Patient's Perspective on Psychiatric Drugs: A Multicenter Survey-Based Study.

OBJECTIVE: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. METHODS: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. RESULTS: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. CONCLUSION: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Kaempferol Alleviates Mitochondrial Damage by Reducing Mitochondrial Reactive Oxygen Species Production in Lipopolysaccharide-Induced Prostate Organoids.

Common prostate diseases such as prostatitis and benign prostatic hyperplasia (BPH) have a high incidence at any age. Cellular stresses, such as reactive oxygen species (ROS) and chronic inflammation, are implicated in prostate enlargement and cancer progression and development. Kaempferol is a flavonoid found in abundance in various plants, including broccoli and spinach, and has been reported to exhibit positive biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we introduced prostate organoids to investigate the protective effects of kaempferol against various cellular stresses. The levels of COX-2, iNOS, p-IκB, a pro-inflammatory cytokine, and ROS were increased by LPS treatment but reversed by kaempferol treatment. Kaempferol activated the nuclear factor erythroid 2-related factor 2(Nrf2)-related pathway and enhanced the mitochondrial quality control proteins PGC-1α, PINK1, Parkin, and Beclin. The increase in mitochondrial ROS and oxygen consumption induced by LPS was stabilized by kaempferol treatment. First, our study used prostate organoids as a novel evaluation platform. Secondly, it was demonstrated that kaempferol could alleviate the mitochondrial damage in LPS-induced induced prostate organoids by reducing the production of mitochondrial ROS.

Polarization of THP-1-Derived Macrophage by Magnesium and MAGT1 Inhibition in Wound Healing.

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.

Impact of a Psychiatric Consultation Program on COVID-19 Patients: An Experimental Study.

OBJECTIVE: Following the coronavirus disease-2019 (COVID-19) outbreak, the importance of addressing acute stress induced by psychological burdens of diseases became apparent. This study attempted to evaluate the effectiveness of a new mode of psychiatric intervention designed to target similar psychological crises. METHODS: Participants included 32 out of 114 COVID inpatients at a hospital in Daegu, Korea, who were assessed between March 30 and April 7, 2020. Multiple scales for screening psychological difficulties such as depressed mood, anxiety, insomnia, acute stress, and suicidality were done. Psychological problem evaluations and interventions were conducted in the form of consultations to alleviate participants' psychological challenges via telepsychiatry. The interventions' effects, as well as clinical improvements before and after the intervention, were analyzed. RESULTS: As a result of screening, 21 patients were experiencing psychological difficulties beyond clinical thresholds after COVID-19 infection (screening positive group). The remaining 11 were screening negative groups. The two groups differed significantly in past psychiatric histories (p=0.034), with the former having a higher number of diagnoses. The effect of the intervention was analyzed, and clinical improvement before and after the intervention was observed. Our intervention was found to be effective in reducing the overall emotional difficulties. CONCLUSION: This study highlighted the usefulness of new interventions required in the context of healthcare following the COVID-19 pandemic.

The Cytoprotective Effects of Baicalein on H2O2-Induced ROS by Maintaining Mitochondrial Homeostasis and Cellular Tight Junction in HaCaT Keratinocytes.

Reactive oxygen species (ROS) promote oxidative stress, which directly causes molecular damage and disrupts cellular homeostasis, leading to skin aging. Baicalein, a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi has antioxidant, anticancer, anti-inflammatory, and other medicinal properties. We aimed to investigate the protective effect of baicalein on the disruption of tight junctions and mitochondrial dysfunction caused by H2O2-induced oxidative stress in HaCaT keratinocytes. The cells were pretreated with 20 and 40 µM baicalein followed by treatment with 500 µM H2O2. The results revealed that baicalein exerted antioxidant effects by reducing intracellular ROS production. Baicalein attenuated the degradation of the ECM (MMP-1 and Col1A1) and the disruption of tight junctions (ZO-1, occludin, and claudin-4). In addition, baicalein prevented mitochondrial dysfunction (PGC-1α, PINK1, and Parkin) and restored mitochondrial respiration. Furthermore, baicalein regulated the expression of antioxidant enzymes, including NQO-1 and HO-1, via the Nrf2 signaling pathway. Our data suggest that the cytoprotective effects of baicalein against H2O2-induced oxidative stress may be mediated through the Nrf2/NQO-1/HO-1 signaling pathway. In conclusion, baicalein exerts potent antioxidant effects against H2O2-induced oxidative stress in HaCaT keratinocytes by maintaining mitochondrial homeostasis and cellular tight junctions.

