ABSTRACT
Screen-printed electrodes (SPEs) are reliable, portable, affordable, and versatile electrochemical platforms for the real-time analytical monitoring of emerging analytes in the environmental, clinical, and agricultural fields. The aim of this study was to evaluate the electrochemical behavior of gold screen-printed electrodes (SPGEs) modified with molecules containing amino (Tr-N) or α-aminophosphonate (Tr-P) groups for the selective and sensitive detection of the toxic metal ions Pb2+ and Hg2+ in aqueous samples. After optimizing the analytical parameters (conditioning potential and time, deposition potential and time, pH and concentration of the supporting electrolyte), anodic square wave stripping voltammetry (SWASV) was used to evaluate and compare the electrochemical performance of bare or modified electrodes for the detection of Hg2+ and Pb2+, either alone or in their mixtures in the concentration range between 1 nM and 10 nM. A significative improvement in the detection ability of Pb2+ ions was recorded for the amino-functionalized gold sensor SPGE-N, while the presence of a phosphonate moiety in SPGE-P led to greater sensitivity towards Hg2+ ions. The developed sensors allow the detection of Pb2+ and Hg2+ with a limit of detection (LOD) of 0.41 nM and 35 pM, respectively, below the legal limits for these heavy metal ions in drinking water or food, while the sensitivity was 5.84 µA nM-1cm-2 and 10 µA nM-1cm-2, respectively, for Pb2+ and Hg2+. The reported results are promising for the development of advanced devices for the in situ and cost-effective monitoring of heavy metals, even in trace amounts, in water resources.
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Hydrogen peroxide (H2O2) detection is paramount in biological and clinical domains due to its pivotal role in various physiological and pathological processes. This molecule is a crucial metabolite and effector in cellular redox mechanisms, influencing diverse cellular signaling pathways and bolstering the body's defense mechanisms against infection and oxidative stress. Organic molecule-based electrodes present unique advantages such as operational versatility and scalability, rendering them attractive candidates for sensor development across diverse fields encompassing food safety, healthcare, and environmental monitoring. This study explores the electrochemical properties of a tris(3-hydroxypyridin-4-one) THP, which has been unexplored in electrochemical sensing. Leveraging THP's chelating properties, we aimed to develop an electrochemical probe for hydrogen peroxide detection. Our investigations reveal promising results, with the developed sensor exhibiting a low limit of detection (LOD) of 144 nM, underscoring its potential utility in sensitive and selective H2O2 detection applications. In addition, the new sensor was also tested on fetal bovine serum (FBS) to emphasize future applications on biological matrices. This research signifies a significant stride in advancing electrochemical sensor technologies for hydrogen peroxide detection with several novelties related to the usage of THP, such as high sensitivity and selectivity, performance in biological matrices, repeatability, stability, and reproducibility, economical and practical advantages. This research opens new avenues for enhanced biomedical diagnostics and therapeutic interventions.
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PURPOSE: To compare diabetic retinopathy screening among patients with type 1 or type 2 diabetes under care in two distinct setups: hospital-based multidisciplinary and general practice-based. MATERIALS AND METHODS: In this retrospective observational case series, we collected data from a total of 133 diabetic patients: subjects from the hospital-based multidisciplinary setting were referred by the diabetologist and screened by an ophthalmologist using the Optomed Aurora IQ fundus camera. These patients were compared with those who underwent DR screening arranged through a general practice-based setting. RESULTS: The proportion of patients treated with insulin was higher in the hospital-based multidisciplinary group, both considering the totality patients and those affected by type 2 diabetes (71.6% vs. 32.2%; p < 0.001, and 58.8% vs. 31.0%; p = 0.004 respectively). Patients from the hospital-based multidisciplinary group had a longer mean diabetes duration (19.6 vs 14.9 years, p < 0.001), underwent DR screening more frequently in the previous three years (2.9 vs 1.4, p < 0.001), the mean time between two DR screenings was shorter (14.6 vs 77.9 weeks, p < 0.001), and DR was detected more frequently (32,4% vs 13.5%; p = 0.011). CONCLUSION: We were able to demonstrate that patients screened in the multidisciplinary center, which had characteristics predisposing to a higher risk of DR, were more likely to be diagnosed with DR on time, with a higher mean number of DR screenings and a shorted interval between diabetic and ophthalmological assessments.
