Calcium transport through the luminal membrane of the distal tubule. I. Interrelationship with sodium

Calcium transport through the luminal membrane of the distal tubule. I. Interrelationship with sodium.Calcium (Ca2+) transport by isolated luminal membranes from rabbit renal distal tubule has been characterized. Ca2+ uptake by these membrane vesicles exhibited saturation kinetics. In the absence of sodium (Na+) in the incubation medium, a low affinity system was observed with a KmCa2+ of 2.83 ± 0.64 mM and Vmax of 3.03 ± 0.48 pmoL/µg/10 sec. A second type of kinetics was also detected with a high affinity and a low velocity (KmCa2+ 0.04 ± 0.01 mM, Vmax 1.18 ± 0.22 pmol/µg/10 sec). The luminal membranes from proximal tubules showed a single system with a KmCa2+ of 0.49 ± 0.20 mM and Vmax of 1.26 ± 0.17 pmol/µg/10 sec. The presence of Na+ sharply decreased Ca2+ uptake by the high affinity system of the membranes from distal tubules, increasing the KmCa2+ to 0.07 mM ± 0.01 (P < 0.01) and decreasing the Vmax to 0.27 pmol/µg/10 sec (P < 0.005). This effect of Na+ was concentration-dependent, with a half-maximal effect at 38 mM Na+ and a Hill coefficient of 0.9. In contrast, Na+ had no effect on Ca2+ transport through the luminal membranes of proximal tubules nor on the low affinity system of the distal tubule. The composition of the intravesicular medium also influenced Ca2+ uptake by the membranes from distal tubules. Compared to mannitol, trans-Na+ or K+ significantly reduced Ca2+ transport. Finally, cis-K+ induced an increase in this transport. As found with Na+, the effect of K+ was concentration-dependent, with a Hill coefficient of 0.42. It is concluded that: 1) the luminal membrane of the distal tubule fundamentally differs from the brush border membrane of the proximal tubule; 2) Na+ has an inhibitory effect on Ca2+ uptake when applied on either side of the distal tubule membrane, and therefore probably binds at two different sites of the carriers in the membrane; 3) trans-K+ inhibits whereas cis-K+ enhances Ca2+ transport in this membrane; and 4) the actions of Na+ and K+ are not dependent upon any exchange mechanism

A history of helminth exposure protects against pneumovirus infection in an IL-4Rα-independent manner

peer reviewe

Répercussions hémodynamiques rénales de la surcharge salée aiguë isotonique chez le chien

Intrarenal hemodynamic changes during acute isotonic saline loading in the dog. 85Kr autoradiograms, perfusions of silastic and injections of thioflavine S labelled red blood cells (R.B.C.) have been used to study the intrarenal hemodynamic changes induced in the dog by an acute isotonic expansion of the extracellular fluid volume. The silastic injected specimens showed a generalized vasodilatation, without however, any change of the diameter of the glomerular tufts. As the ratio of the number of labelled R.B.C. of the superficial glomeruli to the number of the R.B.C. of the juxtamedullary glomeruli has decreased, we can conclude that the relative juxtamedullary glomerular capillary volume has increased. The autoradiographs showed that the velocity of the blood flow increased in the superficial cortex and the vasa recta and decreases in the juxtamedullary cortical region. This slowing seems to be due to the marked dilatation of the capillary bed of the latter region. It is then concluded that the natriuresis could be linked mainly to changes of peritubular factors induced by the vasodilatation which is itself more marked in the juxtamedullary cortex.Répercussions hémodynamiques rénales de la surcharge salée aiguë isotonique chez le chien. Les changements hémodynamiques intrarénaux ont été étudiés chez des chiens soumis à une surcharge salée isotonique aiguë, à l'aide d'autoradiographies au Kr85, de perfusion de silastic et d'injections de globules rouges marqués à la Thioflavine S. La surcharge a entraîné une vasodilatation rénale généralisée (moules au silastic). Le décompte des globules rouges marqués par glomérule montra une diminution du leur nombre dans les glomérules superficiels par rapport aux glomérules juxtamédullaires. Ceci traduit une augmentation relative du volume capillaire glomérulaire juxtamédullaire. Par ailleurs, la vitesse du flux sanguin (autoradiographies) a augments dans le cortex superficiel, les vasa recta et diminué dans la région juxtamédullaire. Une dilatation excessive du lit capillaire de cette dernière semble expliquer le ralentissement de son flux sanguin. Le diamètre des floculi glomérulaires n'a pas changé sous l'effet de la surcharge. La natriurèse peut ainsi être reliée principalement à la baisse de réabsorption tubulaire secondaire aux changements des facteurs péritubulaires induits par la vasodilatation, elle-même maximale au niveau du cortex interne

IL-4 induces CD22 expression to restrain the effector program of self-reactive virtual memory T cells

Parasitic helminths induce the production of interleukin (IL)-4 which causes the expansion of virtual memory CD8+ T cells (TVM), a cell subset contributing to the control of viral coinfection. However, the mechanisms regulating IL-4-dependent TVM activation and expansion during worm infection remain ill defined. We used single-cell RNA sequencing of CD8+ T cells to investigate IL-4-dependent TVM responses upon helminth infection in mice. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a specific and selective surface marker of IL-4-induced TVM cells. CD22+ TVM were enriched for IFN-γ and granzyme A and retained a diverse TCR repertoire, while enriched in CDR3 sequences with features of self-reactivity. Deletion of CD22 expression in CD8+ T cells enhanced TVM responses to helminth infection, indicating that this inhibitory receptor modulates TVM responses. Thus, helminth-induced IL-4 drives the expansion and activation of self-reactive TVM in the periphery that is counter-inhibited by CD22

Elevation as a proxy for mosquito-borne Zika virus transmission in the Americas.

