Impact of Dialectical Behavioral Therapy on Anxiety Levels Among African American Adolescents.

Anxiety and depression among adolescents in the United States has steadily increased. In addition, significant disparities in access to mental health care exist for African Americans. The purpose of the current project was to support the mental health of African American adolescents involved in faith-based youth groups through implementation of dialectical behavioral therapy (DBT). The community partner was an African American church in Southwest Georgia. Mindfulness training modules are offered in monthly sessions. Pre- and post-intervention surveys and the Generalized Anxiety Disorder-7 (GAD-7) were analyzed, comparing mean GAD-7 scores before and after participation. Nurse-led quality improvement initiatives support adolescent mental health and provide sustainable resources for mental health in rural areas. Results of the quality improvement project reveal improvement in self-reported anxiety symptoms among participants after the 4-month DBT intervention. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Spatiotemporal transitions in Pseudo-nitzschia species assemblages and domoic acid along the Alaska coast.

The toxic diatom genus Pseudo-nitzschia is distributed from equatorial to polar regions and is comprised of >57 species, some capable of producing the neurotoxin domoic acid (DA). In the Pacific Arctic Region spanning the Bering, Chukchi, and Beaufort seas, DA is recognized as an emerging human and ecosystem health threat, yet little is known about the composition and distribution of Pseudo-nitzschia species in these waters. This investigation characterized Pseudo-nitzschia assemblages in samples collected in 2018 during summer (August) and fall (October-November) surveys as part of the Distributed Biological Observatory and Arctic Observing Network, encompassing a broad geographic range (57.8° to 73.0°N, -138.9° to -169.9°W) and spanning temperature (-1.79 to 11.7°C) and salinity (22.9 to 32.9) gradients associated with distinct water masses. Species were identified using a genus-specific Automated Ribosomal Intergenic Spacer Analysis (ARISA). Seventeen amplicons were observed; seven corresponded to temperate, sub-polar, or polar Pseudo-nitzschia species based on parallel sequencing efforts (P. arctica, P. delicatissima, P. granii, P. obtusa, P. pungens, and two genotypes of P. seriata), and one represented Fragilariopsis oceanica. During summer, particulate DA (pDA; 4.0 to 130.0 ng L-1) was observed in the Bering Strait and Chukchi Sea where P. obtusa was prevalent. In fall, pDA (3.3 to 111.8 ng L-1) occurred along the Beaufort Sea shelf coincident with one P. seriata genotype, and south of the Bering Strait in association with the other P. seriata genotype. Taxa were correlated with latitude, longitude, temperature, salinity, pDA, and/or chlorophyll a, and each had a distinct distribution pattern. The observation of DA in association with different species, seasons, geographic regions, and water masses underscores the significant risk of Amnesic Shellfish Poisoning (ASP) and DA-poisoning in Alaska waters.

Nonsurgical Management of Distal Radius Fractures in the Elderly: Approaches, Risks and Limitations.

The elderly have conventionally been defined as individuals over the age of 65 and are projected to represent about 21% of the United States (US) population by the year 2030. Distal radius fractures (DRF) in particular are one of the most common fractures among elderly patients and their incidence continues to rise in part due to increased activity levels among the elderly, increased life expectancy, rising rates of obesity, changes to dietary habits, and the prevalence of osteoporosis. Although various treatment options exist for these injuries, nonsurgical treatment of distal radius fractures remains a mainstay among elderly patients with mounting evidence of its non-inferiority to surgical fixation in the literature. Here, we summarize the overall approach to nonsurgical treatment of distal radius fractures in the elderly population while examining its supporting data and highlighting potential risks and limitations to it.

Role of E6 in Maintaining the Basal Cell Reservoir during Productive Papillomavirus Infection.

