Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

BACKGROUND AND AIMS: The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation. APPROACH AND RESULTS: Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained. CONCLUSIONS: Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

Examination of Construct Validity of ANX and DEP Scales of the PAI-A.

Anxiety and depression are the two most common psychiatric problems of adolescence. The Personality Assessment Inventory, Adolescent Version (PAI-A) is a broadband instrument designed to assist in the detection and differential diagnosis of common psychiatric disorders in adolescents, and it includes a Depression scale (DEP) to detect the presence of major depressive episodes and an Anxiety scale (ANX) designed to detect clinically significant anxiety. However, there is limited research on this measure. The current study examined both the convergent and discriminant validities of the PAI-A Anxiety and Depression scales by observing their relationships to other self-report measures (e.g., PAI-A scales, MMPI-A), observer ratings (e.g., HPRS), and performance-based measures (e.g., Rorschach CS). The sample consisted of 352 records of the psychological assessments of adolescent inpatients between the ages of 13 to 17; the sample was about equally male (51.6%) and female with a mean age of 15.5 years. The sample was ethnically diverse with 48.7% of individuals identifying as Caucasian, 12.9% Black, 16% Hispanic, 2.6% Asian, 3.2% Other, and 16.6% unknown. There is strong evidence for convergent validity for the PAI-A ANX and DEP scales with r's ranging from .11 to .78. There is moderate evidence for discriminant validity for these scales. Results demonstrated that PAI-A scales correlated strongest with self-report, followed by therapist rating scale, and then performance-based measures. Various strengths of the PAI-A for the assessment of anxiety and depression are discussed.

Simulation Versus Interactive Mobile Learning for Teaching Extracorporeal Membrane Oxygenation to Clinicians: A Randomized Trial.

OBJECTIVES: Extracorporeal membrane oxygenation has become integral to critical care. Data informing optimal extracorporeal membrane oxygenation education modalities are lacking. We aimed to compare the effect of high-fidelity simulation versus interactive mobile learning on extracorporeal membrane oxygenation knowledge acquisition and retention among clinicians. DESIGN: Observer-blinded, randomized controlled trial. SETTING: A single academic medical center. SUBJECTS: Forty-four critical care clinicians with limited extracorporeal membrane oxygenation experience. INTERVENTIONS: Participants were randomized to receive: 1) simulation: three high-fidelity training scenarios, 2) QuizTime: 15 total multiple-choice questions delivered over 3 weeks via mobile device, or 3) experiential: no formal training. Participants completed a survey, written knowledge examination, and simulation assessment prior to randomization, immediately following the intervention, and 4 month postintervention. MEASUREMENTS AND MAIN RESULTS: The primary outcome was knowledge about extracorporeal membrane oxygenation assessed by score on the immediate postintervention written examination. Secondary outcomes included performance in extracorporeal membrane oxygenation simulation postintervention and 4 months later assessed by a rater blinded to group assignment. Clinicians randomized to simulation (n = 15), QuizTime (n = 14), and experiential (n = 15) had similar baseline characteristics. Adjusting for baseline knowledge, postintervention examination scores were higher in the simulation group (90.0%; interquartile range, 85.0-90.0%) than the QuizTime group (70.0%; interquartile range, 65.0-80.0%; p = 0.0003) and the experiential group (75.0%; interquartile range, 65.0-80.0%; p = 0.001). Scores did not differ between the groups at 4 months (p > 0.05 in all analyses). In postintervention extracorporeal membrane oxygenation simulations, the simulation group demonstrated shorter time to critical action compared with QuizTime (80.0 s [interquartile range, 54.0-111.0 s] vs 300.0 s [interquartile range 85.0-300.0 s]; p = 0.02) and compared with both QuizTime (45.0 s [interquartile range, 34.0-92.5 s] vs 255.5 s [interquartile range, 102.0-300.0 s]; p = 0.008) and experiential (300.0 s [interquartile range, 58.0-300.0 s]; p = 0.009) at 4 months. CONCLUSIONS: Simulation was superior to QuizTime and experiential learning with regard to extracorporeal membrane oxygenation knowledge acquisition. Further studies are needed to ascertain the effect of these interventions on knowledge retention, clinical performance, and patient outcomes.

Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplant.

Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary technology capable of supporting cardiac and respiratory function in the presence of end-stage lung disease. Initial experiences using ECMO as a bridge to lung transplant (ECMO-BTLT) were characterized by high rates of ECMO-associated complications and poor posttransplant outcomes. More recently, ECMO-BTLT has garnered success in preserving patients' physiologic condition and candidacy prior to lung transplant due to technological advances and improved management. Despite recent growth, clinical practice surrounding use of ECMO-BTLT remains variable, with little data to inform optimal patient selection and management. Although many questions remain, the use of ECMO-BTLT has shown promising outcomes suggesting that ECMO-BTLT can be an effective strategy to ensure that complex and rapidly decompensating patients with end-stage lung disease can be safely transplanted with good outcomes. Further studies are needed to refine and inform practice patterns, management, and lung allocation in this high-risk and fragile patient population.

Impact of out-of-pocket costs on patient initiation, adherence and persistence rates for patients treated with anti-vascular endothelial growth factor medicines.

IMPORTANCE: Out-of-pocket costs are a key driver of patient decisions to access, adhere and persist with anti-vascular endothelial growth factor (VEGF) therapy. The Medicare Benefits Schedule Review Taskforce proposes a 69% reduction in the scheduled fee for intravitreal injections (item 42 738) which risks increasing out-of-pocket costs for patients and worsening visual outcomes. BACKGROUND: To determine the impact of out-of-pocket costs on current anti-VEGF utilization rates in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). DESIGN: This is a retrospective cohort drug-utilization analysis. PARTICIPANTS: This study involved 11 592 patients in Australia diagnosed with nAMD or DMO. METHODS: A retrospective analysis of electronic, de-identified dispensing records of patients diagnosed with nAMD or DMO who initiated anti-VEGF therapy between January 1, 2016 and December 2018 across Australia. Patients were categorized by treatment facility type: bulk-billing clinics (BBCs) and "rest of market" clinics (ROMCs). MAIN OUTCOME MEASURES: Dispensing quantities, intervals and persistence rates. RESULTS: For patients with nAMD who initiated therapy between 2016 and 2018 the mean number of medicines dispensed up to September 30, 2019 was 17.0 for BBC and 13.8 for ROMC patients. For patients with DMO, the mean number of medicines dispensed was 16.5 for BBC patients and 12.5 for ROMC patients. Patients treated at BBCs had higher persistence rates than those treated at ROMCs. DMO patients had higher initiation rates BBCs (46%) vs ROMCs (25%). CONCLUSIONS AND RELEVANCE: Lower out-of-pocket costs are associated with higher adherence and persistence rates for anti-VEGF therapy in patients with AMD and DMO and higher initiation rates for DMO patients.

Assessing Repeated-Sprint Ability in Division I Collegiate Women Soccer Players.

