MB2033, an anti-PD-L1 × IL-2 variant fusion protein, demonstrates robust anti-tumor efficacy with minimal peripheral toxicity.

Interleukin-2 (IL-2), a cytokine with pleiotropic immune effects, was the first approved cancer immunotherapy agent. However, IL-2 is associated with systemic toxicity due to binding with its ligand IL-2Rα, such as vascular leakage syndrome, limiting its clinical applications. Despite efforts to extend the half-life of IL-2 and abolish IL-2Rα interactions, the risk of toxicity remains unresolved. In this study, we developed the bispecific fusion protein MB2033, comprising a novel IL-2 variant (IL-2v) connected to anti-programmed death ligand 1 (PD-L1) via a silenced Fc domain. The IL-2v of MB2033 exhibits attenuated affinity for IL-2Rßγ without binding to IL-2Rα. The binding affinity of MB2033 for PD-L1 is greater than that for IL-2Rßγ, indicating its preferential targeting of PD-L1+ tumor cells to induce tumor-specific immune activation. Accordingly, MB2033 exhibited significantly reduced regulatory T cell activation, while inducing comparable CD8+ T cell activation to recombinant human IL-2 (rhIL-2). MB2033 induced lower immune cell expansion and reduced cytokine levels compared with rhIL-2 in human peripheral blood mononuclear cells, indicating a decreased risk of peripheral toxicity. MB2033 exhibited superior anti-tumor efficacy, including tumor growth inhibition and complete responses, compared with avelumab monotherapy in an MC38 syngeneic mouse model. In normal mice, MB2033 was safer than non-α IL-2v and tolerable up to 30 mg/kg. These preclinical results provide evidence of the dual advantages of MB2033 with an enhanced safety and potent clinical efficacy for cancer treatment.

Comparative In Vivo Study of Solid-Type Pure Hyaluronic Acid in Thread Form: Safety and Efficacy Compared to Hyaluronic Acid Filler and Polydioxanone Threads.

INTRODUCTION: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. METHOD: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. RESULTS: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-ß1 compared to the HA group. CONCLUSION: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Suppression of cuticular wax biosynthesis mediated by rice LOV KELCH REPEAT PROTEIN 2 supports a negative role in drought stress tolerance.

Drought tolerance is important for grain crops, including rice (Oryza sativa); for example, rice cultivated under intermittent irrigation produces less methane gas compared to rice grown in anaerobic paddy field conditions, but these plants require greater drought tolerance. Moreover, the roles of rice circadian-clock genes in drought tolerance remain largely unknown. Here, we show that the mutation of LOV KELCH REPEAT PROTEIN 2 (OsLKP2) enhanced drought tolerance by increasing cuticular wax biosynthesis. Among ZEITLUPE family genes, OsLKP2 expression specifically increased under dehydration stress. OsLKP2 knockdown (oslkp2-1) and knockout (oslkp2-2) mutants exhibited enhanced drought tolerance. Cuticular waxes inhibit non-stomatal water loss. Under drought conditions, total wax loads on the leaf surface increased by approximately 10% in oslkp2-1 and oslkp2-2 compared to the wild type, and the transcript levels of cuticular wax biosynthesis genes were upregulated in the oslkp2 mutants. Yeast two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays revealed that OsLKP2 interacts with GIGANTEA (OsGI) in the nucleus. The osgi mutants also showed enhanced tolerance to drought stress, with a high density of wax crystals on their leaf surface. These results demonstrate that the OsLKP2-OsGI interaction negatively regulates wax accumulation on leaf surfaces, thereby decreasing rice resilience to drought stress.

An Effective Design Formula for Single-Layer Printed Spiral Coils with the Maximum Quality Factor (Q-Factor) in the Megahertz Frequency Range.

This paper presents a design formula for a printed spiral coil to ensure the maximum quality factor (Q-factor). The formula is composed of a pattern's metal thickness, single pattern width, total pattern width, and turn number, and is effective in the megahertz (MHz) frequency range. During the formula's design, the resistance, self-inductance, and Q-factor are calculated according to the ratio of each pattern's width and total pattern width and the turn number for different metal thicknesses, frequencies, and total pattern widths using a volume filament model (VFM). With a given turn number and metal thickness, the optimal ratio of individual and total pattern widths can be determined to ensure the maximum Q-factor. To verify the formula, some optimal coils were fabricated, and the calculations and measurements were shown to have good agreement. Furthermore, the optimized coils were shown to have higher coupling efficiency than the coils without optimal dimensions.

