bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational modeling and in vitro evaluation identified natural product—Z218 as a novel Janus kinase 2 (JAK2) inhibitor to combat β‐thalassemia
Authors: Shaikh Ahmad
Published: March 2023

Aberrant activity of Janus kinase 2 (JAK2) is a known driver of several myeloproliferative disorders, including polycythemia vera, and thalassemia. Several inhibitors have been proposed to inhibit JAK2 activity in order to control the disease progression. Ruxolitinib and fedratinib that targets JAK2 kinase have been approved for use in myeloproliferative neoplasms patients. Experimental structures of JAK2 complexed with ruxolitinib provide insights into critical interactions of ruxolitinib. In this work, using a high‐throughput virtual screening followed by experimental validations, we have identified a novel natural product from ZINC database that interacts with JAK2 in a manner similar to ruxolitinib and inhibits the activity of JAK2 kinase. Molecular dynamics simulations and MMPBSA method show binding dynamics and stability of our identified lead compound. Kinase inhibition assays show that our identified lead molecule inhibits JAK2 kinase at a nanomolar range, indicating a plausibility that the identified lead molecule can be further studied as natural product inhibitor of JAK2 kinase.
Antimicrobial effect of pimozide by targeting ROS‐mediated killing in Staphylococcus aureus
Authors: Kumar Siddhartha , Sandeep Kumar , Kumar Rakesh , Kumar Antresh
Published: March 2023

In spite of the higher nosocomial and community‐acquired infections caused by Staphylococcus aureus, emerging drug resistance is a leading cause of increased mortality and morbidity associated with the overuse of antimicrobials. It is an emergent need to find out new molecules to combat such infections. In the present study, we analyzed the antibacterial effect of pimozide (PMZ) against gram‐positive and gram‐negative bacterial strains, including methicillin‐sensitive (MSSA) and methicillin‐resistant (MRSA) S. aureus. The growth of MSSA and MRSA was completely inhibited at concentrations of 12.5 and 100 μg/mL, respectively, which is referred to as 1× minimum inhibitory concentration (MIC). The cell viability was completely eliminated within 90 min of PMZ treatment (2× MIC) through reactive oxygen species (ROS)‐mediated killing without affecting cell membrane permeability. It suppressed α‐hemolysin production and biofilm formation of different S. aureus strains by almost 50% at 1× MIC concentration, and was found to detach matured biofilm. PMZ treatment effectively eliminates S. aureus infection in Caenorhabditis elegans and improves its survival by 90% and is found safe to use with no hemolytic effect on human and chicken blood tissues. Taken together, it is concluded that PMZ may turn out to be an effective antibacterial for treating bacterial infections including MSSA and MRSA.
Advances in Regioselective Functionalization of Endohedral Metallofullerenes†
Authors: Li Yanbang , Sun Yue , Kopcha William P. , Zhang Jianyuan
Published: March 2023

Comprehensive Summary

Endohedral metallofullerenes (EMFs) are a family of molecules with metal clusters or ions encapsulated inside a fullerene cage. Their unique structures provide a powerful interface for organic chemists to manipulate metal elements. Over a decade ago, many reactions on empty fullerenes were adopted for EMFs, resulting in a series of reactions that are well‐established and reviewed in the literature. In recent years, new topics have emerged in EMF chemistry. First, new addition reactions were developed, notably some that are not based on known empty‐fullerene reactions. Second, considerable progress has been made on regioselective multi‐additions on EMFs. Finally, EMFs have been covalently conjugated with fullerene C60 to form functional materials. This Recent Advances article will focus on these new developments and discuss their implication for future directions of EMFs.
Optimal multiwave validation of secondary use data with outcome and exposure misclassification
Authors: Lotspeich Sarah C. , Amorim Gustavo G. C. , Shaw Pamela A. , Tao Ran , Shepherd Bryan E.
Published: March 2023

Observational databases provide unprecedented opportunities for secondary use in biomedical research. However, these data can be error‐prone and must be validated before use. It is usually unrealistic to validate the whole database because of resource constraints. A cost‐effective alternative is a two‐phase design that validates a subset of records enriched for information about a particular research question. We consider odds ratio estimation under differential outcome and exposure misclassification and propose optimal designs that minimize the variance of the maximum likelihood estimator. Our adaptive grid search algorithm can locate the optimal design in a computationally feasible manner. Because the optimal design relies on unknown parameters, we introduce a multiwave strategy to approximate the optimal design. We demonstrate the proposed design's efficiency gains through simulations and two large observational studies.
Effects of sulforaphane on breast cancer based on metabolome and microbiome
Authors: Cao Shuyuan , Hu Shengjie , Jiang Ping , Zhang Zhan , Li Lei , Wu Qian
Published: March 2023

Sulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF‐7 cell‐transplanted nude mice with 50 mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate‐related metabolites and glutathione‐related metabolites and decreased tryptophan metabolites and methyl‐purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate‐reducing bacterium Desulfovibrio, which is related to reduced methylation capacity, and increased the genus Lactobacillus related to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.
Local‐level exposure to conflicts and child health: Evidence from Côte d'Ivoire
Authors: Wayoro Didier
Published: March 2023

This paper analyses the impact of the 2002–2011 period of instability in Côte d'Ivoire on child health. It uses two rounds of DHS surveys (1998–1999 and 2011–2012) and geo‐referenced data on conflict event locations, which gives more precise estimates of the effects of conflict on child welfare. Regressions using both spatial and temporal variations of conflict events across birth cohorts show a negative association between proximity to conflict events and child height‐for‐age z‐score. The study also suggests that maternal stress and disruptions of healthcare services are possible channels through which conflict affects child wellbeing.
Optimizing microdisplay requirements for pancake VR applications
Authors: Hsiang En‐Lin , Yang Zhiyong , Wu Shin‐Tson
Published: March 2023

Virtual reality (VR) devices use imaging optics to magnify the microdisplay images for providing an immersive viewing experience. A microdisplay is preferred to have high‐resolution density and high dynamic range to meet the demanding requirements of human vision system (HVS), for example, visual acuity >60 pixels per degree and grayscale depth >10 bits. However, increasing resolution density and dynamic range often lead to a reduced optical efficiency and sophisticated fabrication process of the microdisplay panels. In this paper, we systematically analyze the image degradation mechanisms of VR devices caused by both imaging optics and microdisplay and find that the image degradation caused by imaging optics significantly unleash the requirements of microdisplay, such as contrast ratio, number of local dimming zones, and resolution density. For example, aberrations of the imaging optics reduce the resolution density requirement of the microdisplay, and stray light of the imaging optics relieves the contrast ratio requirement of the microdisplay. These results help prevent excessive design of microdisplay, for example, mini‐light‐emitting diode (LED) backlit liquid‐crystal displays (LCDs), organic LEDs, or micro‐LEDs, in a pancake lens‐based VR headset.
Einführung: Eltern im Stress?
Authors: Maly-Motta Hanna
Published: March 2023

„Eltern, was habt ihr euch erwartet?“ – titelt die Süddeutsche Zeitung unter der Rubrik Stress. Stress im Rahmen von Elternschaft bzw. das Wohlbefinden von Eltern stehen immer wieder im Mittelpunkt medialer Aufmerksamkeit. Auch die Forschung hat sich aus unterschiedlichen Blickwinkeln mit dem Wohlbefinden und mit Belastungsaspekten im Rahmen von Elternschaft auseinandergesetzt, vor allem mit Elterneffekten (z. B. Effekten elterlicher Belastung oder von Paarkonflikten) auf das Kind. Aufgrund der Interdisziplinarität der Forschungsbefunde stehen diese teilweise unverknüpft nebeneinander. Das Ziel der vorliegenden Arbeit ist es daher, die Rolle des Kindes für das Wohlbefinden von Eltern auf systematische Weise theorie- und datenbasiert zu betrachten um herauszufinden, unter welchen Umständen oder in welchen Lebenssituationen das Kind einen wichtigen Ausgangspunkt für das Wohlbefinden der Eltern darstellen kann.
Extremal metrics on the total space of destabilising test configurations
Authors: Sektnan Lars Martin , Spotti Cristiano
Published: March 2023

We construct extremal metrics on the total space of certain destabilising test configurations for strictly semistable Kähler manifolds. This produces infinitely many new examples of manifolds admitting extremal Kähler metrics. It also shows for such metrics a new phenomenon of jumping of the complex structure along fibres.
Automatic tree detection and attribute characterization using portable terrestrial lidar
Authors: Solares-Canal Ana , Alonso Laura , Picos Juan , Armesto Julia
Published: March 2023

Key message

This study details a methodology to automatically detect the positions of and dasometric information about individual Eucalyptus trees from a point cloud acquired with a portable LiDAR system.

