Conditionally mutant animal model for investigating the invasive trophoblast cell lineage.

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade the uterus, where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome-editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 (Prl7b1) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption of Prl7b1 did not adversely affect placental development. We demonstrated that the Prl7b1 locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their roles in trophoblast-guided uterine spiral artery remodeling.

CITED2 is a conserved regulator of the uterine-placental interface.

Establishment of the hemochorial uterine-placental interface requires exodus of trophoblast cells from the placenta and their transformative actions on the uterus, which represent processes critical for a successful pregnancy, but are poorly understood. We examined the involvement of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) in rat and human trophoblast cell development. The rat and human exhibit deep hemochorial placentation. CITED2 was distinctively expressed in the junctional zone (JZ) and invasive trophoblast cells of the rat. Homozygous Cited2 gene deletion resulted in placental and fetal growth restriction. Small Cited2 null placentas were characterized by disruptions in the JZ, delays in intrauterine trophoblast cell invasion, and compromised plasticity. In the human placentation site, CITED2 was uniquely expressed in the extravillous trophoblast (EVT) cell column and importantly contributed to the development of the EVT cell lineage. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.

TAF7L regulates early stages of male germ cell development in the rat.

Male germ cell development is dependent on the orchestrated regulation of gene networks. TATA-box binding protein associated factors (TAFs) facilitate interactions of TATA-binding protein with the TATA element, which is known to coordinate gene transcription during organogenesis. TAF7 like (Taf7l) is situated on the X chromosome and has been implicated in testis development. We examined the biology of TAF7L in testis development using the rat. Taf7l was prominently expressed in preleptotene to leptotene spermatocytes. To study the impact of TAF7L on the testis we generated a global loss-of-function rat model using CRISPR/Cas9 genome editing. Exon 3 of the Taf7l gene was targeted. A founder was generated possessing a 110 bp deletion within the Taf7l locus, which resulted in a frameshift and the premature appearance of a stop codon. The mutation was effectively transmitted through the germline. Deficits in TAF7L did not adversely affect pregnancy or postnatal survival. However, the Taf7l disruption resulted in male infertility due to compromised testis development and failed sperm production. Mutant germ cells suffer meiotic arrest at late zygotene/early pachynema stages, with defects in sex body formation. This testis phenotype was more pronounced than previously described for the subfertile Taf7l null mouse. We conclude that TAF7L is essential for male germ cell development in the rat.

A new objective method for determining exercise gas exchange thresholds by respiratory frequency in middle-aged men.

PURPOSE: To evaluate the agreement between the two Gas Exchange Thresholds (GETs = GET1 and GET2), identified by the conventional V-Slope method, and two Respiratory Frequency Thresholds (fRTs = fRT1 and fRT2) obtained from a novel, low-cost, and simple method of breakpoint determination. METHODS: Fifty middle-aged males (age: 50-58 years; V ˙ o2peak: 37.5 ± 8.6 mL·Kg-1·min-1), either healthy or with chronic illnesses, underwent an incremental cycle exercise test to determine maximal oxygen uptake ( V ˙ o2max/ V ˙ o2peak), GETs and fRTs. RESULTS: There were no statistical differences [P > 0.05; ES: 0.17 to 0.32, small] between absolute and relative (56-60% V ˙ o2peak) oxygen uptake ( V ˙ o2) values at GET1 with those obtained at fRT1, nor between V ˙ o2 values at GET2 with those at fRT2 (76-78% V ˙ o2peak). Heart rate (HR) at fRT1, and V ˙ o2 and HR at fRT2 showed very large correlations (r = 0.75-0.82; P < 0.001) and acceptable precision (SEE < 7-9%) in determination of their corresponding values at GET1 and GET2. The precision in the estimation of V ˙ o2 at GET1 from fRT1 was moderate (SEE = 15%), while those of power output at GET1 (SEE = 23%) and GET2 (SEE = 12%) from their corresponding fRTs values were very poor to moderate. CONCLUSION: HR at fRT1 and V ˙ o2 and HR at fRT2, determined using a new objective and portable approach, may potentially serve as viable predictors of their respective GETs. This method may offer a simplified, cost-effective, and field-based approach for determining exercise threshold intensities during graded exercise.