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were evaluated and their anti-arthritogenic properties were determined in collagen-induced arthritis (CIA) mice. Transplantation of AMM/I attenuates CIA progression. In addition, the regulatory T cell population was increased, while T helper-17 cell activation was suppressed by AMM/I administration in CIA mice. Consistently, AMM/I injection increased proteoglycan expression, while reducing inflammation and the expression levels of the pro-inflammatory factors, IL-1 ß, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor- α, in joint tissues. In conclusion, use of IL-10-edited human AMM/I may be a novel therapeutic strategy for the treatment of arthritis.

Comparison of anterior-only versus combined anterior and posterior fusion for unstable subaxial cervical injuries: a meta-analysis of biomechanical and clinical studies.

OBJECTIVE: The purpose of the present study was to perform a meta-analysis comparing biomechanical and clinical outcomes between anterior-only and combined anterior and posterior fusions to determine which method of cervical fusion yielded better results for unstable cervical injuries. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and SCOPUS electronic databases were searched for relevant articles published through 2000-2019 that compared the biomechanical and clinical outcomes of anterior-only and combined anterior and posterior fusion for unstable cervical fracture. RESULTS: Eight biomechanical and four clinical studies were included in the analysis. There were significant biomechanical differences between the groups with respect to flexion-extension, axial rotation and lateral bending. Combined fusion provided better biomechanical stability for unstable cervical injuries than anterior-only fusion, regardless of the number of corpectomies or the presence of a posterior column injury. However, despite significant biomechanical differences, there were no significant differences in clinical outcomes, such as the degree of neurologic improvement and complications between the two groups. CONCLUSION: Anterior-only and combined anterior and posterior fusions for unstable subaxial cervical injuries can both restore cervical stability. Although combined fusion might have some advantages in terms of stability biomechanically, there were no significant differences in clinical outcomes, such as the degree of neurologic improvement and perioperative complications. Therefore, rather than the routine use of combined fusion for unstable cervical injuries, the selective use of anterior-only or combined fusion according to the type of injury is recommended.

Maximizing Thread Usage for Facial Rejuvenation: A Preliminary Patient Study.

BACKGROUND: Surgical facial rejuvenation techniques with thread lifting have gained popularity. To effectively rejuvenate an aging face, it is necessary to perform both soft tissue envelop repositioning and volume restoration procedures. With the trend toward less invasive techniques and long-lasting results with minimal complications, many surgeons have continued changing the techniques. OBJECTIVES: In the present study, we developed the 4 M (Multi-target, Multi-vector, Multi-layer, Multi-material) thread lift technique for long-lasting results. METHODS: A prospective study was conducted on 73 patients who underwent the 4 M thread lifting procedure between January 2016 and February 2018. To evaluate the surgical outcomes objectively, two plastic surgeons compared photographs using a 5-point Global Aesthetic Improvement Scale (GAIS) at 1, 3, 6, 12, 18, and 24 months of follow-up. RESULTS: Based on the GAIS objective assessment, in most patients (85%) experienced better than 3 score ("improved") changes. Approximately 42.5% of the patients experienced better than 4 score ("much improved") changes. The mean GAIS grade improved significantly (p < 0.005) without decline throughout a period of 12 months. No serious adverse complication was observed except one patient, who experienced skin irregularities and dimpling for up to 9 months after the procedure. CONCLUSIONS: This 4 M thread lifting is the multiple layer lifting and rejuvenation using different materials in addition to the multiple targets. Using the concepts of structural rejuvenation, the 4 M thread lifting technique presented modest to significant improvement, maintaining good results at 12 months after procedure. LEVEL OF EVIDENCE IV: 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 .

Anti-Inflammatory and Anti-Allergic Effects of Saponarin and Its Impact on Signaling Pathways of RAW 264.7, RBL-2H3, and HaCaT Cells.

