Dual drug nanoparticle synergistically induced apoptosis, suppressed inflammation, and protected autophagic response in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic immune-mediated joint inflammatory disorder associated with aberrant activation of fibroblast-like synoviocytes (FLS). Recently, FLS gained importance due to its crucial role in RA pathogenesis, and thus, targeting FLS is suggested as an attractive treatment strategy for RA. FLS-targeted approaches may be combined with disease-modifying antirheumatic drugs (DMARDs) and natural phytochemicals to improve efficacy in RA control and negate immunosuppression. In this study, we assessed the therapeutic effectiveness of DD NP HG in primary RA-FLS cells isolated from the synovial tissue of FCA-induced RA rats. We observed that DD NP HG had good biosafety for healthy FLS cells and, at higher concentrations, a mild inhibitory effect on RA-FLS. The combination therapy (DD NP HG) of MTX NP and PEITC NE in RA-FLS showed a higher rate of apoptosis with significantly reduced LPS-induced expression of pro-inflammatory cytokines (TNF-α, IL-17A, and IL-6) in arthritic FLS. Further, the gene expression studies showed that DD NP HG significantly down-regulated the mRNA expression of IL-1ß, RANKL, NFATc1, DKK1, Bcl-xl, Mcl-1, Atg12, and ULK1, and up-regulated the mRNA expression of OPG, PUMA, NOXA and SQSTM1 in LPS-stimulated RA-FLS cells. Collectively, our results demonstrated that DD NP HG significantly inhibited the RA-FLS proliferation via inducing apoptosis, down-regulating pro-inflammatory cytokines, and further enhancing the expression of genes associated with bone destruction in RA pathogenesis. A nanotechnology approach is a promising strategy for the co-delivery of dual drugs to regulate the RA-FLS function and achieve synergistic treatment of RA.

The performance of an artificial intelligence-based computer vision mobile application for the image diagnosis of genital dermatoses: a prospective cross-sectional study.

BACKGROUND: There is a huge demand-supply gap between the incidence of genital dermatoses (including sexually transmitted infections and non-venereal genital dermatoses) and physicians trained to manage them. OBJECTIVES: To find out the performance of an artificial intelligence (AI)-based mobile application in the image diagnosis of genital dermatoses, and to compare it with primary care physicians (PCPs) and dermatologists. METHODS: Photos of the genital diseases of consecutive patients presenting to the STD and genital diseases clinic were included. The gold standard diagnosis was established by the consensus of two certified dermatologists after examination and one positive investigation. Image diagnoses by the DermaAId application, two PCPs, and two dermatologists were recorded and compared to the gold standard diagnosis and to each other. RESULTS: A total of 257 genital disease images, including 95 (37.0%) anogenital warts, 60 (22.2%) lichen sclerosus, 20 (7.8%) anogenital herpes, 15 (5.8%) tinea cruris, 14 (5.4%) molluscum contagiosum, 9 (3.5%) candidiasis, 8 (3.1%) scabies, 6 (2.3%) squamous cell carcinomas, were included. The top-1 correct diagnosis rate of the application was 68.9%, compared to the 50.4% of the PCPs and 73.2% of the dermatologists. The application significantly outperformed PCPs with regard to the correlation with the gold standard diagnosis (P < 0.0001), and matched that of the dermatologists. CONCLUSIONS: AI-based image diagnosis platforms can potentially be a low-cost rapid decision support tool for PCPs, integrated with syndromic management programs and direct-to-consumer services, and address healthcare inequities in managing genital dermatoses.

Palladium Nanocapsules for Photothermal Therapy in the Near-Infrared II Biological Window.