Reassembling the Field-based Applicability of the Lactate Threshold for Old Age.

This study aimed to investigate the applicability of the Lactate Threshold (LT) to predict maximal oxygen uptake (˙VO2max) and demarcate the boundary between the moderate- to heavy-intensity domain (HRm-h) in old age in comparison to the most utilized methods. A cross-sectional validation study was conducted. Participants aged 61 to 77 performed a familiarization procedure, an incremental maximal exercise treadmill test (CPX) for ˙VO2max determination, the Six-minute Walk Test (6MWT), and a discontinuous incremental field test for LT determination. Lower (P<0.01) internal effort was required for LT testing (76±8%HRmax) compared to 6MWT (92±9%HRmax). The application of the 6MWT reference equations overestimated ˙VO2max by 10-23%. LTs better estimated the ˙VO2max (r ≈0.90, SEE: ≈3.0] compared to the 6MWT (r=0.68, SEE=5.5). HRm-h determined by the CPX differed (20%; P=0.001) from that obtained by LT. HRm-h stratification indicated participants fall into the very light to the vigorous intensity domains. LT testing is more submaximal than the 6MWT, and is a valuable tool to estimate the ˙VO2max in older male adults. Implementation of LT testing in physical activity programs might help improving the quality of aerobic exercise training in older men.

Effect of silk fibroin microparticles on cellular immunity and liver of gilthead seabream (Sparus aurata L.) with and without experimental skin injuries.

Silk fibroin (SF) microparticles were administered in the diet of gilthead seabream with or without experimental skin wounds to study the effects on cellular immunity and liver. A commercially available diet was enriched with varying amount of SF: 0, 50 and 100 mg kg-1 (representing the control, SF50 and SF100 diets respectively). The animals were fed for 30 days and half of them were sampled. Similar experimental wounds were then performed on the rest of fish, and they continued to be fed the same diet. At 7 days post-wounding, samples were taken from the wounded fish. Cellular immunity was studied on head kidney leucocytes (phagocytosis, respiratory and peroxidase content) and liver status (histological study and gene expression) were studied. Our results showed that experimental wounds affect both cellular immunity (by decreasing leucocyte respiratory burst and peroxidase activity) and altered liver histology (by inducing vascularisation and congestion of blood vessels). In addition, it influences the expression of genes that serve as markers of oxidative stress, endoplasmic reticulum stress and apoptosis. The highest dose of SF (SF100) increased the phagocytic capacity of leucocytes the most, as well as the expression of genes related to blood vessel formation in the liver. Furthermore, increased expression of antioxidant genes (cat and gsr) and decreased expression of genes related to reticulum endoplasmic stress (grp94 and grp170) and apoptosis (nos and jnk) were detected in these fish fed with SF100 and wounded. In conclusion, fed fish with SF100 had many beneficial effects as cellular immunostimulant and hepatoprotection in wounded fish. Its use could be of great interest for stress management in farmed fish conditions.

Early life stress induces visual dysfunction and retinal structural alterations in adult mice.

Early life stress (ELS) is defined as a period of severe and/or chronic trauma, as well as environmental/social deprivation or neglect in the prenatal/early postnatal stage. Presently, the impact of ELS on the retina in the adult stage is unknown. The long-term consequences of ELS at retinal level were analyzed in an animal model of maternal separation with early weaning (MSEW), which mimics early life maternal neglect. For this purpose, mice were separated from the dams for 2 h at postnatal days (PNDs) 4-6, for 3 h at PNDs 7-9, for 4 h at PNDs 10-12, for 6 h at PNDs 13-16, and weaned at PND17. At the end of each separation period, mothers were subjected to movement restriction for 10 min. Control pups were left undisturbed from PND0, and weaned at PND21. Electroretinograms, visual evoked potentials, vision-guided behavioral tests, retinal anterograde transport, and retinal histopathology were examined at PNDs 60-80. MSEW induced long-lasting functional and histological effects at retinal level, including decreased retinal ganglion cell function and alterations in vision-guided behaviors, likely associated to decreased synaptophysin content, retina-superior colliculus communication deficit, increased microglial phagocytic activity, and retinal ganglion cell loss through a corticoid-dependent mechanism. A treatment with mifepristone, injected every 3 days between PNDs 4 and16, prevented functional and structural alterations induced by MSEW. These results suggest that retinal alterations might be included among the childhood adversity-induced threats to life quality, and that an early intervention with mifepristone avoided ELS-induced retinal disturbances.

