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Yael Yagur,1– 3 Sarah Choi,1,2 Jessica A Robertson,1,2 Orla Donohoe,1,2 Mohammed Almoqren,1,2 Danny Chou,1,2 David MB Rosen1,2 1Sydney Women’s Endosurgery Centre (SWEC), St George Hospital, Sydney, NSW, Australia; 2University of New South Wales, Sydney, NSW, Australia; 3School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Yael Yagur, Sydney Women’s Endosurgery Centre (SWEC), Suite 10b, Level 3, St George Private Hospital, 1 South St Kogarah, Sydney, NSW, 2217, Australia, Tel +610434174885, Email yaelyagur@gmail.comObjective: We aimed to explore the abnormal pathology findings in appendix specimens removed based on intraoperative abnormal appearance during elective surgery for benign gynaecological conditions by a minimally invasive gynaecologist, as well as the associated complication rate.Materials and Methods: This retrospective cohort study was conducted in a tertiary referral surgical centre for benign gynaecological conditions between the years 2004– 2023. It included patients who underwent appendicectomy by a trained minimally invasive gynaecologist based on observations during surgery for benign gynaecological conditions. Data included demographic, clinical, surgical and pathological information followed by postoperative complication data obtained from electronic medical records and direct communication with surgical colleagues. The primary outcome was the evaluation of the abnormal pathological findings in the appendix. The secondary outcome was the complication rate associated with appendicectomy in these cases.Results: The study cohort included 34 women who met inclusion criteria and underwent a laparoscopic surgery for endometriosis, chronic pelvic pain or a benign ovarian mass. Indications for appendicectomy included twelve cases (38.2%) with apparent appendiceal immobility (stiffness), fourteen cases (41.2%) with an appendix adherent to ovaries or the pelvic side walls, and seven cases (20.6%) with an abnormal appearance (large, wide, long, coiled, or curved). Pathological findings revealed six cases (17.6%) of acute or chronic appendicitis, four cases (11.8%) of endometriosis, five cases (14.7%) of abnormal pathological conditions, and three cases (8.8%) of cancer (two cases of well-differentiated adenocarcinoma and one case of low-grade appendiceal mucinous cystadenoma). Postoperative complication rate was 5.8% (two cases).Conclusion: This study supports incorporating appendicectomy by trained gynaecological specialists during gynaecological elective surgery when abnormal findings are encountered. Further research and guidelines in this area can provide even greater clarity and direction for the future of gynaecological surgical practice.Keywords: appendicectomy, cancer, minimally invasive gynaecology surgery, training

Background: Identification of predictors of hyporesponsiveness to erythropoietin-stimulating agents (ESAs) in hemodialysis (HD) patients may help improve anemia management and reduce hemoglobin level variability.Study Design: We conducted repeated-measure and logistic regression analyses in a retrospective cohort of long-term HD patients to examine the association of iron markers and measures of renal osteodystrophy with ESA responsiveness. The ESA response coefficient at the individual level, ie, the least confounded dose-response association, was separated from the population level, assumed to represent confounding by medical indication.Setting/participants: The national database of a large dialysis organization (DaVita Inc, El Segundo, CA) with 38,328 surviving prevalent HD patients during 12 months who received ESA for at least 3 consecutive calendar quarters was examined.Predictors: Serum levels of ferritin, iron saturation ratio, intact parathyroid hormone, and alkaline phosphatase. OUTCOMES/OTHER MEASUREMENTS: The main outcome was case-mix-adjusted hemoglobin response to quarterly averaged ESA dose at the individual level. The odds ratio (OR) of the greatest versus poorest ESA-response quartile at the patient level was calculated. OR less than 1.0 indicated ESA hyporesponsiveness, and OR greater than 1.0, enhanced responsiveness.Results: Mean ESA-response coefficients of the least to most responsive quartiles were 0.301 +/- 0.033 (SD), 0.344 +/- 0.004, 0.357 +/- 0.004, and 0.389 +/- 0.026 g/dL greater hemoglobin level per 1,000 U/wk greater ESA dose in each quarter, respectively. The ORs of greatest versus poorest ESA responsiveness at the patient level were serum ferritin level less than 200 ng/mL (0.77; 95% confidence interval [CI], 0.70 to 0.86; reference, 200 to 500 ng/mL), iron saturation ratio less than 20% (0.54; 95% CI, 0.49 to 0.59; reference, 20% to 30%), intact parathyroid hormone level of 600 pg/mL or greater (0.54; 95% CI, 0.49 to 0.60; reference, 150 to 300 pg/mL), and alkaline phosphatase level of 160 IU/L or greater (0.64; 95% CI, 0.58 to 0.70; reference, 80 to 120 IU/L). Lower estimated dietary protein intake and serum levels of nutritional markers were also associated with greater risk of ESA hyporesponsiveness.Limitations: Our results may incorporate uncontrolled confounding. Achieved hemoglobin level may have different associations than targeted hemoglobin level.Conclusions: In long-term HD patients, low iron stores, hyperparathyroidism, and high-turnover bone disease are associated with significant ESA hyporesponsiveness. Prospective studies are needed to verify these associations. [ABSTRACT FROM AUTHOR]