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Despite a variety of glucose sensors being available today, the development of nonenzymatic devices for the determination of this biologically relevant analyte is still of particular interest in several applicative sectors. Here, we report the development of an impedimetric, enzyme-free electrochemical glucose sensor based on carbon nanofibers (CNFs) functionalized with an aromatic diamine via a simple wet chemistry functionalization. The electrochemical performance of the chemically modified carbon-based screen-printed electrodes (SPCEs) was evaluated by electrical impedance spectroscopy (EIS), demonstrating a high selectivity of the sensor for glucose with respect to other sugars, such as fructose and sucrose. The sensing parameters to obtain a reliable calibration curve and the selective glucose sensing mechanism are discussed here, highlighting the performance of this novel electrochemical sensor for the selective sensing of this important analyte. Two linear trends were noted, one at low concentrations (0-1200 µM) and the other from 1200 to 5000 µM. The limit of detection (LOD), calculated as the (standard error/slope)*3.3, was 18.64 µM. The results of this study highlight the performance of the developed novel electrochemical sensor for the selective sensing of glucose.
ABSTRACT
High-performance hydrogen sulfide (H2S) sensors are mandatory for many industrial applications. However, the development of H2S sensors still remains a challenge for researchers. In this work, we report the study of a TiO2-based conductometric sensor for H2S monitoring at low concentrations. TiO2 samples were first synthesized using the sol-gel route, annealed at different temperatures (400 and 600 °C), and thoroughly characterized to evaluate their morphological and microstructural properties. Scanning electronic microscopy, Raman scattering, X-ray diffraction, and FTIR spectroscopy have demonstrated the formation of clusters of pure anatase in the TiO2 phase. Increasing the calcination temperature to 600 °C enhanced TiO2 crystallinity and particle size (from 11 nm to 51 nm), accompanied by the transition to the rutile phase and a slight decrease in band gap (3.31 eV for 400 °C to 3.26 eV for 600 °C). Sensing tests demonstrate that TiO2 annealed at 400 °C displays good performances (sensor response Ra/Rg of ~3.3 at 2.5 ppm and fast response/recovery of 8 and 23 s, respectively) for the detection of H2S at low concentrations in air.
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Background and objectives: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative stage. This review aims to summarize the use of deep learning in neovascular AMD. Materials and Methods: Pubmed search. Results: Deep learning has demonstrated effectiveness in analyzing structural OCT images in patients with neovascular AMD. This review outlines the role of deep learning in identifying and measuring biomarkers linked to an elevated risk of transitioning to the neovascular form of AMD. Additionally, deep learning techniques can quantify critical OCT features associated with neovascular AMD, which have prognostic implications for these patients. Incorporating deep learning into the assessment of neovascular AMD eyes holds promise for enhancing clinical management strategies for affected individuals. Conclusion: Several studies have demonstrated effectiveness of deep learning in assessing neovascular AMD patients and this has a promising role in the assessment of these patients.
Subject(s)
Deep Learning , Macular Degeneration , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methodsABSTRACT
The one-pot synthesis of N-doped graphene quantum dots (GQDs), capped with a positively charged polyamine (trien), has been realized through a microwave-assisted pyrolysis on solid L-glutamic acid and trien in equimolar amounts. The resulting positively charged nanoparticles are strongly emissive in aqueous solutions and are stable for months. The interaction with the anionic tetrakis(4-sulphonatophenyl)porphyrin (TPPS4) has been investigated at neutral and mild acidic pH using a combination of UV/vis absorption spectroscopy together with static and time-resolved fluorescence emission. At pH = 7, the experimental evidence points to the formation of a supramolecular adduct mainly stabilized by electrostatic interactions. The fluorescence emission of the porphyrin is substantially quenched while GQDs remain still emissive. On decreasing the pH, protonation of TPPS4 leads to formation of porphyrin J-aggregates through the intermediacy of the charged quantum dots.
