Acetogenins from the Stem of Uvaria rufa and Their Cytotoxic Activity.

Four new adjacent bis-tetrahydrofuran acetogenins, bullacin C (7), uvarirufin (9), and uvariasolins III (12) and IV (13), along with 11 known acetogenins, were isolated from the stem of Uvaria rufa. Their structures were elucidated based on spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and MALDI-MS/MS of the lithium adducts. Absolute configurations were assigned using Mosher ester analysis and ECD measurements. Uvarirufin (9) possesses a unique C-39 skeleton among acetogenins. Most tested acetogenins exhibited cytotoxicity against human cancer cell lines (HCT 116, 22Rv1, MDA-MB-435, OVCAR3). Squamocin (8) and uvarirufin (9) were found to be the most potent, with an IC50 value of 1.2 µM for both in HCT 116 colon cancer cells. Additionally, a new application of Dragendorff's reagent is proposed herein for the TLC detection of acetogenins.

The purple mangosteen (Garcinia mangostana): Defining the anticancer potential of selected xanthones.

The purple mangosteen (Garcinia mangostana) is a popular Southeast Asian fruit that has been used traditionally for its health promoting benefits for years. Unique to the mangosteen are a class of phytochemicals known as xanthones that have been reported to display significant anti-cancer and anti-tumor activities, specifically through the promotion of apoptosis, targeting of specific cancer-related proteins, or modulation of cell signaling pathways. α-Mangostin, the most abundant xanthone isolated from the mangosteen, has received substantial attention as it has proven to be a potent phytochemical, specifically as an anticancer agent, in numerous different cancer cell studies and cancer animal models. While the mechanisms for these anticancer effects have been reported in many studies, lesser xanthones, including gartanin, ß-mangostin, γ-mangostin, garcinone C, and garcinone E, and mangosteen extracts from the pericarp, roots, rind, and stem show promise for their anticancer activity but their mechanisms of action are not as well developed and remain to be determined. Mangosteen products appear safe and have been well tolerated in human clinical trials where they show antioxidant activity, though their clinical anticancer activity has not yet been evaluated. This review summarizes the work that has been done to explore and explain the anticancer and antitumor activities of α-mangostin, lesser xanthones, and mangosteen extracts in vitro, in vivo, and in humans in various cancers.

Traumatic Pediatric Fatalities: Are They Preventable?

INTRODUCTION: Trauma related injury remains the leading cause of mortality in pediatric patients, many of which are preventable. The goal of our study was to identify the mechanism of injury (MOI) in pediatric trauma-related fatalities and determine if these injuries were preventable to direct future injury prevention efforts within trauma programs. METHODS: After IRB approval, a retrospective, single-institution review of pediatric (age ≤18) trauma fatalities from 2010 to 2019 was performed. MOI, use of protective devices, demographics, and whether the injury was preventable were collected. Patients were divided into five age cohorts, and frequencies and proportions were used to summarize data. Bivariate testing was done using Fisher's exact and Monte Carlo estimates for the exact test. RESULTS: MOI was found to vary by age with non-accidental trauma found to be the most common cause of trauma related deaths in children <1 (88.5%) and 1-4 (33.3%). MVC was the most common MOI in children >5 y, with 68.4% in the 5-9, 34.4% in the 10-14, and 45.8% in the 15-18 age group. The majority of fatalities resulted from a preventable injury (P < 0.0001) in the younger children with a negative association as age increased: 92.3% <1, 53.3% in 1-4, 36.8% in 5-9, 46.9% in 10-14 and 48.6% in 15-18. Of the preventable injuries, non-accidental trauma was the most common MOI in children <5, while GSW was the most common MOI in children >10. CONCLUSIONS: This study demonstrates many pediatric fatalities are the result of a preventable traumatic injury. This data can guide focused traumatic injury prevention efforts.

Pharmacokinetic characterization of carnosol from rosemary (Salvia Rosmarinus) in male C57BL/6 mice and inhibition profile in human cytochrome P450 enzymes.