Environment and shipping drive environmental DNA beta-diversity among commercial ports.

The spread of nonindigenous species by shipping is a large and growing global problem that harms coastal ecosystems and economies and may blur coastal biogeographical patterns. This study coupled eukaryotic environmental DNA (eDNA) metabarcoding with dissimilarity regression to test the hypothesis that ship-borne species spread homogenizes port communities. We first collected and metabarcoded water samples from ports in Europe, Asia, Australia and the Americas. We then calculated community dissimilarities between port pairs and tested for effects of environmental dissimilarity, biogeographical region and four alternative measures of ship-borne species transport risk. We predicted that higher shipping between ports would decrease community dissimilarity, that the effect of shipping would be small compared to that of environment dissimilarity and shared biogeography, and that more complex shipping risk metrics (which account for ballast water and stepping-stone spread) would perform better. Consistent with our hypotheses, community dissimilarities increased significantly with environmental dissimilarity and, to a lesser extent, decreased with ship-borne species transport risks, particularly if the ports had similar environments and stepping-stone risks were considered. Unexpectedly, we found no clear effect of shared biogeography, and that risk metrics incorporating estimates of ballast discharge did not offer more explanatory power than simpler traffic-based risks. Overall, we found that shipping homogenizes eukaryotic communities between ports in predictable ways, which could inform improvements in invasive species policy and management. We demonstrated the usefulness of eDNA metabarcoding and dissimilarity regression for disentangling the drivers of large-scale biodiversity patterns. We conclude by outlining logistical considerations and recommendations for future studies using this approach.

Hepcidin and piscidin modulation and antibacterial response in gilthead seabream (Sparus aurata) infected with Vibrio harveyi.

Vibriosis is an infectious disease that generates large economic losses in Mediterranean aquaculture. Vibrio harveyi is one of the marine bacteria causing this disease, it is widespread in the Mediterranean Sea and causes ulcers on the skin of the fish it infects. In addition, the skin is a route of entry and colonization of this pathogen. In this study, one group of fish was injected intraperitoneally with phosphate buffered saline (control group) and another with V. harveyi (infected group). At 4 h after injection, samples of skin mucus, blood, skin, head kidney, liver, and spleen were collected to study the immune response generated. Liver histology showed notable alterations in hepatocyte morphology, such as increased vacuolization. Bactericidal activity was measured in skin mucus and serum against V. harveyi and V. anguillarum, different changes in this activity were recorded depending on the bacteria target and sample (skin mucus or serum) used. Gene expression of genes encoding hepcidins and piscidins (antimicrobial peptides) was performed in the mentioned organs. The results indicated a different expression according to the type of AMP and the tissue studied. Hepcidin appeared involved in all tissues studied while piscidins were in the spleen. In this study we have integrated hepcidin-piscidin modulation with the effects of infection on skin mucosa, serum and hepatocyte morphology. Knowing the changes produced in all these parameters improves the understanding of the infection in the first hours in sea bream and could have applications in the diagnosis or treatment of vibriosis in fish farms.

Immunity elicited by AMP-encoding plasmids fails to increase the protection of European sea bass against nodavirus.

