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Background and Objectives Sodium-glucose cotransporter type 2 inhibitors have evolved into a novel drug class utilized for reductions in cardiovascular risk and heart failure hospitalization. We aimed to describe the impact of sodium-glucose cotransporter type 2 inhibitors on diuretic prescribing patterns and intermediate laboratory outcomes in patients with and without diuretic use. Methods This retrospective cohort study included patients taking empagliflozin as of 1 July, 2021. Patients were assigned to the intervention group if prescribed a diuretic concomitantly or a control group otherwise. The primary outcome was the impact of empagliflozin on diuretic prescribing (i.e., no change, discontinuation, decrease, increase). Secondary outcomes were change in weight, hemoglobin A1c, estimated glomerular filtration rate, hemoglobin, hematocrit, blood pressure, and electrolytes at 90 and 180 days. Mean differences were compared using the t-test between groups or the paired t-test within groups. Patients without diuretic use were matched 1:1 to patients taking diuretics using propensity scores. Results This study included 1189 patients: 750 in the control group and 439 in the intervention group. After propensity score matching, baseline characteristics were well balanced. Of the 439 patients in the intervention group, 118 had changes in the diuretic regimen. There were 131 changes: 109 (83.2%) discontinuations, 13 (9.92%) decreases, and nine (6.87%) increases. The mean furosemide equivalent loop dose was reduced after empagliflozin initiation (50.62 mg vs 43.13 mg; p < 0.001). Among all patients, there was a decrease in weight ( p = 0.01), estimated glomerular filtration rate ( p < 0.001), and hemoglobin A1c ( p < 0.001). There was an increase in hemoglobin ( p < 0.001), hematocrit ( p < 0.001), and magnesium ( p < 0.001). In the propensity score-matched cohort, there was a significant reduction from baseline in mean weight in the intervention group compared with the control group ( p < 0.001). Conclusions This hypothesis-generating study suggests that sodium-glucose cotransporter type 2 inhibitors may lower diuretic requirements, further supported by a reduction in weight in the intervention cohort. Graphical Abstract

Sexual selection theory predicts that males will compete vigorously for access to mates. It is therefore surprising that in a few species, males form partnerships and cooperate to attract females. Manakins in the genus Chiroxiphia are known for their unusual cooperative courtship displays. My research investigated the adaptive benefits of cooperation in a previously unstudied member of this genus, the Lance-tailed Manakin ( Chiroxiphia lanceolata). Pairs of male Lance-tailed Manakins form long-term partnerships to court females, but only one male per pair copulates with females, raising in the question of why the second, subordinate male cooperates. To investigate this question, I characterized the courtship display and vocal behavior of this species, determined the social structure through observations of associations among color-banded individuals, identified age-specific plumage stages and the associated interaction patterns of males of different plumages, and tested three key hypotheses about the adaptive benefits of cooperation for subordinate males. Lance-tailed Manakins have a complex courtship display consisting of both paired and solo elements. Displays are performed at “display areas” where one dominant, alpha male and usually one subordinate, beta partner perform dance displays for females, but at which several other adult and subadult males are present and display in duet songs or dance displays when females are not present. Beta males were never observed copulating, and genetic analysis of paternity using microsatellites confirmed that betas did not sire offspring. Alpha and beta partners were not more closely related than randomly selected pairs of males, indicating that beta males did not receive indirect fitness benefits from cooperation. Betas became alphas more frequently than other males in the population, but an alpha removal experiment demonstrated that even when alpha positions were vacant, beta males sometimes moved to another display area rather than assume the alpha position on their original territory. The variability in alpha-beta affiliations and the variety of behaviors exhibited by betas whose alpha partners were removed suggest that males ascend to alpha status through a population-wide rather than territory-specific queue, and that factors in addition to alpha vacancies affect the transition to a breeding role.

We have a delightful family heirloom handed down to us from our grandmother, Mrs. Charles H.K. Halsey, who was Eliza Gracie King, daughter of Charles King, President of Columbia College, and son of Rufus King, who represented our country at the Court of St. James's under General Washington.

The following letter gives an interesting account of the good Christmas cheer that reached to a far away island in the Pacific, through the kindness of T. S. S. members. It reads as follows:

Dynamic body acceleration (DBA) has been used as a proxy for energy expenditure in logger-equipped animals, with researchers summing the acceleration (overall dynamic body acceleration--ODBA) from the three orthogonal axes of devices. The vector of the dynamic body acceleration (VeDBA) may be a better proxy so this study compared ODBA and VeDBA as proxies for rate of oxygen consumption using humans and 6 other species. Twenty-one humans on a treadmill ran at different speeds while equipped with two loggers, one in a straight orientation and the other skewed, while rate of oxygen consumption (VO2) was recorded. Similar data were obtained from animals but using only one (straight) logger. In humans, both ODBA and VeDBA were good proxies for VO2 with all r(2) values exceeding 0.88, although ODBA accounted for slightly but significantly more of the variation in VO2 than did VeDBA (P<0.03). There were no significant differences between ODBA and VeDBA in terms of the change in VO2 estimated by the acceleration data in a simulated situation of the logger being mounted straight but then becoming skewed (P = 0.744). In the animal study, ODBA and VeDBA were again good proxies for VO2 with all r(2) values exceeding 0.70 although, again, ODBA accounted for slightly, but significantly, more of the variation in VO2 than did VeDBA (P<0.03). The simultaneous contraction of muscles, inserted variously for limb stability, may produce muscle oxygen use that at least partially equates with summing components to derive DBA. Thus, a vectorial summation to derive DBA cannot be assumed to be the more 'correct' calculation. However, although within the limitations of our simple study, ODBA appears a marginally better proxy for VO2. In the unusual situation where researchers are unable to guarantee at least reasonably consistent device orientation, they should use VeDBA as a proxy for VO2.

