Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

National Income and Income Inequality, Family Affluence and Life Satisfaction Among 13 year Old Boys and Girls: A Multilevel Study in 35 Countries

Adolescence is a critical period where many patterns of health and health behaviour are formed. The objective of this study was to investigate cross-national variation in the relationship between family affluence and adolescent life satisfaction, and the impact of national income and income inequality on this relationship. Data from the 2006 Health Behaviour in School-aged Children: WHO collaborative Study (N = 58,352 across 35 countries) were analysed using multilevel linear and logistic regression analyses for outcome measures life satisfaction score and binary high/low life satisfaction. National income and income inequality were associated with aggregated life satisfaction score and prevalence of high life satisfaction. Within-country socioeconomic inequalities in life satisfaction existed even after adjustment for family structure. This relationship was curvilinear and varied cross-nationally. Socioeconomic inequalities were greatest in poor countries and in countries with unequal income distribution. GDP (PPP US$) and Gini did not explain between country variance in socioeconomic inequalities in life satisfaction. The existence of, and variation in, within-country socioeconomic inequalities in adolescent life satisfaction highlights the importance of identifying and addressing mediating factors during this life stage

Sequence Defined Disulfide-Linked Shuttle for Strongly Enhanced Intracellular Protein Delivery

Intracellular protein transduction technology is opening the door for a promising alternative to gene therapy. Techniques have to address all critical steps, like efficient cell uptake, endolysosomal escape, low toxicity, while maintaining full functional activity of the delivered protein. Here, we present the use of a chemically precise, structure defined three-arm cationic oligomer carrier molecule for protein delivery. This carrier of exact and low molecular weight combines good cellular uptake with efficient endosomal escape and low toxicity. The protein cargo is covalently attached by a bioreversible disulfide linkage. Murine 3T3 fibroblasts could be transduced very efficiently with cargo nlsEGFP, which was tagged with a nuclear localization signal. We could show subcellular delivery of the nlsEGFP to the nucleus, confirming cytosolic delivery and expected subsequent subcellular trafficking. Transfection efficiency was concentration-dependent in a directly linear mode and 20-fold higher in comparison with HIV-TAT-nlsEGFP containing a functional TAT transduction domain. Furthermore, β-galactosidase as a model enzyme cargo, modified with the carrier oligomer, was transduced into neuroblastoma cells in enzymatically active form

Biodiversity of Indigenous Saccharomyces Populations from Old Wineries of South-Eastern Sicily (Italy): Preservation and Economic Potential

In recent years, the preservation of biodiversity has become an important issue. Despite much public discussion, however, current practices in the food industry seldom take account of its potential economic importance: on the contrary, the introduction of industrialized agriculture practices over large areas has often resulted in a dramatic reduction in biodiversity

Airway smooth muscle as a target of asthma therapy: history and new directions

Ultimately, asthma is a disease characterized by constriction of airway smooth muscle (ASM). The earliest approach to the treatment of asthma comprised the use of xanthines and anti-cholinergics with the later introduction of anti-histamines and anti-leukotrienes. Agents directed at ion channels on the smooth muscle membrane (Ca(2+ )channel blockers, K(+ )channel openers) have been tried and found to be ineffective. Functional antagonists, which modulate intracellular signalling pathways within the smooth muscle (β-agonists and phosphodiesterase inhibitors), have been used for decades with success, but are not universally effective and patients continue to suffer with exacerbations of asthma using these drugs. During the past several decades, research energies have been directed into developing therapies to treat airway inflammation, but there have been no substantial advances in asthma therapies targeting the ASM. In this manuscript, excitation-contraction coupling in ASM is addressed, highlighting the current treatment of asthma while proposing several new directions that may prove helpful in the management of this disease

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Contraindications of sentinel lymph node biopsy: Áre there any really?

BACKGROUND: One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient. METHODS: In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery. RESULTS: Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure. CONCLUSION: When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer

The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models

A compelling association has been observed between cardiovascular disease (CVD) and depression, suggesting individuals with depression to be at significantly higher risk for CVD and CVD-related mortality. Systemic immune activation, hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, arterial stiffness and endothelial dysfunction have been frequently implicated in this relationship. Although a differential epidemiological association between CVD and depression subtypes is evident, it has not been determined if this indicates subtype specific biological mechanisms. A comprehensive systematic literature search was conducted using PubMed and PsycINFO databases yielding 147 articles for this review. A complex pattern of systemic immune activation, endothelial dysfunction and HPA axis hyperactivity is suggestive of the biological relationship between CVD and depression subtypes. The findings of this review suggest that diagnostic subtypes rather than a unifying model of depression should be considered when investigating the bidirectional biological relationship between CVD and depression. The suggested model of a subtype-specific biological relationship between depression and CVDs has implications for future research and possibly for diagnostic and therapeutic processes

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field