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Background: IgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU. Methods: Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (

Objective : To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Methods: Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Results: Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial–mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. Conclusion: SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.

Providing opportunities for individuals with mental retardation and other significant disabilities to participate in educational, vocational, and recreational activities on college campuses has been a topic of interest among educators and adult service providers for the past 30 years. We reviewed the literature on post-secondary programs and supports for these individuals to (a) identify a philosophical basis for providing such opportunities, (b) identify practices, and (c) summarize research on the efficacy of these efforts. The literature from the 1970's to 1990's provided descriptions of programs or advocated for the inclusion of adults with mental retardation on college campuses in position papers. Limited empirical data supported the efficacy of these programs. The literature during the 1990's shifted to providing post-secondary programs or individual supports to students with mental retardation and other significant disabilities, ages 18--22, who were still enrolled in public schools. Implications for emerging trends, research and program evaluation, and replication of practices are discussed. [ABSTRACT FROM AUTHOR]

Tattooing and use of permanent makeup (PMU) have dramatically increased over the last decade, with a concomitant increase in ink-related infections. Studies have shown evidence that commercial tattoo and PMU inks are frequently contaminated with pathogenic microorganisms. Considering that tattoo inks are placed into the dermal layer of the skin where anaerobic bacteria can thrive and cause infections in low-oxygen environments, the prevalence of anaerobic and aerobic bacteria should be assessed in tattoo and PMU inks. In this study, we tested 75 tattoo and PMU inks using the analytical methods described in the FDA Bacteriological Analytical Manual Chapter 23 for the detection of both aerobic and anaerobic bacterial contamination, followed by 16S rRNA gene sequencing for microbial identification. Of 75 ink samples, we found 26 contaminated samples with 34 bacterial isolates taxonomically classified into 14 genera and 22 species. Among the 34 bacterial isolates, 19 were identified as possibly pathogenic bacterial strains. Two species, namely Cutibacterium acnes (four strains) and Staphylococcus epidermidis (two strains) were isolated under anaerobic conditions. Two possibly pathogenic bacterial strains, Staphylococcus saprophyticus and C. acnes , were isolated together from the same ink samples ( n = 2), indicating that tattoo and PMU inks can contain both aerobic ( S. saprophyticus ) and anaerobic bacteria ( C. acnes ). No significant association was found between sterility claims on the ink label and the absence of bacterial contamination. The results indicate that tattoo and PMU inks can also contain anaerobic bacteria., Importance: The rising popularity of tattooing and permanent makeup (PMU) has led to increased reports of ink-related infections. This study is the first to investigate the presence of both aerobic and anaerobic bacteria in commercial tattoo and PMU inks under aerobic and anaerobic conditions. Our findings reveal that unopened and sealed tattoo inks can harbor anaerobic bacteria, known to thrive in low-oxygen environments, such as the dermal layer of the skin, alongside aerobic bacteria. This suggests that contaminated tattoo inks could be a source of infection from both types of bacteria. The results emphasize the importance of monitoring these products for both aerobic and anaerobic bacteria, including possibly pathogenic microorganisms., Competing Interests: The authors declare no conflict of interest.

Use of a template triggers an epitaxial interaction with the depositing material during synthesis. Recent studies have demonstrated that two-dimensional tellurium (tellurene) can be directionally oriented when grown on transition metal dichalcogenide (TMD) templates. Specifically, employing a T-phase TMD, such as WTe 2 , restricts the growth direction even further due to its anisotropic nature, which allows for the synthesis of well-oriented tellurene films. Despite this, producing large-area epitaxial films still remains a significant challenge. Here, we report the continuous synthesis of a 1T'-MoTe 2 template via chemical vapor deposition and tellurene via vapor transport. The interaction between helical Te and the 1T'-MoTe 2 template facilitates the Te chains to collapse into ribbon shapes, enhancing lateral growth at a rate approximately 6 times higher than in the vertical direction, as confirmed by scanning electron microscopy and atomic force microscopy. Interestingly, despite the predominance of the lateral growth, cross-sectional transmission electron microscopy analysis of the tellurene ribbons revealed a consistent 60-degree incline at the edges. This suggests that the edges of the tellurene ribbons, where they contact the template surface, are favorable sites for additional Te absorption, which then stacks along the incline angle to expand. Furthermore, controlling the synthesis temperature, duration, and preheating time has facilitated the successful synthesis of tellurene films. The resultant tellurene exhibited hole mobility as high as ∼400 cm 2 /V s. After removing the underlying metallic template with plasma treatment, the film showed a current on/off ratio of ∼10 3 . This ratio was confirmed by two-terminal field-effect transistor measurements and supported by near-field terahertz (THz) spectroscopy mapping.

Background: Epstein-Barr virus-associated gastric cancer (EBVaGC) is a distinct molecular subgroup showing excellent outcomes after surgery for localized disease. Prominent immune cell infiltration in EBVaGC reflects the immunogenicity of Epstein-Barr virus (EBV) and, as suggested by some investigators, responsiveness to immune checkpoint inhibitors in the palliative setting. However, few data are available on the prevalence, clinical characteristics, and prognosis of EBVaGC patients receiving palliative cytotoxic chemotherapy., Methods: In this retrospective study, we identified 1061 patients with metastatic, recurrent, or locally advanced unresectable gastric cancer (GC) who started first-line fluoropyrimidine/platinum (FP) doublet chemotherapy with or without trastuzumab from January 2015 to August 2018. For 766 patients with available tumor tissue, the presence of EBV in cancer cells was evaluated by EBV-encoded RNA in situ hybridization and correlated with clinical characteristics and treatment outcomes., Results: Among the patients evaluated (n = 766), 40 (5.0%) were EBV-positive. EBVaGC was associated with male sex (p = 0.009) and lower neutrophil-lymphocyte ratio (NLR < 2.46, p = 0.03). Efficacy of first-line FP chemotherapy, in terms of response rate ad progression-free survival (PFS), did not differ between EBVaGC and EBV-negative GC (overall response rate: 53.8% vs. 51.8%, p = 0.99; median PFS: 6.4 vs. 6.7 months, p = 0.90). However, overall survival tended to be better with EBVaGC than EBV-negative GC (16.4 vs. 14.0 months, p = 0.07)., Conclusions: EBVaGC accounted for 5% of metastatic/unresectable GCs. While EBVaGC was not associated with better response to or PFS following first-line cytotoxic chemotherapy, it showed a trend toward better overall survival., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

