Terrestriality across the primate order: A review and analysis of ground use in primates.

Terrestriality is relatively rare in the predominantly arboreal primate order. How frequently, and when, terrestriality appears in primate evolution, and the factors that influence this behavior, are not well understood. To investigate this, we compiled data describing terrestriality in 515 extant nonhuman primate taxa. We describe the geographic and phylogenetic distribution of terrestriality, including an ancestral state reconstruction estimating the frequency and timing of evolutionary transitions to terrestriality. We review hypotheses concerning the evolution of primate terrestriality and test these using data we collected pertaining to characteristics including body mass and diet, and ecological factors including forest structure, food availability, weather, and predation pressure. Using Bayesian analyses, we find body mass and normalized difference vegetation index are the most reliable predictors of terrestriality. When considering subsets of taxa, we find ecological factors such as forest height and rainfall, and not body mass, are the most reliable predictors of terrestriality for platyrrhines and lemurs.

Manipulation Under Anesthesia and/or Lysis of Adhesions After Anterior Cruciate Ligament Reconstruction in Female Basketball Players: Does Race Play a Role?

BACKGROUND: Arthrofibrosis can limit function and return to sport after anterior cruciate ligament (ACL) reconstruction. Previously reported risk factors for developing arthrofibrosis after ACL reconstruction include female sex, age <18 years, time from injury to surgery <28 days, concomitant meniscal repair, prolonged immobilization, and genetic factors. There is a lack of evidence regarding whether race plays a significant role. HYPOTHESIS: The risk of undergoing manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA) after primary ACL reconstruction with bone-patellar tendon-bone (BTB) autograft in female basketball players is higher in African American players than in White players. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Using a computerized relational database, the authors identified competitive female basketball players who underwent primary ACL reconstruction with BTB autograft by the senior author over a 13-year period. Data previously entered from examinations and surgical findings were reviewed retrospectively. Univariate statistics and multivariable logistic regression were used to assess the relationship between undergoing subsequent MUA and/or LOA and study predictors. RESULTS: A total of 186 knees (114 African American knees and 72 White knees) met inclusion criteria. The overall rate of MUA and/or LOA was 8.6%. Thirteen African American knees (11.4%) and 3 White knees (4.2%) underwent MUA and/or LOA for treatment of arthrofibrosis. No study predictor was found to have a statistically significant relationship with the rate of MUA and/or LOA on univariate analysis. However, when controlling for body mass index and previously described risk factors (age <18 years, time from injury to surgery ≤28 days, and concomitant meniscal repair) in the logistic regression model, the authors found that MUA and/or LOA was more likely in African American (odds ratio, 4.01 [95% CI, 1.01-15.92]; P = .049) than in White female players and in patients who underwent ACL reconstruction within 28 days of injury (odds ratio, 4.01 [95% CI, 1.18-13.57]; P = .026) compared with those with surgery delayed beyond 28 days. CONCLUSION: In female basketball players, the present study found a statistically significantly increased risk for undergoing MUA and/or LOA after primary ACL reconstruction with BTB autograft in African American females compared with White females and in patients who underwent ACL reconstruction within 28 days of injury.

Persistent vascular congestion in male spontaneously hypertensive rats contributes to delayed recovery of renal function following renal ischemia perfusion compared with females.

