Targeting Fn14 as a therapeutic target for cachexia reprograms the glycolytic pathway in tumour and brain in mice.

PURPOSE: Cachexia is a complex syndrome characterized by unintentional weight loss, progressive muscle wasting and loss of appetite. Anti-Fn14 antibody (mAb 002) targets the TWEAK receptor (Fn14) in murine models of cancer cachexia and can extend the lifespan of mice by restoring the body weight of mice. Here, we investigated glucose metabolic changes in murine models of cachexia via [18F]FDG PET imaging, to explore whether Fn14 plays a role in the metabolic changes that occur during cancer cachexia. METHODS: [18F]FDG PET/MRI imaging was performed in cachexia-inducing tumour models versus models that do not induce cachexia. SUVaverage was calculated for all tumours via volume of interest (VOI) analysis of PET/MRI overlay images using PMOD software. RESULTS: [18F]FDG PET imaging demonstrated increased tumour and brain uptake in cachectic versus non-cachectic tumour-bearing mice. Therapy with mAb 002 was able to reduce [18F]FDG uptake in tumours (P < 0.05, n = 3). Fn14 KO tumours did not induce body weight loss and did not show an increase in [18F]FDG tumour and brain uptake over time. In non-cachectic mice bearing Fn14 KO tumours, [18F]FDG tumour uptake was significantly lower (P < 0.01) than in cachectic mice bearing Fn14 WT counterparts. As a by-product of glucose metabolism, l-lactate production was also increased in cachexia-inducing tumours expressing Fn14. CONCLUSION: Our results demonstrate that Fn14 receptor activation is linked to glucose metabolism of cachexia-inducing tumours.

Radiolabelling and preclinical characterisation of [89Zr]Zr-Df-ATG-101 bispecific to PD-L1/4-1BB.

PURPOSE: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo. METHODS: ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies. RESULTS: The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo. CONCLUSION: [89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101.

Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993.

BACKGROUND: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial. METHODS: CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelator p-isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/c nu/nu mice bearing pancreatic Capan-2 tumours. RESULTS: Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/c nu/nu mice. CONCLUSIONS: We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.

Effectiveness of a native vein arteriovenous fistula tracking system.

OBJECTIVE: This study aims to evaluate the effectiveness of a tracking program on the functional maturation rate of arteriovenous fistula (AVF). METHODS: Two major clinical outcomes (commencement of cannulation and functional maturation) of created AVFs were compared between two cohorts. (i) Cohort 1: historical cohort; (ii) Cohort 2: AVFs created after implementation of the tracking project. Multivariable Cox regression models were used to assess the association between cohort allocation and the two major clinical outcomes. RESULTS: Data of 114 and 141 patients were analyzed respectively from Cohorts 1 (historical data) and 2 (with AVF tracking). After adjustment of covariates in the multivariable analysis, the AVFs created in Cohort 2 were more likely to be cannulated earlier (adjusted HR: 2.82; 95% CI: 1.97-4.05; p < 0.001), compared to those in Cohort 1. Similarly, the AVFs of Cohort 2 patients had significantly higher probability of functional maturation (adjusted HR: 1.81; 95% CI: 1.31-2.48; p < 0.001) than fistulas in Cohort 1. Cannulation was commenced for half of the AVFs by 4.1 months post-creation in the historical cohort (Cohort 1), whereas in the post-tracking cohort, 50% of the AVFs were cannulated by 2.3 months after creation (p < 0.001). It took 5.5 and 4.3 months for 50% of the AVFs created in Cohort 1 and Cohort 2 patients to achieve catheter-free functional maturation, respectively (p = 0.06). CONCLUSION: An AVF tracking program with maturation target for the access surgeons, together with a standardized tracking, feedback, and clinical strategy adjustment system is able to improve the AVF functional maturation rate.

Impact of temperature on physical and cognitive performance in elite female football players during intermittent exercise.