The Usefulness of Quantitative Electroencephalography in Diagnosis and Severity Evaluation of Delirium: A Retrospective Study.

OBJECTIVE: Incontrovertible disease markers are absent in delirium. This study investigated the usefulness of quantitative electroencephalography (qEEG) in diagnosing delirium. METHODS: This retrospective case-control study reviewed medical records and qEEG data of 69 age/sex-matched patients (delirium group, n=30; control group, n=39). The first minute of artifact-free EEG data with eyes closed was selected. Nineteen electrodes' sensitivity, specificity, and correlation with delirium rating scale-revised-98 were analyzed. RESULTS: On comparing the means of absolute power by frontal, central, and posterior regions, the delta and theta powers showed significant differences (p<0.001) in all regions, and the magnitude of the absolute power was higher in the delirium group than in the control group; only the posterior region showed a significant (p<0.001) difference in beta power. The spectral power of theta at the frontal region (area under the curve [AUC]=0.84) and theta at the central and posterior regions (AUC=0.83) showed 90% sensitivity and 79% specificity, respectively, in differentiating delirious patients and controls. The beta power of the central region showed a significant negative correlation with delirium severity (R=-0.457, p=0.011). CONCLUSION: Power spectrum analysis of qEEG showed high accuracy in screening delirium among patients. The study suggests qEEG as a potential aid in diagnosing delirium.

Borderline Personality Pathology in Major Depressive Disorder, Bipolar I and II Disorder, and Its Relationship With Childhood Trauma.

OBJECTIVE: Mood disorder and borderline personality pathology (BPP) are frequently comorbid and relate to childhood trauma. We investigated the relationship between childhood trauma and BPP features in mood disorder patients versus controls. METHODS: A total of 488 mood disorder patients, particularly major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II), and 734 controls were included. We examined between-group BPP-related differences and correlated between BPP and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ) and the Personality Assessment Inventory-Borderline Features Scale. RESULTS: BD II patients showed significantly higher BPP. Emotional abuse and neglect were prominently associated with BPP, while affective instability and negative relationships exhibited a stronger association with childhood trauma. We also found a positive relationship between childhood trauma and BPP in MDD, BD I, and BD II patients. CONCLUSION: The findings of the present study imply that BPP features are more likely to be found in patients with BD II than BD I or MDD. Mood disorder patients with severe childhood trauma may have higher BPP features. Thus, further study of the relationship between childhood trauma and BPP features could improve the therapeutic approaches and help understand patients with mood disorders.

Bioactive Compounds and Quality Evaluation of Red-Pigmented Rice Processed by Germination and Roasting.

Red-pigmented rice was germinated and processed to develop germinated red rice tea, and the changes in physicochemical, bioactive, and microbial properties due to germination and roasting were investigated. The moisture and crude ash contents of red rice decreased after germination and roasting. Crude protein and crude fat contents increased after germination but slightly decreased after roasting. Total phenolics, flavonoids, and antioxidant activities (DPPH and ABTS radical scavenging activities) increased following germination and heat treatment. However, the increased levels of γ-amino butyric acid after germination significantly decreased during the subsequent roasting step. In addition, total bacteria, yeast, and mold counts increased during the germination process but decreased after heat treatment as compared to those in the original grain; Escherichia coli was not detected. Therefore, germination and subsequent roasting could effectively enhance the contents of the most bioactive compounds and maintain microbial stability in red-pigmented rice.

Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression.

