bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of parental age and polymer composition on short tandem repeat de novo mutation rates
Authors: Goldberg Michael E , Noyes Michelle D , Eichler Evan E , Quinlan Aaron R , Harris Kelley
Published: February 2024

Short tandem repeats (STRs) are hotspots of genomic variability in the human germline because of their high mutation rates, which have long been attributed largely to polymerase slippage during DNA replication. This model suggests that STR mutation rates should scale linearly with a father's age, as progenitor cells continually divide after puberty. In contrast, it suggests that STR mutation rates should not scale with a mother's age at her child's conception, since oocytes spend a mother's reproductive years arrested in meiosis II and undergo a fixed number of cell divisions that are independent of the age at ovulation. Yet, mirroring recent findings, we find that STR mutation rates covary with paternal and maternal age, implying that some STR mutations are caused by DNA damage in quiescent cells rather than polymerase slippage in replicating progenitor cells. These results echo the recent finding that DNA damage in oocytes is a significant source of de novo single nucleotide variants and corroborate evidence of STR expansion in postmitotic cells. However, we find that the maternal age effect is not confined to known hotspots of oocyte mutagenesis, nor are postzygotic mutations likely to contribute significantly. STR nucleotide composition demonstrates divergent effects on de novo mutation (DNM) rates between sexes. Unlike the paternal lineage, maternally derived DNMs at A/T STRs display a significantly greater association with maternal age than DNMs at G/C-containing STRs. These observations may suggest the mechanism and developmental timing of certain STR mutations and contradict prior attribution of replication slippage as the primary mechanism of STR mutagenesis.
Assessing the Nepalese health system’s readiness to manage gender-based violence and deliver psychosocial counselling
Authors: Deuba Keshab , Shrestha Rachana , Koju Reena , Jha Vijay Kumar , Lamichhane Achyut , Mehra Devika , Ekström Anna Mia
Published: February 2024

Violence against women (VAW), particularly intimate partner violence (IPV) or domestic violence, is a major public health issue, garnering more attention globally post-coronavirus disease 2019 (COVID-19) lockdown. Health providers often represent the first point of contact for IPV victims. Thus, health systems and health providers must be equipped to address survivors’ physical, sexual and mental health care needs. However, there is a notable lack of evidence regarding such readiness in Nepal. This study, utilizing a concurrent triangulation design, evaluated the readiness of public health facilities in Nepal’s Madhesh Province in managing VAW, focusing on providers’ motivation to offer psychosocial counselling to survivors. A cross-sectional study was conducted across 11 hospitals and 17 primary health care centres, where 46 health care providers were interviewed in February–April 2022. The study employed the World Health Organization’s tools for policy readiness and the Physician Readiness to Manage IPV Survey for data collection. Quantitative and qualitative data were collected via face-to-face interviews and analysed using descriptive and content analysis, respectively. Only around 28% of health facilities had trained their staff in the management of VAW. Two out of 11 hospitals had a psychiatrist, and a psychosocial counsellor was available in four hospitals and two out of 17 primary health care centres. Two-thirds of all health facilities had designated rooms for physical examinations, but only a minority had separate rooms for counselling. Though a few health facilities had guidelines for violence management, the implementation of these guidelines and the referral networks were notably weak. Hospitals with one-stop crisis management centres demonstrated readiness in VAW management. Health providers acknowledged the burden of IPV or domestic violence and expressed motivation to deliver psychosocial counselling, but many had limited knowledge. This barrier can only be resolved through appropriate training and investment in violence management skills at all tiers of the health system.
Ion Transport Basis of Diarrhea, Paneth Cell Metaplasia, and Upregulation of Mechanosensory Pathway in Anti-CD40 Colitis Mice
Authors: Jayawardena Dulari , Anbazhagan Arivarasu N , Majumder Apurba , Akram Ramsha , Nazmi Ali , Kaur Ramandeep , Kumar Anoop , Saksena Seema , Olivares-Villagómez Danyvid , Dudeja Pradeep K
Published: February 2024

Background

Anti-Cluster of differentiation (CD)-40-induced colitis, driven by innate inflammatory responses in the intestine, is a potent animal model exhibiting IBD pathophysiology including diarrhea. However, the ion transport basis of diarrhea and some key mucosal pathways (Paneth cells, stem cell niche, and mechanosensory) in this model have not been investigated.

Methods

Mucosal scrapings and intestinal tissue from control and CD40 antibody (150 µg) treated Rag2−/− mice were examined for gut inflammation, Paneth cell numbers, expression of key transporters, tight/adherens junction proteins, stem cell niche, and mechanosensory pathway via hematoxylin and eosin staining, quantitative polymerase chain reaction, and western blotting.