Lockie, RG, Liu, TM, Stage, AA, Lazar, A, Giuliano, DV, Hurley, JM, Torne, IA, Beiley, MD, Birmingham-Babauta, SA, Stokes, JJ, Risso, FG, Davis, DL, Moreno, MR, and Orjalo, AJ. Assessing repeated-sprint ability in Division I collegiate women soccer players. J Strength Cond Res 34(7): 2015-2023, 2020-Repeated-sprint ability (RSA) is a key component of soccer, and is the capacity to repeatedly produce near-maximal to maximal sprints with short recovery periods. Repeated-sprint ability has received little analysis in collegiate women soccer players. The purpose of this study was to investigate relationships between RSA and tests of soccer-specific performance. Nineteen players from the same Division I collegiate women's soccer team were recruited. The RSA test consisted of six 20-m sprints completed on 15-second cycles. The measurements taken were total time (TT) and percent decrement (PD; percent change from first to last sprint). Subjects also completed tests of: lower-body strength (1 repetition maximum [1RM] back squat); jump performance (vertical and standing long jumps); linear (0-5, 0-10, and 0-30 m sprint intervals) and change-of-direction (505 from each leg) speed; and soccer-specific fitness (Yo-Yo intermittent recovery test level 1 [YYIRT1]). Pearson's correlations (p ≤ 0.05) were used to calculate relationships between RSA TT and PD with the performance tests. Total time exhibited significant relationships with the 0-10 (r = 0.50) and 0-30 m (r = 0.71) sprint intervals, and the left-leg 505 (r = 0.57). However, lower-body strength measured by the 1RM back squat and jump performance did not relate to TT. Percent decrement correlated only with the left-leg 505 (r = 0.53) and no other performance test. This included the YYIRT1, although both PD and YYIRT1 performance are limited by fatigue. The results from this study indicated that faster linear sprinting speed could positively influence RSA in Division I collegiate women soccer players.

Use of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator During Preoperative Risk Discussion: The Patient Perspective.

BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality Improvement Program Surgical Risk Calculator (ACS Calculator) provides empirically derived, patient-specific risks for common adverse perioperative outcomes. The ACS Calculator is promoted as a tool to improve shared decision-making and informed consent for patients undergoing elective operations. However, to our knowledge, no data exist regarding the use of this tool in actual preoperative risk discussions with patients. Accordingly, we performed a survey to assess (1) whether patients find the tool easy to interpret, (2) how accurately patients can predict their surgical risks, and (3) the impact of risk disclosure on levels of anxiety and future motivations to decrease personal risk. METHODS: Patients (N = 150) recruited from a preoperative clinic completed an initial survey where they estimated their hospital length of stay and personal perioperative risks of the 12 clinical complications analyzed by the ACS Calculator. Next, risk calculation was performed by entering participants' demographics into the ACS Calculator. Participants reviewed their individualized risk reports in detail and then completed a follow-up survey to evaluate their perceptions. RESULTS: Nearly 90% of participants desire to review their ACS Calculator report before future surgical consents. High-risk patients were 3 times more likely to underestimate their risk of any complication, serious complication, and length of stay compared to low-risk patients (P < .001). After reviewing their calculated risks, 70% stated that they would consider participating in prehabilitation to decrease perioperative risk, and nearly 40% would delay their surgery to do so. Knowledge of personal ACS risk calculations had no effect on anxiety in 20% and decreased anxiety in 71% of participants. CONCLUSIONS: The ACS Calculator may be of particular benefit to high-risk surgical populations by providing realistic expectations of outcomes and recovery. Use of this tool may also provide motivation for patients to participate in risk reduction strategies.

Repeated-Sprint Ability in Division I Collegiate Male Soccer Players: Positional Differences and Relationships With Performance Tests.

Lockie, RG, Moreno, MR, Orjalo, AJ, Stage, AA, Liu, TM, Birmingham-Babauta, SA, Hurley, JM, Torne, IA, Beiley, MD, Risso, FG, Davis, DL, Lazar, A, Stokes, JJ, and Giuliano, DV. Repeated-sprint ability in Division I collegiate male soccer players: positional differences and relationships with performance tests. J Strength Cond Res 33(5): 1362-1370, 2019-Repeated-sprint ability (RSA) in essential for soccer. Important considerations when assessing RSA is whether there are differences between positions (defenders, midfielders, and forwards), and what physiological characteristics may contribute to RSA. This has not been assessed in collegiate male players. Eighteen Division I male field players from one school performed several performance tests. The RSA test involved 7 × 30-m sprints completed on 20-second cycles. Measurements included total time (TT), and performance decrement (percent change in time from the first to last sprint; PD). Subjects also completed tests of lower-body power (vertical [VJ] and standing broad jump [SBJ]); linear (30-m sprint; 0-5 m, 0-10 m, 0-30 m intervals) and change-of-direction (505) speed; and soccer-specific endurance (Yo-Yo Intermittent Recovery Test Level 2; YYIRT2). A one-way analysis of variance (p < 0.05) determined between-position differences, and effect sizes were calculated. Pearson's correlations (p < 0.05) calculated relationships between RSA TT and PD with the other tests. There were no significant between-position differences for any test. There were large effects for the faster right-leg 505 and greater YYIRT2 distance for midfielders compared with defenders and forwards. Nonetheless, no between-position differences in RSA TT and PD were documented. There were relationships between RSA TT and the VJ (r = -0.59), SBJ (r = -0.61), 0-10 m (r = 0.64) and 0-30-m (r = 0.83) sprint intervals. There were no significant correlations for RSA PD. Male field players from one collegiate soccer team can demonstrate similar RSA across different positions. Greater lower-body power and sprinting speed could augment RSA.