Background: There is increasing recognition of the importance of obtaining children's reports of their health, but significant challenges must be overcome to do so in a systematic, population-based manner.Objective: The objective of this study was to present the initial tests of the Child Report Form of the Child Health and Illness Profile-Child Edition (CHIP-CE/CRF), a self-report health status instrument for children 6 to 11 years old.Methods: Three studies iteratively evaluated revisions of the CHIP-CE/CRF in 4 geographic locations in the United States. Children (N=1708) whose families represent the low to middle socioeconomic strata and predominant U.S. racial/ethnic groups were involved.Results: The final CHIP-CE/CRF includes 5 domains: Satisfaction (with self and health), Comfort (emotional and physical symptoms and limitations), Resilience (positive activities that promote health), Risk Avoidance (risky behaviors that influence future health), and Achievement (of social expectations in school and with peers). The internal consistency and test-retest reliability of the domains are good to excellent, with a definite age gradient such that younger children's responses are less reliable although still acceptable. Validity is supported through criterion and construct validity tests and structural analyses. Standard scores (mean, 50; standard deviation, 10) were established.Conclusions: Health status can be reliably and validly assessed directly from children 6 to 11 years old on the CHIP-CE/CRF. In combination with the CHIP-AE, self-reported health status can now be obtained from youth 6 to 18 years old using a consistent conceptual framework. This can greatly improve the precision and comparability of health assessments of youth, enhancing the validity of outcome research and longitudinal studies across childhood and adolescence. [ABSTRACT FROM AUTHOR]

Background: Valid, comprehensive instruments to describe, monitor, and evaluate health from childhood through adolescence are almost nonexistent, but are critical for health resource planning, evaluation of policy, preventive, and clinical interventions, and understanding trajectories of health during this important period of life.Objectives: The objectives of this study were to describe the development, testing, and final versions of the Parent Report Form of the Child Health and Illness Profile-Child Edition (CHIP-CE/PRF), designed to measure the health of children 6 to 11 years old from the caregiver perspective.Methods: Parents (N=1049) completed a version of the CHIP-CE/PRF in 4 locations in the United States, either in clinic waiting rooms or their homes. They differed in race/ethnicity, socioeconomic level, and native language.Results: The Parent CHIP-CE is feasible; parents with a 5th-grade reading level complete the 76-item PRF in 20 minutes. Its domains (Satisfaction, Comfort, Risk Avoidance, Resilience, and Achievement) measure structurally distinct, interrelated aspects of health. Domain reliability is high: internal consistency=0.79-0.88; retest reliability (ICC)=0.71-0.85. Validity is supported. The scale scores are sensitive to predicted age, gender, and socioeconomic status differences in health.Conclusion: The CHIP-Child Edition/Parent Report Form is a psychometrically sound, conceptually based measure of child health that works well in diverse populations. It produces scores that parallel those of children on the CHIP-CE/CRF and adolescents on the CHIP-AE and allows health to be consistently assessed from childhood through adolescence. It should meet many needs for describing, monitoring, and understanding child health and evaluating outcomes of interventions. [ABSTRACT FROM AUTHOR]