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The Simpson-Golabi-Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait, with variable expressivity in males and reduced penetrance and expressivity in females. The clinical spectrum is broad, ranging from mild manifestations in both males and females to multiple malformations and neonatal death in the more severely affected cases. An increased risk of neoplasia is reported, requiring periodical surveillance. Intellectual development is normal in most cases. SGBS is caused by a loss-of-function mutation of the GPC3 gene, either deletions or point mutations, distributed all over the gene. Notably, GPC3 deletion/point mutations are not found in a significant proportion of clinically diagnosed SGBS cases. The protein product GPC3 is a glypican functioning as a receptor for Hh at the cell surface, involved in the Hh-Ptc-Smo signaling pathway, a regulator of cellular growth.
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The synthesis techniques used for metal oxide semiconductors strongly influence their chemical, physical and gas sensing characteristics. In this context, hematite (α-Fe2O3) nanoparticles (NPs) were synthesized using two different techniques, namely, sol-gel (named HSG) and Pechini sol-gel (named HPSG). The average crystallite size and surface area were 15 nm and 76 m2 g-1 and 20 nm and 57 m2 g-1 for HPSG and HSG, respectively. Morphological studies showed that the HSG material was composed of ellipsoid-shaped particles, while the HPSG material had peanut-shaped particles with open pores and channels. The comparison between the sensing performances of HPSG and HSG toward ethanol indicated HPSG to be a better sensing material for ethanol detection. The HPSG sensor exhibited a response of 12 toward 500 ppm ethanol at 250 °C, a fast response time of 5 s and excellent selectivity. The enhanced characteristics were mainly related to the peculiar morphology with a porous nature, which led to more gas adsorption and diffusion. In addition to shape influence, the size of NPs also has an effect on the gas sensing performance. In fact, a decrease in the crystallite size led to an increase in the surface area of the material where the gas molecule-sensing layer interaction took place. The increase in the surface area created more interaction sites, and thus the sensitivity was improved. From these results, the HPSG sensor can be regarded as a promising candidate for ethanol detection.
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Mitochondria are involved in multiple aspects of neurodevelopmental processes and play a major role in the pathogenetic mechanisms leading to neuro-degenerative diseases. Fragile-X-related disorders (FXDs) are genetic conditions that occur due to the dynamic expansion of CGG repeats of the FMR1 gene encoding for the RNA-binding protein FMRP, particularly expressed in the brain. This gene expansion can lead to premutation (PM, 56-200 CGGs), full mutation (FM, >200 CGGs), or unmethylated FM (UFM), resulting in neurodegeneration, neurodevelopmental disorders, or no apparent intellectual disability, respectively. To investigate the mitochondrial mechanisms that are involved in the FXD patients, we analyzed mitochondrial morphology and bioenergetics in fibroblasts derived from patients. Donut-shaped mitochondrial morphology and excessive synthesis of critical mitochondrial proteins were detected in FM, PM, and UFM cells. Analysis of mitochondrial oxidative phosphorylation in situ reveals lower respiration in PM fibroblasts. Importantly, mitochondrial permeability transition-dependent apoptosis is sensitized to reactive oxygen species in FM, PM, and UFM models. This study elucidated the mitochondrial mechanisms that are involved in the FXD phenotypes, and indicated altered mitochondrial function and morphology. Importantly, a sensitization to permeability transition and apoptosis was revealed in FXD cells. Overall, our data suggest that mitochondria are novel drug targets to relieve the FXD symptoms.
