Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells.

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.

External Load Fluctuations Across an Amateur Athletic Union Basketball Season.

ABSTRACT: Kutson, CW, Russell, JL, Strack, D, Coutts, AJ, and McLean, BD. External load fluctuations across an Amateur Athletic Union basketball season. J Strength Cond Res 38(3): 592-598, 2024-Amateur Athletic Union (AAU) competitions are an important component of the developmental pathway for youth basketball athletes. Despite its relative importance, there is currently a paucity of research investigating the physical demands in AAU basketball. Therefore, the purpose of this study was to examine the physical demands encountered over the course of an AAU basketball season. External training load was quantified using inertial sensors (Catapult T6) from one male AAU basketball team (age: 17.5 ± 0.5 years, height: 197.3 ± 10.0 cm, and mass: 89.4 ± 11.6 kg) over the course of the 2021 AAU season and categorized post hoc into high-, medium-, and low-minute groups based on mean playing minutes. After player categorization, 2 linear mixed models were constructed, one for PlayerLoad (PL) and one for duration, to examine the differences across player category, month of the season, and activity types (practices or games). The results show that the highest training loads were encountered by high-minute players, who had total PLs of 9,766 ± 1,516 AU, 13,207 ± 2,561 AU, and 7,071 ± 2,122 AU during April, May, and June, respectively. Highly variable training loads were also evident over the course of a season, with peak PL values as high as 4,921 AU per week. Practitioners should be aware that AAU basketball players experience variable loads throughout the season, which peak around congested competition/tournament periods. In addition, players with high game minutes accumulate the most load over the course of a season. This information may be used to better inform planning and periodizing strategies during developmental phases.

Height Restrictions for Dual-energy X-ray Absorptiometry: What Are Our Options for Body Composition and Bone Health Precision?

ABSTRACT: Redinger, AL, Russell, JL, Allen, SMF, and Baker, BS. Height restrictions for dual-energy X-ray absorptiometry: what are our options for body composition and bone health precision? J Strength Cond Res 38(7): e359-e365, 2024-Dual-energy X-ray absorptiometry (DXA) is commonly used for testing athlete's body composition, but many athletes are too tall. The first aim was to assess the viability of combining upper- and lower-body regions of interest (ROI), creating a combined scan for tall athletes who do not fit on the table and second, to provide practical solutions to DXA users who routinely scan tall athletes. Sixty subjects (34.8 ± 11.9 years; 171 ± 9 cm) completed 2 total-body DXA scans for baseline precision testing, using GE Lunar Prodigy (LP) or Hologic Horizon A (HA) models. Next, an upper body ROI from the skull to the distal femoral condyles was combined with a flipped scan (feet-to-head) ROI encompassing the proximal tibial plateau to the distal foot. Soft and bone tissue coefficient of variance (CV%) were calculated between the baseline scans and for the newly combined ROI scan. The combined ROI scan added 0.25-0.63% and 0.01-4.35% error rates for the LP and HA, respectively. An exploratory assessment of a GE Lunar iDXA demonstrated results similar to the HA with 4%+ error. The combined ROI scan is a user-friendly and precise method for older LP systems adding less than 1% error; however, newer DXA systems cannot use the stitched scan technique. Coaches and practitioners who use newer DXAs must prioritize consistently using the same boney landmarks (head, jaw, or feet) and ROI heights to provide precise longitudinal assessments of tall athletes' bone and body composition, until larger DXA tables become available.

Combined Atrial Volume is Associated with Significant Atrial Arrhythmias in Total Cavopulmonary Connection Fontan Patients.

Atrial arrhythmias are a common late manifestation after Fontan palliation and are known to contribute to significant morbidity and mortality. Atrial volume by cardiac magnetic resonance imaging has been increasingly used in patients with congenital heart disease with no reports in those with Fontan palliation. In acquired heart disease, left atrial volume has been shown to be a strong predictor of outcomes of sustained atrial arrhythmias, including recurrence of atrial fibrillation. We hypothesized that combined atrial volume (CAV) in patients with total cavopulmonary connection (TCPC) Fontan palliation may be associated with increased risk of significant atrial arrhythmias (SAA). This is a single center retrospective case-control study. Cases were defined as patients with TCPC Fontan palliation ≥ 18 years of age, with SAA requiring intervention. Only those with advanced imaging for 3D rendering between 2013 and 2022 were included. CAV was analyzed from a 3-dimensional (3D) data set, including both the left and right atria, excluding the Fontan baffle. Seventeen TCPC Fontan case patients and 17 control patients were included. There was no difference in age between the two groups. There was no difference between gender, type of Fontan palliation, atrio-ventricular valve regurgitation, or combined ventricular function between the two groups. CAV was higher in SAA group compared to controls, and all control patients had indexed CAV ≤ 80 mL/kg. This is the first data suggesting CAV is associated with SAA in TCPC Fontan patients. Indexed CAV ≥ 80 mL/kg may be a valuable marker for SAA risk.

