"Next top" mouse models advancing CTCL research.

This review systematically describes the application of in vivo mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL's intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models' strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4+ T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.

Validation of the eyeTelemed IOPvet indentation tonometer for use in dogs.

OBJECTIVE: To assess the accuracy of canine intraocular pressure (IOP) estimates from the eyeTelemed IOPvet indentation tonometer. ANIMALS STUDIED: Part 1 included 54 eyes from 28 Beagle dogs-23 ADAMTS10-mutants with open-angle glaucoma and 5 normals. Part 2 involved five normal canine ex vivo globes. PROCEDURE: Part 1 (in vivo) compared IOPvet estimates in normal and glaucomatous dogs to Reichert Tono-Vera® Vet rebound tonometry. The three IOPvet estimates were green (normal; <20 mmHg, according to the manufacturer), yellow (elevated; 20-30 mmHg), and red (high; >30 mmHg). In Part 2 (ex vivo), the pressure inside freshly enucleated normal canine eyes was progressively increased from 5 to 80 mmHg and compared to IOPvet estimates. Descriptive statistics compared IOPvet estimates to rebound tonometry and direct manometry, with the threshold from normal to glaucoma set at 30 mmHg. RESULTS: In Part 1 (in vivo), normal pressures (≤30 mmHg) were mainly identified correctly as green or yellow-110 of 111 estimates, corresponding to a specificity of 99%. Only 16 of 125 affected estimates were correctly displayed in the >30-mmHg range; the remaining 109 showed ≤30 mmHg, corresponding to a sensitivity of 13%. In Part 2 (ex vivo), all normal pressures were correctly estimated with green, but 64 of 88 manometric IOPs >30 mmHg were falsely estimated as 20-30 mmHg. CONCLUSIONS: The IOPvet is inaccurate in estimating canine IOP with a low sensitivity at identifying dogs with IOP > 30 mmHg. Canine-specific instrument revision is required to correctly identify elevated (yellow = 20-30 mmHg) and high (red >30 mmHg) IOPs.

LC-ESI-QTOF-MS/MS characterization of phenolic compounds in Australian native passion fruits and their potential antioxidant activities.

Passion fruits, renowned globally for their polyphenolic content and associated health benefits, have enjoyed growing attention from consumers and producers alike. While global cultivar development progresses, Australia has pioneered several native cultivars tailored for its distinct planting conditions. Despite their cultivation, comprehensive studies on the phenolic profiles and antioxidant capacities of these Australian-native passion fruits are notably lacking. This study aims to investigate and compare the polyphenolic content present in the by-products, which are peel (L), and consumable portions, which are the pulp and seeds (P), of four indigenous cultivars: 'Misty Gem' (MG), 'Flamengo' (FG), 'Sweetheart' (SW), and 'Panama' (SH). Employing LC-ESI-QTOF-MS/MS for profiling, a comprehensive list of polyphenols was curated. Additionally, various antioxidant assays-DPPH, FRAP, ABTS, RPA, FICA, and •OH-RSA-were performed to evaluate their antioxidant potential. A total of 61 polyphenols were identified, categorized into phenolic acid (19), flavonoids (33), and other phenolic substances (9). In the antioxidant assays, the SHP sample exhibited the highest •OH--RSA activity at 98.64 ± 1.45 mg AAE/g, while the FGL sample demonstrated prominent DPPH, FRAP, and ABTS activities with values of 32.47 ± 1.92 mg TE/g, 62.50 ± 3.70 mg TE/g, and 57.84 ± 1.22 mg AAE/g, respectively. Additionally, TPC and several antioxidant assays had a significant positive correlation, including DPPH, FRAP, and ABTS. The Australian-native passion fruits revealed distinct polyphenolic profiles and diverse antioxidant capacities, establishing a foundation for deeper health benefit analyses. This study accentuates the significance of understanding region-specific cultivars and their potential nutraceutical applications.

Return to Sports in Patients Aged 50 Years or Younger After Robotic-Assisted Patellofemoral Arthroplasty: A 10-Year Experience Reporting High Clinical Benefits and High Patient Satisfaction With Return to an Active Lifestyle.

