Triiodothyronine supplementation in a sheep model of intensive care.

Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3 supplementation in disease have revealed little or no effect. It is uncertain if short term supplementation of T3 has any discernible effect in a healthy animals. Observational study of intravenous T3 (1 µg/kg/h) for 24 h in a healthy sheep model receiving protocol-guided intensive care supports (T3 group, n=5). A total of 45 endpoints were measured including hemodynamic, respiratory, renal, hematological, metabolic and endocrine parameters. Data were compared with previously published studies of sheep subject to the same support protocol without administered T3 (No T3 group, n=5). Plasma free T3 concentrations were elevated 8-fold by the infusion (pmol/l at 24 h; T3 group 34.9±9.9 vs. No T3 group 4.4±0.3, P<0.01, reference range 1.6 to 6.8). There was no significant physiological response to administration of T3 over the study duration. Supplementation of intravenous T3 for 24 h has no physiological effect on relevant physiological endpoints in healthy sheep. Further research is required to understand if the lack of effect of short-term T3 may be related to kinetics of T3 cellular uptake, metabolism and action, or acute counterbalancing hormone resistance. This information may be helpful in design of clinical T3 supplementation trials.

Temporal and spectral electrooculographic features in a discrete precision task.

This study aimed to evaluate the utility and applicability of electrooculography (EOG) when studying ocular activity during complex motor behavior. Due to its lower spatial resolution relative to eye tracking (ET), it is unclear whether EOG can provide valid and accurate temporal measurements such as the duration of the Quiet Eye (QE), that is the uninterrupted dwell time on the visual target prior to and during action. However, because of its greater temporal resolution, EOG is better suited for temporal-spectral decomposition, a technique that allows us to distinguish between lower and higher frequency activity as a function of time. Sixteen golfers of varying expertise (novices to experts) putted 60 balls to a 4-m distant target on a flat surface while we recorded EOG, ET, performance accuracy, and putter kinematics. Correlational and discrepancy analyses confirmed that EOG yielded valid and accurate QE measurements, but only when using certain processing parameters. Nested cross-validation indicated that, among a set of ET and EOG temporal and spectral oculomotor features, EOG power was the most useful when predicting performance accuracy through robust regression. Follow-up cross-validation and correlational analyses revealed that more accurate performance was preceded by diminished lower-frequency activity immediately before movement initiation and elevated higher-frequency activity during movement recorded from the horizontal channel. This higher-frequency activity was also found to accompany a smoother movement execution. This study validates EOG algorithms (code provided) for measuring temporal parameters and presents a novel approach to extracting temporal and spectral oculomotor features during complex motor behavior.

The Cost-Effectiveness of Early High-Acuity Postoperative Care for Medium-Risk Surgical Patients.

BACKGROUND: Initiatives in perioperative care warrant robust cost-effectiveness analysis in a cost-constrained era when high-value care is a priority. A model of anesthesia-led early high-acuity postoperative care, advanced recovery room care (ARRC), has shown benefit in terms of hospital and patient outcomes, but its cost-effectiveness has not yet been formally determined. METHODS: Data from a previously published single-center prospective cohort study of ARRC in medium-risk patients were used to generate a Markov model, which described patient transition between care locations, each with different characteristics and costs. The incremental cost-effectiveness ratio (ICER), using days at home (DAH) and hospital costs, was calculated for ARRC compared to usual ward care using deterministic and probabilistic sensitivity analysis. RESULTS: The Markov model accurately described patient disposition after surgery. For each patient, ARRC provided 4.3 more DAH within the first 90 days after surgery and decreased overall hospital costs by $1081 per patient. Probabilistic sensitivity analysis revealed that ARRC had a 99.3% probability of increased DAH and a 77.4% probability that ARRC was dominant from the perspective of the hospital, with improved outcomes and decreased costs. CONCLUSIONS: Early high-acuity care for approximately 24 hours after surgery in medium-risk patients provides highly cost-effective improvements in outcomes when compared to usual ward care.

The Telluride YAP/TAZ and TEAD Workshop: A Small Meeting with a Big Impact.

Funding the research needed to advance our understanding of rare cancers is very challenging [...].

