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INTRODUCTION: The Nominal Group Technique (NGT) is a consensus group method used to synthesize expert opinions. Given the global shift to virtual meetings, the extent to which researchers leveraged virtual platforms is unclear. This scoping review explores the use of the vNGT in healthcare research during the COVID-19 pandemic. METHODS: Following the Arksey and O'Malley's framework, eight cross-disciplinary databases were searched (January 2020-July 2022). Research articles that reported all four vNGT stages (idea generation, round robin sharing, clarification, voting) were included. Media Synchronicity Theory informed analysis. Corresponding authors were surveyed for additional information. RESULTS: Of 2,589 citations, 32 references were included. Articles covered healthcare (27/32) and healthcare education (4/32). Platforms used most were Zoom, MS Teams and GoTo but was not reported in 44% of studies. Only 22% commented on the benefits/challenges of moving the NGT virtually. Among authors who responded to our survey (16/32), 80% felt that the vNGT was comparable or superior. CONCLUSIONS: The vNGT provides several advantages such as the inclusion of geographically dispersed participants, scheduling flexibility and cost savings. It is a promising alternative to the traditional in-person meeting, but researchers should carefully describe modifications, potential limitations, and impact on results.
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COVID-19 , Humanos , COVID-19/epidemiología , Investigación sobre Servicios de Salud , SARS-CoV-2 , Pandemias , Atención a la SaludRESUMEN
PURPOSE: We hypothesized that multiple absorbable screws/K-wires would be effective for native head preservation in comminuted radial head fracture fixation (com-RHFs). METHODS: Seventeen patients who met the inclusion criteria between 2018 and 2020 were included. Radiologic findings indicating proper union and clinical outcomes such as the range of elbow motion, visual analog scale score, and Mayo Elbow Performance Score were assessed prospectively after surgery and at least three years of follow-up. RESULTS: The mean follow-up period was 4.6 years. Eleven, one, three, and two patients presented with isolated com-RHFs, type 2 (accompanied injury of medial collateral ligament), type 4 ("terrible triad") fractures, and type 5 posterior olecranon fracture-dislocations, respectively. Union was achieved after a mean of nine weeks postoperatively. The head and shaft angles did not differ significantly from the contralateral normal values (p = 0.778 and 0.872, coronal and sagittal, respectively). At the final follow-up, the mean flexion-extension/pronation-supination arcs were 126.47 ± 4.92°/135.59 ± 10.13°, and thus were significantly different from those on the contralateral side (p < 0.001, both), however the arcs were functional ranges for ordinary daily life. Also, functional status was satisfactory in all individuals. The arthritis grade and extent of heterotrophic ossification were satisfactory in all cases, and there were no serious complications requiring revision surgery. CONCLUSIONS: Absorbable screw/K-wire fixation for com-RHFs is an option before radial head arthroplasty associated with a low complication rate and no need for revision.
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Implantes Absorbibles , Tornillos Óseos , Hilos Ortopédicos , Fijación Interna de Fracturas , Fracturas Conminutas , Fracturas del Radio , Rango del Movimiento Articular , Humanos , Masculino , Fracturas Conminutas/cirugía , Fracturas del Radio/cirugía , Femenino , Persona de Mediana Edad , Adulto , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Articulación del Codo/cirugía , Articulación del Codo/fisiopatología , Magnesio , Anciano , Adulto Joven , Resultado del Tratamiento , Fracturas Radiales de Cabeza y CuelloRESUMEN
Traditional monoclonal antibodies such as Trastuzumab encounter limitations when treating Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer, particularly in cases that develop resistance. This study introduces plant-derived anti-HER2 variable fragments of camelid heavy chain domain (VHH) fragment crystallizable region (Fc) KEDL(K) antibody as a potent alternative for overcoming these limitations. A variety of biophysical techniques, in vitro assays, and in vivo experiments uncover the antibody's nanoscale binding dynamics with transmembrane HER2 on living cells. Single-molecule force spectroscopy reveals the rapid formation of two robust bonds, exhibiting approximately 50 pN force resistance and bond lifetimes in the second range. The antibody demonstrates a specific affinity for HER2-positive breast cancer cells, including those that are Trastuzumab-resistant. Moreover, in immune-deficient mice, the plant-derived anti-HER2 VHH-FcK antibody exhibits superior antitumor activity, especially against tumors that are resistant to Trastuzumab. These findings underscore the plant-derived antibody's potential as an impactful immunotherapeutic strategy for treating Trastuzumab-resistant HER2-positive breast cancer.