Rosemary (Salvia Rosmarinus) is a rich source of dietary diterpenes with carnosol as one of the major polyphenols used to standardize rosemary extracts approved as a food preservative, however, at present there is not any information on the murine pharmacokinetic profile of carnosol or its potential for drug interactions. The present study utilizes cell-free, cell-based, and animal-based experiments to define the pharmacokinetic profile of the food based phytochemical carnosol. Mice were administered carnosol (100 mg/kg body weight) by oral gavage and plasma levels were analyzed by LC-MS/MS to establish a detailed pharmacokinetic profile. The maximum plasma concentration exceeded 1 µM after a single administration. The results are significant as they offer insights on the potential for food-drug interactions between carnosol from rosemary and active pharmaceutical ingredients. Carnosol was observed to inhibit selected CYP450 enzymes and modulate metabolic enzymes and transporters in in vitro assays.

Infant Essential Fatty Acid Status Is Not Associated With Postoperative Wound Complication Severity.

BACKGROUND: Neonates are susceptible to postoperative wound complications (POWCs), as prematurity, hypoxia, steroid use, immunosuppression, and malnutrition are all common comorbidities. Critically ill infants, dependent on parenteral nutrition, are at even further risk of developing essential fatty acid deficiency (EFAD). We hypothesized that POWC severity and EFAD were associated because of increased susceptibility to infections and impaired wound healing seen with EFAD. METHODS: Institutional review board-approved (OUHSC10554), retrospective review from our academic Level IV Neonatal Intensive Care Unit. Infants aged <1 y who underwent a fascial-compromising gastrointestinal surgery from June 1, 2015, to March 15, 2019, and who had essential fatty acids (EFAs) measured ±2 wk from surgery were included. Three blinded investigators independently categorized POWC using the World Union of Wound Healing Society Surgical Wound Grading System. Infants were categorized into three groups: no POWC, POWC Grades 1 and 2 (superficial tissue nonintegrity), and POWC Grades 3 and 4 (deep tissue nonintegrity and complete dehiscence). EFA status and other possible POWC-associated factors were analyzed to determine any association with wound severity. RESULTS: Fifty infants met the inclusion criteria. Half (25/50) had no POWC, 30% (15/50) had Grade 1 or 2, and 20% (10/50) had Grade 3 or 4. We found no association between EFAD and POWC severity. CONCLUSIONS: In our cohort, EFA status did not predict POWC severity. At this time, we cannot suggest delaying elective surgical procedures to correct EFAD as an approach to preventing POWC.

Carnosic acid promotes degradation of the androgen receptor and is regulated by the unfolded protein response pathway in vitro and in vivo.

Androgen deprivation therapy in prostate cancer is extremely effective; however, due to the continuous expression and/or mutagenesis of androgen receptor (AR), the resistance to antihormonal therapy is a natural progression. Consequently, targeting the AR for degradation offers an alternate approach to overcome this resistance in prostate cancer. In this study, we demonstrate that carnosic acid, a benzenediol diterpene, binds the ligand-binding domain of the AR and degrades the AR via endoplasmic reticulum (ER) stress-mediated proteasomal degradative pathway. In vitro, carnosic acid treatment induced degradation of AR and decreased expression of prostate-specific antigen in human prostate cancer cell lines LNCaP and 22Rv1. Carnosic acid also promoted the expression of ER proteins including BiP and CHOP in a dose-dependent manner. Downregulation of CHOP by small interfering RNA somewhat restored expression of AR suggesting that AR degradation is dependent on ER stress pathway. Future studies will need to evaluate other aspects of the unfolded protein response pathway to characterize the regulation of AR degradation. Furthermore, cotreating cells individually with carnosic acid and proteasome inhibitor (MG-132) and carnosic acid and an ER stress modulator (salubrinal) restored protein levels of AR, suggesting that AR degradation is mediated by ER stress-dependent proteasomal degradation pathway. Degradation of AR and induction of CHOP protein were also evident in vivo along with a 53% reduction in growth of xenograft prostate cancer tumors. In addition, carnosic acid-induced ER stress in prostate cancer cells but not in normal prostate epithelial cells procured from patient biopsies. In conclusion, these data suggest that molecules such as carnosic acid could be further evaluated and optimized as a potential therapeutic alternative to target AR in prostate cancer.

Targeting the mammalian target of rapamycin pathway with everolimus: implications for the management of metastatic breast cancer.