Saponarin{5-hydroxy-2-(4-hydroxyphenyl)-6-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-7-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one}, a flavone found in young green barley leaves, is known to possess antioxidant, antidiabetic, and hepatoprotective effects. In the present study, the anti-inflammatory, anti-allergic, and skin-protective effects of saponarin were investigated to evaluate its usefulness as a functional ingredient in cosmetics. In lipopolysaccharide-induced RAW264.7 (murine macrophage) cells, saponarin (80 µM) significantly inhibited cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, inducible nitric oxide synthase, and cyclooxygenase (COX)-2. Saponarin (80 µM) also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 involved in the mitogen-activated protein kinase signaling pathway in RAW264.7 cells. Saponarin (40 µM) significantly inhibited ß-hexosaminidase degranulation as well as the phosphorylation of signaling effectors (Syk, phospholipase Cγ1, ERK, JNK, and p38) and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, IL-4, IL-5, IL-6, IL-13, COX-2, and FcεRIα/γ) in DNP-IgE- and DNP-BSA-stimulated RBL-2H3 (rat basophilic leukemia) cells. In addition, saponarin (100 µM) significantly inhibited the expression of macrophage-derived chemokine, thymus and activation-regulated chemokine, IL-33, thymic stromal lymphopoietin, and the phosphorylation of signaling molecules (ERK, p38 and signal transducer and activator of transcription 1 [STAT1]) in TNF-α- and interferon (IFN)-γ-stimulated HaCaT (human immortalized keratinocyte) cells. Saponarin (100 µM) also significantly induced the expression of hyaluronan synthase-3, aquaporin 3, and cathelicidin antimicrobial peptide (LL-37) in HaCaT cells, which play an important role as skin barriers. Saponarin remarkably inhibited the essential factors involved in the inflammatory and allergic responses of RAW264.7, RBL-2H3, and HaCaT cells, and induced the expression of factors that function as physical and chemical skin barriers in HaCaT cells. Therefore, saponarin could potentially be used to prevent and relieve immune-related skin diseases, including atopic dermatitis.

Improvement of Obesity and Dyslipidemic Activity of Amomum tsao-ko in C57BL/6 Mice Fed a High-Carbohydrate Diet.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

A novel role for α-viniferin in suppressing angiogenesis by blocking the VEGFR-2/p70S6K signaling pathway.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

No differences in mid- to long-term outcomes of computer-assisted navigation versus conventional total knee arthroplasty.

PURPOSE: Accurate implant position in total knee arthroplasty (TKA) can potentially lead to better long-term functional outcomes and implant survival. Recent studies on whether better clinical results could be obtained from computer-navigated or conventional TKA were inconclusive. In addition, recent reviews only included short-term follow-up studies without performing quantitative mid- to long-term follow-up analysis. Thus, the purpose of the present study was to perform a meta-analysis comparing mid- to long-term clinical outcomes (such as knee scoring and functional results) and radiological outcomes (such as normal alignment of the limb axis or component) between computer-navigated TKA and conventional TKA to determine which method of TKA could obtain better clinical and radiological results. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and SCOPUS electronic databases were searched for relevant articles published through August 2018 that compared outcomes of computer-navigated TKA and conventional TKA. Data search, extraction, analysis, and quality assessment were performed according to the Cochrane Collaboration guidelines. Clinical and radiological outcomes of both techniques were evaluated using various outcome measures. RESULTS: Seven randomized controlled trials were included. Based on Knee Society Scores, the Western Ontario and McMaster Universities Osteoarthritis Index, pain, and range of motion, there were no significant differences in clinical outcomes between the two techniques. Based on outliers from the normal axis, outliers of femoral components in the coronal plane, and outliers of tibial components in the coronal plane, radiologic outcomes showed no significant differences between the two techniques either. CONCLUSIONS: The present study revealed that there were no significant differences in clinical or radiological outcomes between computer-navigated TKA and conventional TKA. It remains unclear which TKA technique yields better results in terms of mid- to long-term clinical and radiological outcomes. LEVEL OF EVIDENCE: I.

Ergosterol Peroxide from the Medicinal Mushroom Ganoderma lucidum Inhibits Differentiation and Lipid Accumulation of 3T3-L1 Adipocytes.

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.

Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities.

Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 µM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1ß, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 µM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human ß-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.

Retropubic versus Transobturator Mid Urethral Slings in Patients at High Risk for Recurrent Stress Incontinence: A Systematic Review and Meta-Analysis.