Papillomaviruses exclusively infect stratified epithelial tissues and cause chronic infections. To achieve this, infected cells must remain in the epithelial basal layer alongside their uninfected neighbors for years or even decades. To examine how papillomaviruses achieve this, we used the in vivo MmuPV1 (Mus musculus papillomavirus 1) model of lesion formation and persistence. During early lesion formation, an increased cell density in the basal layer, as well as a delay in the infected cells' commitment to differentiation, was apparent in cells expressing MmuPV1 E6/E7 RNA. Using cell culture models, keratinocytes exogenously expressing MmuPV1 E6, but not E7, recapitulated this delay in differentiation postconfluence and also grew to a significantly higher density. Cell competition assays further showed that MmuPV1 E6 expression led to a preferential persistence of the cell in the first layer, with control cells accumulating almost exclusively in the second layer. Interestingly, the disruption of MmuPV1 E6 binding to MAML1 protein abrogated these phenotypes. This suggests that the interaction between MAML1 and E6 is necessary for the lower (basal)-layer persistence of MmuPV1 E6-expressing cells. Our results indicate a role for E6 in lesion establishment by facilitating the persistence of infected cells in the epithelial basal layer, a mechanism that is most likely shared by other papillomavirus types. Interruption of this interaction is predicted to impede persistent papillomavirus infection and consequently provides a novel treatment target. IMPORTANCE Persistent infection with high-risk HPV types can lead to development of HPV-associated cancers, and persistent low-risk HPV infection causes problematic diseases, such as recurrent respiratory papillomatosis. The management and treatment of these conditions pose a considerable economic burden. Maintaining a reservoir of infected cells in the basal layer of the epithelium is critical for the persistence of infection in the host, and our studies using the mouse papillomavirus model suggest that E6 gene expression leads to the preferential persistence of epithelial cells in the lower layers during stratification. The E6 interaction with MAML1, a component of the Notch pathway, is required for this phenotype and is linked to E6 effects on cell density and differentiation. These observations are likely to reflect a common E6 role that is preserved among papillomaviruses and provide us with a novel therapeutic target for the treatment of recalcitrant lesions.

Children's and Adults' Beliefs about the Stability of Traits from Infancy to Adulthood: Contributions of Age and Executive Function.

We examined developmental differences and sources of variability in trait reasoning. Four- to 10-year-olds and adults (N=198) rated how mean or nice "medium-mean" and "medium-nice" babies, kids, and teenagers were earlier in their lifetime and would be at older ages. Participants expected nice-labeled characters to be nice throughout their lives (participant age effects were null). In contrast, we documented age-related differences in judgments about meanness. With increasing participant age, individuals expected that meanness present in infancy, childhood, and adolescence would persist into adulthood. We discovered a curvilinear pattern in assessments of whether meanness originates during infancy: Four- to 5-year-olds and adults expected mean-labeled kids and teenagers to have been nicer as babies than did 6- to 10-year-olds. Controlling for age and working memory, participants with better inhibitory control more frequently expected mean-labeled individuals to remain mean across the lifespan, but inhibitory control was unrelated to judgments about nice-labeled individuals.

Delta-Like Ligand-Notch1 Signaling Is Selectively Modulated by HPV16 E6 to Promote Squamous Cell Proliferation and Correlates with Cervical Cancer Prognosis.