Results

Compared with control, anti-CD40 antibody treatment resulted in a significant loss of body weight (P < .05) and diarrhea at day 3 postinjection. Distal colonic tissues of anti-CD40 mice exhibited increased inflammatory infiltrates, higher claudin-2 expression, and appearance of Paneth cell–like structures indicative of Paneth cell metaplasia. Significantly reduced expression (P < .005) of downregulated in adenoma (key Cl- transporter), P-glycoprotein/multidrug resistantance-1 (MDR1, xenobiotic transporter), and adherens junction protein E-cadherin (~2-fold P < .05) was also observed in the colon of anti-CD40 colitis mice. Interestingly, there were also marked alterations in the stem cell markers and upregulation of the mechanosensory YAP-TAZ pathway, suggesting the activation of alternate regeneration pathway post-tissue injury in this model.

Conclusion

Our data demonstrate that the anti-CD40 colitis model shows key features of IBD observed in the human disease, hence making it a suitable model to investigate the pathophysiology of ulcerative colitis (UC).
The knowledge, attitude, and practice of the public regarding household pharmaceutical waste disposal: a systematic review (2013–2023)
Authors: Hiew Sheng Yuan , Low Bee Yean
Published: February 2024

Objective

The improper disposal of household pharmaceutical waste (HPW) is an emerging cause of environmental pollution. Behavioural practices are intricately linked to individuals’ knowledge levels and attitudes. Thus, this systematic review aims to assess the knowledge, attitude, and practice (KAP) of HPW disposal among the public and to examine the interconnectedness of these KAP components.

Methods

A literature review for articles published from 2013 to 2023 was carried out in scientific databases PubMed, Scopus, and Web of Science, identifying quantitative studies involving the assessment of KAP of the public concerning HPW disposal.

Results

This review incorporated 12 studies conducted in Africa, South Asia, and Southeast Asia. Nine studies highlighted a consistent trend of limited to inadequate knowledge regarding safe medication disposal. Notwithstanding, respondents largely exhibited a positive attitude towards proper medication disposal. This encouraging disposition, unfortunately, stands in stark contrast to the reported practices, which appeared to be inadequate. This dissonance might be due to a deficit in accessible disposal facilities and information, compounded with insufficient guidance from healthcare professionals. Interestingly, the majority expressed support for take-back programs aimed at managing unused and expired medications.

Conclusion

This review identified a need for a comprehensive understanding of the interconnected dynamics among KAP components regarding safe medication disposal. The exploration of theoretical behavioural frameworks could help predict public intentions to adopt safe medication disposal practices. Ultimately, a multi-faceted approach that addresses knowledge gaps, reinforces positive attitudes, and promotes accessible safe medication disposal services can collectively safeguard the environment and public health.
The slow viscous flow around a general rectangular doubly-periodic arrays of infinite slender cylinders
Authors: Koens Lyndon , Vernekar Rohan , Krüger Timm , Lisicki Maciej , Inglis David W
Published: February 2024

The slow viscous flow through a doubly-periodic array of cylinders does not have an analytical solution. However, as a reduced model for the flow within fibrous porous media and microfluidic arrays, this solution is important for many real-world systems. We asymptotically determine the flow around a general rectangular doubly-periodic array of infinite slender cylinders, extending the existing asymptotic solution for square arrays. The flow in the cell is represented by a collection of doubly-periodic, rapidly-convergent two-dimensional singularity solutions, and the boundary condition on the surface of the cylinder is solved asymptotically in powers of the cylinder radius. The asymptotic solution provides an easily computed closed-form estimate for the flow and forces as a function of the radius and the dimensions of the cell. The force is compared to results from lattice-Boltzmann simulations of low-Reynolds-number flows in the same geometry, and the accuracy of the no-slip condition on the surface of the cylinder, predicted by the asymptotic theory, is assessed. Finally, the behaviour of the flow, flux, force and effective permeability of the cell is investigated as a function of the geometric parameters. The structure of the asymptotic permeability is consistent with previous single-geometry predictions but provides a closed-form estimate for how the aspect ratio of the cell changes the leading-order behaviour. These models could be used to help understand the flows within porous systems composed of fibres and systems involving periodic arrays such as systems based on deterministic lateral displacement .
Norm critique and the dialectics of Hegelian recognition
Authors: Iversen Simon Nørgaard
Published: February 2024

This article examines the relevance of Hegel’s theory of recognition within educational theory and practice in relation to the development of a non-affirmative theory of education. The article argues that Hegel’s theory of recognition can serve as a fruitful starting point for articulating an educational theory that can contribute to the subject’s open-ended formation in modern society. To start with, the article surveys the connection between Hegel’s educational thought and his concept of recognition. Against this backdrop, the article singles out how Hegel’s theory of recognition provides a compelling theory of intersubjectivity that calls attention to the role of norms in personal development and the construction of the social world. In continuation of a non-affirmative principle, it is argued that Hegelian recognition underlines, first, that the subject’s formation can fruitfully be an open-ended and dynamic process and, second, that in order to underpin this process it is necessary to critically assess norms and norm-generating practices within an educational context.
Rationale and Precautioning Clauses: Insights from A’ingae
Authors: Dąbkowski Maksymilian , AnderBois Scott
Published: February 2024

We describe and analyze the semantics of rationale and precautioning clauses (i.e. in order to- and lest-clauses) through a detailed case study of two operators in A’ingae (or Cofán, iso 639-3: con, an Amazonian isolate): the infinitive -ye ‘inf’ and the apprehensional -sa’ne ‘appr.’