PURPOSE: The efficacy and safety of retropubic and transobturator tension-free vaginal tape mid urethral slings remain controversial in patients with stress urinary incontinence and risk factors for recurrence. We compared the techniques after initial mid urethral sling insertion in select groups, including patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence. MATERIALS AND METHODS: We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to report the methods and results of the current review. Randomized controlled trials and observational studies were included. We assessed the objective and subjective cure rates, and the complication rate using the OR with the 95% CI. The protocol of the current meta-analysis was registered on PROSPERO (No. CRD42018102233). RESULTS: We retrieved 28 studies in a total of 2,607 patients to compare the efficacy and safety of retropubic vs transobturator tension-free vaginal tape in select groups (mean followup 26.9 months). Meta-analysis of the objective cure rate showed the significant superiority of retropubic compared to transobturator tension-free vaginal tape in patients overall (OR 3.37, 95% CI 2.55-4.43, p <0.00001, I2 = 37%) and in each subpopulation. The subjective cure rate of retropubic tension-free vaginal tape was also significantly superior to that of transobturator tension-free vaginal tape in in patients overall (OR 2.01, 95% CI 1.45-2.80, p <0.0001, I2 = 0%) and in those with intrinsic sphincter deficiency and recurrent stress urinary incontinence after mid urethral sling insertion. There was no significant difference in overall complications between retropubic and transobturator tension-free vaginal tape (OR 1.22, 95% CI 0.89-1.66, p = 0.21, I2 = 0%). CONCLUSIONS: The meta-analysis showed the superiority of retropubic tension-free vaginal tape over transobturator tension-free vaginal tape in terms of the objective and subjective cure rates in patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence after mid urethral sling insertion. Retropubic tension-free vaginal tape also has morbidity comparable to that of transobturator tension-free vaginal tape.

Clinical outcome of single-incision slings, excluding TVT-Secur, vs standard slings in the surgical management of stress incontinence: an updated systematic review and meta-analysis.

The aim of the present paper was to assess and compare the long-term efficacy and safety of single-incision mini-slings (SIMSs), except tension-free vaginal tape (TVT)-Secur, with standard midurethral slings (SMUSs) for female stress urinary incontinence through an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing these two surgical methods. A literature review of all RCTs comparing SIMSs (Mini-Arc, Contasure-Needleless, Ophira, Tissue Fixation System and Ajust), except TVT-Secur, with SMUSs was performed. The Medline, Embase, Scopus, Web of Science and Cochrane Controlled Trial Register databases were reviewed. We retrieved 29 RCTs (including a total of 2 986 patients) that compared SIMSs, except TVT-Secur, with SMUSs. Meta-analysis of long-term results showed no significant difference in the patient-reported cure rate (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.60); however, we found that SMUSs had a significantly superior objective cure rate (OR 0.68, 95% CI 0.47-0.99; P = 0.04). SIMSs were associated with a significantly shorter operation time, lower immediate postoperative pain based on a visual analogue scale score, lower intra-operative blood loss, and lower postoperative voiding dysfunction. The meta-analysis showed clear evidence of the superiority of SMUSs over SIMSs, except TVT-Secur, in terms of the objective cure rate, after long-term follow-up; however, SIMSs were superior with respect to immediate postoperative pain, intra-operative blood loss, and postoperative voiding dysfunction.

The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis.

INTRODUCTION: The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. AIM: To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. METHODS: Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. MAIN OUTCOME MEASURE: The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. RESULTS: In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. CLINICAL IMPLICATIONS: Arginine supplements can be recommended to patients with mild to moderate ED. STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. CONCLUSION: The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED. Rhim HC, Kim MS, Park Y-J, et al. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med 2019;16:223-234.

Novel symptom questionnaire for the differential diagnosis of detrusor underactivity and bladder outlet obstruction in men.

