 preschoolers (ages 4-0 to 5-11 years) admitted to an early childhood psychiatric day treatment program. DMDD symptoms were common in this acute clinical sample, with 63 children (45.3 %) presenting with frequent temper outbursts and chronic irritability. As compared to children who did not present with DMDD symptoms, these children demonstrated more aggression and emotional reactivity and lower receptive language skills, with high rates of comorbidity with the disruptive behavior disorders. Findings contribute to an emerging literature on preschool DMDD, with implications for early childhood psychiatric assessment and clinical interventions.

Hand1 overexpression inhibits medulloblastoma metastasis.

Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of ß-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, ß-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis.

Sleep Onset and Night Waking Insomnias in Preschoolers with Psychiatric Disorders.

This study examined the nature and prevalence of diagnostically defined sleep disorders, including Sleep Onset Insomnia (SOI) and Night Waking Insomnia (NWI), in a sample of 183 young children admitted to an early childhood psychiatric day treatment program. A semi-structured diagnostic interview, the Diagnostic Infant and Preschool Assessment, was used to assess for sleep and other psychiatric disorders. Daily sleep diaries and the Child Behavior Checklist were also examined. 41 % of children met criteria for a sleep disorder; 23 % met diagnostic criteria for SOI and 4 % met criteria for NWI, with an additional 14 % meeting criteria for both (SOI + NWI). Sleep-disordered children demonstrated longer latency to sleep onset, longer and more frequent night awakenings, less total sleep, and lower sleep efficiency than non-sleep disordered participants. Diagnosable sleep disorders, particularly SOI, were quite common in this acute clinical sample, exceeding previous estimates obtained in community and pediatric practice samples.

The effect of a night shift nap on post-night shift performance, sleepiness, mood, and first recovery sleep: A randomized crossover trial.

OBJECTIVES: This study aimed to test the effect of a 30-minute nap versus a 2-hour nap opportunity taken during a simulated night shift on performance, fatigue, sleepiness, mood, and sleep at the end of shift and during post-night shift recovery. METHODS: We conducted a randomized crossover trial of three nap conditions (30-minute, 2-hour, and no-nap) during 12-hour simulated night shifts. We tested for differences in performance, fatigue, sleepiness, mood, and sleep during in-lab and at-home recovery. Performance was measured with the Brief Psychomotor Vigilance Test (PVT-B). Subjective ratings were assessed with single-item surveys. RESULTS: Twenty-eight individuals consented to participate [mean age 24.4 (standard deviation 7.2) years; 53.6% female; 85.7% Emergency Medical Services clinicians]. PVT-B false starts at the end of the 12-hour night shift (at 07:00 hours) and at the start of in-lab recovery (08:00 hours) were lower following the 2-hour nap versus other conditions (P<0.05). PVT-B response time at +0 minutes post-recovery nap was poorer compared to pre-recovery nap for the no-nap condition (P=0.003), yet not detected for other nap conditions (P>0.05). Sleepiness, fatigue, and some mood states were lower at most hourly assessments during the in-lab recovery period following the 2-hour nap condition compared to the other conditions. Sleep during recovery did not differ by duration of night shift nap. CONCLUSIONS: A 2-hour nap opportunity versus a 30-minute or no-nap opportunity is beneficial for performance, alertness, and mood post-night shift. No differences were detected in sleep during recovery.

Partial hospitalization treatment for preschoolers with severe behavior problems: child age and maternal functioning as predictors of outcome.

BACKGROUND: This study focused on the behavioral functioning and treatment outcomes of preschool-aged children who attended a specialized, family focused psychiatric partial hospitalization program. METHOD: Study data were collected between 2002 and 2007. Maternal reports of child behavioral functioning were obtained at program admission and discharge. Maternal parenting stress and psychiatric impairment were assessed at admission. RESULTS: Children's symptom severity decreased from admission to discharge, particularly with respect to externalizing symptoms. Both child age and maternal functioning emerged as predictors of treatment outcome. CONCLUSIONS: Specialized partial hospitalization may be an effective approach to treatment for preschool children with severe psychopathology.

The Emergency Medical Services Sleep Health Study: A cluster-randomized trial.

