Today's children and adolescents are immersed in both traditional and new forms of digital media. Research on traditional media, such as television, has identified health concerns and negative ...outcomes that correlate with the duration and content of viewing. Over the past decade, the use of digital media, including interactive and social media, has grown, and research evidence suggests that these newer media offer both benefits and risks to the health of children and teenagers. Evidence-based benefits identified from the use of digital and social media include early learning, exposure to new ideas and knowledge, increased opportunities for social contact and support, and new opportunities to access health promotion messages and information. Risks of such media include negative health effects on sleep, attention, and learning; a higher incidence of obesity and depression; exposure to inaccurate, inappropriate, or unsafe content and contacts; and compromised privacy and confidentiality. This technical report reviews the literature regarding these opportunities and risks, framed around clinical questions, for children from birth to adulthood. To promote health and wellness in children and adolescents, it is important to maintain adequate physical activity, healthy nutrition, good sleep hygiene, and a nurturing social environment. A healthy Family Media Use Plan (www.healthychildren.org/MediaUsePlan) that is individualized for a specific child, teenager, or family can identify an appropriate balance between screen time/online time and other activities, set boundaries for accessing content, guide displays of personal information, encourage age-appropriate critical thinking and digital literacy, and support open family communication and implementation of consistent rules about media use.
Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense ...peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during M. tuberculosis infection has not been clarified. Monocyte-derived macrophages were infected with M. tuberculosis strain H37Rv and then treated with 1, 5, or 15 μg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor β (TGF-β) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines.
The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound ...dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD.
Background. Neurocognitive disorders remain common among human immunodeficiency virus (HIV)–positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral ...therapy (ART). Methods. Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice. Results. HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4⁺ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months. Conclusions. Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4⁺ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.
The secreted periostin protein, which marks mesenchymal cells in endocardial cushions following epithelial-mesenchymal transformation and in mature valves following remodeling, is a putative ...valvulogenesis target molecule. Indeed, periostin is expressed throughout cardiovascular morphogenesis and in all 4 adult mice valves (annulus and leaflets). Additionally, periostin is expressed throughout the fibrous cardiac skeleton and endocardial cushions in the developing heart but is absent from both normal and/or pathological mouse cardiomyocytes. Periostin (peri(lacZ)) knockout mice exhibit viable valve disease, with neonatal lethality in a minority and latent disease with leaflet abnormalities in the viable majority. Surviving peri(lacZ)-null leaflets are truncated, contain ectopic cardiomyocytes and smooth muscle, misexpress the cartilage proteoglycan aggrecan, demonstrate disorganized matrix stratification, and exhibit reduced transforming growth factor-beta signaling. Neonatal peri(lacZ) nulls that die (14%) display additional defects, including leaflet discontinuities, delamination defects, and deposition of acellular extracellular matrix. Assessment of collagen production, 3D lattice formation ability, and transforming growth factor-beta responsiveness indicate periostin-deficient fibroblasts are unable to support normal valvular remodeling and establishment of a mature cardiac skeleton. Furthermore, pediatric stenotic bicuspid aortic valves that have lost normal extracellular matrix trilaminar stratification have greatly reduced periostin. This suggests that loss of periostin results in inappropriate differentiation of mesenchymal cushion cells and valvular abnormalities via a transforming growth factor-beta-dependent pathway during establishment of the mature heart. Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease.