Complete intravenous (IV) drug administration to a pediatric patient is an important nursing intervention. Verification of the amount of flush solution that is necessary to deliver > 95% of an IV medication to the patient was the goal of a laboratory demonstration and a clinical study. In the laboratory, it was determined that three times the volume of the dead space of the IV tubing was the required volume needed to flush dye from IV administration sets. This principle was then applied to pediatric patients receiving tobramycin medication therapy. Nurses administered tobramycin through 27 IV solusets of patients using three measured volumes of IV flush solution. Samples were collected from the IV tubing and analyzed to measure the concentration of tobramycin in the tubing. All three resulted in administration of > 95% of the medication. A nursing procedure was written to standardize the administration of IV medications to pediatric patients using two times the volume of the dead space of the IV tubing as the flush volume. [ABSTRACT FROM AUTHOR]

Chris Bradford’s Young Samurai series, and his more recent Bodyguard Series draw on a strong sense of hegemonic masculinity to secure popularity for the protagonist. The success of these books is particularly interesting when one considers the gender agendas that are embraced by modern western society and the extent to which general opinion has altered in terms of the performance of masculinity.

Abstract Background In Australia generally, smoking prevalence more than halved after 1980 and recently commenced to decline among Australia's disadvantaged Indigenous peoples. However, in some remote Indigenous Australian communities in the Northern Territory (NT), extremely high rates of up to 83% have not changed over the past 25 years. The World Health Organisation has called for public health and political leadership to address a global tobacco epidemic. For Indigenous Australians, unprecedented policies aim to overcome disadvantage and close the 'health gap' with reducing tobacco use the top priority. This study identifies challenges and opportunities to implementing these important new tobacco initiatives in remote Indigenous communities. Methods: With little empirical evidence available, we interviewed 82 key stakeholders across the NT representing operational- and management-level service providers, local Indigenous and non-Indigenous participants to identify challenges and opportunities for translating new policies into successful tobacco interventions. Data were analysed using qualitative approaches to identify emergent themes. Results The 20 emergent themes were classified using counts of occasions each theme occurred in the transcribed data as challenge or opportunity. The 'smoke-free policies' theme occurred most frequently as opportunity but infrequently as challenge while 'health workforce capacity' occurred most frequently as challenge but less frequently as opportunity, suggesting that policy implementation is constrained by lack of a skilled workforce. 'Smoking cessation support' occurred frequently as opportunity but also frequently as challenge suggesting that support for individuals requires additional input and attention. Conclusions These results from interviews with local and operational-level participants indicate that current tobacco policies in Australia targeting Indigenous smoking are sound and comprehensive. However, for remote Indigenous Australian communities, local and operational-level participants' views point to an 'implementation gap'. Their views should be heard because they are in a position to provide practical recommendations for effective policy implementation faithful to its design, thereby translating sound policy into meaningful action. Some recommendations may also find a place in culturally diverse low- and middle-income countries. Key words: tobacco policy implementation, challenges, opportunities, remote Indigenous Australian communities.

Abstract Background In upper limb injuries it is important to assess associated neurological injury. The aim of this study was to assess the initial (Emergency Department (ED)) documentation of neurological status in paediatric patients presenting with upper limb injuries. Findings Case notes of paediatric patients admitted to the orthopaedic ward with upper limb injuries were retrospectively collected over a three month period. Initial ED documentation was recorded and case notes examined for any neurological deficit on admission. Of the 121 patients, 107 (88.4%) of case notes had some form of neurological documentation. The remaining case notes (n = 14, 11.6%) had no mention of neurological examination. There were 10 (8.2%) patients with pre-operative neurological deficits identified; none of these had been previously identified by the ED. Conclusion There are failings of neurological documentation on the part of ED staff. It is likely that these reflect a knowledge deficit in the examination of the injured upper limb in paediatric patients.