In this study, we collected voluntary recall records of tattoo and permanent makeup ink from the U.S. Food and Drug Administration (US FDA) Enforcement Report Database. The recall records contain information, such as recall date, manufacturer, ink color, reason for recall, and the microorganisms detected from the ink samples. Between 2003 and 2021, a total of 15 voluntary tattoo ink recalls occurred in the U.S. market, involving over 200 tattoo inks marketed by 13 manufacturers and one distributor. Fourteen recalls were due to microbial contamination, and one recall was due to allergic reaction. As follow-up, a microbiological survey of 28 tattoo inks of new batches from seven manufacturers having products that were previously recalled was conducted. Aerobic plate count (APC) and enrichment culture methods based on the FDA's Bacteriological Analytical Manual (BAM) were used to detect microbial contamination. The results revealed that six out of 28 tattoo inks were contaminated with bacteria and were produced by two manufacturers. The level of microbial contamination was less than 250 CFU/g in three of the tattoo inks and between 1 × 10 3 and 1 × 10 5  CFU/g in the other three inks. Eleven bacterial isolates were identified, including spore-forming Bacillus -related species and potentially pathogenic species. Overall, this study shows that some tattoo ink products produced by manufacturers with a recall history continue to be contaminated with microorganisms. This highlights the need for ongoing monitoring and quality control of such products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yoon, Kondakala, Moon, Huang, Periz, Foley, Kweon and Kim.)

Study Design: Analysis of lumbar spine radiograms of 1,496 Jeju islanders of Korea., Purpose: To look into the age- and gender-matched incidences of morphological changes and their severities., Overview of Literature: There have been several prior research on the prevalence and severity of age-related diseases, both related and unrelated. Those offer some fundamental clinical data for clinicians., Methods: Radiograms of 1,496 patients (555 males and 941 females) from the first to 9th decade were examined for this study. Sagittal and coronal alignment, disc space narrowing, spur formation including diffuse idiopathic spinal hyperostosis (DISH), spondylolisthesis, and ballooned discs associated with biconcave bodies due to osteoporosis were among the parameters of lumbar spine morphologies examined on high-quality radiographs by both human observers and computers., Results: The alignment of the lumbar spine altered after birth and set at growth maturity, and then the curve was maintained till the end of the 5th decade afterward and the curve gradually hypolordotic. There were three types of coronal alignment abnormalities can be seen: idiopathic, osteopathic, and discogenic (degenerative lumbar scoliosis [DLS]). DLS developed after 6th decade. There was no scoliosis associated with spondylolysis or the post-laminofacetectomy period. Disc space narrowing and corporal spur formation were not seen till the end of 3rd decade comparatively speaking, the corporal spurs generated in the non-scoliotic spine were smaller than those in the scoliotic spine. DISH began to appear in the 5th-decade patients and its incidences increased gradually afterward. Porosis-related vertebral body collapse started to happen after 6th decade. There are three different types of spondylolisthesis: anterior, posterior, and lateral. The lateral slip occurred only in the scoliotic spine. All types were related to degenerative discs., Conclusions: It has been shown that the morphology of the lumbar spine changes throughout time.

Background: Percutaneous pedicle screw fixation (PPSF) without fusion has been recently recommended in the treatment of thoracolumbar fracture to reduce the adverse effects associated with the conventional open approaches and to restore range of motion. However, those studies report on the thoracolumbar junction, and there is no report on lower lumbar fracture., Purpose: To assess effectiveness of PPSF without fusion for treating lower lumbar burst (A3 and A4) fractures., Methods: A retrospective analysis was made to evaluate consecutive 50 patients with AO type A3 and A4 thoracolumbar fracture underwent PPSF. Patients were divided into a thoracolumbar junction (TLJ) group (T11-L2) and lower lumbar (LL) group (L3-5). The following items were measured and compared between the two groups. Vertebral height and consolidation, retropulsed fragment, sagittal curve and fixation failure were assessed with certain interval regularly., Results: The average height at pre- and post-reduction were 56.2% (36.2-74.3), 95.3% (84.2-98.3) in TLJ group and 65.7% (45.7-86.2), 91% (73.1-100) in LL group. The average canal area occupancy rate at pre- and post-reduction were 46.1% (37.4%-67.5%), 38.1% (31.3%-40.8%) in TLJ group and 40.4% (15.0-65.7), 19.3% (9.4-26.6) in LL group. Consolidation was completed within 12 months after surgery in both groups. There was no significant difference between two groups in clinical and radiographic parameters except cobb angle loss., Conclusion: Patients with lower lumbar fracture can be effectively managed with PPSF without fusion. PPSF following the implant removal can restore the movement of the lower lumbar spine, which is essential for daily life., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In two previous surveys, the U.S. Food and Drug Administration (FDA) identified microbial contamination in 53 of 112 (47%) unopened tattoo inks and tattoo-ink-related products (e.g., diluents) from 15 manufacturers in the U.S. In this study, we primarily focused our microbiological survey on permanent makeup (PMU) inks. We conducted a survey of 47 unopened PMU inks from nine manufacturers and a comparative species-centric co-occurrence network (SCN) analysis using the survey results. Aerobic plate count and enrichment culture methods using the FDA's Bacteriological Analytical Manual (BAM) Chapter 23 revealed that 9 (19%) inks out of 47, from five manufacturers, were contaminated with microorganisms. The level of microbial contamination was less than 250 CFU/g in eight inks and 980 CFU/g in one ink. We identified 26 bacteria that belong to nine genera and 21 species, including some clinically relevant species, such as Alloiococcus otitis , Dermacoccus nishinomiyaensis , Kocuria rosea , and Pasteurella canis . Among the identified microorganisms, the SCN analysis revealed dominance and a strong co-occurrence relation of spore-forming extreme environment survivors, Bacillus spp., with close phylogenetic/phenotypic relationships. These results provide practical insights into the possible microbial contamination factors and positive selection pressure of PMU inks.

