Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies.

The pathophysiology of vascular disease is linked to accelerated biological aging and a combination of genetic, lifestyle, biological, and environmental risk factors. Within the scenario of uncontrolled artery wall aging processes, CKD (chronic kidney disease) stands out as a valid model for detailed structural, functional, and molecular studies of this process. The cardiorenal syndrome relates to the detrimental bidirectional interplay between the kidney and the cardiovascular system. In addition to established risk factors, this group of patients is subjected to a plethora of other emerging vascular risk factors, such as inflammation, oxidative stress, mitochondrial dysfunction, vitamin K deficiency, cellular senescence, somatic mutations, epigenetic modifications, and increased apoptosis. A better understanding of the molecular mechanisms through which the uremic milieu triggers and maintains early vascular aging processes, has provided important new clues on inflammatory pathways and emerging risk factors alike, and to the altered behavior of cells in the arterial wall. Advances in the understanding of the biology of uremic early vascular aging opens avenues to novel pharmacological and nutritional therapeutic interventions. Such strategies hold promise to improve future prevention and treatment of early vascular aging not only in CKD but also in the elderly general population.

Deploy the proboscis!: Functional morphology and kinematics of a novel form of extreme jaw protrusion in the hingemouth, Phractolaemus ansorgii (Gonorynchiformes).

Premaxillary protrusion and the performance advantages it confers are implicated in the success of diverse lineages of teleost fishes, such as Cypriniformes and Acanthomorpha. Although premaxillary protrusion has evolved independently at least five times within bony fishes, much of the functional work investigating this kinesis relates to mechanisms found only in these two clades. Few studies have characterized feeding mechanisms in less-diverse premaxilla-protruding lineages and fewer yet have investigated the distinctive anatomy underlying jaw kinesis in these lineages. Here, we integrated dissection, clearing and staining, histology, micro-CT, and high-speed videography to investigate an isolated and independent origin of jaw protrusion in the hingemouth, Phractolaemus ansorgii, which employs a complex arrangement of bones, musculature, and connective tissues to feed on benthic detritus via a deployable proboscis. Our goals were to provide an integrative account of the underlying architecture of P. ansorgii's feeding apparatus and to assess the functional consequences of this drastic deviation from the more typical teleost condition. Phractolaemus ansorgii's cranial anatomy is distinct from all other fishes in that its adducted lower jaw is caudally oriented, and it possesses a mouth at the terminal end of an elongated, tube-like proboscis that is unique in its lack of skeletal support from the oral jaws. Instead, its mouth is supported primarily by hyaline-cell cartilage and other rigid connective tissues, and features highly flexible lips that are covered in rows of keratinous unculi. Concomitant changes to the adductor musculature likely allow for the flexibility to protrude the mouth dorsally and ventrally as observed during different feeding behaviors, while the intrinsic compliance of the lips allows for more effective scraping of irregular surfaces. From our feeding videos, we find that P. ansorgii is capable of modulating the distance of protrusion, with maximum anterior protrusion exceeding 30% of head length. This represents a previously undescribed example of extreme jaw protrusion on par with many acanthomorph species. Protrusion is much slower in P. ansorgii-reaching an average speed of 2.74 cm/s-compared to acanthomorphs feeding on elusive prey or even benthivorous cypriniforms. However, this reorganization of cranial anatomy may reflect a greater need for dexterity to forage more precisely in multiple directions and on a wide variety of surface textures. Although this highly modified mechanism may have limited versatility over evolutionary timescales, it has persisted in solitude within Gonorynchiformes, representing a novel functional solution for benthic feeding in tropical West African rivers.

Two-row, three-row or powered circular stapler, which to choose when performing colorectal anastomosis? A systematic review and meta-analysis.

