Protein-energy restriction-induced lipid metabolism disruption causes stable-to-progressive disease shift in Mycobacterium avium-infected female mice.

BACKGROUND: Disease susceptibility and progression of Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with multiple factors, including low body mass index (BMI). However, the specific impact of low BMI on MAC-PD progression remains poorly understood. This study aims to examine the progression of MAC-PD in the context of low BMI, utilising a disease-resistant mouse model. METHODS: We employed a MAC infection-resistant female A/J mouse model to compare the progression of MAC-PD under two dietary conditions: one group was fed a standard protein diet, representing protein-energy unrestricted conditions, and the other was fed a low protein diet (LPD), representing protein-energy restriction. FINDINGS: Our results reveal that protein-energy restriction significantly exacerbates MAC-PD progression by disrupting lipid metabolism. Mice fed an LPD showed elevated fatty acid levels and related gene expressions in lung tissues, similar to findings of increased fatty acids in the serum of patients who exhibited the MAC-PD progression. These mice also exhibited increased CD36 expression and lipid accumulation in macrophages upon MAC infection. In vitro experiments emphasised the crucial role of CD36-mediated palmitic acid uptake in bacterial proliferation. Importantly, in vivo studies demonstrated that administering anti-CD36 antibody to LPD-fed A/J mice reduced macrophage lipid accumulation and impeded bacterial growth, resulting in remarkable slowing disease progression. INTERPRETATION: Our findings indicate that the metabolic status of host immune cells critically influences MAC-PD progression. This study highlights the potential of adequate nutrient intake in preventing MAC-PD progression, suggesting that targeting CD36-mediated pathways might be a host-directed therapeutic strategy to managing MAC infection. FUNDING: This research was funded by the National Research Foundation of Korea, the Korea Research Institute of Bioscience and Biotechnology, and the Korea National Institute of Health.

Effect of United States Medical Licensing Examination Score Cutoffs on Recruitment of Underrepresented Applicants in the Urology Match.

OBJECTIVE: To determine how the use of United States Medical Licensing Examination (USMLE) score cutoffs during the screening process of the Urology Residency Match Program may affect recruitment of applicants who are underrepresented in medicine (URM). MATERIALS AND METHODS: Deidentified data from the Association of American Medical Colleges' (AAMC) Electronic Residency Application Service (ERAS) system was reviewed, representing all applicants to our institution's urology residency program from 2018 to 2022. We analyzed self-reported demographic variables including race/ethnicity, age, sex/gender, as well as USMLE Step 1 and Step 2 scores. Chi-square tests and ANOVA were used to determine the association between race/ethnicity and other sociodemographic factors and academic metrics. Applicants were stratified according to USMLE Step 1 cutoff scores and the distribution of applicants by race/ethnicity was assessed using a Gaussian nonlinear regression fit. RESULTS: A total of 1258 applicants submitted applications to our program during the 5-year period, including 872 males (69.3%) and 386 females (30.7%). Most applicants were White (43.5%), followed by Asian (28.3%), Hispanic/Latino (11.7%), and Black (7.0%). There was an association between race/ethnicity and USMLE scores. Median USMLE Step 1 scores for White, Asian, Hispanic/Latino, and Black applicants were 242, 242, 237, and 232, respectively (P < .001). As cutoff score increases, percentage of URM applicants decreases. CONCLUSION: The use of cutoffs based on USMLE scores disproportionately affects URM applicants. Transitioning from numeric scores to pass/fail may enhance holistic review processes and increase the representation of URM applicants offered interviews at urology residency programs.

Successful Reduction of Unilateral Zygoma Fracture Following Bilateral Malar Reduction Surgery.