Amblyomma maculatum-associated rickettsiae in vector tissues and vertebrate hosts during tick feeding.

Rickettsia parkeri, a causative agent of spotted fever rickettsiosis, is transmitted by Amblyomma maculatum (Gulf Coast tick), a tick that may also carry a non-pathogenic spotted fever group Rickettsia, "Candidatus Rickettsia andeanae". Here, we evaluated R. parkeri and "Candidatus R. andeanae" in tissues from A. maculatum prior to, during, and after blood feeding on rabbits. Using colony-reared A. maculatum that were capillary-fed uninfected cells, R. parkeri, "Candidatus R. andeanae", or both rickettsiae, we detected higher levels of Rickettsia spp. in the respective treatment groups. Rickettsial levels increased during blood feeding for both R. parkeri and "Candidatus R. andeanae", with a greater increase in R. parkeri in co-infected ticks compared to singly-infected ticks. We detected transovarial transmission of "Candidatus R. andeanae" in egg and larval cohorts and confirmed vertical transmission of R. parkeri in one group of larvae. Rabbits from all Rickettsia-exposed groups seroconverted on immunofluorescent antibody testing using R. parkeri antigen. Visualization of "Candidatus R. andeanae" in tick salivary glands suggested potential transmission via tick feeding. Here, rickettsial levels in artificially infected ticks demonstrate changes during feeding and transovarial transmission that may be relevant for interpreting rickettsial levels detected in wild A. maculatum.

A genomic resource for the sedentary semi-endoparasitic reniform nematode, Rotylenchulus reniformis Linford & Oliveira.

The reniform nematode (Rotylenchulus reniformis) is a sedentary semi-endoparasitic species that is pathogenic on many row crops, fruits, and vegetables. Here, the authors present a draft genome assembly of R. reniformis using small- and large-insert libraries sequenced on the Illumina GAIIx and MiSeq platforms.The reniform nematode (Rotylenchulus reniformis) is a sedentary semi-endoparasitic species that is pathogenic on many row crops, fruits, and vegetables. Here, the authors present a draft genome assembly of R. reniformis using small- and large-insert libraries sequenced on the Illumina GAIIx and MiSeq platforms.

Relationships Between Height, Arm Length, and Leg Length on the Mechanics of the Conventional and High-Handle Hexagonal Bar Deadlift.