There is limited research on female football players, especially related to their physical and cognitive performance under different climactic conditions. We analyzed the impact of a hot environmental temperature on physical performance and anticipation in elite female football players during a fatigue-inducing intermittent protocol. Elite female players (n = 21) performed the countermovement jump (CMJ) and responded to filmed sequences of offensive play under two distinct environmental temperatures (i.e., mild environment temperature- 20°C and 30% rh versus hot environment temperature- 38°C and 80% rh), interspersed by 1-week interval. Linear mixed models were used. CMJ performance declined following the intermittent protocol on both temperature conditions (p < 0.05). Moreover, there were significant main effects for protocol on CMJ speed (m/s) (p = 0.001; ηp 2 = 0.12), CMJ power (p = 0.002; ηp 2 = 0.11), and CMJ Heightmax (p = 0.002; ηp 2 = 0.12). After performing the intermittent protocol, exposure to a hot temperature caused a greater decline in anticipation accuracy (mild temperature = 64.41% vs. hot temperature = 53.44%; p < 0.001). Our study shows impaired performance in elite female football players following an intermittent protocol under hot compared with mild environmental conditions. We report decreased performance in both CMJ and anticipation performance under hotter conditions. The results reveal that exposure to hot temperatures had a negative effect on the accuracy of their anticipatory behaviors. We consider the implication of the work for research and training interventions.

Clinical Trials in the Brain Tumour Population: Challenges and Strategies for the Future.

PURPOSE OF REVIEW: This review identifies challenges and barriers to successful development of drugs in neuro-oncology trials at the preclinical, clinical and translational stages that we believe has contributed to poor outcomes for patients over the last 30 years. RECENT FINDINGS: Several key strategies have been proposed by leading groups to address these and improve patient outcomes. Better preclinical testing using more sophisticated and clinically relevant models is needed. A greater focus on assessing blood-brain barrier penetrance and targeting key biological processes such as tumour heterogeneity and immune response is vital. Adopting innovative trial designs permitting faster results and addressing key issues (including molecular heterogeneity and combinatorial approaches) is highly desirable. A stronger translational focus is also clearly needed. Implementation of these strategies is already starting to occur. Maintaining and increasing these novel approaches will require coordinated efforts between clinicians, scientists, industry and funding/regulator bodies.

Cost-utility analysis of normothermic machine perfusion compared to static cold storage in liver transplantation in the Canadian setting.

To estimate the incremental cost-effectiveness of a liver transplant program that utilizes normothermic machine perfusion (NMP) alongside static cold storage (SCS) compared to SCS alone (control). A Markov model compared strategies (NMP vs. control) using 1-year cycle lengths over a 5-year time horizon from the public healthcare payer perspective. Primary micro-costing data from a single center retrospective trial were applied along with utility values from literature sources. Transition probabilities were deduced using the retrospective trial cohort, local transplant data, and supplemented with literature values. Scenario and probabilistic sensitivity analysis (PSA) were conducted. The NMP strategy was cost-effective in comparison to the control strategy, which was dominated. The mean cost for NMP was $456 455 (2021 US$) and the control was $519 222. The NMP strategy had greater incremental quality-adjusted life years (QALYs) gains over 5 years compared to the control, with 3.48 versus 3.17, respectively. The overarching results remained unchanged in scenario analysis. In PSA, NMP was cost-effective in 63% of iterations at a willingness-to-pay threshold of $40 941. The addition of NMP to a liver transplant program results in greater QALY gains and is cost-effective from the public healthcare payer perspective.

Expansion of Human-Specific GGC Repeat in Neuronal Intranuclear Inclusion Disease-Related Disorders.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.

Radiolabelling and preclinical characterization of 89Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-ßRII fusion protein bintrafusp alfa.