Malar reduction surgery can increase its susceptibility to fractures in case of trauma. Patients who had malar reduction surgery and sustained a zygoma fracture pose unique challenges for treatment and management. This is a case of a 28-year-old female patient who presented with a unilateral zygoma fracture following bilateral malar reduction and augmentation rhinoplasty 6 years ago. Physical examination revealed a clicking sound when opening the mouth at the right zygomatic buttress and a depressed preauricular area, suggesting arch fracture. Computed tomography imaging demonstrated a loosened screw at the right zygomatic buttress and a depressed arch fracture. She wanted to remove all plates and treat her right fractured zygoma with absorbable materials. Through the bilateral intraoral incisions, the authors removed the plates and screws and reduced the depression with the Langenbeck elevator through the same right intraoral incision without fixation. The reduction was well-maintained without complications based on postoperative plain x-rays 1 month after surgery. She reported that the pain was mostly gone and that she did not hear any abnormal sounds when opening her mouth after the surgery. In this case, if the zygomaticomaxillary buttress is minimally displaced, but the zygomatic arch fracture is significantly depressed, the authors believe that fracture reduction with only an intraoral incision would be enough to achieve an optimal outcome. If the plates and screws used in the previous malar reduction are not well maintained, it may be necessary to remove them.

Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy.

BACKGRUOUND: Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes. METHODS: We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin. RESULTS: Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. CONCLUSION: We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

The Boot Camp Model in Urology: Preparing PGY1 Urology Interns for Practice.

PURPOSE OF REVIEW: The purpose of this review is to highlight literature regarding resident boot camps published across surgical specialties with a focus on urology. Herein, we discuss different boot camp iterations, their results, and the integration of simulation into their curriculum. We review program elements such as curriculum, course length, and efficacy as well as areas for continued investigation. RECENT FINDINGS: The field of urology has grown in both the breadth of knowledge and the complexity of procedures. With urology now being an integrated surgical subspecialty, interns often start on the urology service despite limited experience navigating this unique specialty. The boot camp model is one method by which interns and junior residents participate in consolidated training programs to best prepare them for a patient-facing role and the day-to-day demands of residency. Urology programs, both in the USA and abroad, have begun integrating boot camps into their training programs with positive results. Urology boot camps can be a valuable part of training programs for interns to quickly establish medical knowledge, skills, and efficiency. Boot camps should be easily accessible, have sufficient support from institutions, and provide effective training through various methods such as didactics and simulation.

Chemotherapy Refractory Spindle-Cell Rhabdomyosarcoma of the Bladder Treated With Consolidative Ovarian-Sparing Radical Surgery.

We present a case of chemotherapy refractory spindle cell rhabdomyosarcoma of the lower urinary tract in a 15-month-old female that ultimately required consolidative surgery with cystectomy, urethrectomy, ovarian-sparing hysterectomy, bilateral salpingectomy, anterior vaginal wall resection, and bilateral pelvic lymph node dissection. Genitourinary reconstruction was performed by ileal conduit creation and vaginoplasty. After completion of her maintenance postoperative chemotherapy regimen, the patient has remained disease-free for approximately 27 months.

Preference Signaling in the 2022 Urology Residency Match - The Applicant Perspective.

OBJECTIVE: To evaluate the applicant experience with preference signaling during the 2022 Urology Residency Match. METHODS: An anonymous electronic survey was emailed to all urology residency applicants who applied to Rutgers Robert Wood Johnson Medical School during the 2021-2022 application cycle. The survey collected information regarding applicant demographics, applicant characteristics, preference signal destinations, match outcomes, and attitude towards preference signaling. RESULTS: A total of 601 applicants applied to the 2022 Urology Residency Match, 283 of which applied to the urology residency program at Rutgers Robert Wood Johnson Medical School. Of the 283 applicants, 53 (19%) responded to our survey. Rate of interview for preference signaled programs was 54.23%, with a significantly lower rate of interview for comparative, non-signaled programs (40.54%; P = .001). Of respondents, 14.29%, 26.19%, and 35.71% matched to their home program, a program they signaled, or a program where they completed an away rotation, respectively. 96% of applicants favored continuation of the preference signaling program. CONCLUSION: Our study suggests preference signaling in the 2022 Urology Match may have been an effective method of expressing interest in a program. Respondents of our survey overwhelmingly favor continuation of the program in future urology matches. However, it may not address the underlying, growing problem of the increasing application burden on applicants and programs alike. We encourage more comprehensive studies to further clarify the effects of preference signaling on the Urology Match.

Plasma Membrane Localization of CD36 Requires Vimentin Phosphorylation; A Mechanism by Which Macrophage Vimentin Promotes Atherosclerosis.

Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis. We demonstrated that vimentin null (Vim -/ - ) mouse peritoneal macrophages take up less oxidized LDL (oxLDL) than vimentin wild type (Vim +/+) macrophages. Despite less uptake of oxLDL in Vim -/ - macrophages, Vim +/+ and Vim -/ - macrophages did not show difference in expression of CD36 known to mediate oxLDL uptake. However, CD36 localized in plasma membrane was 50% less in Vim -/ - macrophages than in Vim +/+ macrophages. OxLDL/CD36 interaction induced protein kinase A (PKA)-mediated vimentin (Ser72) phosphorylation. Cd36 -/ - macrophages did not exhibit vimentin phosphorylation (Ser72) in response to oxLDL. Experiments using phospho-mimetic mutation of vimentin revealed that macrophages with aspartate-substituted vimentin (V72D) showed more oxLDL uptake and membrane CD36. LDL receptor null (Ldlr -/ - ) mice reconstituted with Vim -/ - bone marrow fed a western diet for 15 weeks showed 43% less atherosclerotic lesion formation than Ldlr -/ - mice with Vim +/+ bone marrow. In addition, Apoe -/ -Vim- / - (double null) mice fed a western diet for 15 weeks also showed 57% less atherosclerotic lesion formation than Apoe -/ - and Vim +/+mice. We concluded that oxLDL via CD36 induces PKA-mediated phosphorylation of vimentin (Ser72) and phosphorylated vimentin (Ser72) directs CD36 trafficking to plasma membrane in macrophages. This study reveals a function of vimentin in CD36 trafficking and macrophage foam cell formation and may guide to establish a new strategy for the treatment of atherosclerosis.

Understanding Metabolic Regulation Between Host and Pathogens: New Opportunities for the Development of Improved Therapeutic Strategies Against Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb) causes chronic granulomatous lung disease in humans. Recently, novel strategies such as host-directed therapeutics and adjunctive therapies that enhance the effect of existing antibiotics have emerged to better control Mtb infection. Recent advances in understanding the metabolic interplay between host immune cells and pathogens have provided new insights into how their interactions ultimately influence disease outcomes and antibiotic-treatment efficacy. In this review, we describe how metabolic cascades in immune environments and relevant metabolites produced from immune cells during Mtb infection play critical roles in the progression of diseases and induction of anti-Mtb protective immunity. In addition, we introduce how metabolic alterations in Mtb itself can lead to the development of persister cells that are resistant to host immunity and can eventually evade antibiotic attacks. Further understanding of the metabolic link between host cells and Mtb may contribute to not only the prevention of Mtb persister development but also the optimization of host anti-Mtb immunity together with enhanced efficacy of existing antibiotics. Overall, this review highlights novel approaches to improve and develop host-mediated therapeutic strategies against Mtb infection by restoring and switching pathogen-favoring metabolic conditions with host-favoring conditions.

Multi-institutional Clinical Tool for Predicting High-risk Lesions on 3Tesla Multiparametric Prostate Magnetic Resonance Imaging.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer detection without careful patient selection may lead to excessive resource utilization and costs. OBJECTIVE: To develop and validate a clinical tool for predicting the presence of high-risk lesions on mpMRI. DESIGN, SETTING, AND PARTICIPANTS: Four tertiary care centers were included in this retrospective and prospective study (BiRCH Study Collaborative). Statistical models were generated using 1269 biopsy-naive, prior negative biopsy, and active surveillance patients who underwent mpMRI. Using age, prostate-specific antigen, and prostate volume, a support vector machine model was developed for predicting the probability of harboring Prostate Imaging Reporting and Data System 4 or 5 lesions. The accuracy of future predictions was then prospectively assessed in 214 consecutive patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic, calibration, and decision curves were generated to assess model performance. RESULTS AND LIMITATIONS: For biopsy-naïve and prior negative biopsy patients (n=811), the area under the curve (AUC) was 0.730 on internal validation. Excellent calibration and high net clinical benefit were observed. On prospective external validation at two separate institutions (n=88 and n=126), the machine learning model discriminated with AUCs of 0.740 and 0.744, respectively. The final model was developed on the Microsoft Azure Machine Learning platform (birch.azurewebsites.net). This model requires a prostate volume measurement as input. CONCLUSIONS: In patients who are naïve to biopsy or those with a prior negative biopsy, BiRCH models can be used to select patients for mpMRI. PATIENT SUMMARY: In this multicenter study, we developed and prospectively validated a calculator that can be used to predict prostate magnetic resonance imaging (MRI) results using patient age, prostate-specific antigen, and prostate volume as input. This tool can aid health care professionals and patients to make an informed decision regarding whether to get an MRI.

