System Dynamics of Cognitive Vulnerabilities and Family Support Among Latina Children and Adolescents

The paper describes an approach to developing a data-driven development of a feedback theory of cognitive vulnerabilities and family support focused on understanding the dynamics experienced among Latina children, adolescents, and families. Family support is understood to be a response to avoidant and maladaptive behaviors that may be characteristic of cognitive vulnerabilities commonly associated depression and suicidal ideation. A formal feedback theory is developed, appraised, and analyzed using a combination of secondary analysis of qualitative interviews (N = 30) and quantitative analysis using system dynamics modeling and simulation. Implications for prevention practice, treatment, and future research are discussed

Lifestyle, dietary factors and antibody levels to oral bacteria in cancer-free participants of a European cohort study

Background—Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria. Methods—Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured. Results—IgG antibody levels were substantially lower among current and former smokers (1697 and 1677 ng/mL, respectively) than never smokers (1960 ng/mL; p-trend = 0.01), but did not vary by other factors, including BMI, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country and smoking status. The highest levels of total IgG were found among individuals with low education (2419 ng/mL). Conclusions—Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria

Changes in symptom clusters in patients undergoing radiation therapy

The goals of the study were to determine the occurrence rates for and the severity of symptoms at the middle, end, and 1 month after the completion of radiation therapy (RT), to determine the number and types of symptom clusters at these three time points, and to evaluate for changes over time in these symptom clusters. Symptom occurrence and severity were evaluated using the Memorial Symptom Assessment Scale (MSAS) in a sample of patients (n = 160) who underwent RT for breast or prostate cancer. At each time point, an exploratory factor analysis was done to determine the number of symptom clusters (i.e., symptom factors) based on the MSAS symptom severity ratings. The majority of the patients were male and married with a mean age of 61.1 years. The five symptoms with the highest occurrence rates across all three time points were lack of energy, pain, difficulty sleeping, feeling drowsy, and sweats. Although the number of symptoms and the specific symptoms within each symptom cluster were not identical across the three time points, three relatively similar symptom clusters (i.e., “mood-cognitive” symptom cluster, “sickness-behavior” symptom cluster, “treatment-related”, or “pain” symptom cluster) were identified in this sample. The internal consistency coefficients for the mood-cognitive symptom cluster and sickness-behavior symptom cluster were adequate at ≥0.68. Three relatively stable symptom clusters were found across RT. The majority of the symptom cluster severity scores were significantly higher in patients with breast cancer compared to patients with prostate cancer

Molecular Longitudinal Tracking of Mycobacterium abscessus spp. during Chronic Infection of the Human Lung

<div><p>The <i>Mycobacterium abscessus</i> complex is an emerging cause of chronic pulmonary infection in patients with underlying lung disease. The <i>M. abscessus</i> complex is regarded as an environmental pathogen but its molecular adaptation to the human lung during long-term infection is poorly understood. Here we carried out a longitudinal molecular epidemiological analysis of 178 <i>M. abscessus</i> spp. isolates obtained from 10 cystic fibrosis (CF) and 2 non CF patients over a 13 year period. Multi-locus sequence and molecular typing analysis revealed that 11 of 12 patients were persistently colonized with the same genotype during the course of the infection while replacement of a <i>M. abscessus sensu stricto</i> strain with a <i>Mycobacterium massiliense</i> strain was observed for a single patient. Of note, several patients including a pair of siblings were colonized with closely-related strains consistent with intra-familial transmission or a common infection reservoir. In general, a switch from smooth to rough colony morphology was observed during the course of long-term infection, which in some cases correlated with an increasing severity of clinical symptoms. To examine evolution during long-term infection of the CF lung we compared the genome sequences of 6 sequential isolates of <i>Mycobacterium bolletii</i> obtained from a single patient over an 11 year period, revealing a heterogeneous clonal infecting population with mutations in regulators controlling the expression of virulence factors and complex lipids. Taken together, these data provide new insights into the epidemiology of <i>M. abscessus</i> spp. during long-term infection of the CF lung, and the molecular transition from saprophytic organism to human pathogen.</p></div

Infected Dendritic Cells Facilitate Systemic Dissemination and Transplacental Passage of the Obligate Intracellular Parasite Neospora caninum in Mice

The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites

Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

<p>Abstract</p> <p>Background</p> <p>Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the <it>SLX4 </it>gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of <it>SLX4 </it>in German or Byelorussian familial cases of breast cancer without detected mutations in <it>BRCA1 </it>or <it>BRCA2 </it>has been completed, with globally negative results.</p> <p>Methods</p> <p>The genomic region of <it>SLX4</it>, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of <it>BRCA1 </it>or <it>BRCA2 </it>mutations.</p> <p>Results</p> <p>This mutational analysis revealed extensive genetic variation of <it>SLX4</it>, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.</p> <p>Conclusions</p> <p>Overall, while the results of this study do not identify clearly pathogenic mutations of <it>SLX4 </it>contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts