High-Resolution Single-Molecule Magnetic Tweezers.

Single-molecule magnetic tweezers deliver magnetic force and torque to single target molecules, permitting the study of dynamic changes in biomolecular structures and their interactions. Because the magnetic tweezer setups can generate magnetic fields that vary slowly over tens of millimeters-far larger than the nanometer scale of the single molecule events being observed-this technique can maintain essentially constant force levels during biochemical experiments while generating a biologically meaningful force on the order of 1-100 pN. When using bead-tether constructs to pull on single molecules, smaller magnetic beads and shorter submicrometer tethers improve dynamic response times and measurement precision. In addition, employing high-speed cameras, stronger light sources, and a graphics programming unit permits true high-resolution single-molecule magnetic tweezers that can track nanometer changes in target molecules on a millisecond or even submillisecond time scale. The unique force-clamping capacity of the magnetic tweezer technique provides a way to conduct measurements under near-equilibrium conditions and directly map the energy landscapes underlying various molecular phenomena. High-resolution single-molecule magnetic tweezerscan thus be used to monitor crucial conformational changes in single-protein molecules, including those involved in mechanotransduction and protein folding.

Enantioselective sensing by collective circular dichroism.

Quantitative determination and in situ monitoring of molecular chirality at extremely low concentrations is still challenging with simple optics because of the molecular-scale mismatch with the incident light wavelength. Advances in spectroscopy1-4 and nanophotonics have successfully lowered the detection limit in enantioselective sensing, as it can bring the microscopic chiral characteristics of molecules into the macroscopic scale5-7 or squeeze the chiral light into the subwavelength scale8-17. Conventional nanophotonic approaches depend mainly on the optical helicity density8,9 by localized resonances within an individual structure, such as localized surface plasmon resonances (LSPRs)10-16 or dielectric Mie resonances17. These approaches use the local chiral hotspots in the immediate vicinity of the structure, whereas the handedness of these hotspots varies spatially. As such, these localized resonance modes tend to be error-prone to the stochasticity of the target molecular orientations, vibrations and local concentrations18,19. Here we identified enantioselective characteristics of collective resonances (CRs)20 arising from assembled 2D crystals of isotropic, 432-symmetric chiral gold nanoparticles (helicoids)21,22. The CRs exhibit a strong and uniform chiral near field over a large volume above the 2D crystal plane, resulting from the collectively spinning, optically induced dipoles at each helicoid. Thus, energy redistribution by molecular back action on the chiral near field shifts the CRs in opposite directions, depending on the handedness of the analyte, maximizing the modulation of the collective circular dichroism (CD).

Stability-limiting heterointerfaces of perovskite photovoltaics.

Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics1. Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments.

Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer.

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, binds Toll-like receptor 4 (TLR4)-MD2 complex and activates innate immune responses. LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14. To define the sequential molecular interactions underlying this transfer, we reconstituted in vitro the entire LPS transfer process from LPS micelles to TLR4-MD2. Using electron microscopy and single-molecule approaches, we characterized the dynamic intermediate complexes for LPS transfer: LBP-LPS micelles, CD14-LBP-LPS micelle, and CD14-LPS-TLR4-MD2 complex. A single LBP molecule bound longitudinally to LPS micelles catalyzed multi-rounds of LPS transfer to CD14s that rapidly dissociated from LPB-LPS complex upon LPS transfer via electrostatic interactions. Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner. The definition of the structural determinants of the LPS transfer cascade to TLR4 may enable the development of targeted therapeutics for intervention in LPS-induced sepsis.

Profiling of BCLxL Protein Complexes in Non-Small Cell Lung Cancer Cells via Multiplexed Single-Molecule Pull-Down and Co-Immunoprecipitation.

We introduce multiplexed single-molecule pull-down and co-immunoprecipitation, named m-SMPC, an analysis tool for profiling multiple protein complexes within a single reaction chamber using single-molecule fluorescence imaging. We employed site-selective conjugation of biotin and fluorescent dye directly onto the monoclonal antibodies, which completed an independent sandwich immunoassay without the issue of host cross-reactivity. We applied this technique to profile endogenous B-cell lymphoma extra-large (BCLxL) complexes in non-small cell lung cancer (NSCLC) cells. Up to three distinct BCLxL complexes were successfully detected simultaneously within a single reaction chamber without fluorescence signal crosstalk. Notably, the NSCLC cell line EBC-1 exhibited high BCLxL-BAX and BCLxL-BAK levels, which closely paralleled a strong response to the BCLxL inhibitor A-1331852. This streamlined method offers the potential for quantitative biomarkers derived from protein complex profiling, paving the way for their application in protein complex-targeted therapies.

Efficacy of natural killer cell therapy combined with chemoradiotherapy in murine models of head and neck squamous cell carcinoma.

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.

Evolutionary balance between foldability and functionality of a glucose transporter.

Despite advances in resolving the structures of multi-pass membrane proteins, little is known about the native folding pathways of these complex structures. Using single-molecule magnetic tweezers, we here report a folding pathway of purified human glucose transporter 3 (GLUT3) reconstituted within synthetic lipid bilayers. The N-terminal major facilitator superfamily (MFS) fold strictly forms first, serving as a structural template for its C-terminal counterpart. We found polar residues comprising the conduit for glucose molecules present major folding challenges. The endoplasmic reticulum membrane protein complex facilitates insertion of these hydrophilic transmembrane helices, thrusting GLUT3's microstate sampling toward folded structures. Final assembly between the N- and C-terminal MFS folds depends on specific lipids that ease desolvation of the lipid shells surrounding the domain interfaces. Sequence analysis suggests that this asymmetric folding propensity across the N- and C-terminal MFS folds prevails for metazoan sugar porters, revealing evolutionary conflicts between foldability and functionality faced by many multi-pass membrane proteins.

Effectiveness of Early Thiopurine Use in Korean Patients With Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) Study.

BACKGROUND: Thiopurines play an important role in the management of steroid-refractory and steroid-dependent ulcerative colitis. However, the effectiveness of the early use of thiopurines in ulcerative colitis remains controversial. MATERIALS AND METHODS: In this multicenter prospective cohort (MOSAIK) study, we divided patients with ulcerative colitis into those who underwent early (within 6 mo of diagnosis) and late (6 mo after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. RESULTS: Overall, 333 patients with moderate-to-severe ulcerative colitis were included. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.9% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3 to 2.0); the median maintenance dose was 1.1 mg/kg (0.3 to 2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis (P=0.712). The presence of extraintestinal manifestations (hazard ratio: 4.674, 95% CI: 1.210-18.061, P=0.025) independently predicted an increased risk of clinical relapse. CONCLUSIONS: Patients with ulcerative colitis who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

Robot-assisted gastric endoscopic submucosal dissection significantly improves procedure time at challenging dissection locations.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early malignant stomach lesions. However, this procedure is technically demanding and carries a high complication risk. The level of difficulty in performing ESD is influenced by the location of the lesion. In our study, we aimed to investigate and analyze the effectiveness of robot-assisted ESD for lesions situated in challenging locations within the stomach. METHODS: We developed a gastric simulator that could be used to implement various gastric ESD locations. An EndoGel (Sunarrow, Tokyo, Japan) was attached to the simulator for the dissection procedures. Robot-assisted or conventional ESD was performed at challenging or easy locations by two ESD-trainee endoscopists. RESULTS: The procedure time was remarkably shorter for robotic ESD than conventional dissection at challenging locations (6.2 vs. 10.2 min, P < 0.05), mainly due to faster dissection (220.3 vs. 101.9 mm2/min, P < 0.05). The blind dissection rate was significantly lower with robotic ESD than with the conventional method (17.6 vs. 35.2%, P < 0.05) at challenging locations. CONCLUSION: The procedure time was significantly shortened when robot-assisted gastric ESD procedures were performed at challenging locations. Therefore, our robotic device provides simple, effective, and safe multidirectional traction for endoscopic submucosal dissection at challenging locations, thereby reducing difficulty of the procedure.

Linking excess entropy and acentric factor in spherical fluids.

Introduced by Pitzer in 1955, the acentric factor (ω) has been used to evaluate a molecule's deviation from the corresponding state principle. Pitzer devised ω based on a concept called perfect liquid (or centric fluid), a hypothetical species perfectly adhering to this principle. However, its physical significance remains unclear. This work attempts to clarify the centric fluid from an excess entropy perspective. We observe that the excess entropy per particle of centric fluids approximates -kB at their critical points, akin to the communal entropy of an ideal gas in classical cell theory. We devise an excess entropy dissection and apply it to model fluids (square-well, Lennard-Jones, Mie n-6, and the two-body ab initio models) to interpret this similarity. The dissection method identifies both centricity-independent and centricity-dependent entropic features. Regardless of the acentric factor, the attractive interaction contribution to the excess entropy peaks at the density where local density is most enhanced due to the competition between the local attraction and critical fluctuations. However, only in centric fluids does the entropic contribution from the local attractive potential become comparable to that of the hard sphere exclusion, making the centric fluid more structured than acentric ones. These findings elucidate the physical significance of the centric fluid as a system of particles where the repulsive and attractive contributions to the excess entropy become equal at its gas-liquid criticality. We expect these findings to offer a way to find suitable intermolecular potentials and assess the physical adequacy of equations of state.

scRNA-seq analysis discovered suppression of immunomodulatory dependent inflammatory response in PMBCs exposed to silver nanoparticles.