Subject(s)
Fragile X Syndrome , Intellectual Disability , Mitochondrial Diseases , Humans , Fragile X Syndrome/metabolism , Fragile X Mental Retardation Protein/genetics , Intellectual Disability/genetics , Cell Death/genetics , Mitochondrial Diseases/genetics , Mutation , Trinucleotide Repeat ExpansionABSTRACT
In this paper, we present a novel fluorescent material based on the herbal tea of Lavandula multifida (Lm). The fluorescence properties of Lm aqueous extract were analyzed under various excitation wavelengths in the range of 290-450 nm. The Lm herbal infusion was found to be highly fluorescent, with an emission maximum at 450 nm under excitation at 390 nm. Consequently, it was exploited to develop a fluorescence method for detecting metal ions. Results obtained upon the addition of Hg2+, Na+, K+, Ca2+, Mg2+, Pb2+, Cd2+, Cu2+, Ni2+, Bi3+, Mn2+, Fe3+ and Co2+ ions showed that the fluorescence intensity of the Lm aqueous extract decreased strongly with the presence of mercury ions. A solid-state fluorescent sensor, based on Lm embedded into a Nafion membrane and deposited on a transparent polyethylene terephthalate (PET) sheet, has also been developed for the effective detection of Hg2+ ions. The Lm-Nafion-PET sensor exhibited good stability, high repeatability, and reproducibility. Furthermore, the Lm-Nafion/PET sensor demonstrated remarkable sensitivity to Hg2+ in sea water, with a limit of detection of 0.25 fM. To our knowledge, this is the first study which reports Lavandula multifida plant for making a novel eco-friendly fluorescent solid-state sensor for the detection of mercury ions at femto-molar concentrations in seawater.
Subject(s)
Fluorocarbon Polymers , Lavandula , Mercury , Reproducibility of Results , Limit of Detection , Coloring Agents , Water , Seawater , Ions , Fluorescent DyesABSTRACT
Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.
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Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.
Subject(s)
Genetics, Medical , Humans , History, 20th Century , History, 21st Century , Human GeneticsABSTRACT
Among the existing nanosystems used in electrochemical sensing, gold nanoparticles (AuNPs) have attracted considerable attention owing to their intriguing chemical and physical properties such as good electrical conductivity, high electrocatalytic activity, and high surface-to-volume ratio. However, despite these useful characteristics, there are some issues due to their instability in solution that can give rise to aggregation phenomena and the use of hazardous chemicals in the most common synthetic procedures. With an aim to find a solution to these issues, recently, we prepared and characterized carbon dots (CDs), from olive solid wastes, and employed them as reducing and capping agents in photo-activated AuNP synthesis, thus creating CD-Au nanohybrids. These nanomaterials appear extremely stable in aqueous solutions at room temperature, are contemporary, and have been obtained using CDs, which are exclusively based on non-toxic elements, with an additional advantage of being generated from an otherwise waste material. In this paper, the synthesis and characterization of CD-Au nanohybrids are described, and the electrochemical experiments for hydroquinone detection are discussed. The results indicate that CD-Au acts as an efficient material for sensing hydroquinone, matching a wide range of interests in science from industrial processes to environmental pollution.
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The development of novel nanomaterials as highly efficient gas-sensing materials is envisaged as one of the most important routes in the field of gas-sensing research. However, developing stable, selective, and efficient materials for these purposes is a highly challenging task requiring numerous design attempts. In this work, a ZrO2/Co3O4 composite is reported, for the first time, as a gas-sensing material for the detection of ethanol. The sensitive and selective detection of ethanol gas at 200 °C has been demonstrated for the ZrO2/Co3O4 (0.20 wt%/0.20 wt%)-based sensor. Furthermore, the sensor showed a very low response/recovery time of 56 s and 363 s, respectively, in response to a pulse of 20 ppm of ethanol and good stability. The interesting gas-sensing property of ZrO2/Co3O4 can be ascribed to both the porous structure, which facilitates the interaction between the target gas and the sensing site, and the p-p-junction-induced built-in electric field. These results indicate that the ZrO2/Co3O4 composite can serve as a heterostructured nanomaterial for the detection of ethanol gas.
