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Introduction Seclusion is part of the clinical practice in European psychiatric hospital care with the aim to maintain the safety of patients and staff. Adverse events and harm have been reported for patients and staff resulting from seclusion. Safety hazards, which are the prerequisite of adverse events, can be identified using video observation methods. Identifying safety hazards can be used to prevent adverse events and improve the quality of psychiatric care. Objectives To identify safety hazards during seclusion in psychiatric hospital care. Methods Descriptive design with non-participant video-observation of seclusion care practice. Data consisted of video recordings (n = 36) from six wards of one psychiatric hospital in Finland. The data were analysed with inductive thematic analysis. Results Clinical practice of seclusion included safety hazards stemming from the actions of patients and staff. Patients’ actions were as follows: aggressive behaviour, attempting to escape, precarious movements, preventing the visibility of staff, exposing themselves to contamination, and falls during seclusion. Staff actions included: leaving dangerous items to seclusion, issues in the administration of medication, performing physical and mechanical restraints in unsecure way, and precarious movements and postures. Conclusions According to our results, the use of seclusion has safety hazards that can result in harm for patients and staff. To improve the quality and safety of seclusion in clinical practice, the guidelines, practices, and staff training need to consider the various safety hazards. While the work in Europe to abolish the use of seclusion is still in progress, this topic requires attention in clinical practice, education, and policymaking. Disclosure No significant relationships.

BackgroundPancreatic islets are exposed to strong pro-apoptotic stimuli: inflammation and hyperglycemia, during the progression of the autoimmune diabetes (T1D). We found that the Cdk11(Cyclin Dependent Kinase 11) is downregulated by inflammation in the T1D prone NOD (non-obese diabetic) mouse model. The aim of this study is to determine the role of CDK11 in the pathogenesis of T1D and to assess the hierarchical relationship between CDK11 and Cyclin D3 in beta cell viability, since Cyclin D3, a natural ligand for CDK11, promotes beta cell viability and fitness in front of glucose.MethodsWe studied T1D pathogenesis in NOD mice hemideficient for CDK11 (N-HTZ), and, in N-HTZ deficient for Cyclin D3 (K11HTZ-D3KO), in comparison to their respective controls (N-WT and K11WT-D3KO). Moreover, we exposed pancreatic islets to either pro-inflammatory cytokines in the presence of increasing glucose concentrations, or Thapsigargin, an Endoplasmic Reticulum (ER)-stress inducing agent, and assessed apoptotic events. The expression of key ER-stress markers (Chop, Atf4 and Bip) was also determined.ResultsN-HTZ mice were significantly protected against T1D, and NS-HTZ pancreatic islets exhibited an impaired sensitivity to cytokine-induced apoptosis, regardless of glucose concentration. However, thapsigargin-induced apoptosis was not altered. Furthermore, CDK11 hemideficiency did not attenuate the exacerbation of T1D caused by Cyclin D3 deficiency.ConclusionsThis study is the first to report that CDK11 is repressed in T1D as a protection mechanism against inflammation-induced apoptosis and suggests that CDK11 lies upstream Cyclin D3 signaling. We unveil the CDK11/Cyclin D3 tandem as a new potential intervention target in T1D.

Despite the progress made in HIV treatment and prevention, HIV remains a major cause of adolescent morbidity and mortality in sub-Saharan Africa. As perinatally infected children increasingly survive into adulthood, the quality of life and mental health of this population has increased in importance. This review provides a synthesis of the prevalence of mental health problems in this population and explores associated factors. A systematic database search (Medline, PsycINFO, Scopus) with an additional hand search was conducted. Peer-reviewed studies on adolescents (aged 10–19), published between 2008 and 2019, assessing mental health symptoms or psychiatric disorders, either by standardized questionnaires or by diagnostic interviews, were included. The search identified 1461 articles, of which 301 were eligible for full-text analysis. Fourteen of these, concerning HIV-positive adolescents, met the inclusion criteria and were critically appraised. Mental health problems were highly prevalent among this group, with around 25% scoring positive for any psychiatric disorder and 30–50% showing emotional or behavioral difficulties or significant psychological distress. Associated factors found by regression analysis were older age, not being in school, impaired family functioning, HIV-related stigma and bullying, and poverty. Social support and parental competence were protective factors. Mental health problems among HIV-positive adolescents are highly prevalent and should be addressed as part of regular HIV care.