Background: New prognostic factors have been reported in patients with metastatic or recurrent gastric cancer (MRGC), necessitating modifications to the previous prognostic model., Aim: To develop a new model, MRGC patients who received fluoropyrimidines/ platinum doublet chemotherapy between 2008 and 2015 were analyzed., Methods: A total of 1883 patients was divided into a training set ( n = 937) and an independent validation set ( n = 946)., Results: Multivariate analysis showed that the following six factors were associated with poor overall survival (OS) in the training set: Eastern Cooperative Oncology Group performance score ≥ 2 and bone metastasis (2 points each), peritoneal metastasis, high alkaline phosphatase level, low albumin level, and high neutrophil-lymphocyte ratio (1 point each). A prognostic model was developed by stratifying patients into good (0-1 point), moderate (2-3 points), and poor (≥ 4 points) risk groups. In the validation set, the median OS of the three risk groups was 15.8, 10.1, and 5.7 mo, respectively, and those differences were significant ( P < 0.001)., Conclusion: We identified six factors readily measured in clinical practice that are predictive of poor prognosis in patients with MRGC. The new model is simpler than the old and more easily predicts OS., Competing Interests: Conflict-of-interest statement: No conflicts of interest relevant to this article are reported., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: There has been an interest in the microbial azo dye degradation as an optional method for the treatment of azo dye-containing wastes. Tattoo ink is an extremely unique azo dye-rich environment, which have never been explored in terms of microorganisms capable of degrading azo dyes. Previously, we isolated 81 phylogenetically diverse bacteria, belonging to 18 genera and 52 species, contaminated in tattoo inks. In this study, we investigated if these bacteria, which can survive in the azo dye-rich environment, have an ability to degrade azo dyes., Methods: We conducted a two-step azo dye degradation (or decolorization) assay. In step 1, a high-throughput degradability assay was done for 79 bacterial isolates using Methyl Red and Orange II. In step 2, a further degradation assay was done for 10 selected bacteria with a representative of 11 azo dyes, including 3 commercial tattoo ink azo dyes. Degradation of azo dyes were calculated from measuring optical absorbance of soluble dyes at specific wavelengths., Results: The initial high-throughput azo dye assay (step 1) showed that 79 isolates had a complete or partial degradation of azo dyes; > 90% of Methyl Red and Orange II were degraded within 24 h, by 74 and 20 isolates, respectively. A further evaluation of azo dye degradability for 10 selected isolates in step 2 showed that the isolates, belonging to Bacillus , Brevibacillus , Paenibacillus , and Pseudomonas , exhibited an excellent decolorization ability for a wide range of azo dyes., Conclusions: This study showed that phylogenetically diverse bacteria, isolated from azo dye-rich tattoo inks, is able to degrade a diverse range of azo dyes, including 3 azo dyes used in commercial tattoo inks. Some of the strains would be good candidates for future studies to provide a systematic understanding of azo dye degradation mechanisms., Competing Interests: Competing interests The authors declare that they have no competing interests.

This study was conducted to investigate doubled haploid (DH) lines produced between high GSL (HGSL) B rassica rapa ssp. trilocularis (yellow sarson) and low GSL (LGSL) B. rapa ssp. chinensis (pak choi) parents. In total, 161 DH lines were generated. GSL content of HGSL DH lines ranged from 44.12 to 57.04 μmol·g -1 ·dry weight (dw), which is within the level of high GSL B. rapa ssp. trilocularis (47.46 to 59.56 μmol g -1 dw). We resequenced five of the HGSL DH lines and three of the LGSL DH lines. Recombination blocks were formed between the parental and DH lines with 108,328 single-nucleotide polymorphisms in all chromosomes. In the measured GSL, gluconapin occurred as the major substrate in HGSL DH lines. Among the HGSL DH lines, BrYSP&#95;DH005 had glucoraphanin levels approximately 12-fold higher than those of the HGSL mother plant. The hydrolysis capacity of GSL was analyzed in HGSL DH lines with a Korean pak choi cultivar as a control. Bioactive compounds, such as 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, 2-phenethyl isothiocyanate, and sulforaphane, were present in the HGSL DH lines at 3-fold to 6.3-fold higher levels compared to the commercial cultivar. The selected HGSL DH lines, resequencing data, and SNP identification were utilized for genome-assisted selection to develop elite GSL-enriched cultivars and the industrial production of potential anti-cancerous metabolites such as gluconapin and glucoraphanin.

