Fitzsimmonsrooney4103

Emerging research on epigenetics has resulted in many novel discoveries in atherosclerosis (AS), an inflammaging-associated disease characterized by chronic inflammation primarily driven by macrophages. The bulk of evidence has demonstrated the central role of epigenetic machinery in macrophage polarization to pro- (M1-like) or anti-inflammatory (M2-like) phenotype. An increasing number of epigenetic alterations and their modifiers involved in reprogramming macrophages by regulating DNA methylation or histone modifications (e.g., methylation, acetylation, and recently lactylation) have been identified. They may act to determine or skew the direction of macrophage polarization in AS lesions, thereby representing a promising target. Here we describe the current understanding of the epigenetic machinery involving macrophage polarization, to shed light on chronic inflammation-driving onset and progression of inflammaging-associated diseases, using AS as a prototypic example, and discuss the challenge for developing effective therapies targeting the epigenetic modifiers against these diseases, particularly highlighting a potential strategy based on epigenetically-governed repolarization from M1-like to M2-like phenotype.Stereotactic body radiotherapy (SBRT) has been reported as an attractive option for cases of failed catheter ablation of ventricular tachycardia (VT) in structural heart disease. However, even this strategy can fail for various reasons. For the first time, this case series describes three re-do cases of SBRT which were indicated for three different reasons. The purpose in the first case was the inaccuracy of the determination of the treatment volume by indirect comparison of the electroanatomical map and CT scan. A newly developed strategy of co-registration of both images allowed precise targeting of the substrate. In this case, the second treatment volume overlapped by 60% with the first one. The second reason for the re-do of SBRT was an unusual character of the substrate-large cardiac fibroma associated with different morphologies of VT from two locations around the tumor. The planned treatment volumes did not overlap. The third reason for repeated SBRT was the large intramural substrate in the setting of advanced heart failure. The first treatment volume targeted arrhythmias originating in the basal inferoseptal region, while the second SBRT was focused on adjacent basal septum without significant overlapping. Our observations suggested that SBRT for VT could be safely repeated in case of later arrhythmia recurrences (i.e., after at least 6 weeks). No acute toxicity was observed and in two cases, no side effects were observed during 32 and 22 months, respectively. To avoid re-do SBRT due to inaccurate targeting, the precise and reproducible strategy of substrate identification and co-registration with CT image should be used.

Cardiac rehabilitation (CR) is an evidence-based intervention promoting risk factor modification following coronary artery disease events but the relative benefits for patient subgroups is not clear. This review synthesizes the available evidence on the effectiveness of modern CR programs and determines outcomes for age, sex and prior level of fitness.

MEDLINE, CINAHL, and EMBASE were examined for RCT and cohort studies involving exercise prescription or phase II or III CR following Myocardial Infarction (MI), Percutaneous Coronary Intervention (PCI) and cardiac surgery from January 2010 to February 2021. Outcomes assessed included peakVO

max, 6-min walk test and Metabolic Equivalent of Task. Meta-regression was used to determine CR impact for change in fitness and age and sex influences.

The mean age of study participants was 59.5 years and 82.7% were male. Females, younger people and those of average or above cardiorespiratory fitness were substantially under-represented in data and attendance, with and accessible for all.

The uncertainties of grafts' ostium and patency would cause prolonged procedure/fluoroscopy time and extra contrast agent consumption of the invasive coronary angiography (ICA) in patients with coronary artery bypass grafting (CABG) history. This study was conducted to evaluate whether the identification of grafts' ostium and patency by coronary computed tomographic angiography (CTA) could facilitate ICA procedure.

Patients with acute coronary syndrome (ACS) and CABG history who underwent ICA during hospitalization were enrolled. The patients were divided into the CTA-ICA group and the direct ICA group according to whether a coronary CTA was performed before ICA. The complete direct ICA was defined by successful selective angiography of all recorded grafts. The procedure/fluoroscopy time and contrast agent consumption of ICA were compared.

There were 14 patients in the CTA-ICA group and 24 patients in the direct ICA group. In the direct ICA group, twelve cases were conducted complete ICA. The CTA-ICA group had reduced procedure time (17.8 ± 7.1 vs. 25.9 ± 15.4 min,

= 0.03) and fluoroscopy time (fluor-time; 4.6 ± 2.3 vs. 9.8 ± 5.3 min,

< 0.01), and less contrast agent consumption (30.4 ± 5.6 vs. 49.8 ± 20.9 ml,

< 0.01) than the direct ICA group. In a subgroup analysis, the incomplete direct ICA had the longest procedure time (32.8 ± 16.5 min) or fluor-time (12.0 ± 5.5 min) and the most contrast agent consumption (58.3 ± 25.8 ml), whereas the difference between CTA-ICA and complete direct ICA groups was non-significant.

The CTA would facilitate invasive angiography in patients with CABG by reducing procedure/fluoroscopy time and contrast agent consumption.