Cancer cells have various immune evasion mechanisms that resist the immune cells by reprogramming the tumor microenvironment (TME), such as programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase-1 (IDO1) overexpression. One of the approaches to restore antitumor immune response by T-cells is through induction of immunogenic cell death (ICD). Thus, drug carrier containing IDO1 siRNA and ICD inducer would be effective anticancer regimen to modulate the immunosuppressive TME by reversing the IDO1-mediated immunosuppression in a synergistic combination with ICD induction. However, numerous nanocarrier platforms for co-delivery of multiple drugs mostly depend on the enhanced permeation and retention (EPR), which is insufficient to achieve selectivity in tumor sites harboring various types of cells. We designed a targeted drug delivery system using nano-sized liposomes functionalized with anti-CD44 and anti-PD-L1 DNA aptamers, which target breast cancer cells and inhibit PD-1/PD-L1 interaction between cancer cells and T-cells. To reverse immunosuppressive TME and reactivate immune response, cancer-targeting nano-liposomes were prepared to contain immunogenic cell death inducer (Doxorubicin, DOX) and IDO1 siRNA, namely Aptm[DOX/IDO1]. The Aptm[DOX/IDO1] specifically delivered the loaded DOX and IDO1 siRNA into target breast cancer cells through aptamer-mediated endocytosis. Cancer-targeted DOX/IDO1 siRNA delivery enhanced ICD and suppressed IDO1 expression with significantly high toxicity in cancer cells. We demonstrated that Aptm[DOX/IDO1] could achieve synergistic antitumor effects by facilitating ICD response and simultaneous reversal of the immunosuppressive TME with IDO1 knockdown in the subcutaneous breast cancer model mice, thus reducing tumor size. These antitumor effects were exerted with intratumoral infiltration of CD8+ cytotoxic T lymphocyte as well as attenuation of regulatory T-cell recruitment in the tumor sites. We further proved that our Aptm[DOX/IDO1] strategy significantly reduced tumor metastasis in tumor-xenograft mice through a synergistic combination of cancer cell-targeted ICD induction and reversal of the IDO1-mediated immunosuppressive TME. Our nanocarrier platform based on cationic liposomes containing DOX and IDO1 siRNA, which are conjugated with two DNA aptamers targeting the cancer cell surface, accomplished synergistic chemoimmunotherapy through tumor-specific immune modulation into immune-favorable TME in vivo.

Prediction and identification of new type holin protein of Escherichia coli phage ECP26.

Bacteriophages (phages) infecting specifically target bacteria utilize a unique lysis module known as the holin-endolysin cassette to release progeny. Studies on the phage lytic proteins could contribute to the development of alternatives to antibiotics. Here, we predicted and identified the holin protein of rV5-like phage ECP26 for increasing lytic activity of the phage endolysin. In silico analysis revealed that open reading frame 151 (ORF151) of ECP26 contained two transmembrane domains. Co-expression of endolysin with ORF151 resulted in the cell lysis of Escherichia coli, suggesting that ORF151 protein functioned as the holin that disrupted the cytoplasmic membrane. The putative holin showed a high amino acid homology by more than 80% to the predicted holins of rV5-like phages. Therefore, the holin protein would be helpful for developing efficient lysis strategies with endolysin against gram-negative E. coli. Supplementary information: The online version contains supplementary material available at 10.1007/s10068-022-01089-w.

Application time and persistence of transcranial direct current stimulation (tDCS) against neuronal death resulting from transient cerebral ischemia.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been studied as a tool to stimulate the functional recovery of neurons after stroke. Although this device has recently begun to be utilized for providing neuroprotection in stroke, research on its application conditions is lacking. This study aimed to examine the effects of various tDCS application conditions on cerebral ischemia. Ischemia was induced for 5 min in a gerbil model. The application of tDCS comprised a 20 min stimulation-20 min rest-20 min stimulation protocol, which was implemented simultaneously with the induction of cerebral ischemia. Application time of the tDCS effect on ischemia was confirmed by sampling brain tissues after stimulation using 0.2 mA tDCS at 0, 5, 10 and 60 min after ischemia. RESULTS: Persistence of the tDCS effect on ischemia was confirmed by sampling brain tissues 5, 7, and 10 days post stimulation, with 0.2 mA tDCS after ischemia. Furthermore, the tissues were stained with cresyl violet and Fluoro-Jade C so as to determine the reduction in neuronal death under all application conditions. CONCLUSIONS: The application of tDCS can be used as a useful intervention for acute phase stroke due to its sustained neuroprotective effect.

Role of Graphene Family Nanomaterials in Skin Wound Healing and Regeneration.

Owing to astonishing properties such as the large surface area to volume ratio, mechanical stability, antimicrobial property, and collagen crosslinking, graphene family nanomaterials (GFNs) have been widely used in various biomedical applications including tissue regeneration. Many review literatures are available to compile the role of GFNs in cardiac, bone, and neuronal tissue regeneration. However, the contribution of GFNs in skin wound healing and tissue regeneration was not yet discussed. In the present review, we have highlighted the properties of GFNs and their application in skin wound healing. In addition, we have included challenges and future directions of GFNs in skin tissue regeneration in the portion of conclusion and perspectives.