Recent developments in nanomaterials with programmable optical responses and their capacity to modulate the photothermal effect induced by an extrinsic source of light have elevated plasmonic photothermal therapy (PPTT) to the status of a favored treatment for a variety of malignancies. However, the low penetration depth of near-infrared-I (NIR-I) lights and the need to expose the human body to a high laser power density in PPTT have restricted its clinical translation for cancer therapy. Most nanostructures reported to date exhibit limited performance due to (i) activity only in the NIR-I region, (ii) the use of intense laser, (iii) need of large concentration of nanomaterials, or (iv) prolonged exposure times to achieve the optimal hyperthermia state for cancer phototherapy. To overcome these shortcomings in plasmonic nanomaterials, we report a bimetallic palladium nanocapsule (Pd Ncap)─with a solid gold bead as its core and a thin, perforated palladium shell─with extinction both in the NIR-I as well as the NIR-II region for PPTT applications toward cancer therapy. The Pd Ncap demonstrated exceptional photothermal stability with a photothermal conversion efficiency of ∼49% at the NIR-II (1064 nm) wavelength region at a very low laser power density of 0.5 W/cm2. The nanocapsules were further surface-functionalized with Herceptin (Pd Ncap-Her) to target the breast cancer cell line SK-BR-3 and exploited for in vitro PPTT applications using NIR-II light. Pd Ncap-Her caused more than 98% cell death at a concentration of just 50 µg/mL and a laser power density of 0.5 W/cm2 with an output power of only 100 mW. Flow cytometric and microscopic analyses revealed that Pd Ncap-Her-induced apoptosis in the treated cancer cells during PPTT. Additionally, Pd Ncaps were found to have reactive oxygen species (ROS) scavenging ability, which can potentially reduce the damage to cells or tissues from ROS produced during PPTT. Also, Pd Ncap demonstrated excellent in vivo biocompatibility and was highly efficient in photothermally ablating tumors in mice. With a high photothermal conversion and killing efficiency at very low nanoparticle concentrations and laser power densities, the current nanostructure can operate as an effective phototherapeutic agent for the treatment of different cancers with ROS-protecting ability.

Quaternary Pullulan-Functionalized 2D MoS2 Glycosheets: A Potent Bactericidal Nanoplatform for Efficient Wound Disinfection and Healing.

Rapid emergence of multidrug-resistant bacterial strains has posed a global threat to public health. Hospital-acquired infections, especially in diabetic and burn patients, severely impede the process of wound healing, thereby causing high mortality. This calls for developing a new biomaterial that synergistically destroys pathogenic strains and also helps in promoting wound healing without causing any resistance generation. A new and highly potent antibacterial agent has been developed by integrating the bactericidal and wound healing properties of MoS2 nanosheets and a recently developed quaternized polysaccharide, pullulan (CP), into a single nanoplatform for accelerated wound therapy. MoS2 nanosheets are noncovalently functionalized with quaternized pullulan to yield glycosheets (MCP) that efficiently eradicate both Gram-negative Escherichia coli (5 µg/mL) and Gram-positive Staphylococcus aureus (10 µg/mL) within a short period of 4 h, through a synergistic action of membrane damage and chemical oxidation. MoS2 nanosheets coupled with CP exert a membrane-directed bactericidal action through distinct mechanisms of "pore-forming" and "non-pore-forming" pathways, respectively, whereas oxidative stress is induced by MoS2 nanosheets alone to collectively kill the pathogens. The MCP glycosheets have good biocompatibility and are also capable of disrupting and eradicating mature biofilms. Rapid and highly efficient in vivo wound disinfection and healing occurred upon MCP treatment through the reduction of inflammation and promotion of cellular proliferation and tissue remodeling. Thus, MCP glycosheets can emerge as a safe and potential biomaterial for better wound care management.

Clinicodemographic features of mixed vitiligo: a case-control study.

BACKGROUND: Mixed vitiligo (MV) is the coexistence of segmental vitiligo (SV) and non-segmental vitiligo (NSV). The literature on MV is sparse. OBJECTIVE: To assess the clinicodemographic and treatment parameters in MV and compare them with SV. METHODS: Clinical data of MV and SV patients enrolled in our pigmentary clinic from July 2015 to December 2019 were reviewed retrospectively and compared. RESULTS: Out of a total of 4,371 vitiligo patients, 293 (6.7%) were SV while 74 (1.69%) were MV. As compared to SV, MV had significantly lower mean age of onset of segmental component (SC) (13.33 ± 9.01 vs. 15.70 ± 8.60 years, P = 0.03) and significantly higher proportion of patients with more than 1% body surface involvement by SC (66.2% vs. 51.5%, P = 0.03) and presence of leukotrichia in the SC (66.2% vs. 51.5%, P = 0.03). Topical agents and systemic immunosuppressive agents were significantly more effective in non-segmental component (NSC) as compared to SC of MV. Surgical modalities were the only effective treatment modality for SC. LIMITATIONS: Retrospective design, heterogeneity of treatment regimens. CONCLUSION: Early age of onset, larger (>1%) body surface area involvement, and leukotrichia in SV predict its progression into MV with time. Treatment response to different modalities varies significantly between SC and NSC of MV.

A Retrospective Study to Evaluate the Impact of In-Patient Dermatological Consultations on Diagnostic Accuracy in a Tertiary Care Setting.