Background: Micronutrient folate is crucial in neural development. Folate metabolism is affected by genomic variation in methylenetetrahydrofolate reductase (MTHRF) gene. We set out to study the effects of prenatal maternal folate levels and genomic variation in the MTHFR on offspring developmental delay (DD), and whether candidate maternal single nucleotide polymorphisms (SNPs) modify the effect of folate on the risk of DD in the offspring. Methods: The mother-child dyads in this study (n1= 456, n2 = 415, n3= 184, n4 = 192) are part of the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) - cohort. Folate levels were measured from the plasma maximum of three times during pregnancy. Maternal MTHFR SNPs (rs1801131, rs1801133, rs1999594) were genotyped with Illumina Global Screening Array. Developmental milestones were assessed by Ages and Stages Questionnaire Third edition (ASQ-3) completed by mothers between the years 2 to 5. Results: Maternal folate levels during pregnancy did not associate with the risk of DD in the offspring. Any C-alleles in the maternal rs1801131 associated with both higher folate levels during pregnancy in the mother and lower risk of DD in the offspring. Moreover, maternal rs1801131 modified the association between the early pregnancy folate levels and the risk of DD in the offspring (p-value for interaction < .05). With low early pregnancy folate levels, the risk of DD in the offspring was lower if mother carried any C-alleles compared to AA genotype. While CC genotype in the rs1801133 associated with higher folate levels during pregnancy in the mother, we found no associations between maternal rs1801133 or rs1999594 and the risk of DD in the offspring. Conclusions: The current findings suggest that C-alleles in the MTHFR SNP rs1801131 may protect early neurodevelopment in the offspring when maternal folate levels during pregnancy are low.

Abstract Background Tooth filling treatment is utilized at low levels in many low and middle-income countries (LMICs), further, little is known about the prevailing attitudes towards such treatment. This study aimed to assess attitudes towards tooth filling among Tanzanian adults and how previous tooth filling experience is associated with these attitudes. Methods A pretested structured questionnaire was distributed among 1522 out-patients in four regional hospitals in Tanzania in 2015–16. The questionnaire had eight statements on a 6-point Likert scale measuring attitudes towards tooth filling. Responses were analyzed independently and through a constructed attitude sum score. Linear regression analysis was used to assess the association of previous tooth fillings on attitudes towards tooth filling treatment. Results The respondents were mostly female (57.3%), with a mean age of 33.1 years (SD 11.3). About one third of the respondents (36.4%) had primary level of education. Attitudes towards tooth filling treatment were generally negative. Low levels of education and income were associated with more negative attitudes. A small proportion (11.5%) had a previous tooth filling. Having a previous tooth filling was associated with a more positive attitude towards tooth fillings regardless of socioeconomic status. Conclusions This study shows that even in areas with limited resources and availability of services, previous experience of tooth fillings is related to more positive attitudes towards restorative treatment, which should be taken into account when planning oral health care programs.

A number of persistent 2,6-di-tert-butylphenoxyl based radicals were synthesized as models for unpaired spin delocalization as a function of conjugation pathway, and were investigated by ESR and UV-vis spectroscopy. Phenoxyl spin delocalizes significantly onto a para-phenyl ring, but further delocalization through a meta-vinyl or meta-carbonyl linkage is not detectable by ESR hyperfine coupling. UV- vis spectra do show a red shift of the longest wavelength transition for a carbonyl-type substituent by comparison to a vinyl substituent in the meta-position of a para-phenyl group. By comparison, a para-styryl substituent on the phenoxyl causes very large spin delocalization from the phenoxyl unit, with the largest hyperfine coupling being found on the ethenyl unit of the assemblage. This large delocalization accounts for the reactivity of radicals that incorporate such units.

To determine how tetraspanin KAI1/CD82, a tumor metastasis suppressor, inhibits cell migration, we assessed which cellular events critical for motility are altered by KAI1/CD82 and how KAI1/CD82 regulates these events. We found that KAI1/CD82-expressing cells typically exhibited elongated cellular tails and diminished lamellipodia. Live imaging demonstrated that the polarized protrusion and retraction of the plasma membrane became deficient upon KAI1/CD82 expression. The deficiency in developing these motility-related cellular events was caused by poor formations of actin cortical network and stress fiber and by aberrant dynamics in actin organization. Rac1 activity was reduced by KAI1/CD82, consistent with the diminution of lamellipodia and actin cortical network; while the growth factor-stimulated RhoA activity was blocked by KAI1/CD82, consistent with the loss of stress fiber and attenuation in cellular retraction. Upon KAI1/CD82 expression, Rac effector cofilin was not enriched at the cell periphery to facilitate lamellipodia formation while Rho kinase exhibited a significantly lower activity leading to less retraction. Phosphatidylinositol 4, 5-biphosphate, which initiates actin polymerization from the plasma membrane, became less detectable at the cell periphery in KAI1/CD82-expressing cells. Moreover, KAI1/CD82-induced phenotypes likely resulted from the suppression of multiple signaling pathways such as integrin and growth factor signaling. In summary, at the cellular level KAI1/CD82 inhibited polarized protrusion and retraction events by disrupting actin reorganization; at the molecular level, KAI1/CD82 deregulated Rac1, RhoA, and their effectors cofilin and Rho kinase by perturbing the plasma membrane lipids.

Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer.

The heat capacity of the title organic free radical, PhBABI, was measured over 0.3−300 K by adiabatic calorimetry and relaxation methods in the presence of external magnetic fields up to 9 T. A hump in the magnetic heat capacity was observed with a maximum at about 15 K in zero field, which did not shift at fields up to 9 T. The experimental magnetic entropy was in good agreement with the theoretical value of Rln 2 (= 5.76 J K −1mol −1) for S= 1/2 systems. The higher temperature, field-insensitive feature was fitted to several antiferromagnetic Heisenberg models. The best fits were obtained using spin ladder and coupled spin bilayer models. [ABSTRACT FROM AUTHOR]

2,7-Bis(1′-pyrenylvinylene)-9,9-diethylfluorene (1) and 2,7-bis(1′-pyrenylvinylene-4″-phenylenevinylene)-9,9-diethylfluorene (2) were synthesized and their static luminescence behavior assessed. They show solution photoluminescence (PL) maxima in chloroform at 475 nm and 467 nm, with quantum efficiencies of 54% and 52%, respectively. Double-layer LED devices with configuration ITO/PEDOT-PSS/(1 or 2)/Ca–Al emitted blue-green light with turn-on voltages of 2.5 V and emission maxima at 500 nm (2.48 eV); their luminance efficiencies were 0.36 and 0.30 cd A−1, respectively. Blending of 1 at 20% (w/w) in PVK improved the luminance efficiency to 1.81 cd A−1 for the same device configuration, with only a small increase in turn-on voltage to 3 V; the emission maximum was 497 nm (blue-green emission), the maximum luminance 7600 cd m−2 with CIE color coefficients of (0.12, 0.45). For a 10% (w/w) blend of 2 in PVK using the same device configuration, the luminance efficiency was 1.47 cd A−1, turn-on voltage 3 V, maximum luminance 2600 cd m−2 with CIE coefficients of (0.13, 0.45). Simple π-MO calculations show that structural extension of the nominal conjugation length in 2 does not significantly decrease the effective band gap relative to 1, consistent with the observed lack of red shift in 2. [ABSTRACT FROM AUTHOR]

Soil temperature is a main factor limiting root growth in the boreal forest. To simulate the possible soil-warming effect of future climate change, 5-year-old Norway spruce (Picea abies (L.) Karst.) seedlings were subjected to three simulated growing seasons in controlled environment rooms. The seedlings were acclimated to a soil temperature of 16 °C during the first (GS I) and third growing seasons (GS III), but were assigned to random soil-temperature treatments of 9, 13, 18 and 21 °C during the second growing season (GS II). In GS II, shoot diameter growth was lowest in the 21 °C treatment and root growth was lowest in the 9 °C treatment. In GS III, shoot height and root length growth improved in seedlings that had been kept at 9 °C during GS II, indicating compensatory growth in response to increased soil temperature. The temporary decrease in soil temperature had no long-lasting significant effect on seedling biomass or total nutrient uptake. At the end of GS III, fine roots of seedlings exposed to a soil temperature of 21 °C in GS II were distributed more evenly between the organic and mineral soil layers than roots of seedlings in the other treatments. During GS II and GS III, root growth started earlier than shoot growth, decreased during the rapid shoot elongation phase and increased again as shoot growth decreased. [ABSTRACT FROM AUTHOR]

Stable radicals 2-(6-uradinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (Ur6IN) and 4-(p-tert-butylaminoxylphenyl)-2,6-di(propylamido)pyridine (DAPPN) form heterospin radical pair complexes due to complementary multi-point hydrogen-bonds. [ABSTRACT FROM AUTHOR]

2,5-Bis(2-hydroxyethoxy)-1,4-bis(phenylethynyl)benzene (BHE-PE2.5) was synthesized and characterized by X-ray single-crystal diffraction analysis:  formula = C26H22O4, M = 398.44, orthorhombic unit cell, Pbcn, a = 22.5520(9) Å, b = 12.9259(4) Å, c = 7.2463(2) Å, α = β = γ = 90.00(0)°, V = 2112.33(12) Å3, Z = 4, R1 = 0.1194, vs2 = 0.1455. The molecules are somewhat deplanarized, with a 19.8° interplane torsion between phenyl rings. They form π-stacks with a centroid−centroid distance of 3.62 Å along the stack axis, a cant angle of the central phenyl ring of 13.2° relative to the π-stack c-axis, and a 99.2° rotation of each molecule along the π-stack, yielding crossed-dipole stacks in which the molecular long axes alternate nearly perpendicularly to one another. This unusual crossed dipole pattern is induced by a network of hydrogen bonds that assembles the BHE-PE2.5 molecules into the stacks and further associates the stacks into two-dimensional sheets. [ABSTRACT FROM AUTHOR]