bluuebunny/crossref_metadata_2025 huggingface dataset:
Lung Volumes and Capacity
Authors: Ahmed Muhammad Fayyaz , Ahmed Furqan
Published: May 2024

Lung volumes are vital parameters in clinical medicine, and changes in lung volumes can give useful information about lung function. Lung volumes are measured with a spirometer. Lung capacities are a sum of two or more lung volumes. Furthermore, lung volumes are classified into dynamic and static lung volumes, depending on how the breaths are measured in a spirometer. Slow breaths measure static lung volumes, whereas fast breaths measure dynamic lung volumes . Static lung volumes are residual volume, expiratory reserve volume, inspiratory reserve volume, inspiratory capacity, tidal volume, vital capacity, forced residual capacity, and total lung capacity. Dynamic lung volumes are forced expiratory volume in one second and forced vital capacity.
Pulmonary Function Tests and Spirometry
Authors: Sidagam Vasu
Published: May 2024

This chapter discusses common pulmonary function tests (PFTs) and spirometry in the diagnosis and management of pulmonary symptoms and diseases. Common patterns of PFT abnormalities are described and diagrams are self-explanatory. Perioperative implications are highlighted.
Apneic Oxygenation and Diffusion Hypoxia
Authors: Parniani Ahmad Reza , White Peggy
Published: May 2024

Apneic oxygenation is the process of oxygenation with no spontaneous breathing or mechanical ventilation. It can be used in a number of clinical settings, including as a means of delaying hypoxemia during airway management. The addition of high-flow nasal cannula has introduced another effective method for apneic oxygenation. Diffusion hypoxia is a consequence of rapid outgassing from the tissues of patients who receive nitrous oxide. This chapter summarizes the current methods used to perform apneic oxygenation, in addition to the benefits, applications, and potential complications of this technique. Lastly, it presents a detailed description of diffusion hypoxia.
Systemic Effects of Hyperoxia and Hypoxemia
Authors: Smith Sarah C.
Published: May 2024

Oxygen is required for ongoing cellular metabolism, with prolonged periods of ischemia resulting in cell death. Therefore, oxygen homeostasis is a tightly regulated process throughout the body such that systemic adaptations to hypoxia manifest almost immediately so that oxygen delivery is maintained to the most sensitive end-organs, namely the brain and the heart. Patients who experience chronic hypoxia due to lung disease, intracardiac shunts, or simply living at high altitude, will manifest systemic adaptations that should be considered when developing a plan for anesthetic management. Despite the critical importance of adequate oxygen delivery to maintain life, iatrogenic hyperoxia can also be deleterious due to the formation of oxygen free radicals that overwhelm the body’s normal antioxidant defense mechanisms. Therefore, prolonged periods of high FiO2 (greater than 70%) should generally be avoided in the perioperative period when possible.
Muscles of Respiration
Authors: Eng Lauren K. , Kaye Alan D.
Published: May 2024

Primary and accessory muscles of respiration provide for both inspiration and expiration. Primary muscles include the diaphragm, external, and internal intercostal muscles. The accessory muscles of inspiration include the scalenes, sternocleidomastoid, levator scapulae, trapezius, iliocostalis thoracis, subclavius, and omohyoid. The accessory muscles of expiration include the interosseous intercostals, abdominal muscles, transversus thoracis, subcostalis, quadratus lumborum, iliocostalis lumborum, latissimus dorsi, and serratus posterior.
Mast Cell Stabilizers
Authors: Reilly Eric , Manders Larry
Published: May 2024

Mast cells are key mediators in allergic diseases and can be activated through both immunoglobulin E (IgE) dependent and independent mechanisms. When an allergen comes into contact with the IgE complex on a sensitized mast cell, it starts a tyrosine kinase signaling cascade, which leads to a calcium influx and ultimately the release of chemical mediators such as histamine, prostaglandins, leukotrienes, cytokines, and chemokines. These mediators are responsible for the symptoms seen in primary, secondary, and idiopathic mast cell disorders which cause bronchoconstriction and increase airway resistance. Medications such as sodium cromoglycate stabilize mast cells to inhibit the release of allergic mediators, thus providing symptomatic relief. This outlines the physiology of mast cells, medications, and anesthetic considerations.
Immunoglobulin E (IgE) Blockers (Anti-IgE Therapy)
Authors: Reilly Eric , Manders Larry
Published: May 2024

Immunoglobulin E (IgE), composed of two light chains and two identical heavy chains, is a key component of many allergic diseases such as asthma. It is produced via communication between B and T cells after exposure to foreign allergens. Once produced and released, IgE can remain free in the plasma, or it can bind to membrane-bound receptors on mast cells, basophils, and other effector cells. Once bound with IgE, cells are considered sensitized. When an allergen binds to a membrane-bound IgE, the sensitized cell undergoes an activation signaling cascade which results in the release of preformed mediators and the production of inflammatory cytokines. These mediators and cytokines are what cause allergic responses in diseases such as asthma. Anti-IgE therapies have been created in an effort to prevent these allergic responses. These therapies have shown strong evidence for clinical benefits in allergic asthma and chronic urticaria.
The Cardiac Cycle
Authors: Pellicer Robert , Abd-Elsayed Alaa
Published: May 2024

