Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated ...with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.
Shooting range soils contain mixed heavy metal contaminants including lead (Pb), cadmium (Cd), and zinc (Zn). Phosphate (P) compounds have been used to immobilize these metals, particularly Pb, ...thereby reducing their bioavailability. However, research on immobilization of Pb’s co-contaminants showed the relative importance of soluble and insoluble P compounds, which is critical in evaluating the overall success of in situ stabilization practice in the sustainable remediation of mixed heavy metal contaminated soils. Soluble synthetic P fertilizer (diammonium phosphate; DAP) and reactive (Sechura; SPR) and unreactive (Christmas Island; CPR) natural phosphate rocks (PR) were tested for Cd, Pb and Zn immobilization and later their mobility and bioavailability in a shooting range soil. The addition of P compounds resulted in the immobilization of Cd, Pb and Zn by 1.56–76.2%, 3.21–83.56%, and 2.31–74.6%, respectively. The reactive SPR significantly reduced Cd, Pb and Zn leaching while soluble DAP increased their leachate concentrations. The SPR reduced the bioaccumulation of Cd, Pb and Zn in earthworms by 7.13–23.4% and 14.3–54.6% in comparison with earthworms in the DAP and control treatment, respectively. Bioaccessible Cd, Pb and Zn concentrations as determined using a simplified bioaccessibility extraction test showed higher long-term stability of P-immobilized Pb and Zn than Cd. The differential effect of P-induced immobilization between P compounds and metals is due to the variation in the solubility characteristics of P compounds and nature of metal phosphate compounds formed. Therefore, Pb and Zn immobilization by P compounds is an effective long-term remediation strategy for mixed heavy metal contaminated soils.
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•Compared various P sources for their effectiveness in the immobilization of metals.•The bioavailability of mixed contaminants in a shooting range soil was examined.•Bioavailability was examined using plant growth and earthworm toxicity experiments.•The solubility of P compound impacts the immobilization of metals.•P-induced metal immobilization results from adsorption and precipitation reactions.
Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an ...overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.
This paper examines transmitter optimization for wirelessly powering a small implant embedded in tissue. The wireless link between the transmitter and receiver is first modeled as a two-port network ...and an expression for the power transfer efficiency derived. For a given small receiver in a multilayer tissue model, the transmitter is abstracted as a sheet of magnetic current density for which the optimal distribution is analytically found. The optimal transmitter is compared to the point and uniform source across a range of frequencies. At higher frequencies, the optimal current distribution is shown to induce fields that exhibit focusing. The effects of constructive and destructive interference substantially improves the power transfer efficiency and reinforces operation in the low GHz-range. The optimal transmitter establishes an upper bound on the power transfer efficiency for a given implant and provides insight on the design of the optimal transmit antenna.
Summary
Background
There are increasing reports of paradoxical psoriasiform diseases secondary to anti‐tumour necrosis factor (TNF) agents.
Aims
To determine the risks of paradoxical psoriasiform ...diseases secondary to anti‐TNF agents in patients with inflammatory bowel disease (IBD).
Methods
A nationwide population study was performed using the Korea National Health Insurance Claim Data. A total of 50 502 patients with IBD were identified between 2007 and 2016. We compared 5428 patients who were treated with any anti‐TNF agent for more than 6 months (anti‐TNF group) and 10 856 matched controls who had never taken anti‐TNF agents (control group).
Results
Incidence of psoriasis was significantly higher in the anti‐TNF group (36.8 per 10 000 person‐years) compared to the control group (14.5 per 10 000 person‐years) (hazard ratio HR 2.357, 95% confidence interval CI 1.668‐3.331). Palmoplantar pustulosis (HR 9.355, 95% CI 2.754‐31.780) and psoriatic arthritis (HR 2.926, 95% CI 1.640‐5.218) also showed higher risks in the anti‐TNF group. In subgroup analyses, HRs for psoriasis by IBD subtype were 2.549 (95% CI 1.658‐3.920) in Crohn's disease and 2.105 (95% CI 1.155‐3.836) in ulcerative colitis. Interestingly, men and younger (10‐39 years) patients have significantly higher risks of palmoplantar pustulosis (HR 19.682 95% CI 3.867‐100.169 and HR 14.318 95% CI 2.915‐70.315, respectively), whereas women and older (≥40 years) patients showed similar rates between the two groups.
Conclusions
The risks of psoriasiform diseases are increased by anti‐TNF agents in patients with IBD. Among psoriasiform diseases, the risk of palmoplantar pustulosis shows the biggest increase particularly in male and younger patients.