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Stimulus-responsive fluorescent-modified biopolymers have received significant attention in the field of chemosensors. Herein, four new fluorescent dyes, namely, S1: (PDA-DANC), S2: (SAL-PDA-DANC), S3: (BrSAL-PDA-DANC) and S4: (ClSAL-PDA-DANC) have been successfully synthesized from 2,3-dialdehyde nanocellulose (DANC) for the detection of heavy metals. The microstructural and photophysical properties of nanocellulose (NC), microcrystalline cellulose (DANC) and the synthesized S1 to S4 dyes were investigated by FT-IR, SEM-EDX, XRD, TGA, DLS and photoluminescence. NC, obtained from conversion of MCC, shows an average size of 802.4 nm with 0.141 of polydispersity index (PdI), and a crystalline index (CI) of 82.40 % and crystallite size of 4.68 nm. The synthesized dyes present good fluorescent properties and have been therefore exploited for developing new probes for heavy metal ions detection. Remarkable "turn off" and/or "turn on" behaviors with Fe3+ and Cu2+ and with Zn2+ in DMF/water solution have been demonstrated, allowing the sensitive and selective determination of these heavy metal ions with a low limit of detection (LOD). Finally, the evaluation of the Fe3+ sensing in a real seawater sample was investigated.
Subject(s)
Copper , Schiff Bases , Copper/chemistry , Schiff Bases/chemistry , Spectroscopy, Fourier Transform Infrared , Metals , Fluorescent Dyes/chemistry , Water/chemistry , Ions , Seawater , Zinc/chemistryABSTRACT
BACKGROUND AIMS: The proapoptotic protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is physiologically expressed by immune cells and performs regulatory functions in infections, autoimmune diseases and cancer, where it acts as a tumor suppressor. Adipose-derived mesenchymal stromal cells (AD-MSCs) also may play immunomodulatory roles in both primary and acquired immune responses. We have previously demonstrated the efficacy of an anticancer gene therapy based on AD-MSC engineered to secrete a soluble TRAIL variant (sTRAIL) against pancreatic cancer. However, the impact of AD-MSC sTRAIL on leukocyte subsets has been not yet considered also to predict a possible immunotoxicity profile in the clinical translation of this cell-based anticancer strategy. METHODS: Monocytes, polymorphonuclear cells and T lymphocytes were freshly isolated from the peripheral blood of healthy donors. Immunophenotype and functional (DR4 and DR5) and decoy (DcR1 and DcR2) TRAIL receptors were tested by flow cytometry. The viability of white blood cells treated with sTRAIL released by gene-modified AD-MSC or co-cultured with AD-MSC sTRAIL was then evaluated by both metabolic assays and flow cytometry. In addition, cytokine profile in co-cultures was analyzed by multiplex enzyme-linked immunosorbent assay. RESULTS: Monocytes and polymorphonuclear cells showed high positivity for DR5 and DcR2, respectively, whereas T cells revealed negligible expression of all TRAIL receptors. Irrespective of TRAIL receptors' presence on the cell membrane, white blood cells were refractory to the proapoptotic effect displayed by sTRAIL secreted by gene-modified AD-MSC, and direct cell-to-cell contact with AD-MSC sTRAIL had negligible impact on T-cell and monocyte viability. Cytokine crosstalk involving interleukin 10, tumor necrosis factor alpha, and interferon gamma secreted by T lymphocytes and vascular endothelial growth factor A and interleukin 6 released by AD-MSC was highlighted in T-cell and AD-MSC sTRAIL co-cultures. CONCLUSIONS: In summary, this study demonstrates the immunological safety and thus the clinical feasibility of an anticancer approach based on AD-MSC expressing the proapoptotic molecule sTRAIL.
