Prior history of anterior cruciate ligament (ACL) reconstruction is associated with a greater risk of subsequent ACL injury in female collegiate athletes.

OBJECTIVES: The risk of a subsequent anterior cruciate ligament (ACL) sprain is greater in high school aged female athletes with prior history of ACL reconstruction (ACLR) than in age-matched controls. The risk of a subsequent ACL injury in female collegiate athletes with prior ACLR is unknown. The primary purpose of this study was to determine the relative risk of a subsequent ACL injury in female collegiate athletes with prior ACLR when compared to age-matched controls. The secondary purpose of this study was to evaluate the ability of jump and hop tests to discriminate ACL injury risk. DESIGN: Prospective cohort. METHODS: Three hundred and sixty female collegiate athletes (mean age 19.3 ±â€¯1.4 years) representing the following sports: volleyball, soccer, and basketball were recruited. Subjects reported prior history of ACLR and standing long jump (SLJ) and single-leg hop (SLH) scores were collected during the preseason. Noncontact time-loss ACL and lower quadrant (i.e., low back and lower extremities) injuries were tracked by university athletic trainers. RESULTS: Female collegiate athletes with a prior history of ACLR were 6 times (RR = 6.8 [95% CI: 1.4, 32.9] p-value = 0.007) more likely to experience an ACL injury than controls. Suboptimal performance on a battery of tests (SLJ ≤ 79% height, (B) SLH ≤ 69% height) was associated with a greater risk of lower quadrant injury (RR = 1.6 [95% CI: 1.1, 2.4] p-value = 0.028); however performance on these tests was not associated with ACL injury. CONCLUSIONS: Female collegiate athletes should be screened for history of ACLR.

COMPARISON OF NON-CONTACT AND CONTACT TIME-LOSS LOWER QUADRANT INJURY RATES IN MALE COLLEGIATE BASKETBALL PLAYERS: A PRELIMINARY REPORT.

BACKGROUND: Male collegiate basketball (BB) players are at risk for musculoskeletal injury. The rate of time-loss injury in men's collegiate BB, for all levels of National Collegiate Athletic Association (NCAA) competition, ranges from 2.8 to 4.3 per 1000 athletic exposures (AE) during practices and 4.56 to 9.9 per 1000 AE during games. The aforementioned injury rates provide valuable information for sports medicine professionals and coaching staffs. However, many of the aforementioned studies do not provide injury rates based on injury mechanism, region of the body, or player demographics. HYPOTHESIS/ PURPOSE: The purpose of this study is two-fold. The first purpose of this study was to report lower quadrant (LQ = lower extremities and low back region) injury rates, per contact and non-contact mechanism of injury, for a cohort of male collegiate basketball (BB) players. The second purpose was to report injury risk based on prior history of injury, player position, and starter status. STUDY DESIGN: Prospective, descriptive, observational cohort. METHODS: A total of 95 male collegiate BB players (mean age 20.02 ± 1.68 years) from 7 teams (NCAA Division II = 14, NCAA Division III = 43, NAIA = 21, community college = 17) from the Portland, Oregon region were recruited during the 2016-2017 season to participate in this study. Each athlete was asked to complete an injury history questionnaire. The primary investigator collected the following information each week from each team's athletic trainer: athletic exposures (AE; 1 AE = game or practice) and injury updates. RESULTS: Thirty-three time-loss LQ injuries occurred during the study period. The overall time-loss injury rate was 3.4 per 1000 AE. Division III BB players had the highest rates of injury. There was no difference in injury rates between those with or without prior injury history. Guards had a significantly greater rate of non-contact time-loss injuries (p = 0.04). CONCLUSIONS: Guards experienced a greater rate of LQ injury than their forward/center counterparts. Starters and athletes with a prior history of injury were no more likely to experience a non-contact time-loss injury than nonstarters or those without a prior history of injury. These preliminary results are a novel presentation of injury rates and risk for this population and warrant continued investigation. LEVEL OF EVIDENCE: 2.

PRESEASON JUMP AND HOP MEASURES IN MALE COLLEGIATE BASKETBALL PLAYERS: AN EPIDEMIOLOGIC REPORT.