Sunflower seeds (
L.) accumulate large quantities of triacylglycerols (TAG) between 12 and 28 days after flowering (DAF). This is the period of maximal acyl-acyl carrier protein (acyl-ACP) ...thioesterase activity
, the enzymes that terminate the process of
fatty acid synthesis by catalyzing the hydrolysis of the acyl-ACPs synthesized by fatty acid synthase. Fatty acid thioesterases can be classified into two families with distinct substrate specificities, namely FatA and FatB. Here, some new aspects of these enzymes have been studied, assessing how both enzymes contribute to the acyl composition of sunflower oil, not least through the changes in their expression during the process of seed filling. Moreover, the binding pockets of these enzymes were modeled based on new data from plant thioesterases, revealing important differences in their volume and geometry. Finally, the subcellular location of the two enzymes was evaluated and while both possess an N-terminal plastid transit peptide, only in FatB contains a hydrophobic sequence that could potentially serve as a transmembrane domain. Indeed, using
imaging and organelle fractionation,
thioesterases,
FatA and
FatB, appear to be differentially localized in the plastid stroma and membrane envelope, respectively. The divergent roles fulfilled by
FatA and
FatB in oil biosynthesis are discussed in the light of our data.
Modifications to leaf structural components that drive variation in leaf mass per area (LMA) may substantially impact leaf physiology by changing how easily CO₂ diffuses through intercellular air ...space to carboxylation sites in mesophyll tissues. Mesophyll conductance (gₘ) is inversely proportional to the total pathway length for CO₂, including the structural resistances encountered. In balsam poplar (Populus balsamifera L.), gₘ increases with latitude, paralleled by an increase in LMA. We investigated a family of P.balsamifera (K4×C) with high variation in LMA for different characteristics (tissues, nitrogen content, ultrastructural attributes). We interpreted trait variability using a developmental scale quantified by the leaf plastochron index (LPI). Developmental age significantly affected LMA, but those effects were lost at LPI ≥ 6. We outlined contributions of anatomical components to LMA and found palisade mesophyll properties were the primary drivers of variation in LMA within mature leaves (LPI ≥ 6). Using anatomical data, we derived components corresponding to structural resistances for gₘ. Perimeters of palisade cells and surface area of palisade exposed to intercellular air space, which may strongly influence CO₂ diffusion, were correlated to LMA. Variation in LMA is positively related to differences in structural features expected to increase the conductance to CO₂ diffusion within palisade mesophyll.
It is well accepted that near‐infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light ...penetrates deep (3–5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore indocyanine green (ICG), dye can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7–9 mm) were irradiated with a 808‐nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG‐treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69–70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular‐targeted ICG–NIR laser therapy appears to have potential for treating superficial tumors.
Vitamin D deficiency and physical inactivity have been associated with bone loss and fractures, but their combined effect has scarcely been studied either in younger or older adults. Therefore, we ...aimed to assess the associations between physical activity, age and 25-hydroxyvitamin D (25(OH)D) status separately and in combination with the incidence of fracture risk in the EPIC-Norfolk cohort study. Baseline (1993-1998) self-reported physical activity and serum 25(OH)D concentrations at follow-up (1998-2000) were collected in 14,624 men and women (aged 42-82 y between 1998 and 2000). Fracture incidence was ascertained up to March 2015. Cox proportional hazard model was used to determine HRs of fractures by plasma 25(OH)D (<30, 30 to <50, 50 to <70, 70 to <90, >90 nmol/L), age (<65 y and >65 y) and physical activity (inactive and active) categories, by follow-up time per 20 nmol/L increase in serum 25(OH)D and to explore age-25(OH)D and physical activity-25(OH)D interactions. The age-, sex-, and month-adjusted HRs (95% CIs) for all fractures (1183 fractures) by increasing vitamin D category were not significantly different. With additional adjustment for body mass index, smoking status, alcohol intake, supplement use and history of fractures, the fracture risk was 29% lower in those participants with 50 to 70 nmol/L compared with those in the lowest quintile (<30 nmol/L). Physical inactivity based on a single baseline assessment was not associated with fracture risk. Vitamin D status appeared inversely related to fractures in middle aged adults. In older adults, the relationship between vitamin D status and fracture risk was observed to be J-shaped. Clinical and public health practice in vitamin D supplementation could partially explain these findings, although definitive conclusions are difficult due to potential changes in exposure status over the long follow up period.
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