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Neoplasias de la Mama , Resistencia a Antineoplásicos , Receptor ErbB-2 , Trastuzumab , Trastuzumab/química , Trastuzumab/farmacología , Humanos , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/inmunología , Animales , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Ratones , Línea Celular Tumoral , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/química , Proliferación Celular/efectos de los fármacosRESUMEN
Background: The incidence of thyroid cancer has increased over the decades, and patients prefer short thin scars after thyroidectomy due to their cosmetic visibility. Several scar assessment methods have been used to determine the most cosmetically optimal surgical method, but a widely accepted measurement tool is still lacking. This study investigates the usage status in the thyroid scar scale according to time, region, and study method. Methods: The authors searched for articles on thyroid scars published between January 2000 and September 2022 in the PubMed database. The study included clinical studies that mentioned thyroid scar and scar scale, excluding articles that did not evaluate neck scars. Statistical analysis was performed using IBM SPSS Statistics 29. Results: A total of 35 studies were included. Among them, 17 used the Vancouver Scar Scale (VSS), 17 used the Patient and Observer Scar Assessment Scale (POSAS), four used the Manchester Scar Scale (MSS), and four used the Stony Brook Scar Evaluation Scale (SBSES). VSS and POSAS were the most commonly used scar evaluation methods. VSS tended to be used frequently in Asia, while POSAS was used frequently in Europe and in randomized controlled trials. Conclusion: VSS and POSAS are popular thyroid scar assessment methods, with regional variations. Standardization is needed for meaningful comparisons. Patient's subjective evaluations should be considered, given the cosmetic importance of thyroid scars.
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Probiotics are functional microorganisms that exhibit various biological activities, such as allergic reactions, inflammation, and aging. The aim of this study is to evaluate the effects of Bifidobacterium lactis CBT BL3 (BL) on the amyloid beta (Aß)-mediated cognitive impairments. Oral administration of live BL to intracerebroventricularly Aß-injected mice significantly attenuated short- and long-term memory loss estimated using the Y-maze and Morris water maze tests. We found that expression of apoptosis-related proteins such as caspase-9, caspase-3, and cleaved poly (ADP-ribose) polymerase was significantly elevated in the brain tissues of Aß-injected mouse brains when compared to that of the control mouse group. Interestingly, these expression levels were significantly decreased in the brain tissue of mice fed BL for 6 wk. In addition, the abnormal over-phosphorylation of mitogen-activated protein kinases (MAPKs) such as ERK1/2, p38 MAPK, and JNK in the brain tissue of intracerebroventricularly Aß-injected mice was significantly attenuated by oral administration of BL. Taken together, the results indicate that Aß-induced cognitive impairment may be ameliorated by the oral administration of BL by controlling the activation of MAPKs/apoptosis in the brain. This study strongly suggests that BL can be developed as a functional probiotic to attenuate Aß-mediated cognitive deficits.
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Copper-based nanomaterials have been employed as therapeutic agents for cancer therapy and diagnosis. Nevertheless, persistent challenges, such as cellular toxicity, non-uniform sizes, and low photothermal efficiency, often constrain their applications. In this study, we present Cu2+-loaded silica nanoparticles fabricated through the chelation of Cu2+ ions by silanol groups. The integration of Cu2+ ions into uniformly sized silica nanoparticles imparts a photothermal therapy effect. Additionally, the amine functionalization of the silica coating facilitates the chemical conjugation of tumor-specific fluorescence probes. These probes are strategically designed to remain in an 'off' state through the Förster resonance energy transfer mechanism until exposed to cysteine enzymes in cancer cells, inducing the recovery of their fluorescence. Consequently, our Cu2+-loaded silica nanoparticles demonstrate an efficient photothermal therapy effect and selectively enable cancer imaging.
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In this paper, we propose a novel method for monocular depth estimation using the hourglass neck module. The proposed method has the following originality. First, feature maps are extracted from Swin Transformer V2 using a masked image modeling (MIM) pretrained model. Since Swin Transformer V2 has a different patch size for each attention stage, it is easier to extract local and global features from images input by the vision transformer (ViT)-based encoder. Second, to maintain the polymorphism and local inductive bias of the feature map extracted from Swin Transformer V2, a feature map is input into the hourglass neck module. Third, deformable attention can be used at the waist of the hourglass neck module to reduce the computation cost and highlight the locality of the feature map. Finally, the feature map traverses the neck and proceeds through a decoder, comprised of a deconvolution layer and an upsampling layer, to generate a depth image. To evaluate the objective reliability of the proposed method in this paper, we used the NYU Depth V2 dataset to compare and evaluate the methods published in other papers. As a result of the experiment, the RMSE value of the novel method for monocular depth estimation using the hourglass neck module proposed in this paper was 0.274, which was lower than those published in other papers. The lower the RMSE value, the better the depth estimation method; therefore, its efficiency compared to other techniques has been proven.
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[This corrects the article on p. 151 in vol. 30, PMID: 37476674.].