Advanced fellowship training for cardiology fellows in acute care cardiology.

Hospitalised children have become more medically complex and increasingly require specialised teams and units properly equipped to care for them. Within paediatric cardiology, this trend, which is well demonstrated by the expansion of cardiology-specific ICUs, has more recently led to the development of acute care cardiology units to deliver team-based and condition-focused inpatient care. These care teams are now led by paediatric cardiologists with particular investment in the acute care cardiology environment. Herein, we describe the foundation and development of an Acute Care Cardiology Advanced Training Fellowship to meet the clinical, scholarly, and leadership training needs of this emerging care environment.

Empowering self-critical perfectionistic students: A waitlist controlled feasibility trial of an explanatory feedback intervention on daily coping processes.

This study of 176 university students tested a single-session explanatory feedback intervention (EFI), derived from the perfectionism coping processes model. Participants with higher self-critical perfectionism completed daily measures of stress appraisals, coping, and affect for 7 days. A randomized control design was used to compare an EFI condition with a waitlist control condition over 4 weeks with individualized feedback delivered one-on-one by student trainees in-person or remotely through videoconferencing. The feasibility of the individualized analyses of each participant's daily data was supported by identifying daily trigger patterns, maintenance tendencies, strengths, common triggers, and best targets for reducing negative mood and increasing positive mood across several stressors for each participant. Participant ratings indicated that the comprehensive feedback was coherent and functional. Participants in the EFI condition, compared to those in the control condition, reported increases in empowerment, coping self-efficacy, and problem-focused coping, as well as decreases in depressive and anxious symptoms. Between-group effect sizes were moderate-to-large. There were reliable improvements in empowerment and depressive symptoms for 56% and 36%, respectively, of participants in the EFI condition. These findings demonstrate the broad applicability, conceptual utility, and effectiveness of the EFI for self-critical perfectionistic individuals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Finding the Signal in the Noise-Interday Reliability and Seasonal Sensitivity of 84 Countermovement Jump Variables in Professional Basketball Players.

ABSTRACT: Mercer, RAJ, Russell, JL, McGuigan, LC, Coutts, AJ, Strack, DS, and McLean, BD. Finding the signal in the noise-interday reliability and seasonal sensitivity of 84 countermovement jump variables in professional basketball players. J Strength Cond Res 37(2): 394-402, 2023-This study examined the measurement characteristics of countermovement jump (CMJ) variables in basketball athletes using different variable selection criteria. Test-retest reliability (noise) and seasonal variability (signal) CMJ data were collected from 13 professional basketball athletes playing for the same club throughout 1 competitive season. Interday reliability (coefficient of variation [CV] and intraclass correlation coefficients) were calculated over 3 preseason tests conducted on 3 consecutive days. To evaluate sensitivity, signal-to-noise ratio (SNR) was calculated by dividing seasonal variability (CV) from 8 in-season CMJ tests (collected from November to February) by preseason reliability (CV). Players performed 3 CMJs each testing day, and 3 data analysis techniques were applied: a single variable from the trial with either the best jump height (BestJH; calculated by flight time) or the best flight time to contraction time (BestFT:CT) and mean output across 3 jumps (Mean3). Mean3 was the most reliable data analysis technique, with 79 and 82 of 84 variables displaying lower interday CVs compared with BestJH and BestFT:CT, respectively. Overall, many CMJ measures display seasonal changes that are greater than the inherent noise, with 77 variables producing SNR of >1.00 for Mean3 compared with 65 and 58 variables for BestJH and BestFT:CT, respectively. To improve reliability and sensitivity, it is recommended that practitioners use the average of multiple CMJ trials and regularly reassess measurement characteristics specific to their cohort and environment.

Peer mentorship to improve outcomes in patients on hemodialysis (PEER-HD): a randomized controlled trial protocol.