Subject(s)
Mesenchymal Stem Cells , Pancreatic Neoplasms , Humans , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , Ligands , Apoptosis/physiology , Pancreatic Neoplasms/therapy , Leukocytes/metabolism , TNF-Related Apoptosis-Inducing Ligand/genetics , TNF-Related Apoptosis-Inducing Ligand/metabolismABSTRACT
In the biomedical field, the demand for the development of broad-spectrum biomaterials able to inhibit bacterial growth is constantly increasing. Chronic infections represent the most serious and devastating complication related to the use of biomaterials. This is particularly relevant in the orthopaedic field, where infections can lead to implant loosening, arthrodesis, amputations and sometimes death. Antibiotics are the conventional approach for implanted-associated infections, but they have the limitation of increasing antibiotic resistance, a critical worldwide healthcare issue. In this context, the development of anti-infective biomaterials and infection-resistant surfaces can be considered the more effective strategy to prevent the implant colonisation and biofilm formation by bacteria, so reducing the occurrence of implant-associated infections. In the last years, inorganic nanostructures have become extremely appealing for chemical modifications or coatings of Ti surfaces, since they do not generate antibiotic resistance issues and are featured by superior stability, durability, and full compatibility with the sterilization process. In this work, we present a simple, rapid, and cheap chemical nanofunctionalization of titanium (Ti) scaffolds with colloidal ZnO and Mn-doped ZnO nanoparticles (NPs), prepared by a sol-gel method, exhibiting antibacterial activity. ZnO NPs and ZnxMn(1-x)O NPs formation with a size around 10-20nm and band gap values of 3.42â¯eV and 3.38â¯eV, respectively, have been displayed by characterization studies. UV-Vis, fluorescence, and Raman investigation suggested that Mn ions acting as dopants in the ZnO lattice. Ti scaffolds have been functionalized through dip coating, obtaining ZnO@Ti and ZnxMn(1-x)O@Ti biomaterials characterized by a continuous nanostructured film. ZnO@Ti and ZnxMn(1-x)O@Ti displayed an enhanced antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacterial strains, compared to NPs in solution with better performance of ZnxMn(1-x)O@Ti respect to ZnO@Ti. Notably, it has been observed that ZnxMn(1-x)O@Ti scaffolds reach a complete eradication for S. aureus and 90â¯% of reduction for P. aeruginosa. This can be attributed to Zn2+ and Mn2+ metal ions release (as observed by ICP MS experiments) that is also maintained over time (72â¯h). To the best of our knowledge, this is the first study reported in the literature describing ZnO and Mn-doped ZnO NPs nanofunctionalized Ti scaffolds with improved antibacterial performance, paving the way for the realization of new hybrid implantable devices through a low-cost process, compatible with the biotechnological industrial chain method.
Subject(s)
Nanostructures , Zinc Oxide , Titanium/pharmacology , Zinc Oxide/pharmacology , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanostructures/chemistry , Biocompatible Materials/pharmacology , Zinc/pharmacologyABSTRACT
RASopathies are rare genetic disorders caused by germline pathogenic variants in genes belonging to the RAS/MAPK pathway, which signals cell proliferation, differentiation, survival and death. The dysfunction of such signaling pathway causes syndromes with overlapping clinical manifestations. Skin and adnexal lesions are the cardinal clinical signs of RASopathies, such as cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, formerly known as LEOPARD syndrome, Costello syndrome, neurofibromatosis (NF1), Legius syndrome, Noonan-like syndrome with loose anagen hair (NSLH) and Noonan syndrome. As NF1, one of the most common RASopathies, described in 1882, has its clinical features well delineated, we will focus on the dermatological diagnosis, management and care of non-NF1 RASopathies, which are less known and more recently described. Dermatological manifestations are important clinical diagnostic elements that can aid differential diagnosis among RASopathies. They can affect dermis and epidermis, causing pigmented lesions (melanocytic nevi, café-au-lait spots, and lentigines), hyperkeratosis (keratosis pilaris, ulerythema ophryogenes, and palmoplantar keratosis) or hyperplasia. To date there are rare known links to malignancy, but oftentimes skin lesions require close attention because they can highly affect quality of life.