BACKGROUND: Greater than half of emergency medical services (EMS) clinician shift workers report poor sleep, fatigue, and inadequate recovery between shifts. We hypothesized that EMS clinicians randomized to receive tailored sleep health education would have improved sleep quality and less fatigue compared to wait-list controls after 3 months. METHODS: We used a cluster-randomized, 2-arm, wait-list control study design (clinicaltrials.gov identifier: NCT04218279). Recruitment of EMS agencies (clusters) was nationwide. Our study was powered at 88% to detect a 0.4 standard deviation difference in sleep quality with 20 agencies per arm and a minimum of 10 individuals per agency. The primary outcome was measured using the Pittsburgh Sleep Quality Index (PSQI) at 3-month follow-up. Our intervention was accessible in an online, asynchronous format and comprised of 10 brief education modules that address fatigue mitigation topics prescribed by the American College of Occupational Environmental Medicine. RESULTS: In total, 36 EMS agencies and 678 individuals enrolled. Attrition at 3 months did not differ by study group (Intervention = 17.4% vs. Wait-list control = 18.2%; p = .37). Intention-to-treat analyses detected no differences in PSQI and fatigue scores at 3 months. Per protocol analyses showed the greater the number of education modules viewed, the greater the improvement in sleep quality and the greater the reduction in fatigue (p < .05). CONCLUSIONS: While intention-to-treat analyses revealed no differences in sleep quality or fatigue at 3 months, per protocol findings identified select groups of EMS clinician shift workers who may benefit from sleep health education. Our findings may inform fatigue risk management programs.

Glioblastoma occurring at the site of a previous medulloblastoma following a 5-year remission period.

We describe a case of a 14-year-old boy who developed a cerebellar and brainstem glioblastoma 5 years after treatment for a medulloblastoma. The patient first presented in 2003 with 9 months of vomiting and a 9-kg weight loss. A head MRI showed a heterogeneously enhancing posterior fossa mass with hydrocephalus. Gross total resection was performed and the tumor was consistent with a classic medulloblastoma. Postoperative chemotherapy and craniospinal radiation was administered. The patient remained tumor-free until 2008, at which time he presented with right-sided weakness and numbness, left eye pain, vomiting and weight loss. Imaging showed abnormalities within the posterior pons, medulla, inferior cerebellar peduncles, cerebellar hemispheres and cervicomedullary junction with expansion of the medulla and cervical spinal cord. Due to the location of the lesion, biopsy was felt to be too risky and was avoided. Despite receiving chemotherapy, his symptoms continued to worsen and he died 4 months later. Post mortem examination limited to the brain and spinal cord confirmed the radiographic extent of the tumor. Microscopic examination showed a highly cellular infiltrative glial neoplasm with extensive palisading necrosis. A diagnosis of glioblastoma was rendered. The question of whether the first and second tumors were related is of potential clinical and academic interest. The first tumor was synaptophysin-positive and GFAP-negative, consistent with medulloblastoma. The second tumor was synaptophysin-negative and focally GFAP-positive, consistent with glioblastoma. The glioblastoma displayed EGF receptor amplification, and interestingly, it also displayed MYCN amplification; both tumors showed low level PTEN deletion. The medulloblastoma displayed a signal pattern consistent with an isochromosome 17q, while the glioblastoma showed some cells with an isochromosome 17q signal pattern amid a background of cells with abundant chromosomal instability. The relationship between these two tumors, particularly with regard to various molecular events, is discussed.

Temporal and optic pathway pilomyxoid astrocytoma mimicking dural-based lesion: case report and review of the literature.

Pilomyxoid astrocytomas (PMAs) are low-grade tumors that share many common traits with pilocytic astrocytomas. However, PMAs have a more worrisome clinical course, with a higher recurrence rate, lower survival rate, and higher risk of leptomeningeal spread compared to pilocytic tumors. These tumors tend to occur in younger children and are typically located in the area of the optic chiasm or hypothalamus. There are few studies examining the radiographic appearance of these lesions. In this case report, the authors present an unusual radiographic appearance of a PMA in an 11-year-old child. Preoperative images suggested a dural-based, homogenously enhancing lesion coupled with an enlarged optic nerve. Surgery revealed an intraparenchymal lesion of the right temporal lobe. There was hyperintensity on T2 MRI sequences, suggesting infiltration of the tumor along the optic tracts.

Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: an immunohistochemical and immunoelectron microscopic study.

TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin sections from 38 rhabdomyosarcomas, five leiomyomas, five leiomyosarcomas, five rhabdomyomas, five rhabdomyomatous Wilms tumors, three normal cardiac muscles, one medullomyoblastoma, one pleuropulmonary blastoma with rhabdomyomatous differentiation, and one teratoma with prominent rhabdomyoblasts. Each case was also stained with desmin. Unlike the nuclear staining scored in myoepithelial cells, only cytoplasmic staining for p63 was considered positive. Of 38 cases of rhabdomyosarcoma, 36 showed cytoplasmic p63 staining; 24 of these showed highlighting of cross-striations superior to that of desmin. In addition, 5/5 rhabdomyomas, 5/5 rhabdomyomatous Wilms tumors, 1/1 pleuropulmonary blastoma with rhabdomyomatous differentiation, 1/1 teratoma with atypical rhabdoblasts, and 1/1 medullomyoblastoma exhibited cytoplasmic p63 staining. Normal cardiac muscle samples (3/3) also demonstrated positive cytoplasmic staining and distinct cross-striations. Smooth muscle tumors exhibited only very focal and faint cytoplasmic staining in 5/5 leiomyomas and 4/5 leiomyosarcomas. Immunoelectron microscopic study of skeletal muscle showed p63 localization to the Z bands of sarcomeres. We conclude that p63 immunostain is a sensitive marker for skeletal muscle differentiation and highlights the cross-striations of strap cells with exceptional definition.

Napping on the night shift and its impact on blood pressure and heart rate variability among emergency medical services workers: study protocol for a randomized crossover trial.

BACKGROUND: There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. METHODS: We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. DISCUSSION: Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020.

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases.

Primary central nervous system lymphomas are rare neoplasms characterized by a dismal prognosis relative to other extranodal lymphomas. Approximately 98% of primary central nervous system lymphomas are of B-cell origin, and most belong to the diffuse large B-cell type. Recently, diffuse large B-cell lymphomas have been subcategorized into germinal center and nongerminal center types based on gene expression profiles and immunohistochemical expression of CD10, Bcl-6, and MUM1. Studies have shown that the overall survival rate of the germinal center group is better than that of the nongerminal center lymphomas. In this study, 31 cases of primary central nervous system lymphomas of the diffuse large B-cell type were retrieved, reviewed, and immunostained for CD10, Bcl-6, MUM1, and Ki-67. Subclassification was carried out as described earlier, where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered characteristic of germinal center subtype and the opposite expression of nongerminal center subtype. Furthermore, the proliferative activity was semiquantitatively assessed using percent positive cells staining with Ki-67. Of the 31 cases examined, 26 (84%) were found to belong to the nongerminal center type. The Ki-67 index in these 26 cases ranged from 30 to 90% (mean, 69%). Five cases were categorized as the germinal center subtype. They had an Ki-67 index between 70 and 90% (mean, 78%). Interestingly, none of our patients were known to be HIV positive. One patient had a 10-year history of orthotopic liver transplant. We also performed fluorescence in situ hybridization analysis on formalin-fixed material and found that 38% of the cases where tissue was available had abnormalities of MYC/IGH and/or IGH/BCL2. We conclude that most primary central nervous system diffuse large B-cell lymphomas are of the nongerminal center origin. Regardless of the germinal center status, all cases showed a high proliferative rate. A statistically significant difference in the overall survival between the two groups was not seen.

Anger and sadness perception in clinically referred preschoolers: emotion processes and externalizing behavior symptoms.

This study examined emotion perception processes in preschool aged children presenting with clinically significant emotional and behavior problems, with emphasis on sadness perception accuracy (i.e., the ability to correctly identify sadness from expressive and situational cues) and anger perception bias (i.e., the tendency to perceive anger in the absence of concordant cues) as related to children's externalizing symptoms. Participants were 82 children (3-5 years of age) admitted to a psychiatric day treatment program. Children participated in a structured puppet play activity to assess emotion understanding. Mothers reported on children's externalizing symptoms and program staff reported on children's emotion regulation and negative emotional lability. Young children in this clinical sample demonstrated generally age-appropriate ability to identify basic emotions as expressed within prototypical social situations. Most emotion perception errors involved the over-identification of sadness. Children's decreased accuracy in sadness perception was associated with increased externalizing symptoms. Children's negative emotional lability contributed unique variance to the prediction of externalizing symptoms, with more labile children also demonstrating increased symptoms. Results underscore the role of emotion processes in early childhood mental health problems, with implications for emotion-based treatments of early externalizing behavior symptoms.