Antimicrobial peptides (AMPs) are a potent arm of the innate immune system that can directly kill pathogens and induce immunomodulation. In the marine aquaculture, European sea bass (Dicentrarchus labrax L.) is one of the most prosperous species but is highly susceptible to nodavirus (NNV), which produces high rates of mortality in larvae and juvenile stages. Thus, we aimed to evaluate whether AMPs exert immunomodulatory and/or NNV-preventive actions in sea bass. To do this, plasmids encoding the sea bass AMPs dicentracin (pDIC), beta-defensin (pDB1), hepcidin (pHAMP2) or NK-lysin (pNKL) were generated and intramuscularly injected into sea bass juveniles to evaluate their immunomodulatory and anti-NNV roles. Sea bass muscle transcribes the AMPs and produces an increase in their circulating levels, along with an increase of the antibacterial activity. Immune-related gene analysis revealed a great activation of the inflammatory response and the recruitment of neutrophilic granulocytes at the site of injection. However, AMP-encoding plasmids, namely pHAMP2, negatively affected to NNV disease by increasing fish mortality. In conclusion, plasmids encoding AMPs show immunostimulatory effects on European sea bass but do not improve the resistance to NNV.

Effects of okra (Abelmoschus esculentus L.) leaves, fruits and seeds extracts on European sea bass (Dicentrarchus labrax) leukocytes, and their cytotoxic, bactericidal and antioxidant properties.

Okra, Abelmoschus esculentus L., is a popular vegetable crop with many bioactive compounds. The in vitro immunostimulant, cytotoxic, bactericidal and antioxidant activities of ethanolic extracts obtained from different parts of okra (leaves, fruits, and seeds) were studied. Phytochemical screening of hydroalcoholic extracts of okra leaves, fruits and seeds revealed a significant content of total phenols and flavonoids. Notable effects on the activities of leukocytes in the head kidney of European sea bass (Dicentrarchus labrax) (viability, phagocytic ability and capacity, and respiratory burst), as well as on peroxidase leukocyte contents were detected after incubation for 24 h with different concentrations (0.01-1 mg mL-1) of the extracts. The mean concentrations (0.1 and 0.5 mg mL-1) of the different extracts increased the phagocytic ability and respiratory activity of head kidney leukocytes. However, the mean concentrations (0.1 mg mL-1) of leaf and fruit extracts significantly decreased the peroxidase activity of leukocytes. In addition, all ethanolic okra extracts at higher concentrations (1 mg mL-1) produced a marked reduction in the viability of the DLB-1 cell line compared to the viability recorded in the control samples. In addition, ethanolic extracts used at 0.5 and 1 mg mL-1 had a significant cytotoxic effect on the viability of PLHC-1 cells. Finally, all doses of seed and leaf extracts at higher concentrations (0.5 and 1 mg mL-1) showed significant bactericidal activity on two fish pathogenic bacteria, Vibrio anguillarum and V. harveyi strains. Finally, a remarkable antioxidant activity was detected on the ethanolic extracts. All these results point to their possible use as an alternative to chemical compounds in farmed fish.

An extension of the 16th Hilbert problem for continuous piecewise linear-quadratic centers separated by a non-regular line.

In the last few decades, there has been much interest in studying piecewise differential systems. This is mainly due to the fact that these differential systems allow us to modelize many natural phenomena. In order to describe the dynamics of a differential system, we need to control its periodic orbits and, especially, its limit cycles. In particular, providing an upper bound for the maximum number of limit cycles that such differential systems can exhibit would be desirable, that is solving the extended 16th Hilbert problem. In general, this is an unsolved problem. In this paper, we give an upper bound for the maximum number of limit cycles that a class of continuous piecewise differential systems formed by an arbitrary linear center and an arbitrary quadratic center separated by a non-regular line can exhibit. So for this class of continuous piecewise differential systems, we have solved the extended 16th Hilbert problem, and the upper bound found is seven. The question whether this upper bound is sharp remains open.

Infective endocarditis in children and adolescents: a different profile with clinical implications.