INTRODUCTION: When Zika virus (ZIKV) first began its spread from Brazil to other parts of the Americas, national-level travel notices were issued, carrying with them significant economic consequences to affected countries. Although regions of some affected countries were likely unsuitable for mosquito-borne transmission of ZIKV, the absence of high quality, timely surveillance data made it difficult to confidently demarcate infection risk at a sub-national level. In the absence of reliable data on ZIKV activity, a pragmatic approach was needed to identify subnational geographic areas where the risk of ZIKV infection via mosquitoes was expected to be negligible. To address this urgent need, we evaluated elevation as a proxy for mosquito-borne ZIKV transmission. METHODS: For sixteen countries with local ZIKV transmission in the Americas, we analyzed (i) modelled occurrence of the primary vector for ZIKV, Aedes aegypti, (ii) human population counts, and (iii) reported historical dengue cases, specifically across 100-meter elevation levels between 1,500m and 2,500m. Specifically, we quantified land area, population size, and the number of observed dengue cases above each elevation level to identify a threshold where the predicted risks of encountering Ae. aegypti become negligible. RESULTS: Above 1,600m, less than 1% of each country's total land area was predicted to have Ae. aegypti occurrence. Above 1,900m, less than 1% of each country's resident population lived in areas where Ae. aegypti was predicted to occur. Across all 16 countries, 1.1% of historical dengue cases were reported above 2,000m. DISCUSSION: These results suggest low potential for mosquito-borne ZIKV transmission above 2,000m in the Americas. Although elevation is a crude predictor of environmental suitability for ZIKV transmission, its constancy made it a pragmatic input for policy decision-making during this public health emergency

Cost-Effectiveness of Comprehensive, Integrated Care for First Episode Psychosis in the NIMH RAISE Early Treatment Program

This study compares the cost-effectiveness of Navigate (NAV), a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis (FEP) and usual Community Care (CC) in a cluster randomization trial. Patients at 34 community treatment clinics were randomly assigned to either NAV (N = 223) or CC (N = 181) for 2 years. Effectiveness was measured as a one standard deviation change on the Quality of Life Scale (QLS-SD). Incremental cost effectiveness ratios were evaluated with bootstrap distributions. The Net Health Benefits Approach was used to evaluate the probability that the value of NAV benefits exceeded its costs relative to CC from the perspective of the health care system. The NAV group improved significantly more on the QLS and had higher outpatient mental health and antipsychotic medication costs. The incremental cost-effectiveness ratio was $12 081/QLS-SD, with a .94 probability that NAV was more cost-effective than CC at$40 000/QLS-SD. When converted to monetized Quality Adjusted Life Years, NAV benefits exceeded costs, especially at future generic drug prices

Long-term full-scale intelligent quotient outcomes following pediatric and childhood epilepsy surgery: A systematic review and meta-analysis

OBJECTIVE: Cognitive measures are an important primary outcome of pediatric, adolescents, and childhood epilepsy surgery. The purpose of this systematic review and meta-analysis is to assess whether there are long-term alterations (≥ 5 years) in the Full-Scale Intelligence Quotient (FSIQ) of pediatric patients undergoing epilepsy surgery. METHODS: Electronic databases (EMBASE, MEDLINE, and Scopus) were searched for English articles from inception to October 2022 that examined intelligence outcomes in pediatric epilepsy surgery patients. Inclusion criteria were defined as the patient sample size of ≥ 5, average follow- up of ≥5 years, and surgeries performed on individuals ≤ 18 years old at the time of surgery. Exclusion criteria consisted of palliative surgery, animal studies, and studies not reporting surgical or FSIQ outcomes. Publication bias was assessed using a funnel plot and the Quality in Prognosis Studies (QUIPS) toolset was used for quality appraisal of the selected articles. A random-effects network meta-analysis was performed to compare FSIQ between surgical patients at baseline and follow-up and Mean Difference (MD) was used to calculate the effect size of each study. Point estimates for effects and 95% confidence intervals for moderation analysis were performed on variables putatively associated with the effect size. RESULTS: 21,408 studies were screened for abstract and title. Of these, 797 fit our inclusion and exclusion criteria and proceeded to full-text screening. Overall, seven studies met our requirements and were selected. Quantitative analysis was performed on these studies (N = 330). The mean long-term difference between pre- and post- operative FSIQ scores across all studies was noted at 3.36 [95% CI: (0.14, 6.57), p = 0.04, I2 = 0%] and heterogeneity was low. CONCLUSION: To our knowledge, this is the first meta-analysis to measure the long-term impacts of FSIQ in pediatric and adolescent epilepsy patients. Our overall results in this meta-analysis indicate that while most studies do not show long-term FSIQ deterioration in pediatric patients who underwent epilepsy surgery, there was an increase of 3.36 FSIQ points, however, the observed changes were not clinically significant. Moreover, at the individual patient level analysis, while most children did not show long-term FSIQ deterioration, few had significant decline. These findings indicate the importance of surgery as a viable option for pediatric patients with medically refractory epilepsy

Are groups more rational than individuals? A review of interactive decision making in groups

Many decisions are interactive; the outcome of one party depends not only on its decisions or on acts of nature but also on the decisions of others. In the present article, we review the literature on decision making made by groups of the past 25 years. Researchers have compared the strategic behavior of groups and individuals in many games: prisoner's dilemma, dictator, ultimatum, trust, centipede and principal-agent games, among others. Our review suggests that results are quite consistent in revealing that groups behave closer to the game-theoretical assumption of rationality and selfishness than individuals. We conclude by discussing future research avenues in this area