Abstract Background The burden of patients with heart failure on health care systems is widely recognised, although there have been few attempts to quantify individual patterns of care and differences in health service utilisation related to age, socio-economic factors and the presence of co-morbidities. The aim of this study was to assess the typical profile, trajectory and resource use of a cohort of Australian patients with heart failure using linked population-based, patient-level data. Methods Using hospital separations (Admitted Patient Data Collection) with death registrations (Registry of Births, Deaths and Marriages) for the period 2000–2007 we estimated age- and gender-specific rates of index admissions and readmissions, risk factors for hospital readmission, mean length of stay (LOS), median survival and bed-days occupied by patients with heart failure in New South Wales, Australia. Results We identified 29,161 index admissions for heart failure. Admission rates increased with age, and were higher for males than females for all age groups. Age-standardised rates decreased over time (256.7 to 237.7/100,000 for males and 235.3 to 217.1/100,000 for females from 2002–3 to 2006–7; p = 0.0073 adjusted for gender). Readmission rates (any cause) were 27% and 73% at 28-days and one year respectively; readmission rates for heart failure were 11% and 32% respectively. All cause mortality was 10% and 28% at 28 days and one year. Increasing age was associated with more heart failure readmissions, longer LOS and shorter median survival. Increasing age, increasing Charlson comorbidity score and male gender were risk factors for hospital readmission. Cohort members occupied 954,888 hospital bed-days during the study period (any cause); 383,646 bed-days were attributed to heart failure admissions. Conclusions The rates of index admissions for heart failure decreased significantly in both males and females over the study period. However, the impact on acute care hospital beds was substantial, with heart failure patients occupying almost 200,000 bed-days per year in NSW over the five year study period. The strong age-related trends highlight the importance of stabilising elderly patients before discharge and community-based outreach programs to better manage heart failure and reduce readmissions.

Abstract Background This paper examines the specificity and sensitivity of a breath carbon monoxide (BCO) test and optimum BCO cutoff level for validating self-reported tobacco smoking in Indigenous Australians in Arnhem Land, Northern Territory (NT). Methods In a sample of 400 people (≥16 years) interviewed about tobacco use in three communities, both self-reported smoking and BCO data were recorded for 309 study participants. Of these, 249 reported smoking tobacco within the preceding 24 hours, and 60 reported they had never smoked or had not smoked tobacco for ≥6 months. The sample was opportunistically recruited using quotas to reflect age and gender balances in the communities where the combined Indigenous populations comprised 1,104 males and 1,215 females (≥16 years). Local Indigenous research workers assisted researchers in interviewing participants and facilitating BCO tests using a portable hand-held analyzer. Results A BCO cutoff of ≥7 parts per million (ppm) provided good agreement between self-report and BCO (96.0% sensitivity, 93.3% specificity). An alternative cutoff of ≥5 ppm increased sensitivity from 96.0% to 99.6% with no change in specificity (93.3%). With data for two self-reported nonsmokers who also reported that they smoked cannabis removed from the analysis, specificity increased to 96.6%. Conclusion In these disadvantaged Indigenous populations, where data describing smoking are few, testing for BCO provides a practical, noninvasive, and immediate method to validate self-reported smoking. In further studies of tobacco smoking in these populations, cannabis use should be considered where self-reported nonsmokers show high BCO.