The cardiac cycle is a series of physiological events in which blood moves through the chambers of the heart in alternating phases of systole and diastole. Movement of blood throughout the cardiac chambers is dependent on pressure changes and gradients, generated by alternating contraction and relaxation of myocardium. The cardiac cycle is generally described as having four phases: filling phase, isovolumetric contraction, ejection phase, and isovolumetric relaxation. Each of these phases is regulated by the cardiac conduction system, a complex network of specialized myocytes that ensures synchronized contraction and relaxation of myocardium.
Control of Heart Rate
Authors: Chuba Emuejevoke , Ahmed Muhammad Fayyaz
Published: May 2024

In this chapter the authors review heart rate and factors responsible for controlling it. Factors controlling the heart rate are the autonomic system, reflexes, and hormonal and local factors. A stepwise approach of managing tachycardia and bradycardia in the operating room is described, including the management of bradycardia in a heart-transplant recipient.
The Frank-Starling Law
Authors: Daklallah Youssef , Manders Larry
Published: May 2024

The Frank-Starling law is the observation that under normal limits, cardiac output increases as preload increases. There is a link between the force generated by a myocardial contraction and the initial length of myocardial fibers. The greater the diastolic volume in the left ventricle, the more myocardial fibers are stretched before contraction and the more tension in these fibers. This chapter describes the Frank-Starling Law and outlines major anesthetic considerations related to it.
Intracardiac, Pulmonary, and Venous Pressures
Authors: Martin Adriana , Chhabada Surendrasingh
Published: May 2024

Intravascular and intracardiac pressure measurements are routinely performed in intensive care units, operating rooms, and catheterization laboratories. Throughout the cardiac cycle there are pressure changes in all the heart chambers. It is important to know the normal values and pressure waveforms, so one can easily identify pathological processes where these values are abnormally increased or decreased. Central venous access can provide right-sided filling pressure values, and pulmonary artery catheter (PAC) can help estimate left-sided filling pressures via pulmonary capillary wedge pressure (PCWP). The central venous pressure (CVP) waveform consists of three peaks and two descends. Each of these components represents an event in the cardiac cycle and will be affected by numerous pathologies. The clinical use of CVP to estimate preload and fluid responsiveness has been a topic of debate and should not be used alone when making clinical decisions. Pulmonary artery catheters can indirectly provide estimation of left-sided pressures and left ventricle preload. The use of PAC has been questioned due to risk of severe complications like pulmonary artery rupture, pulmonary infarct, and arrhythmias. Because of that, this type of monitoring is only indicated in patients with severe pathologies where the data provided by the catheter can aid in making important clinical decisions.
Coronary Circulation
Authors: Andrews Keith A. , Helou Mada
Published: May 2024

This chapter reviews the arterial and venous anatomy of the heart. Regarding coronary arterial supply, special attention is paid to the difference between right versus left dominant circulation, clinical manifestations of the arterial occlusion in various territories, and clinical correlation to ischemic changes seen on ECG tracing. Venous return is also reviewed, and both systems are detailed in an illustration that can be easily reproduced under exam conditions.
Antiarrhythmics
Authors: Nemergut Greta
Published: May 2024

Antiarrhythmics are divided into four main Vaughan-Williams classifications based on their primary actions on the myocardial cell action potential (AP). The different classes of drugs exert their action on different phastes of the cardiac AP. New drugs and actions have become available or are being researched, including class 0, the pacemaker channel HCN4 modulators that affect the pacemaker current If. However, the original four overarching classes (class 1–4) remain the primary mechanisms for antiarrhythmic therapy: sodium channel blockade, beta receptor blockade, potassium channel blockade, and calcium channel blockade. This chapter reviews the classes of antiarrhythmic agents, drugs that are in each class, and their primary modes of action.
Non-Adrenergic Vasoconstrictors
Authors: Lee Albert , Schulman Nathan
Published: May 2024

Non-adrenergic vasoconstrictors, including vasopressin, methylene blue, and angiotensin II, are used for their vasoconstriction effects in states such as septic shock and other forms of vasoplegia. Methylene blue acts to inhibit an endogenous vasodilatory pathway by decreasing nitric oxide and cyclic guanosine monophosphate (cGMP) production. Though its use has repeatedly been shown to increase mean arterial pressure, data have yet to demonstrate robust benefits in mortality or oxygen delivery. Vasopressin produces intense peripheral vasoconstriction through its action on smooth-muscle V1 receptors. The Surviving Sepsis campaign currently recommends consideration of vasopressin as a second-line agent in septic shock refractory to a single vasopressor. As an end-product of the renin-angiotensin pathway, angiotensin II is responsible for triggering multiple downstream pathways resulting in vasopressin release and vasoconstriction. Recently, it has garnered much attention as an incredibly potent non-adrenergic vasopressor in septic shock due to its ability to effectively increase mean arterial pressures in otherwise refractory patients. Though it failed to demonstrate a mortality benefit, its novelty has led to continued interest and studies exploring its use.
Anatomy of the Kidney
Authors: El-Sabbahy Marwa , Fikry Karim
Published: May 2024

