Evaluation of hematological inflammatory parameters in patients with palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease of ill-defined etiopathology. Recent studies have proposed complete blood count-based hematological parameters, such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), as biomarkers to monitor disease status in many inflammatory diseases. This study aimed to analyze for the first time the clinical significance of hematological parameters, including NLR, monocyte/lymphocyte ratio (MLR), PLR, mean platelet volume (MPV), plateletcrit (PCT), and pan-immune-inflammation value (PIV) in PPP patients. METHODS: We retrospectively investigated the clinical and laboratory data of 237 patients with PPP and 250 sex-age-matched healthy controls (HCs). Hematological parameters were compared between patients with PPP and HCs. The correlations between these parameters and disease severity, as well as treatment response, were analyzed. RESULTS: NLR, MLR, MPV, PCT, and PIV values were significantly higher in PPP patients than in HCs. But in receiver-operating characteristic analyses, only monocyte count (Youden Index = 0.53), PCT (Youden Index = 0.65), and PIV (Youden Index = 0.52) performed relatively accurate distinguishment between moderate-to-severe cases and mild cases. PCT and PIV values were significantly correlated with disease severity. After treatment, both PIV and PCT values decreased significantly in the responder group but not in the non-responder group. CONCLUSIONS: Hematological parameters altered significantly in PPP patients. PCT and PIV can be used as simple and inexpensive biomarkers for systemic inflammation in PPP patients.

Solvation Structure of Methanol-in-Salt Electrolyte Revealed by Small-Angle X-ray Scattering and Simulations.

The solvation structure of water-in-salt electrolytes was thoroughly studied, and two competing structures─anion solvated structure and anion network─were well-defined in recent publications. To further reveal the solvation structure in those highly concentrated electrolytes, particularly the influence of solvent, methanol was chosen as the solvent for this proposed study. In this work, small-angle X-ray scattering, small-angle neutron scattering, Fourier-transform infrared spectroscopy, and Raman spectroscopy were utilized to obtain the global and local structural information. With the concentration increment, the anion network formed by TFSI- became the dominant structure. Meanwhile, the hydrogen bonds among methanol were interrupted by the TFSI- anion and formed a new connection with them. Molecular dynamic simulations with two different force fields (GAFF and OPLS-AA) are tested, and GAFF agreed with synchrotron small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS) results well and provided insightful information about molecular/ion scale solvation structure. This article not only deepens the understanding of the solvation structure in highly concentrated solutions, but more importantly, it provides additional strong evidence for utilizing SAXS/WAXS to validate molecular dynamics simulations.

Characteristics and Burdens of Disease in Patients from Beijing with Generalized Pustular Psoriasis and Palmoplantar Pustulosis: Multicenter Retrospective Cohort Study Using a Regional Database.

BACKGROUND AND OBJECTIVE: Pustular psoriasis is a chronic and recurrent autoimmune disease, although little is known about the disease burden of pustular psoriasis in China. We analyzed the characteristics and disease burdens of patients from Beijing who had generalized pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). METHODS: This multicenter retrospective cohort study used a regional electronic health database that covered 30 public hospitals in Beijing. From June 2016 to June 2021, all patients with a diagnosis of GPP, PPP, or psoriasis vulgaris (PV) were identified by International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. The GPP and PPP cohorts were separately matched with patients with PV in a 3:1 ratio for comparisons. Demographic data, clinical characteristics, healthcare resource utilization, and costs were collected. Descriptive and comparative analyses were used to compare the cohorts. RESULTS: There were 744 patients with GPP (46.8% men; age 42.14 ± 21.47 years) and 4808 patients with PPP (35.5% men; age 51.65 ± 16.12 years); 14.5% of patients with GPP had concomitant PV and 7.5% of patients with PPP had concomitant PV. Relative to matched patients with PV, patients with GPP had a higher prevalence of erythrodermic psoriasis (5.9% vs 0.4%, p < 0.0001), psoriatic arthritis (3.1% vs 1.5%, p = 0.007), and organ failure (1.1% vs 0.2%, p = 0.002). Relative to matched patients with PV, patients with PPP had a higher prevalence of cerebrovascular disease (4.7% vs 1.2%, p < 0.0001), thyroid dysfunction (3.9% vs 3.3%, p = 0.035), and type 2 diabetes mellitus (6.8% vs 5.9%, p = 0.030). More patients with GPP than patients with PV received systemic non-biological agents (27.9% vs 3.3%, p < 0.0001) and biologic agents (4.8% vs 2.0%, p = 0.010). More patients with PPP than patients with PV received topical agents (50.9% vs 34.7%, p < 0.0001) and systemic non-biological agents (17.8% vs 2.7%, p < 0.0001). More patients with GPP than patients with PV required inpatient hospitalization (22.0% vs 7.8%, p < 0.0001). Hospitalization stay was longer in patients with GPP than patients with PV (11.72 ± 0.45 vs 10.38 ± 0.45 days, p = 0.022). More patients with PPP than patients with PV had emergency visits (16.3% vs 12.8%, p < 0.0001). The GPP and PPP cohorts and their matched PV cohorts had no significant differences in costs. However, patients with PPP had lower outpatient costs than patients with PV (368.20 ± 8.19 vs 445.38 ± 5.90 Chinese Yuan per patient per month, p < 0.0001). CONCLUSIONS: Patients from Beijing with GPP and PPP had higher disease burdens than matched PV cohorts, including the prevalence of comorbidities, healthcare resource utilization, and medication burden. However, the economic burden of pustular psoriasis was similar to that of PV. Practical and specific therapies are needed to reduce the burdens of pustular psoriasis.