The inhibitors of mammalian target of rapamycin (mTOR) have documented antitumor activity via disruption of various signaling pathways leading to impaired cellular growth, proliferation, and survival. In preclinical studies, mTOR inhibitors use in combination with hormonal therapy has shown promising results in overcoming endocrine resistance in breast cancer cells. The role of everolimus in breast cancer was established in the Breast Cancer Trial of Oral Everolimus-2 (BOLERO-2) trial in combination with exemestane for patients with advanced metastatic hormone receptor-positive (HR+) breast cancer, who relapsed after initial hormonal manipulation. The study met its primary endpoint of significant improvement in progression free survival (PFS) with a median time to progression of 6.9 months in the combination group versus 2.8 months in exemestane group. Favorable improvements in PFS were reported across all patient subgroups regardless of age, Eastern Cooperative Oncology Group performance status, number of prior therapies, and presence of visceral metastases. Adverse events were mostly mild to moderate in severity and consistent with the known safety profile of everolimus. Major toxicities reported include stomatitis, non-infectious pneumonitis, and hyperglycemia. The purpose of this review is to discuss the role of everolimus as a valuable component in advanced metastatic breast cancer and delineate current strategies to prevent and manage the most common toxicities associated with this combination regimen.

Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells.

The mangosteen (Garcinia mangostana) fruit has been a popular food in Southeast Asia for centuries and is increasing in popularity in Western countries. We identified α-Mangostin as a primary phytochemical modulating ER stress proteins in prostate cancer cells and propose that α-Mangostin is responsible for exerting a biological effect in prostate cancer cells. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two patients undergoing radical prostatectomy were treated with α-Mangostin and evaluated by RT-PCR, Western blot, fluorescent microscopy and siRNA transfection to evaluate ER stress. Next, we evaluated α-Mangostin for microsomal stability, pharmacokinetic parameters, and anti-cancer activity in nude mice. α-Mangostin significantly upregulated ER stress markers in prostate cancer cells. Interestingly, α-Mangostin did not promote ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. CHOP knockdown enhanced α-Mangostin-induced apoptosis in prostate cancer cells. α-Mangostin significantly suppressed tumor growth in a xenograft tumor model without obvious toxicity. Our study suggests that α-Mangostin is not the only active constituent from the mangosteen fruit requiring further work to understand the complex chemical composition of the mangosteen.

Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) - protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids.

INTRODUCTION: Uterine fibroids affect 30%-77% of reproductive-age women and are a significant cause of infertility. Surgical myomectomies can restore fertility, but they often have limited and temporary benefits, with postoperative complications such as adhesions negatively impacting fertility. Existing medical therapies, such as oral contraceptives, gonadotropin hormone-releasing hormone (GnRH) analogues and GnRH antagonists, can manage fibroid symptoms but are not fertility friendly. This study addresses the pressing need for non-hormonal, non-surgical treatment options for women with fibroids desiring pregnancy. Previous preclinical and clinical studies have shown that epigallocatechin gallate (EGCG) effectively reduces uterine fibroid size. We hypothesise that EGCG from green tea extract will shrink fibroids, enhance endometrial quality and increase pregnancy likelihood. To investigate this hypothesis, we initiated a National Institute of Child Health and Human Development Confirm-funded trial to assess EGCG's efficacy in treating women with fibroids and unexplained infertility. METHODS AND ANALYSIS: This multicentre, prospective, interventional, randomised, double-blinded clinical trial aims to enrol 200 participants with fibroids and unexplained infertility undergoing intrauterine insemination (IUI). Participants will be randomly assigned in a 3:1 ratio to two groups: green tea extract (1650 mg daily) or a matched placebo, combined with clomiphene citrate-induced ovarian stimulation and timed IUI for up to four cycles. EGCG constitutes approximately 45% of the green tea extract. The primary outcome is the cumulative live birth rate, with secondary outcomes including conception rate, time to conception, miscarriage rate, change in fibroid volume and symptom severity scores and health-related quality of life questionnaire scores. ETHICS AND DISSEMINATION: The FRIEND trial received approval from the Food and Drug adminstration (FDA) (investigational new drug number 150951), the central Institutional Review Board (IRB) at Johns Hopkins University and FRIEND-collaborative site local IRBs. The data will be disseminated at major conferences, published in peer-reviewed journals and support a large-scale clinical trial. TRIAL REGISTRATION NUMBER: NCT05364008.