We provide a new account of rationale semantics and the first formal account of precautioning semantics. We propose that in structures such as [$p$ [(in order) to$q$]] or [$p$ [$q$-ye]], the rationale operator (underlined) encodes modal semantics where the goal worlds of the actor responsible for $p$ achieve $q$.

In structures such as [$p$ [lest$q$]] or [$p$ [$q$-sa’ne]], the precautioning operator encodes modal semantics where the actor’s goal worlds avoid a recoverable situation $r$ which entails $q$ ($r\Rightarrow q$).

We observe and account for three apparent asymmetries within the domain of rationale and precautioning semantics, which we dub precautioning semantics asymmetry, rationale polarity asymmetry, and precautioning encoding asymmetry. We thus elucidate the relation between rationale and precautioning clauses and make substantial predictions with respect to the cross-linguistic inventories of rationale and precautioning operators.
Quelques in French: a Clustered Plural
Authors: Gréa Philippe
Published: February 2024

We present the result of a corpus study on the difference between quelques ‘a few’ and plusieurs ‘several’. On this basis, we propose a categorization of the nouns significantly attracted by quelques and argue for an understanding of the distinction in topological terms ( Grimm, 2012a, 2012b; Wągiel, 2018, 2019). A series of observations, focusing successively on the aggregate nouns (pomme de terre ‘potato’), a sub-class of ‘fence’ nouns (gribouillis ‘scrawl’) and the mass plurals (victuailles ‘victuals’) leads us to argue that quelques Npl ‘a few Npl’ is a ‘clustered’ plural, which is true of a (more or less) cohesive set of connected entities, while plusieurs ‘several’ quantifies over sets of maximally strongly self-connected (mssc) entities. We will show that this principle can also be generalized to the temporal domain. We shall see that this distinction between the two determiners has numerous consequences on atomicity, the mass-count distinction, the possibility of counting individuals, and especially, on the existence of an individuation scale in the nominal domain.
Primary prostate lymphoma: a rare presentation of lower urinary tract symptoms in young aged patient
Authors: Alhamadani Mohammed Ali , Pecherkin Aleksandr , Doyle Terrence
Published: February 2024

Primary prostatic lymphoma is a rare prostate malignancy that accounts for 0.09% of prostate cancer and 0.1% of lymphoma. Clinical misdiagnosis is common as majority of cases present with non-specific urinary symptoms like other prostatic diseases or prostatic cancer. Early diagnosis is of significant paramount as prognosis is dependent on histological type and tumour staging at the time of diagnosis. Urologists should remain aware of rare histological types of prostate cancer as delayed diagnosis of primary prostate lymphoma can be detrimental and lead to advanced disease causing serious sequelae i.e renal failure in addition to the primary pathology.
Torsion of Meckel’s diverticulum—a case report and literature review
Authors: Ho Kah A , Srinivasan Rajkumar
Published: February 2024

Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Torsion is a rare complication of MD with only 48 cases described in the English literature to date. We describe a case of a 22-year-old male who presented to the emergency department with lower abdominal pain. Pre-operative computed tomography scan suggested a torted MD. This was confirmed on diagnostic laparoscopy and managed with segmental resection of the MD and a concurrent appendicectomy. Histopathology confirmed torsion of MD and a normal appendix. The patient recovered well without any complications. Torsion occurs invariably with giant MD defined as a length of >5 cm. Surgical options for MD include diverticulectomy, wedge resection and segmental resection via laparoscopic or open approach. The rate of pre-operative diagnosis remains low but with advances in imaging and awareness of this condition, this is likely to increase with time.
Yesterday and the Day Before in Semitic
Authors: Rubin Aaron D
Published: February 2024

In addition to reflexes of Proto-Semitic*timāli, the Semitic languages use a variety of innovative words meaning ‘yesterday’, as well as numerous different words and phrases used to mean ‘the day before yesterday’ and sometimes even earlier days. This article examines these various adverbs or adverbial phrases in the diverse Semitic languages, both ancient and modern, coming from a variety of semantic developments, some of which are typologically unusual.
Treadmill Exercise Testing
Authors: Thomas Gregory S. , Wann L. Samuel
Published: February 2024

Developed over a century ago, exercise testing remains a powerful tool in the detection of cardiac disease. Its current chief role is to evaluate for myocardial ischemia with and without adjunctive imaging. Thoroughly updated and referenced, the chapter reviews the underlying foundation of exercise testing and provides tips and tricks to make the most of exercise testing. These include which leads best predict CAD during exercise testing, how to use lead aVR to detect severe CAD, and why ST depression in the inferior leads is unreliable in the detection of ischemia. A rule of thumb to estimate METs achieved on the Bruce protocol by adding 1 to the number of minutes of exercise is discussed. An updated formula to estimate maximum predicted heart rate is reviewed, as is the rationale for achieving maximum exercise with at least 85% of maximum predicted heart rate or an ischemic endpoint.
SPECT MPI for Risk Assessment in Special Groups
Authors: Cuocolo Alberto , Zampella Emilia , Gaudieri Valeria , Assante Roberta
Published: February 2024