Abstract Background Injection drug use is an important public health problem. Epidemiological understanding of this problem is incomplete as longitudinal studies in the general population are difficult to undertake. In particular little is known about early life risk factors for later drug injection or about the life course of injection once established including the influence of medical and social interventions. Methods Individuals thought to be drug injectors were identified through a single primary medical care facility in Edinburgh between 1980 and 2006 and flagged with the General Registry Office. From October 2005 - October 2007, these cases were traced and invited to undergo interview assessment covering early life experience, substance use, health and social histories. Age and sex matched controls for confirmed cases (alive and dead) were later recruited through the same health facility. Controls for living cases completed the same structured interview schedule. Data were also collected on cases and controls through linkage to routine primary care records, death registrations, hospital contact statistics and police and prison records. All interviews were conducted with the knowledge and permission of the current GP. Results The initial cohort size was 814. At start of follow up 227 had died. Of the remaining 587: 20 had no contact details and 5 had embarked from the UK; 40 declined participation; 38 did not respond to invitations; 14 were excluded by their GP on health or social grounds and 22 had their contact details withheld by administrative authorities. 448 were interviewed of whom 16 denied injection and were excluded. Of 191 dead cases with medical records 4 were excluded as their records contained no evidence of injection. 5 interviewed cases died before follow up was concluded though these individuals were counted as "live" cases. 1 control per case (dead and alive) was recruited. Linkage to Scottish Morbidity Records data (available from 1981 onwards) on general acute inpatient and day cases, mental health inpatient and day cases and cancer was provided by Information Services, NHS Scotland, for all cases interviewed and all dead cases. The Scottish Prison Service provided records for 198 (46%) of cases interviewed, 48 cases not interviewed and 34 (18%) of dead cases. For a sub-sample of 100 interviewees a search of the Lothian and Borders police database was made for official criminal records and 94 had criminal records. Data linkage for controls is ongoing. Conclusions Injecting drug users recruited from a community setting can be successfully followed-up through interviews and record linkage. Information from injecting cases is being analysed in terms of injecting patterns and possible influences on these. Comparisons between cases and controls will allow identification of possibly modifiable early life risk factors for drug injection and will also clarify the burden of disease associated with injection and the influence on this of different health and social interventions.

Abstract Background Computerised clinical decision support systems (CDSSs) are used widely to improve quality of care and patient outcomes. This systematic review evaluated the impact of CDSSs in targeting specific aspects of prescribing, namely initiating, monitoring and stopping therapy. We also examined the influence of clinical setting (institutional vs ambulatory care), system- or user-initiation of CDSS, multi-faceted vs stand alone CDSS interventions and clinical target on practice changes in line with the intent of the CDSS. Methods We searched Medline, Embase and PsychINFO for publications from 1990-2007 detailing CDSS prescribing interventions. Pairs of independent reviewers extracted the key features and prescribing outcomes of methodologically adequate studies (experiments and strong quasi-experiments). Results 56 studies met our inclusion criteria, 38 addressing initiating, 23 monitoring and three stopping therapy. At the time of initiating therapy, CDSSs appear to be somewhat more effective after, rather than before, drug selection has occurred (7/12 versus 12/26 studies reporting statistically significant improvements in favour of CDSSs on = 50% of prescribing outcomes reported). CDSSs also appeared to be effective for monitoring therapy, particularly using laboratory test reminders (4/7 studies reporting significant improvements in favour of CDSSs on the majority of prescribing outcomes). None of the studies addressing stopping therapy demonstrated impacts in favour of CDSSs over comparators. The most consistently effective approaches used system-initiated advice to fine-tune existing therapy by making recommendations to improve patient safety, adjust the dose, duration or form of prescribed drugs or increase the laboratory testing rates for patients on long-term therapy. CDSSs appeared to perform better in institutional compared to ambulatory settings and when decision support was initiated automatically by the system as opposed to user initiation. CDSSs implemented with other strategies such as education were no more successful in improving prescribing than stand alone interventions. Cardiovascular disease was the most studied clinical target but few studies demonstrated significant improvements on the majority of prescribing outcomes. Conclusion Our understanding of CDSS impacts on specific aspects of the prescribing process remains relatively limited. Future implementation should build on effective approaches including the use of system-initiated advice to address safety issues and improve the monitoring of therapy.

Author advances the discussion about positive genetic selection by looking at the use of oocyte cytoplasm transfers as a possible means to prevent disease and to overcome fertility, focusing on the issues of family and kinship, commodification of eggs and egg donors, and germ-line alterations. [ABSTRACT FROM AUTHOR]