BACKGROUND: Limited data are available on return to sports and patient psychometric ratings of success after patellofemoral arthroplasty (PFA) in younger patients with high expectations to return to an active lifestyle. PURPOSE/HYPOTHESIS: The purpose of this article was to determine the role of PFA and its success in meeting patient expectations regarding the return to low-impact recreational sports and an active lifestyle in younger, active patients. It was hypothesized that PFA would allow younger patients to return to low-impact sports and an active lifestyle and achieve high patient psychometric ratings. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In this 10-year prospective study (2009-2018), robotic-assisted PFA was performed on 44 patients (32 women and 12 men; n = 51 consecutive knees), with a mean age of 37.2 years (range, 21-50 years). The follow-up rate was 98%, with a mean of 5.3 years (range, 2-9.3 years). Primary clinical outcomes were as follows: the validated Cincinnati Knee Rating System sports activity and symptom rating scales, patient psychometric ratings of the substantial clinical benefit (SCB), and the Patient Acceptable Symptom State (PASS). Secondary outcomes were the Cincinnati Knee Rating System occupational rating, visual analog pain scale, and the 12-Item Short Form Health Survey. Survivorship was defined by conversion to total knee replacement (TKR). RESULTS: Before PFA, 78% of patients (35/45 knees) were symptomatic and unable to perform recreational sports, with only 20% of patients (9/45 knees) performing some low-impact sports. After PFA, 80% of patients (36/45 knees) were able to perform low-impact sports, and 7% (3/45 knees) performed jumping-pivoting sports (P < .001). The SCB scored by the patient showed 87% of knees as good, very good, or normal. On the PASS analysis, 89% of patients (95% CI, 76%-96%) were "pleased," and 93% (95% CI, 82%-99%) would undergo surgery again. There were clinically relevant improvements in symptoms of pain, swelling, and giving way (P = .0001). Preoperatively, 91% of knees had moderate to severe pain with activities of daily living, and only 11% of knees had pain at the follow-up. Five of the 50 knees (10%) underwent TKR conversion with one patient lost to follow-up. CONCLUSION: PFA resulted in a high return of patients to low-impact sports with high SCB and PASS psychometric ratings. The robotic-assisted 3-dimensional preoperative planning allowed precise intraoperative trochlear implant alignment in knees with severe trochlear dysplasia. PFA is recommended as an alternative treatment in younger patients with end-stage symptomatic patellofemoral arthritis. REGISTRATION: NCT02738476 (ClinicalTrials.gov identifier).

Bioaccessibility of Phenolic Compounds, Resistant Starch, and Dietary Fibers from Australian Green Banana during In Vitro Digestion and Colonic Fermentation.

Green bananas contain a substantial amount of resistant starch (RS), dietary fiber (DF), and phytochemicals, which exhibit potent antioxidant capabilities, primarily attributable to the abundance of polyphenols. The objective of this study was to assess the variations in the contents and bioaccessibility of RS, DF, and phenolic compounds in three types of Australian green bananas (Cavendish "Musa acuminata", Ladyfinger "Musa paradisiaca L.", and Ducasse "Musa balbisiana"), along with their antioxidant capacities, and the production of short-chain fatty acids (SCFAs) following in vitro simulated gastrointestinal digestion and colonic fermentation. The studied cultivars exhibited significant levels of RS, with Ladyfinger showing the greatest (49%). However, Ducasse bananas had the greatest DF concentration (38.73%). Greater TPC levels for Ladyfinger (2.32 mg GAE/g), as well as TFC and TTC (0.06 mg QE/g and 3.2 mg CE/g, respectively) in Cavendish, together with strong antioxidant capacities (DPPH, 0.89 mg TE/g in Cavendish), have been detected after both intestinal phase and colonic fermentation at 12 and 24 h. The bioaccessibility of most phenolic compounds from bananas was high after gastric and small intestinal digestion. Nevertheless, a significant proportion of kaempferol (31% in Cavendish) remained detectable in the residue after colonic fermentation. The greatest production of SCFAs in all banana cultivars was observed after 24 h of fermentation, except valeric acid, which exhibited the greatest output after 12 h of fermentation. In conclusion, the consumption of whole green bananas may have an advantageous effect on bowel health and offer antioxidant characteristics.

Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society.

Electrical storm (ES) is a state of electrical instability, manifesting as recurrent ventricular arrhythmias (VAs) over a short period of time (three or more episodes of sustained VA within 24 h, separated by at least 5 min, requiring termination by an intervention). The clinical presentation can vary, but ES is usually a cardiac emergency. Electrical storm mainly affects patients with structural or primary electrical heart disease, often with an implantable cardioverter-defibrillator (ICD). Management of ES requires a multi-faceted approach and the involvement of multi-disciplinary teams, but despite advanced treatment and often invasive procedures, it is associated with high morbidity and mortality. With an ageing population, longer survival of heart failure patients, and an increasing number of patients with ICD, the incidence of ES is expected to increase. This European Heart Rhythm Association clinical consensus statement focuses on pathophysiology, clinical presentation, diagnostic evaluation, and acute and long-term management of patients presenting with ES or clustered VA.

Utilization of coronary computed tomography angiography and computed tomography-derived fractional flow reserve in a critical limb-threatening ischemia cohort.

Objective: Patients with peripheral arterial disease (PAD) have a significant risk of myocardial infarction and death secondary to concomitant coronary artery disease (CAD). This is particularly true in patients with critical limb-threatening ischemia (CLTI) who exceed a 20% mortality rate at 6 months despite standard treatment with risk factor modification. Although systematic preoperative coronary testing is not recommended for patients with PAD without cardiac symptoms, the clinical manifestations of CAD are often muted in patients with CLTI due to poor mobility and activity intolerance. Thus, the true incidence and impact of "silent" CAD in a CLTI cohort is unknown. This study aims to determine the prevalence of ischemia-producing coronary artery stenosis in a CLTI cohort using coronary computed tomography angiography (cCTA) and computed tomography (CT)-derived fractional flow reserve (FFRCT), a noninvasive imaging modality that has shown significant correlation to cardiac catheterization in the detection of clinically relevant coronary ischemia. Methods: Patients presenting with newly diagnosed CLTI at our institution from May 2020 to April 2021 were screened for underlying CAD. Included subjects had no known history of CAD, no cardiac symptoms, and no anginal equivalent complaints at presentation. Patients underwent cCTA and FFRCT evaluation and were classified by the anatomic location and severity of CAD. Significant coronary ischemia was defined as FFRCT ≤0.80 distal to a >30% coronary stenosis, and severe coronary ischemia was documented at FFRCT ≤0.75, consistent with established guidelines. Results: A total of 170 patients with CLTI were screened; 65 patients (38.2%) had no coronary symptoms and met all inclusion/exclusion criteria. Twenty-four patients (31.2%) completed cCTA and FFRCT evaluation. Forty-one patients have yet to complete testing secondary to socioeconomic factors (insurance denial, transportation inaccessibility, testing availability, etc). The mean age of included subjects was 65.4 ± 7.0 years, and 15 (62.5%) were male. Patients presented with ischemic rest pain (n = 7; 29.1%), minor tissue loss (n = 14; 58.3%) or major tissue loss (n = 3; 12.5%). Significant (≥50%) coronary artery stenosis was noted on cCTA in 19 of 24 patients (79%). Significant left main coronary artery stenosis was identified in two patients (10%). When analyzed with FFRCT, 17 patients (71%) had hemodynamically significant coronary ischemia (FFRCT ≤0.8), and 54% (n = 13) had lesion-specific severe coronary ischemia (FFRCT ≤0.75). The mean FFRCT in patients with coronary ischemia was 0.70 ± 0.07. Multi-vessel disease pattern was present in 53% (n = 9) of patients with significant coronary stenosis. Conclusions: The use of cCTA-derived fractional flow reserve demonstrates a significant percentage of patients with CLTI have silent (asymptomatic) coronary ischemia. More than one-half of these patients have lesion-specific severe ischemia, which may be associated with increased mortality when treated solely with risk factor modification. cCTA and FFRCT diagnosis of significant coronary ischemia has the potential to improve cardiac care, perioperative morbidity, and long-term survival curves of patients with CLTI. Systemic improvements in access to care will be needed to allow for broad application of these imaging assessments should they prove universally valuable. Additional study is required to determine the benefit of selective coronary revascularization in patients with CLTI.

