Rare Metastasis of Prostate Cancer in a Man With Ulcerative Colitis After Creation of an Ileal Pouch.

Prostate cancer is one of the most common globally diagnosed cancers in men. It most frequently metastasizes to bones, lymph nodes, lungs, or the liver. There are limited data investigating the impact of prostate cancer on patients who have undergone ileal pouch-anal anastomosis.

Clinician Response to the 2021 USPSTF Recommendation for Colorectal Cancer Screening in Average Risk Adults Aged 45-49 Years.

Introduction: In 2021, the USPSTF lowered the recommended age of colorectal cancer (CRC) screening initiation from 50 to 45 years. This study assessed clinician response to the updated guideline in a major health system.

Methods: This was a retrospective cohort study of average-risk, CRC screening-naïve adults aged 45-50 years with a primary care appointment between July 2018 and February 2023.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

Background: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs).

Machine learning meets Monte Carlo methods for models of muscle's molecular machinery to classify mutations.

The timing and magnitude of force generation by a muscle depend on complex interactions in a compliant, contractile filament lattice. Perturbations in these interactions can result in cardiac muscle diseases. In this study, we address the fundamental challenge of connecting the temporal features of cardiac twitches to underlying rate constants and their perturbations associated with genetic cardiomyopathies.

Nuclear mechanosignaling in striated muscle diseases.

Mechanosignaling describes processes by which biomechanical stimuli are transduced into cellular responses. External biophysical forces can be transmitted structural protein networks that span from the cellular membrane to the cytoskeleton and the nucleus, where they can regulate gene expression through a series of biomechanical and/or biochemical mechanosensitive mechanisms, including chromatin remodeling, translocation of transcriptional regulators, and epigenetic factors. Striated muscle cells, including cardiac and skeletal muscle myocytes, utilize these nuclear mechanosignaling mechanisms to respond to changes in their intracellular and extracellular mechanical environment and mediate gene expression and cell remodeling.

Primary care physician referral practices regarding BRCA1/2 genetic counseling in a major health system.

Purpose: The United States Preventive Services Task Force recommends primary care physicians refer patients at high risk for BRCA1/2 mutations to genetic testing when appropriate. The objective of our study was to describe referrals for BRCA1/2 testing in a large integrated health system and to assess factors associated with referral.

Methods: This retrospective cohort study includes female patients between 18 and 50 years who had a primary care visit in the Cleveland Clinic Health System between 2010 and 2019.

Subcellular Remodeling in Filamin C Deficient Mouse Hearts Impairs Myocyte Tension Development during Progression of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a life-threatening form of heart disease that is typically characterized by progressive thinning of the ventricular walls, chamber dilation, and systolic dysfunction. Multiple mutations in the gene encoding filamin C (FLNC), an actin-binding cytoskeletal protein in cardiomyocytes, have been found in patients with DCM. However, the mechanisms that lead to contractile impairment and DCM in patients with FLNC variants are poorly understood.

The Sliding Filament Theory Since Andrew Huxley: Multiscale and Multidisciplinary Muscle Research.

Two groundbreaking papers published in 1954 laid out the theory of the mechanism of muscle contraction based on force-generating interactions between myofilaments in the sarcomere that cause filaments to slide past one another during muscle contraction. The succeeding decades of research in muscle physiology have revealed a unifying interest: to understand the multiscale processes-from atom to organ-that govern muscle function. Such an understanding would have profound consequences for a vast array of applications, from developing new biomimetic technologies to treating heart disease.

The effect of variable troponin C mutation thin filament incorporation on cardiac muscle twitch contractions.

One of the complexities of understanding the pathology of familial forms of cardiac diseases is the level of mutation incorporation in sarcomeres. Computational models of the sarcomere that are spatially explicit offer an approach to study aspects of mutational incorporation into myofilaments that are more challenging to get at experimentally. We studied two well characterized mutations of cardiac TnC, L48Q and I61Q, that decrease or increase the release rate of Ca from cTnC, k, resulting in HCM and DCM respectively [1].

In vitro characterization of hierarchical 3D scaffolds produced by combining additive manufacturing and thermally induced phase separation.

This paper reports on the hybrid process we have used for producing hierarchical scaffolds made of poly(lactic-co-glycolic) acid (PLGA) and nanohydroxyapatite (nHA), analyzes their internal structures scanning electron microscopy, and presents the results of our proliferation of MC3T3-E1 cells and alkaline phosphatase activity (ALP) for 0 and 21 days. These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Slow cooling at a rate of 1.

Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.

Dilated cardiomyopathy (DCM) is often associated with sarcomere protein mutations that confer reduced myofilament tension-generating capacity. We demonstrated that cardiac twitch tension-time integrals can be targeted and tuned to prevent DCM remodeling in hearts with contractile dysfunction. We employed a transgenic murine model of DCM caused by the D230N-tropomyosin (Tm) mutation and designed a sarcomere-based intervention specifically targeting the twitch tension-time integral of D230N-Tm hearts using multiscale computational models of intramolecular and intermolecular interactions in the thin filament and cell-level contractile simulations.

A strategic mindset: An orientation toward strategic behavior during goal pursuit.