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD.
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Benzo(a)pireno , Hígado , Benzo(a)pireno/toxicidad , Citocromo P-450 CYP1B1/genética , Hígado/metabolismo , Sistema Enzimático del Citocromo P-450 , Serina-Treonina Quinasas TOR/genética , Receptores de Hidrocarburo de Aril/metabolismo , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Lípidos , Citocromo P-450 CYP1A1/genéticaRESUMEN
Orthohantaviruses, etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) outbreaks are particularly endemic in Gyeonggi Province in northern area of the Republic of Korea (ROK). Small mammals were collected from three regions in the Gyeonggi Province during 2017 and 2018. Serological and molecular prevalence of HTNV was 25/201 (12.4%) and 10/25 (40%), respectively. A novel nanopore-based diagnostic assay using a cost-efficient Flongle chip was developed to rapidly and sensitively detect HTNV infection in rodent specimens within 3 h. A rapid phylogeographical surveillance of HTNV at high-resolution phylogeny was established using the amplicon-based Flongle sequencing. In total, seven whole-genome sequences of HTNV were newly obtained from wild rodents collected in Paju-si (Gaekhyeon-ri) and Yeoncheon-gun (Hyeonga-ri and Wangnim-ri), Gyeonggi Province. Phylogenetic analyses revealed well-supported evolutionary divergence and genetic diversity, enhancing the resolution of the phylogeographic map of orthohantaviruses in the ROK. Incongruences in phylogenetic patterns were identified among HTNV tripartite genomes, suggesting differential evolution for each segment. These findings provide crucial insights into on-site diagnostics, genome-based surveillance, and the evolutionary dynamics of orthohantaviruses to mitigate hantaviral outbreaks in HFRS-endemic areas in the ROK.
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Virus Hantaan , Fiebre Hemorrágica con Síndrome Renal , Orthohantavirus , Animales , Filogenia , Virus Hantaan/genética , Orthohantavirus/genética , Roedores , Mamíferos , República de Corea/epidemiologíaRESUMEN
With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, making them a promising platform for pharmaceutical development. In this study, a novel toxin peptide with antibacterial and anti-inflammatory activities was discovered from the spider venom gland transcriptome by implementing computational approaches. Lycotoxin-Pa2a (Lytx-Pa2a) showed homology to known-spider toxin, where functional prediction indicated the potential of both antibacterial and anti-inflammatory peptides without hemolytic activity. The colony-forming assay and minimum inhibitory concentration test showed that Lytx-Pa2a exhibited comparable or stronger antibacterial activity against pathogenic strains than melittin. Following mechanistic studies revealed that Lytx-Pa2a disrupts both cytoplasmic and outer membranes of bacteria while simultaneously inducing the accumulation of reactive oxygen species. The peptide exerted no significant toxicity when treated to human primary cells, murine macrophages, and bovine red blood cells. Moreover, Lytx-Pa2a alleviated lipopolysaccharide-induced inflammation in mouse macrophages by suppressing the expression of inflammatory mediators. These findings not only suggested that Lytx-Pa2a with dual activity can be utilized as a new antimicrobial agent for infectious diseases but also demonstrated the implementation of in silico methods for discovering a novel functional peptide, which may enhance the future utilization of biological resources.
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The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches.
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Antiinfecciosos , Venenos de Araña , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Pseudomonas aeruginosa , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Bacterias , Venenos de Araña/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Introduction: Antisense oligonucleotides (ASOs) with therapeutic potential have recently been reported to target the SARS-CoV-2 genome. Peptide nucleic acids (PNAs)-based ASOs have been regarded as promising drug candidates, but intracellular delivery has been a significant obstacle. Here, we present novel modified PNAs, termed OPNAs, with excellent cell permeability that disrupt the RNA genome of SARS-CoV-2 and HCoV-OC43 by introducing cationic lipid moiety onto the nucleobase of PNA oligomer backbone. Methods: HCT-8 cells and Caco-2 cells were treated with 1 µM antisense OPNAs at the time of viral challenge and the Viral RNA levels were measured by RT-qPCR three days post infection. Results: NSP 14 targeting OPNA 5 and 11, reduced the viral titer to a half and OPNA 530, 531 and 533 lowered viral gene expression levels to less than 50% of control by targeting the 5' UTR region. Several modifications (oligo size and position, etc.) were introduced to enhance the efficacy of selected OPNAs. Improved OPNAs exhibited a dose-dependent reduction in viral replication and nucleoprotein (NP) protein. When a mixture of oligomers was applied to infected cells, viral titer and NP levels decreased by more than eightfold. Discussion: In this study, we have developed a modified PNA ASO platform with exceptional chemical stability, high binding affinity, and cellular permeability. These findings indicate that OPNAs are a promising platform for the development of antivirals to combat future pandemic viral infections that do not require a carrier.