Human papillomavirus (HPV) drives high-grade intraepithelial neoplasia and cancer; for unknown reasons, this occurs most often in the cervical transformation zone. Either mutation or HPV E6-driven inhibition of Notch1 can drive neoplastic development in stratified squamous epithelia. However, the contribution of Notch1 and its Delta-like ligands (DLL) to site susceptibility remains poorly understood. Here, we map DLL1/DLL4 expression in cell populations present in normal cervical biopsies by immunofluorescence. In vitro keratinocyte 2D monolayer models, growth assays, and organotypic raft cultures were used to assess the functional role of DLL-Notch signaling in uninfected cells and its modulation by HPV16 in neoplasia. An RNA sequencing-based gene signature was used to suggest the cell of origin of 279 HPV-positive cervical carcinomas from The Cancer Genome Atlas and to relate this to disease prognosis. Finally, the prognostic impact of DLL4 expression was investigated in three independent cervical cancer patient cohorts. Three molecular cervical carcinoma subtypes were identified, with reserve cell tumors the most common and linked to relatively good prognosis. Reserve cells were characterized as DLL1-/DLL4+, a proliferative phenotype that is temporarily observed during squamous metaplasia and wound healing but appears to be sustained by HPV16 E6 in raft models of low-grade and, more prominently, high-grade neoplasia. High expression of DLL4 was associated with an increased likelihood of cervical cancer-associated death and recurrence. Taken together, DLL4-Notch1 signaling reflects a proliferative cellular state transiently present during physiologic processes but inherent to cervical reserve cells, making them strongly resemble neoplastic tissue even before HPV infection has occurred. SIGNIFICANCE: This study investigates cervical cancer cell-of-origin populations and describes a DLL-Notch1 phenotype that is associated with disease prognosis and that might help identify cells that are susceptible to HPV-induced carcinogenesis.

Dynamics of papillomavirus in vivo disease formation & susceptibility to high-level disinfection-Implications for transmission in clinical settings.

BACKGROUND: High-level disinfection protects tens-of-millions of patients from the transmission of viruses on reusable medical devices. The efficacy of high-level disinfectants for preventing human papillomavirus (HPV) transmission has been called into question by recent publications, which if true, would have significant public health implications. METHODS: Evaluation of the clinical relevance of these published findings required the development of novel methods to quantify and compare: (i) Infectious titres of lab-produced, clinically-sourced, and animal-derived papillomaviruses, (ii) The papillomavirus dose responses in the newly developed in vitro and in vivo models, and the kinetics of in vivo disease formation, and (iii) The efficacy of high-level disinfectants in inactivating papillomaviruses in these systems. FINDINGS: Clinical virus titres obtained from cervical lesions were comparable to those obtained from tissue (raft-culture) and in vivo models. A mouse tail infection model showed a clear dose-response for disease formation, that papillomaviruses remain stable and infective on fomite surfaces for at least 8 weeks without squames and up to a year with squames, and that there is a 10-fold drop in virus titre with transfer from a fomite surface to a new infection site. Disinfectants such as ortho-phthalaldehyde and hydrogen peroxide, but not ethanol, were highly effective at inactivating multiple HPV types in vitro and in vivo. INTERPRETATION: Together with comparable results presented in a companion manuscript from an independent laboratory, this work demonstrates that high-level disinfectants inactivate HPV and highlights the need for standardized and well-controlled methods to assess HPV transmission and disinfection. FUNDING: Advanced Sterilization Products, UK-MRC (MR/S024409/1 and MC-PC-13050) and Addenbrookes Charitable Trust.

Glomus tumors with malignant features of the extremities: a case series.

BACKGROUND: Malignant glomus tumors are exceedingly rare, however they can be locally aggressive and have the potential to metastasize. There is limited information available in the literature regarding treatment and outcomes, therefore we present a case series of 5 patients with glomus tumors with malignant features confined to the extremities that have presented to our tertiary sarcoma center within the last 20 years. This is the largest case series of its kind in the malignant glomus tumor literature, to our knowledge. METHODS: We performed a retrospective chart review of all patients with histologically confirmed glomus tumors with malignant features in the extremities found within the University of Michigan EMERSE database since January 1st, 2000. RESULTS: Five patients met our inclusion and exclusion criteria. Three patients were diagnosed with malignant glomus tumors, one patient with glomus tumor with uncertain malignant potential, and the last patient with malignant glomus tumor with leiomyosarcomatous features. Males and females were equally represented. Age range was 9-49 years at time of first presentation. All patients underwent an initial surgical resection. Three of the five patients (60%) underwent initial resection at an outside hospital prior to referral to tertiary sarcoma center, and all three required re-resection. One of these patients had local tumor recurrence after a planned positive margin resection and radiotherapy. Another patient had distant metastasis after a positive margin surgical resection and a short course of radiotherapy. All patients are still alive according to their medical record with the average time from initial treatment to last follow up of 59.2 months. CONCLUSIONS: Our study supports the current literature that wide-local resection with the goal of negative margins is still the current gold standard treatment for glomus tumors with malignant features. Studies with larger cohorts are necessary before recommending for or against radiotherapy or chemotherapy. Early biopsy and referral to a tertiary sarcoma center prior to surgical resection may help reduce the re-resection rate and potential seeding of the tumor in these patients, thereby improving outcomes.