Understanding the anatomy of the kidney is critical to understanding its physiology and multiple roles in blood pressure control, fluid and electrolyte balance, as well as other hormonal functions. The kidneys consist of glomeruli and tubules. The glomerulus consists of a network of capillaries that branch from the afferent arteriole. Each tubule consists of proximal tubule, loop of Henle, distal convoluted tubule, collecting tubule, and ends with the papilla. Each part of the tubule has a distinct function. In addition, the kidney is a very vascular organ. The complex vasculature of the kidney is also discussed in this chapter.
Specific Organ Metabolism
Authors: Hallman Matthew J. , James Dominika Lipowska
Published: May 2024

Metabolism is a broad topic that describes the complex biochemical reactions required to sustain life. The liver serves as a center of multiple complex metabolic processes and is capable of converting glucose for storage into glycogen (in liver) or triglycerides (also occurs in peripheral tissues). Conversely, the liver is also capable of extracting glucose from glycogen when energy is required. In times of glucose and fatty acid scarcity, the liver has a capacity of using protein as an energy source by converting it into ketone bodies. Only cells containing mitochondria are capable of obtaining energy from fatty acids; thus human red blood cells must rely on energy formulated from glucose metabolism.
Postjunctional Components and Events
Authors: Roche Shaun , Moncayo Ruth E.
Published: May 2024

Neuromuscular transmission and skeletal muscle contraction occur when acetylcholine released from the nerve ending binds to the endplate nicotinic acetylcholine receptors (AChRs) on the postjunctional muscle membrane. The postsynaptic apparatus of the skeletal neuromuscular junction contains acetylcholine receptors that are densely packed at the motor end plate and organized by signals from the presynaptic nerve terminal. These postjunctional receptors change in shape and molecular architecture as they mature, and have the capacity for remodeling in response to altered input or pathologic states such as burns, denervation, immobilization, and inflammation. This chapter covers the postjunctional components, the acetylcholine receptor, and the postjunctional events that occur in the neuromuscular junction, as well as anesthetic considerations for patients suffering from disorders that impact the postjunctional receptors.
Perijunctional Channels
Authors: Roche Shaun , Moncayo Ruth E.
Published: May 2024

The area of muscle in close proximity to the motor end plate is known as the perijunctional zone. It is here where the membrane potential developed at the end plate is converted to an action potential, which propagates through the muscle to initiate muscle contraction. A basic understanding of the mechanism behind the opening and closing of these perijunctional sodium channels will assist in the understanding of different blocks seen within the practice of anesthesia. This chapter will cover the perijunctional zone, and perijunctional channels associated with the neuromuscular junction, as well as the mechanism of action and clinical presentation behind phase I, phase II, desensitization, and channel blocks.
Physician Wellness
Authors: Hanna Joseph Salama , Saad Ramsey
Published: May 2024

The World Health Organization (WHO) defines mental health as “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community.” One in four people worldwide are affected by mental health concerns. Physicians are particularly vulnerable to experiencing mental illness due to the nature of their work, which is often stressful and characterized by shift work, irregular work hours, and a high-pressure environment. This chapter reviews the definition of burnout, components of wellness, and keys to boost physicians’ well-being.
Professionalism and Licensure
Authors: Hanna Joseph Salama , Saad Ramsey
Published: May 2024

This chapter reviews the concept of medical professionalism with focus on its core components including ethical value system, medical knowledge and technical skills required for a good effective medical practice as well as interpersonal skills for the healthcare provider necessary to work with patients which can be referred to collectively as “Art” of medicine. It also discusses the requirements of licensure and certification in the field of Anesthesiology by reviewing important information obtained from the 2021 ABA policy book. It also sheds light on the updated MOCA-2 components including medical licensure, continued medical education CME, Moca Minute and quality improvement.
Informed Consent
Authors: Hanna Joseph Salama , Saad Ramsey
Published: May 2024

Physicians have a legal and ethical responsibility to provide sufficient information to the patient so that he or she can make appropriate decisions. An educated patient also benefits the physician, both in terms of cooperation in the planned intervention and in reducing frustrations and possibility of litigation in case of complications. The physician is expected to carefully bring the patient into the medical decision-making process, addressing the patient’s concerns, and creating reasonable expectations regarding outcomes. This chapter reviews the principles and components of the informed consent with focus on informed decision making, communication as well as documentation of the obtained consent.
Disclosure of Errors to Patients
Authors: Hanna Joseph Salama , Saad Ramsey
Published: May 2024