Risk assessment in patients with suspected CAD is an important step to identify those at high risk of disease who require a specified diagnostic and therapeutic approach to prevent adverse events at follow-up. At present many cardiac prediction models are available for risk assessment in order to guide lifestyle modification and treatment decisions and to estimate future population trends in cardiovascular morbidity and mortality. Yet, most CAD risk prediction tools do not account for the high event rates in some populations, such as diabetic individuals or kidney and liver transplantation candidates. Gated SPECT MPI provides important prognostic information on LV function and on the extent and severity of myocardial perfusion abnormalities, including stress-induced ischemia. MPI has an important diagnostic and prognostic rule in specific patient populations, including subjects with asymptomatic CAD, diabetes mellitus, obesity, and kidney or liver disease, which are indicated as CAD equivalent populations. This chapter focuses on the role of SPECT MPI in risk assessment of specific populations at higher risk of cardiac events.
Nuclear Cardiology Report Generation
Authors: AlJaroudi Wael A.
Published: February 2024

Stress SPECT MPI remains one of the most commonly ordered noninvasive imaging modalities. Yet, significant diversity in report format, content, and language exists. In part, this is due to the variation in style and heterogeneity of lexicon used by providers across many specialties (cardiology, nuclear medicine, and radiology); the complexity of data elements and not uncommonly discordant results; and resistance to change. While such flexibility allows for more subjectivity in reporting, it also causes confusion and increases the risk of medico-legal litigation. Report standardization offers a structured way to list all the important and required data elements; creates an infrastructure for consistent expression; improves communication among providers; and establishes a format to audit quality metrics and ensure best practice for patient management. The aim of this chapter is to offer a practical approach to a nuclear stress SPECT MPI report that embodies the main concepts and framework set forth by the professional guidelines and societies. A good report must follow a standard template containing key headlines and elements and must be consistently clear, concise, and clinically relevant. It should answer the question raised by the requesting physician. The reader must pay careful attention to the terminology used in the report, while avoiding pragmatic interpretations that add confusion to the mix and may lead to unwanted downstream testing. The chapter highlights common pitfalls and suggests alternatives to inaccurate or confusing language. The chapter concludes with a future perspective in the era of digitization, machine learning, and artificial intelligence.
Essentials of Nuclear Cardiac Imaging
Authors: Iskandrian Ami E. , Hage Fadi G. , Bhambhvani Pradeep , Garcia Ernest V.
Published: February 2024

This chapter is a quick reference to common questions encountered by practitioners in the field on a regular basis. It is intended to be short, concise, and accurate. We do not provide references, tables, or figures; these belong in the chapters, and there are plenty of them. The opinions expressed are those of the authors. We could have selected a thousand more questions, but we opted for a few common and recurring ones. We recognize that some of the measurements discussed here could be made just as good or even better by other imaging modalities, but our emphasis is on nuclear imaging. The nature of these questions is either technical or clinical, as it should be, and if we missed a burning question in your mind, we apologize in advance. We adopted the rule of 10—devoting 10 points to answer each question.
Radiation Physics and Radiation Safety
Authors: Murphy Paul H. , Galt James R.
Published: February 2024

Nuclear cardiology requires tracers, or radiopharmaceuticals, based on radionuclides that provide photons suitable for imaging, give a radiation dose to the patient that is as low as possible, and can be handled safely by personnel. Atomic processes involve the whole atom (the nucleus and its bound electrons), while nuclear processes are restricted to the nucleus (neutrons and protons). All emissions that radiate from atoms and nuclei are due to excess energy and are released in order to reach a stable ground state. X-rays are produced outside of the nucleus, while alpha particles, beta particles, and gamma rays originate inside the nucleus. As radiation in the form of rays and particles travels through tissue, it imparts energy to the tissue that can result in damage. Dosimetry is the measurement of this radiation absorbed dose. Radionuclides that are used in nuclear cardiology can be produced in nuclear reactors, in particle accelerators called cyclotrons, or in portable devices called generators. Handling and administering radiopharmaceuticals requires strict attention to radiation safety and to the principle of ALARA.
Gated SPECT MPI
Authors: Henzlova Milena J. , McMahon Sean R. , Duvall W. Lane
Published: February 2024