BACKGROUND: Our aim was to compare pediatric infective endocarditis (IE) with the clinical profile and outcomes of IE in adults. METHODS: Prospective multicenter registry in 31 Spanish hospitals including all patients with a diagnosis of IE from 2008 to 2020. RESULTS: A total of 5590 patients were included, 49 were <18 years (0.1%). Congenital heart disease (CHD) was present in 31 children and adolescents (63.2%). Right-sided location was more common in children/adolescents than in adults (46.9% vs. 6.3%, P < 0.001). Pediatric pulmonary IE was more frequent in patients with CHD (48.4%) than in those without (5.6%), P = 0.004. Staphylococcus aureus etiology tended to be more common in pediatric patients (32.7%) than in adults (22.3%), P = 0.082. Heart failure was less common in pediatric patients than in adults, due to the lower rate of heart failure in children/adolescents with CHD (9.6%) with respect to those without CHD (44.4%), P = 0.005. Inhospital mortality was high in both children, and adolescents and adults (16.3% vs. 25.9%; P = 0.126). CONCLUSIONS: Most IE cases in children and adolescents are seen in patients with CHD that have a more common right-sided location and a lower prevalence of heart failure than patients without CHD. IE in children and adolescents without CHD has a more similar profile to IE in adults. IMPACT: Infective endocarditis (IE) in children and adolescents is often seen in patients with congenital heart disease (CHD). Right-sided location is the most common in patients with CHD and heart failure is less common as a complication compared with patients without CHD. Infective endocarditis (IE) in children/adolescents without CHD has a more similar profile to IE in adults. In children/adolescents without CHD, locations were similar to adults, including a predominance of left-sided IE. Acute heart failure was the most frequent complication, seen mainly in adults, and in children/adolescents without CHD.

Induction and characterization of extracellular traps by gilthead seabream (Sparus aurata L.) head-kidney leucocytes.

The aim of this study was the induction and characterization of extracellular traps (ETs) produced by gilthead seabream (Sparus aurata L.) head-kidney leucocytes. The cells were incubated several times (10, 30, 60, 120, and 180 min) with different concentrations of the stimulants diluted in RPMI-1640 culture medium: RPMI-1640 (control), ß-glucan from Saccharomyces cerevisiae (BG, 0-400 µg mL-1), lipopolysaccharide from Escherichia coli (LPS, 0-10 µg mL-1), calcium ionophore A23187 (CaI, 0-5 µg mL-1), Phorbol 12-myristate 13-acetate (PMA, 0-1000 ng mL-1) and polyinosinic-polycytidylic acid sodium salt (Poly I:C, 0-200 µg mL-1). BG, LPS and CaI exerted only weak stimulatory activity, while PMA and poly I:C exerted a potent one. After stimulation of the leucocytes, ETs structures were quantified and visualised through staining of the chromatin with nucleic acid-specific dyes and immunocytochemical probing of characteristic proteins expected to decorate the structure. ETs structures had DNA and myeloperoxidase. The ETs morphology was studied by light and scanning electron microscopy. These data confirm that seabream leucocytes form ETs with different morphological properties, depending on the used stimulant. These results will be the basis for new studies to analyse the implication of this mechanism in fish immunity. All this new knowledge will have its application in fish farms when we learn to manipulate the innate immune response in order to mitigate microbial infections.

Two duplicated piscidin genes from gilthead seabream (Sparus aurata) with different roles in vitro and in vivo.

From the discovery of pleurocidin in skin mucus of winter flounder, many new related sequences have been found, forming a fish-exclusive family of antimicrobial peptides (AMP) called piscidin. Their mature peptides have a broad-spectrum antimicrobial activity and can be involved in the innate immune response. In the present work, two paralogous tripartite piscidin genes are formally described for the first time in gilthead seabream (Sparus aurata), an important marine farmed fish. Gene synteny and protein phylogeny clearly indicated a massive pisc gene expansion in a cluster of the chromosome 22 as well as a special evolution of piscidin in gilthead seabream compared to the rest of piscidins studied in other fish species. Despite being highly similar genes, they show totally different expression patterns in tissues and head-kidney leucocytes under both naïve and Vibrio/nodavirus-stimulated conditions. Moreover, these paralogous genes coded very different proteins according to their physicochemical properties. In this way, these piscidin genes have distinct roles not only related to their microbicide activity but also to their immune modulation. In addition, the present study improves the knowledge of duplication of AMP genes and adaptative diversification of teleost immune system.