Partial artemisinin resistance is suspected if delayed parasite clearance (ie, persistence of parasitaemia on day 3 after treatment initiation) is observed. Validated markers of artemisinin partial resistance in southeast Asia, Plasmodium falciparum kelch13 (Pfkelch13) R561H and P574L, have been reported in Rwanda but no association with parasite clearance has been observed. We aimed to establish the efficacy of artemether–lumefantrine and genetic characterisation of Pfkelch13 alleles and their association with treatment outcomes. This open-label, single-arm, multicentre, therapeutic efficacy study was done in 2018 in three Rwandan sites: Masaka, Rukara, and Bugarama. Children aged 6–59 months with P falciparum monoinfection and fever were eligible and treated with a 3-day course of artemether–lumefantrine. Treatment response was monitored for 28 days using weekly microscopy screenings of blood samples for P falciparum. Mutations in Pfkelch13 and P falciparum multidrug resistance-1 (Pfmdr1) genes were characterised in parasites collected from enrolled participants. Analysis of flanking microsatellites surrounding Pfkelch13 was done to define the origins of the R561H mutations. The primary endpoint was PCR-corrected parasitological cure on day 28, as per WHO protocol. 228 participants were enrolled and 224 (98·2%) reached the study endpoint. PCR-corrected efficacies were 97·0% (95% CI 88–100) in Masaka, 93·8% (85–98) in Rukara, and 97·2% (91–100) in Bugarama. Pfkelch13 R561H mutations were present in 28 (13%) of 218 pre-treatment samples and P574L mutations were present in two (1%) pre-treatment samples. 217 (90%) of the 240 Pfmdr1 haplotypes observed in the pretreatment samples, had either the NFD (N86Y, Y184F, D1246Y) or NYD haplotype. Eight (16%) of 51 participants in Masaka and 12 (15%) of 82 participants in Rukara were microscopically positive 3 days after treatment initiation, which was associated with pre-treatment presence of Pfkelch13 R561H in Masaka (p=0·0005). Genetic analysis of Pfkelch13 R561H mutations suggest their common ancestry and local origin in Rwanda. We confirm evidence of emerging artemisinin partial resistance in Rwanda. Although artemether–lumefantrine remains efficacious, vigilance for decreasing efficacy, further characterisation of artemisinin partial resistance, and evaluation of additional antimalarials in Rwanda should be considered. The US President's Malaria Initiative. For the French translation of the abstract see Supplementary Materials section.

Pea seeds are widely consumed in their immature form, known as garden peas and petit pois, mostly after preservation by freezing or canning. Mature dry peas are rich in iron in the form of ferritin, but little is known about the content, form or bioavailability of iron in immature stages of seed development. Using specific antibodies and in-gel iron staining, we show that ferritin loaded with iron accumulated gradually during seed development. Immunolocalization and high-resolution secondary ion mass spectrometry (NanoSIMS) revealed that iron-loaded ferritin was located at the surface of starch-containing plastids. Standard cooking procedures destabilized monomeric ferritin and the iron-loaded form. Iron uptake studies using Caco-2 cells showed that the iron in microwaved immature peas was more bioavailable than in boiled mature peas, despite similar levels of soluble iron in the digestates. By manipulating the levels of phytic acid in the digestates we demonstrate that phytic acid is the main inhibitor of iron uptake from mature peas in vitro . Taken together, our data show that immature peas and mature dry peas contain similar levels of ferritin-iron, which is destabilized during cooking. However, iron from immature peas is more bioavailable because of lower phytic acid levels compared to mature peas.

With blustery winds blowing against them and wild cheers boosting them, some 30,000 runners yesterday notched blisters, sore muscles and the bragging rights to say they completed the 30th New York City Marathon. Joseph Chebet of Kenya and Adriana Fernandez of Mexico won the grueling annual 26.2-mile race through the five boroughs, which began in Staten Island and ended in Central Park. Running with friends and bodyguards in the middle of the pack, controversial right-wing Austrian politician and Nazi sympathizer Joerg Haider slipped past the 10-mile mark in Williamsburg, Brooklyn, apparently unnoticed by a group of Austrian students protesting his hard-line policies.

Marine phytoplankton produce ∼10 9  tonnes of dimethylsulfoniopropionate (DMSP) per year 1 , 2 , an estimated 10% of which is catabolized by bacteria through the DMSP cleavage pathway to the climatically active gas dimethyl sulfide 3 , 4 . SAR11 Alphaproteobacteria (order Pelagibacterales), the most abundant chemo-organotrophic bacteria in the oceans, have been shown to assimilate DMSP into biomass, thereby supplying this cell's unusual requirement for reduced sulfur 5 , 6 . Here, we report that Pelagibacter HTCC1062 produces the gas methanethiol, and that a second DMSP catabolic pathway, mediated by a cupin-like DMSP lyase, DddK, simultaneously shunts as much as 59% of DMSP uptake to dimethyl sulfide production. We propose a model in which the allocation of DMSP between these pathways is kinetically controlled to release increasing amounts of dimethyl sulfide as the supply of DMSP exceeds cellular sulfur demands for biosynthesis. Pelagibacter simultaneously produces the biogenic gases methanethiol and dimethyl sulfide from dimethylsulfoniopropionate, regulated by a kinetic switch that balances DMSP allocation between each pathway depending on cellular sulfur demands.