Purpose: This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns., Materials and Methods: A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000-2003 (period 1), 2004-2007 (period 2), 2008-2011 (period 3), and 2012-2015 (period 4)., Results: There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The overall survival (OS) rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% confidence interval [CI], 15.5 to 20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8 to 11.6)., Conclusion: The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2-targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Backgroud: There are many studies on the vertebral body-to-canal ratio, the so-called Pavlov's ratio of the cervical spine. However, there are no studies on its relation with age to clarify each bony component's contribution to the spinal canal formation and its size. The aim of this study was to investigate differences and changes in the vertebral body-to-canal ratio according to age in an asymptomatic population., Methods: This is a cross-sectional study of 280 asymptomatic individuals. A total of 140 men and 140 women representing each decade of life from the first to the seventh were included in this study. The anteroposterior length of the vertebral body and canal from C3 to C6 was measured on sagittal radiographs to calculate the vertebral body-to-canal ratio., Results: The average Pavlov's ratio was significantly larger ( p < 0.001) in the first decade of life. The average Pavlov's ratio of the individuals in the first decade of life was 1.09 between C3 and C6 (1.08 at C3, 1.07 at C4, 1.11 at C5, and 1.13 at C6; range, 0.78-1.51). There was no significant difference among the other decades of life., Conclusions: We assessed the Pavlov's ratio of the cervical spine in an asymptomatic population. It is our belief that the spinal canal size is the largest in the first decade of life, and the Pavlov's ratio becomes almost fixed throughout life after maturity., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2021 by The Korean Orthopaedic Association.)

Background: Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. Microbial translocation has yet to be completely defined in chronic hepatitis B virus (HBV) and chronic hepatitis delta virus (HDV)., Methods: Our aim was to characterize MT and associated immune response in chronic HBV and HDV at various stages of disease. Serum from 53 HBV, 43 HDV, and 36 healthy control (HC) subjects was obtained. Subjects were categorized by aspartate aminotransferase-to-platelet ratio index into mild (<0.5), moderate, and severe (>1.0) disease. Cytokines, microbial products, and microbial deoxyribonucleic acid (DNA) levels were assessed in a single treatment-naive time point for each patient. Next-generation sequencing identified bacterial species present within patient sera., Results: The HBV and HDV subjects display higher serum concentrations of Gram-negative (G - ) bacterial lipopolysaccharide and fungal beta-glucan compared with HC (all P < .01). Gram-positive (G + ) bacterial peptidoglycan is higher in HBV compared to HDV and HC (both P < .0001). Within both disease cohorts, peptidoglycan correlates with interleukin (IL)-1b, IL-8, IL-12p70, and IL-13 (all Spearman's rho >0.45; P < .05). Next-generation sequencing from 7 subjects with detectable serum bacterial DNA revealed changes in abundance of bacterial taxa and a higher proportion of Gram-positive genera in severe disease. Greater G + /G - taxa ratio is associated with higher cytokine levels and disease markers., Conclusions: The HBV and HDV patients display increased translocation of bacterial and fungal products into serum. An increased proportion of Gram-positive genera is associated with disease progression. Correlations of peptidoglycan with antimicrobial cytokines suggest that particular microbial classes may contribute to systemic inflammation and possibly disease progression., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)

In a 2018 survey, U.S. Food and Drug Administration (FDA) identified microbial contamination in 42 (49%) of 85 unopened tattoo and permanent makeup (PMU) inks purchased from 13 manufacturers in the US between November 2015 and April 2016. To confirm the results of our previous survey, we evaluated the level of microbial contamination in an additional 27 samples from 10 manufacturers from September 2017 to December 2017, including 21 unopened tattoo and PMU inks which were selected based on our previous survey results and 6 ink diluents that were not previously analysed. Aerobic plate count and enrichment culture methods from the FDA's Bacteriological Analytical Manual revealed 11 (52%) out of 21 inks, from six manufacturers, were contaminated with micro-organisms, with contamination levels up to 3·6 × 10 8  CFU per gram, consistent with our previous survey results. We identified 25 bacterial strains belonging to nine genera and 19 species. Strains of Bacillus sp. (11 strains, 44%) were dominant, followed by Paenibacillus sp. (5 strains, 20%). Clinically relevant strains, such as Kocuria rhizophila and Oligella ureolytica, were also identified, as similar to the findings in our previous survey. No microbial contamination was detected in any of the six ink diluents., (© 2020 The Society for Applied Microbiology.)

The bHLH transcription factor Hes1 is a key downstream effector for the Notch signaling pathway. During embryogenesis neural progenitors express low levels of Hes1 in an oscillating pattern, whereas glial brain boundary regions (e.g., isthmus) have high, sustained Hes1 levels that suppress neuronal fates. Here, we show that in the embryonic mouse retina, the optic nerve head and stalk express high Hes1, with the ONH constituting a boundary between the neural retina and glial cells that ultimately line the optic stalk. Using two Cre drivers with distinct spatiotemporal expression we conditionally inactivated Hes1 , to delineate the requirements for this transcriptional repressor during retinal neurogenesis versus patterning of the optic cup and stalk. Throughout retinal neurogenesis, Hes1 maintains proliferation and blocks retinal ganglion cell formation, but surprisingly we found it also promotes cone photoreceptor genesis. In the postnatal eye, Hes1 inactivation with Rax-Cre resulted in increased bipolar neurons and a mispositioning of Müller glia. Our results indicate that Notch pathway regulation of cone genesis is more complex than previously assumed, and reveal a novel role for Hes1 in maintaining the optic cup-stalk boundary. SIGNIFICANCE STATEMENT The bHLH repressor Hes1 regulates the timing of neurogenesis, rate of progenitor cell division, gliogenesis, and maintains tissue compartment boundaries. This study expands current eye development models by showing Notch-independent roles for Hes1 in the developing optic nerve head (ONH). Defects in ONH formation result in optic nerve coloboma; our work now inserts Hes1 into the genetic hierarchy regulating optic fissure closure. Given that Hes1 acts analogously in the ONH as the brain isthmus, it prompts future investigation of the ONH as a signaling factor center, or local organizer. Embryonic development of the ONH region has been poorly studied, which is surprising given it is where the pan-ocular disease glaucoma is widely believed to inflict damage on RGC axons., (Copyright © 2020 the authors.)