Massive gene expansion of hepcidin, a host defense peptide, in gilthead seabream (Sparus aurata).

Host defense peptides (HDP) are among the most ancient immune molecules in animals and clearly reflect an ancestral evolutionary history involving pathogen-host interactions. Hepcidins are a very widespread family of HDPs among vertebrates and are especially diverse in teleosts. We have investigated the identification of new hepcidins in gilthead seabream (Sparus aurata), a fish farmed in the Mediterranean. Targeted gene predictions supported with expressed sequence tags (ESTs) derived from Hidden Markov Models were used to find the hamp genes in the seabream genome. The results revealed a massively clustered hamp duplication on chromosome 17. In fact, the seabream genome contains the largest number of hepcidin copies described in any vertebrate. The evolutionary history of hepcidins in seabream, and vertebrates generally, clearly indicates high adaptation in teleosts and novel subgroups within hepcidin type II. Furthermore, basal hepcidin gene expression analysis indicates specific-tissue expression profiles, while the presence and distribution of transcription factor binding sites (TFBS) in hamp promoters as well as their transcription profile upon bacterial challenge indicates different immune roles depending on the type of hepcidin and tissue. This massive duplication of HDP genes in a bony fish could point to a far more specific and adaptive innate immune system than assumed in the classic concept of immunity in mammals. Hence, a new world of knowledge regarding hepcidins in fish and vertebrates is being initiated.

Dietary administration of silk microparticles improves the epidermal and dermal regeneration after a skin wounding in gilthead seabream (Sparus aurata L.).

The impact of dietary supplementation with silk fibroin (SF) microparticles on the wound healing process in gilthead seabream (Sparus aurata) skin was studied. A control diet was enriched with different SF levels: 0 (control), 50 (SF50 diet), and 100 (SF100 diet) mg Kg-1 to form three experimental diets and was fed to seabream for 30 days. Experimental wounds were performed and after 7 days post-wounding (dpw) skin mucus immunity, macroscopic wound closure, and skin regeneration were studied at a microscopic and genetic level. Results indicated that fish fed SF100 did not suffer the decreases in protease and IgM levels observed in the skin mucus of wounded fish fed with the control diet. Macroscopic findings illustrated that dietary SF100 significantly improved the wound closure ratio compared to those reared in the control group. At a microscopic level, changes in the shape of keratocyte cells were evident in the wounded fish. In addition, the intercellular spaces present between epidermal cells and their proliferation in the epidermis, as well as the presence of blood vessels in the dermis were significantly statistically higher in the skin of fish fed the SF100 diet and sampled at 7 dpw compared to those observed in the skin of fish fed the control or SF50 diets. Moreover, regarding the RNA: DNA ratio, statistically significant increases and decreases were observed in fish fed the control and SF100 diet, respectively, in non-wounded and wounded fish. Interestingly, dietary SF100 supplementation improved skin cell proliferation, enhanced the inflammatory phase, and increased the expression of important genes involved in tissue repair and extracellular matrix formation. In conclusion, the SF100 diet can be considered as an appropriate feed additive to improve wound healing in gilthead seabream.

Over 55 years of critical power: Fact or artifact?