The acquisition of high-quality nuclear cardiac imaging requires coordination of a number of elements that are optimized for each patient. Equipment must be calibrated and up to date while lab personnel need to be proficient with pre-imaging quality control, imaging protocols, and processing. Three radiotracers for myocardial perfusion imaging are currently available for clinical use in the United States: thallium 201 (Tl-201) and two technetium-99m (Tc-99m)-labeled agents, Tc-99m sestamibi and Tc-99m tetrofosmin. Myocardial perfusion imaging protocols respect the characteristics of available radiotracers, with Tc-99m-based 1-day, rest–stress protocols being the most common. Imaging has been performed for decades with conventional NaI SPECT cameras but new, more efficient solid-state cameras now allow for either lower tracer dose or shorter imaging time, or a combination of both.
Diagnosis and Risk Assessment with SPECT MPI
Authors: Gomez Javier , Doukky Rami
Published: February 2024

Over the last four decades, the diagnostic and prognostic value of MPI with SPECT has been established by a wealth of data. The value of SPECT MPI has been consistently demonstrated regardless of the stress modality, radiotracer, or instrumentation used. The diagnostic performance of MPI depends on the pretest probability of CAD in the population studied, with the highest yield being among patients with an intermediate pretest probability. The excellent prognostic value of a normal SPECT MPI has been documented in tens of thousands of patients, conferring an annualized MACE risk of less than 1% for exercise stress and less than 1.5% for pharmacologic stress. An abnormal SPECT MPI is associated with a multi-fold increase in the risk of MACE with multiple factors predicting high risk, such as the presence, extent, reversibility, severity, and number of perfusion abnormalities. Furthermore, several non-perfusion variables are associated with increased risk; these include LV dysfunction, TID, and abnormal lung uptake. The incorporation of CACS from hybrid SPECT/CT systems adds incremental prognostic value beyond perfusion data alone. The use of SPECT MPI as a gatekeeper to ICA has been shown to be cost-effective, reducing rates of coronary angiography and revascularization and their associated costs, without a significant difference in cardiovascular outcomes. In summary, the use of SPECT MPI for detection and prognostication of CAD is supported by a vast amount of data and decades of clinical use. SPECT MPI can guide management decisions, can identify patients likely to benefit from revascularization, and is cost-effective.
Evaluation of Patients with Chest Pain in the Emergency Department
Authors: Kaso Elona Rrapo , Bourque Jamieson M.
Published: February 2024

This chapter on the evaluation of patients with chest pain who present to the ED examines the unique benefits and challenges of applying nuclear cardiac and other noninvasive imaging modalities in the triage and management of patients in this care setting. It reviews the robust evidence for SPECT MPI and new advances in this imaging modality. SPECT MPI results in a comprehensive evaluation with increased prognostic and diagnostic value and superior clinical outcomes as well as reductions in cost, hospitalizations, and inappropriate discharges from the ED. The unique advantages and challenges of PET MPI will also be discussed, including specific populations in which this advanced modality is most likely to be helpful, such as evaluation of microvascular angina. Sections on the use of acute chest pain rest imaging and the role and utility of noninvasive imaging in the era of high-sensitivity troponin are included. The chapter will conclude with analysis of the comparative effectiveness and relative strengths and weaknesses of the use of stress echocardiography, stress cardiovascular magnetic resonance imaging, and computed tomographic coronary angiography in evaluation of chest pain in the ED.
Imaging Sarcoid Heart Disease
Authors: Rosenthal David G. , Bravo Paco E.
Published: February 2024

Cardiac sarcoidosis is a chronic inflammatory disorder that can affect the heart in up to one-fifth of cases, often coexists with myocardial fibrosis, and can lead to sudden cardiac death and heart failure progression. It is characterized by infiltration of noncaseating granulomas anywhere within the myocardium and surrounding tissues, most commonly affecting the basal segments of the interventricular septum. Recent advancements in the early diagnosis, risk stratification, and monitoring of disease activity have improved and changed the approach to the management of this complex condition. The present chapter summarizes the current contemporary use of advanced cardiovascular imaging in the evaluation and management of individuals with suspected or known cardiac sarcoidosis.
Imaging Amyloid Heart Disease
Authors: Bois John P. , Grogan Martha , Chareonthaitawee Panithaya
Published: February 2024

Advanced cardiac imaging coupled with heightened clinical awareness has resulted in the recognition of the increasing role of cardiac amyloidosis (CA) in patients with heart failure with preserved ejection fraction. Light chain (AL) and transthyretin (ATTR) CA are the two most common subtypes of amyloid that involve the heart; if unrecognized, high morbidity and mortality result. Unfortunately, diagnosis is often delayed 2 to 3 years from symptom onset. In the current era of rapid development of new therapeutic agents to treat CA, timely diagnosis is critical not only for diagnostic purposes but also for prognostic and therapeutic ones. Nuclear cardiac imaging has emerged as a leading diagnostic tool that has transformed the management of this population. The most utilized radiotracers to date are the radiolabeled bisphosphonate agents (such as 99mTc pyrophosphate), which demonstrate robust uptake in ATTR CA relative to AL and in the right clinical context (including serologic assessment of AL) can differentiate between the two CA subtypes. Furthermore, these radiotracers are widely available and relatively straightforward to utilize and interpret. Conversely, direct amyloid SPECT and PET imaging agents have been hampered by their higher cost, lower availability, lack of FDA approval, and general inability to differentiate between ATTR and AL amyloid. However, agents such as 18F-florbetaben are emerging that demonstrate the potential to differentiate among amyloid subtypes. Future investigations are warranted to determine appropriate use of myocardial scintigraphy agents for screening different populations for amyloidosis and assessing their role in therapeutic decision-making.
Gastroesophageal Reflux Disease
Authors: Kamboj Amrit K. , Murray Joseph A.
Published: February 2024