BACKGROUND: Patients receiving in-center hemodialysis experience disproportionate morbidity and incur high healthcare-related costs. Much of this cost stems from potentially avoidable hospitalizations. Peer mentorship has been used effectively to improve outcomes for patients with complex chronic diseases. We propose testing the efficacy of peer mentorship on hospitalization rates among patients receiving hemodialysis. METHODS: This is a multicenter parallel group randomized controlled pragmatic trial of patients treated at hemodialysis facilities in Bronx, NY and Nashville, TN. The study has two phases. Phase 1 will enroll and train 16 hemodialysis patients (10 in Bronx, NY and 6 in Nashville TN) to be mentors using a program focused on enhancing self-efficacy, dialysis self-management and autonomy-supportive communication skills. Phase 2 will enroll 200 high risk adults receiving hemodialysis (140 in Bronx, NY and 60 in Nashville, TN), half of whom will be randomized to intervention and half to usual care. Intervention participants are assigned to weekly telephone calls with trained mentors (see Phase 1) for a 3-month period. The primary outcome of Phase 1 will be engagement of mentors with training and change in knowledge scores and autonomy skills from pre- to post-training. The primary outcome of Phase 2 will be the composite count of ED visits and hospitalizations at the end of study follow-up in patient participants assigned to intervention as compared to those assigned to usual care. Secondary outcomes for Phase 2 include the change over the trial period in validated survey scores measuring perception of social support and self-efficacy, and dialysis adherence metrics, among intervention participants as compared to usual care participants. DISCUSSION: The PEER-HD study will test the feasibility and efficacy of a pragmatic peer-mentorship program designed for patients receiving hemodialysis on ED visit and hospitalization rates. If effective, peer-mentorship holds promise as a scalable patient-centered intervention to decrease hospital resource utilization, and by extension morbidity and cost, for patients receiving maintenance in-center hemodialysis. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03595748 ; 7/23/2018. TRIAL SPONSOR: National Institutes of Diabetes, Digestive and Kidney Disease (NIDDK) 5R18DK118471. FUNDING: Funding for this study was provided by the National Institutes of Diabetes, Digestive and Kidney Disease: R18DK118471. STUDY STATUS: This is an ongoing study and not complete. We are still collecting data for observational follow-up on participants. RELATED ARTICLES: No related articles for this study have been submitted to any journal. The study sponsor and funders had no role in the design, analysis or interpretation of this data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

DEVELOPMENT OF A MOBILITY ASSESSMENT SCORE FOR EVALUATION OF THE EFFECTS OF ORAL HYALURONIC ACID ON CLINICAL LAMENESS IN ASIAN SMALL-CLAWED OTTERS (AONYX CINEREA) AND AFRICAN SPOT-NECKED OTTERS (HYDRICTIS MACULICOLIS) UNDER HUMAN CARE.

Oral hyaluronic acid has been shown to reduce inflammation and pain in humans with osteoarthritis. Eight Asian small-clawed otters (Aonyx cinerea) and two African spot-necked otters (Hydrictis maculicolis) with varying degrees of osteoarthritic changes identified on radiographs were selected for a randomized, double-blinded, placebo-controlled clinical trial. Animal husbandry staff completed otter mobility assessment (OMA) questionnaires for each animal prior to study commencement and following either oral hyaluronic acid at a loading dose of 4 mg/kg PO SID for 10 d followed by a maintenance dose of 2 mg/kg PO SID for 20 d, or placebo for 30 d. Four veterinarians with experience assessing otters watched randomized videos of otter gaits and assigned a clinical lameness score. Two additional evaluators watched the videos: an experienced veterinarian in small animal practice and a final-year veterinary student. All evaluators for OMA and clinical lameness score were blinded to treatment group. Radiographs performed prior to, and following, the study were assessed by a board-certified radiologist (Dennison). The OMA questionnaire had high reliability coefficients and correlated strongly with clinical gait scores and radiographic assessment. Although hyaluronic acid appears to be safe for use in otters at the dose described, there was no observed significant effect of hyaluronic acid on clinical lameness scores, OMA scores, or radiographic assessment of the limbs. The development of the OMA questionnaire is a promising tool for evaluating lameness in managed-care otters and may be further validated in future studies investigating therapeutics or incorporated as a component of animal welfare assessment.

Patient Education for Kidney Failure Treatment: A Mixed-Methods Study.

