Intraoperative Myocardial Infarction During Elective Laparoscopic Cholecystectomy: A Case Report.

Laparoscopic cholecystectomy has become the gold standard for treating symptomatic cholelithiasis due to its minimally invasive nature and faster recovery times compared to traditional open surgery, but it is not without risks. A key component of this procedure is the creation of pneumoperitoneum. This is achieved by insufflating the abdomen with carbon dioxide (CO2).

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies.

Physiological role for S-nitrosylation of RyR1 in skeletal muscle function and development.

Excitation-contraction coupling in skeletal muscle myofibers depends upon Ca release from the sarcoplasmic reticulum through the ryanodine receptor/Ca-release channel RyR1. The RyR1 contains ∼100 Cys thiols of which ∼30 comprise an allosteric network subject to posttranslational modification by S-nitrosylation, S-palmitoylation and S-oxidation. However, the role and function of these modifications is not understood.

Disease-driven domain generalization for neuroimaging-based assessment of Alzheimer's disease.

Development of deep learning models to evaluate structural brain changes caused by cognitive impairment in MRI scans holds significant translational value. The efficacy of these models often encounters challenges due to variabilities arising from different data generation protocols, imaging equipment, radiological artifacts, and shifts in demographic distributions. Domain generalization (DG) techniques show promise in addressing these challenges by enabling the model to learn from one or more source domains and apply this knowledge to new, unseen target domains.

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an AI model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations, and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies.

Disease-driven domain generalization for neuroimaging-based assessment of Alzheimer's disease.

Development of deep learning models to assess the degree of cognitive impairment on magnetic resonance imaging (MRI) scans has high translational significance. Performance of such models is often affected by potential variabilities stemming from independent protocols for data generation, imaging equipment, radiology artifacts, and demographic distributional shifts. Domain generalization (DG) frameworks have the potential to overcome these issues by learning signal from one or more source domains that can be transferable to unseen target domains.

The high-value pharmacy enterprise framework: Advancing pharmacy practice in health systems through a consensus-based, strategic approach.

Purpose: The high-value pharmacy enterprise (HVPE) framework and constituent best practice consensus statements are presented, and the methods used to develop the framework's 8 domains are described.

Summary: A panel of pharmacy leaders used an evidence- and expert opinion-based approach to define core and aspirational elements of practice that should be established within contemporary health-system pharmacy enterprises by calendar year 2025. Eight domains of an HVPE were identified: Patient Care Services; Business Services; Ambulatory and Specialty Pharmacy Services; Inpatient Operations; Safety and Quality; Pharmacy Workforce; Information Technology, Data, and Information Management; and Leadership.

Revisiting Image-Language Networks for Open-Ended Phrase Detection.

Most existing work that grounds natural language phrases in images starts with the assumption that the phrase in question is relevant to the image. In this paper we address a more realistic version of the natural language grounding task where we must both identify whether the phrase is relevant to an image and localize the phrase. This can also be viewed as a generalization of object detection to an open-ended vocabulary, introducing elements of few- and zero-shot detection.

Multifunctional Synthetic Protein Nanoparticles via Reactive Electrojetting.

Protein nanoparticles are a promising approach for nanotherapeutics, as proteins combine versatile chemical and biological function with controlled biodegradability. In this work, the development of an adaptable synthesis method is presented for synthetic protein nanoparticles (SPNPs) based on reactive electrojetting. In contrast to past work with electrohydrodynamic cojetting using inert polymers, the jetting solutions are comprised of proteins and chemically activated macromers, designed to react with each other during the processing step, to form insoluble nanogel particles.

Arrhythmogenic cardiac alternans in heart failure is suppressed by late sodium current blockade by ranolazine.

Background: Cardiac alternans is promoted by heart failure (HF)-induced calcium (Ca) cycling abnormalities. Late sodium current (I) is enhanced in HF and promotes Ca overload; however, mechanisms underlying an antiarrhythmic effect of I blockade in HF remain unclear.

Objective: The purpose of this study was to determine whether ranolazine suppresses cardiac alternans in HF by normalizing Ca cycling.

Arrhythmogenic Delayed Afterdepolarizations Are Promoted by Severe Hypothermia But Not Therapeutic Hypothermia.

Background: Severe hypothermia (SH) is known to be arrhythmogenic, but the effect of therapeutic hypothermia (TH) on arrhythmias is unclear. It is hypothesized that susceptibility to Ca-mediated arrhythmia triggers would be increased only by SH.

Methods and results: Spontaneous Ca release (SCR) and resultant delayed afterdepolarizations (DADs) were evaluated by optical mapping in canine wedge preparations during normothermia (N, 36℃), TH (32℃) or SH (28℃; n=8 each).

Manipulating walking path configuration influences gait variability and six-minute walk test outcomes in older and younger adults.

This study determined whether manipulations to walking path configuration influenced six-minute walk test (6MWT) outcomes and assessed how gait variability changes over the duration of the 6MWT in different walking path configurations. Healthy older (ODR) and younger (YNG) (n=24) adults completed familiarisation trials and five randomly ordered experimental trials of the 6MWT with walking configurations of; 5, 10 and 15m straight lines, a 6m by 3m rectangle (RECT), and a figure of eight (FIG8). Six-minute walk distance (6MWD) and walking speed (m.