Multi-ancestry tandem repeat association study of hair colour using exome-wide sequencing.

Hair colour variation is influenced by hundreds of positions across the human genome but this genetic contribution has only been narrowly explored. Genome-wide association studies identified single nucleotide polymorphisms (SNPs) influencing hair colour but the biology underlying these associations is challenging to interpret. We report 16 tandem repeats (TRs) with effects on different models of hair colour plus two TRs associated with hair colour in diverse ancestry groups. Several of these TRs expand or contract amino acid coding regions of their localized protein such that structure, and by extension function, may be altered. We also demonstrate that independent of SNP variation, these TRs can be used to great an additive polygenic score that predicts darker hair colour. This work adds to the growing body of evidence regarding TR influence on human traits with relatively large and independent effects relative to surrounding SNP variation.

Comparison of phenolic composition in Australian-grown date fruit (Phoenix dactylifera L.) seeds from different varieties and ripening stages.

In this research, different seeds of Australian-grown date palm (Phoenix dactylifera L.) were studied to evaluate the antioxidant potential and analyze their phenolic constituents. Phenolic compounds were extracted from seeds of various Australian-grown date varieties at different ripening stages. Eight varieties of date seeds (Zahidi, Medjool, Deglet nour, Thoory, Halawi, Barhee, Khadrawy, and Bau Strami) at three ripening stages (Kimri, Khalal, and Tamar) were investigated in this study. Date seeds at Khalal (9.87-16.93 mg GAE/g) and Tamar (9.20-27.87 mg GAE/g) stages showed higher total phenolic content than those at Kimri stage (1.81-5.99 mg GAE/g). For antioxidant assays like DPPH, FRAP, ABTS, RAP, FICA, and TAC, date seeds at Khalal and Tamar stages also showed higher antioxidant potential than Kimri stage. However, date seeds at Kimri stage (55.24-63.26 mg TE/g) expressed higher radical scavenging activity than Khalal (13.58-51.88 mg TE/g) and Tamar (11.06-50.92 mg TE/g) stages. Phenolic compounds were characterized using LC-ESI-QTOF-MS/MS, revealing the presence of 37 different phenolic compounds, including 8 phenolic acids, 18 flavonoids, and 11 other phenolic compounds. Further, phenolic compounds were quantified using LC-DAD, revealing that Zahidi variety of date seeds exhibited the highest content during the Kimri stage. In contrast, during the Khalal and Tamar stages, Deglet nour and Medjool date seeds displayed higher concentrations of phenolic compounds. The results indicated an increase in phenolic content in date seeds after the Kimri stage, with significant variations observed among different date varieties.

Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.

Enzymes populate ensembles of structures necessary for catalysis that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography at an x-ray free electron laser to observe catalysis in a designed mutant isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations, and formation of the thioimidate intermediate selects for catalytically competent substates. The influence of cysteine ionization on the ICH ensemble is validated by determining structures of the enzyme at multiple pH values. Large molecular dynamics simulations in crystallo and time-resolved electron density maps show that Asp17 ionizes during catalysis and causes conformational changes that propagate across the dimer, permitting water to enter the active site for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.

Effects of Sugarcane-Derived Polyphenol Supplementation on Methane Production and Rumen Microbial Diversity of Second-Cross Lambs.