Background: Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not entirely understood. The aim was to compare circulating platelets, growth factors, and vascular injury markers (VIMs) in hepatitis C-infected (HCV) patients with early fibrosis and cirrhosis., Methods: Retrospective evaluation of serum GFs and VIMs by ELISA were evaluated from twenty-six HCV patients. Analytes from an earlier time-point were correlated with MELD at a later time-point., Results: Platelets and GFs decreased, and VIMs increased with fibrosis. Platelets correlated positively with PDGF-AA, PDGF-BB, TGFB1, EGF, and P-selectin, and negatively with ICAM-3 and VCAM-1. P-selectin showed no correlations with VIMs but positively correlated with PDGF-AA, PDGF-BB, TGFB1, and EGF. Soluble VCAM-1 and ICAM-3 were linked to increasing fibrosis, liver enzymes, and synthetic dysfunction. Higher VCAM-1 and ICAM-3 and lower P-selectin at an earlier time-point were linked to higher MELD score at a later time-point., Conclusion: In chronic HCV, progressive decline in platelets and growth factors with fibrosis and their associations suggest that platelets are an important source of circulating GFs and influence GF decline with fibrosis. Enhanced markers of vascular injury in patients with early fibrosis suggest an earlier onset of endothelial dysfunction preceding cirrhosis. Associations of VIMs with platelets suggest a critical link between platelets and vascular homeostasis. Circulating markers of vascular injury may not only have prognostic importance but emphasize the role of vascular dysfunction in liver disease pathogenesis (NCT00001971).

Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, and β-D-glucan in addition to their pattern recognition receptors and degree of hepatic macrophage uptake. The findings suggest that regulation of serum peptidoglycan and β-D-glucan differs from that of lipopolysaccharide. Additionally, macrophage activation in the liver may be better reflected by the degree of macrophage uptake than by circulating levels of microbial markers. These findings allow for a greater understanding of bacterial translocation and host immune activation during HCV infection., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019.)

Study Design: Retrospective study (level of evidence: level 3)., Purpose: To study the anatomy of the conus medullaris in Koreans., Overview of Literature: The anatomical position of the conus medullaris is well-documented in anatomy textbooks; however, the shape of the conus in the canal rarely described. Furthermore, to our knowledge, no study in Korea has not yet assessed the shape of the conus as well as its position in the canal via cadavaric dissection and/or magnetic resonance imaging (MRI)., Methods: MRI findings of 189 Korean patients aged 2-94 years (93 men and 94 women) were assessed. No subjects from other ethnicities were included. The method proposed by Arai and colleagues was used to assess the termination point and shape of the conus in the canal. The position of the intervertebral disc trisection of the vertebral body closest to the tip of the conus was recorded at the canal level., Results: The tip of the conus medullaris was positioned from the upper T12 body to the L2-L3 disc, mostly in L1 bodies (52.4%), followed by the L2 bodies (22.5%), the L1-L2 disc, and the L2-L3 disc (1.1%). The shape of the conus was classified as type A in 74 (39.6%), type B in 58 (31%), and type C in 55 patients (29.4%). The conus did not terminate at the L3 body in any patient. In the first decade ones (five children) conus positioned rather lowly from L1 bodies to L2-L3 disc, and no type A conus shape, and mostly type B (80%)., Conclusions: The conus medullaris was positioned mostly in the lower one-third of L1 and it in the first decades terminated lowly. No type A in the first decade one, and type B was mostly frequently formed which was followed by type C.

Surgery-related infections have not been irradicated until now. To solve this problem, it is important to know the relationship between bacterial anatomy and bacterial behavior in the tug-of-war between host and pathogen. In this article, bacterial anatomy and functional behavior, host phagocytic activity, immune system, nutrition and antibiotics are reviewed to win the war against the tiny invaders and leave the host unharmed. My suggestion is that scientists should direct their studies not only to developing potent new antibiotics that will never give rise to drug-resistant mutants, but also to developing a very competitive immune system that can suppress or control infection without the aid of antibiotics.

Background and Aim: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages., Methods: A total of 129 subjects were evaluated: 53 HBV, 43 HDV, and 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment-naïve time-point., Results: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher tumor necrosis factor-α (TNF-α), interleukin (IL)-12p40, and C-X-C motif chemokine ligand 9 when compared with controls (all P < 0.05). However, only HBV group displayed elevated γ-interferon compared with controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL-4, IL-13, and C-C motif chemokine ligand (CCL) 26 compared with healthy controls and HDV. Chemokines CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher γ-interferon/IL-4, TNF-α/IL-4, and TNF-α/IL-13 ratios than HBV and controls., Conclusion: Hepatitis B virus and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease. Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV-associated disease progression., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Study Design: A case study., Purpose: To assess the chronological changes of the disease-related kyphosis after chemotherapy alone, secondly to clarify the role of growth cartilage in the healed lesion on kyphosis change, and to define the accurate prediction time in assessing residual kyphosis., Overview of Literature: None of the previous papers up to now dealt with the residual kyphosis, stability and remodeling processes of the affected segments., Methods: One hundred and one spinal tuberculosis children with various stages of disease processes, age 2 to 15 years, were the subject materials, between 1971 to 2010. They were treated with two different chemotherapy formula: before 1975, 18 months of triple chemotherapy (isoniazid [INH], para-aminosalicylic acid, streptomycin); and since 1976, 12 months triple chemotherapy (INH, rifampicin, ethambutol, or pyrazinamide). The first assessment at post-chemotherapy one year and at the final discharge time from the follow-up (36 months at minimum and 20 years at maximum) were analyzed by utilizing the images effect of the remaining growth plate cartilage on chronological changes of kyphosis after initiation of chemotherapy., Results: Complete disc destruction at the initial examination were observed in two (5.0%) out of 40 cervical spine, eight (26.7%) out of 30 dorsal spine, and six (19.4%) out of 31 lumbosacral spine. In all those cases residual kyphosis developed inevitably. In the remainders the discs were partially preserved or remained intact. Among 101 children kyphosis was maintained without change in 20 (19.8%), while kyphosis decreased in 14 children (13.7%), and increased in 67 children (66.3%) with non-recoverably damaged growth plate, respectively., Conclusions: It could tentatively be possible to predict the deformity progress or non-progress and spontaneous correction at the time of initial treatment, but it predictive accuracy was low. Therefore, assessment of the trend of kyphotic change is recommended at the end of chemotherapy. In children with progressive curve change, the deformity assessment should be continued till the maturity.