Variations in procedure time based on surgery resident postgraduate year level.

BACKGROUND: With increasing scrutiny being placed on the allocation of health care dollars, data supporting the increased resources used to teach residents in the operating room (OR) are lacking. METHODS: All cases of patients undergoing laparoscopic cholecystectomies (LCs) and pancreaticoduodenectomies (PDs) from July 1, 2006 to July 1, 2011 were analyzed. Procedures were excluded based on the following: more than one resident listed in the operative report, with the exception of interns; LC requiring cholangiogram or conversion to an open procedure; or if a PD required additional procedures. Multiple linear regression was used to evaluate the association between procedure time and postgraduate year (PGY), adjusting for patient age and estimated blood loss. RESULTS: A total of 236 PDs and 357 LCs were included in the study. For LCs, after multiple linear regression, the association between procedure time and resident PGY was marginally significant (P = 0.0519) and suggested an inverse relationship; for every increase in resident PGY, there was a 2.66-min decrease in OR time. Based on our institution's figure of $18.13/min of OR time, the cost difference between PGYs 1 and 5 performing a LC would be $192.90 per case. For PDs, however, the association between procedure time and resident PGY was not significant. CONCLUSIONS: Junior residents likely prolong procedure times for more basic procedures such as LC but not for more complex procedures such as PD.

Establishing a swine model to compare vascular prostheses in a contaminated field.

OBJECTIVE: Patch arteriotomies are performed during many vascular procedures. Whereas synthetic materials are generally felt to be inappropriate for infected environments, the suitability of glutaraldehyde-treated bovine pericardium (GBP), a biologic material, in such instances is unknown. Our main objectives were to develop an animal model to study vascular prostheses while comparing the infectability of polyester (Dacron) and GBP in a topically infected environment. METHODS: Twenty-three pigs underwent transabdominal patch arteriotomy of the infrarenal aorta with either Dacron or GBP. The patches were inoculated with sterile saline (1 per group), Staphylococcus aureus 10(4) colony-forming units (CFUs) (4 per group), or S. aureus 10(5) CFUs (6 per group). At 3 wk, the animals were euthanized, and the patches were removed via a left retroperitoneal approach. Specimens were collected for microbiologic and histologic analysis. RESULTS: One animal from each group inoculated with 10(5) CFUs died during the study period, and another died immediately postoperatively of an airway complication. All aortas were patent and without evidence of pseudoaneurysm formation. Gross abscesses were found in 4/6 Dacron and 5/6 GBP animals receiving 10(5) CFUs. Similarly, 4/6 animals implanted with Dacron and 5/6 animals implanted with GBP had positive tissue cultures. A histologic grading system of inflammation substantiated the culture results. CONCLUSIONS: No significant difference exists between Dacron and GBP to resist bacterial infection at 3 wk. We have established a reproducible in vivo model to study arterial patch materials in a topically infected environment.

Intraoperative Extracorporeal Membrane Oxygenation Rescue of a Polytrauma Patient With a Complete Right Mainstem Bronchus Avulsion: A Pediatric Case Report.

In pediatric patients experiencing blunt chest trauma, tracheobronchial avulsion injuries are rare but frequently fatal. We report the case of a 13-year-old boy who presented to our trauma center following a semitruck versus pedestrian collision. During his operative course, he developed refractory hypoxemia requiring emergency venovenous (VV) extracorporeal membrane oxygenation (ECMO) support. After stabilization, a complete right mainstem bronchus avulsion was identified and treated.

Chemical constituents of the stem of Marsypopetalum modestum and their bioactivities.

Phytochemical investigation of Marsypopetalum modestum (Annonaceae) led to the isolation of a new phenylpropanoid glycoside, lyciumphenylpropanoid B (10), along with nine known compounds (1-9) from an aqueous methanolic extract of the stem. Most compounds are reported from this genus for the first time. The structures of the isolated compounds were elucidated using spectroscopic methods including NMR spectroscopy, high-resolution mass spectrometry, and quantum chemical electronic circular dichroism (ECD) calculations. Cytotoxic and antitubercular activities of several isolated compounds were evaluated. Dipyrithione (1) displayed anti-mycobacterial (MIC = 0.23 µM) and cytotoxic (IC50 = 0.8 µM in Hep G2 cells; 4.1 µM in HCT 116 cells) activities. Kelampayoside A (8) showed moderate cytotoxic activity against cancer cells.