BACKGROUND: Injuries are inherent in basketball with lower extremity (LE) injury rates reported as high as 11.6 per 1000 athletic exposures (AEs); many of these injuries result in time loss from sport participation. A recent trend in sports medicine research has been the attempt to identify athletes who may be at risk for injury based on measures of preseason fitness. HYPOTHESIS/PURPOSE: The purpose of this prospective cohort study was to determine if the standing long jump (SLJ) and/or the single-leg hop (SLH) for distance functional performance tests (FPT) are associated with non-contact time loss lower quadrant (LQ, defined as lower extremities or low back) injury in collegiate male basketball players. It was hypothesized that basketball players with shorter SLJ or SLH measures would be at an increased risk for LQ injury. METHODS: Seventy-one male collegiate basketball players from five teams completed a demographic questionnaire and performed three SLJ and six SLH (three per lower extremity) tests. Team athletic trainers tracked non-contact LQ time loss injuries during the season. STUDY DESIGN: Prospective cohort. RESULTS: Mean SLJ distance (normalized to height) was 0.99 (± 0.11) and mean SLH distances for the right and left were 0.85 ± 0.11 and 0.87 ± 0.10, respectively. A total of 29 (18 initial, 11 subsequent) non-contact time loss LQ injuries occurred during the study. At risk athletes (e.g., those with shorter SLJ and/or SLH) were no more likely to experience a non-contact time loss injury than their counterparts [OR associated with each FPT below cut scores = 0.9 (95% CI: 0.2, 4.9)]. The results from this study indicate that preseason performance of the SLJ and the SLH were not associated with future risk of LQ injury in this population. CONCLUSIONS: Preseason SLJ and SLH measures were not associated with non-contact time loss injuries in male collegiate basketball players. However, the descriptive data presented in this study can help sports medicine professionals evaluate athletic readiness prior to discharging an athlete back to sport after a LQ injury. LEVEL OF EVIDENCE: 2.

Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT) on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA) were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA). All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 104 CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence and induction of protective immunity.

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts.

OBJECTIVES: The underlying premise of these investigations was that the lipophilic hormone progesterone, which partitions into and (at relatively high concentrations) impedes the fluid mechanics of the plasmalemma, would perturb integral associations between membrane lipids and exporter pumps that otherwise confer drug resistance. That progesterone can affect susceptibility of ovarian adenocarcinoma cells and xenografts to cisplatin was tested. METHODS: The cisplatin-resistant human cell lines SKOV-3 and OVCAR-3 were treated for 24 hours with cisplatin (0.1 microg/ml)+/-progesterone (0.01, 0.1 microg/ml). Cytotoxicity and platinum were measured by MTT assay and inductively coupled plasma mass spectrometry, respectively. Athymic mice were inoculated intraperitoneal (ip) with SKOV-3 cells. Cisplatin (2 mg/kg/week)+/-progesterone (25 mg sustained-release pellet) regimens were initiated ip at one week (when micrometastases were present) and continued to six weeks post-xenograft. Tumor burdens, histopathology, and platinum concentrations were assessed upon necropsy at 24 hours after the final injection of cisplatin. RESULTS: There were no significant in vitro/vivo anticancer effects of cisplatin alone. High-dose progesterone enhanced platinum accretion and induced drug toxicity in both cell lines. Tumorigenesis was suppressed by cisplatin+progesterone. The treatment synergy was related to elevated tumor platinum and morphological evidence of apoptosis. CONCLUSION: It appears that the addition of progesterone to ovarian cancer therapeutic modalities represents a step in improving responses.

Degradable cisplatin-releasing core-shell nanogels from zwitterionic poly(beta -aminoester)-graft-PEG for cancer chemotherapy.