Background: Several previous studies reported on the impact of upright standing and chair sitting on the sagittal spinopelvic alignment. However, there are no studies on the impact of the two Asian (Korean and Japanese) style floor-sitting positions on the sagittal spinopelvic alignment. The purpose of this study was to evaluate the impact of four different body postures (standing, chair sitting, kneel sitting, and cross-legged sitting) on the sagittal spinopelvic alignment., Methods: Sixteen selected healthy volunteers (10 males and six females) were subjects of this pilot study. In all subjects, radiographs were taken in comfortable standing and sitting positions. All spinal curvatures including lumbar lordotic angle (LLA), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI) were measured on the radiographs., Results: In standing position, the average LLA, SS, PT, and PI were 37.1°, 35.3°, 15.7°, and 51.0°, respectively. In chair sitting, the average LLA, SS, PT, and PI were 17.9°, 20.3°, 28.2°, and 49.5°, respectively. In kneel sitting (Japanese style), the average LLA, SS, PT, and PI were 31.8°, 38.3°, 14.2°, and 52.5°, respectively. In cross-legged sitting (Korean style), the average LLA, SS, PT, and PI were 9.8°, 13.4°, 38.3°, and 51.7°, respectively. LLA in standing (37.1°) and kneel sitting (31.8°) were very similar. Remarkable reduction in LLA was observed in Korean-style cross-legged sitting (9.8°), and LLA in chair sitting (17.9°) was about half of that in standing. SS was similar in standing (35.3°) and kneel sitting (38.3°), and it was reduced remarkably in cross-legged sitting (13.4°). PT was largest in cross-legged sitting (38.3°), and it was similar between standing (15.7°) and kneel sitting (14.2°). PIs were similar in all positions., Conclusions: The kneel sitting position did not show significant differences with the standing position when assessed using four parameters related to the sagittal spinopelvic alignment, whereas chair sitting and cross-legged sitting positions significantly altered the spinopelvic alignment compared to the standing position., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

In vertebrate retinal progenitor cells, the proneural factor Atoh7 exhibits a dynamic tissue and cellular expression pattern. Although the resulting Atoh7 retinal lineage contains all seven major cell types, only retinal ganglion cells require Atoh7 for proper differentiation. Such specificity necessitates complex regulation of Atoh7 transcription during retina development. The Notch signaling pathway is an evolutionarily conserved suppressor of proneural bHLH factor expression. Previous in vivo mouse genetic studies established the cell autonomous suppression of Atoh7 transcription by Notch1, Rbpj and Hes1. Here we identify four CSL binding sites within the Atoh7 proximal regulatory region and demonstrate Rbpj protein interaction at these sequences by in vitro electromobility shift, calorimetry and luciferase assays and, in vivo via colocalization and chromatin immunoprecipitation. We found that Rbpj simultaneously represses Atoh7 transcription using both Notch-dependent and -independent pathways.