PURPOSE: Three types of circular staplers can be used to perform a colorectal anastomosis: two-row (MCS), three-row (TRCS) and powered (PCS) devices. The objective of this meta-analysis has been to provide the existing evidence on which of these circular staplers would have a lower risk of presenting a leak (AL) and/or anastomotic bleeding (AB). METHODS: An in-depth search was carried out in the electronic bibliographic databases Embase, PubMed and SCOPUS. Observational studies were included, since randomized clinical trials comparing circular staplers were not found. RESULTS: In the case of AL, seven studies met the inclusion criteria in the PCS group and four in the TRCS group. In the case of AB, only four studies could be included in the analysis in the PCS group. The AL OR reported for PCS was 0.402 (95%-confidence interval (95%-CI): 0.266-0.608) and for AB: 0.2 (95% CI: 0.08-0.52). The OR obtained for AL in TRCS was 0.446 (95%-CI: 0.217 to 0.916). Risk difference for AL in PCS was - 0.06 (95% CI: - 0.07 to - 0.04) and in TRCS was - 0.04 (95%-CI: - 0.08 to - 0.01). Subgroup analysis did not report significant differences between groups. On the other hand, the AB OR obtained for PCS was 0.2 (95% CI: 0.08-0.52). In this case, no significant differences were observed in subgroup analysis. CONCLUSION: PCS presented a significantly lower risk of leakage and anastomotic bleeding while TRCS only demonstrated a risk reduction in AL. Risk difference of AL was superior in the PCS than in TRCS.

Mechanisms by which feeding synthetic zeolite A and dietary cation-anion difference diets affect feed intake, energy metabolism, and milk performance: Part II.

The objectives of this study were to assess the effects of feeding 2 different diets, a diet with low dietary cation-anion difference (DCAD) or a diet with synthetic zeolite A, to multiparous Holstein cows during the close-up period on dry matter intake (DMI) and energy metabolism, as well as to evaluate colostrum and milk production. A total of 121 multiparous Holstein cows, blocked by lactation number and expected parturition date were enrolled at 254 d of gestation and randomly assigned to 1 of 3 dietary treatments: control (CON; +190 mEq/kg; n = 40), negative DCAD (-DCAD, -65 mEq/kg; n = 41; Ultra Chlor; Vita Plus, Lake Mills, WI), or a diet containing sodium aluminum silicate zeolite (XZ; +278 mEq/kg, fed at 3.3% dry matter, targeting 500 g/d; n = 40; X-Zelit, Protekta Inc., Lucknow, ON, Canada/Vilofoss, Graasten, Denmark). Prepartum DMI was measured daily using Insentec roughage intake control (RIC) gates (RIC System, Holofarm Group, the Netherlands). All cows received the same postpartum diet. Blood and urine samples were collected daily beginning 14 d before parturition (d -14) until parturition (d 0), and on 1, 2, 3, 6, 9, 12, 15, 18, 21, 35, and 49 d postpartum. Colostrum collected within 6 h of parturition, weighed, and based on samples' Brix value, IgG concentrations, and nutrient composition were analyzed. Prepartum, cows fed the XZ diet had decreased DMI (11.70 ± 0.26, 13.88 ± 0.26, and 13.45 ± 0.25 kg/d for XZ, CON, and -DCAD, respectively) and lower rumination (487 ± 8.1, 531 ± 8.3, and 527 ± 8.5 min for XZ, CON, and -DCAD, respectively) compared with CON and -DCAD. However, rumination was not different postpartum due to treatment. No prepartum or postpartum differences were observed for glucose or BHB concentrations in blood between dietary treatments. Colostrum collected from cows fed XZ had the highest IgG concentrations (91.10 ± 2.63, 78.00 ± 2.63, and 78.90 ± 2.63 mg/mL for XZ, CON, and -DCAD, respectively), but yield did not differ between dietary treatments. Additionally, cows in their third lactation or greater fed XZ had the highest milk production (51.0 ± 1.1 kg) during the first 49 d in milk. This study demonstrates that despite a decrease in DMI and rumination in cows fed XZ prepartum, blood BHB concentrations were not altered. Additionally, cows fed XZ had higher colostral IgG concentrations and cows in their third lactation or greater fed XZ produced the most milk. These data suggest that feeding XZ prepartum may improve colostrum quality and milk yield in mature cows, and does not affect energy metabolism.

Influence of prepartum dietary cation-anion difference and the magnitude of calcium decline at the onset of lactation on mineral metabolism and physiological responses.

The onset of lactation is characterized by substantially altered calcium (Ca) metabolism; recently, emphasis has been placed on understanding the dynamics of blood Ca in the peripartal cow in response to this change. Thus, the aim of our study was to delineate how prepartum dietary cation-anion difference (DCAD) diets and the magnitude of Ca decline at the onset of lactation altered blood Ca dynamics in the periparturient cow. Thirty-two multiparous Holstein cows were blocked by parity, previous 305-d milk yield and expected parturition date, and randomly allocated to either a positive (+120 mEq/kg) or negative (-120 mEq/kg) DCAD diet from 251 d of gestation until parturition (n = 16/diet). Immediately after parturition cows were continuously infused for 24 h with (1) an intravenous solution of 10% dextrose or (2) Ca gluconate (CaGlc) to maintain blood ionized (iCa) concentrations at ∼1.2 mM (normocalcemia) to form 4 treatment groups (n = 8/treatment). Blood was sampled every 6 h from 102 h before parturition until 96 h after parturition and every 30 min during 24 h continuous infusion. Cows fed a negative DCAD diet prepartum exhibited a less pronounced decline in blood iCa approaching parturition with lesser magnitude of decline relative to positive DCAD-fed cows. Cows fed a negative DCAD diet prepartum required lower rates of CaGlc infusion to maintain normocalcemia in the 24 h postpartum relative to positive DCAD-fed cows. Infusion of CaGlc disrupted blood Ca and P dynamics in the immediate 24 h after parturition and in the days following infusion. Collectively, these data demonstrate that prepartum negative DCAD diets facilitate a more transient hypocalcemia and improve blood Ca profiles at the onset of lactation whereas CaGlc infusion disrupts mineral metabolism.

Mechanisms by which feeding synthetic zeolite A and dietary cation-anion difference diets affect mineral metabolism in multiparous Holstein cows: Part I.

The periparturient period is characterized by the increased demand for calcium (Ca) in dairy cows. This has resulted in the use of several different prepartal nutritional strategies to prevent hypocalcemia postpartum. The objective of our study was to determine the effects of feeding synthetic zeolite A (XZ), a diet with negative dietary cation-anion difference (-DCAD), or a positive-DCAD diet (CON) during the close-up period on peripartal mineral dynamics and hormones involved in calcium metabolism. To this end, 121 multiparous Holstein cows, blocked by lactation number and expected due date, were enrolled at 254 d of gestation and randomly assigned to 1 of 3 prepartum diets: CON (+190 mEq/kg; n = 40), -DCAD (-65 mEq/kg; n = 41), or a diet supplemented with sodium aluminum silicate (XZ; +278 mEq/kg, fed at 3.3% DM, targeting 500 g/d; n = 40; Protekta Inc.). Blood, urine, and saliva samples were collected from enrollment until parturition, with data analyzed and presented beginning 14 d before parturition (d -14) until parturition (d 0), and on d 1, 2, 3, 6, 9, 12, 15, 18, 21, 35, and 49 postpartum, to assess mineral and hormone dynamics. Total fecal collections were performed in a subset of 8 cows per treatment group to assess fecal mineral loss. Data were analyzed as a randomized complete block design in SAS. Cows fed XZ and -DCAD had higher blood Ca concentrations compared with CON-fed cows, with XZ-fed cows exhibiting the highest blood Ca concentrations pre- and postpartum. Cows fed XZ had decreased blood and salivary phosphorus (P), increased fecal water-extractable phosphate, and the highest blood calcium concentrations pre- and postpartum. Parathyroid hormone was unaffected by diet but was increased at parturition in all treatments. Serotonin concentrations were increased in -DCAD and XZ cows compared with CON during the prepartum period. Our data indicate that the XZ group's improvement in blood Ca concentrations pre- and postpartum is most likely regulated by a dietary P restriction. Taken together, these data suggest that XZ and -DCAD diets improve postpartum calcium metabolism; however, they appear to work through different mechanisms.