Physicians have a duty to communicate and disclose complications that result from interventional procedures to the patient; however, this may place the provider in a difficult position. On one hand, the provider is encouraged to disclose adverse outcomes, and his/her human instinct is to empathize with the patient and their families. On the other hand, providers are warned that apologies and disclosures can be seen as inviting lawsuits and lessening the ability to defend oneself if sued. In conclusion, what constitutes a protected apology in the medical setting should be carefully considered and composed; this will often need the help of malpractice insurer personnel, hospital counsel, and, perhaps, the provider’s own legal counsel. Care must be taken that the resulting dialogue does not lose the intended moral and social benefits.
Bullying, Impact on Health, and Beyond
Authors: Srabstein Jorge C.
Published: May 2024

This book is intended to promote awareness of the evolving understanding of the multifaceted and toxic nature of bullying, a psychosocial stressor that is associated with morbidity and mortality and that is globally prevalent across social settings and the life span. The recognition that bullying is a type of maltreatment that may be associated with other forms of victimization prompts us to go beyond the notion of bullying and to examine the spectrum of maltreatment. Reviewing at least 2,000 peer-reviewed articles published in the last two decades, this book examines what is known, so far, about the nature, prevalence, and health/psychosocial risks of bullying and other forms of victimization, how they occur across different social environments, and the strategies developed for their prevention, detection, and treatment.
Year-round carryover effects are driven by migration phenology for Hirundo rustica (Barn Swallow) wintering in West Africa
Authors: López-Calderón Cosme , Magallanes Sergio , García-Longoria Luz , Marzal Alfonso , Balbontín Javier
Published: May 2024

Recently, population declines have been reported for many migratory birds. Because of complex life cycles, determining the causes for such declines is often difficult. Thus, migratory birds are of special conservation interest. We studied the migratory behavior of Hirundo rustica (Barn Swallow) tagged with solar geolocators and determined carryover effects during the entire annual cycle from one breeding season to the next. We used a partial least squares path model (PLS-PM) to disentangle migratory and breeding events that occur in chronological order. In addition, we controlled for broad environmental conditions in the wintering grounds (NDVI and latitude) and the specific molting habitat (δ13C). We did not find a carryover effect from reproduction investment in the attachment year to breeding success in the subsequent year. Individuals that invested more in reproduction departed earlier from the breeding colonies, but this in turn did not affect the onset of autumn migration. Thus, the premigratory period should be acting as a buffer stage counteracting any previous carryover effects from reproduction investment. On the other hand, we found a long-lasting domino effect from the onset of autumn migration to subsequent breeding success, consistent with the notion of a migratory race. Specifically, individuals which started earlier in the autumn migration arrived earlier to the wintering grounds, started earlier in the spring migration arrived earlier to the breeding colonies, and had a higher breeding success. We highlight that the premigratory period (i.e., the time elapsed between departure from breeding areas and the onset of autumn migration) should be important for the life cycle of migratory species, but it has been frequently overlooked.
CVAs in Wider Restructurings
Authors: Watson James , Crawford Hannah
Published: May 2024

This chapter highlights the versatility of the company voluntary arrangement (CVA) as part of the UK's restructuring and insolvency toolkit. CVAs are used in various matters such as implementing a complex multi-party settlement with a diverse range of financial and intercompany creditors, compromising certain pension liabilities, preserving the key assets and value of the relevant business in line with the rules and regulations applied to the CVA company, and facilitating swifter distributions to creditors in line with long-tail administration process. Additionally, the chapter notes the CVA cases of interest correlated to TXU, T&N, Dana, Rangers Football Club plc, and EMF Global.
Jurisdiction, Effect of Approval, and Implementation
Authors: Phillips Henry , Jones Madeleine , Judd Daniel
Published: May 2024

This chapter looks into the jurisdiction, effect of approval and implementation of CVAs. Proposals made in respect of and for a company and its creditors, and composition in satisfaction of the company's debts are the core elements of jurisdiction. Thus, the company's financial position stays highly relevant with the CVA jurisdiction even if it does not depend on the company's insolvency. Moreover, the binding effect of a CVA depends on the statutory hypothesis and creditors will be treated like they have given consent to the arrangement. The chapter expounds on the definition of composition, scheme of the arrangement, creditors, ancillary rights, and necessary compromises in line with CVAs.
CVAs in the Cross-Border Context
Authors: Nolan Elaine , Stephenson Kate , O’Reilly SC Patrick F.
Published: May 2024

This chapter tackles the cross-border context of CVAs. In line with Brexit's effective date, companies registered under COMI, the UK, EU, EEA, and the CA 2006 in England, Wales, or Scotland are eligible for a CVA. The UNICTRAL Model Law and the Insolvency Regulations have been used as frameworks for greater international cooperation when it comes to outbound or cross-border recognitions. The chapter also notes the inbound assistance to foreign proceedings which could be offered by the English court. It mentions the types of assistance the English court could provide under the common law and Insolvency Act 1986 such as evidence and information gathering.
A survey on mean glandular dose in mammography examination and the factors affecting it in Shahid Sadoughi Hospital, Yazd, Iran
Authors: Asadollahzadeh Najmeh , Razavi SeidKazem , Zare Mohammad Hossein
Published: May 2024