Blunt Cerebrovascular Injury in Pediatric Hanging Victims.

INTRODUCTION: Incidence of blunt cerebrovascular injury (BCVI) following hanging in the pediatric population is ill-defined. Current guidelines recommend screening imaging during the initial trauma evaluation. Necessity of screening is questioned given BCVI is considered rare after hanging, especially when asymptomatic. This study aims to elucidate the incidence of BCVI in pediatric hangings and determine the value of radiographic work-up. METHODS: A retrospective cohort study was performed of pediatric hangings reported to the National Trauma Data Bank (NTDB), 2017-2019. Imaging, diagnoses, and findings suggestive of BCVI, such as Glasgow Coma Scale (GCS) ≤8, presence of cervical injury, and soft tissue injury were considered. Statistical analysis was carried out to compare incidence. RESULTS: 197 patients met study criteria, with 179 arriving in the trauma bay with signs of life. BCVI incidence was 5.6% (10 of 179). Computed Tomography Angiography (CTA) of the neck was the only reported screening modality in this data set. A CTA was completed in 46% of the cases. DISCUSSION: BCVI incidence following pediatric hanging is more common than previously thought. Less than half of patients had a CTA reported in this cohort. This may result in an underestimate. Given the potentially devastating consequences of a missed BCVI, the addition of CTA to initial work-up may be worthwhile to evaluate for cervical vascular injury, but further studies into the outcomes of children who do receive prophylactic therapy are needed.

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells.

A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because FDA approved anti-androgens are associated with adverse events and can eventually drive drug-resistant prostate cancer. This study evaluated α-mangostin for its novel ability to degrade the androgen receptor and androgen receptor variants. α-Mangostin is one of more than 70 isoprenylated xanthones isolated from Garcinia mangostana that we have been evaluating for their anticancer potential. Prostate cancer cells treated with α-mangostin exhibited decreased levels of wild-type and mutated androgen receptors. Immunoblot, immunoprecipitation, and transfection experiments demonstrated that the androgen receptor was ubiquitinated and subsequently degraded via the proteasome, which we hypothesize occurs with the assistance of BiP, an ER chaperone protein that we have shown to associate with the androgen receptor. We also evaluated α-mangostin for its antitumor activity and promotion of androgen receptor degradation in vivo. In summary, our study demonstrates that androgen receptor degradation occurs through the novel activation of BiP and suggests a new therapeutic approach for prostate cancer.

Polyoxygenated cyclohexene derivatives and other constituents of Uvaria rufa stem.

Six undescribed compounds, uvarirufols D and E, (+)-uvarigranol B, (-)-uvarigranol E, 6-acetoxy-5-hydroxy-7-methoxyflavanone and cherrevenaphthalene D, along with twelve known compounds, including polyoxygenated cyclohexenes, flavonoids, and lignans, were isolated from the methanol extract of Uvaria rufa stems. Their structures were elucidated by spectroscopic analyses and the absolute configurations were determined using electronic circular dichroism. Several isolates were evaluated for cytotoxic, antitubercular and anti-inflammatory potentials. (-)-6-Acetylzeylenol showed moderate inhibitory activity against Mycobacterium tuberculosis, with MIC value of 47.10 µg/mL. Cherrevenaphthalene D exhibited weak antimycobacterial activity and potent inhibitory effect on lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells (EC50 = 8.54 µM). 8-Hydroxy-5,7-dimethoxyflavanone displayed moderate level of NO inhibition (EC50 = 43.62 µM) with little cytotoxicity. The polyoxygenated cyclohexenes and lignans were inactive against HCT 116 and 22Rv1 cancer cells (IC50 > 100 µM).

Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women.