We compare life course characteristics of a cohort of African American women (N=457) by their smoking status at age 42: never smoker (34.1%), former smoker (27.8%), or current smoker (38.1%). The Woodlawn population from which our sample is drawn has been followed from first grade (1966-67) to mid adulthood (2002-3) and is a cohort of children from a disadvantaged Chicago community. Examination of the effects of cumulative disadvantage on smoking behavior showed that nearly half of women who first lived in poverty as children, dropped out of school, became teen mothers, and were poor as young adults currently smoked; less than 22% of women with none of these difficulties were current smokers. Regression analyses focusing on smoking and evidence of social disadvantage in childhood, adolescence, and young adulthood showed that women with more education were much less likely to be current smokers. Women reporting low parental supervision in adolescence and less frequent church attendance in young adulthood and those whose mothers' reported regular smoking were significantly more likely to be current smokers. Poverty and marital status in young adulthood varied significantly among smoking categories in bivariate relationships, but not in final multivariate regression models. Few other studies have examined smoking careers with data from age 6-42, comparing social disadvantage characteristics over the life course. While marital status, church involvement and parental supervision are not usually included as measures of socioeconomic status, they represent advantages in terms of social capital and should be considered mechanisms for transmitting disparities. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinical and pathological findings of rabbits diagnosed with lymphoma., Animals: 16 rabbits., Procedures: The medical and pathology records database of the Veterinary Medical Teaching Hospital at the University of California, Davis was searched for rabbits diagnosed with lymphoma from 1996 to 2019., Results: Mean age of the 16 rabbits was 8 years (range, 4.5 to 12 years). Immunophenotyping was performed in 14 cases. Diffuse, large, B-cell lymphoma was most common (n = 7) followed by epitheliotropic, T-cell lymphoma (2); type II enteropathy-associated, T-cell lymphoma (2); marginal-zone, B-cell lymphoma (1); peripheral, T-cell lymphoma not otherwise specified (cutaneous nonepitheliotropic lymphoma; 1); primary, mediastinal (thymic) large B-cell lymphoma (1), and unclassified (cytology only with no immunophenotyping; 2). Multiple chemotherapy protocols were used on the basis of each individual animal's disease state. Initial clinical improvement was reported for most rabbits receiving chemotherapy (5/6), with diffuse B-cell lymphoma responding most favorably to treatment. The 11 rabbits included in the survival analysis had a median survival time of 60 days (range, 1 to 480 days), and those diagnosed with B- and T-cell lymphoma had a median survival time of 8 and 36 days (range, 1 to 150 and 1 to 90 days), respectively., Clinical Relevance: Rabbits develop a range of lymphoma subtypes and, similar to humans and dogs, diffuse large B-cell lymphoma appears to be the most common. Chemotherapy treatments followed multiple protocols, which were mostly well tolerated and had a highly variable response. Further research into chemotherapy protocols is needed to optimize treatment of lymphoma in rabbits.

Background: Mutations in the ubiquitin ligase scaffold protein Cullin 3 ( CUL3 ) gene cause the disease familial hyperkalemic hypertension (FHHt). In the kidney, mutant CUL3 ( CUL3-Δ9 ) increases abundance of With-No-Lysine (K) Kinase 4 (WNK4), inappropriately activating sterile 20/SPS-1-related proline/alanine-rich kinase (SPAK), which then phosphorylates and hyperactivates the Na + Cl - cotransporter (NCC). The precise mechanism by which CUL3-Δ9 causes FHHt is unclear. We tested the hypothesis that reduced abundance of CUL3 and of Kelch-like 3 (KLHL3), the CUL3 substrate adaptor for WNK4, is mechanistically important. Because JAB1, an enzyme that inhibits CUL3 activity by removing the ubiquitin-like protein NEDD8, cannot interact with CUL3-Δ9, we also determined whether Jab1 disruption mimicked the effects of CUL3-Δ9 expression., Methods: We used an inducible renal tubule-specific system to generate several mouse models expressing CUL3-Δ9 , mice heterozygous for both CUL3 and KLHL3 ( Cul3 +/- /Klhl3 +/- ), and mice with short-term Jab1 disruption (to avoid renal injury associated with long-term disruption)., Results: Renal KLHL3 was higher in Cul3 -/- mice, but lower in Cul3 -/-/Δ9 mice and in the Cul3 +/-/Δ9 FHHt model, suggesting KLHL3 is a target for both WT and mutant CUL3 . Cul3 +/- /Klhl3 +/- mice displayed increased WNK4-SPAK activation and phospho-NCC abundance and an FHHt-like phenotype with increased plasma [K + ] and salt-sensitive blood pressure. Short-term Jab1 disruption in mice lowered the abundance of CUL3 and KLHL3 and increased the abundance of WNK4 and phospho-NCC., Conclusions: Jab1 -/- mice and Cul3 +/- /Klhl3 +/- mice recapitulated the effects of CUL3-Δ9 expression on WNK4-SPAK-NCC. Our data suggest degradation of both KLHL3 and CUL3 plays a central mechanistic role in CUL3-Δ9-mediated FHHt., (Copyright © 2022 by the American Society of Nephrology.)