Gastroesophageal reflux is the reflux of gastric contents other than air into or through the esophagus. Gastroesophageal reflux disease (GERD) refers to reflux that produces frequent symptoms or results in damage or dysfunction to the esophageal mucosa or contiguous organs of the upper aerodigestive system and occasionally the respiratory tract. Gastroesophageal reflux results from several factors that lead to symptoms or injury of the esophageal mucosa or the airway by reflux of corrosive material from the stomach.
Barrett Esophagus and Esophageal Cancer
Authors: Iyer Prasad G. , Vantanasiri Kornpong
Published: February 2024

Barrett esophagus is an acquired condition characterized by the replacement of the squamous epithelium lining the esophagus by partially intestinalized columnar epithelium. It is thought to be a complication of gastroesophageal reflux and may reflect an adaptive response to reflux of gastric contents into the esophagus. Squamous cell carcinoma and adenocarcinoma are the most common types of esophageal cancer. Esophageal carcinoma is the seventh leading cause of death in the world.
Nonvariceal Gastrointestinal Tract Bleeding
Authors: Bruining David H. , Alexander Jeffrey A.
Published: February 2024

Upper gastrointestinal (UGI) tract bleeding constitutes 75% to 80% of all cases of acute gastrointestinal tract bleeding. Although the incidence has decreased considerably, the mortality rate from acute UGI bleeding has decreased minimally in the past 50 years, ranging from 2.5% to 10%. This lack of change in the mortality rate likely is related to the older age of patients who present with UGI bleeding and the increase in associated comorbid conditions. Peptic ulcers re the most common source of UGI bleeding. Gastrointestinal tract bleeding has been classified according to the level of the tract: 1) upper—proximal to the ampulla of Vater; 2) mid—from the ampulla of Vater to the terminal ileum; and 3) lower—distal to the terminal ileum.
Gastrointestinal Manifestations of Systemic Disease
Authors: Sweetser Seth R.
Published: February 2024

Many systemic diseases can have gastrointestinal (GI) manifestations. Both the gut and the liver may be the main targets of the disease process, or they may be affected indirectly; in either case, the GI symptoms or signs may be the initial reason for seeking medical attention. This chapter is an overview of the more common systemic disorders that have well-recognized GI and liver manifestations, with an emphasis on disorders not considered elsewhere in this book.
Inflammatory Bowel Disease: Clinical Aspects
Authors: Chedid Victor G. , Coelho-Prabhu Nayantara
Published: February 2024

Inflammatory bowel disease (IBD) is a disease process characterized by chronic idiopathic intestinal inflammation along a spectrum that ranges from ulcerative colitis (UC) at one end to Crohn disease (CD) at the other. UC affects the colonic mucosa and extends proximally from the anal verge in an uninterrupted pattern that involves all or part of the colon. In contrast, CD is a transmural process that primarily affects the small bowel. However, CD can occur anywhere in the gastrointestinal tract from mouth to anus, manifesting as patchy inflammation with intervening areas of normal mucosa. Indeterminate colitis, now termed IBD colitis, unclassified type, in the middle of the spectrum, affects a small number of patients who have chronic colonic inflammation with features consistent with both UC and CD. All IBD, regardless of where it lies on the spectrum, can be associated with extraintestinal manifestations.
Nonalcoholic Fatty Liver Disease
Authors: Parthasarathy Gopanandan , Malhi Harmeet
Published: February 2024

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of disorders defined by accumulation of fat in hepatocytes and includes isolated hepatic steatosis, also known as nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH), which is characterized by the presence of inflammation and hepatocyte injury (including ballooning), with or without fibrosis. NAFLD is the most common chronic liver disease in the Western world, affecting a quarter of the population. NAFL, defined by steatosis without inflammation, is generally benign, whereas NASH may progress to cirrhosis, liver failure, and hepatocellular carcinoma. Hence, distinguishing between NAFL and NASH has important prognostic and management implications.
A 77-Year-Old Man With Chronic Cough and Recurrent Pneumonia
Authors: Al-Ghoula Faysal K. , Aksamit Timothy R.
Published: February 2024