Traumatic absence of the entire radial shaft in children has not been reported though there are a few reports of adult cases. We report a 5-year-old boy with traumatic absence of the entire right radial shaft. The Define's reconstruction procedure was chosen to localize the surgery only to the distal forearm and avoid further additional damage to the forearm muscles. The child's forearm was successfully reconstructed by the authors' modified Define's procedure, which was followed until his maturity. Hand function was well maintained., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Aims: Tattooing and use of permanent makeup (PMU) has dramatically increased over the last decade, with a concomitant increase in ink-related infections. The aim of this study was to determine whether micro-organisms are present, and if so, the number and their identification in the commercial tattoo and PMU inks available in the United States., Methods and Results: We surveyed 85 unopened tattoo and PMU inks, purchased from 13 companies. We incubated 100 μl of ink samples on trypticase soy agar plates for bacterial growth, 7H10 Middlebrook medium for mycobacterial growth, and Sabouraud dextrose medium for fungal growth. In total, 42 inks were contaminated with micro-organisms (49%). Thirty-three inks were contaminated with bacteria, 2 inks with fungi, and 7 inks had both bacterial and fungal growth. Mycobacteria were not detected in any of the examined tattoo and PMU inks. In 26 inks, microbial concentrations ranged between 10 1 and 10 3 CFU per ml, but higher counts (>10 3 CFU per ml) were recorded in 16 inks. We identified 83 bacteria by their 16S rDNA sequences, including 20 genera and 49 species. Strains of Bacillus spp. (53%) were dominant, followed by Lysinibacillus fusiformis (7%) and Pseudomonas aeruginosa (5%). Thirty-four (41%) possibly clinically relevant strains were identified, including P. aeruginosa, Dermacoccus barathri and Roseomonas mucosa, some of which have been previously reported to be associated with human skin infections., Conclusions: The results indicate that commercial tattoo and PMU inks on the US market surveyed in this study contain a wide range of micro-organisms, including pathogenic bacteria., Significance and Impact of the Study: Microbial contaminants in tattoo and PMU inks are an emerging safety concern for public health. This study provides evidence that microbial contamination of tattoo and PMU inks available in the United States is more common than previously thought and highlights the importance of monitoring these products for potentially pathogenic micro-organisms., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of the enthesis. The diagnosis has been mainly based on the chest or whole spine lateral plain film. Recently, chest or thoracolumbar computed tomography (CT) has been reported to be more reliable for the diagnosis of DISH. The purposes of this study were to investigate the prevalence and location of DISH and evaluate the prevalence of comorbidities, such as ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF), using whole spine CT., Methods: Whole spine CT scans of patients over 16 years of age who were examined at Cheju Halla General Hospital between February 2011 and December 2016 were reviewed for this study. The diagnosis of DISH was made according to the modified Resnick criteria. The prevalence of DISH in each age decade and its location were evaluated. Also, the prevalence of OPLL and OLF in DISH patients was investigated., Results: The overall incidence of DISH was 24.4% (40 of 164 cases). There was no case of DISH in patients in their 40s and younger. The percentile incidences of DISH in patients in their fifth, sixth, seventh, eighth, and ninth decades were 20.0% (4 of 20 cases), 32.3% (10 of 31 cases), 40.0% (10 of 25 cases), 34.5% (10 of 29 cases), and 27.3% (6 of 22 cases), respectively. A strong positive correlation between the age decade and the incidence of DISH was noted (r = 0.853, p = 0.007). DISH patients had higher incidences of OLF (22.5%) and OPLL (37.5%). The most common location of DISH was the middle thoracic spine (90.0%) followed by the lower thoracic spine (87.5%). There was one case of DISH involving only the cervical spine., Conclusions: The incidence of DISH diagnosed by CT was higher than we expected. Whole spine CT can be a valuable modality to evaluate the location of DISH in the cervical and lumbar spine and the comorbidity rates of OLF and OPLL., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

There exist some restrictions and difficulties in performing follicular unit extraction (FUE) in white-haired patients, for several reasons. In this paper, we introduce a novel technique for visualizing white hair during the punching procedure and graft preparation in FUE for white-haired patients. In white-haired older male patients, we dyed the surrounding scalp skin purple with a gentian violet solution-stained toothpick. Our method has several advantages: surgeons can easily focus on the center of the follicular unit and rapidly perform punching, they can recognize the condition of the harvested follicular units during FUE, and the hair transplant team can secure a clear view for trimming and loading into the implanter. We suggest that scalp dyeing in difficult FUE procedures, especially in patients with white hair, may be a simple method that provides a good visualization for donor site harvesting and for microdissection., Competing Interests: No potential conflict of interest relevant to this article was reported.

Even in an era of remarkable medical advances, there is an issue of why tuberculosis remains in the list of disastrous diseases, afflicting humans and causing suffering. There has not been a plausible answer to this, and it has been suggested that clinicians and medical scientists could presently not win the war against the tubercle bacilli. With regards to this issue, based on the authors' own clinical and research experiences, in this review, the available literature was revisited in order to address the raised questions and to provide recent information on characteristics of tubercle bacilli and possible ways to more effectively treat tuberculosis., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: The sacrococcygeal morphology of Arabs and Europeans has been studied using computed tomography (CT) or magnetic resonance imaging to determine the cause of coccydynia. Studies have suggested differences in sacrococcygeal morphology among ethnic groups. However, there are no data on the sacrococcygeal anatomy of Koreans., Methods: We conducted a retrospective analysis of 606 pelvic CT scans that were taken at Cheju Halla General Hospital between 2008 and 2014. Fractures of the sacrum or coccyx were excluded. Differences in the sacrococcygeal morphology among age groups stratified by decade of life and between genders were analyzed using sagittal plane pelvic CT scans. The morphological parameters studied were the sacral and coccygeal curved indexes, sacrococcygeal angle, intercoccygeal angle, coccygeal type, coccygeal segmental number, and sacrococcygeal fusion., Results: The average sacral and coccygeal curved indexes were 6.15 and 7.41, respectively. The average sacrococcygeal and intercoccygeal angles were 110° and 49°, respectively. Type II coccyx was most common, and the rate of sacrococcygeal fusion was 34%. There was a moderate positive correlation between age and the sacral curved index ( r = 0.493, p = 0.000) and a weak negative correlation between age and the coccyx curved index ( r = -0.257, p = 0.000). There was a weak negative correlation between age and the intercoccygeal angle ( r = -0.187, p = 0.000). The average intercoccygeal angle in males and females was 53.9° and 44.7°, respectively., Conclusions: The sacrum tended to be more curved and the coccyx straighter with age. The coccyx was straighter in females than males. Knowledge of the sacrococcygeal anatomy of Koreans will promote better understanding of anatomical differences among ethnicities and future studies on coccydynia., Competing Interests: No potential conflict of interest relevant to this article was reported.