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Amplifying local serotonin signaling prior to dry-off hastens mammary gland involution and redevelopment in dairy cows.

The monoamine serotonin (5-hydroxytryptamine, 5-HT) has been reported to inhibit milk protein gene expression and increase mammary epithelial cell (MEC) tight junction permeability after milk stasis. We hypothesized that increasing serotonin synthesis and signaling within the mammary epithelium before milk stasis would increase systemic and local involution markers, and downregulate the expression of milk protein and tight junction during involution, leading to more efficient tissue growth during the redevelopment phase. Herein, we examined the outcomes of increasing local mammary 5-HT synthesis before milk stasis on involution biomarkers, mammary gland microstructure, and gene and protein expression during the dry period. Multiparous Holstein cows were administered intramammary infusions (via the teat canal) of sterile water (CON, 4 mL/teat, n = 7) or 5-hydroxy-l-tryptophan (5-HTP, serotonin precursor, 20 mg/teat, n = 7) once daily for 5 d before dry-off (d 0). Blood, milk, and mammary secretions were collected and analyzed for components and metabolites. Mammary secretions were collected 12 h after the last milking and on d 1 to 4 during the dry period at 1200 h. Mammary gland biopsies were performed on d 4 (i.e., involution phase) and d 36 (i.e., redevelopment phase) of the dry period for histological and molecular evaluation. Milk protein and tight junction gene expression was quantified via real-time PCR. Hematoxylin and eosin staining, immunohistochemistry (Ki67), and immunofluorescence (serotonin, cleaved caspase 3) were performed to visualize tissue microstructure and to quantify serotonin intensity and cell turnover. Data were analyzed in SAS (SAS Institute Inc.) using 2-way ANOVA. After d 0, mammary secretions of 5-HTP cows had increased concentrations of 5-HT, lactoferrin, and bovine serum albumin. On d 1, 5-HTP cows had greater α-lactalbumin concentrations in plasma relative to CON. Serotonin intensity was increased in the mammary tissue of 5-HTP cows on d 4, relative to CON. On d 4, milk protein and tight junction gene expression was downregulated, MEC number was reduced, and cleaved caspase 3 protein was greater in mammary tissue of 5-HTP cows, relative to CON. On d 36, milk protein genes were upregulated, and the lumen:outer alveolar area and Ki67-positive cells were increased in the mammary tissue of 5-HTP cows, relative to CON. Amplifying serotonin signaling in the mammary epithelium before milk stasis at dry-off achieves greater apoptosis, leading to a reduction in MEC, allowing for greater cell proliferation, which results in more MEC during the redevelopment phase preceding the onset of lactation.

Eucalcemia during lipopolysaccharide challenge in postpartum dairy cows: II. Calcium dynamics.

Hypocalcemia induced by immune activation is a conserved response among mammals. Early postpartum cows will experience decreased circulating Ca concentrations following acute immune activation; however, the cause for decreased Ca concentration is unknown. Our objectives were to (1) describe Ca dynamics following an intravenous (IV) LPS challenge in early postpartum cows, and (2) compare inflammatory-induced changes in Ca dynamics between IV Ca-treated cows and control cows. Cows (n = 14, 8 ± 1 d in milk) were enrolled in a matched-pair randomized controlled design to receive IV Ca (IVCa) in a eucalcemic clamp for 12 h, or 0.9% NaCl (CTRL) following an IV LPS infusion (0.040 or 0.045 µg of LPS/kg of body weight over 1 h). During the 24 h following LPS infusion, circulating concentrations of parathyroid hormone and serotonin were measured, serum and urine samples were collected to calculate urinary fractional excretion of Ca (FECa), and fecal samples were collected to calculate Ca apparent digestibility (ADCa) using amylase-treated and ash-corrected undigested neutral detergent fiber after 240 h (uNDFom240) as an internal marker. Changes in Ca intake and milk Ca secretion were also quantified and compared with baseline values. Cows were fasted during challenge and dry matter intake was 20 ± 5% less than baseline values on the day of challenge and did not differ between groups. On the day of challenge, milk Ca concentration increased, but milk yield decreased such that total Ca secreted in milk did not change from baseline. Urine FECa was low overall, but an interaction of treatment and time was identified such that FECa increased in IVCa but decreased in CTRL. Concentrations of parathyroid hormone increased and serotonin decreased following challenge. Fecal dry matter decreased from baseline, but did not differ between 6, 12, and 24 h, and did not differ between groups. An interaction of treatment and time was identified for ADCa and apparent digestibility of dry matter such that digestibility was decreased in CTRL but not IVCa at 6 h. Acute immune activation induced hypocalcemia in CTRL, and although urinary Ca excretion was not a primary cause, it is unclear to what degree hypocalcemia was due to altered ADCa. Eucalcemia appeared to alter adaptations in Ca homeostasis during immune activation as FECa was increased in IVCa animals.

Characterizing ruminal acidosis risk: A multiherd, multicountry study.

A multicenter observational study was conducted on early lactation Holstein cows (n = 261) from 32 herds from 3 regions (Australia, AU; California, CA; and Canada, CAN) to characterize their risk of acidosis into 3 groups (high, medium, or low) using a discriminant analysis model previously developed. Diets ranged from pasture supplemented with concentrates to total mixed ration (nonfiber carbohydrates = 17 to 47 and neutral detergent fiber = 27 to 58% of dry matter). Rumen fluid samples were collected <3 h after feeding and analyzed for pH, and ammonia, d- and l-lactate, and volatile fatty acid (VFA) concentrations. Eigenvectors were produced using cluster and discriminant analysis from a combination of rumen pH, and ammonia, d-lactate, and individual VFA concentrations and were used to calculate the probability of the risk of ruminal acidosis based on proximity to the centroid of 3 clusters. Bacterial 16S ribosomal DNA sequence data were analyzed to characterize bacteria. Individual cow milk volume, fat, protein, and somatic cell count values were obtained from the closest herd test to the rumen sampling date (median = 1 d before rumen sampling). Mixed model analyses were performed on the markers of rumen fermentation, production characteristics, and the probability of acidosis. A total of 26.1% of the cows were classified as high risk for acidosis, 26.8% as medium risk, and 47.1% as low risk. Acidosis risk differed among regions with AU (37.2%) and CA (39.2%) having similar prevalence of high-risk cows and CAN only 5.2%. The high-risk group had rumen phyla, fermentation, and production characteristics consistent with a model of acidosis that reflected a rapid rate of carbohydrate fermentation. Namely, acetate to propionate ratio (1.98 ± 0.11), concentrations of valerate (2.93 ± 0.14 mM), milk fat to protein ratio (1.11 ± 0.047), and a positive association with abundance of phylum Firmicutes. The medium-risk group contains cows that may be inappetant or that had not eaten recently or were in recovery from acidosis. The low-risk group may represent cattle that are well fed with a stable rumen and a slower rumen fermentation of carbohydrates. The high risk for acidosis group had lower diversity of bacteria than the other groups, whereas CAN had a greater diversity than AU and CA. Rumen fermentation profile, abundance of ruminal bacterial phyla, and production characteristics of early lactation dairy cattle from 3 regions were successfully categorized in 3 different acidosis risk states, with characteristics differing between acidosis risk groups. The prevalence of acidosis risk also differed between regions.

Prurigiform Angiomatosis: A New Term for Describing the Prominent Dermal Angiomatoid Proliferation Underlying Epidermal Changes in Prurigo Nodularis/Lichen Simplex Chronicus. / Angiomatosis prurigiforme: una nueva entidad propuesta para la proliferación angiomatoide dérmica prominente subyacente a los cambios epidérmicos de prurigo nodularis/liquen simple crónico.

Vascular hyperplasia is a common finding in prurigo nodularis/lichen simplex chronicus (LSC). The term prurigiform angiomatosis was recently proposed to describe a histologic pattern characterized by prominent vascular hyperplasia in patients with LSC. The aim of this study was to identify cases of LSC with this pattern and analyze associations with clinical and pathologic features and disease course. We reviewed 54 cases of histologically confirmed LSC and detected findings consistent with prurigiform angiomatosis in 10 (18.5%). The patients (7 men, 3 women) had a mean age of 59.7 years. The lesions were pruritic and predominantly located on the extremities and trunk. The most notable histologic finding was vascular proliferation in the superficial dermis associated with a lymphocytic inflammatory infiltrate. Recognition of prurigiform angiomatosis is important as it helps not only to distinguish LSC from other entities (mainly vascular tumors) but also to detect lesions that need to be surgically excised due to poor response to topical treatment.

The role of heterotopy and heterochrony during morphological diversification of otocephalan epibranchial organs.

Epibranchial organs (EBOs), found in at least five of the eight otomorphan families, are used to aggregate small prey inside the buccopharyngeal cavity and range in morphological complexity from a singular, small slit on the pharyngeal roof to several, elongated soft tissue tubes. Despite broad phylogenetic representation, little is known about the origin, development, or evolution of EBOs. We hypothesize that both heterochronic and heterotopic changes throughout the evolution of EBOs are at the root of their morphological diversity. Heterochrony is a foundational explanation in developmental studies, however, heterotopy, a developmental change in spatial or topographical relationships, can have even more profound effects on a given structure but has received relatively little attention. Here, we investigate how developmental mechanisms may drive morphological diversity of EBOs within otomorphan fishes. We compare early pharyngeal development in three species, Anchoa mitchilli (Engraulidae) which has the most basic EBO, B. tyrannus (Clupeidae) which has a more complex EBO, and Hypophthalmichthys molitrix (Cyprinidae) which has the most complex EBO yet described. Using branchial arch growth rates and morphological analyses, we illustrate how both heterochronic and heterotopic mechanisms are responsible for some of the phenotypic diversity seen in otomorphan EBOs. Importantly, we also identify conserved developmental patterns that further our understanding of how EBOs may have first originated and evolved across actinopterygian fishes.

Phylogenomics of Piranhas and Pacus (Serrasalmidae) Uncovers How Dietary Convergence and Parallelism Obfuscate Traditional Morphological Taxonomy.

The Amazon and neighboring South American river basins harbor the world's most diverse assemblages of freshwater fishes. One of the most prominent South American fish families is the Serrasalmidae (pacus and piranhas), found in nearly every continental basin. Serrasalmids are keystone ecological taxa, being some of the top riverine predators as well as the primary seed dispersers in the flooded forest. Despite their widespread occurrence and notable ecologies, serrasalmid evolutionary history and systematics are controversial. For example, the sister taxon to serrasalmids is contentious, the relationships of major clades within the family are inconsistent across different methodologies, and half of the extant serrasalmid genera are suggested to be non-monophyletic. We analyzed exon capture to reexamine the evolutionary relationships among 63 (of 99) species across all 16 serrasalmid genera and their nearest outgroups, including multiple individuals per species to account for cryptic lineages. To reconstruct the timeline of serrasalmid diversification, we time-calibrated this phylogeny using two different fossil-calibration schemes to account for uncertainty in taxonomy with respect to fossil teeth. Finally, we analyzed diet evolution across the family and comment on associated changes in dentition, highlighting the ecomorphological diversity within serrasalmids. We document widespread non-monophyly of genera within Myleinae, as well as between Serrasalmus and Pristobrycon, and propose that reliance on traits like teeth to distinguish among genera is confounded by ecological homoplasy, especially among herbivorous and omnivorous taxa. We clarify the relationships among all serrasalmid genera, propose new subfamily affiliations, and support hemiodontids as the sister taxon to Serrasalmidae. [Characiformes; exon capture; ichthyochory; molecular time-calibration; piscivory.].