A similar abstract of the interim analysis was previously published in Fertility and Sterility. EPIGALLOCATECHIN GALLATE (EGCG) FOR TREATMENT OF UNEXPLAINED INFERTILITY ASSOCIATED WITH UTERINE FIBROIDS (PRE-FRIEND TRIAL): EARLY SAFETY ASSESSMENT. Uterine fibroids are the most common cause of unexplained infertility in reproductive-aged women. Epigallocatechin gallate (EGCG), a green tea catechin, has demonstrated its ability to shrink uterine fibroids in prior preclinical and clinical studies. Hence, we developed an NICHD Confirm-funded trial to evaluate the use of EGCG for treating women with fibroids and unexplained infertility (FRIEND trial). Prior to embarking on that trial, we here conducted the pre-FRIEND study (NCT04177693) to evaluate the safety of EGCG in premenopausal women. Specifically, our aim was to assess any adverse effects of EGCG alone or in combination with an ovarian stimulator on serum liver function tests (LFTs) and folate level. In this randomized, open-label prospective cohort, participants were recruited from the FRIEND-collaborative clinical sites: Johns Hopkins University, University of Chicago, University of Illinois at Chicago, and Yale University. Thirty-nine women, ages ≥18 to ≤40 years, with/without uterine fibroids, were enrolled and randomized to one of three treatment arms: 800 mg of EGCG daily alone, 800 mg of EGCG daily with clomiphene citrate 100 mg for 5 days, or 800 mg of EGCG daily with Letrozole 5 mg for 5 days. No subject demonstrated signs of drug induced liver injury and no subject showed serum folate level outside the normal range. Hence, our data suggests that a daily dose of 800 mg of EGCG alone or in combination with clomiphene citrate or letrozole (for 5 days) is well-tolerated and is not associated with liver toxicity or folate deficiency in reproductive-aged women.

Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.

Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.

α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth.

There is a need to characterize promising dietary agents for chemoprevention and therapy of prostate cancer (PCa). We examined the anticancer effect of α-mangostin, derived from the mangosteen fruit, in human PCa cells and its role in targeting cell cycle-related proteins involved in prostate carcinogenesis. Using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, we found that α-mangostin significantly decreases PCa cell viability in a dose-dependent manner. Further analysis using flow cytometry identified cell cycle arrest along with apoptosis. To establish a more precise mechanism of action, we performed a cell free biochemical kinase assay against multiple cyclins/cyclin-dependent kinases (CDKs) involved in cell cycle progression; the most significant inhibition in the cell free-based assays was CDK4, a critical component of the G1 phase. Through molecular modeling, we evaluated α-mangostin against the adenosine triphosphate-binding pocket of CDK4 and propose three possible orientations that may result in CDK4 inhibition. We then performed an in vivo animal study to evaluate the ability of α-mangostin to suppress tumor growth. Athymic nude mice were implanted with 22Rv1 cells and treated with vehicle or α-mangostin (100 mg/kg) by oral gavage. At the conclusion of the study, mice in the control cohort had a tumor volume of 1190 mm(3), while the treatment group had a tumor volume of 410 mm(3) (P < 0.01). The ability of α-mangostin to inhibit PCa in vitro and in vivo suggests α-mangostin may be a novel agent for the management of PCa.

Retrospective review of intervention for traumatic blunt spleen injuries in adolescents by trauma center type.

BACKGROUND: Management guidelines for pediatric blunt spleen injuries (BSI) include adolescent patients but few studies have compared current management of adolescents with respect to other age groups by center type. METHODS: A retrospective review of 2017-2018 National Trauma Quality Improvement (TQIP) data of children (6-12), adolescents (13-17) and young adults (18-24) with BSI presenting to an adult, pediatric only, or adult/pediatric trauma center, comparing the rate of splenic intervention for adolescents by trauma center was performed. RESULTS: Children had lower odds of spleen intervention than adolescents at both adult (OR 0.61 95%CI 0.39, 0.95) and adult/pediatric (OR 0.55 95%CI 0.35, 0.87) centers but did not differ at pediatric centers (OR 0.94 95%CI 0.39, 2.2) (n = 10,494). Adolescents adjusted odds of intervention was equal to adults at adult trauma centers (OR 1.2 95%CI 0.95, 1.4). CONCLUSION: Adolescents are more likely to undergo interventions for BSI as compared to children at both adult and adult/pediatric trauma centers.