The objective of this study was to evaluate the effects of feeding sugarcane-derived polyphenolic supplement (Polygain, The Product Makers Australia, Keysborough, VIC, Australia) on enteric methane (CH4) emission, rumen microbiota, and performance of second-cross lambs. For this purpose, 24 Poll Dorset × (Border Leicester × Merino) lambs were allocated to 3 different treatments: Control (C), 0.25% Polygain (0.25 PG), and 1% Polygain (1 PG) diets with a uniform basal feed (25% cracked wheat grain, 25% cracked barley grain, 25% oaten chaff, 25% lucerne chaff). Both doses of Polygain reduced the total CH4 production (g/day; p = 0.006), CH4 yield (CH4, g/kg of dry matter intake; p = 0.003) and CH4 intensity (CH4, g/kg of BW; p = 0.003). Dry matter intake tended to be greater (p = 0.08) in sheep fed 1 PG compared to the C group, with the 0.25 PG group being intermediate. The average daily gain of the lambs was improved (p = 0.03) with 1% Polygain supplementation. The relative abundance of genera Methanobrevibacter_unidentified, Methanomethylophilaceae_uncultured, Methanogenic archaeon mixed culture ISO4-G1, Methanosphaera uncultured rumen methanogen, Methanogenic archaeon ISO4-H5, and Methanobrevibacter boviskoreani JH1 were reduced with Polygain supplementation. In conclusion, feeding Polygain reduced lambs' enteric CH4 emissions, altered the rumen microbiome, and improved the growth performance of lambs.

The Rhinoplasty Rosetta Stone: using Rasch analysis to create and validate crosswalks between the NOSE and SCHNOS functional subscale.

BACKGROUND: The NOSE and SCHNOS functional subscale are widely used PROMs to measure functional outcomes of rhinoplasty. However, as different instruments produce scores on different metrics, results of these instruments cannot be linked directly. This hinders comparing and aggregating rhinoplasty outcome data from practices using either instrument. The aim of this study was to develop and validate crosswalks between the NOSE and SCHNOS-O. METHODS: In a sample of 552 rhinoplasty patients who completed both instruments, the NOSE and SCHNOS-O scales were co-calibrated onto a common interval-scaled metric using Rasch analysis. Separate Rasch models were run per instrument and the latent constructs were estimated using the calibrated item parameters. By anchoring original PROM scores of both instruments to this Rasch computed measurement scale, the scores of both instruments were linked. A second independent sample was used to validate the created crosswalks. RESULTS: Total scores on the NOSE and SCHNOS-O were strongly correlated. The Rasch-based co-calibration of the NOSE and SCHNOS-O items resulted in a model that adequately fitted the data. Back-and-forth crosswalk tables were created from the NOSE to the SCHNOS-O. For patients with moderate nasal obstruction, predicted SCHNOS-O scores were slightly higher for a given level of the NOSE. Intraclass correlation coefficients between predicted and actual scores were 0.93 for both directions, indicating adequate agreement for group-level comparisons. CONCLUSION: This study developed and validated Rasch-based crosswalks from the NOSE to the SCHNOS-O and vice-versa. The provided crosswalks enhance comparison and harmonization of functional rhinoplasty outcomes.

Recombinant Production of Pseudomonas aeruginosa Rhamnolipids in P. putida KT2440 on Acetobacterium woodii Cultures Grown Chemo-Autotrophically with Carbon Dioxide and Hydrogen.

The establishment of sustainable processes for the production of commodity chemicals is one of today's central challenges for biotechnological industries. The chemo-autotrophic fixation of CO2 and the subsequent production of acetate by acetogenic bacteria via anaerobic gas fermentation represents a promising platform for the ecologically sustainable production of high-value biocommodities via sequential fermentation processes. In this study, the applicability of acetate-containing cell-free spent medium of the gas-fermenting acetogenic bacterium A. woodii WP1 as the feeder strain for growth and the recombinant production of P. aeruginosa PAO1 mono-rhamnolipids in the well-established nonpathogenic producer strain P. putida KT2440 were investigated. Additionally, the potential possibility of a simplified production process without the necessary separation of feeder strain cells was elucidated via the cultivation of P. putida in cell-containing A. woodii culture broth. For these cultures, the content of both strains was investigated by examining the relative quantification of strain-exclusive genes via qPCR. The recombinant production of mono-rhamnolipids was successfully achieved with maximum titers of approximately 360-400 mg/L for both cell-free and cell-containing A. woodii spent medium. The reported processes therefore represent a successful proof of principle for gas fermentation-derived acetate as a potential sustainable carbon source for future recombinant rhamnolipid production processes by P. putida KT2440.