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-ß, are potential biomarkers for dystrophic muscle characterization. METHODS: To investigate disease progression and aging, we utilized young (1 month old) and old (21-25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-ß were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. RESULTS: The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine, and the proteins TNF-α and TGF-ß had no difference in the analysis between groups (p > 0.05). CONCLUSIONS: Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-ß do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.

Rise in intraocular pressure with elevator travel in post-vitrectomy patients.

To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA (Reichert, USA) on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (- 0.43 mmHg) and statistically significantly different (95% CI 1.17-2.48, P < 0.0001). Patients undergoing vitreoretinal surgery with gas insertion had statistically significant intraocular pressure rise even with 8-floor ascent in the immediate post-operative period. Further studies are needed to evaluate the change in intraocular pressure with a larger range of altitudes and different gases.

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle.

Background: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-ß, are potential biomarkers for dystrophic muscle characterization. Methods: To investigate disease progression and aging, we utilized young (1-month old) and old (21-25 months old) mdx and wild-type mice. Metabolite changes were analyzed using 1-H Nuclear Magnetic Resonance, while TNF-α and TGF-ß were assessed using Western blotting to examine inflammation, and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. Results: The histological analysis of the tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild type or mdx animals of the same age. The metabolites alanine, methionine, 3-methylhistidine were higher, and taurine and glycerol were lower in young animals in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine and the proteins TNF-α and TGF-ß had no difference in the analysis between groups (p > 0.05). Conclusions: Surprisingly, histological and protein analysis reveals that the tongue of young and old mdx animals is protected from severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-ß do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.

Effect of SiO2/Al2O3 ratio on the electrochemical performance of amorphous zeolite loaded with cobalt oxide grown via steam-assisted crystallization method.

Improving the performance of a supercapacitor is one of the main approaches to solve the energy shortage problem. Electrode material is one of the key components limiting the efficiency of a supercapacitor. Discovering, tuning, and improving electrode materials are very important. This work reports the effect of SiO2/Al2O3 ratio on electrochemical performances of amorphous zeolites ZSM5 (AZ) and H-ZSM5 (H-AZ) loaded with cobalt oxide. Two SiO2/Al2O3 ratios (1 = 6.2 and 2 = 8.3) of AZ1, AZ2 and H-AZ1, H-AZ2 were synthesized by a facile impregnation method. Then, controlled masses of cobalt oxide were introduced to enhance the supercapacitive performances of the amorphous zeolite. Investigation of the SiO2/Al2O3 ratio in the cobalt oxide/zeolite composite (Co/AZ and Co/H-AZ) was carried out to unveil its effect on the electrochemical properties. Worthy of note is the fact that the resulting electrode materials exhibited supercapacitive behavior that is effective over a potential window ranging from 0 to 0.5 V in potassium hydroxide (1 M KOH) aqueous electrolyte. Results from Galvanometry Charging and Discharging (GCD) analyses show that the modified Ni-foam electrodes loaded with Co/H-AZ1 and Co/H-AZ2 are capable of delivering a relatively high specific capacity from 45.97 mA h g-1 to a high value of 72.5 mA h g-1 at 1 A g-1 and Ni-foam electrodes loaded with Co/AZ1 and Co/AZ2 exhibited values from 26 mA h g-1 to 52.83 mA h g-1 respectively. It is clearly shown that, when the mass ratio SiO2/Al2O3 increases, the specific capacity increases as well. It was also noticed that after 2000 cycles, Co/H-AZ1 and Co/AZ1 have a poor coulombic efficiency while Co/H-AZ2 and Co/AZ2 exhibited 98% for coulombic efficiency. Finally, this study shows that to fabricate high performance supercapacitors with amorphous zeolite loaded with cobalt oxide, one should keep the ratio of SiO2/Al2O3 as high as possible during synthesis.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Special Issue "Pediatric Eye Disease: Screening, Causes and Treatment".

Clinical manifestations and courses of eye diseases in children are profoundly variable, from minor irritations, pain, infections, inflammations, ocular misalignment, refractive errors and visual impairment, to permanent blindness [...].

Cell based dATP delivery as a therapy for chronic heart failure.

