Glaciolacustrine deposits formed in an ice-dammed tributary valley in the south-central Pyrenees: new evidence for late Pleistocene climate

Combined geomorphic features, stratigraphic characteristics and sedimentologic interpretation, coupled with optically stimulated luminescence (OSL) dates, of a glacio-fluvio-lacustrine sequence (Linás de Broto, northern Spain) provide new information to understand the palaeoenvironmental significance of dynamics of glacier systems in the south-central Pyrenees during the Last Glacial Cycle (≈130 ka to 14 ka). The Linás de Broto depositional system consisted of a proglacial lake fed primarily by meltwater streams emanating from the small Sorrosal glacier and dammed by a lateral moraine of the Ara trunk glacier. The resulting glacio-fluvio-lacustrine sequence, around 55 m thick, is divided into five lithological units consisting of braided fluvial (gravel deposits), lake margin (gravel and sand deltaic deposits) and distal lake (silt and clay laminites) facies associations. Evolution of the depositional environment reflects three phases of progradation of a high-energy braided fluvial system separated by two phases of rapid expansion of the lake. Fluvial progradation occurred during short periods of ice melting. Lake expansion concurred with ice-dam growth of the trunk glacier. The first lake expansion occurred over a time range between 55 ± 9 ka and 49 ± 11 ka, and is consistent with the age of the Viu lateral moraine (49 ± 8 ka), which marks the maximum areal extent of the Ara glacier during the Last Glacial Cycle. These dates confirm that the maximum areal extent of the glacier occurred during Marine Isotope Stages 4 and 3 in the south-central Pyrenees, thus before the Last Glacial Maximum. The evolution of the Linás de Broto depositional system during this maximum glacier extent was modulated by climate oscillations in the northern Iberian Peninsula, probably related to latitudinal shifts of the atmospheric circulation in the southern North-Atlantic Ocean, and variations in summer insolation intensity

DSM-5 Attenuated Psychosis Syndrome in Adolescents Hospitalized With Non-psychotic Psychiatric Disorders

Introduction: Although attenuated psychotic symptoms often occur for the first time during adolescence, studies focusing on adolescents are scarce. Attenuated psychotic symptoms form the criteria to identify individuals at increased clinical risk of developing psychosis. The study of individuals with these symptoms has led to the release of the DSM-5 diagnosis of Attenuated Psychosis Syndrome (APS) as a condition for further research. We aimed to characterize and compare hospitalized adolescents with DSM-5-APS diagnosis vs. hospitalized adolescents without a DSM-5-APS diagnosis. Methods: Interviewing help-seeking, hospitalized adolescents (aged 12–18 years) and their caregivers independently with established research instruments, we (1) evaluated the presence of APS among non-psychotic adolescents, (2) characterized and compared APS and non-APS individuals regarding sociodemographic, illness and intervention characteristics, (3) correlated psychopathology with levels of functioning and severity of illness and (4) investigated the influence of individual clinical, functional and comorbidity variables on the likelihood of participants to be diagnosed with APS. Results: Among 248 consecutively recruited adolescents (age=15.4 ± 1.5 years, females = 69.6%) with non-psychotic psychiatric disorders, 65 (26.2%) fulfilled APS criteria and 183 (73.8%) did not fulfill them. Adolescents with APS had higher number of psychiatric disorders than non-APS adolescents (3.5 vs. 2.4, p < 0.001; Cohen’s d = 0.77), particularly, disruptive behavior disorders (Cramer’s V = 0.16), personality disorder traits (Cramer’s V = 0.26), anxiety disorders (Cramer’s V = 0.15), and eating disorders (Cramer’s V = 0.16). Adolescents with APS scored higher on positive (Cohen’s d = 1.5), negative (Cohen’s d = 0.55), disorganized (Cohen’s d = 0.51), and general symptoms (Cohen’s d = 0.84), and were more severely ill (Cohen’s d = 1.0) and functionally impaired (Cohen’s d = 0.31). Negative symptoms were associated with lower functional levels (Pearson ρ = −0.17 to −0.20; p = 0.014 to 0.031). Global illness severity was associated with higher positive, negative, and general symptoms (Pearson ρ = 0.22 to 0.46; p = 0.04 to p < 0.001). APS status was independently associated with perceptual abnormalities (OR = 2.0; 95% CI = 1.6–2.5, p < 0.001), number of psychiatric diagnoses (OR = 1.5; 95% CI = 1.2–2.0, p = 0.002), and impaired stress tolerance (OR = 1.4; 95% CI = 1.1–1.7, p = 0.002) (r 2 = 0.315, p < 0.001). Conclusions: A considerable number of adolescents hospitalized with non-psychotic psychiatric disorders meet DSM-5-APS criteria. These help-seeking adolescents have more comorbid disorders and more severe symptoms, functional impairment, and severity of illness than non-APS adolescents. Thus, they warrant high intensity clinical care.John and Maxine Bendheim FoundationAlicia Koplowitz FoundationSpanish GovernmentERDF Funds from the European Commission, A way of making Europe, CIBERSAM PI17/02227Madrid Regional Government B2017/BMD-3740 AGES-CM-2European Union (EU) FP7-4-HEALTH-2009-2.2.1-2-241909 FP7-HEALTH-2013-2.2.1-2-603196 FP7-HEALTH-2013-2.2.1-2-602478European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking 115916 777394Fundacion Familia AlonsoInstituto de Salud Carlos II