The assessment of AgNPs toxicity in vitro and in vivo models are frequently conflicting and inaccurate. Nevertheless, single cell immunological responses in a heterogenous environment have received little attention. Therefore, in this study, we have performed in-depth analysis which clearly revealed cellular-metal ion association as well as specific immunological response. Our study didn't show significant population differences in PMBC between control and AgNPs group implying no toxicological response. To confirm it further, deep profiling identified differences in subsets and differentially expressed genes (DEGs) of monocytes, B cells and T cells. Notably, monocyte subsets showed significant upregulation of metallothionein (MT) gene expression such as MT1G, MT1X, MT1E, MT1A, and MT1F. On the other hand, downregulation of pro-inflammatory genes such as IL1ß and CCL3 in both CD16 + and CD16- monocyte subsets were observed. This result indicated that AgNPs association with monocyte subsets de-promoted inflammatory responsive genes suggesting no significant toxicity observed in AgNPs treated group. Other cell types such as B cells and T cells also showed negligible differences in their subsets suggesting no toxicity response. Further, AgNPs treated group showed upregulation of cell proliferation, ribosomal synthesis, downregulation of cytokine release, and T cell differentiation inhibition. Overall, our results conclude that treatment of AgNPs to PMBC cells didn't display immunological related cytotoxicity response and thus motivate researchers to use them actively for biomedical applications.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan.

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl2, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables-DMPC (X1, 70.58 mol%), cholesterol (X2, 22.54 mol%), and DCP (X3, 6.88 mol%)-and three response variables: encapsulation efficiency (Y1, 76.92%), released amount of free fatty acid at 2 h (Y2, 39.82%), and released amount of RVP at 6 h (Y3, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Disposable electrochemical sensors based on reduced graphene oxide/polyaniline/poly(alizarin red S)-modified integrated carbon electrodes for the detection of ciprofloxacin in milk.

An electrochemical sensor based on an electroactive nanocomposite was designed for the first time consisting of electrochemically reduced graphene oxide (ERGO), polyaniline (PANI), and poly(alizarin red S) (PARS) for ciprofloxacin (CIPF) detection. The ERGO/PANI/PARS-modified screen-printed carbon electrode (SPCE) was constructed through a three-step electrochemical protocol and characterized using FTIR, UV-visible spectroscopy, FESEM, CV, LSV, and EIS. The new electrochemical CIPF sensor demonstrated a low detection limit of 0.0021 µM, a broad linear range of 0.01 to 69.8 µM, a high sensitivity of 5.09 µA/µM/cm2, and reasonable selectivity and reproducibility. Moreover, the ERGO/PANI/PARS/SPCE was successfully utilized to determine CIPF in milk with good recoveries and relative standard deviation (< 5%), which were close to those with HPLC analysis.

Humeral stem alignment of curved short stem in reverse shoulder arthroplasty: Varus/Valgus alignment is not a determinant for clinical outcomes.

BACKGROUND: This study aimed to investigate the influence of curved short stem alignment within the proximal humerus on the clinical outcomes of reverse shoulder arthroplasty. We hypothesized that the varus/valgus alignment would yield clinical outcomes comparable to those of a neutral alignment. METHODS: We retrospectively reviewed 167 patients who underwent reverse shoulder arthroplasty using the Aequalis Ascend Flex implant between January 2017 and December 2021. The study categorized the patients into three groups based on the angle difference between the humeral axis and the stem axis: neutral group (GN, defined as within ±5 degrees), valgus group (GL), and varus group (GR). Functional outcomes were assessed using the visual analog scale pain score, subjective shoulder value, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and active range of motion. Routine radiographic evaluations were also conducted to assess the filling ratio and bone resorption. RESULTS: Among 138 patients, 89 were in the GN group, 37 (27%) in the GL group, and 12 (9%) in the GR group. The average degree of varus alignment was 6 (range from 5 to 7 degrees), while the average degree of valgus alignment was -7 (range from -8 to -5 degrees). According to our findings, the clinical outcomes did not exhibit significant differences between the three groups. Furthermore, the radiological outcomes showed no significant differences among the three groups. CONCLUSIONS: Compared to neutral alignment, varus or valgus alignment of the humeral stem in reverse shoulder arthroplasty using a curved short stem does not significantly affect clinical outcomes.

Effect of home-based tongue-strengthening exercise using a portable tool on oropharyngeal muscles in older adults with sarcopenic dysphagia: A randomised controlled study.

