PENCIL imaging: A novel approach for neuromelanin sensitive MRI in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with the loss of neuromelanin (NM) and increased iron in the substantia nigra (SN). Magnetization transfer contrast (MTC) is widely used for NM visualization but has limitations in brain coverage and scan time. This study aimed to develop a new approach called Proton-density Enhanced Neuromelanin Contrast in Low flip angle gradient echo (PENCIL) imaging to visualize NM in the SN. METHODS: This study included 30 PD subjects and 50 healthy controls (HCs) scanned at 3T. PENCIL and MTC images were acquired. NM volume in the SN pars compacta (SNpc), normalized image contrast (Cnorm), and contrast-to-noise ratio (CNR) were calculated. The change of NM volume in the SNpc with age was analyzed using the HC data. A group analysis compared differences between PD subjects and HCs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations were used to evaluate the diagnostic performance of NM volume and CNR in the SNpc. RESULTS: PENCIL provided similar visualization and structural information of NM compared to MTC. In HCs, PENCIL showed higher NM volume in the SNpc than MTC, but this difference was not observed in PD subjects. PENCIL had higher CNR, while MTC had higher Cnorm. Both methods revealed a similar pattern of NM volume in SNpc changes with age. There were no significant differences in AUCs between NM volume in SNpc measured by PENCIL and MTC. Both methods exhibited comparable diagnostic performance in this regard. CONCLUSIONS: PENCIL imaging provided improved CNR compared to MTC and showed similar diagnostic performance for differentiating PD subjects from HCs. The major advantage is PENCIL has rapid whole-brain coverage and, when using STAGE imaging, offers a one-stop quantitative assessment of tissue properties.

Effect of Epidermoid Cysts on the Efficacy of Intralesional Corticosteroid Therapy for Hypertrophic Scars and Keloids: A Prospective Pilot Study.

BACKGROUND: Patients with hypertrophic scars (HSs) or keloids occasionally have epidermoid cysts (ECs), and the effect of ECs on the effectiveness of intralesional corticosteroids (ILCs) treatment in these patients has not been reported. OBJECTIVE: This study aims to evaluate the influence of ECs on the outcomes of ILCs treatment in patients with HSs or keloids. MATERIALS AND METHODS: This prospective study included 572 patients with keloids ( n = 461) or HSs ( n = 111). Patients received intralesional triamcinolone acetonide injection (0.05 mL/injection) at a concentration of 40 mg/mL and every 28 days for 4 sessions, with a 1-year follow-up. RESULTS: A higher incidence of ECs was observed in keloid patients (16.92%) compared with HSs patients (7.21%). Keloid patients with ECs were older ( p = .008) and had a longer disease duration ( p = .0148), higher Vancouver scar scale (VSS) scores ( p = .04), and greater thickness ( p = .006). Keloid patients with ECs showed less improvement in VSS scores ( p < .0001) and thickness ( p < .0001) after ILCs treatment, with a higher recurrence rate ( p < .0001). The overall complication rate in keloid patients with ECs after ILCs treatment was 49.51%. CONCLUSION: Epidermoid cysts under keloids were associated with a poor response to ILCs therapy. Therefore, it is recommended to incorporate ultrasonography as a routine examination for keloid patients to aid in better decision making in clinical practice.

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

Visualizing the deep cerebellar nuclei using quantitative susceptibility mapping: An application in healthy controls, Parkinson's disease patients and essential tremor patients.

The visualization and identification of the deep cerebellar nuclei (DCN) (dentate [DN], interposed [IN] and fastigial nuclei [FN]) are particularly challenging. We aimed to visualize the DCN using quantitative susceptibility mapping (QSM), predict the contrast differences between QSM and T2* weighted imaging, and compare the DCN volume and susceptibility in movement disorder populations and healthy controls (HCs). Seventy-one Parkinson's disease (PD) patients, 39 essential tremor patients, and 80 HCs were enrolled. The PD patients were subdivided into tremor dominant (TD) and postural instability/gait difficulty (PIGD) groups. A 3D strategically acquired gradient echo MR imaging protocol was used for each subject to obtain the QSM data. Regions of interest were drawn manually on the QSM data to calculate the volume and susceptibility. Correlation analysis between the susceptibility and either age or volume was performed and the intergroup differences of the volume and magnetic susceptibility in all the DCN structures were evaluated. For the most part, all the DCN structures were clearly visualized on the QSM data. The susceptibility increased as a function of volume for both the HC group and disease groups in the DN and IN (p < .001) but not the FN (p = .74). Only the volume of the FN in the TD-PD group was higher than that in the HCs (p = .012), otherwise, the volume and susceptibility among these four groups did not differ significantly. In conclusion, QSM provides clear visualization of the DCN structures. The results for the volume and susceptibility of the DCN can be used as baseline references in future studies of movement disorders.

APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. OBJECTIVE: To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. METHODS: We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. RESULTS: The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P = .004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P = .118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. LIMITATIONS: The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. CONCLUSION: Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.

Topsoil selenium (Se) under Se-rich farming in China: Current status, cropping impacts and ecological risk assessment.

Selenium (Se), as an essential microelement, can be supplied through Se-biofortified food from Se-rich soils and associated farming practices for human health, while it can also cause eco-risks if overapplied. In this study, a multi-scale spatiotemporal meta-analysis was conducted to guide sustainable Se-rich farming in China by combining a long-term survey with a reviewed database. The weighted mean concentration, spatial distribution of soil Se, nationwide topsoil Se variation from cropping impacts and its bioavailability-based ecological risks were assessed and quantified. The results showed that the weighted mean content (0.3 mg kg-1) of China was slightly higher than that of previous nationwide topsoil Se surveys, as more Se-rich areas were found in recent high-density sampling surveys. Cropping has overall reduced Se content by 9.5% from farmland across China and deprived more with the increase in farming rotation driven by geo-climatic conditions. Long-term cropping removed Se from Se-rich areas but accumulated it in Se-deficient areas. Additionally, the bioavailable Se content of topsoil in China ranged from 0 to 332 µg kg-1, and the bioavailability-based eco-risks indicated that high eco-risks only existed in overfertilized and extremely high-Se soils, such as in Enshi, Ziyang and some coalfield areas. This work provides evidence for the development of sustainable Se-rich farming with proper utilization of soil Se resources, simultaneously protecting the soil eco-environment.

Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators.

Chronic inflammatory disease (CID) is a category of medical conditions that causes recurrent inflammatory attacks in multiple tissues. The occurrence of CID is related to inappropriate immune responses to normal tissue substances and invading microbes due to many factors, such as defects in the immune system and imbalanced regulation of commensal microbes. Thus, effectively keeping the immune-associated cells and their products in check and inhibiting aberrant activation of the immune system is a key strategy for the management of CID. Canthin-6-ones are a subclass of ß-carboline alkaloids isolated from a wide range of species. Several emerging studies based on in vitro and in vivo experiments reveal that canthin-6-ones may have potential therapeutic effects on many inflammatory diseases. However, no study has yet summarized the anti-inflammatory functions and the underlying mechanisms of this class of compounds. This review provides an overview of these studies, focusing on the disease entities and the inflammatory mediators that have been shown to be affected by canthin-6-ones. In particular, the major signaling pathways affected by canthin-6-ones, such as the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NF-κB signaling pathway, and their roles in several CIDs are discussed. Moreover, we discuss the limitations in studies of canthin-6-ones and provide possible solutions. In addition, a perspective that may suggest possible future research directions is provided. This work may be helpful for further mechanistic studies and possible therapeutic applications of canthin-6-ones in the treatment of CID.

Pembrolizumab associated Stevens-Johnson syndrome with porokeratosis in a patient in the setting of primary hepatocellular carcinoma.

Pembrolizumab is a humanised therapeutic antibody against the PD-1 receptor. It has been used in various advanced cancer immunotherapies. Here, we report an extremely rare case of a 32-year-old man who developed Stevens-Johnson syndrome (SJS) with porokeratosis simultaneously during pembrolizumab treatment for primary hepatocellular carcinoma (T3N1M1).

The role of the inflammasomes in the pathogenesis of uveitis.

Uveitis is a diverse group of sight-threatening intraocular inflammatory diseases usually causing eye redness, pain, blurred vision, and sometimes blindness. Although the exact pathogenesis of uveitis is not yet clear, accumulating evidences have shown that an imbalanced regulation of immune responses caused by a combination of genetic and environmental factors are implicated in the pathogenesis of this disease. As critical regulators of inflammation, inflammasomes have been assumed to play a role in the pathogenesis of uveitis. Recent studies have reported the association between a number of genetic variants in inflammasome related genes (such as NLRP3, NLRP1, NLRC4 and AIM2) with increased risk to uveitis. Mounting evidence have shown an aberrant activation of the NLRP3 inflammasome in both uveitis patients and murine models of uveitis. Some studies explored the intervention of uveitis via modulating inflammasome activity in the eye. This review aims at summarizing the main findings of these studies, proposing the possible mechanism whereby inflammasomes affect the susceptibility to develop uveitis, and giving a perspective for future studies, which may further improve our understanding about the role of inflammasomes and related cytokines in the pathogenesis of uveitis, and may hopefully lead to new therapeutics by targeting inflammasomes.

Malignant atrophic papulosis (Degos disease).

Malignant atrophic papulosis (Degos disease) is a rare syndrome of multiple-system vascular diseases with unknown etiology. It can affect the skin, gastrointestinal tract and central nervous system. Here, we report a 58-year-old woman with extensive porcelain-white atrophic papules. Based on the clinical manifestations, skin biopsy and colonoscopy, a diagnosis of malignant atrophic papulosis was confirmed.