Lockie, RG, Moreno, MR, Orjalo, AJ, Lazar, A, Liu, TM, Stage, AA, Birmingham-Babauta, SA, Stokes, JJ, Giuliano, DV, Risso, FG, Davis, DL, and Callaghan, SJ. Relationships between height, arm length, and leg length on the mechanics of the conventional and high-handle hexagonal bar deadlift. J Strength Cond Res 32(11): 3011-3019, 2018-The study investigated relationships between arm length (AL) and leg length (LL) and conventional deadlift (CD) and high-handle hexagonal bar deadlift (HHBD) mechanics. Twenty-three resistance-trained subjects (14 men and 9 women) completed a 1 repetition maximum CD and HHBD. A linear position transducer was used to measure lift distance and duration; peak and mean power, velocity, and force; time to peak power and velocity; and work. Right AL and LL were measured, and AL-to-LL ratio (AL:LL) was also calculated. Spearman's correlations (ρ; p ≤ 0.05) computed relationships between anthropometry and deadlift mechanics separately for men and women. For the HHBD, greater height and LL related to greater lift distance and work (ρ = 0.54-0.68); a higher AL:LL related to time to peak power and velocity occurring sooner (ρ = -0.67 to 0.78). For the HHBD, greater height and LL related to greater lift distance and work; a higher AL:LL related to time to peak power and velocity occurring sooner in the lift (ρ = 0.54-0.77). In women, greater height, AL, and LL related to a longer CD lift distance (ρ = 0.67-0.92). For the HHBD, greater height, AL, and LL related to a longer lift distance and greater mean velocity (ρ = 0.69-0.96). There was a negative relationship between AL and lift time (ρ = -0.83), which meant longer arms resulted in a lower HHBD lift time. Arm length may have influenced women more because of the fixed dimensions of the hexagonal bar. Coaches should be cognizant of potential differences in CD and HHBD work when performed by individuals of different body sizes.

The 1 Repetition Maximum Mechanics of a High-Handle Hexagonal Bar Deadlift Compared With a Conventional Deadlift as Measured by a Linear Position Transducer.

Lockie, RG, Moreno, MR, Lazar, A, Risso, FG, Liu, TM, Stage, AA, Birmingham-Babauta, SA, Torne, IA, Stokes, JJ, Giuliano, DV, Davis, DL, Orjalo, AJ, and Callaghan, SJ. The 1 repetition maximum mechanics of a high-handle hexagonal bar deadlift compared with a conventional deadlift as measured by a linear position transducer. J Strength Cond Res 32(1): 150-161, 2018-The high-handle hexagonal bar deadlift (HHBD), a variation of the conventional deadlift (CD), is said to reduce the lift range of motion, which may change the mechanics of the lift. However, no research has investigated this. This study compared the mechanics between a 1 repetition maximum (1RM) CD and HHBD. Thirty-one strength-trained subjects (21 men, 10 women) completed a 1RM CD and HHBD. A linear position transducer measured lift distance, duration, and work; and peak and mean power, velocity, and force. The presence of a sticking region (SR) was determined for each lift. A repeated-measures analysis of variance (ANOVA) calculated differences between 1RM CD and HHBD mechanics. A one-way ANOVA compared the mechanics of each lift between subjects who exhibited an SR or not, and the SR between the CD and HHBD. Significance was set at p < 0.01. Subjects lifted a greater load in the HHBD (154.50 ± 45.29 kg) compared with the CD (134.72 ± 40.63 kg). Lift distance and duration were 22 and 25% shorter during the 1RM HHBD, respectively. The HHBD featured greater peak power and velocity, and peak and mean force; more work was done in the CD. Most subjects did not exhibit a CD (68%) or HHBD (77%) SR. There were no differences in CD or HHBD mechanics between subjects with or without an SR, and no differences in SR region distance or duration between the CD and HHBD. Greater force can be generated in the HHBD, which could have implications for strength-training adaptations over time.

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation.

Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been described in immune responses induced by strong immunological stimuli. It has also been shown that CBD enhances IL-2 production in response to low-level T cell stimulation. Since IL-2, in combination with TGF-ß1, are critical for Treg induction, we hypothesized that CBD would induce CD4+CD25+FOXP3+ Tregs in response to low-level stimulation. Low-level T cell stimulation conditions were established based on minimal CD25 expression in CD4+ cells using suboptimal PMA/Io (4nM/0.05µM, S/o), ultrasuboptimal PMA/Io (1nM/0.0125µM, Us/o) or soluble anti-CD3/28 (400-800ng each, s3/28). CBD increased CD25+FOXP3+ cells from CD4+, CD4+CD25+, and CD4+CD25- T cells, as well as in CD4+ T cells derived from FOXP3-GFP mice. Most importantly, the Us/o+CBD-induced CD4+CD25+ Tregs robustly suppressed responder T cell proliferation, demonstrating that the mechanism by which CBD is immunosuppressive under low-level T cell stimulation involves induction of functional Tregs.