RATIONALE & OBJECTIVE: Education programs are needed for people with advanced chronic kidney disease to understand kidney failure treatment options and participate in shared decision-making (SDM). Little is known about the content and accessibility of current education programs or whether they support SDM. STUDY DESIGN: Stakeholder-engaged, mixed-methods design incorporating qualitative observations and interviews, and a quantitative content analysis of slide presentations. SETTING & PARTICIPANTS: Four sites located in Boston, Chicago, Portland (Maine), and San Diego. ANALYTICAL APPROACH: Thematic analysis based on the Ottawa Framework (observations and interviews) and descriptive statistical analysis (slide presentations). RESULTS: Data were collected from observations of 9 education sessions, 5 semistructured interviews with educators, and 133 educational slide presentations. Sites offered group classes or one-on-one sessions. Development, quality, and accuracy of educational materials varied widely. Educators emphasized dialysis (often in-center hemodialysis), with little mention of conservative management. Educators reported patients were often referred too late to education sessions and that some patients become overwhelmed if they learn of the implications of kidney failure in a group setting. Commonly, sessions were general and did not provide opportunities for tailored information most supportive of SDM. Few nephrologists were involved in education sessions or aware of the educational content. Content gaps included prognosis, decision support, mental health and cognition, advance care planning, cost, and diet. Slide presentations used did not consistently reflect best practices related to health literacy. LIMITATIONS: Findings may not be broadly generalizable. CONCLUSIONS: Education sessions focused on kidney failure treatment options do not consistently follow best practices related to health literacy or for supporting SDM. To facilitate SDM, the establishment of expectations for kidney failure treatment options should be clearly defined and integrated into the clinical workflow. Addressing content gaps, health literacy, and communication with nephrologists is necessary to improve patient education in the setting of advanced chronic kidney disease.

Emotional and interpersonal mechanisms in community SSRI treatment of social anxiety disorder.

BACKGROUND: Affective and interpersonal behavioural patterns characteristic of social anxiety disorder show improvement during treatment with serotonin agonists (e.g., selective serotonin reuptake inhibitors), commonly used in the treatment of social anxiety disorder. The present study sought to establish whether, during community psychopharmacological treatment of social anxiety disorder, changes in positive or negative affect and agreeable or quarrelsome behaviour mediate improvement in social anxiety symptom severity or follow from it. METHODS: Adults diagnosed with social anxiety disorder (n = 48) recorded their interpersonal behaviour and affect naturalistically in an event-contingent recording procedure for 1-week periods before and during the first 4 months of treatment with paroxetine. Participants and treating psychiatrists assessed the severity of social anxiety symptoms monthly. A multivariate latent change score framework examined temporally lagged associations of change in affect and interpersonal behaviour with change in social anxiety symptom severity. RESULTS: Elevated agreeable behaviour and positive affect predicted greater subsequent reduction in social anxiety symptom severity over the following month of treatment. Elevated negative affect, but not quarrelsome behaviour, predicted less subsequent reduction in symptom severity. LIMITATIONS: Limitations included limited assessment of extreme behaviour (e.g., violence) that may have precluded examining the efficacy of paroxetine because of the lack of a placebo control group. CONCLUSION: The present study suggests that interpersonal behaviour and affect may be putative mechanisms of action for serotonergic treatment of social anxiety disorder. Prosocial behaviour and positive affect increase during serotonergic treatment of social anxiety disorder. Specifically, modulating agreeable behaviour, positive affect and negative affect in individuals' daily lives may partially explain and refine clinical intervention.

Image-guided chest tube drainage in the management of chylothorax post cardiac surgery in children: a single-center case series.