Bronchiectasis is a pathologic, irreversible dilatation of bronchi resulting from chronic damage to the bronchi (eg, from infection). Risk factors for bronchiectasis include cystic fibrosis, immune deficiency syndromes, chronic inflammatory lung disease, and chronic lung infections. Mycobacterium avium complex (MAC) is a common cause of bronchiectasis in the US. The diagnosis of either of the 2 types of MAC infection, cavitary and nodular-bronchiectatic, requires 2 sputum cultures positive for MAC or 1 bronchial washing culture positive for MAC. Treatment is with combination antibiotic therapy (azithromycin, rifampin, and ethambutol) that should be continued for at least 12 months after culture results are negative.
A 28-Year-Old Woman With Worsening Cough and Hemoptysis
Authors: Pfeifle Daniel O. , Chalmers Sarah J.
Published: February 2024

Cystic fibrosis (CF) is characterized by worsening lung function due to chronic inflammation and impaired mucociliary clearance. Symptoms include increased cough, increased sputum production, and dyspnea. Treatment includes hospital admission, IV antibiotics targeted to culture-specific microbes, long-term therapies with intensification of airway clearance therapies, and initiation of CF transmembrane conductance regulator modulator therapy. Hemoptysis can occur independently of CF, or it may indicate acute pulmonary exacerbation and can range from scant, which can be managed in the outpatient setting, to massive, which requires hospitalization. Bronchial artery embolization is first-line therapy for massive hemoptysis, particularly with hemodynamic instability.
A 51-Year-Old Man With Fever, Dyspnea, and Productive Cough
Authors: Herzog Tyler L. , Kelly Bryan T. , Kelm Diana J.
Published: February 2024

Pneumomediastinum and pneumoperitoneum are rare pulmonary disorders. They can occur spontaneously or result from medical treatment (iatrogenic causes), underlying disorders, or trauma. In patients receiving ventilation, pneumomediastinum and pneumoperitoneum result from barotrauma and alveolar rupture. Currently, no guidelines exist to guide evaluation and management of either disorder. Most patients present with mild, self-limited disease that resolves with conservative treatment. Administration of high concentrations of oxygen may help speed resorption of the free air. An underlying cause should be sought and treated as necessary. Rarely, patients may have a more serious complication, such as tension pneumomediastinum or abdominal compartment syndrome, that necessitates emergent treatment with decompression.
A 49-Year-Old Man With Massive Upper Gastrointestinal Tract Bleeding
Authors: Pennington Kelly M. , Wilson Michael E.
Published: February 2024

Inferior vena cava filters are indicated in patients with acute venothrombembolic disease and in patients with active bleeding or a high risk for bleeding. Complications associated with inferior vena cava filters are rare but can be associated with morbidity and mortality. Massive pulmonary embolism requires treatment with systemic or catheter-directed thrombolysis or mechanical clot evacuation.
A 63-Year-Old Woman With Back Pain, Weakness, Tachycardia, and Hypertension
Authors: Aragon Pinto Catarina N. , de Moraes Alice Gallo
Published: February 2024

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis. Attention should be given to neuromuscular respiratory failure and arrhythmias. Regular measurement of respiratory pressures and forced vital capacity and continuous cardiac monitoring are lifesaving for patients with Guillain-Barré syndrome. Intravenous immunoglobulin and plasma exchange are the currently available immunotherapies. However, pharmacologic treatment does not improve survival, and supportive therapy is extremely important in the care of these patients.
A 48-Year-Old Woman With Shortness of Breath and Cough
Authors: Albitar Hasan A. , de Moraes Alice Gallo
Published: February 2024

With its high risk of morbidity and mortality, ICI-induced pneumonitis must be considered in all patients receiving an ICI and presenting with respiratory distress and hypoxemic respiratory failure.
A 60-Year-Old Man With Persistent Coma
Authors: Subat Yosuf W. , DuBrock Hilary M.
Published: February 2024

The classic presentation of patients with Miller Fisher syndrome (MFS) is the triad of ataxia, ophthalmoplegia, and areflexia. MFS most often occurs after an antecedent illness most likely caused by an autoimmune process involving molecular mimicry. The diagnosis of acute inflammatory demyelinating polyneuropathy (AIDP) is supported by a cerebrospinal fluid profile that shows an albuminocytologic dissociation and electromyographic findings that show demyelination. Serum anti-GQ1b antibody levels are increased in nearly 90% of patients with MFS. AIDP is often self-limited, but treatment with intravenous immunoglobulin or plasma exchange can shorten the recovery time.
An 83-Year-Old Woman With Obstructive Sleep Apnea at High Altitude
Authors: Dupuy-McCauley Kara L. , Selim Bernardo J.
Published: February 2024

Sleep-disordered breathing can worsen at high altitude because of increased frequency of centrally mediated disordered breathing events and subsequent increased arousal from sleep with changes in sleep architecture. Consequences may include worse blood pressure control, decreased daytime alertness, and sleep fragmentation (insomnia). Before travel to high altitude, patients should be counseled about the potential for worsening of obstructive sleep apnea and the emergence of high-altitude periodic breathing from central sleep apnea. If descent from high altitude is not feasible, a change in CPAP or APAP pressure settings with or without either supplemental oxygen or acetazolamide should be considered.
A 71-Year-Old Woman With Diarrhea and Recurrent Fever
Authors: Sangli Swathi S. , O’Horo John C. , Scanlon Paul D.
Published: February 2024