OBJECTIVE: To develop a questionnaire for the differential diagnosis of detrusor underactivity (DUA) and bladder outlet obstruction (BOO) without performing invasive pressure flow studies. STUDY DESIGN AND METHODS: Symptoms of men with DUA were analyzed and compared with those of men with BOO using eight questions from the developing questionnaire. Patients with DUA have a bladder contractility index (PdetQmax+5xQmax) less than 100, whereas those with BOO have a BOO index (PdetQmax-2xQmax) greater than 40 in urodynamic studies (UDS). Men with detrusor overactivity in UDS and neurogenic issues were excluded from the analysis. One urologist reviewed patients' medical records, and responded to eight questions without using information from UDS. Scores in the developing questionnaire were then compared to make a differential diagnosis between DUA and BOO. RESULTS: Overall, 318 men who underwent UDS were included. Symptoms were compared in patients diagnosed with DUA without BOO (n = 165) and BOO without DUA (n = 153). Questions 1, 2, 4, 5, 6, and 7 were significantly different between groups. The sensitivity and specificity of the questionnaire were 95.8% and 95.4%, respectively, for predicting DUA in patients with scores greater than 45 points (cutoff value). CONCLUSIONS: Men with DUA and BOO may be distinguished using a developing questionnaire without invasive evaluation. Men with scores greater than 45 points would be expected to have DUA but not BOO.

Clinical Application of Three-Dimensionally Printed Biomaterial Polycaprolactone (PCL) in Augmentation Rhinoplasty.

BACKGROUND: This clinical study aimed to investigate the safety and surgical outcome of three-dimensionally (3D) fabricated polycaprolactone (PCL) mesh in rhinoplasty. In particular, this study explored how a 3D-printed PCL mesh performs as a bioabsorbable scaffold after a long period following implantation. METHODS: A retrospective review of 101 patients who received primary or secondary rhinoplasty with a PCL mesh was performed. Patient demographics and surgery-related outcomes were examined. Clinical efficacy and safety were evaluated using the Global Aesthetic Improvement Scale at postoperative 18 months. From two revisional cases, a biopsy specimen of implanted PCL was acquired and histopathological analysis was performed. RESULTS: Of all the patients, 98.0% showed no postoperative infection-related foreign body reaction or distinct abnormal reaction, and the implants were observed to maintain long-term efficacy until 18-month follow-up. In patients who received spreader grafts, significant differences between preoperative and postoperative Cottle sign scores were found. Histopathological analysis showed features of adjacent tissue infiltration into pores of the PCL mesh and regeneration of neo-cartilaginous tissue and collagen around the mesh 20 months after implantation. CONCLUSION: This study demonstrates that a novel biodegradable PCL mesh with a 3D structure is a safe and effective material for corrective rhinoplasty because it is easy to use and capable of maintaining its volume in the long term without foreign body response. This biocompatible material will have a wide range of applications as the most suitable alternative to nonabsorbable materials in rhinoplasty and reconstruction surgeries, such as fashioning spreader grafts and septal extension grafts. LEVEL OF EVIDENCE IV: 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 .

WHO disability assessment schedule 2.0 is related to upper and lower extremity disease-specific quality of life.

PURPOSE: We evaluated whether two disease-specific quality of life instruments (Disabilities of the Arm, Shoulder and Hand, DASH and Western Ontario & McMaster Universities Osteoarthritis Index, WOMAC) reflect a patient's perception of general disability using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) and determined whether disability components are explained by upper and lower extremity HRQOL. METHODS: We recruited 421 participants, 50 years or older without stroke, cancer, or history of surgery for musculoskeletal disease, who participated in the NAMGARAM Cohort. Upper extremity HRQOL was determined with the DASH score and lower extremity HRQOL with the WOMAC; as a measure of disability, we obtained WHODAS 2.0 component. Multiple regression modeling was used to assess the relative contributions made by upper and lower extremity HRQOL to disability. RESULTS: When adjusted for covariates, the DASH total score was correlated with getting around (ß = 0.217, p < 0.001) and social participation (ß = 0.226, p < 0.001), and the WOMAC total score was correlated with getting around (ß = 0.363, p < 0.001), life activation (ß = 0.363, p < 0.001), and social participation (ß = 0.301, p < 0.001). QOL significantly correlated with upper extremity disorders (ß = 0.081, p = 0.018) or lower extremity disorders (ß = 0.095 p = 0.004). CONCLUSION: We found that in a community-based population, perceived activity limitation and social participation were associated with upper and lower extremity HRQOL. Since the WHODAS 2.0 does not target a specific disease (as opposed to DASH and WOMAC), it can be used to compare disabilities caused by different diseases.