Background: mammography is the gold standard in the early detection of breast cancer. Due to the increase in the rate of women suffering from this malignancy all over the world, this imaging modality has been widely used. Considering the side effects caused by ionizing radiation to measure the carcinogenic risk of mammography X-rays, mean glandular dose (MGD) is the best parameter to evaluate the dose received by patients undergoing mammography. The aims of this study were to measure MGD in mammography in mammographic craniocaudal (CC) and mediolateral oblique (MLO) projections and investigate the relationship of MGD with compressed breast thickness (CBT), body mass index, age of the patient, and device exposure conditions. Materials and methods: this cross-sectional analytical study was conducted on women aged 30–70 referring to the mammography unit of Shahid Sadoughi Hospital in Yazd city from May to August 2022. The TLD-GR 200 (thermoluminescence dosimeter) was placed on the breast of the patients for CC and MLO projections, and then the MGD was obtained by multiplying the entrance surface dose and the normalized glandular dose. Analysis of data (such as demographic information of patients, CBT, kVp, and mAs) was done by SPSS 23 software. The normality of the data was checked using Shapiro–Wilk tests. It was found that except for age, other variables did not have a normal distribution; therefore, equivalent parametric and nonparametric tests were used. In this regard, Spearman’s correlation was used to assess the correlation between variables. P-value < .05 was considered as level of significance. Results: The mean ± standard deviation (SD) age of patients was 47.3 ± 7.1 years. The median ± IQR (the interquartile range (IQR) is a measure of statistical dispersion, which is the spread of the data. It is defined as the difference between the 75th and 25th percentiles of the data.) (mean ± SD) value of MGD per woman was 1.2 ± 0.4 mGy (1.3 ± 0.3 mGy). The median ± IQR MGD in the MLO and CC projections was 1.6 ± 0.6 mGy and 0.9 ± 0.4 mGy, respectively. Significant relationships (P-value ≤ .001) were observed between MGD with CBT (R = 0.62) and age (R = −0.85). Conclusion: The results showed that the mammography unit at Shahid Sadoughi Hospital in Yazd is functioning properly. The calculated median ± IQR MGD per woman referring to this unit (1.2 ± 0.4 mGy) was clearly below the dose limit recommended by American College of Radiology and International Commission on Radiological Protection (3 mGy). Moreover, among the factors affecting MGD, the highest correlation was seen between MGD and age (R = −0.85).
“Close to My Community”: A Qualitative Study of Community Health Worker-Supported Teleaudiology Hearing Aid Services
Authors: Coco Laura , Leon Kimberly , Navarro Cecilia , Piper Rosie , Carvajal Scott , Marrone Nicole
Published: May 2024

Objectives:

Given well-documented disparities in rural and minority communities, alternative service delivery models that help improve access to hearing care are needed. This article reports on a study of older Latino adults with hearing loss who received hearing aid services with Community Health Workers (CHWs) providing support via teleaudiology. The present study used qualitative data to explore perceptions of this novel service delivery model.

Design:

Participants completed semistructured interviews related to their experiences in the intervention approximately 17 weeks after the hearing aid fitting appointment. Two coders independently coded the data, using an iterative deductive and inductive thematic analysis approach. Inter-rater reliability was good (κ = 0.80).

Results:

Of the 28 participants, 19 were interviewed (CHW group: n = 9, 8 females; non-CHW group: n = 10, 9 females). Both groups of participants reported experiencing barriers in access to care and reported positive experiences with teleaudiology and with hearing aids as part of the trial. CHW group participants reported interactions with patient-site facilitators that were indicative of patient-centeredness.

Conclusions:

Results demonstrate the feasibility and potential effectiveness of trained CHWs as patient-site facilitators in teleaudiology-delivered hearing aid services for adults.
Nerve compression after opponensplasty: a cadaveric study
Authors: Brown Chelsea R. , Deistler Kyle A. , Jain Lakshmi K. , Goyal Kanu S.
Published: May 2024

Background:

We describe the differences in thumb opposition between different opponensplasty tendon transfers and determine the immediate pressure on the median and ulnar nerves incurred by each transfer.

Methods:

Using fresh frozen cadavers (8 specimens), opponensplasties were performed using extensor indicis proprius (EIP), flexor digitorum superficialis (FDS) with flexor carpi ulnaris (FCU) pulley, palmaris longus (PL, Camitz procedure), and PL utilizing the thenar fascia as a pulley (PLwP). Each tendon transfer was tensioned, and the thumb flexion, abduction and pronation were measured. The pressure on the median and ulnar nerves were measured for each tendon transfer at varying tensions.