PURPOSE: Τhis study aimed to optimize the 89Zr-radiolabelling of bintrafusp alfa investigational drug product and controls, and perform the in vitro and in vivo characterization of 89Zr-Df-bintrafusp alfa and 89Zr-Df-control radioconjugates. METHODS: Bintrafusp alfa (anti-PD-L1 human IgG1 antibody fused to TGF-ß receptor II (TGF-ßRII), avelumab (anti-PD-L1 human IgG1 control antibody), isotype control (mutated inactive anti-PD-L1 IgG1 control antibody), and trap control (mutated inactive anti-PD-L1 human IgG1 fused to active TGF-ßRII) were chelated with p-isothiocyanatobenzyl-desferrioxamine (Df). After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. In vivo biodistribution and imaging studies were performed with PET/CT to identify and quantitate 89Zr-Df-bintrafusp alfa tumour uptake in a PD-L1/TGF-ß-positive murine breast cancer model (EMT-6). Specificity of 89Zr-Df-bintrafusp alfa was assessed via a combined biodistribution and imaging experiment in the presence of competing cold bintrafusp alfa (1 mg/kg). RESULTS: Nanomolar affinities for PD-L1 were achieved with 89Zr-Df-bintrafusp alfa and 89Zr-avelumab. Biodistribution and imaging studies in PD-L1- and TGF-ß-positive EMT-6 tumour-bearing BALB/c mice demonstrated the biologic similarity of 89Zr-Df-bintrafusp alfa and 89Zr-avelumab indicating the in vivo distribution pattern of bintrafusp alfa is driven by its PD-L1 binding arm. Competition study with 1 mg of unlabelled bintrafusp alfa or avelumab co-administered with trace dose of 89Zr-labelled bintrafusp alfa demonstrated the impact of dose and specificity of PD-L1 targeting in vivo. CONCLUSION: Molecular imaging of 89Zr-Df-bintrafusp alfa biodistribution was achievable and allows non-invasive quantitation of tumour uptake of 89Zr-Df-bintrafusp alfa, suitable for use in bioimaging clinical trials in cancer patients.

Physical fitness is associated with better technical performance in adolescent alpine ski racers after controlling for practice time: A retrospective regression analysis.

In an effort to evaluate the mechanisms underpinning performance in alpine ski racing, researchers have focused on the predictive validity of measures derived from fitness assessments. However, a limitation of this literature is the absence of practice time, since prolonged training may naturally develop specific fitness capacities, making some tests of physical ability less predictive of performance. We examine the relationship between fitness tests, practice, and performance using linear regressions with fitness test data, practice history data, and performance results from adolescent alpine ski racers attending professional development academies in the United States (N = 82). Only aerobic capacity (i.e. 20 m shuttle run) was significantly associated with more practice time. After controlling for practice hours, 5.5-6.5% of variance in ski performance was significantly explained by assessments of lower body power (i.e. standing long jump, triple jump), anaerobic capacity (i.e. 60 s box jump), and upper body strength/endurance (i.e. push-ups). Findings highlight the important role of anaerobic power on alpine ski racing performance, which may be developed outside of regular practice, possibly through weight training or physical maturation. The small variance explained by physical/physiological measures suggests that superior ski performance is likely a product of various skills and characteristics (e.g. technical, tactical, perceptual-cognitive, psychosocial).

Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0.

(1) Background: Virtual screening studies on the therapeutically relevant proteins of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) require a detailed characterization of their druggable binding sites, and, more generally, a convenient pocket mapping represents a key step for structure-based in silico studies; (2) Methods: Along with a careful literature search on SARS-CoV-2 protein targets, the study presents a novel strategy for pocket mapping based on the combination of pocket (as performed by the well-known FPocket tool) and docking searches (as performed by PLANTS or AutoDock/Vina engines); such an approach is implemented by the Pockets 2.0 plug-in for the VEGA ZZ suite of programs; (3) Results: The literature analysis allowed the identification of 16 promising binding cavities within the SARS-CoV-2 proteins and the here proposed approach was able to recognize them showing performances clearly better than those reached by the sole pocket detection; and (4) Conclusions: Even though the presented strategy should require more extended validations, this proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which are clearly amenable for virtual screening campaigns and drug repurposing studies. All results generated by the study and the Pockets 2.0 plug-in are available for download.

Use of the wide-awake local anaesthetic no tourniquet in the management of distal radius fractures.

OBJECTIVE: To evaluate the Wide-Awake Local Anaesthesia with No Tourniquet (WALANT) method in fixation of distal radial fractures. METHODS: Forty patients admitted to the Jinnah Postgraduate Medical Centre, Karachi, Pakistan were recruited from March 2017 to December 2018. All patients had a distal radial fracture which was appropriate for internal fixation with a locked volar distal radial plate. The surgical site was infiltrated to achieve tumescent local anaesthesia using a solution of 0.9% normal saline and 1% lidocaine with 1:1,000,000 epinephrine. The patients were followed up until fracture union and were evaluated clinically, with goniometry, radiologically and with standard outcome scores (Mayo and qDASH). RESULTS: The patients were marginally more male than female (55% versus 45%), and mostly the dominant hand was injured (65%). The mean time to union was just over 3 months (15.2 weeks). All were united by 11 months. Good outcomes were achieved at final review with mean qDASH and Mayo scores of 13.3 and 81.6 respectively. The mean flexion and extension range at finalreview was 64 and 53 degrees respectively, and the mean grip strength was 73% when compared with the opposite side. CONCLUSIONS: The WALANT technique seems to be an acceptable and safe technique for fixation of distal radial fractures. There seem to be added benefits in terms of costs, reduced disposables, and intra-operative assessment of active movement.