Enzymatic Synthesis of ß-Glucosylglycerol and Its Unnatural Glycosides Via ß-Glycosidase and Amylosucrase.

ß-Glucosylglycerol (ß-GG) and their derivatives have potential applications in food, cosmetics and the healthcare industry, including antitumor medications. In this study, ß-GG and its unnatural glycosides were synthesized through the transglycosylation of two enzymes, Sulfolobus shibatae ß-glycosidase (SSG) and Deinococcus geothermalis amylosucrase (DGAS). SSG catalyzed a transglycosylation reaction with glycerol as an acceptor and cellobiose as a donor to produce 56% of ß-GGs [ß-D-glucopyranosyl-(1→1/3)-D-glycerol and ß-D-glucopyranosyl- (1→2)-D-glycerol]. In the second transglycosylation reaction, ß-D-glucopyranosyl-(1 → 1/3)-Dglycerol was used as acceptor molecules of the DGAS reaction. As a result, 61% of α-Dglucopyranosyl-( 1→4)-ß-D-glucopyranosyl-(1→1/3)-D-glycerol and 28% of α-D-maltopyranosyl- (1→4)-ß-D-glucopyranosyl-(1→1/3)-D-glycerol were synthesized as unnatural glucosylglycerols. In conclusion, the combined enzymatic synthesis of the unnatural glycosides of ß-GG was established. The synthesis of these unnatural glycosides may provide an opportunity to discover new applications in the biotechnological industry.

Skin depigmenting action of silkworm (Bombyx mori L.) droppings in zebrafish.

The excrement of silkworms (Bombyx mori L.), referred to here as silkworm droppings (SDs), is used as a traditional drug in eastern medicine to treat skin diseases such as urticaria and atopy. However, the depigmentation effects of SDs have not previously been evaluated. We focused on the depigmentation effect of a methanol extract of SDs and isolated components of the extract using a zebrafish model system. (+)-Dehydrovomifoliol (M-1), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one (M-2), (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (M-3), roseoside (M-4), and citroside A (M-5) were isolated from only SDs extract (SDE), and chemical structures were identified through spectroscopic methods. Toxicity of SDE was evaluated by assessing its effect on the viability of human fibroblast cells and the hatching rate of zebrafish embryos. In addition, the depigmentation ability of SDE and isolated constituents was evaluated using a zebrafish model. Binary threshold, histograms, and the size of the black spots on the dorsal region of zebrafish larvae were analyzed using image analysis tools. Finally, SDE is a non-toxic material and has a dose-dependent depigmentation effect in zebrafish larvae. Moreover, various doses of compounds isolated from SDE, namely, M-1 to M-5, had a depigmentation effect. In particular, M-5 inhibited melanin synthesis in melanocytes stimulated by α-melanocyte stimulating hormone (α-MSH). Together, our results suggest that SDs can be used for depigmentation purposes in health and/or cosmetic applications.

Institutional Learning Curve Associated with Implementation of a Magnetic Resonance/Transrectal Ultrasound Fusion Biopsy Program Using PI-RADS™ Version 2: Factors that Influence Success.