BACKGROUND: Tongue-strengthening exercises may be used at home to strengthen swallowing-related oropharyngeal muscles in community-dwelling older adults with sarcopenic dysphagia; however, evidence of their effectiveness remains unclear. OBJECTIVE: This study aimed to investigate the effects of a home-based tongue-strengthening exercise (hTSE) using portable tool on swallowing-related oropharyngeal muscles in community-dwelling older adults with sarcopenic dysphagia. METHODS: Forth community-dwelling older adults with sarcopenic dysphagia were enrolled in the study. The participants were randomly assigned to the experimental and control groups. 1-Repetition Maximum (1-RM) of tongue muscle was measured in the experimental group using the Iowa Oral Performance Instrument, and hTSE was performed using a portable tool with an intensity corresponding to approximately 70%-80% of the range based on the 1-RM value (90 times/day, 5 days/week, for 8 weeks). The control group did not perform any tongue exercises. The primary outcome measures were tongue strength and thickness. The secondary outcome measure was suprahyoid muscle strength (digastric and mylohyoid muscles). RESULTS: The experimental group showed significantly greater increases in suprahyoid muscle (mylohyoid and digastric) thickness (p = .01 and .011, d = 1.0 and .55), as well as tongue strength and thickness (p < .001 and .029, d = 2.2 and .6) than the control group. CONCLUSION: This study confirmed that hTSE using a portable tool is effective in increasing swallowing-related oropharyngeal muscle activity in older adults with sarcopenic dysphagia. Therefore, hTSE is recommended as an inexpensive, safe, and easy-to-use therapy for sarcopenic dysphagia in older adults.

A comprehensive and systemic review of ginseng-based nanomaterials: Synthesis, targeted delivery, and biomedical applications.

Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng. The use of nano-ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis.

CyGate Provides a Robust Solution for Automatic Gating of Single Cell Cytometry Data.

To gain a better understanding of the complex human immune system, it is necessary to measure and interpret numerous cellular protein expressions at the single cell level. Mass cytometry is a relatively new technology that offers unprecedented information about the protein expression of a single cell. Conversely, the analysis of high-dimensional and multiparametric mass cytometric data sets presents a new computational challenge. For instance, conventional "manual gating" analysis was inefficient and unreliable for multiparametric phenotyping of the heterogeneous immune cellular system; consequently, automated methods have been developed to address the high dimensionality of mass cytometry data and enhance the reproducibility of the analysis. Here, we present CyGate, a semiautomated method for classifying single cells into their respective cell types. CyGate learns a gating strategy from a reference data set, trains a model for cell classification, and then automatically analyzes additional data sets using the trained model. CyGate also supports the machine learning framework for the classification of "ungated" cells, which are typically disregarded by automated methods. CyGate's utility was demonstrated by its high performance in cell type classification and the lowest generalization error on various public data sets when compared to the state-of-the-art semiautomated methods. Notably, CyGate had the shortest execution time, allowing it to scale with a growing number of samples. CyGate is available at https://github.com/seungjinna/cygate.

Immediate-release tablet formulation of rebamipide and a pharmacokinetic study in healthy human subjects.

OBJECTIVE: To develop an immediate-release tablet preparation containing rebamipide (RBM) and perform the bioavailability assessment in the healthy human subjects. MATERIALS AND METHODS: Raw RBM powder was characterized using differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy (SEM). RBM tablets were manufactured by the wet granulation method, and their dissolution behavior was compared with the reference tablet (Mucosta). A phase I study (n = 47; sequence-randomized, open-label, single-dose, and two-way cross-over design) was designed for oral administration of a test formulation (F4) and Mucosta to healthy human male subjects, and pharmacokinetic parameters including the maximum plasma concentration (Cmax) and area under the curve from 0 to 12 hours (AUC0-12h) were compared. RESULTS: RBM powder had a multimodal size distribution with typical crystallinity, and the needle-like and elongated morphologies of RBM were visualized using SEM. Various tablet formulations (F1 - F6) were successfully manufactured using wet granulation method. F4 formulation was selected based on the dissolution profile most equivalent to that of Mucosta. F4 was stable for 6 months under accelerated and long-term storage conditions. Based on one-way analysis of variance, the AUC0-12h (F(1,92) = 2.40, p = 0.13) and tmax (F(1,92) = 0.04, p = 0.85) were not significantly different; however, the Cmax (F(1,92) = 5.45, p = 0.022) showed significant difference between F4 and reference tablets. CONCLUSION: Despite similar in vitro dissolution profiles, in vivo pharmacokinetic results revealed a partial difference between F4 and reference tablets. Thus, further study on formulation development is still needed.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.