Exposure to an environmentally relevant mixture of organochlorine compounds and polychlorinated biphenyls Promotes hepatic steatosis in male Ob/Ob mice.

Hepatic steatosis is recognized as an independent risk factor for the development of cardiovascular disease. While obesity and type 2 diabetes are well-established risk factors in the development of hepatic steatosis, recent studies have revealed exposure to mixtures of persistent organic pollutants (POPs), which are environmental contaminants in various fatty foods, can promote steatosis. Thus, the present study was designed to determine if exposure to a defined mixture of prevalent polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides or their metabolites promote hepatic steatosis in a genetically induced model of type 2 diabetes, the leptin-deficient ob/ob mouse. Male C57BL/6J wild type (WT) or ob/ob mice were administered an environmentally relevant mixture of PCBs and OCs for 7 weeks via oral gavage. Exposure to POPs did not significantly alter fasting serum glucose or insulin levels. However, POPs exposure significantly increased hepatic triglyceride content in ob/ob animals, while decreasing serum triglyceride levels. This POPs-mediated increase in hepatic triglyceride content did not appear to be associated with significantly increased inflammation in either the liver or adipose. Exposure to POPs significantly induced the expression of cytochrome P450 3a11 in WT animals, yet the expression of this cytochrome was significantly downregulated in ob/ob animals regardless of POPs exposure. Taken together, the present data indicate exposure to an environmentally relevant mixture of both PCBs and OC pesticides in ob/ob mice promotes hepatic steatosis while decreasing hypertriglyceridemia, which demonstrates exposure to a defined mixture of POPs alters systemic lipid metabolism in a genetically induced model of obesity and type 2 diabetes. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1399-1411, 2017.

Cognitive changes associated with switching to frequent nocturnal hemodialysis or renal transplantation.

BACKGROUND: It is uncertain whether switching to frequent nocturnal hemodialysis improves cognitive function in well-dialyzed patients and how this compares to patients who receive a kidney transplant. METHODS: We conducted a multicenter observational study with longitudinal follow-up of the effect on cognitive performance of switching dialysis treatment modality from conventional thrice-weekly hemodialysis to frequent nocturnal hemodialysis, a functioning renal transplant or remaining on thrice-weekly conventional hemodialysis. Neuropsychological tests of memory, attention, psychomotor processing speed, executive function and fluency as well as measures of solute clearance were performed at baseline and again after switching modality. The change in cognitive performance measured by neuropsychological tests assessing multiple cognitive domains at baseline, 4 and 12 months after switching dialysis modality were analyzed using a linear mixed model. RESULTS: Seventy-seven patients were enrolled; 21 of these 77 patients were recruited from the randomized Frequent Hemodialysis Network (FHN) Nocturnal Trial. Of these, 18 patients started frequent nocturnal hemodialysis, 28 patients received a kidney transplant and 31 patients remained on conventional thrice-weekly hemodialysis. Forty-eight patients (62 %) returned for the 12-month follow-up. Despite a significant improvement in solute clearance, 12 months treatment with frequent nocturnal hemodialysis was not associated with substantial improvement in cognitive performance. By contrast, renal transplantation, which led to near normalization of solute clearance was associated with clinically relevant and significant improvements in verbal learning and memory with a trend towards improvements in psychomotor processing speed. Cognitive performance in patients on conventional hemodialysis remained stable with the exception of an improvement in psychomotor processing speed and a decline in verbal fluency. CONCLUSIONS: In patients on conventional thrice-weekly hemodialysis, receiving a functioning renal transplant was associated with improvement in auditory-verbal memory and psychomotor processing speed, which was not observed after 12 months of frequent nocturnal hemodialysis.