INTRODUCTION: We assessed the institutional learning curve associated with adopting fusion biopsy using PI-RADS™ (Prostate Imaging-Reporting and Data System) Version 2 (v2) to detect clinically significant prostate cancer, defined as Gleason 7 or greater in men with prior negative biopsies, and identified patient and technical factors that predict success in detecting clinically significant prostate cancer. METHODS: A total of 113 consecutive patients with at least 1 prior negative biopsy and multiparametric magnetic resonance imaging examination of the prostate with a PI-RADS 3 or greater index lesion underwent fusion biopsy at a single academic center previously naïve to fusion biopsy technology. Outcomes include detection rates for Gleason 6 cancer, clinically significant prostate cancer and any cancer. Multiple logistic regression with model selection was used to select covariates having significant effects on the outcome. RESULTS: Prostate cancer was identified in 52% of patients with prior negative prostate biopsies. Among the patients diagnosed with prostate cancer 80% had clinically significant cancer. The clinically significant prostate cancer detection rates using fusion biopsy when a PI-RADS 3, 4 or 5 index lesion was present on multiparametric magnetic resonance imaging were 6%, 46% and 66%, respectively. PI-RADS v2 score had a predictive accuracy (AUC) of 0.79 for clinically significant prostate cancer detection. Institutional experience over time, magnetic resonance imaging estimated prostate volume and PI-RADS v2 score were independent predictors of clinically significant prostate cancer using fusion biopsy. CONCLUSIONS: Since fusion biopsy is a highly technique driven process, development of internal quality measures to assess the institutional learning curve and the quality of PI-RADS v2 scoring is critical with the adoption of this technology.

Three New Isoprenylated Flavonoids from the Root Bark of Morus alba.

Phytochemical investigation of the root bark of Morus alba has led to the isolation and identification of three new isoprenylated flavonoids, namely sanggenon U (1), sanggenon V (2), and sanggenon W (3), along with four known isoprenylated flavonoids: euchrenone a7 (4), sanggenon J (5), kuwanon E (6), and kuwanon S (7). All compounds were isolated by repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 open column chromatography. The structure of the compounds were determined based on spectroscopic analyses, including nuclear magnetic resonance (NMR), mass spectrometry (MS), circular dichroism (CD), and infrared (IR). In addition, compounds 1-4 were isolated for the first time from the root bark of M. alba in this study.

Botulinum Toxin A Upregulates Rac1, Cdc42, and RhoA Gene Expression in a Dose-Dependent Manner: In Vivo and in Vitro Study.

UNLABELLED: Angiogenesis is the development of new capillaries from existing blood vessels and is a prerequisite for the wound-healing process. Many lines of scientific evidences have shown that complicated roles of small guanosine triphosphatases (GTPases) (ras-related C3 botulinum toxin substrate 1 [Rac1], cell division control protein 42 [Cdc42], and ras homolog gene family, member A [RhoA]) in regulation of signal transduction pathways exist to transmit distinct cellular effects on the modulation of actin cytoskeleton remodeling such as cell cycle progression, cell survival, and cell motility. In addition, these small GTPases activate mitogen-activated protein kinase kinase kinases (MAP3Ks) leading to activated mitogen-activated protein kinase kinases (MAPKK), mitogen-activated protein kinase (MAPK), and various transcription factors such as vascular endothelial growth factor with involvement of MAPK signaling pathways.In this study, the authors hypothesized that botulinum toxin A increases angiogenesis via the expression of small GTPases in vivo and in vitro studies.In vivo experiment, 24 Sprague-Dawley rats were randomly divided into 2 groups: a control group and a botulinum toxin A group. Five days prior to superiorly based transverse rectus abdominis myocutaneous flap elevation, the botulinum toxin A (BoTA) group was pretreated with BoTA, while the control group was pretreated with normal saline. quantitative real-time polymerase chain reaction was performed to evaluate the expression of Rac1, RhoA, and Cdc42.The angiogenic effects of botulinum toxin A on human dermal fibroblasts were measured in vitro experiment. To understand the mechanism of botulinum toxin A on small GTPases production of fibroblasts, Rac1, Cdc42, and RhoA were measured using qRT-PCR.The relative messenger ribonucleic acid expression of Rac1, RhoA, and Cdc42 was significantly higher in the BoTA group than in the control group, in every zone and pedicle muscle, on postoperative days 1, 3, and 5. Levels of these molecules increased significantly in human dermal fibroblasts grown in the presence of BoTA compared with control group over 5 IU.Our in vivo and in vitro studies suggest that administration of BoTA upregulates the expression of RhoA, Rac1, and Cdc42 in a dose-dependent manner. MAPK signaling pathway might be involved in BoTA-induced angiogenesis mechanism. LEVEL OF EVIDENCE: N/A.

Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer.

UNLABELLED: Appropriate patient selection for active surveillance is challenging.Our study of 217 patients demonstrated that the preoperative absolute neutrophil and lymphocyte counts were better predictors of aggressive oncologic features than were the neutrophil-to-lymphocyte ratio in the assessment of low-risk prostate cancer patients. Our findings suggest that routine hematologic workup could be used to further stratify low-risk prostate cancer patients. INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. MATERIALS AND METHODS: We identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. RESULTS: On multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148-2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043-2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258-14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 10(9)/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043-1.173). CONCLUSION: NLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.

Foreign body reactions may not influence the keloid recurrence.

PURPOSE: The foreign body reactions are comprised of macrophages and foreign body giant cells and are considered possible risk factors for recurrence in several conditions. The purpose of this study was to determine the effect of pathologically proven foreign body reactions on the recurrence of the auricular keloids. METHODS: This study was carried out in 76 cases in 70 patients reaching the pathologic diagnosis of auricular keloids from March 2006 to February 2012. Patients with auricular keloids were included in the study according to the following criteria: The keloid scar was caused by ear piercing and confirmed pathologically; surgical excision with primary closure was performed; and female patients who have not underwent any previous treatments. To compare any differences of recurrence rate between categorical variables (the presence/absence of foreign body reactions), Fisher's exact tests were used. All patients completed the treatment protocol with a follow-up interval of 18 months. RESULTS: Of these patients, 90.9% (69 keloids) had successful irradication of their auricular keloids, whereas 9.2% (seven keloids) had recurrences. Of the seven recurrent cases, two exhibited foreign body reactions at pathology, while five revealed no foreign body reactions (28.6% vs. 71.4%, P = 0.092). CONCLUSIONS: Detection of foreign body reactions in keloid tissue may not predict recurrence in auricular keloids.

Phytochemical constituents from the florets of tiger grass Thysanolaena latifolia from Nepal.

Phytochemical investigation on the florets of Thysanolaena latifolia leads to the isolation of a new compound 6″-O-acetylorientin-2″-O-α-L-rhamnopyranoside (1), named amrisoside and other 34 known compounds. The chemical structures of the compounds were determined from the interpretation of spectroscopic data including NMR, MS, and IR. This is the first report of phytochemical constituents from the monotypic genus Thysanolaena.

The Protective Effects of Botulinum Toxin A Against Flap Necrosis After Perforator Twisting and Its Underlying Molecular Mechanism in a Rat Model.

PURPOSE: The purpose of this study was to examine our hypotheses that botulinum toxin A (BoTA) protect necrosis of perforator flap from perforator twisting. METHODS: Twenty-four rats were randomly divided into 2 groups. Twelve International Units of BoTA versus 1.2 mL normal saline was injected subdermally 3 days before flap elevation. In each group, bilateral before deep inferior epigastric perforator (DIEP) flaps, 5 × 3 cm in size, were created. The right and left (180 and 360 degrees of perforator twisting) DIEP flaps were separated. At 1 and 3 days postoperatively, skin above the perforator of the DIEP flaps was harvested to examine the degrees of gene expressions. Final survival percentage of flap and histology were assessed at postoperative day 5. RESULTS: The survival percentage of flap was significantly higher in the BoTA group than in the control group at both DIEP flaps after 180 and 360 degrees of perforator twisting at postoperative day 5 (95.23 ± 2.85% vs 91.00 ± 3.77%; P = 0.021 and 91.59 ± 2.87% vs 30.03 ± 6.91%; P < 0.001, respectively).Higher fibroblast density, enhanced epithelial necrosis, and inflammation were noted in the control group than in the BoTA group. In 180 degrees of perforator twisting group, BoTA may augment angiogenesis possibly via nuclear factor-κB-induced destabilization and the nuclear factor-κB/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway, whereas in the 360 degrees of perforator twisting group, the mechanistic target of rapamycin/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway may participate in BoTA-induced effective angiogenesis. CONCLUSIONS: We demonstrated that pretreatment with BoTA protects perforator flap caused by perforator at the pathological and molecular level using an experimental rat model.

Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito.

A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides--adonioside A (1) and adonioside B (6)--as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3).