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence - a retrospective study.

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post-transplant follow-up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post-transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Hand-Sewn versus Stapled Closure of Loop Ileostomy: A Meta-Analysis.

BACKGROUND: Individual trials comparing hand-sewn with stapled closure of loop ileostomy show different outcomes due to lack of statistical power. A systematic review, with a pooled analysis of results, might provide a more definitive answer. This review aimed to compare hand-sewn with stapled anastomotic technique for closure of a loop ileostomy and looked at the effect of bowel resection on the complication rates. METHODOLOGY: Relevant studies were identified from MEDLINE, EMBASE and the Cochrane database. All randomised clinical trials, prospective and retrospective studies comparing hand-sewn with stapled closure of loop ileostomy were included. RESULTS: Of the 4,917 patients in 15 identified studies, 3,406 had hand-sewn and 1,511 stapled anastomosis. There was no difference in the rate of anastomotic leak between the hand-sewn (2.93%, 55/1,877) and the stapled group (2.08%, 25/1,202) (OR 0.81, 95% CI 0.43-1.54, p = 0.52, I2 = 33%). The rate of small-bowel obstruction was higher in the hand-sewn group (7.03%, 231/3,284) compared to the stapled group (5.58%, 73/1,308; OR 0.69, 95% CI 0.51-0.92, p = 0.01, I2 = 0%). There was no difference in the incidence of anastomotic leak and small-bowel obstruction in the hand-sewn anastomosis between patients with or without bowel resection. CONCLUSIONS: There was no significant difference in the rate of anastomotic leakage between the hand-sewn and stapled techniques. The rate of small-bowel obstruction was higher in the hand-sewn group. Performance of bowel resection does not significantly increase the incidence of anastomotic leak or small-bowel obstruction.

Transitional journeys into, and through medical education for First-in-Family (FiF) students: a qualitative interview study.

BACKGROUND: There has been much interest in the transitions along the medical education continuum. However, little is known about how students from non-traditional backgrounds experience both the move to, and through Medical School, and their ambitions post-graduation. This research sought to understand the transitional journey into, and through undergraduate medical education, and future career aspirations for first-in-family (FiF) medical students. METHODS: Based on a interpretivist epistemological perspective, 20 FiF students from one English Medical School participated in semi-structured interviews. Participants were identified according to purposive inclusion criteria and were contacted by email via the student association at the Medical School and academic year leaders. The team approach to the thematic analysis enhanced the findings credibility. This research was part of an international collaboration. RESULTS: In the first transition, 'The Road to Medical School', a passion for science with an interest in people was a motivator to study medicine. Participants' parents' shared the elation of acceptance into Medical School, however, the support from school/college teachers was a mixed experience. In 'The Medical School Journey' transition, knowledge about the medical curriculum was variable. 'Fitting' in at Medical School was a problem for some, but studying for an elite degree elevated social status for many study participants. A source of support derived from senior medical student peers, but a medical degree could sacrifice students' own health. In the final transition, 'Future Plans', a medical career was perceived to have intrinsic value. Clarity about future aspirations was related to clinical experience. For some, career trajectories were related to a work-life balance and future NHS working conditions for Junior Doctors. CONCLUSIONS: The transitions highlighted in this article have important implications for those educators interested in a life cycle approach to widening participation in medical education. Future research should explore the post-graduation transitions for doctors from first-in-family University backgrounds.

A Multicenter, Prospective, Randomized, Contralateral Study of Tissue Liquefaction Liposuction vs Suction-Assisted Liposuction.