Many attractive jobs in today's world require people to take on new challenges and figure out how to master them. As with any challenging goal, this involves systematic strategy use. Here we ask: Why are some people more likely to take a strategic stance toward their goals, and can this tendency be cultivated? To address these questions, we introduce the idea of a domain-general "strategic mindset.

Adult Mosquitoes Infected with Bacteria Early in Life Have Stronger Antimicrobial Responses and More Hemocytes after Reinfection Later in Life.

The immunological strategies employed by insects to overcome infection vary with the type of infection and may change with experience. We investigated how a bacterial infection in the hemocoel of the African malaria mosquito, , prepares the immune system to face a subsequent bacterial infection. For this, adult female mosquitoes were separated into three groups-unmanipulated, injured, or infected with -and five days later all the mosquitoes were infected with a different strain of .

Multiscale Models of Cardiac Muscle Biophysics and Tissue Remodeling in Hypertrophic Cardiomyopathies.

Myocardial hypertrophy is the result of sustained perturbations to the mechanical and/or neurohormonal homeostasis of cardiac cells and is driven by integrated, multiscale biophysical and biochemical processes that are currently not well defined. In this brief review, we highlight recent computational and experimental models of cardiac hypertrophy that span mechanisms from the molecular level to the tissue level. Specifically, we focus on: (i) molecular-level models of the structural dynamics of sarcomere proteins in hypertrophic hearts, (ii) cellular-level models of excitation-contraction coupling and mechanosensitive signaling in disease-state myocytes, and (iii) organ-level models of myocardial growth kinematics and predictors thereof.

Contracting striated muscle has a dynamic I-band spring with an undamped stiffness 100 times larger than the passive stiffness.

Key Points: Fast sarcomere-level mechanics in contracting intact fibres from frog skeletal muscle reveal an I-band spring with an undamped stiffness 100 times larger than the known static stiffness. This undamped stiffness remains constant in the range of sarcomere length 2.7-3.

Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin.

The naturally occurring nucleotide 2-deoxy-adenosine 5'-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer and millisecond time scales, demonstrating the ability to make both structural measurements and quantitative kinetic estimates of weak actin-myosin interactions that underpin sarcomere dynamics.

Inotropic interventions do not change the resting state of myosin motors during cardiac diastole.

When striated (skeletal and cardiac) muscle is in its relaxed state, myosin motors are packed in helical tracks on the surface of the thick filament, folded toward the center of the sarcomere, and unable to bind actin or hydrolyze ATP (OFF state). This raises the question of whatthe mechanism is that integrates the Ca-dependent thin filament activation, making myosin heads available for interaction with actin. Here we test the interdependency of the thin and thick filament regulatory mechanisms in intact trabeculae from the rat heart.

A Spatially Explicit Model Shows How Titin Stiffness Modulates Muscle Mechanics and Energetics.

In striated muscle, the giant protein titin spans the entire length of a half-sarcomere and extends from the backbone of the thick filament, reversibly attaches to the thin filaments, and anchors to the dense protein network of the z-disk capping the end of the half-sarcomere. However, little is known about the relationship between the basic mechanical properties of titin and muscle contractility. Here, we build upon our previous multi-filament, spatially explicit computational model of the half-sarcomere by incorporating the nonlinear mechanics of titin filaments in the I-band.

Afterload promotes maturation of human induced pluripotent stem cell derived cardiomyocytes in engineered heart tissues.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) grown in engineered heart tissue (EHT) can be used for drug screening, disease modeling, and heart repair. However, the immaturity of hiPSC-CMs currently limits their use. Because mechanical loading increases during development and facilitates cardiac maturation, we hypothesized that afterload would promote maturation of EHTs.

Vacuum impregnation of firming agents in red raspberries.

Background: Red raspberries are a delicate and highly perishable fruit with a fragile pulp tissue. In this study we used vacuum impregnation (VI) methods to incorporate pectin and calcium chloride into whole red raspberries to improve their firmness. Specifically, we impregnated low methoxyl pectin (LMP) at 10 g of pectin kg of solution and calcium chloride (CaCl ·2H O) at 30 g calcium kg of pectin, and on the other side pectin methylesterase (PME) at 10 g of enzyme kg of solution, and (CaCl ·2H O) at 10 g of calcium kg of solution, into whole red raspberries.

Myosin filament activation in the heart is tuned to the mechanical task.

The mammalian heart pumps blood through the vessels, maintaining the dynamic equilibrium in a circulatory system driven by two pumps in series. This vital function is based on the fine-tuning of cardiac performance by the Frank-Starling mechanism that relates the pressure exerted by the contracting ventricle (end systolic pressure) to its volume (end systolic volume). At the level of the sarcomere, the structural unit of the cardiac myocytes, the Frank-Starling mechanism consists of the increase in active force with the increase of sarcomere length (length-dependent activation).

Minimum number of myosin motors accounting for shortening velocity under zero load in skeletal muscle.

Key Points: Myosin filament mechanosensing determines the efficiency of the contraction by adapting the number of switched ON motors to the load. Accordingly, the unloaded shortening velocity (V ) is already set at the end of latency relaxation (LR), ∼10 ms after the start of stimulation, when the myosin filament is still in the OFF state. Here the number of actin-attached motors per half-myosin filament (n) during V shortening imposed either at the end of LR or at the plateau of the isometric contraction is estimated from the relation between half-sarcomere compliance and force during the force redevelopment after shortening.