This report aims to generate an evidence-based debate of the Critical Power (CP), or its analogous Critical Speed (CS), concept. Race times of top Spanish runners were utilized to calculate CS based on three (1500-m to 5000-m; CS1.5-5km ) and four (1500-m to 10000-m; CS1.5-10km ) distance performances. Male running world records from 1000 to 5000-m (CS1-5km ), 1000 to 10,000-m (CS1-10km ), 1000-m to half marathon (CS1km-half marathon ), and 1000-m to marathon (CS1km-marathon ) distance races were also utilized for CS calculations. CS1.5-5km (19.62 km h-1 ) and CS1.5-10km (18.68 km h-1 ) were different (p < 0.01), but both approached the average race speed of the longest distance chosen in the model, and were remarkably homogeneous among subjects (97% ±1% and 98% ±1%, respectively). Similar results were obtained using the world records. CS values progressively declined, until reaching a CS1km-marathon value of 20.77 km h-1 (10% lower than CS1-5km ). Each CS value approached the average speed of the longest distance chosen in the model (96.4%-99.8%). A power function better fitted the speed-time relationship compared with the standardized hyperbolic function. However, the horizontal asymptote of a power function is zero. This better approaches the classical definition of CP: the power output that can be maintained almost indefinitely without exhaustion. Beyond any sophisticated mathematical calculation, CS corresponds to 95%-99% of the average speed of the longest distance chosen as an exercise trial. CP could be considered a mathematical artifact rather than an important endurance performance marker. In such a case, the consideration of CP as a physiological "gold-standard" should be reevaluated.

Pyridinium Salts of Dehydrated Lanthanide Polychlorides.

The reaction of lanthanide (Ln) chloride hydrates ([Ln(H2O)n(Cl)3]) with pyridine (py) yielded a set of dehydrated pyridinium (py-H) Ln-polychloride salts. These species were crystallographically characterized as [[py-H-py][py-H]2[LnCl6]] (Ln-6; Ln = La, Ce, Pr, Nd, Sm, Eu, Gd) or [[py-H]2[LnCl5(py)]] ((Ln-5; Ln = Tb, Dy, Ho, Er, Tm, Yb, Lu). The Ln-6 metal centers adopt an octahedral (OC-6) geometry, binding six Cl ligands. The -3 charge is off-set by two py-H moieties and a di-pyridinium (py-H-py) ion. For the Ln-5 species, an OC-6 anion is formed by the Ln cation binding a single py and five Cl ligands. The remaining -2 charge is offset by two py-H+ cations that H-bond to the anion. Significant H-bonding occurs between the various cation/anion moieties inducing the molecular stability. The change in structure from the Ln-6 to Ln-5 is believed to be due to the Ln-contraction producing a smaller unit cell, which prevents formation of the py-H-py+ cation, leading to the loss of the H-bonding-induced stability. Based on this, it was determined that the Ln-5 structures only exist when the lattice energy is small. While dehydrated polychloride salts can be produced by simply mixing in pyridine, the final structures adopted result from a delicate balance of cation size, Coulombic charge, and stabilizing H-bonding.

Characteristics and Outcome of Acute Heart Failure in Infective Endocarditis: Focus on Cardiogenic Shock.

BACKGROUND: Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. METHODS: Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality. RESULTS: Among 4856 endocarditis patients, 1652 (34%) had acute heart failure (AHF) and 244 (5%) CS. Compared with patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5%, and 68%; P < .001) and in-hospital mortality (16.3%, 39.1%, and 52.5%). Compared with patients with septic shock, CS patients presented higher rates of surgery (42.5% vs 68%; P < .001) and lower rates of in-hospital and 1-year mortality (62.3% vs 52.5%, P = .008, and 65.3% vs 57.4%, P = .030). Severe aortic and mitral regurgitation (OR [95% CI], 2.47 [1.82-3.35] and 3.03 [2.26-4.07]; both P < .001), left-ventricle ejection fraction <60% (1.72; 1.22-2.40; P = .002), heart block (2.22; 1.41-3.47; P = .001), tachyarrhythmias (5.07; 3.13-8.19; P < .001), and acute kidney failure (2.29; 1.73-3.03; P < .001) were associated with higher likelihood of developing CS. Prosthetic endocarditis (2.03; 1.06 -3.88; P = .032), Staphylococcus aureus (3.10; 1.16 -8.30; P = .024), tachyarrhythmias (3.09; 1.50-10.13; P = .005), and not performing cardiac surgery (11.40; 4.83-26.90; P < .001) were associated with a higher risk of mortality. CONCLUSIONS: AHF is common among patients with endocarditis. CS is associated with high mortality and should be promptly identified and assessed for cardiac surgery.