Cisplatin conjugated onto macromolecules or loaded in micelles can be preferentially delivered to tumors to minimize its toxicity to healthy tissues and increase its drug efficacy. Herein, we report cisplatin-containing nanogels possibly useful for targeted delivery of cisplatin. Carboxylic acid-functionalized poly(beta -aminoester)graft-poly(ethylene glycol) copolymers were synthesized by cocondensation polymerization of piperazine with 2,2-bis(acryloxymethyl)propionic acid, PEG 2,2-bis(acryloxymethyl)propionate macromonomer (mPEG). The graft copolymers formed 100-200 nm nanogels with low size-distribution by the complexation of their carboxylic groups with cisplatin. The nanogels were negatively charged and had a PEG outer layer. Thus, they had "stealth properties" suitable for in vivo applications. The nanogels had significantly lower in vitro cytotoxicity to SKOV-3 ovarian cancer cells than free cisplatin, but similar anticancer activity toward SKOV-3 tumors xenografted to immunocompromised mice.

Anticancer efficacies of cisplatin-releasing pH-responsive nanoparticles.

The objective of these investigations was to test the hypothesis that a rapid cytoplasmic release profile from nanoparticles would potentiate the anticancer activity of cisplatin. Cisplatin-loaded nanoparticles with pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEA) cores were synthesized from PDEA-block-poly(ethylene glycol) (PDEA-PEG) copolymer by using a solvent-displacement (acetone-water) method. Nanoparticles with pH-nonresponsive poly(epsilon-caprolactone) (PCL) cores made from PCL-block-PEG (PCL-PEG) were used for comparison. Nanoparticle sizes, zeta potentials, drug-loading capacities, and pH responsiveness were characterized. The cellular uptakes and localization in lysosomes were visualized by using confocal fluorescence microscopy. Cytostatic effects of free and encapsulated cis-diammineplatinum(II) dichloride (cisplatin) toward human SKOV-3 epithelial ovarian cancer cells were estimated by using the MTT assay. Intraperitoneal tumor responses to cisplatin and cisplatin/PDEA-PEG were evaluated in athymic mice at 4-6 weeks postinoculation of SKOV-3 cells. PDEA-PEG nanoparticles dissolved at pH < 6 and rapidly internalized and transferred to lysosomes; it therefore was predicted that the PDEA nanoparticles would rapidly release cisplatin into cytoplasm upon integration into acidic lysosomes and thereby overwhelm the chemoresistant properties of SKOV-3 cells. Indeed, relative proportions of viable cells were diminished to a greater extent by exposure in vitro to fast-releasing nanoparticles compared to slow-releasing nanoparticles or an equivalent dose of free cisplatin. Incidences of cellular pyknosis (a morphological indicator of apoptosis) were most evident within intestinal/mesentery tumors of mice treated with cisplatin/PDEA-PEG; tumor burdens were correspondingly reduced.

Effects of progesterone on ovarian tumorigenesis in xenografted mice.

Circumstantial evidence indicates that progestins reduce the risk of epithelial ovarian cancer. We report that the tumorigenic capacity of human ovarian carcinoma (SKOV-3) cells inoculated into the peritoneal cavity of athymic mice is suppressed by pretreatment with subcutaneous progesterone-releasing pellets. Numbers of tumor implants on the intestines/mesentery and invasiveness into underlying host tissues were reduced at 6 weeks following exposure to progesterone. Progesterone prevented tumors from forming on the liver. Life spans of progesterone-treated animals were prolonged. There was no beneficial effect of administration of progesterone if initiated after ovarian tumors had become established on organ surfaces. Our findings implicate a role for progesterone in ovarian cancer prophylaxis.

Inhibitory effects of progesterone on plasma membrane fluidity and tumorigenic potential of ovarian epithelial cancer cells.

The lethality of common (surface) epithelial ovarian cancer is contingent on its metastatic capacity. Dissemination of the neoplasia throughout the abdominal cavity has been associated with secretion of proteolytic enzymes from vesicles shed by ovarian cancer cells. We report that the lipophilic steroid hormone progesterone decreases the fluid dynamics of plasma membranes of human SKOV-3 adenocarcinoma cells. The decrease in membrane fluidity was related to an inhibition in vitro of exocytotic vesicle release, cellular invasiveness into Matrigel, and colony formation in three-dimensional collagen matrix. Tumorigenesis was suppressed by progesterone in immunocompromised nude mice inoculated intraperitoneally with SKOV-3 cells. Progestins could therefore be of benefit in the prevention and(or) treatment of early-stage ovarian carcinomatosis.