Acute kidney injury (AKI) due to ischemia is a serious and frequent clinical complication with mortality rates as high as 80%. Vascular congestion in the renal outer medulla occurs early after ischemia reperfusion (IR) injury, and congestion has been linked to worsened outcomes following IR. There is evidence implicating both male sex and preexisting hypertension as risk factors for poor outcomes following IR. The present study tested the hypothesis that male spontaneously hypertensive rats (SHR) have greater vascular congestion and impaired renal recovery following renal IR vs. female SHR and normotensive male Sprague-Dawley rats (SD). Thirteen-week-old male and female SHR and SD were subjected to sham surgery or 30 min of warm bilateral ischemia followed by reperfusion. Rats were euthanized 24 h or 7 days post-IR. IR increased renal injury in all groups vs. sham controls at 24 h. At 7 days post-IR, injury remained elevated only in male SHR. Histological examination of SD and SHR kidneys 24 h post-IR showed vascular congestion in males and females. Vascular congestion was sustained only in male SHR 7 days post-IR. To assess the role of vascular congestion on impaired recovery following IR, additional male and female SHR were pretreated with heparin (200 U/kg) prior to IR. Heparin pretreatment reduced IR-induced vascular congestion and improved renal function in male SHR 7 days post-IR. Interestingly, preventing increases in blood pressure (BP) in male SHR did not alter sustained vascular congestion. Our data demonstrate that IR-induced vascular congestion is a major driving factor for impaired renal recovery in male SHR.

Behavioral and ERP evidence that object-based attention utilizes fine-grained spatial mechanisms.

Valdes-Sosa, Cobo, and Pinilla (1998) introduced a transparent-motion design that provided evidence of object-based attention whereby attention embraces all features of an attentionally cued perceptual object including new unpredictable features such as a brief translation. Subsequent studies using variants of that design appeared to provide further behavioral, electrophysiological, and brain imaging evidence of object-based attention. Stoner and Blanc (2010) observed, however, that these previous results could potentially be explained by feature-based competition/normalization models of attention. To distinguish between the object-based and feature-based accounts, they introduced "feature swaps" into a delayed-onset variant of the transparent-motion design (Reynolds, Alborzian, & Stoner, 2003). Whereas the object-based attention account predicted that the effect of cueing would survive these feature swaps, the motion-competition account predicted that the effect of cueing would be reversed by these feature swaps. The behavioral results of Stoner and Blanc (2010) supported the object-based account, and in doing so, provided evidence that the attentional advantage in this design is spatially selective at the scale of the intermixed texture elements (i.e., dots) of the overlapping and moving dot fields. In the present study, we used the design of Stoner and Blanc (2010) to investigate both psychophysical performance and evoked activities under different cueing and feature swapping conditions. We confirmed that the behavioral effects of attentional cueing survived feature swaps and found event-related potential (ERP) correlates of those effects in the N1 component range over occipital and parieto-occipital scalp sites. These modulations of the neural activity were, moreover, significantly associated with variation in behavioral performance values across the different conditions. Our findings thus provide the first evidence of the role of the N1 component in object-based attention in this transparent-motion design under conditions that rule out feature-based mechanisms and that reveal selective processing at a fine spatial scale.

A 17-Month-old Boy With Pancytopenia Caused by a Rare Genetic Defect of Vitamin B12 Malabsorption.

Imerslund-Gräsbeck syndrome is an autosomal recessive disorder of vitamin B12 malabsorption presenting with megaloblastic anemia and mild proteinuria in childhood. The disorder is caused by biallelic pathogenic variants in the CUBN or AMN genes, which encode proteins involved in B12 absorption. We present the case of a 17-month-old boy with failure to thrive, pancytopenia, and fevers. His megaloblastic anemia was overlooked leading to unnecessary invasive testing. Findings on bone marrow biopsy prompted investigation for genetic disorders of B12 metabolism. Exome sequencing uncovered 1 known pathogenic variant and 1 novel likely pathogenic variant in CUBN, confirming the diagnosis of Imerslund-Gräsbeck syndrome.

An Analysis of Symptomatic Meniscal Re-Tear Incidence in Two Age Populations: Differences in Older versus Younger Adults.