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OBJECTIVE: Accurate correction is a prerequisite for the favorable outcomes of open-wedge high tibial osteotomy (OWHTO). However, previous studies have reported disappointing results regarding correction accuracy despite the use of intra-operative navigation, which implies that a certain factor other than bony components is involved in the inaccurate correction (mainly overcorrection). The joint-line convergence angle (JLCA) can represent soft tissue effects in OWHTO. This study tried to determine whether the postoperative change in the JLCA (∆JLCA) led to inaccurate correction. METHODS: Medical records of 78 OWHTO patients from 2005 to 2021 were retrospectively reviewed. The hip-knee-ankle angle (HKA) was measured with a positive value indicating varus alignment. Inaccurate correction was defined as postoperative HKA < - 3°. The JLCA was measured before and 6 months after surgery on long-standing hip-to-ankle radiographs, and ∆JLCA was defined as the difference between the preoperative and 6-month postoperative JLCAs. ∆JLCA was compared between the accurate correction group and the inaccurate correction group, and a receiver operating characteristic (ROC) curve was used to obtain the cutoff ∆JLCA at which the sensitivity and the specificity for inaccurate correction were maximized. Clinical outcomes were also compared between the groups using the knee injury and osteoarthritis outcome score (KOOS) at final follow-up (60.9 ± 53.3 months postoperatively). RESULTS: Of the 78 patients, inaccurate correction was noted in 10 patients. The overall preoperative and postoperative HKAs were 7.0 ± 3.1° and - 0.4 ± 1.5°, respectively. The accurate correction group and the inaccurate correction group had a difference in ∆JLCA (p = 0.010). However, no significant difference was found in the preoperative HKA (p = 0.529). An ROC curve showed that the cutoff ∆JLCA was 1.9°. In the patients having ∆JLCA ≥ 1.9°, the mean JLCA was 4.9 ± 1.6° preoperatively and 1.7 ± 1.2° postoperatively. In the other patients having ∆JLCA < 1.9°, the mean preoperative and postoperative JLCA were 2.5 ± 1.8° and 2.3 ± 1.8°, respectively. The difference in the preoperative JLCA was significant (p < 0.001). The postoperative KOOS subscales did not differ according to correction accuracy. CONCLUSION: Inaccurate correction in OWHTO, specifically valgus overcorrection, is associated with large ∆JLCA which represents the postoperative change of soft tissue effects. Overcorrection should be checked in cases of large preoperative JLCAs.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Tibia/diagnóstico por imagen , Tibia/cirugía , Estudios Retrospectivos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteotomía/métodosRESUMEN
BACKGROUND AND PURPOSE: GPR119 activation has been suggested to improve hyperglycemia, dyslipidemia and hepatic steatosis. But its therapeutic potential for metabolic dysfunction-associated steatohepatitis (MASH) are underexplored. Here, we investigated the effects of DA-1241, a novel GPR119 agonist, on MASH and explored its underlying mechanism of anti-inflammatory effects. EXPERIMENTAL APPROACH: The in vivo anti-MASH effect was assessed by examining the preventive effect in MS-MASH and Ob-MASH mice and the therapeutic effect in MASH with severe hyperglycemia and diet-induced obese (DIO)-MASH mice. Histological and biochemical changes in liver tissue were assessed. Both plasma and hepatic biomarkers related to inflammation and fibrosis were comprehensively analyzed. To understand its mode of action, changes in NFκB signaling were determined in HepG2 and THP-1 cells. KEY RESULTS: DA-1241 attenuated MASH progression and alleviated the MASH phenotypes in MASH mouse models with different etiologies, regardless of glucose-lowering activity. In DIO-MASH mice, DA-1241 significantly reduced biochemical parameters related to steatosis, inflammation and fibrosis in the liver with reduced plasma liver enzymes. When used in combination with a dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1241 further improved the MASH phenotype by increasing endogenous glucagon-like peptide-1 effect. Notably, DA-1241 alone and in combination reduced liver inflammation and restored inflammation-related hepatic gene expression, leading to remission of systemic inflammation as assessed by plasma inflammatory cytokines and chemokines. We demonstrated that DA-1241 reduces macrophage differentiation through downregulation of NFκB signaling by activating GPR119. CONCLUSION: Our data suggest the therapeutic potential of DA-1241, alone and in combination with a DPP4 inhibitor, for MASH.
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Inhibidores de la Dipeptidil-Peptidasa IV , Hígado Graso , Animales , Ratones , Antivirales , Fibrosis , Inflamación/tratamiento farmacológico , FN-kappa B/efectos de los fármacosRESUMEN
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.