Results:

There were no differences seen in flexion or pronation between any of the four tendon transfers. FDS, PL and PLwP demonstrated more abduction than the EIP transfer, however differences were less than 10°. EIP and FDS transfers caused significantly more pressure on the median nerve than PL or PLwP at high tendon tensions. Both EIP and FDS tendon transfers caused significantly more pressure on the ulnar nerve than PL or PLwP, and the pressure increased as tension on the transfer increased. No pressure differences were seen between PL and PLwP.

Conclusions:

No significant differences were seen in thumb flexion or pronation between the four tendon transfers. Differences were seen for abduction with EIP showing the least amount of abduction. EIP and FDS caused more median nerve compression than PL transfers at high tension. Both EIP and FDS tendon transfers cause more ulnar nerve compression than PL transfers at all tensions.

Level of Evidence

Level: V
Nanotechnology: The Future for Diagnostic and Therapeutic Intervention in Cardiovascular Diseases is Here
Authors: Elsaygh Jude , Zaher Anas , Parikh Manish A. , Frishman William H. , Peterson Stephen J.
Published: May 2024

With advances in technology and medicine over the last 3 decades, cardiovascular medicine has evolved tremendously. Nanotechnology provides a promising future in personalized precision medicine. In this review, we delve into the current and prospective applications of nanotechnology and nanoparticles in cardiology. Nanotechnology has allowed for point-of-care testing such as high-sensitivity troponins, as well as more precise cardiac imaging. This review is focused on 3 diseases within cardiology: coronary artery disease, heart failure, and valvular heart disease. The use of nanoparticles in coronary stents has shown success in preventing in-stent thrombosis, as well as using nanosized drug delivery medications to prevent neointimal proliferation in a way that spares systemic toxicity. In addition, by using nanoparticles as drug delivery systems, nanotechnology can be utilized in the delivery of goal-directed medical therapy in heart failure patients. It has also been shown to improve cell therapy in this patient population by helping in cell retention of grafts. Finally, the use of nanoparticles in the manufacturing of bioprosthetic valves provides a promising future for the longevity and success of cardiac valve repair and replacement.
Association between triglyceride-glucose index and femoral bone mineral density in community-dwelling, nondiabetic men and women: a NHANES analysis of 1,928 US individuals
Authors: Chen Hailing , Hu Jianpeng , Li Jufen , Li Quan , Lan Ling
Published: May 2024

Objective

To determine the potential association between the triglyceride-glucose (TyG) index and bone mineral density (BMD) in community-dwelling adults without diabetes using a nationally representative database from the United States (US).

Methods

Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, 2013-2014, and 2017-2018. Men and postmenopausal women aged ≥50 years with complete data on femoral neck BMD, triglycerides, and fasting plasma glucose levels were eligible for inclusion. Participants with diabetes, history of malignancy, thyroid disease, underweight status, end-stage kidney disease, rheumatoid arthritis, estrogen/selective estrogen receptor modulators, bisphosphonate or bone resorption inhibitors, or missing dataset weight values were excluded. Univariate and multivariable logistic regression analyses were performed to determine the associations between low BMD, TyG index, and other study variables.

Results

A total of 1,844 participants (1,161 men and 683 women) were included, representing 31,517,106 community-dwelling individuals in the US. The mean age of the study population was 60.7 years old, and 26.7% of the men and 60.4% of the women had low bone density. In both males and females, the mean TyG index was 8.6. After adjusting for demographic, lifestyle, and clinical factors, no significant association was observed between TyG and femoral neck BMD among men (adjusted odds ratio [aOR] = −0.0002, 95% confidence interval [CI]: −0.02 to 0.02) and women (aBeta = 0.005, 95% CI: −0.02 to 0.04). Similarly, no significant association was observed between TyG index and the odds for low bone density among men (aOR = 1.09, 95% CI: 0.73-1.63) and women (aOR = 0.99, 95% CI: 0.49-2.01).

Conclusions

Based on data from a large sample in the US, this study did not find an association between the TyG index and femoral neck BMD or the occurrence of low bone density in community-dwelling males and females without diabetes.
Vision of the future: large language models in ophthalmology
Authors: Tailor Prashant D. , D'Souza Haley S. , Li Hanzhou , Starr Matthew R.
Published: May 2024

Purpose of review

Large language models (LLMs) are rapidly entering the landscape of medicine in areas from patient interaction to clinical decision-making. This review discusses the evolving role of LLMs in ophthalmology, focusing on their current applications and future potential in enhancing ophthalmic care.

Recent findings

LLMs in ophthalmology have demonstrated potential in improving patient communication and aiding preliminary diagnostics because of their ability to process complex language and generate human-like domain-specific interactions. However, some studies have shown potential for harm and there have been no prospective real-world studies evaluating the safety and efficacy of LLMs in practice.