BACKGROUND: Dermatology is primarily an outpatient specialty. However, dermatology consultations play an important role in care of inpatients. Data on inpatient dermatological consultations in tertiary care settings is limited. OBJECTIVES: To evaluate clinical characteristics of inpatient dermatological consultations and effect on clinical outcomes in a tertiary care setting. METHODS: This was a single-center retrospective study where the records of all dermatological consultations for patients admitted under various specialties, emergency services, and intensive care units (ICU) at our tertiary care institute over 2 years period were reviewed. The details of patients, primary care unit, dermatological complaints, diagnosis, investigations performed, treatment given, and follow-up were recorded and analyzed. RESULTS: Total of 1717 dermatologic consultations (1000 males) were recorded, with mean age of study population being 33.6 ± 21.6 years (median - 32 years). Out of total 1717 patients, 136 (7.9%), 321 (18.7%), 1135 (66.1%), and 125 (7.3%) patients were infants, children, adolescents, adults, and elderly, respectively. The most frequent diagnostic group was infective diseases (586; 34.1%) followed by inflammatory diseases (442; 25.7%), mucocutaneous adverse drug reactions (160; 9.3%), and autoimmune diseases (65; 3.8%). Primary team's diagnosis was concordant with the dermatology consultation in 1112 (64.8%) patients and discordant observations were recorded in 605 patients (35.2%). Most discordant dermatological diagnoses included inflammatory disorders such as lichen planus, atopic dermatitis, bullous pemphigoid; mechanical disorders; nutritional deficiency disorders, and benign neoplasms. CONCLUSION: Common skin conditions account for a large majority of dermatologic consultations in a hospital setting. Inpatient dermatology consultations improve the diagnostic accuracy.

Factors Predicting the Outcome of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A 5-Year Retrospective Study.

BACKGROUND: Clinicodemographic and laboratory parameters predicting the outcome of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) may vary among populations owing to genotypic and environmental variations. There is a scarcity of studies evaluating these parameters in Indian population. AIMS: To analyze clinicodemographic and laboratory parameters predicting disease outcome in patients of SJS/TEN. MATERIALS AND METHODS: Clinical records of patients admitted with a diagnosis of SJS/TEN from January 2014 to December 2018 were reviewed retrospectively with respect to data pertaining to clinicodemographic details, laboratory parameters, and disease outcome. RESULTS: Of 51 patients included in the study, 24 (47.06%) were females. Anticonvulsants [phenytoin (19.6%), carbamazepine (13.7%), others (5.88%)] were the most commonly implicated drugs followed by NSAIDs (19.6%). The overall mortality was 21.6% [SJS (0%), SJS-TEN overlap (18.8%), and TEN (28.6%)]. The mean detached body surface area (BSA) (35.4% ± 10.4% vs. 25.7% ± 11.8%; P = 0.02) was significantly higher among patients with mortality. Blood urea nitrogen, serum HCO3 - levels, and random blood sugar were significantly associated with mortality. Presence of sepsis during the disease course was associated with higher mortality (9/12 vs. 2/39; P = 0.001). Other components of SCORTEN like age and heart rate were not significantly associated with poor outcome in our study. None of our patients had associated malignancy. CONCLUSION: A higher detached BSA, presence of sepsis, higher blood urea nitrogen and random blood sugar, and lower serum HCO3 - levels were associated with mortality. Refinement of scoring systems predicting the outcome of SJS-TEN is needed for better disease prognostication.

Clinical, biochemical, and serologic predictors of drug reaction with eosinophilia and systemic symptoms syndrome: A prospective case-control study.

BACKGROUND: Detailed scoring systems such as the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) score for validating a diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are available, but there is no rapid, easy tool to identify DRESS at presentation. OBJECTIVE: To identify the clinical, biochemical, and serologic markers predicting the DRESS syndrome and its severity. METHODS: In this prospective observational study, 25 patients with the DRESS syndrome and 25 control patients with maculopapular drug rash were recruited. Baseline clinical, biochemical, and serologic markers, such as high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate, and thymus and activation-regulated chemokine (TARC) levels, were recorded and their utility in identifying the DRESS syndrome at presentation and predicting severity was analyzed. RESULTS: The effectiveness of TARC level (>613.25 pg/mL), total body surface area (TBSA, >35%), hsCRP (>5 mg/L), eosinophils (>6%), absolute eosinophil count (>450 cells/mm3), and aspartate transaminase (>92 U/L) were statistically similar to the effectiveness of the RegiSCAR DRESS validation score (≥2) in diagnosing the DRESS syndrome. A combination model (TBSA at baseline, eosinophil count, and hsCRP) at the cutoff of 6.8 had a sensitivity of 96% and a specificity of 100%. Baseline serum TARC levels did not predict the DRESS severity or outcome. LIMITATIONS: Small sample size. CONCLUSION: The combination of TBSA involvement, eosinophil count, and hsCRP levels can predict the DRESS syndrome at presentation.