A symptomatic meniscal tear is one of the most common problems treated by an orthopaedic surgeon. Treatment ranges from observation to complete meniscectomy. Prior research has shown that contact stresses increase within the joint compartment after partial meniscectomy, thus leading to arthritis of the compartment. The purpose of the current study was to determine the incidence of meniscal re-tears in two populations of patients and identify potential factors predisposing to re-tear. A retrospective review of our relational database identified 1,930 arthroscopic partial meniscectomies from 1993 to 2003. Meniscectomies were divided into two groups, 430 patients < 45 years of age (YOUNG) and 712 patients ≥ 45 (OLD). Age, onset date, Lysholm, Tegner, tear type, radial and circumferential location, as well as degree and location of chondromalacia, were analyzed. Of the YOUNG group, 1.16% experienced re-tears, versus 0.42% of the OLD group. From the younger re-tear group, 80% were chronic and 20% had grade 2 chondromalacia in one compartment. The YOUNG re-tear group was slightly more active with higher Tegner (5.6 vs. 4.3) and Lysholm (66.2 vs. 60) scores than the rest of the YOUNG group. The OLD re-tear group was less active with a lower Tegner (2.5 vs. 4.1) and Lysholm (62 vs. 66) score compared with the rest of the older group. In this study, patients under 45 years and with chronic tears had slightly higher incidence of re-tears. Results indicated that the lateral meniscus is more likely to re-tear.

Hepatitis C virus screening at a Veterans Administration Hospital in New York City.

BACKGROUND: Asymptomatic hepatitis C virus (HCV) infection has the highest prevalence in "baby boomers" born in 1945 through 1965. New York State mandates that all persons born during this period be screened at least once for hepatitis C. LOCAL PROBLEM: Military veteran HCV screening is often missed during primary care visits. METHODS: After baseline screening, provider education with and without an HCV education dashboard of information in the Electronic Medical Record system was used to determine if screening proportions could be improved. The Chi-square and Z-test for independent proportions compared after with before education screening. The odds ratio compared after versus before screening odds. INTERVENTIONS: Two interventions were tested. One was provider education with a 30-minute lecture. The second was the lecture with addition of an HCV education computer dashboard. RESULTS: The Chi-square test and Z-test comparing the month immediately after provider education was significant for increased screening (p < .01) compared with baseline. There was a 2.04-fold (95% confidence interval, 1.31-3.20) greater odds of screening in the month after education. If two or more months went by after education, the effect of education no longer improved screening proportions. Provider education plus the use of HCV education dashboard did not improve screening from baseline to the month immediately after screening (p = .95). CONCLUSION: Provider education significantly improved HCV screening the month immediately after education, then regressed toward baseline. Adding an HCV education dashboard to education did not improve screening. To maintain elevated screening proportions, provider screening education must be reinforced on a frequent basis for sustained effect.

A Case of Right Ventricular Dysfunction with Right Ventricular Failure Secondary to Obesity Hypoventilation Syndrome.

BACKGROUND Obesity hypoventilation syndrome (OHS) is characterized by a body mass index (BMI) ≥30 kg/m², daytime hypercapnia, an arterial carbon dioxide tension ≥45 mmHg, and obstructive sleep apnea (OSA). OHS can lead to pulmonary hypertension. It has not been clearly demonstrated that OHS with pulmonary hypertension can lead to right ventricular dysfunction and right heart failure. A case is presented of right ventricular dysfunction and right ventricular failure secondary to OHS. CASE REPORT A 53-year-old man, who was morbidly obese with a BMI of 75 kg/m², presented with shortness of breath (SOB) and hypercapnia. He had never smoked but had a history of severe OSA and hypertension. On examination, the patient was obese with normal lung auscultation and mild pitting edema of the lower extremities. A spiral computed tomography (CT) angiogram showed no evidence of pulmonary embolism or interstitial lung disease. Pulmonary function testing showed no obstructive airway disease and a normal diffusion capacity. Two-dimensional transthoracic echocardiogram (TTE) showed normal left ventricular function and a dilated right ventricle (RV) with a flattened septal wall, moderate tricuspid regurgitation, and an estimated right ventricular systolic pressure of 55-60 mmHg. The patient was discharged on continuous positive airway pressure (CPAP) and oxygen at night, and as needed during the day. CONCLUSIONS This report has shown that OHS without underlying causes of alveolar hypoventilation can result in isolated right ventricular dysfunction and right ventricular failure.

Missed diagnosis of cancer in primary care: Insights from malpractice claims data.