We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach . Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

The renal nephron consists of a series of distinct cell types that function in concert to maintain fluid and electrolyte balance and blood pressure. The renin-angiotensin system (RAS) is central to Na + and volume balance. We aimed to determine how loss of angiotensin II signaling in the proximal tubule (PT), which reabsorbs the bulk of filtered Na + and volume, impacts solute transport throughout the nephron. We hypothesized that PT renin-angiotensin system disruption would not only depress PT Na + transporters but also impact downstream Na + transporters. Using a mouse model in which the angiotensin type 1a receptor (AT 1a R) is deleted specifically within the PT (AT 1a R PTKO), we profiled the abundance of Na + transporters, channels, and claudins along the nephron. Absence of PT AT 1a R signaling was associated with lower abundance of PT transporters (Na + /H + exchanger isoform 3, electrogenic Na + -bicarbonate cotransporter 1, and claudin 2) as well as lower abundance of downstream transporters (total and phosphorylated Na + -K + -2Cl - cotransporter, medullary Na + -K + -ATPase, phosphorylated NaCl cotransporter, and claudin 7) versus controls. However, transport activities of Na + -K + -2Cl - cotransporter and NaCl cotransporter (assessed with diuretics) were similar between groups in order to maintain electrolyte balance. Together, these results demonstrate the primary impact of angiotensin II regulation on Na + reabsorption in the PT at baseline and the associated influence on downstream Na + transporters, highlighting the ability of the nephron to integrate Na + transport along the nephron to maintain homeostasis. NEW & NOTEWORTHY Our study defines a novel role for proximal tubule angiotensin receptors in regulating the abundance of Na + transporters throughout the nephron, thereby contributing to the integrated control of fluid balance in vivo.

Atorvastatin is a synthetic statin administered in its active form and used for the treatment of dyslipidemias. In the current study, the effects of atorvastatin were evaluated on plasma lipid profiles and the potential for adverse effects after once daily PO dosing of atorvastatin for 30 days in Hispaniolan Amazon parrots ( Amazona ventralis ). Sixteen adult parrots (10 female, 6 male) with hypercholesterolemia were used for this study. Birds were assigned to 2 groups (treatment and control) of 8 parrots each (3 male, 5 female) after balancing for age, sex, originating institution, and baseline plasma cholesterol values. Compounded atorvastatin oral suspension (10 mg/kg) was administered PO once daily via gavage into the crop. Equivalent volumes of placebo suspension were administered to the control group. Plasma biochemistry and plasma lipid profile analysis (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TGs]) were analyzed on days 0, 14, and 30. Plasma samples and HDL-C fractions were evaluated for cholesterol and TG concentrations via enzymatic assays. Subtraction of HDL-C values from total cholesterol yielded the non-HDL-C concentration for each bird. Birds were routinely assessed for appetite, activity, and urofeces. Plasma atorvastatin concentrations were obtained from 7 of 8 birds in the treatment group from banked samples. Those samples were obtained on days 14 and 30, with drug administration 6 to 8 hours before collection. No significant differences were observed in total cholesterol, HDL-C, non-HDL-C, or TG between treatment and control groups at days 0, 14, and 30. Plasma atorvastatin concentrations were variable on day 14 (0.54-5.41 ng/ mL for 6 of 7 samples, with 1 outlier of 307 ng/mL) and on day 30 (0.79-6.74 ng/mL). No adverse effects were noted in any of the birds during the study period. When dosed PO at 10 mg/kg once daily, atorvastatin did not result in significant changes to plasma lipid profiles (eg, lowering of plasma total or non-HDL-C concentrations) at any time point during this study. Future studies to investigate pharmacokinetic and pharmacodynamic properties of atorvastatin in parrots may require increased doses and/or frequency of administration.