Gestational age is related to symptoms of attention-deficit/hyperactivity disorder in late-preterm to full-term children and adolescents with down syndrome.

Attention-deficit/hyperactivity disorder is frequently reported in individuals with Down syndrome, with considerable variation in the expression and severity of the symptoms. Despite growing evidence that gestational age predicts later symptoms of attention-deficit/hyperactivity disorder in the euploid population, this has not been studied in down syndrome. The current study is designed to investigate the influence of gestational age in later symptoms of attention-deficit/hyperactivity disorder in 105 individuals (49 males and 56 females; aged 6-18 years) with Down syndrome who were born at or after 35 weeks gestation. Maternal age at birth, maternal level of education, household income, as well as sex, chronological age, and cognitive level of the participant with Down syndrome were considered in our analysis. Results from this study show that gestational age is related to inattentive and hyperactive/impulsive symptoms in children and adolescents with Down syndrome. Therefore, gestational age should be addressed when considering symptoms of attention-deficit/hyperactivity disorder, as it may have implications for early interventions. More attention is needed toward the advancement of care and follow-up for infants with down syndrome who are born even late preterm or early term.

Chryseobacterium bacteraemia in a patient with heart failure: case report and literature review.

BACKGROUND: A 29-year-old male with recently diagnosed biventricular failure from myopericarditis and subsequent constrictive pericarditis on home milrinone presented to the Emergency Department with fevers/chills. CASE SUMMARY: On arrival to the Emergency Department, he was found to have septic shock and required vasopressor therapy. Chryseobacterium indologenes grew on his admission blood cultures, and he was treated with ciprofloxacin and piperacillin/tazobactam. He quickly improved, allowing for a successful pericardiectomy, was weaned off inotropes and discharged from the hospital. DISCUSSION: Chryseobacterium indologenes is an environmental Gram-negative rod found in groundwater. It is rarely associated with human infection, but is associated with indwelling lines and has been documented in immunocompromised patients. Treatment typically involves line removal and a fluoroquinolone or piperacillin/tazobactam; the most optimal antimicrobial regimen and duration of treatment are unknown.

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development.

RATIONALE: Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue. OBJECTIVE: To develop a new large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs. This approach is developed to enable growth-scaled measurements per-cell of the MC proteome and sarcomeric proteins (i.e. myosin heavy chain (MyHC) and alpha-actin (α-actin)) content. METHODS AND RESULTS: Individual cardiac cells were isolated from 21 to 94days old mice. An LP-FACS jet-in-air system with a 200-µm nozzle was defined for the first time to purify adult MCs. Cell-type specific immunophenotyping and sorting yielded ≥95% purity of adult MCs independently of cell morphology and size. This approach excluded other cell types and tissue contaminants from further analysis. MC proteome, MyHC and α-actin proteins were measured in linear biochemical assays normalized to cell numbers. Using the allometric coefficient α, we scaled the MC-specific rate of protein accumulation to growth post-weaning. MC-specific volumes (α=1.02) and global protein accumulation (α=0.94) were proportional (i.e. isometric) to body mass. In contrast, MyHC and α-actin accumulated at a much greater rate (i.e. hyperallometric) than body mass (α=1.79 and 2.19 respectively) and MC volumes (α=1.76 and 1.45 respectively). CONCLUSION: Changes in MC proteome and cell volumes measured in LP-FACS purified MCs are proportional to body mass post-weaning. Oppositely, MyHC and α-actin are concentrated more rapidly than what would be expected from MC proteome accumulation, cell enlargement, or animal growth alone. LP-FACS provides a new standard for adult MC purification and an approach to scale the biochemical content of specific proteins or group of proteins per cell in enlarging MCs.