A comparative analysis of gastrointestinal tract barrier function and immune markers in gilt vs. sow progeny at birth and weaning.

Progeny born to primiparous sows (gilt progeny; GP) have lower birth, weaning and slaughter weights than sow progeny (SP). GP also have reduced gastrointestinal tract (GIT) development, as evidenced by lower organ weights. Therefore, the aim of this experiment was to quantify changes in GIT barrier function that occur in birth and weaning, representing two major challenges to the young piglet. The effects of parity (GP vs. SP) in GIT barrier integrity function were quantified at four timepoints: birth (~0 h), 24 h after birth (24 h), 1-d preweaning (PrW), and 1-d postweaning (PoW) in commercially reared piglets. Due to inherent differences between newborn and weanling pigs, the results were analyzed in two cohorts, birth (0 vs. 24 h, n = 31) and weaning (PrW vs. PoW, n = 40). Samples of the stomach, jejunum, ileum, and colon were excised after euthanasia and barrier integrity was quantified by measuring transepithelial resistance (TER), macromolecular permeability, the abundance of inflammatory proteins (IL-8, IL-1ß, and TNF-α) and tight junction proteins (claudin-2 and -3). Papp was characterized using a dual tracer approach comprising 4 KDa fluorescein isothiocyanate (FD4) and 150 kDa tetramethyl rhodamine isothiocyanate (T150)-labeled dextrans. Characteristic effects of the initiation of feeding and weaning were observed on the GIT with the initiation of feeding, such as increasing TER and reducing Papp at 24 h, consistent with mucosal growth (P = 0.058) This was accompanied by increased cytokine abundance as evidenced by elevations in TNF-α and IL-1ß. However, GP had increased IL-8 abundance (P = 0.011 and 0.063 for jejunum and ileum respectively) at birth than 24 h overall. In the weaning cohort, jejunal and ileal permeability to FD4 was higher in GP (P = 0.05 and 0.022, respectively) while only higher ileal T150 was observed in GP (P = 0.032). Ileal claudin-2 abundance tended to be higher in SP overall (P = 0.063), but GP ileal claudin-2 expression was upregulated weaning while no change was observed in SP (P = 0.043). Finally, other than a higher jejunal TNF-α abundance observed in SP (P = 0.016), no other effect of parity was observed on inflammatory markers in the weaning cohort. The results from this study indicate that the GIT of GP have poorer adaptation to early life events, with the response to weaning, being more challenging which is likely to contribute to poorer postweaning growth.

The progeny of primiparous sows (gilt progeny; GP) have poorer lifetime growth performance in comparison to progeny from multiparous sows (sow progeny; SP). Previous research suggests that there is an underlying biological basis for reduced growth performance which is attributed to differences in gastrointestinal tract (GIT) barrier development during early life. This study aimed to clarify the timeframes of when these differences are in effect by investigating GIT development during two major events of a piglet's life: birth and weaning. To do this, GIT tissue was collected from GP and SP at four time points; birth, 24 h after birth, 1-d preweaning, and 1-d postweaning and assessed for functional development. The main findings from this study indicate there are early signs of variation in GIT development within the first 24 h of life between GP and SP, and that these differences increase through the preweaning period, with GP entering weaning with poorer GIT development and function. Possible explanations for the reduced GI development may be reduced maternal nutrition during the suckling period.

Complete genome sequences of Blautia hydrogenotrophica DSM 10507T isolated from human feces and Blautia coccoides DSM 935T isolated from mouse feces.

We report on the closed genome sequences of the acetogen Blautia hydrogenotrophica S5a33T (DSM 10507T) and of Blautia coccoides CLC-1T (DSM 935T). The B. hydrogenotrophica S5a33T genome harbors a chromosome (3,590,609 bp) and a plasmid (7,176 bp). The B. coccoides CLC-1T genome consists of a single chromosome (6,097,890 bp).