BACKGROUND: In the ambulatory setting, missed cancer diagnoses are leading contributors to patient harm and malpractice risk; however, there are limited data on the malpractice case characteristics for these cases. OBJECTIVE: The aim of this study was to examine key features and factors identified in missed cancer diagnosis malpractice claims filed related to primary care and evaluate predictors of clinical and claim outcomes. METHODS: We analyzed 2155 diagnostic error closed malpractice claims in outpatient general medicine. We created multivariate models to determine factors that predicted case outcomes. RESULTS: Missed cancer diagnoses represented 980 (46%) cases of primary care diagnostic errors, most commonly from lung, colorectal, prostate, or breast cancer. The majority (76%) involved errors in clinical judgment, such as a failure or delay in ordering a diagnostic test (51%) or failure or delay in obtaining a consult or referral (37%). These factors were independently associated with higher-severity patient harm. The majority of these errors were of high severity (85%). CONCLUSIONS: Malpractice claims involving missed diagnoses of cancer in primary care most often involve routine screening examinations or delays in testing or referral. Our findings suggest that more reliable closed-loop systems for diagnostic testing and referrals are crucial for preventing diagnostic errors in the ambulatory setting.

On-call transthoracic echocardiographic interpretation by first year cardiology fellows: comparison with attending cardiologists.

BACKGROUND: Transthoracic echocardiograms (TTE) performed and interpreted by cardiology fellows during off-duty hours are critical to patient care, however limited data exist on their interpretive accuracy. Our aims were to determine the discordance rate between TTEs performed and interpreted by cardiology fellows and National Board of Echocardiography certified attending cardiologists and to identify factors associated with discordance. METHODS: Consecutive on-call TTEs acquired and interpreted by 1st year cardiology fellows over 4.6 years at an academic center were prospectively evaluated by attending cardiologists. Fellow interpretations were classified as concordant or discordant with the attending interpretation. We assessed the association of patient, imaging and fellow characteristics with discordance. RESULTS: A total of 777 TTE interpretations (730 patients) were performed/interpreted by 40 first year fellows and overread by 13 attendings. The most common indications were assessment of left ventricular function (40.9%) and pericardial effusion (37.3%). There was a major or minor discordance in 4.1 and 17.4% of studies, respectively with 42.1% of disagreements occurring in assessment of left ventricular size and function. The indication to assess left ventricular function [OR 2.19, 95% CI (1.32, 3.62), P = 0.002 vs. pericardial effusion] and greater duration of echocardiographic image acquisition (OR 1.02, 95% CI 1.01, 1.03, P = 0.004) were independently associated with overall discordance. CONCLUSIONS: In this large prospective study we found that attending cardiologists disagreed with 1 in 5 fellow TTE interpretations. Standardized tools for evaluation of echocardiograms performed by fellows are needed to ensure quality of training and patient safety.

A Meta-Analysis of Arthroscopic Meniscal Repair: Inside-Out versus Outside-In versus All-Inside Techniques.

Meniscal repair has been introduced to preserve knee function and limit the accelerated degenerative changes associated with meniscal tissue resection. Arthroscopic techniques have evolved to improve morbidity. However, there are few clinical outcome studies in the peer-reviewed literature that compare the use of these approaches. Therefore, our purpose was to perform a meta-analysis of the existing literature on arthroscopic meniscal repair techniques. Specifically, we evaluated differences in: (1) operating time; (2) incidence of postoperative meniscal healing; (3) functional outcomes, using various scoring systems; and (4) incidence of complications. We searched the peer-reviewed literature using SCOPUS, Medline, EMBASE, and Web of Science. Eight studies were eligible for the meta-analysis. These included one prospective, randomized trial (level I), three prospective, comparative studies (level II), and four retrospective, comparative studies (level III). There were a total of 476 patients who had a mean follow-up between 3 and 156 months. When evaluating objective outcomes, the inside-out technique had a significantly higher mean operating time than the all-inside technique. The inside-out and all-inside techniques had comparable meniscal healing rates, but the outside-in repair had a significantly higher rate of meniscal healing than the all-inside repair. Upon assessment of functional outcomes, the inside-out and all-inside methods had comparable International Knee Documentation Committee and Tegner activity scores, but the all-inside method had greater improvements in Lysholm scores. The inside-out and all-inside repairs had similar overall complication rates. All-inside repair may demonstrate lower operating times, but the outside-in repair may have superior meniscal healing rates. Functional outcomes are overall comparable between the techniques. However, there are limited clinical data on the outcome differences between these procedures, and further comparative studies with longer follow-up are needed.