Targeted antioxidant treatment decreases cardiac alternans associated with chronic myocardial infarction.

Background: In myocardial infarction (MI), repolarization alternans is a potent arrhythmia substrate that has been linked to Ca2+ cycling proteins, such as sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), located in the sarcoplasmic reticulum. MI is also associated with oxidative stress and increased xanthine oxidase (XO) activity, an important source of reactive oxygen species (ROS) in the sarcoplasmic reticulum that may reduce SERCA2a function. We hypothesize that in chronic MI, XO-mediated oxidation of SERCA2a is a mechanism of cardiac alternans.

The Academic Diligence Task (ADT): Assessing Individual Differences in Effort on Tedious but Important Schoolwork.

The current study reports on the development and validation of the Academic Diligence Task (ADT), designed to assess the tendency to expend effort on academic tasks which are tedious in the moment but valued in the long-term. In this novel online task, students allocate their time between solving simple math problems (framed as beneficial for problem solving skills) and, alternatively, playing Tetris or watching entertaining videos. Using a large sample of high school seniors ( = 921), the ADT demonstrated convergent validity with self-report ratings of Big Five conscientiousness and its facets, self-control and grit, as well as discriminant validity from theoretically unrelated constructs, such as Big Five extraversion, openness, and emotional stability, test anxiety, life satisfaction, and positive and negative affect.

A Behind-the-Scenes Guide to School-Based Research.

Schools are an important context for both basic and applied scientific research. Unlike the laboratory, however, the physical and social conditions of schools are not under the exclusive control of scientists. In this article, we liken collecting data in schools to putting on a theatrical production.

Regulation of the skeletal muscle ryanodine receptor/Ca2+-release channel RyR1 by S-palmitoylation.

The ryanodine receptor/Ca(2+)-release channels (RyRs) of skeletal and cardiac muscle are essential for Ca(2+) release from the sarcoplasmic reticulum that mediates excitation-contraction coupling. It has been shown that RyR activity is regulated by dynamic post-translational modifications of Cys residues, in particular S-nitrosylation and S-oxidation. Here we show that the predominant form of RyR in skeletal muscle, RyR1, is subject to Cys-directed modification by S-palmitoylation.

Aberrant S-nitrosylation mediates calcium-triggered ventricular arrhythmia in the intact heart.

Nitric oxide (NO) derived from the activity of neuronal nitric oxide synthase (NOS1) is involved in S-nitrosylation of key sarcoplasmic reticulum (SR) Ca(2+) handling proteins. Deficient S-nitrosylation of the cardiac ryanodine receptor (RyR2) has a variable effect on SR Ca(2+) leak/sparks in isolated myocytes, likely dependent on the underlying physiological state. It remains unknown, however, whether such molecular aberrancies are causally related to arrhythmogenesis in the intact heart.

Targeted sarcoplasmic reticulum Ca2+ ATPase 2a gene delivery to restore electrical stability in the failing heart.

Background: Recently, we reported that sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), the pump responsible for reuptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, deficient SERCA2a, and increased susceptibility to cardiac alternans. Therefore, we hypothesized that restoring deficient SERCA2a by gene transfer will significantly reduce arrhythmogenic cardiac alternans in the failing heart.

Parental follow-through of neuropsychological recommendations for childhood-cancer survivors.

In the past 40 years, outcomes for children with cancer have changed considerably. The survival rate has increased to approximately 80%. With success and survival come detriments that often occur over time called late effects of cancer treatment.

Exome sequencing supports a de novo mutational paradigm for schizophrenia.

Despite its high heritability, a large fraction of individuals with schizophrenia do not have a family history of the disease (sporadic cases). Here we examined the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exomes of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 cases affecting 40 genes, including a potentially disruptive mutation in DGCR2, a gene located in the schizophrenia-predisposing 22q11.

Spontaneous calcium oscillations during diastole in the whole heart: the influence of ryanodine reception function and gap junction coupling.

Triggered arrhythmias due to spontaneous cytoplasmic calcium oscillations occur in a variety of disease conditions; however, their cellular mechanisms in tissue are not clear. We hypothesize that spontaneous calcium oscillations in the whole heart are due to calcium release from the sarcoplasmic reticulum and are facilitated by calcium diffusion through gap junctions. Optical mapping of cytoplasmic calcium from Langendorff perfused guinea pig hearts (n = 10) was performed using oxygenated Tyrode's solution (in mM): 140 NaCl, 0.

Spontaneous calcium release in tissue from the failing canine heart.

Abnormalities in calcium handling have been implicated as a significant source of electrical instability in heart failure (HF). While these abnormalities have been investigated extensively in isolated myocytes, how they manifest at the tissue level and trigger arrhythmias is not clear. We hypothesize that in HF, triggered activity (TA) is due to spontaneous calcium release from the sarcoplasmic reticulum that occurs in an aggregate of myocardial cells (an SRC) and that peak SCR amplitude is what determines whether TA will occur.

Stage-based expert systems to guide a population of primary care patients to quit smoking, eat healthier, prevent skin cancer, and receive regular mammograms.

Background: Treating multiple health behavior risks on a population basis is one of the most promising approaches to enhancing health and reducing health care costs. Previous research demonstrated the efficacy of expert system interventions for three behaviors in a population of parents. The interventions provide individualized feedback that guides participants through the stages of change for each of their risk behaviors.