Impairment of the adrenergic reserve associated with exercise intolerance in a murine model of heart failure with preserved ejection fraction.

AIM: Exercise intolerance is the central symptom in patients with heart failure with preserved ejection fraction. In the present study, we investigated the adrenergic reserve both in vivo and in cardiomyocytes of a murine cardiometabolic HFpEF model. METHODS: 12-week-old male C57BL/6J mice were fed regular chow (control) or a high-fat diet and L-NAME (HFpEF) for 15 weeks. At 27 weeks, we performed (stress) echocardiography and exercise testing and measured the adrenergic reserve and its modulation by nitric oxide and reactive oxygen species in left ventricular cardiomyocytes. RESULTS: HFpEF mice (preserved left ventricular ejection fraction, increased E/e', pulmonary congestion [wet lung weight/TL]) exhibited reduced exercise capacity and a reduction of stroke volume and cardiac output with adrenergic stress. In ventricular cardiomyocytes isolated from HFpEF mice, sarcomere shortening had a higher amplitude and faster relaxation compared to control animals. Increased shortening was caused by a shift of myofilament calcium sensitivity. With addition of isoproterenol, there were no differences in sarcomere function between HFpEF and control mice. This resulted in a reduced inotropic and lusitropic reserve in HFpEF cardiomyocytes. Preincubation with inhibitors of nitric oxide synthases or glutathione partially restored the adrenergic reserve in cardiomyocytes in HFpEF. CONCLUSION: In this murine HFpEF model, the cardiac output reserve on adrenergic stimulation is impaired. In ventricular cardiomyocytes, we found a congruent loss of the adrenergic inotropic and lusitropic reserve. This was caused by increased contractility and faster relaxation at rest, partially mediated by nitro-oxidative signaling.

In vitro digestion and colonic fermentation of phenolic compounds and their antioxidant potential in Australian beach-cast seaweeds.

Beach-cast seaweed has recently garnered attention for its nutrient-rich composition, including proteins, carbohydrates, vitamins, minerals, and phytochemicals. This study focuses on the phenolic content and antioxidant potential of five Australian beach-cast seaweed species during in vitro digestion and colonic fermentation. The bioaccessibility of the selected phenolic compounds was estimated and short chain fatty acids (SCFAs) production was determined. Cystophora sp., showed a notable increase in phenolic content (23.1 mg GAE/g) and antioxidant capacity (0.42 mg CE/g) during the intestinal and gastric phases of in vitro digestion. Durvillaea sp. demonstrated a significant release of flavonoids (0.35 mg QE/g), while Phyllosphora comosa released high levels of tannins (0.72 mg CE/g) during the intestinal phase. During colonic fermentation, P. comosa released the highest levels of phenolic compounds (4.3 mg GAE/g) after 2 h, followed by an increase in flavonoids (0.15 mg QE/g), tannins (0.07 mg CE/g), and antioxidant activity (DPPH: 0.12 mg CE/g; FRAP: 0.61 mg CE/g) after 4 h. Moreover, P. comosa released a considerable amount of phenolic compounds during both in vitro digestion and colonic fermentation. All species consistently released phenolic compounds throughout the study. Phloroglucinol, gallic acid, and protocatechuic acid were identified as the most bioaccessible phenolic compounds in all five Australian beach-cast seaweeds in the in vitro digestion. Nevertheless, compound levels declined during the colonic fermentation phase due to decomposition and fermentation by gut microbiota. With regard to SCFAs, P. comosa displayed elevated levels of acetic (0.51 mmol/L) and propionic acid (0.36 mmol/L) at 2 h, while Durvillaea sp. showed increased butyric (0.42 mmol/L) and valeric (0.26 mmol/L) production acid after 8 h. These findings suggest that seaweed such as Cystophora sp., Durvillaea sp., and P. comosa are promising candidates for food fortification or nutraceutical applications, given their rich phenolic content and antioxidant properties that potentially offer gut health benefits.