While current applications are largely theoretical and require rigorous safety testing before implementation, LLMs exhibit promise in augmenting patient care quality and efficiency. Challenges such as data privacy and user acceptance must be overcome before LLMs can be fully integrated into clinical practice.
Peripherally restricted cannabinoid and mu-opioid receptor agonists synergistically attenuate neuropathic mechanical hypersensitivity in mice
Authors: Limerick Gerard , Uniyal Ankit , Ford Neil , He ShaoQiu , Grenald Shaness A. , Zhang Chi , Cui Xiang , Sivanesan Eellan , Dong Xinzhong , Guan Yun , Raja Srinivasa N.
Published: May 2024

Many medications commonly used to treat neuropathic pain are associated with significant, dose-limiting adverse effects, including sedation, dizziness, and fatigue. These adverse effects are due to the activity of these medications within the central nervous system. The objective of this work was to investigate the interactions between peripherally restricted cannabinoid receptor and mu-opioid receptor (MOR) agonists on ongoing and evoked neuropathic pain behaviors in mouse models. RNAscope analysis of cannabinoid receptor type 1 (CB1R) and MOR mRNA demonstrated that the mRNA of both receptors is colocalized in both mouse and human dorsal root ganglion. Single-cell RNAseq of dorsal root ganglion from chronic constriction injury mice showed that the mRNA of both receptors (Cnr1 and Oprm1) is coexpressed across different neuron clusters. Myc-CB1R and FLAG-MOR were cotransfected into immortalized HEK-293T cells and were found to interact at a subcellular level. We also find that CB-13 (a peripherally restricted dual CB1R and cannabinoid receptor type 2 agonist) and DALDA (a peripherally restricted MOR agonist) both attenuate mechanical hypersensitivity in a murine model of neuropathic pain. Using isobolographic analysis, we demonstrate that when coadministered, these agents synergistically attenuate mechanical hypersensitivity. Importantly, combination dosing of these agents does not cause any detectable preferential behaviors or motor impairment. However, repeated dosing of these agents is associated with the development of tolerance to these drugs. Collectively, these findings suggest that leveraging synergistic pain inhibition between cannabinoid receptor and MOR agonists in peripheral sensory neurons may be worth examining in patients with neuropathic pain.
INHIBITION OF INTEGRIN VLA-3 AND TETRASPANIN CD151 PROTECTS AGAINST NEUTROPHIL-MEDIATED ENDOTHELIAL DAMAGE
Authors: Ciambella Chelsey , Witt Hadley , Dickinson Catherine M. , Smith Madison L. , Coburn Nicholas , Messina Nicholas , Heffernan Daithi S. , Kim Minsoo , Reichner Jonathan S.
Published: May 2024

Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. However, in cases of sepsis, the interaction of endothelial cells with highly activated neutrophils can cause damage vascular damage. The identification of molecules that are essential for neutrophil diapedesis may reveal targets of therapeutic opportunity for preservation of endothelial function in the presence of critical illness. We tested the hypothesis that inhibition of neutrophil β1 integrin very late antigen-3 (VLA-3; α3β1) and/or inhibition of the tetraspanin (TM4) family member CD151 would protect against neutrophil-mediated loss of endothelial function. Methods: Blood was obtained from septic patients or healthy donors. Neutrophils were purified, and aliquots were treated with/without proinflammatory molecules. Confluent human umbilical vascular endothelial cells were activated with TNF-α. Electric cell impedance sensing was used to determine monolayer resistance over time after the addition of neutrophils that were treated with blocking antibodies against VLA-3 and/or CD151 or isotype controls. Groups (depending on relevancy) were analyzed by Mann-Whitney U test, Wilcoxon test, or repeated-measures one-way ANOVA. Results: Neutrophils from septic patients and neutrophils activated ex vivo reduced endothelial monolayer resistance to a greater extent than neutrophils from healthy donors. Antibody blockade of VLA-3 and/or CD151 significantly reduced activation-associated endothelial damage. Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.
PET-based brain molecular connectivity in neurodegenerative disease
Authors: Hanania Jordan U. , Reimers Erik , Bevington Connor W.J. , Sossi Vesna
Published: May 2024

Purpose of review

Molecular imaging has traditionally been used and interpreted primarily in the context of localized and relatively static neurochemical processes. New understanding of brain function and development of novel molecular imaging protocols and analysis methods highlights the relevance of molecular networks that co-exist and interact with functional and structural networks. Although the concept and evidence of disease-specific metabolic brain patterns has existed for some time, only recently has such an approach been applied in the neurotransmitter domain and in the context of multitracer and multimodal studies. This review briefly summarizes initial findings and highlights emerging applications enabled by this new approach.

Recent findings

Connectivity based approaches applied to molecular and multimodal imaging have uncovered molecular networks with neurodegeneration-related alterations to metabolism and neurotransmission that uniquely relate to clinical findings; better disease stratification paradigms; an improved understanding of the relationships between neurochemical and functional networks and their related alterations, although the directionality of these relationships are still unresolved; and a new understanding of the molecular underpinning of disease-related alteration in resting-state brain activity.