The CTA would facilitate invasive angiography in patients with CABG by reducing procedure/fluoroscopy time and contrast agent consumption.Exoskeletons and more in general wearable mechatronic devices represent a promising opportunity for rehabilitation and assistance to people presenting with temporary and/or permanent diseases. However, there are still some limits in the diffusion of robotic technologies for neuro-rehabilitation, notwithstanding their technological developments and evidence of clinical effectiveness. One of the main bottlenecks that constrain the complexity, weight, and costs of exoskeletons is represented by the actuators. This problem is particularly evident in devices designed for the upper limb, and in particular for the hand, in which dimension limits and kinematics complexity are particularly challenging. Commisterone This study presents the design and prototyping of a hand finger exoskeleton. In particular, we focus on the design of a gear-based differential mechanism aimed at coupling the motion of two adjacent fingers and limiting the complexity and costs of the system. The exoskeleton is able to actuate the flexion/extension motion of the fingers and apply bidirectional forces, that is, it is able to both open and close the fingers. The kinematic structure of the finger actuation system has the peculiarity to present three DoFs when the exoskeleton is not worn and one DoF when it is worn, allowing better adaptability and higher wearability. The design of the gear-based differential is inspired by the mechanism widely used in the automotive field; it allows actuating two fingers with one actuator only, keeping their movements independent.Teleoperation is one of the oldest applications of human-robot interaction, yet decades later, robots are still difficult to control in a variety of situations, especially when used by non-expert robot operators. That difficulty has relegated teleoperation to mostly expert-level use cases, though everyday jobs and lives could benefit from teleoperated robots by enabling people to get tasks done remotely. Research has made great progress by improving the capabilities of robots, and exploring a variety of interfaces to improve operator performance, but many non-expert applications of teleoperation are limited by the operator's ability to understand and control the robot effectively. We discuss the state of the art of user-centered research for teleoperation interfaces along with challenges teleoperation researchers face and discuss how an increased focus on human-centered teleoperation research can help push teleoperation into more everyday situations.In nuclear magnetic resonance spectroscopy of proteins, methyl protons play a particular role as extremely sensitive reporters on dynamics, allosteric effects, and protein-protein interactions, accessible even in high-molecular-weight systems approaching 1 MDa. The notorious issue of their chemical shift assignment is addressed here by a joint use of solid-state 1H-detected methods at very fast (nearly 100 kHz) magic-angle spinning, partial deuteration, and high-magnetic fields. The suitability of a series of RF schemes is evaluated for the efficient coherence transfer across entire 13C side chains of methyl-containing residues, which is key for establishing connection between methyl and backbone 1H resonances. The performance of ten methods for recoupling of either isotropic 13C-13C scalar or anisotropic dipolar interactions (five variants of TOBSY, FLOPSY, DIPSI, WALTZ, RFDR, and DREAM) is evaluated experimentally at two state-of-the-art magic-angle spinning (55 and 94.5 kHz) and static magnetic field conditions (18.8 and 23.5 T). Model isotopically labeled compounds (alanine and Met-Leu-Phe tripeptide) and ILV-methyl and amide-selectively protonated, and otherwise deuterated chicken α-spectrin SH3 protein are used as convenient reference systems. Spin dynamics simulations in SIMPSON are performed to determine optimal parameters of these RF schemes, up to recently experimentally attained spinning frequencies (200 kHz) and B 0 field strengths (28.2 T). The concept of linearization of 13C side chain by appropriate isotope labeling is revisited and showed to significantly increase sensitivity of methyl-to-backbone correlations. A resolution enhancement provided by 4D spectroscopy with non-uniform (sparse) sampling is demonstrated to remove ambiguities in simultaneous resonance assignment of methyl proton and carbon chemical shifts.Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is gaining much interest for its regulating role in the central nervous system and its value as a drug target. Structures of CB1 in inactive and active states have revealed conformational change details that are not common in other GPCRs. Here, we performed molecular dynamics simulations of CB1 in different ligand binding states and with mutations to reveal its activation mechanism. The conformational change of the "twin toggle switch" residues F2003.36 and W3566.48 that correlates with ligand efficacy is identified as a key barrier step in CB1 activation. Similar conformational change of residues 3.36/6.48 is also observed in melanocortin receptor 4, showing this "twin toggle switch" residue pair is crucial for the activation of multiple GPCR members.Silencing of transposable elements (TEs) by Piwi-interacting RNAs (piRNAs) is crucial for maintaining germline genome integrity and fertility in animals. To repress TEs, PIWI clade Argonaute proteins cooperate with several Tudor domain-containing (Tdrd) proteins at membraneless perinuclear organelles, called nuage, to produce piRNAs to repress transposons. Here, we identify and characterize Kotsubu (Kots), one of the Drosophila Tudor domain-containing protein-1 (Tdrd1) orthologs, encoded by the CG9925 gene, that localizes to the nuage in gonads. We further show the dynamic localization of Kots in the male germline, where it shows perinuclear signals in spermatogonia but forms large cytoplasmic condensates in the spermatocytes that overlap with components of piNG-body, a nuage-associated organelle. The loss of kots results in a notable upregulation of stellate and a corresponding reduction in the suppressor of stellate piRNAs in the mutants. Furthermore, a moderate yet significant reduction of other piRNAs was observed in kots mutant testes.