Selective Serotonin Reuptake Inhibitors and Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: An Analysis From the ROCKET AF Trial.

Background There is concern that selective serotonin reuptake inhibitors ( SSRI s) substantially increase bleeding risk in patients taking anticoagulants. Methods and Results We studied 737 patients taking SSRI s in the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Embolism and Stroke Trial in Atrial Fibrillation) trial of rivaroxaban compared with warfarin for the prevention of stroke/systemic embolism in patients with atrial fibrillation. These patients were propensity score matched 1:1 to 737 patients not taking SSRI s. The primary outcome measure was major and nonmajor clinically relevant bleeding events, the principal safety outcome in ROCKET AF . Over a mean 1.6 years of follow-up, the rate of major/ nonmajor clinically relevant bleeding was 18.57 events/100 patient-years for SSRI users versus 16.84 events/100 patient-years for matched comparators, adjusted hazard ratio ( aHR ) of 1.16 (95% confidence interval [CI], 0.95-1.43). The aHR s were similar in patients taking rivaroxaban ( aHR 1.11 [95% CI, 0.82-1.51]) and those taking warfarin ( aHR 1.21 [95% CI, 0.91-1.60]). For the rarer outcome of major bleeding, the aHR for SSRI users versus those not taking SSRI s was 1.13 (95% CI, 0.62-2.06) for rivaroxaban; for warfarin, the aHR was higher, at 1.58 (95% CI , 0.96-2.60) but not statistically significantly elevated. Conclusions We found no significant increase in bleeding risk when SSRI s were combined with anticoagulant therapy, although there was a suggestion of increased bleeding risk with SSRI s added to warfarin. While physicians should be vigilant regarding bleeding risk, our results provide reassurance that SSRI s can be safely added to anticoagulants in patients with atrial fibrillation . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00403767.

Functionally specific optogenetic modulation in primate visual cortex.

In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection methods to confer light sensitivity to neurons in monkey primary visual cortex. Using intrinsic signal optical imaging and single-unit electrophysiology to assess effects of targeted optogenetic stimulation, we found that (i) optogenetic stimulation of single ocular dominance columns (eye-specific nodes) revealed preferential activation of nearby same-eye columns but not opposite-eye columns, and (ii) optogenetic stimulation of single orientation domains increased visual response of matching orientation domains and relatively suppressed nonmatching orientation selectivity. These findings demonstrate that optical stimulation of single nodes leads to modulation of functionally specific cortical networks related to underlying neural architecture.

Creatinine Excretion as a Determinant of Accelerated Skeletal Muscle Loss with Critical Illness.

OBJECTIVE: The 24-h urinary creatinine excretion rate has been used as an approximation of the skeletal muscle (SM) mass in non-intensive care unit (ICU) settings. The study goal or aim was to determine reductions in SM mass in patients with recurrent critical illness who are admitted to a medical ICU. METHODS: Retrospective ICU patient records between 2013 and 2015 were reviewed. Inclusion of ICU patients with repeat 24-h urinary creatinine excretion levels at two different ICU admissions done routinely as part of care. The study design is a case series with patients as their own control. RESULTS: Three patients were found to have data on two separate ICU admissions. The reduction in creatinine excretion among ICU patients was correlated with estimated SM mass. All patients had >50% reduction in creatinine excretion and ≥47% reduction in estimated SM mass over 4 months. All patients were bed-bound after the first ICU admission and met the definition of sarcopenia by the second ICU admission; all patients died during the second ICU admission. The final SM mass in all patients was <4 kg m-2. CONCLUSION: Patients with chronic critical illness admitted to the medical ICU, who become bed bound, can experience up to 50% reduction in SM mass as gleaned from creatinine excretion within 4 months. Low SM mass may predispose patients to increased mortality. Measurement of 24-h urinary creatinine excretion may be a useful ICU biomarker to determine SM mass for diagnostic and prognostic purposes.