Inflammasome Regulation: Therapeutic Potential for Inflammatory Bowel Disease.

Inflammasomes are multiprotein complexes formed to regulate the maturation of pro-inflammatory caspases, in response to intracellular or extracellular stimulants. Accumulating studies showed that the inflammasomes are implicated in the pathogenesis of inflammatory bowel disease (IBD), although their activation is not a decisive factor for the development of IBD. Inflammasomes and related cytokines play an important role in the maintenance of gut immune homeostasis, while its overactivation might induce excess immune responses and consequently cause tissue damage in the gut. Emerging studies provide evidence that some genetic abnormalities might induce enhanced NLRP3 inflammasome activation and cause colitis. In these cases, the colonic inflammation can be ameliorated by blocking NLRP3 activation or its downstream cytokine IL-1ß. A number of natural products were shown to play a role in preventing colon inflammation in various experimental colitis models. On the other hand, lack of inflammasome function also causes intestinal abnormalities. Thus, an appropriate regulation of inflammasomes might be a promising therapeutic strategy for IBD intervention. This review aims at summarizing the main findings in these studies and provide an outline for further studies that might contribute to our understanding of the role of inflammasomes in the pathogenesis and therapeutic treatment of IBD.

Monitoring the topical delivery of ultrasmall gold nanoparticles using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is a promising imaging modality for skin cancer diagnosis. However, this capability has been hindered by the low contrast between normal and neoplastic tissue. To overcome this limitation, gold nanoparticles have been used to enhance the contrast in OCT images and are topically administered to reduce the risk of systematic side effects associated with intravenous injection. To ensure efficient penetration and distribution of the nanoparticles, an enhanced delivery strategy is required. In this porcine study, we assessed two delivery methods: (a) using dimethyl sulfoxide (DMSO) and (b) via sonophoresis. MATERIALS AND METHODS: The gold nanoparticles were topically applied on pig skin before evaluating DMSO and sonophoresis as penetration enhancers in topical administration. The OCT images were taken from the same locations to monitor signal change. CONCLUSION: The combination of DMSO and sonophoresis is an effective method to enhance the penetration and diffusion rate of nanoparticles during topical administration. SIGNIFICANCE: Topical administration of nanoparticles is advantageous in dermatological applications. Nevertheless, efficient topical delivery remains a challenge. DMSO and sonophoresis can be used as two effective approaches to enhance topical delivery of nanoparticles.

Melanoma Biomarkers and Their Potential Application for In Vivo Diagnostic Imaging Modalities.

Melanoma is the deadliest form of skin cancer and remains a diagnostic challenge in the dermatology clinic. Several non-invasive imaging techniques have been developed to identify melanoma. The signal source in each of these modalities is based on the alteration of physical characteristics of the tissue from healthy/benign to melanoma. However, as these characteristics are not always sufficiently specific, the current imaging techniques are not adequate for use in the clinical setting. A more robust way of melanoma diagnosis is to "stain" or selectively target the suspect tissue with a melanoma biomarker attached to a contrast enhancer of one imaging modality. Here, we categorize and review known melanoma diagnostic biomarkers with the goal of guiding skin imaging experts to design an appropriate diagnostic tool for differentiating between melanoma and benign lesions with a high specificity and sensitivity.

An overview of methods to mitigate artifacts in optical coherence tomography imaging of the skin.

BACKGROUND: Optical coherence tomography (OCT) of skin delivers three-dimensional images of tissue microstructures. Although OCT imaging offers a promising high-resolution modality, OCT images suffer from some artifacts that lead to misinterpretation of tissue structures. Therefore, an overview of methods to mitigate artifacts in OCT imaging of the skin is of paramount importance. Speckle, intensity decay, and blurring are three major artifacts in OCT images. Speckle is due to the low coherent light source used in the configuration of OCT. Intensity decay is a deterioration of light with respect to depth, and blurring is the consequence of deficiencies of optical components. METHOD: Two speckle reduction methods (one based on artificial neural network and one based on spatial compounding), an attenuation compensation algorithm (based on Beer-Lambert law) and a deblurring procedure (using deconvolution), are described. Moreover, optical properties extraction algorithm based on extended Huygens-Fresnel (EHF) principle to obtain some additional information from OCT images are discussed. RESULTS: In this short overview, we summarize some of the image enhancement algorithms for OCT images which address the abovementioned artifacts. The results showed a significant improvement in the visibility of the clinically relevant features in the images. The quality improvement was evaluated using several numerical assessment measures. CONCLUSION: Clinical dermatologists benefit from using these image enhancement algorithms to improve OCT diagnosis and essentially function as a noninvasive optical biopsy.