The ability for cocaine and cocaine-associated cues to compete for attention.

In humans, reward cues, including drug cues in individuals experiencing addiction, are especially effective in biasing attention towards them, so much so they can disrupt ongoing task performance. It is not known, however, whether this happens in rats. To address this question, we developed a behavioral paradigm to assess the capacity of an auditory drug (cocaine) cue to evoke cocaine-seeking behavior, thus distracting thirsty rats from performing a well-learned sustained attention task (SAT) to obtain a water reward. First, it was determined that an auditory cocaine cue (tone-CS) reinstated drug-seeking equally in sign-trackers (STs) and goal-trackers (GTs), which otherwise vary in the propensity to attribute incentive salience to a localizable drug cue. Next, we tested the ability of an auditory cocaine cue to disrupt performance on the SAT in STs and GTs. Rats were trained to self-administer cocaine intravenously using an Intermittent Access self-administration procedure known to produce a progressive increase in motivation for cocaine, escalation of intake, and strong discriminative stimulus control over drug-seeking behavior. When presented alone, the auditory discriminative stimulus elicited cocaine-seeking behavior while rats were performing the SAT, but it was not sufficiently disruptive to impair SAT performance. In contrast, if cocaine was available in the presence of the cue, or when administered non-contingently, SAT performance was severely disrupted. We suggest that performance on a relatively automatic, stimulus-driven task, such as the basic version of the SAT used here, may be difficult to disrupt with a drug cue alone. A task that requires more top-down cognitive control may be needed.

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease.

Oxyntomodulin is a hormone and a growth factor. It activates two receptors, the Glucagon-like peptide 1 (GLP-1) and the glucagon receptor. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. These drugs have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a clinical trial in PD patients showed promising first positive results. D-Ser2-oxyntomodulin (Oxy) is a protease resistant oxyntomodulin analogue that has been developed to treat diabetes. Here we demonstrate for the first time that such analogues have neuroprotective effects. The drug showed protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected daily (20 mg/kg i.p.) for 7 days, and Oxy injected once-daily for 14 days i.p. Oxy treatment prevented or reversed the MPTP- induced motor impairment (Rotarod, spontaneous locomotion, swim activity, muscle strength test), the MPTP-induced reduction in Tyrosine Hydroxylase (TH) levels (dopamine synthesis) in the substantia nigra and basal ganglia, the reduction of the synaptic marker synapstophysin, the inactivation of the growth factor kinase Akt/PKB and of the anti-apoptotic signaling molecule Bcl-2, and the increase of levels of the pro-inflammatory cytokine TNF-α. The results demonstrate that oxyntomodulin analogues show promise as a novel treatment of PD.

Dehydro[12]annulenes: structures, energetics, and dynamic processes.

Density functional and coupled cluster calculations on neutral monodehydro[12]annulenes (C(12)H(10)) reveal a global minimum that should be kinetically stable. At the CCSD(T)/cc-pVDZ//BHLYP/6-31G* level, the unsymmetrical CTCTC conformer 1a lies at least 3 kcal/mol below all other isomers studied. The two isomers closest in energy to 1a are Möbius structure 5a (CCTCC) and all-cis 6a. Isomer 1a can undergo conformational automerization with E(a) = 3.9 kcal/mol, implying that this process would be rapid on the NMR time scale, and computed (1)H NMR parameters (GIAO-B3LYP/6-311+G**//RHF/6-31G*) are presented. Cumulenic dehydro[12]annulene isomers, with 1,2,3-butatriene subunits, were found to be reactive intermediates in the interconversion of different configurations of the alkyne forms. Pathways for configuration change of 1a, and for subsequent rearrangement to biphenyl, were investigated. The 28 kcal/mol overall barrier for the lowest energy pathway connecting 1a to biphenyl suggests that 1a is kinetically stable with respect to valence isomerization.