Transplanted human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) improve ventricular performance when delivered acutely post-myocardial infarction but are ineffective in chronic myocardial infarction/heart failure. 2'-deoxy-ATP (dATP) activates cardiac myosin and potently increases contractility. Here we engineered hPSC-CMs to overexpress ribonucleotide reductase, the enzyme controlling dATP production. In vivo, dATP-producing CMs formed new myocardium that transferred dATP to host cardiomyocytes via gap junctions, increasing their dATP levels. Strikingly, when transplanted into chronically infarcted hearts, dATP-producing grafts increased left ventricular function, whereas heart failure worsened with wild-type grafts or vehicle injections. dATP-donor cells recipients had greater voluntary exercise, improved cardiac metabolism, reduced pulmonary congestion and pathological cardiac hypertrophy, and improved survival. This combination of remuscularization plus enhanced host contractility offers a novel approach to treating the chronically failing heart.

Micro-dystrophin gene therapy demonstrates long-term cardiac efficacy in a severe Duchenne muscular dystrophy model.

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model. We now show that gene therapy using a micro-dystrophin optimized for skeletal muscle efficacy (AAV-µDys5), and which is currently in a clinical trial, is able to fully prevent cardiac pathology and cardiac strain abnormalities and maintain normal (>45%) ejection fraction through 18 months of age in Fiona/dko mice. Early treatment with AAV-µDys5 prevents inflammation and fibrosis in Fiona/dko hearts. Collagen in cardiac fibrotic scars becomes more tightly packed from 12 to 18 months in Fiona/dko mice, but the area of fibrosis containing tenascin C does not change. Increased tight collagen correlates with unexpected improvements in Fiona/dko whole-heart function that maintain impaired cardiac strain and strain rate. This study supports micro-dystrophin gene therapy as a promising intervention for preventing DMD cardiomyopathy progression.

Iron and Manganese Alginate for Rechargeable Battery Electrodes.

We present a sustainable, inherently safe battery chemistry that is based on widely available and cheap materials, that is, iron and manganese hosted in alginate bio-material known from the food and medical industry. The resulting battery can be recycled to allow circularity. The electrodes were synthesised by the alginate caging the multi-valent metals to form a hydrogel in an aqueous environment. Characterisation includes FTIR, XPS and Mössbauer spectroscopy. The electrochemical performance of the electrodes was investigated by performing cyclic voltammetry (CV) and (dis)charge experiments. Mn and Fe ions show good co-ordination with the alginic acid with higher oxidation states demonstrating complex bonding behaviour. The non-optimised iron and manganese alginate electrodes already exhibit a cycling efficiency of 98% and 69%, respectively. This work shows that Fe and Mn atomically disperse in a bio-based host material and can act as electrodes in an aqueous battery chemistry. While demonstrated at cell level, it is furthermore explained how these materials can form the basis for a (semi-solid) flow cell.

Impact of telehealth on the current and future practice of lipidology: a scoping review.

Telehealth services have been implemented to deliver care for patients living with many chronic conditions and have expanded greatly during the COVID-19 pandemic. Little is known about the current or future impacts of telehealth on lipid management practices. The PubMed database was searched from inception to June 25, 2021, with the keywords "lipids or cholesterol" and "telehealth," which yielded 376 published articles. Telehealth was defined as a synchronous visit between a patient and clinician that replaced an in-office appointment. Studies that solely used remote monitoring, mobile health technologies, or callbacks of results, were excluded. Articles must have measured lipid values. Review articles and protocol papers were not included. After evaluation, 128 abstracts were included for full text evaluation, with 55 full-text articles eventually included. Of the articles, 29 were randomized clinical trials, 15 were pre-post evaluations, and 11 were other study designs. Telehealth had positive to neutral impacts on lipid management. Reported facilitators include easier implementation of multidisciplinary approaches to care, and utilization of patient-centered programs. Reported barriers to telehealth services include technological barriers, such as various skill levels with technology; systems barriers, such as cost and reimbursement; patient-related barriers, including patient non-adherence; and clinician-related barriers, such as difficulty standardizing care. Clinicians reported improved satisfaction among patients but had mixed feelings regarding their ability to deliver quality care. Telemedicine use to provide care for individuals with lipid conditions has expanded during the COVID-19 pandemic, but more research is needed to determine its potential as a sustainable tool for lipid management.