Connectivity approaches are poised to greatly enhance the information that can be extracted from molecular imaging. While currently mostly contributing to enhancing understanding of brain function, they are highly likely to contribute to the identification of specific biomarkers that will improve disease management and clinical care.
Phloretin inhibits transmissible gastroenteritis virus proliferation via multiple mechanisms
Authors: Duan Yuting , Li Haichuan , Huang Shuai , Li Yaoming , Chen Shuyi , Xie Lilan
Published: May 2024

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpro might be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.
Electroencephalogram (EEG) Classification using a bio-inspired Deep Oscillatory Neural Network
Authors: Ghosh Sayan , Vigneswaran C. , Rohan NR , Chakravarthy V.Srinivasa
Published: May 2024

In this paper, we propose two models of oscillatory neural networks - the Deep Oscillatory Neural Network (DONN) and a convolutional variation of it named Oscillatory Convolutional Neural Network (OCNN) – and apply the models to a variety of problems involving the classification and prediction of Electroencephalogram (EEG) signals. Deep neural networks applied to signal processing problems will have to incorporate various architectural features to remember the history of the input signals e.g., loops between the layers, “gated” neurons, and tapped delay lines. But real brains have rich dynamics expressed in terms of frequency bands like alpha, beta, gamma, delta, etc. To incorporate this aspect of brain dynamics in a Recurrent Neural Network (RNN) we propose to use nonlinear oscillators as dynamic neuron models in the hidden layers. The two oscillatory deep neural networks proposed are applied to the following EEG classification and prediction problems: Prediction of nearby EEG channels, classification of single-channel EEG data (healthy vs. epileptic, different stages of sleep stage classification), and multi-channel EEG data (Epileptic vs. Normal, Left vs. right-hand Motor imagery movement, and healthy vs. Claustrophobic EEG).
The Fat4 intracellular domain controls turnover of Fat4/Dchs1 planar polarity membrane complexes
Authors: Easa Yathreb , Loza Olga , cohen Roie , Sprinzak David
Published: May 2024

The Fat/Dachsous (Ft/Ds) pathway is a highly conserved pathway regulating planar cell polarity (PCP) across different animal species. Proteins from the Ft and Ds family are large transmembrane protocadherins that form heterophilic complexes on the boundaries between cells. Fat4 and Dchs1, the main mammalian homologues of this pathway, have been implicated in PCP in various epithelial tissues and were shown to form extremely stable complexes at the boundaries between cells. It is unclear however, what are the dynamics controlling such stable boundary complexes, and how the formation and turnover of these complexes is regulated. Here, we use quantitative live imaging to elucidate the role of the intracellular domains (ICD) of Fat4 and Dchs1 in regulating Fat4/Dchs1 complex dynamics. We show that removing the ICD of Fat4 results in a reduction of both Trans-endocytosis (TEC) of Dchs1 into the Fat4 cells and boundary accumulation, but does not affect the diffusion of the complexes at the boundary. We further show that the ICD of Fat4 controls the turnover rate of Fat4/Dchs1 complexes. Finally, we find that while actin polymerization is required for maintaining the boundary accumulation of Fat4/Dchs1 complexes, we do not identify correlations between Fat4/Dchs1 complexes and local actin accumulation. Overall, we suggest that the Fat4 ICD is important for the turnover and plasticity of the highly stable Fat4/Dchs1 complexes associated with PCP.

Statement of Significance

The purpose of this study is to elucidate the dynamics leading to the formation and maintenance of Fat4/Dchs1 complexes at the cell boundary and how it is affected by the ICD of Fat4 in mammals. The insights from this work are important for obtaining a mechanistic molecular framework for understanding formation of planar cell polarity as well as for highlighting how cell boundary membrane complexes are regulated.
Pioneer factor ETV2 safeguards endothelial cell specification by recruiting the repressor REST to restrict alternative lineage commitment
Authors: Chen Danyang , Fan Xiaonuo , Wang Kai , Gong Liyan , Melero-Martin Juan M. , Pu William T.
Published: May 2024

Mechanisms of cell fate specification remain a central question for developmental biology and regenerative medicine. The pioneer factor ETV2 is a master regulator for the endothelial cell (EC) lineage specification. Here, we studied mechanisms of ETV2-driven fate specification using a highly efficient system in which ETV2 directs human induced pluripotent stem cell-derived mesodermal progenitors to form ECs over two days. By applying CUT&RUN, single-cell RNA-sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analyses, we characterized the transcriptomic profiles, chromatin landscapes, dynamic cis-regulatory elements (CREs), and molecular features of EC cell differentiation mediated by ETV2. This defined the scope of ETV2 pioneering activity and identified its direct downstream target genes. Induced ETV2 expression both directed specification of endothelial progenitors and suppressed acquisition of alternative fates. Functional screening and candidate validation revealed cofactors essential for efficient EC specification, including the transcriptional activator GABPA. Surprisingly, the transcriptional repressor REST was also necessary for efficient EC specification. ETV2 recruited REST to occupy and repress non-EC lineage genes. Collectively, our study provides an unparalleled molecular analysis of EC specification at single-cell resolution and identifies the important role of pioneer factors to recruit repressors that suppress commitment to alternative lineages.