Functional Graphene Nanomaterials-Based Hybrid Scaffolds for Osteogenesis and Chondrogenesis.

With the emerging trends and recent advances in nanotechnology, it has become increasingly possible to overcome current hurdles for bone and cartilage regeneration. Among the wide type of nanomaterials, graphene (G) and its derivatives (graphene-based materials, GBMs) have been highlighted due to the specific physicochemical and biological properties. In this review, we present the recent development of GBM-based scaffolds for bone and cartilage engineering, focusing on the formulation/shape/size-dependent characteristics, types of scaffold and modification, biocompatibility, bioactivity and underlying mechanism, drawback and prospect of each study. From the findings described herein, mechanical property, biocompatibility, osteogenic and chondrogenic property of GBM-based scaffolds could be significantly enhanced through various scaffold fabrication methods and conjugation with polymers/nanomaterials/drugs. In conclusion, the results presented in this review support the promising prospect of using GBM-based scaffolds for improved bone and cartilage tissue engineering. Although GBM-based scaffolds have some limitations to be overcome by future research, we expect further developments to provide innovative results and improve their clinical potential for bone and cartilage regeneration.

Clinical Efficacy of Probiotic Therapy on Bowel-Related Symptoms in Patients with Ulcerative Colitis during Endoscopic Remission: An Observational Study.

BACKGROUND: A substantial percentage of patients with ulcerative colitis (UC) have irritable bowel syndrome- (IBS-) like symptoms despite adequate treatment and endoscopic remission. In this study, we evaluated the clinical efficacy of probiotic therapy for residual IBS-like symptoms in patients with UC in endoscopic remission. METHODS: We conducted a multicenter, observational study between April 2018 and December 2020 across two university hospitals in Korea. Patients with UC whose IBS-like symptoms persisted during endoscopic remission were included in this study. Endoscopic remission was defined as a Mayo endoscopic score ≤ 1, and IBS-like symptoms were defined as those meeting the ROME-IV diagnostic criteria. A Biotop capsule® (Lactobacillus acidophilus, 75 mg; Clostridium butyricum TO-A, 25 mg; Bacillus mesentericus TO-A, 25 mg; and Streptococcus faecalis T-110, 5 mg) was administered three times daily for one month. All patients completed bowel-related symptom questionnaires and short inflammatory bowel disease questionnaires (SIBDQs) at the start and end of the 4-week treatment period. RESULTS: A total of 43 patients were enrolled and analyzed. Statistically significant improvements from baseline were observed at the end of the 4-week treatment. The total SIBDQ score improved from 50.6 to 53.6 (P = 0.005). SIBDQ scores of bowel function (P = 0.018), systemic function (P = 0.040), and social function (P = 0.005) improved. Stool frequency and Bristol stool scale scores improved after probiotic therapy (P < 0.05). CONCLUSION: This study showed that probiotic administration improved bowel-related symptoms and quality of life in patients with UC whose IBS-like symptoms persisted during endoscopic remission. As this is an observational study and has no placebo-controlled arm, further prospective randomized controlled trials are needed to confirm these results.

Autophagosome-lysosome fusion is facilitated by plectin-stabilized actin and keratin 8 during macroautophagic process.

Autophagy is a lysosome-mediated degradative process that removes damaged proteins and organelles, during which autophagosome-lysosome fusion is a key step of the autophagic flux. Based on our observation that intermediate cytofilament keratin 8 (KRT8) enhances autophagic clearance in cells under oxidative stress condition, we investigated whether KRT8 supports the cytoplasmic architectural networks to facilitate the vesicular fusion entailing trafficking onto filamentous tracks. We found that KRT8 interacts with actin filaments via the cytolinker, plectin (PLEC) during trafficking of autophagosome. When PLEC was knocked down or KRT8 structure was collapsed by phosphorylation, autophagosome-lysosome fusion was attenuated. Inhibition of actin polymerization resulted in accumulation of autophagosomes owing to a decrease in autophagosome and lysosome fusion. Furthermore, myosin motor protein was found to be responsible for vesicular trafficking along the actin filaments to entail autolysosome formation. Thus, the autophagosome-lysosome fusion is aided by PLEC-stabilized actin filaments as well as intermediate cytofilament KRT8 that supports the structural integrity of actin filaments during macroautophagic process under oxidative stress condition.