Study Design: Cervical spine radiograms of 460 Jeju islanders., Purpose: To investigate the age-matched incidences and severity of the cervical disc degeneration and associated pathologic findings., Overview of Literature: Several related studies on the incidences of disc and Luschka's and facet joint degeneration have provided some basic data for clinicians., Methods: Cervical radiographs of 460 (220 males and 240 females) patients in their fourth to ninth decade were analyzed. Ninety patients in their third decade were excluded because of absence of spondylotic findings., Results: Overall incidence of cervical spondylosis was 47.8% (220 of 460 patients). The percentile incidences of spondylosis in the fourth, fifth, sixth, seventh, eighth and ninth decade was 13.2% (10 of 76 patients), 34.6% (37 of 107 patients), 58.9% (66 of 112 patients), 58.8% (50 of 85 patients), 70.3% (45 of 64 patients) and 75.0% (12 of 16 patients), respectively. The percentile incidences of one, two, three, four and five level spondylosis among 220 spondylosis patients was 45.5% (n=100), 34.1% (n=75), 15.0% (n=33), 4.5% (n=10), and 0.9% (n=2). Severity of disc degeneration ranged from ± to ++++, and was ± in 6.0% (24 segments), + in 49.6% (198 segments), ++ in 35.3% (141 segments), +++ in 9.0% (36 segments) and ++++ in 0.25% (one segment). Spurs and anterior ligament ossicle formed at the spondylotic segments, mostly at C4~6. The rate of posterior corporal spurs formation was very low. Olisthesis and ossification of the posterior longitudinal ligament were rarely combined with spondylosis. Cervical lordotic curve decreased gradually according to the progress of severity of spondylosis., Conclusions: The incidence of cervical spondylosis and number of spondylotic segments increase, and degeneration gradually becomes more severe with age., Competing Interests: No potential conflict of interest relevant to this article was reported.

Study Design: Retrospective case series., Purpose: To assess the effect of non-kyphotic aligned congenital C3-4 synostosis on the adjacent segment in 10 patients., Overview of Literature: In the cervical spine, fusion disease at the adjacent motion segments may be a risk factor for potential neurological compromise and death., Methods: Radiograms of 10 patients 13 to 69 years of age presenting with neck/shoulder discomfort or pain with or without trauma history were examined. C3-4 synostosis was found incidentally in all patients on routine examination radiographs of cervical spine., Results: Adjacent segment disease (ASD) was not found in the three patients younger than 39 years of age. Five of the 10 (50%) patients, including a 67-year-old man, did not develop spondylosis in any of the cervical mobile segments. Spondylosis was observed only in the caudal 1-2 mobile segments in the remaining five patients. The youngest was a 40-year-old male who had spondylosis in the two caudal mobile segments (C4-5 and C5-6). Spondylosis was limited to the two close caudal mobile segments and was not in the cranial segments. Flaring of the lower part of synostotic vertebra associated with advanced narrowed degenerate disc was evident in five patients., Conclusions: Mobile segment spondylosis in the individuals with congenital monosegment C3-4 synostosis over age of 40 years may be a natural manifestation of aging and is not solely an adjacent segment disease directly and fully related with congenital C3-4 synostosis.

Background: There are many potential causes of thrombocytopenia in patients with chronic hepatitis C (CHC)., Aims: We sought to determine the association between thrombopoietin (TPO) level, immature platelet fraction (IPF), immunoglobulin G (IgG) level, spleen size, and the platelet count in CHC., Methods: We studied a consecutive sample of patients enrolled in an observational study at a referral-based research center, excluding subjects based on eligibility criteria. TPO, glycocalicin, and von Willebrand Factor (vWF) levels were determined using stored sera. Hepatic fibrosis was assessed via transient elastography (TE) when available, and clinical laboratory values and radiologic data were obtained from the medical record. We performed analyses of the relationships between independent variables and the platelet count., Results: On univariate analysis, the following variables were significantly associated with the platelet count: age, alanine aminotransferase (ALT), direct bilirubin, total bilirubin, IPF, international normalized ratio (INR), spleen size, vWF, glycocalicin, fibrosis stage on liver biopsy, and TE (P-values all <0.05). A multivariable model determined that imputed TE score, TPO, IPF, and spleen size were independently associated with the platelet count (P-values all<0.05)., Conclusions: The platelet count in CHC is significantly associated with fibrosis, TPO level, IPF, and spleen size. Our findings challenge the proposed mechanism of decreased TPO levels or decreased bone marrow production of platelets as a cause of thrombocytopenia in CHC. Future studies focusing on the effects of fibrosis and splenomegaly on platelets may shed more light on the pathophysiology of thrombocytopenia in patients with CHC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Negative-pressure wound therapy (NPWT) induces angiogenesis and collagen synthesis to promote tissue healing. Although acetic acid soaks normalize alkali wound conditions to raise tissue oxygen saturation and deconstruct the biofilms of chronic wounds, frequent dressing changes are required., Methods: Combined use of NPWT and acetic acid irrigation was assessed in the treatment of chronic wounds, instilling acetic acid solution (1%) beneath polyurethane membranes twice daily for three weeks under continuous pressure (125 mm Hg). Clinical photographs, pH levels, cultures, and debrided fragments of wounds were obtained pre- and posttreatment. Tissue immunostaining (CD31, Ki-67, and CD45) and reverse transcription-polymerase chain reaction (vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor [VEGFR]; procollagen; hypoxia-inducible factor 1 alpha [HIF-1-alpha]; matrix metalloproteinase [MMP]-1,-3,-9; and tissue inhibitor of metalloproteinase [TIMP]) were also performed., Results: Wound sizes tended to diminish with the combined therapy, accompanied by drops in wound pH (weakly acidic or neutral) and less evidence of infection. CD31 and Ki-67 immunostaining increased (P<0.05) post-treatment, as did the levels of VEGFR, procollagen, and MMP-1 (P<0.05), whereas the VEGF, HIF-1-alpha, and MMP-9/TIMP levels declined (P<0.05)., Conclusions: By combining acetic acid irrigation with negative-pressure dressings, both the pH and the size of chronic wounds can be reduced and infections be controlled. This approach may enhance angiogenesis and collagen synthesis in wounds, restoring the extracellular matrix.