Adolescent mental health: Challenges with maternal noncompliance

The leading cause of suicide ideation, attempts, and completion in adolescents is persistent and unresolved parental conflict. National statistics show extremely high rates of childhood neglect and abuse are perpetrated most often by single mothers. Psychiatric disorders arising from maternal–child dysfunction are well-documented. However, resources to prevent offspring victimization are lacking. Here, we report maternal neglect of a 15-year-old male brought to the psychiatric emergency room for suicidal ideation. An inpatient treatment plan including pharmacotherapy, family therapy and psychological testing was initiated. The patient’s mother failed to attend clinic appointments or family therapy sessions. Clinician attempts to engage the mother in the treatment plan was met with verbal assaults, aggression, and threatening behavior. The patient decompensated in relation to the mother’s actions. Child Protective Services were contacted and a follow-up assessment with the patient and mother is pending. Psychiatric treatment of the mother may be a necessary intervention and prevention regimen for both the adolescent and the mother. Without consistent Child Protective Services oversight, medical and psychosocial follow-up, the prognosis and quality of life for this adolescent is considered very poor. Stringent mental health law and institutional policies are needed to adequately intercede and protect adolescents with mental illness

Trees over Infinite Structures and Path Logics with Synchronization

We provide decidability and undecidability results on the model-checking problem for infinite tree structures. These tree structures are built from sequences of elements of infinite relational structures. More precisely, we deal with the tree iteration of a relational structure M in the sense of Shelah-Stupp. In contrast to classical results where model-checking is shown decidable for MSO-logic, we show decidability of the tree model-checking problem for logics that allow only path quantifiers and chain quantifiers (where chains are subsets of paths), as they appear in branching time logics; however, at the same time the tree is enriched by the equal-level relation (which holds between vertices u, v if they are on the same tree level). We separate cleanly the tree logic from the logic used for expressing properties of the underlying structure M. We illustrate the scope of the decidability results by showing that two slight extensions of the framework lead to undecidability. In particular, this applies to the (stronger) tree iteration in the sense of Muchnik-Walukiewicz.Comment: In Proceedings INFINITY 2011, arXiv:1111.267

Upper extremity transplantation in non-human primates: an orthotopic model for translational research

Vascularized composite allotransplantation (VCA) offers unparalleled restoration of function and form following devastating musculoskeletal and soft tissue injury. However, the potential adverse effects of life-long immunosuppression remain a significant cause for concern. Therefore, while the surgical techniques necessary for VCA have developed rapidly, the immunological aspects of these procedures and the potential functional significance of immunological processes on vascularized composite allografts remain areas in which further research is required. The functional complexity of these procedures, combined with the preclinical nature of many of the research questions, necessitates the use of large animal models to most effectively address some of the outstanding hypotheses. Cynomolgus macaques are among the premier large animal models for immunological research. This manuscript describes development of an orthotopic model of upper extremity transplantation in cynomolgus macaques. Following study of the anatomy to determine feasibility, in vivo proof of concept was achieved by autologous amputation and replantation in two animals, following which a preliminary series of four allotransplants was performed. The anatomy encountered and techniques required for successful transplantation are closely comparable to those in clinical upper extremity transplantation. This is a technically challenging model, but offers a rigorous pre-clinical platform for translational research in transplant immunology, and is suitable for detailed study of the impact of immunologic processes on functional outcomes following VCA

The role of social networks in students’ learning experiences

The aim of this research is to investigate the role of social networks in computer science education. The Internet shows great potential for enhancing collaboration between people and the role of social software has become increasingly relevant in recent years. This research focuses on analyzing the role that social networks play in students’ learning experiences. The construction of students’ social networks, the evolution of these networks, and their effects on the students’ learning experience in a university environment are examined

Structural studies reveal the enantiospecific recognition of a DNA G-quadruplex by a ruthenium polypyridyl complex

Using X-ray crystallography, we show an enantiospecificity in DNA G-quadruplex binding, using the complexes Λ/∆-[Ru(TAP)2(dppz-11-CN)]2+ (TAP=1,4,5,8-tetraazaphenanthrene) containing the dppz (dipyridophenazine) ligand, paralleling the specificity of the complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn-guanosine is adjacent to the complex at the 5’ end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ-[Ru(phen)2(11-CN-dppz)]2+ bound to d(TCGGCGCCGA), a duplex forming sequence, and use both structural models to aid in the elucidation of the motif-specific luminescence response of the isostructural phen analogue enantiomers