Integrated Infodemic Surveillance System: The Case of COVID-19 in South Korea.

This study merges multiple COVID-19 data sources from news articles and social media to propose an integrated infodemic surveillance system (IISS) that implements infodemiology for a well-tailored epidemic management policy. IISS is an à-la-carte infodemic surveillance solution that enables users to gauge the epidemic related consensus, which compiles epidemic-related data from multiple sources and equipped with various methodological toolkits - topic modeling, Word2Vec, and social network analysis. IISS can provide reliable empirical evidence for proper policymaking. We demonstrate the heuristic utilities of IISS using empirical data from the first wave of COVID-19 in South Korea. Measuring discourse congruence allows us to gauge the distance between the discourse corpus from different sources, which can highlight consensus and conflicts in epidemic discourse. Furthermore, IISS detects discrepancies between social concerns and main actors.

A Validated Grading Scale for Downturned Oral Commisure in Asian Faces.

BACKGROUND: Downturned oral commissures develop gradually with aging. Tools have been developed to evaluate the marionette line or the lower face. However, there is no validated and reproducible tool to evaluate the progress after oral commissure treatment in clinical practice. OBJECTIVE: The authors aimed to develop a scoring system to evaluate therapeutic interventions for downturned oral commissures and to verify its reliability, reproducibility, and clinical significance. METHODS AND MATERIALS: In the Scale Development Group, the Delphi method was used to establish a 5-graded scoring system to evaluate oral commissure position. The scoring system was applied to 50 participants. The authors recorded and compared the intrarater agreement, interrater agreement, and significance of the grade-dependent scale. RESULTS: Delphi analysis of the scoring system verified the grade description adequacy. Intrarater agreement showed almost perfect agreement, and the intraclass correlation coefficient of the interrater agreement had a significantly higher agreement rate. The differences between the clinical grades were significant. CONCLUSION: The Hugel Downturned Oral Commissure Scale is precise, reproducible, and reflective of the clinical differences for downturned oral commissure. Its novelty lies in the use of specific angles and ratio. This scale has clinical trial potential owing to its standardized and quantitative assessment.

A Single-Center, Randomized, Double-Blind Clinical Trial to Compare the Efficacy and Safety of a New Monophasic Hyaluronic Acid Filler and Biphasic Filler in Correcting Nasolabial Fold.

BACKGROUND: Hyaluronic acid (HA) fillers have been widely used in humans since 1958 because of their biomedical safety. Restylane® was introduced in the1990s as a favorable temporary filler option for facial augmentation. Subsequently, many new HA filler products, including the Sardenyashape®, have been introduced, but comparative studies of these products are limited. Here, we compared tolerability (wrinkle severity rating scale, WSRS), pain (visual analog scale, VAS score), satisfaction (global esthetic improvement scale, GAIS), and safety of a new monophasic HA (MHA) filler (Sardenyashape®) containing lidocaine, used to correct nasolabial folds (NLFs), with those of biphasic HA (BHA) filler (Restylane LYFT®) containing lidocaine. METHODS: We enrolled 96 participants with visible NLFs in this randomized, double-blind, single-center clinical study. Participants were injected with a new MHA filler in one NLF and a BHA filler and were reassessed for cosmetic changes at 8 and 24 weeks. Wrinkle severity was assessed using the 5-point WSRS. RESULTS: At week 24, the mean improvement in WSRS compared to baseline was 1.92 ± 0.75 and 2.24 ± 0.66 for MHA and BHA fillers, respectively, and corresponding average pain values using the VAS score 30 min after the procedure were 0.04 ± 0.25 and 0.02 ± 0.15, respectively, showing no significant difference. Average GAIS values 8 weeks after the procedure with MHA and BHA fillers were 1.89 ± 0.77 and 1.40 ± 0.82, respectively (p < 0.001). Both fillers were well tolerated, with mild adverse reactions. CONCLUSION: The evaluation of the effect of Sardenyashape® with lidocaine on NLF in this study proved its effectiveness and safety for use in correcting NLF. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .