Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

OBJECTIVE: To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. ANIMALS: 74 dogs (control, n = 12; MMVD, n = 62) were included. METHODS: Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. RESULTS: The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. CLINICAL RELEVANCE: Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Oesophageal stricture in a cat with true pleuroperitoneal hernia.

A 2-year-old neutered male Bengal cat presented with solid food dysphagia and chronic regurgitation for >5 months. There were no clinical abnormalities on haematological or radiographic examinations. Thoracic radiography revealed a soft tissue opacity mass adjacent to the diaphragm in the caudoventral thorax. Ultrasonography revealed a protruding liver lobe surrounded by a hyperechoic lining from the diaphragm towards the thorax, and a pleuroperitoneal hernia was diagnosed. An endoscopy was performed to examine the cause of regurgitation, and an oesophageal stricture was observed. Endoscopic balloon dilation of the oesophageal stricture was performed, and the regurgitation was resolved immediately. However, regurgitation relapsed 2 months later, and computed tomography was performed to ascertain the cause. Computed tomography revealed oesophageal mural thickening and true pleuroperitoneal hernia with partial liver lobe herniation. A second endoscopy with balloon dilation was performed to treat the relapsing oesophageal stricture, and the clinical signs resolved without the need for herniorrhaphy. Nevertheless, oesophageal stricture could occur due to gastroesophageal reflux related to a pleuroperitoneal hernia; however, a definite link could not be elucidated in this case. This report describes a case of oesophageal stricture and concurrent true pleuroperitoneal hernia in a cat.

Life under the snow: A year-round transcriptome analysis of Antarctic mosses in natural habitats provides insight into the molecular adaptation of plants under extreme environment.

Mosses are vital components of ecosystems, exhibiting remarkable adaptability across diverse habitats from deserts to polar ice caps. Sanionia uncinata (Hedw.) Loeske, a dominant Antarctic moss survives extreme environmental condition through perennial lifecycles involving growth and dormancy alternation. This study explores genetic controls and molecular mechanisms enabling S. uncinata to cope with seasonality of the Antarctic environment. We analysed the seasonal transcriptome dynamics of S. uncinata collected monthly from February 2015 to January 2016 in King George Island, Antarctica. Findings indicate that genes involved in plant growth were predominantly upregulated in Antarctic summer, while those associated with protein synthesis and cell cycle showed marked expression during the winter-to-summer transition. Genes implicated in cellular stress and abscisic acid signalling were highly expressed in winter. Further, validation included a comparison of the Antarctic field transcriptome data with controlled environment simulation of Antarctic summer and winter temperatures, which revealed consistent gene expression patterns in both datasets. This proposes a seasonal gene regulatory model of S. uncinate to understand moss adaptation to extreme environments. Additionally, this data set is a valuable resource for predicting genetic responses to climatic fluctuations, enhancing our knowledge of Antarctic flora's resilience to global climate change.

Solvent-Dependent Self-Assembly of a Pillar[5]arene-Based Poly-Pseudo-Rotaxane Linked and Threaded by Silver(I) Trifluoroacetate: A Double Role.

In the supramolecule area, the fabrication of a new concept called polyrotaxanes or poly-pseudo-rotaxanes remains challenging. We herein report the formation of a poly-pseudo-rotaxane in which the same salt-type guest serves both linking and threading in the resulting structure. The combination of A1/A2-thiopyridyl pillar[5]arene (L) and silver(I) trifluoroacetate in CHCl3/CH3OH afforded a one-dimensional (1D) poly-pseudo-rotaxane. In this structure, to our surprise, the AgCF3CO2 guest not only links the di-armed L ligands via an infinite -L-Ag-L-Ag- arrangement but also threads into a pillar[5]arene cavity in a dimer form, (AgCF3CO2)2. In contrast, the same reaction in CH2Cl2/CH3OH yielded a simple 1D coordination polymer because an included CH2Cl2 molecule in the pillar[5]arene cavity prevents the threading of the silver(I) trifluoroacetate guest. Comparative 1H- and 19F-NMR studies support the solvent-dependent poly-pseudo-rotaxane formation at a lower concentration of L.

A scoping review of dementia caregiving for Korean Americans and recommendations for future research.

OBJECTIVES: This scoping review aims to examine the caregiving experiences of Korean American caregivers of persons with dementia. METHODS: A comprehensive electronic search was conducted within 5 databases (PubMed, CINAHL, Web of Science, Embase, PsycINFO-ProQuest) for papers published from 01/01/00 -01/24/22. Seventeen articles met the inclusion criteria. Thematic analysis was used to summarize key findings from these papers. RESULTS: Most Korean American dementia caregivers were immigrants and wives/daughters/daughters-in-law. Two themes emerged: 1) how Korean American caregivers perceived their caregiving experiences, and 2) how Korean American caregivers perceived their caregiving support services. Korean American caregivers often experience poor mental health and burden. Social support and familism were found to be two of the most important factors that determine their attitudes toward caregiving. Most reported barriers to utilizing public services. Challenges in finding culturally relevant resources were common. CONCLUSIONS: Dementia caregiving is a significant public health problem facing Korean Americans. Recommendations for future research are provided.

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults.

Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB Ct). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid GeneXpert) from December 2016 to October 2020 (n = 368) at a tertiary medical center were included. All stool samples were further tested by rapid glutamate dehydrogenase (GDH)/toxin B EIA and cell cytotoxin neutralization assay (CCNA). Receiver operating characteristic curves were analyzed. The area under the curve for tcdB Ct predicting toxin result by EIA was 0.795 (95% confidence interval (CI) 0.747−0.843) and by CCNA was 0.771 (95% CI 0.720−0.822). The Youden Ct cutoff for CCNA was ≤27.8 cycles (sensitivity 65.0%, specificity 77.2%). For specimens with Ct ≤ 25.0 cycles (n = 115), CCNA toxin was positive in >90%. The negative predictive value of tcdB Ct for CCNA was no greater than 80% regardless of cutoff chosen. In summary, very low Ct values (≤25.0) could have limited value as a rapid indicator of positive toxin status by CCNA in our patient population. A broad distribution of Ct values for toxin-negative and toxin-positive specimens precluded more robust prediction. Additional data are needed before broader application of Ct values from qualitatively designed assays to clinical laboratory reporting.

Theta low-gamma phase amplitude coupling in the human orbitofrontal cortex increases during a conflict-processing task.

Objective. The human orbitofrontal cortex (OFC) is involved in automatic response inhibition and conflict processing, but the mechanism of frequency-specific power changes that control these functions is unknown. Theta and gamma activity have been independently observed in the OFC during conflict processing, while theta-gamma interactions in other brain areas have been noted primarily in studies of memory. Within the OFC, it is possible that theta-gamma phase amplitude coupling (PAC) drives conflict processing. This study aims to characterize the coupled relationship between theta and gamma frequency bands in the OFC during conflict processing using a modified Stroop task.Approach. Eight epilepsy patients implanted with OFC stereotactic electroencephalography electrodes participated in a color-word modified Stroop task. PAC between theta phase and gamma amplitude was assessed to determine the timing and magnitude of neural oscillatory changes. Group analysis was conducted using a non-parametric cluster-permutationt-test on coherence values.Main results.Theta-low gamma (LG) PAC significantly increased in five out of eight patients during successful trials of the incongruent condition compared with the congruent condition. Significant increases in theta-LG PAC were most prominent during cue processing 200-800 ms after cue presentation. On group analysis, trial-averaged mean theta-LG PAC was statistically significantly greater in the incongruent condition compared to the congruent condition (p< 0.001, Cohen'sd= 0.51).Significance.For the first time, we report that OFC theta phase and LG amplitude coupling increases during conflict resolution. Given the delayed onset after cue presentation, OFC theta-LG PAC may contribute to conflict processing after conflict detection and before motor response. This explanation follows the hypothesis that global theta waves modulate local gamma signals. Understanding this relationship within the OFC will help further elucidate the neural mechanisms of human conflict resolution.

Social Communication in Big Brown Bats.

Bats are social mammals that display a wide array of social communication calls. Among them, it is common for most bats species to emit distress, agonistic, appeasement and infant isolation calls. Big brown bats (Eptesicus fuscus) are no different: They are gregarious animals living in colonies that can comprise hundreds of individuals. These bats live in North America and, typically found roosting in man-made structures like barns and attics, are considered common. They are insectivorous laryngeal echolocators, and while their calls and associated brain mechanisms in echolocation are well-documented, much less is known about their neural systems for analyzing social vocalizations. In this work we review what we know about the social lives of big brown bats and propose how to consolidate the nomenclature used to describe their social vocalizations. Furthermore, we discuss the next steps in the characterization of the social structure of this species and how these studies will advance both research in neuroethology and ecology of big brown bats.

A Longitudinal Study of Assisted Infant Toilet Training During the First Year of Life.

OBJECTIVE: Previous retrospective studies have examined elimination signals, stool toileting refusal, and completion age in Assisted Infant Toilet Training (AITT). The aim of this longitudinal cohort study was to describe the practice of AITT and caregiver satisfaction in a primarily Western setting during the first year of life. METHODS: Families who started AITT before 4 months of age were recruited. Standardized interviews of caregivers were conducted at 1- to 2-month intervals. To identify trends over time, data were fitted to a linear mixed-effect model. Data were analyzed according to five 2-month blocks, starting at 3 to 4 months. RESULTS: Of 85 participating families, 87 children started AITT at a mean age of 2.5 months. At all age intervals, 88% to 94% of caregivers could identify elimination signals. Toileting attempts decreased from 10/day at 3 to 4 months to 7/day at 11 to 12 months (p < 0.001). Many families (45%-53%) practiced AITT on a part-time basis. Daytime dryness was noted in 12% to 14% of infants throughout the first year. Although more than 63% of families used cloth or disposable diapers throughout this study, use of trainers and underwear increased significantly by 2- to 3-fold (p < 0.01 for both). Caregiver satisfaction was high overall. Although negatively associated with potty refusal, it was positively associated with daytime and nighttime dryness, perceived elimination signals, and a better understanding of their infant's needs (p < 0.001 for all). CONCLUSION: This study demonstrates that AITT is a worthy viable alternative to the use of diapers even in Western settings. Better understanding of AITT provides a new perspective to properly meet infants' basic needs.

Amygdaloid theta-band power increases during conflict processing in humans.

The amygdala is a medial temporal lobe structure known to be involved in processing emotional conflict. However, its role in processing non-emotional conflict is not well understood. Previous studies have utilized the Stroop Task to examine brain modulation of humans under the color-word conflict scenario, which is non-emotional conflict processing, and found hippocampal theta-band (4-7 Hz) modulation. This study aims to survey amygdaloid theta power changes during non-emotional conflict processing using intracranial depth electrodes in nine epileptic patients (3 female; age 20-62). All patients were asked to perform a modified Stroop task. During task performance, local field potential (LFP) data was recorded from macro contacts sampled at 2 K Hz and used for analysis. Mean theta power change from baseline was compared between the incongruent and congruent task condition groups using a paired sample t-test. Seven patients were available for analysis after artifact exclusion. In five out of seven patients, statistically significant increases in theta-band power from baseline were noted during the incongruent task condition (paired sample t-test p < 0.001), including one patient exhibiting theta power increases in both task conditions. Average response time was 1.07 s (failure trials) and 1.04 s (success trials). No speed-accuracy tradeoff was noted in this analysis. These findings indicate that human amygdaloid theta-band modulation may play a role in processing non-emotional conflict. It builds directly upon work suggesting that the amygdala processes emotional conflict and provides a neurophysiological mechanism for non-emotional conflict processing as well.

Comparative Assessment of Extracranial-to-Intracranial and Intracranial-to-Intracranial In Situ Bypass for Complex Intracranial Aneurysm Treatment Based on Rupture Status: A Case Series.

BACKGROUND: Comparative outcomes of extracranial-to-intracranial (EC-IC) and intracranial-to-intracranial (IC-IC) bypass for complex aneurysm treatment based on rupture status are not well described in the literature. In this study, we compare outcomes of EC-IC and IC-IC bypass for complex intracranial aneurysm treatment based on rupture status. METHODS: A prospective neurosurgical patient database was retrospectively reviewed. Sixty-three consecutive patients with aneurysm managed with revascularization were identified between July 2014 and December 2018. RESULTS: During the study period, 41 patients with aneurysm underwent EC-IC bypass (65%; 24 [58.5%] ruptured, 17 [41.5%] unruptured) and 22 patients with aneurysm underwent IC-IC bypass (34.9%; 13 [59.1%] ruptured, 9 [40.9%] unruptured). Graft spasm occurred in 4 patients (9.8%) in the EC-IC group (all ruptured aneurysms) and all anastomoses were patent on immediate postoperative imaging. Perioperative mortality occurred in 5 patients who underwent EC-IC bypass (12.2%; 3 ruptured, 2 unruptured) EC-IC and 2 patients who underwent IC-IC bypass (9.1%; both ruptured); (P = 0.709). Bypass-related complications occurred only in patients with ruptured aneurysm (2 [8.3%] in the EC-IC group and 0 [0%] in the IC-IC group; P = 0.285). For unruptured aneurysms, the overall complication rate was lower in IC-IC compared with the EC-IC group (P = 0.006). Modified Rankin Scale scores on discharge were significantly lower in IC-IC compared with EC-IC bypass for unruptured aneurysms (P = 0.008). There was a trend for shorter temporary occlusion and hospitalization times and overall better outcomes with IC-IC compared with EC-IC bypass. CONCLUSIONS: Although often considered riskier than EC-IC bypass, IC-IC in situ bypass showd a favorable technical and safety profile for the treatment of complex, unruptured aneurysms.

Liver Transplantation in Patients with Sickle Cell Disease in the United States.

BACKGROUND: Up to 30% of patients with sickle cell disease (SCD) develop chronic liver disease via etiologies including sickle cell hepatopathy, acquired viral hepatitis, or secondary hemochromatosis. It is unclear how many patients with SCD ultimately undergo liver transplantation (LT) and what factors are associated with survival after LT. In this study, we examined LT outcomes in these patients by reviewing the Scientific Registry of Transplant Recipients (SRTR) and our institutional experience. METHODS: Analysis of the SRTR identified 23 LT recipients and five simultaneous liver and kidney transplantation (SLKT) recipients with SCD. Patient demographics and graft and patient survival were analyzed. Two patients with SCD at our institution underwent SLKT. RESULTS: Review of the SRTR revealed that recipients with SCD had significantly higher model for end-stage liver disease scores (33 versus 21, P = 0.004), preoperative intensive care unit admission (43.5% versus 19.1%, P = 0.007), preoperative dialysis (17.4% versus 4.9%, P = 0.009), and were more likely to be status 1 (26.1% versus 12.1%, P = 0.041) when compared with the reference population of African American LT recipients. Despite being higher risk at the time of LT, patients with SCD had equivalent posttransplant graft and patient survival when compared with the reference population (P = 0.5 and P = 0.2, respectively) and a 2:1 propensity score-matched group (P = 0.5 and P = 0.2, respectively). Two recent SLKT recipients with SCD from our institution have performed well with stable allograft function. CONCLUSIONS: Data from the SRTR demonstrate that patients with SCD can expect equivalent graft and patient survival after LT despite exhibiting more comorbidities at the time of LT. The low number of patients with SCD who underwent LT in the SRTR in comparison with the rate of chronic liver disease in this population raises the question as to whether a disparity in access to LT exists for this complex population.

Novel TAZ modulators enhance myogenic differentiation and muscle regeneration.

BACKGROUND AND PURPOSE: The transcriptional co-activator with PDZ-binding motif (TAZ) is a key controller of mesenchymal stem cell differentiation through its nuclear localization and subsequent interaction with master transcription factors. In particular, TAZ directly associates with myoblast determining protein D (MyoD) and activates MyoD-induced myogenic gene expression, thereby enhancing myogenic differentiation. Here, we have synthesized and characterized low MW compounds modulating myogenic differentiation via induction of TAZ nuclear localization. EXPERIMENTAL APPROACH: COS7 cells stably transfected with GFP-TAZ were used in a high content imaging screen for compounds specifically enhancing nuclear localization of TAZ. We then studied the effects of such TAZ modulators on myocyte differentiation of C2C12 cells and myogenic transdifferentiation of mouse embryonic fibroblast cells in vitro and muscle regeneration in vivo. KEY RESULTS: We identified two TAZ modulators, TM-53, and its structural isomer, TM-54. Each compound strongly enhanced nuclear localization of TAZ by reducing S89-phosphorylation and dose-dependently augmented myogenic differentiation and MyoD-mediated myogenic transdifferentiation through an activation of MyoD-TAZ interaction. The myogenic stimulatory effects of TM-53 and TM-54 were impaired in the absence of TAZ, but retrieved by the restoration of TAZ. In addition, administration of TM-53 and TM-54 enhanced injury-induced muscle regeneration in vivo and attenuated myofiber injury in vitro. CONCLUSIONS AND IMPLICATIONS: The novel TAZ modulators TM-53 and TM-54 accelerated myogenic differentiation and improved muscle regeneration and function after injury, demonstrating that low MW compounds targeting the nuclear localization of TAZ have beneficial effects in skeletal muscle regeneration and in recovery from muscle degenerative diseases.

Preclinical pharmacokinetic characterization of 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid, a novel DGAT-1 inhibitor.

1. A novel diacylglyceride acyltransferase-1 (DGAT-1) inhibitor, 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid (KR-69232), was synthesized for a potential therapeutic use against several metabolic disorders, such as obesity, insulin resistance, and type II diabetes, characterized by excessive triglycerides (TGs) in the blood. 2. The half-lives against phase I metabolism were measured as 75.3 ± 20.9 min and over 120 min in rat and human liver microsomes, respectively. In Caco-2 cell monolayers, extremely low permeability (<0.13 × 10⁻6cm/s) was seen in the absorptive direction, predicting limited intestinal absorption of KR-69232. This compound was highly bound to rat and human plasma proteins (>99.8%). 3. With the intravenous administration of KR-69232 in rats (1, 2, and 5 mg/kg), non-linear kinetics were observed at the highest dose, with significantly higher systemic clearance, higher volume of distribution, and lower dose-normalized AUC. Following oral administration, it exhibited low bioavailability (<10%) and was absorbed slowly (T(max), 3.8-5.2 h) over the dose range. We also confirmed that considerable KR-69232 remained in the intestine at T(max), demonstrating its limited absorption into the systemic circulation.