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn’s disease

Background: The faecal calprotectin (FC) test is a non-invasive marker for gastrointestinal inflammation. Aim: To determine whether higher FC levels in individuals with quiescent Crohn’s disease are associated with clinical relapse over the ensuing 12 months.<p></p> Methods: A single centre prospective study was undertaken in Crohn's disease patients in clinical remission attending for routine review. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse.<p></p> Results: Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) had relapsed by 12 months. The median FC was lower for non-relapsers, 96µg/g (IQR 39-237), than for relapsers, 414µg/g (IQR 259-590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240µg/g to predict relapse of quiescent Crohn’s had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%. FC≥240μg/g was associated with likelihood of relapse 5.7 (95% CI 1.9-17.3) times higher within 2.3 years than lower values (p=0.002).<p></p> Conclusions: In this prospective dataset, FC appears to be a useful, non-invasive tool to help identify quiescent Crohn’s disease patients at a low risk of relapse over the ensuing 12 months. FC of 240µg/g was the optimal cutoff in this cohort.<p></p&gt

Lung Adenocarcinoma Cell Sensitivity to Chemotherapies: A Spotlight on Lipid Droplets and SREBF1 Gene

To explore the relationship between cancer cell SREBF1 expression, lipid droplets (LDs) formation, and the sensitivity to chemotherapies, we cultured lung adenocarcinoma cells H1299 (with LD) and H1563 (without LD) in a serum-free basal medium (BM) or neutrophil degranulation products containing medium (NDM), and tested cell responses to cisplatin and etoposide. By using the DESeq2 Bioconductor package, we detected 674 differentially expressed genes (DEGs) associated with NDM/BM differences between two cell lines, many of these genes were associated with the regulation of sterol and cholesterol biosynthesis processes. Specifically, SREBF1 markedly declined in both cell lines cultured in NDM or when treated with chemotherapeutics. Despite the latter, H1563 exhibited LD formation and resistance to etoposide, but not to cisplatin. Although H1299 cells preserved LDs, these cells were similarly sensitive to both drugs. In a cohort of 292 patients with non-small-cell lung cancer, a lower SREBF1 expression in tumors than in adjacent nontumor tissue correlated with overall better survival, specifically in patients with adenocarcinoma at stage I. Our findings imply that a direct correlation between SREBF1 and LD accumulation can be lost due to the changes in cancer cell environment and/or chemotherapy. The role of LDs in lung cancer development and response to therapies remains to be examined in more detail.The study was supported by German Center for Lung Research, grants number 82DZL002B1 (Janciauskiene) and 82DZL00402 (Schneider).S

Quantitative analysis of regional distribution of tau pathology with 11C-PBB3-PET in a clinical setting.

PURPOSE The recent developments of tau-positron emission tomography (tau-PET) enable in vivo assessment of neuropathological tau aggregates. Among the tau-specific tracers, the application of 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in PET shows high sensitivity to Alzheimer disease (AD)-related tau deposition. The current study investigates the regional tau load in patients within the AD continuum, biomarker-negative individuals (BN) and patients with suspected non-AD pathophysiology (SNAP) using 11C-PBB3-PET. MATERIALS AND METHODS A total of 23 memory clinic outpatients with recent decline of episodic memory were examined using 11C-PBB3-PET. Pittsburg compound B (11C-PIB) PET was available for 17, 18F-flurodeoxyglucose (18F-FDG) PET for 16, and cerebrospinal fluid (CSF) protein levels for 11 patients. CSF biomarkers were considered abnormal based on Aβ42 ( 450 ng/L). The PET biomarkers were classified as positive or negative using statistical parametric mapping (SPM) analysis and visual assessment. Using the amyloid/tau/neurodegeneration (A/T/N) scheme, patients were grouped as within the AD continuum, SNAP, and BN based on amyloid and neurodegeneration status. The 11C-PBB3 load detected by PET was compared among the groups using both atlas-based and voxel-wise analyses. RESULTS Seven patients were identified as within the AD continuum, 10 SNAP and 6 BN. In voxel-wise analysis, significantly higher 11C-PBB3 binding was observed in the AD continuum group compared to the BN patients in the cingulate gyrus, tempo-parieto-occipital junction and frontal lobe. Compared to the SNAP group, patients within the AD continuum had a considerably increased 11C-PBB3 uptake in the posterior cingulate cortex. There was no significant difference between SNAP and BN groups. The atlas-based analysis supported the outcome of the voxel-wise quantification analysis. CONCLUSION Our results suggest that 11C-PBB3-PET can effectively analyze regional tau load and has the potential to differentiate patients in the AD continuum group from the BN and SNAP group

Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC

High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.This study was supported in part by the German Centre for Lung Research, grant numbers 82DZL00402 and 82DZL002A1.S