Linked ContentThis article is linked to Pariente and Blondeaux, and Lee et al papers. To view these articles visit https://doi.org/10.1111/apt.14903 and https://doi.org/10.1111/apt.14917.
The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a central role in switching on the ...angiogenic phenotype during early cervical carcinogenesis. However, the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression, we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.
Abstract Objectives To assess whether fetal-derived hypermethylated RASSF1A concentrations in maternal plasma during pregnancy are altered in pregnancies associated with placental dysfunction ...manifested by intrauterine growth restriction (IUGR), preeclampsia (PE), or placental previa (PP) and whether this alteration can be detected in susceptible subjects before the onset of clinical disease. Methods We performed a real-time quantitative polymerase chain reaction to quantify RASSF1A concentrations before and after methylation-sensitive restriction digestion in maternal plasma at 7–41 gestational weeks of normal pregnancies ( n = 161), IUGR ( n = 43), PE ( n = 22), PP ( n = 14) and non-pregnant women ( n = 20). Results A positive correlation was observed between fetal-derived hypermethylated RASSF1A concentration and gestational age for all study groups ( r = 0.624, p < 0.001 for IUGR; r = 0.381, p = 0.042 for PE; r = 0.697, p < 0.001 for PP; r = 0.560, p < 0.001 for controls). The concentration of hypermethylated RASSF1A was relatively high at 7–14 gestational weeks in all patient groups. Hypermethylated RASSF1A concentration at 15–28 weeks was significantly higher in patients who subsequently developed IUGR ( p = 0.002), PE ( p < 0.001) or PP ( p < 0.001) than in controls. Conclusion We first demonstrated increased concentration of fetal-derived hypermethylated RASSF1A sequences according to advancing gestation and before the onset of the clinical manifestation of pregnancy complications secondary to placental dysfunction, such as IUGR, PE and PP. Hypermethylated RASSF1A in maternal plasma may be useful as a potential biomarker to detect placental-mediated pregnancy complications, regardless of fetal gender and polymorphism.
Phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein kinases (MAPKs) have been implicated in diverse cellular functions, including proliferation, migration, and survival. In this ...study, we examined the involvement of these kinases in osteoclast differentiation by employing specific inhibitors of the kinases. The osteoclast differentiation was assessed in three different culture systems: a coculture of mouse bone marrow cells with mouse calvarial osteoblasts, a mouse bone marrow cell culture in the presence of receptor activator of NF-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), and a culture of bone-resident osteoclast precursor cells driven by RANKL and M-CSF. LY294002, a specific inhibitor of PI 3-kinase, potently inhibited osteoclast differentiation in all culture systems when assessed by both tartrate-resistant acid phosphatase (TRAP) staining and dentine resorption assays. Inhibition of p38 MAPK by SB202190 resulted in a strong suppression in the exogenous RANKL dependent mouse bone marrow and bone resident precursor cell cultures. Another MAPK pathway inhibitor (PD98059), which blocks the activation of extracellular signal-regulated kinase (ERK) by inhibiting the upstream kinase MAPK-ERK kinase (MEK) 1, exerted an inhibitory effect on osteoclast differentiation only at the highest concentration tested (30 micromol/L) in many cases. Whether the signaling pathways involving these kinases are activated by RANKL was also examined. The RANKL-stimulated phosphorylation of Akt, a downstream target of PI 3-kinase, and that of ERK were observed. RANKL also stimulated the activity of p38. These results suggest that PI 3 kinase, p38, and ERK play roles in osteoclast differentiation, at least in part, by participating in RANKL signaling.
Two-dimensional heterostructures combined with vertical geometries are candidates to probe and utilize the physical properties of atomically-thin materials. The vertical configuration enables a ...unique form of hot-carrier spectroscopy as well as atomic-scale devices. Here, we present the room-temperature evolution of heteroepitaxial perovskite hot-electron transistors using a SrRuO
base down to the monolayer limit (∼4 Å). As a fundamental electronic probe, we observe an abrupt transition in the hot-electron mean free path as a function of base thickness, coinciding with the thickness-dependent resistive transition. As a path towards devices, we demonstrate the integrated synthesis of perovskite one-dimensional electrical edge contacts using water-soluble and growth-compatible Sr
Al
O
hard masks. Edge-contacted monolayer-base transistors exhibit on/off ratios reaching ∼10
, complete electrostatic screening by the base manifesting pure hot-electron injection, and excellent scaling of the output current density with device dimensions. These results open new avenues for incorporating emergent phenomena at oxide interfaces and in heterostructures.
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