An update on therapeutic options for palmoplantar pustulosis: a narrative review and expert recommendations.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule formation in palms and soles and a recurrent disease course. Although we have many treatments for PPP, there is no authoritative guidance. AREAS COVERED: A thorough search of PubMed was conducted to identify studies in PPP from 1973 onwards, with additional references to specific articles. Any treatment methods were outcomes of interest, including topical treatment, systemic treatment, biologics, other targeted treatments, phototherapy, and tonsillectomy. EXPERT OPINION: Topical corticosteroids are suggested as first-line therapy. Oral acitretin has become the most applied systemic retinoid recommended in PPP without joint involvement. For patients with arthritis, immunosuppressants like cyclosporin A and methotrexate are more recommended. UVA1, NB-UVB, and 308-nm excimer laser are effective phototherapy options. The combinations of topical or systemic agents and phototherapy may enhance the efficacy, particularly in recalcitrant cases. Secukinumab, ustekinumab, and apremilast are the most investigated targeted therapies. However, heterogeneous reported outcomes in clinical trials provided low-to-moderate quality evidence of their efficacy. Future studies are required to address these evidence gaps. We suggest managing PPP based on the acute phase, maintenance phase, and comorbidities.

One-Pot Synthesis of 2D-2D WO3 /g-C3 N4 Photocatalyst in Reverse Microemulsion System via Supercritical CO2 for Enhanced Hydrogen Generation.

Construction of Z-scheme photocatalyst is an effective approach for using solar energy to produce hydrogen during water splitting. Herein, 2D/2D WO3 /g-C3 N4 heterojunction photocatalyst was synthesized by a convenient and green method including exfoliation and heterojunction procedures, in the reverse microemulsion system via supercritical carbon dioxide (scCO2 ). The resultant W/CN-10.3 composite exhibited enhanced photocatalytic activities towards the hydrogen evolution during water splitting with a hydrogen evolution rate of 688.51 µmol g-1 h-1 , which was more than 16 times higher than bulk g-C3 N4 with the same loading amount of Pt as cocatalyst. Due to its effective separation of photogenerated carriers and prolonged lifetime, more photoexcited electrons with high reduction ability could contribute to the production of H2 . Possible formation mechanism of 2D-2D WO3 /g-C3 N4 nanosheets via scCO2 in the reverse microemulsion system by the one-pot method has been proposed. This work provides an efficient and green strategy to synthesize 2D-2D heterojunction for the utilization in solar-to-fuel conversion.

Update on the aetiology and mechanisms of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a chronic disease characterized by non-bacterial pustules. Variants in several genes, such as IL36RN, AP1S3, and CARD14, are involved in the pathogenesis of GPP. The prevalence of different gene variants varies among ethnicities, and some variants are related to concurrent psoriasis vulgaris or age at onset. Flares can be triggered by medications (most commonly corticosteroids), infections (possibly due to Toll-like receptor [TLR] and antimicrobial peptides), pregnancy (the onset of GPP has been attributed to endocrine abnormalities such as hypoparathyroidism and hypocalcaemia), hypocalcaemia (presumably due to low levels of calcium and vitamin D regulating the proliferation and differentiation of keratinocytes), and other factors including stress and sun exposure. The mechanisms of pustule formation involve: 1) the LL37/TLR pathway, in which LL37 acts as an alarmin, interacting with TLR and activating the NF-κB and MAPK pathways; 2) the balance between calcium and 1,25(OH)2D levels, and 3) neutrophils and the complement system.