BACKGROUND: Tissue liquefaction liposuction (TLL) deploys a novel energy source utilizing a stream of warmed, low-pressurized, and pulsed saline to extract fat tissue. OBJECTIVES: Compare TLL to suction-assisted liposuction (SAL) to determine which device is more efficient for surgeons and provides better recovery for patients. METHODS: Thirty-one adult female patients were followed prospectively in a contralateral study design comparing differences in bruising, swelling, tenderness, and incision appearance ratings between TLL and SAL procedures. Surgical efficiency and appearance of the lipoaspirate were also compared. RESULTS: All 31 patients successfully completed the study. For TLL and SAL procedures, the average volumes of infusion (1.242 vs 1.276 L) and aspirated supernatant fat (704 vs 649 mL) were statistically similar. TLL median fat extraction rate was faster than SAL (35.6 vs 25 mL/min; P < 0.0001), and stroke rate was reduced in TLL vs SAL procedures (48 vs 120 strokes/min; P < 0.0001), and both were statistically significant. The mean total scores for bruising, swelling, treatment site tenderness, and incision appearance were lower, indicating improved patient recovery on the TLL side. CONCLUSIONS: TLL and SAL techniques produced comparable volume of fat aspirate. TLL demonstrated a 42% faster fat extraction rate and a 68% reduction in arm movements needed to complete the procedure compared to SAL, both of these differences are statistically significant. The TLL side was noted to have reduced bruising and swelling and improved incision site appearance with less tenderness compared to the SAL side.

eHealth Literacy and Health Behaviors Affecting Modern College Students: A Pilot Study of Issues Identified by the American College Health Association.

BACKGROUND: The eHealth Literacy Scale (eHEALS) has been widely adopted by researchers to understand how eHealth literacy can be put into context. eHealth researchers need to know how to promote positive health behavior changes across college students, given the importance of the Internet to acquire and use health information. The American College Health Association identified a set of key health issues that affect college students today. By understanding how eHEALS might be related to college students' maintenance of their health and their use of online health resources, researchers will be provided with a better understanding of eHealth literacy and its pragmatic implications for health campaigns and future interventions. OBJECTIVE: The goal of the study was to examine what eHEALS reveals about college student health behaviors identified by the American College Health Association. To understand college student current health maintenance and their intentions to maintain their health and use online resources, the theory of planned behavior was used as the theoretical framework for the study. METHODS: Data were collected via a survey of 422 college students that included the eHEALS measure and questions about health issues based on the recommendations of the American College Health Association. These questions asked about college student current health, subsequent use of online health resources, and their intention to maintain their health and make use of such resources in the future. RESULTS: eHEALS was positively and significantly associated with all 8 areas of health issues identified by the American College Health Association for college student current maintenance of health and use of online health resources and for future intention of health maintenance and use of online resources. Key issues that emerged with eHealth literacy were maintaining safe sex practices and seeking out related information, seeking out information on an exercise regime, information on vaccinations, and maintaining a balanced diet. CONCLUSIONS: These results suggest several areas that may be targeted for future health campaigns toward college students. In addition, eHEALS was found to be a useful instrument for college students in the United States. Lastly, these results point to a need to deliver targeted information to college students, particularly since eHEALS captures literacy based on positively phrased items.

Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.

OBJECTIVES: Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome-wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently developed BD or MDD [ill later (IL)] and those who remained well [well later (WL)]. METHODS: DNA methylation profiles were obtained from whole-blood samples from 22 IL and 23 WL individuals using the Infinium HumanMethylation450 BeadChip. Differential methylation was assessed on a single-locus and regional basis. Pathway analysis was performed to assess enrichment for particular biological processes amongst nominally significantly differentially methylated loci. RESULTS: Although no locus withstood correction for multiple testing, uncorrected P-values provided suggestive evidence for altered methylation at sites within genes previously implicated in neuropsychiatric conditions, such as Transcription Factor 4 (TCF4) and Interleukin 1 Receptor Accessory Protein-Like 1 ([IL1RAPL1]; P≤3.11×10(-5) ). Pathway analysis revealed significant enrichment for several neurologically relevant pathways and functions, including Nervous System Development and Function and Behavior; these findings withstood multiple testing correction (q≤0.05). Analysis of differentially methylated regions identified several within the major histocompatibility complex (P≤.000 479), a region previously implicated in schizophrenia and BD. CONCLUSIONS: Our data provide provisional evidence for the involvement of altered whole-blood DNA methylation in neurologically relevant genes in the aetiology of mood disorders. These findings are convergent with the findings of genome-wide association studies.