BACKGROUND: In children, chylothorax post cardiac surgery can be difficult to treat, may run a protracted course, and remains a source of morbidity and mortality. OBJECTIVE: To analyze the experience with percutaneous image-guided chest-tube drainage in the management of post-cardiac-surgery chylothoraces in children. MATERIALS AND METHODS: We conducted a single-center retrospective case series of 37 post-cardiac-surgery chylothoraces in 34 children (20 boys; 59%), requiring 48 drainage procedures with placement of 53 image-guided chest tubes over the time period 2004 to 2015. We analyzed clinical and procedural details, adverse events and outcomes. Median age was 0.6 years, median weight 7.2 kg. RESULTS: Attempted treatments of chylothoraces prior to image-guided chest tubes included dietary restrictions (32/37, 86%), octreotide (12/37, 32%), steroids (7/37, 19%) and thoracic duct ligation (5/37, 14%). Image-guided chest tubes (n=43/53, 81%) were single unilateral in 29 children, bilateral in 4 (n=8/53, 15%), and there were two ipsilateral tubes in one (2/53, 4%). Effusions were isolated, walled-off, in 33/53 (62%). In 20/48 procedures (42%) effusions were septated/complex. The mean drainage through image-guided chest tubes was 17.3 mL/kg in the first 24 h, and 13.4 mL/kg/day from diagnosis to chest tube removal; total mean drainage from all chest tubes was 19.6 mL/kg/day. Nine major and 27 minor maintenance procedures were required during 1,207 tube-days (rate: 30 maintenance/1,000 tube-days). Median tube dwell time was 21 days (range 4-57 days). There were eight mild adverse events, three moderate adverse events and no severe adverse events related to image-guided chest tubes. Radiologic resolution was achieved in 26/37 (70%). Twenty-three children (68%) survived to discharge; 11 children (32%) died from underlying cardiac disease. CONCLUSION: Management of chylothorax post-cardiac-surgery in children is multidisciplinary, requiring concomitant multipronged approaches, often through a protracted course. Multiple image-guided chest tube drainages can help achieve resolution with few complications. Interventional radiology involvement in tube care and maintenance is required. Overall, mortality remains high.

Standardisation of management after Norwood operation has not improved 1-year outcomes.

INTRODUCTION: Treatment of hypoplastic left heart syndrome varies across institutions. This study examined the impact of introducing a standardised programme. METHODS: This retrospective cohort study evaluated the effects of a comprehensive strategy on 1-year transplant-free survival with preserved ventricular and atrioventricular valve (AVV) function following a Norwood operation. This strategy included standardised operative and perioperative management and dedicated interstage monitoring. The post-implementation cohort (C2) was compared to historic controls (C1). Outcomes were assessed using logistic regression and Kaplan-Meier analysis. RESULTS: The study included 105 patients, 76 in C1 and 29 in C2. Groups had similar baseline characteristics, including percentage with preserved ventricular (96% C1 versus 100% C2, p = 0.28) and AVV function (97% C1 versus 93% C2, p = 0.31). Perioperatively, C2 had higher indexed oxygen delivery (348 ± 67 ml/minute/m2 C1 versus 402 ± 102ml/minute/m2 C2, p = 0.015) and lower renal injury (47% C1 versus 3% C2, p = 0.004). The primary outcome was similar in both groups (49% C1 and 52% C2, p = 0.78), with comparable rates of death and transplantation (36% C1 versus 38% C2, p = 0.89) and ventricular (2% C1 versus 0% C2, p = 0.53) and AVV dysfunction (11% C1 versus 11% C2, p = 0.96) at 1-year. When accounting for cohort and 100-day freedom from hospitalisation, female gender (OR 3.7, p = 0.01) increased and ventricular dysfunction (OR 0.21, p = 0.02) and CPR (OR 0.11, p = 0.002) or ECMO use (OR 0.15, p = 001) decreased the likelihood of 1-year transplant-free survival. CONCLUSIONS: Standardised perioperative management was not associated with improved 1-year transplant-free survival. Post-operative ventricular or AVV dysfunction was the strongest predictor of 1-year mortality.

CEREBROSPINAL FLUID SAMPLING IN A BOTTLENOSE DOLPHIN (TURSIOPS TRUNCATUS) UNDER GENERAL ANESTHESIA.

Brucella ceti, associated with neurobrucellosis, has been isolated from cerebrospinal fluid (CSF) of postmortem cetaceans. A 106-kg, stranded female bottlenose dolphin (Tursiops truncatus) presented with serum antibodies to Brucella spp. via competitive enzyme-linked immunosorbent assay and fluorescence polarization assay. Polymerase chain reaction (PCR) and culture of whole blood, bronchoalveolar fluid, and rectal, nasal, and genital swabs for Brucella spp. were consistently negative. Serial computed tomography revealed mild focal dilatation of brain ventricles. CSF sampling was warranted to exclude neurobrucellosis. Sedation was achieved with 30 mg diazepam (0.28 mg/kg) orally 2.5 hours prior to arrival in hospital, followed by 5.3 mg midazolam (0.05 mg/kg) intramuscularly, and anesthetic induction with 2.5 mg midazolam (0.02 mg/kg) and 200 mg propofol (2 mg/kg) administered slowly intravenously, followed by intubation and maintenance on sevoflurane using controlled mechanical and apneustic anesthesia ventilation. The atlanto-occipital joint was opened by flexing the upper cervical region with the animal in left lateral recumbency. A 20-ga × 6-inch spinal needle was advanced into the cisterna magna using radiographic guidance. CSF was collected successfully with no neurological deficits appreciable on recovery. Brucella spp. was not identified via PCR or culture. This represents the first report of an antemortem CSF tap in a cetacean.

Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.

The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.

Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats.

BACKGROUND: Cognitive deficits after perinatal anesthetic exposure are well established outcomes in animal models. This vulnerability is sex-dependent and associated with expression levels of the chloride transporters NKCC1 and KCC2. The hypothesis was that androgen signaling, NKCC1 function, and the age of isoflurane exposure are critical for the manifestation of anesthetic neurotoxicity in male rats. METHODS: Flutamide, an androgen receptor antagonist, was administered to male rats on postnatal days 2, 4, and 6 before 6 h of isoflurane on postnatal day 7 (ntotal = 26). Spatial and recognition memory were subsequently tested in adulthood. NKCC1 and KCC2 protein levels were measured from cortical lysates by Western blot on postnatal day 7 (ntotal = 20). Bumetanide, an NKCC1 antagonist, was injected immediately before isoflurane exposure (postnatal day 7) to study the effect of NKCC1 inhibition (ntotal = 48). To determine whether male rats remain vulnerable to anesthetic neurotoxicity as juveniles, postnatal day 14 animals were exposed to isoflurane and assessed as adults (ntotal = 30). RESULTS: Flutamide-treated male rats exposed to isoflurane successfully navigated the spatial (Barnes maze probe trial F[1, 151] = 78; P < 0.001; mean goal exploration ± SD, 6.4 ± 3.9 s) and recognition memory tasks (mean discrimination index ± SD, 0.09 ± 0.14; P = 0.003), unlike isoflurane-exposed controls. Flutamide changed expression patterns of NKCC1 (mean density ± SD: control, 1.49 ± 0.69; flutamide, 0.47 ± 0.11; P < 0.001) and KCC2 (median density [25th percentile, 75th percentile]: control, 0.23 [0.13, 0.49]; flutamide, 1.47 [1.18,1.62]; P < 0.001). Inhibiting NKCC1 with bumetanide was protective for spatial memory (probe trial F[1, 162] = 6.6; P = 0.011; mean goal time, 4.6 [7.4] s). Delaying isoflurane exposure until postnatal day 14 in males preserved spatial memory (probe trial F[1, 140] = 28; P < 0.001; mean goal time, 6.1 [7.0] s). CONCLUSIONS: Vulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity.

Associations of perceived information adequacy and knowledge with pursuit of live donor kidney transplants and living donor inquiries among African American transplant candidates.

We studied associations between perceived adequacy of live donor kidney transplant (LDKT) information or knowledge with pursuit of LDKT or receipt of live donor inquiries among 300 African American kidney transplant candidates. Participants reported via questionnaire how informed or knowledgeable they felt regarding LDKT. Participants also reported their pursuit of LDKT, categorized as "low" (no discussion with family or friends about LDKT and no identified donor), "intermediate" (discussed LDKT with family but no identified donor) or "high" (discussed LDKT with family and identified a potential donor). We reviewed participants' electronic health records to identify potential donors' transplant center inquiries on participants' behalves. A minority of participants reported they felt "very" or "extremely" well informed about LDKT (39%) or had "a great deal" of LDKT knowledge (38%). Participants perceiving themselves as "very" or "extremely" (vs "not" or "slightly") well informed about LDKT had statistically significantly greater odds of intermediate or high (vs low) pursuit of LDKT (odds ratio [95% confidence interval] 2.71 [1.02-7.17]). Perceived LDKT knowledge was not associated with pursuit of LDKT. Neither perceived information adequacy nor knowledge was associated with living donor inquiries. Efforts to better understand the role of education in the pursuit of LDKT among African American transplant candidates are needed.

Development of a COVID-19 alternate care site from ground zero: A nursing perspective.

The novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak rapidly generated an unprecedented global, national, and state public health crisis with the need to rapidly develop alternate care sites (ACS) to care for COVID-19 patients within an overburdened health care system. A hospital care model ACS to increase the health care capacity, provide care for mild to moderately symptomatic patients, and offer local self-sustainment for a surge of patients was developed in Memphis, Tennessee located in Shelby County. We completed a temporary conversion of a large unused newspaper publication building to a health care facility for COVID-19 patients. Developing an ACS from ground zero was met with many challenges, and throughout the process important lessons were learned. With the goal to complete the building conversion within a 28-day timeframe, collaboration among the numerous governmental, health care, and private agencies was critical and nursing leadership was key to this process. The purpose of this paper is to describe the development of a COVID-19 ACS in Memphis, TN, which has a large at-risk population with limited access to health care. Specifically, we will discuss the strong leadership role of nursing faculty, key challenges, and lessons learned, as well as provide checklists and models for others in similar circumstances.

Female rats are more vulnerable to lasting cognitive impairment after isoflurane exposure on postnatal day 4 than 7.

BACKGROUND: The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested. METHODS: Female rats were exposed to isoflurane (Iso) 1 minimum alveolar concentration or sham anaesthesia at P4 or P7. Starting at P35, rats underwent a series of behavioural tasks to test their spatial and recognition memory. Cell death immediately after anaesthesia was quantified by Fluoro-Jade C staining in select brain regions, and developmental expression of the chloride transporters KCC2 and NKCC1 was analysed by immunoblotting in male and female rats at P4 and P7. RESULTS: Female rats exposed to Iso at P4 displayed impaired spatial, object-place, -context, and social recognition memory, and increased cell death in the hippocampus and laterodorsal thalamus. Female rats exposed at P7 exhibited only decreased performance in object-context compared with control. The ratio of NKCC1/KCC2 expression in cerebral cortex was higher in P4 females than in P7 females, and similar to that in P7 males. CONCLUSIONS: Female rats exposed to Iso at P4 are sensitive to anaesthetic injury historically observed in P7 males. This is consistent with a comparably immature developmental state in P4 females and P7 males. The window of anaesthetic vulnerability correlates with sex-specific cortical expression of chloride transporters NKCC1 and KCC2. These findings suggest that both sex and developmental age play important roles in determining the outcome after early anaesthesia exposure.

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats.

BACKGROUND: Early life anesthesia exposure results in long-term cognitive deficits in rats. Environmental enrichment consisting of social housing, a stimulating environment, and voluntary exercise can rescue this deficit. We hypothesized that exercise alone is sufficient to rescue the cognitive deficit associated with perinatal anesthesia. METHODS: Postnatal day 7 male rats (P7) underwent isoflurane (Iso) or sham exposure and were subsequently weaned at P21. They were then singly housed in a cage with a running wheel or a fixed wheel. After 3 weeks of exercise, animals underwent behavioral testing for spatial and recognition memory assessments. Animals were killed at various time points to accomplish either bromodeoxyuridine (BrdU) labeling or quantitative real-time polymerase chain reaction (qRT-PCR) to quantify brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) levels. RESULTS: Postweaning voluntary exercise rescued the long-term spatial memory deficit associated with perinatal Iso exposure. Iso-sedentary animals did not discriminate the goal quadrant, spending no more time than chance during the Barnes maze probe trial (1-sample t test, P = .524) while all other groups did (1-sample t test, PIso-exercise = .033; Pcontrol [Con]-sedentary = .004). We did not find a deficit in recognition memory tasks after Iso exposure as we observed previously. BrdU incorporation in the adult hippocampus of Iso-sedentary animals was decreased compared to sedentary controls (Tukey P = .005). Exercise prevented this decrease, with Iso-exercise animals having more proliferation than Iso-sedentary (Tukey P < .001). There was no effect of exercise or Iso on BDNF mRNA in either the cortex or hippocampus (cortex: FExercise[1,32] = 0.236, P = .631; FIso [1,32] = 0.038, P = .847; FInteraction [1,32] = 1.543, P = .223; and hippocampus: FExercise[1,33] = 1.186, P = .284; FIso [1,33] = 1.46, P = .236; FInteraction[1,33] = 1.78, P = .191). CONCLUSIONS: Exercise restores BrdU incorporation and rescues a spatial memory deficit after early life anesthesia exposure. This demonstrates sufficiency of exercise alone in the context of environmental enrichment to recover a behavioral phenotype after a perinatal insult.