Methodologic Differences Across Studies of Patients With Atrial Fibrillation Lead to Varying Estimates of Stroke Risk.

BACKGROUND: Guidelines for anticoagulation in atrial fibrillation (AF) assume that stroke risk scheme point scores correspond to fixed stroke rates. However, reported stroke rates vary widely across AF cohort studies, including studies from the same country. Reasons for this variation are unclear. This study compares methodologies used to assemble and analyze large AF cohorts worldwide and assesses potential bias in estimating stroke rates. METHODS AND RESULTS: From a previous systematic review of AF cohorts, we analyzed studies including at least 5000 patients. We assessed methods used to generate rates of ischemic stroke off anticoagulants, according to a structured inventory of database interrogation methods. Nine studies (497 578 total patients) met our criteria. Overall cohort stroke rates ranged from 0.45% to 7.03% per year. In bivariate study-level analysis, multiple features were associated with higher stroke rates, including AF identified as inpatients versus outpatients (rate ratio 2.60, 95% confidence interval, 1.19, 5.68), and lack of clinical validation of outcome events (rate ratio 4.09, 95% confidence interval, 1.06, 15.70). European studies reported rates more than 4-fold higher than North American studies. International Classification of Diseases (ICD) coding schemes for outcomes varied widely. Multiple high rate features coexisted in the same studies. CONCLUSIONS: Among AF cohort studies, differences in the composition, method of assembly, determination of clinical features and outcomes, and analytic approach were strongly associated with reported stroke rates. Our study highlights the need for standardized and validated methodologies for AF cohort assembly and analysis to generate accurate stroke rates to better support anticoagulation guidelines for patients with AF.

Auditory modulation of spiking activity and local field potentials in area MT does not appear to underlie an audiovisual temporal illusion.

The timing of brief stationary sounds has been shown to alter the perceived speed of visual apparent motion (AM), presumably by altering the perceived timing of the individual frames of the AM stimuli and/or the duration of the interstimulus intervals (ISIs) between those frames. To investigate the neural correlates of this "temporal ventriloquism" illusion, we recorded spiking and local field potential (LFP) activity from the middle temporal area (area MT) in awake, fixating macaques. We found that the spiking activity of most MT neurons (but not the LFP) was tuned for the ISI/speed (these parameters covaried) of our AM stimuli but that auditory timing had no effect on that tuning. We next asked whether the predicted changes in perceived timing were reflected in the timing of neuronal responses to the individual frames of the AM stimuli. Although spiking dynamics were significantly, if weakly, affected by auditory timing in a minority of neurons, the timing of spike responses did not systematically mirror the predicted perception of stimuli. Conversely, the duration of LFP responses in ß- and γ-frequency bands was qualitatively consistent with human perceptual reports. We discovered, however, that LFP responses to auditory stimuli presented alone were robust and that responses to audiovisual stimuli were predicted by the linear sum of responses to auditory and visual stimuli presented individually. In conclusion, we find evidence of auditory input into area MT but not of the nonlinear audiovisual interactions we had hypothesized to underlie the illusion. NEW & NOTEWORTHY We utilized a set of audiovisual stimuli that elicit an illusion demonstrating "temporal ventriloquism" in visual motion and that have spatiotemporal intervals for which neurons within the middle temporal area are selective. We found evidence of auditory input into the middle temporal area but not of the nonlinear audiovisual interactions underlying this illusion. Our findings suggest that either the illusion was absent in our nonhuman primate subjects or the neuronal correlates of this illusion lie within other areas.

Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats.

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.