Boldine inhibits the alveolar bone resorption during ligature-induced periodontitis by modulating the Th17/Treg imbalance

Background During periodontitis, tooth-supporting alveolar bone is resorbed when there is an increased expression of the pro-osteolytic factor termed receptor activator of nuclear factor kappa B ligand (RANKL), which is responsible for osteoclast differentiation and activation. In periodontitis-affected tissues, the imbalance between T-helper type-17 (Th17) and T-regulatory (Treg) lymphocyte activity favors this RANKL overexpression. In this context, immunotherapeutic strategies aimed at modulating this Th17/Treg imbalance could eventually arrest the RANKL-mediated alveolar bone loss. Boldine has been reported to protect from pathological bone loss during rheumatoid arthritis and osteoporosis, whose pathogenesis is associated with a Th17/Treg imbalance. However, the effect of boldine on alveolar bone resorption during periodontitis has not been elucidated yet. This study aimed to determine whether boldine inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during periodontitis. Methods Mice with ligature-induced periodontitis were orally treated with boldine (10/20/40 mg/kg) for 15 consecutive days. Non-treated periodontitis-affected mice and non-ligated mice were used as controls. Alveolar bone loss was analyzed by micro-computed tomography and scanning electron microscopy. Osteoclasts were quantified by histological identification of tartrate-resistant acid phosphatase-positive cells. Production of RANKL and its competitive antagonist osteoprotegerin (OPG) were analyzed by ELISA, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. The Th17 and Treg responses were analyzed by quantifying the T-cell frequency and number by flow cytometry. Also, the expression of their signature transcription factors and cytokines were quantified by qPCR. Results Boldine inhibited the alveolar bone resorption. Consistently, boldine caused a decrease in the osteoclast number and RANKL/OPG ratio in periodontal lesions. Besides, boldine reduced the Th17-lymphocyte detection and response and increased the Treg-lymphocyte detection and response in periodontitis-affected tissues. Conclusion Boldine, administered orally, inhibited the alveolar bone resorption and modulated the Th17/Treg imbalance during experimental periodontitis.Plataforma Experimental Bio-CT (FONDEQUIP, Faculty of Dentistry, Universidad de Chile) EQM150010 FONDECYT from the Chilean Governmental Agencia Nacional de Investigacion y Desarrollo (ANID) 1181780 Graduate School of the Faculty of Dentistry, Universidad de Chile ANID 2119221

Demographic and clinical characteristics, including subsyndromal symptoms across bipolar-spectrum disorders in adolescents

Objectives: Bipolar disorder (BD) is a debilitating illness that often starts at an early age. Prevention of first and subsequent mood episodes, which are usually preceded by a period characterized by subthreshold symptoms is important. We compared demographic and clinical characteristics including severity and duration of subsyndromal symptoms across adolescents with three different bipolar-spectrum disorders. Methods: Syndromal and subsyndromal psychopathology were assessed in adolescent inpatients (age = 12-18 years) with a clinical mood disorder diagnosis. Assessments included the validated Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P). We compared phenomenology across patients with a research consensus conference-confirmed DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnoses of BD-I, BD-not otherwise specified (NOS), or mood disorder (MD) NOS. Results: Seventy-six adolescents (age = 15.6 ± 1.4 years, females = 59.2%) were included (BD-I = 24; BD-NOS = 29; MD-NOS = 23) in this study. Median baseline global assessment of functioning scale score was 21 (interquartile range = 17-40; between-group p = 0.31). Comorbidity was frequent, and similar across groups, including disruptive behavior disorders (55.5%, p = 0.27), anxiety disorders (40.8%, p = 0.98), and personality disorder traits (25.0%, p = 0.21). Mania symptoms (most frequent: irritability = 93.4%, p = 0.82) and depressive symptoms (most frequent: depressed mood = 81.6%, p = 0.14) were common in all three BD-spectrum groups. Manic and depressive symptoms were more severe in both BD-I and BD-NOS versus MD-NOS (p < 0.0001). Median duration of subthreshold manic symptoms was shorter in MD-NOS versus BD-NOS (11.7 vs. 20.4 weeks, p = 0.002) and substantial in both groups. The most used psychotropics upon discharge were antipsychotics (65.8%; BD-I = 79.2%; BD-NOS = 62.1%; MD-NOS = 56.5%, p = 0.227), followed by mood stabilizers (43.4%; BD-I = 66.7%; BD-NOS = 31.0%; MD-NOS = 34.8%, p = 0.02) and antidepressants (19.7%; BD-I = 20.8%; BD-NOS = 10.3%; MD-NOS = 30.4%). Conclusions: Youth with BD-I, BD-NOS, and MD-NOS experience considerable symptomatology and are functionally impaired, with few differences observed in psychiatric comorbidity and clinical severity. Moreover, youth with BD-NOS and MD-NOS undergo a period with subthreshold manic symptoms, enabling identification and, possibly, preventive intervention of those at risk for developing BD or other affective episodes requiring hospitalization