Butyrate administration strengthens the intestinal epithelium and improves intestinal dysbiosis in a cholestasis fibrosis model.

AIM: Intestinal dysfunction in cirrhosis patients is linked to death by bacterial infections. Currently, there is no effective therapy for this complication. This study aims to evaluate butyrate, a novel postbiotic, on the intestinal inflammatory response, tight junction proteins and the microbiota in the cholestasis model. METHODS AND RESULTS: Wistar rats underwent 15 days of bile duct ligation (BDL). We administered butyrate at a concentration of 1%. The BDL group did not receive treatment. The results showed that butyrate could significantly reduce pro-inflammatory cytokines (IL-17A, IFN-γ, TNF-α) in the ileum and colon while promoting IL-10 expression in the colon. Moreover, it significantly promotes tight junction protein (cld-1, occludin and ZO-1) expression in the ileum. A similar effect was observed in the colon except for ZO-1. Additionally, butyrate limited taxa diversity loss and promoted probiotic genera expansion such as Lachnospira, Prevotella and Lactobacillus. The increase in Turicibacter and Clostridiaceae distinguished the BDL group. CONCLUSIONS: Butyrate is effective in regulating the inflammatory response, tight junction proteins and limits bacterial diversity loss. SIGNIFICANCE AND IMPACT OF THE STUDY: This research reveals that butyrate could represent an interesting postbiotic metabolomic intervention for intestinal epithelium dysfunction in liver disease.

Physiological adaptations in early-lactation cows result in differential responses to calcium perturbation relative to nonlactating, nonpregnant cows.

The peripartal cow experiences a rapid change in calcium metabolism at the onset of lactation. Research has focused on understanding how mammary-derived factors, such as serotonin (5HT) and parathyroid hormone like hormone (PTHLH), aid in coordinating these calcemic adaptations to lactation. Therefore, the aim of our study was to determine how induced subclinical hypocalcemia influences physiological responses, specifically the 5HT-PTHLH-Ca axis, in lactating and nonlactating dairy cows to elucidate the potential contribution of the mammary gland. Twelve nonlactating, nonpregnant (NL) multiparous Holstein cows and 12 early-lactation (EL) multiparous Holstein cows received either (1) a continuous 24-h intravenous solution of 0.9% NaCl or (2) 5% ethylene glycol tetraacetic acid (EGTA) solution in 0.9% NaCl (n = 6 EL, n = 6 NL per treatment) with the aim of maintaining blood ionized calcium (iCa) less than 1.0 mM. Mammary gland biopsies were taken immediately after and 48 h after termination of infusion. Blood was sampled hourly during infusion and 4, 8, 12, 24, 48, and 72 h after termination of infusion. Infusion of EGTA successfully decreased blood iCa concentrations. However, EL EGTA-infused cows required increased rates of EGTA infusion to maintain iCa below 1.0 mM. Circulating and mammary serotonin concentrations were increased in EL relative to NL cows, with no difference as a result of EGTA infusion. Mammary PTHLH expression was increased in EL cows, with highest expression observed in EL EGTA-infused cows. Collectively, these data demonstrate the robust adaptations EL cows have to maintain Ca homeostasis and the supporting roles 5HT and PTHLH may play.

Ordinary heterotrophic organisms with aerobic storage capacity provide stable aerobic granular sludge for C and N removal.

The study investigated the mechanisms and microbial communities underlying the long-term stability and removal performances shown by aerobic granular sludge (AGS) reactor involving polyhydroxyalkanoates (PHA) aerobic-storing bacteria. The characteristics of the sludge, removal performances and bacterial community structure were determined. The prevailing metabolic phenotype was similar in the parent conventional activated sludge (CAS) reactor and its upgraded AGS version, showing high COD and NH4 uptake, versus low P and N reduction. Polyphosphate and glycogen accumulating organisms, PAO and GAO, were not enriched in the reactors despite initial targeting of anaerobic-aerobic cycle. Instead, PHA-aerobic storing bacteria (Thauera and Paracoccus) were dominant, but revealing a stable AGS system for BOD and N removal. The PAO/GAO failed selection and Thauera overgrowth were analyzed for beneficial use in developing alternative AGS technology for BOD and N removal applications.

Cycloaddition between nitrogen-doped graphene (6π-component) and benzene (4π-component): a theoretical approach using density functional theory with vdW-DF correction.

The interaction between nitrogen-doped graphene defects (N3V1 and N4V2 pyridinic, and N3V1 and N3V3 pyrrolic) and benzene have been investigated by applying density functional theory (DFT), together with the vdW-DF correction. We discovered that only the N3V3 pyrrolic defect is a reactive site (6π-component), forming a cycloadduct with benzene (4π-component) that has energy barriers below 154.38 kJ mol-1 (1.60 eV). The conduction and valence bands (HOMO and LUMO) for N3V3 form a degenerate pair of orbitals at the gamma point, with the same ionization potential (IP) and electron affinity (EA). Likewise, inspection of the orbital symmetries for both systems confirms that these must undergo concerted reactions based on the Woodward and Hoffmann principles of orbital symmetry, with the appropriate orbital occupancies. This is the first time that substitutionally doped graphene has been demonstrated to participate as a 6π-component for cycloaddition reactions with benzene.

Photoinduced Energy Transfer in Linear Guest-Host Chromophores: A Computational Study.

Polymer-based guest-host systems represent a promising class of materials for efficient light-emitting diodes. The energy transfer from the polymer host to the guest is the key process in light generation. Therefore, microscopic descriptions of the different mechanisms involved in the energy transfer can contribute to enlighten the basis of the highly efficient light harvesting observed in this kind of materials. Herein, the nature of intramolecular energy transfer in a dye-end-capped conjugated polymer is explored by using atomistic nonadiabatic excited-state molecular dynamics. Linear perylene end-capped (PEC) polyindenofluorenes (PIF), consisting of n (n = 2, 4, and 6) repeat units, i.e., PEC-PIFn oligomers, are considered as model systems. After photoexcitation at the oligomer absorption maximum, an initial exciton becomes self-trapped on one of the monomer units (donors). Thereafter, an efficient ultrafast through-space energy transfer from this unit to the perylene acceptor takes place. We observe that this energy transfer occurs equally well from any monomer unit on the chain. Effective specific vibronic couplings between each monomer and the acceptor are identified. These oligomer → end-cap energy transfer steps do not match with the rates predicted by Förster-type energy transfer. The through-space and through-bond mechanisms are two distinct channels of energy transfer. The former dominates the overall process, whereas the through-bond energy transfer between indenofluorene monomer units along the oligomer backbone only makes a minor contribution.

Women and COVID-19: severity and mortality in hospitalized middle-aged and older patients.

OBJECTIVE: The aim of the study was to evaluate the clinical features, severity, and mortality of coronavirus disease-2019 (COVID-19) in hospitalized middle-aged and older women, and the risk factors associated with severity and mortality in women. METHODS: A retrospective study was conducted in hospitalized patients with COVID-19. The clinical features, severity, and mortality of COVID-19 in middle-aged and older women (age 45 years and older) were compared to those of younger women (age <45 years). RESULTS: A higher frequency of hypertension, invasive mechanical ventilation (IMV) requirement, and mortality was evidenced in middle-aged and older women. Age ≥45 years (odds ratio 2.7; 95% confidence interval 1.21-6.27; p = 0.01) and IMV requirement (odds ratio 3.0; 95% confidence interval 1.34-6.76; p = 0.004) predicted mortality. CONCLUSIONS: Severity and mortality are higher in middle-aged and older women with COVID-19 compared to younger women.