Comparison of fixed charge and polarizable models for predicting the structural, thermodynamic, and transport properties of molten alkali chlorides.

Results from extensive molecular dynamics simulations of molten LiCl, NaCl, KCl, and RbCl over a wide range of temperatures are reported. Comparison is made between the "Polarizable Ion Model" (PIM) and the non-polarizable "Rigid Ion Model" (RIM). Densities, self-diffusivities, shear viscosities, ionic conductivities, and thermal conductivities are computed and compared with experimental data. In addition, radial distribution functions are computed from ab initio molecular dynamics simulations and compared with the two sets of classical simulations as well as experimental data. The two classical models perform reasonably well at capturing structural and dynamic properties of the four molten alkali chlorides, both qualitatively and often quantitatively. With the singular exception of liquid density, for which the PIM is more accurate than the RIM, there are few clear trends to suggest that one model is more accurate than the other for the four alkali halide systems studied here.

Structure and dynamics of the molten alkali-chloride salts from an X-ray, simulation, and rate theory perspective.

Molten salts are of great interest as alternative solvents, electrolytes, and heat transfer fluids in many emerging technologies. The macroscopic properties of molten salts are ultimately controlled by their structure and ion dynamics at the microscopic level and it is therefore vital to develop an understanding of these at the atomistic scale. Herein, we present high-energy X-ray scattering experiments combined with classical and ab initio molecular dynamics simulations to elucidate structural and dynamical correlations across the family of alkali-chlorides. Computed structure functions and transport properties are in reasonably good agreement with experiments providing confidence in our analysis of microscopic properties based on simulations. For these systems, we also survey different rate theory models of anion exchange dynamics in order to gain a more sophisticated understanding of the short-time correlations that are likely to influence transport properties such as conductivity. The anion exchange process occurs on the picoseconds time scale at 1100 K and the rate increases in the order KCl < NaCl < LiCl, which is in stark contrast to the ion pair dissociation trend in aqueous solutions. Consistent with the trend we observe for conductivity, the cationic size/mass, as well as other factors specific to each type of rate theory, appear to play important roles in the anion exchange rate trend.

SEM-Drude Model for the Accurate and Efficient Simulation of MgCl2-KCl Mixtures in the Condensed Phase.

There is a long history of models that to different extents reproduce structural and dynamical properties of high-temperature molten salts. Whereas rigid ion models can work fairly well for some of the monovalent salts, polarizability is fundamentally important when small divalent or multivalent cations are combined with significantly polarizable anions such as Cl- to form networked liquids that display a first sharp diffraction peak. There are excellent polarizable ion models (PIMs) for these systems, but there has been little success with the less expensive Core-Shell type models, which are often described as unwieldy or difficult to fit. In this article, we present the Sharma-Emerson-Margulis (SEM)-Drude model for MgCl2/KCl mixtures that with the same ingredients used in the latest and most accurate PIM models overcome the aforementioned obstacles at significantly less computational cost; structural and dynamical properties are for all practical purposes very similar to what we obtain from the PIM but typical simulations can be more than 30 times faster. This has allowed us not only to expand our recent studies on the temperature and composition dependence of intermediate range order in MgCl2/KCl mixtures but also to access transport properties that were simply too costly to properly sample in our recently published studies.

Melting points of alkali chlorides evaluated for a polarizable and non-polarizable model.

Accurate molecular models of pure alkali halides are a prerequisite for developing transferable models of molten salts that can predict the properties of complex salt mixtures, such as those including dissolved actinide species and metal ions. Predicting the melting point of a substance represents a rigorous test of model quality. To this end, we compute the melting points of the alkali chlorides for a popular non-polarizable and polarizable model. Neither model yields more accurate predictions of the melting points across the entire family of alkali chlorides. Further calculations suggest that this may be because neither model simultaneously represents both the solid and liquid phases with sufficient accuracy across all four alkali chlorides. We find that the deviation from experiment in the model enthalpy of melting may be a good indicator of the deviation from experiment in the model melting temperature. Since the enthalpy of melting is easier to calculate in simulation than melting temperature, it may be a useful quantity to target when developing new force fields for molten salts.

Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease that features the abnormal proliferation of keratinocytes. This proliferation could partly result from disturbances in vitamin A metabolism. Changes in psoriasis patients of the levels of retinol-binding protein 4 (RBP4), a carrier of retinol (vitamin A); transmembrane protein stimulated by retinoic acid 6 (STRA6); and other retinol metabolic molecules have not yet been fully established. Therefore, we investigated vitamin A-related proteins in mice with imiquimod (IMQ)-induced psoriasis. METHODS: Thirty mice were divided into four study groups: two groups underwent IMQ application for 3 or 6 days (groups A and B, respectively), and two groups underwent Vaseline application for 3 or 6 days (groups C and D, respectively). Blood and skin samples from both lesional and non-lesional areas of the mice were analyzed using enzyme-linked immunosorbent assays, hematoxylin and eosin staining, immunochemistry, real-time reverse transcription polymerase chain reaction, and RNA sequencing. RESULTS: IMQ-treated mice developed erythema, scales, and skin thickening. Compared with the control groups, IMQ-treated groups had the following changes: 1) interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α levels were raised significantly in both serum and lesional skin (all p < 0.001); 2) retinol levels in lesional skin increased slightly (p = 0.364), but no change was evident in serum retinol levels; 3) STRA6 was upregulated in both lesional skin (p = 0.021) and serum (p = 0.034); 4) RBP4 levels were elevated in serum (p = 0.042), but exhibited only an increasing trend (p = 0.273) in lesional skin; and 5) proteins and enzymes that mediate retinoic acid formation and transformation were upregulated in lesional skin. CONCLUSIONS: As the demand for vitamin A in psoriatic mice increased, retinol underwent relocation from the circulation to target tissues. RBP4, STRA6, and the transformation from retinol to retinoic acid were upregulated, which may be part of the mechanism of psoriasis skin lesion formation. We propose that a positive feedback mechanism was formed that maintained the severity of psoriasis.

Investigation of using very high-frequency ultrasound in the differential diagnosis of early-stage pemphigus vulgaris vs seborrheic dermatitis.

BACKGROUND: Early-stage pemphigus vulgaris (PV) often manifests as erythema alone. We hypothesized that very high-frequency ultrasonography (VHFUS) features could simplify the differential diagnosis of early-stage pemphigus vulgaris versus seborrheic dermatitis (SD). MATERIALS AND METHODS: Fourteen patients with SD or early-stage PV were recruited from our outpatient clinic during 2016-2019. We used 50-MHz VHFUS to image the erythema on the patients' scalp, face, chest, and back and retrospectively evaluated their ultrasonographic features. RESULTS: Very high-frequency ultrasonography images of early-stage PV showed enhanced epidermal echo (8/14, 57%), linear or oval intra-epidermal hypoechoic/anechoic areas (12/14, 86%), linear anechoic areas at the dermal-epidermal junction (14/14, 100%), reduced echo of superficial to whole dermis (9/14, 64%), and slightly increased dermal thickness (14/14, 100%). The intra-epidermal hypoechoic/anechoic bands (100%) showed the greatest specificity. VHFUS images of SD showed enhanced epidermal echo (7/14, 50%), epidermal unevenness (7/14, 50%), linear anechoic bands at the dermal-epidermal junction (8/14, 57%), reduced middle dermis echo (10/14, 71%), and slightly increased dermal thickness (10/14, 71%). The epidermal unevenness (100%) had the greatest specificity. There was a significant difference (P < .05) between early-stage PV and SD regarding the proportion of linear intraepithelial hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction. CONCLUSIONS: Early-stage PV and SD have relatively specific VHFUS erythematous manifestations. Intra-epidermal hypoechoic/anechoic bands for early-stage PV and epidermal unevenness for SD were most specific. VHFUS contributes to the differential diagnosis of PV and SD by highlighting their features, that is, intra-epidermal hypoechoic/anechoic bands and linear anechoic areas at the dermal-epidermal junction.

Nucleation of Salt Crystals in Clay Minerals: Molecular Dynamics Simulation.

Nucleation of salt crystals in confined media occurs in many processes of high importance, such as injection of CO2 in geological formations for its sequestration. In particular, salt precipitation in clays, a main component of sedimentary rock, is an important phenomenon. The crystals precipitate on the pores' surface, modify the pore space morphology, and reduce its flow and transport properties. Despite numerous efforts to understand the mechanisms of nucleation of salt crystals in confined media, the effect of the clay's chemistry on the growth, distribution, and properties of the crystals is not well understood. We report the results of extensive molecular dynamics simulation of nucleation and growth of NaCl crystals in a clay pore using molecular models of two types of clay minerals, Na-montmorillonite and kaolinite. Clear evidence is presented for the nucleation of the salt crystals that indicates that the molecular structure of clay minerals affects their spatial distribution, although the nucleation mechanism is the same in both types of clays.