Histoplasmosis is an important complication in patients receiving TNF-α inhibitors, especially infliximab. If patients have risk factors such as an immunosuppressed state, certain infections, or rheumatologic disease, a high degree of awareness for secondary hemophagocytic lymphohistiocytosis is essential to secure the diagnosis. Prompt treatment of the underlying cause is critical for the resolution of hemophagocytic lymphohistiocytosis.
A 54-Year-Old Woman With Chronic Hoarseness and Cough
Authors: Chalmers Sarah J. , Thomas Charles F.
Published: February 2024

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and most commonly presents as a medially located pulmonary mass with associated mediastinal and hilar lymphadenopathy. SCLC is characterized by its rapidly progressive nature and often presents with widely metastatic disease. Diagnosis and staging should be made by the least invasive method. If results from initial diagnostic evaluations are negative and clinical suspicion is high, further tissue diagnosis should be pursued. Treatment of SCLC consists of chemotherapy, which is often given with radiotherapy and prophylactic cranial radiotherapy. Reoccurrence is common.
A 49-Year-Old Woman With Coital Hemoptysis
Authors: Piccolo Serafim Laura , Clay Ryan D. , Utz James P.
Published: February 2024

Coital hemoptysis is rare, but when it is present, a cardiac cause should be assumed until proved otherwise. Cardiac amyloidosis has a nonspecific presentation and should be part of the differential diagnosis when a patient has heart failure with preserved ejection fraction. Cardiac amyloidosis is frequently present in patients who have systemic AL amyloidosis. Management involves treating the heart failure with diuretics and identifying and treating the underlying cause of the amyloid deposition.
A 64-Year-Old Man With Back Spasms and Dyspnea 3 Weeks After Lung Transplant
Authors: Lau Jessica
Published: February 2024

Lung transplant is an effective option in the treatment of end-stage lung disease, but pulmonary complications can arise after transplant and lead to serious morbidity and death. The present case highlights the importance of recognizing the more subtle complications of transplant such as airway complications. Pulmonary complications do not occur in isolation, though, so it is important to recognize that in the patient described above, the presence of empyema and the later development of a pneumothorax may have been signs of anastomotic complications.
A 23-Year-Old Man With Dyspnea and Pleural Effusions
Authors: Felzer Jamie R. , Egan Ashley M.
Published: February 2024

Malignant mesothelioma is a rare disease that is more common in older male patients who have been exposed to asbestos, but it can occur in younger patients without asbestos exposure. Symptoms are nonspecific and may include fever, weight loss, pain, and lymphadenopathy. Diagnosis should be made from biopsy of the mass. The prognosis is poor overall, but surgery and chemotherapy are options.
A 68-Year-Old Man With Chronic Cough
Authors: Duke Jennifer D. , Long Cameron M.
Published: February 2024

Occupational pneumoconiosis is a reaction of the lung to inhalation and subsequent deposition of inorganic particles and dust. Silicosis is caused by the inhalation of silicon dioxide, which can lead to lung inflammation and fibrosis across a spectrum of severity. No proven treatment exists for silicosis, and lung transplant may be required.
Long-term X-ray temporal and spectral study of a Seyfert galaxy Mrk 6
Authors: Layek Narendranath , Nandi Prantik , Naik Sachindra , Kumari Neeraj , Jana Arghajit , Chhotaray Birendra
Published: February 2024

We present a long-term X-ray study of a nearby Active Galactic Nucleus Mrk 6, utilizing observations from XMM–Newton, Suzaku, Swift, and NuSTAR observatories, spanning 22 years from 2001 to 2022. From timing analysis, we estimated variance, normalized variance, and fractional rms amplitude in different energy bands.The temporal study shows fractional rms amplitude (Fvar) below 10 per cent for the shorter time-scale (∼60 ks) and above 20 per cent for the longer time-scale (∼weeks). A complex correlation is observed between the soft (0.5–3.0 keV) and hard (3.0–10.0 keV) X-ray bands of different epochs of observations. This result prompts a detailed investigation through spectral analysis, employing various phenomenological and physical models on the X-ray spectra. Our analysis reveals a heterogeneous structure of the obscuring material surrounding Mrk 6. A partially ionized absorber exhibits a rapid change in location and extends up to the narrow-line regions or torus. In contrast, another component, located far from the central engine, remained relatively stable. During the observation period, the source luminosity in the 3.0–10.0 keV range varies between (3–15) × 1042 erg s−1.
Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients
Authors: Shannon Kristen M , Patel Devanshi , Jonas Jessica M , Blouch Erica L , Hicks Stephanie R , Wooters Mackenzie , Seidel Meredith , Grant Carly F , Emmet Margaret M , Chung Daniel C , Sepucha Karen
Published: February 2024

Background

Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities.

Materials and Methods

An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content.

Results

Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients’ choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout.

Conclusion

The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.