Currently, the implementation of portable laser scanners (PLS) in forest inventories is being studied, since they allow for significantly reduced field-work time and costs when compared to the traditional inventory methods and other LiDAR systems. However, it has been shown that their operability and efficiency are dependent upon the species assessed, and therefore, there is a need for more research assessing different types of stands and species. Additionally, a few studies have been conducted in Eucalyptus stands, one of the tree genus that is most commonly planted around the world. In this study, a PLS system was tested in a Eucalyptus globulus stand to obtain different metrics of individual trees. An automatic methodology to obtain inventory data (individual tree positions, DBH, diameter at different heights, and height of individual trees) was developed using public domain software. The results were compared to results obtained with a static terrestrial laser scanner (TLS). The methodology was able to identify 100% of the trees present in the stand in both the PLS and TLS point clouds. For the PLS point cloud, the RMSE of the DBH obtained was 0.0716, and for the TLS point cloud, it was 0.176. The RMSE for height for the PLS point cloud was 3.415 m, while for the PLS point cloud, it was 10.712 m. This study demonstrates the applicability of PLS systems for the estimation of the metrics of individual trees in adult Eucalyptus globulus stands.
Understanding the influence of news on society decision making: application to economic policy uncertainty
Authors: Trust Paul , Zahran Ahmed , Minghim Rosane
Published: March 2023

The abundance of digital documents offers a valuable chance to gain insights into public opinion, social structure, and dynamics. However, the scale and volume of these digital collections makes manual analysis approaches extremely costly and not scalable. In this paper, we study the potential of using automated methods from natural language processing and machine learning, in particular weak supervision strategies, to understand how news influence decision making in society. Besides proposing a weak supervision solution for the task, which replaces manual labeling to a certain extent, we propose an improvement of a recently published economic index. This index is known as economic policy uncertainty (EPU) index and has been shown to correlate to indicators such as firm investment, employment, and excess market returns. In summary, in this paper, we present an automated data efficient approach based on weak supervision and deep learning (BERT + WS) for identification of news articles about economical uncertainty and adapt the calculation of EPU to the proposed strategy. Experimental results reveal that our approach (BERT + WS) improves over the baseline method centered in keyword search, which is currently used to construct the EPU index. The improvement is over 20 points in precision, reducing the false positive rate typical to the use of keywords.
Using the COM-B model to identify barriers to and facilitators of evidence-based nurse urine-culture practices
Authors: Advani Sonali D. , Winters Ali , Turner Nicholas A. , Smith Becky A. , Seidelman Jessica , Schmader Kenneth , Anderson Deverick J. , Reynolds Staci S.
Published: March 2023

Our surveys of nurses modeled after the Capability, Opportunity, and Motivation Model of Behavior (COM-B model) revealed that opportunity and motivation factors heavily influence urine-culture practices (behavior), in addition to knowledge (capability). Understanding these barriers is a critical step towards implementing targeted interventions to improving urine-culture practices.
A Review of the Effectiveness of the Nigerian Whistleblowing Stopgap Policy of 2016 and the Whistleblower Protection Bill of 2019
Authors: Ojobo Ejemen
Published: March 2023

The act of whistleblowing is not common in Nigeria; this can be attributed to the cultural norms of Nigerian society where deference is paid to those in positions of power and it is often viewed as taboo to speak up against them. This problem of not speaking up is further compounded by the lack of robust whistleblowing legislation which protects whistleblowers from reprisals. The need to protect whistleblowers was brought to the forefront after the implementation in 2016 of the Nigerian stopgap policy on whistleblowing, leading to the Whistleblower Protection Bill proposed in 2019, legislation that seeks to provide wider protection to whistleblowers. This article examines this bill, identifying its limitations; it does not rehash previous scholarly debates about whether incentives are necessary, but rather focuses on bringing the Nigerian perspective to the fore, thus contributing to the existing literature in this area.
Emergency Department utilisation and diagnoses in adolescents with postural orthostatic tachycardia syndrome
Authors: Boris Jeffrey R. , Bernadzikowski Thomas
Published: March 2023

Introduction:

Data for Emergency Department utilisation and diagnoses in adolescents with postural orthostatic tachycardia syndrome are lacking, making prevention of these visits more difficult to achieve.

Materials and methods:

We performed a retrospective study of patients with postural orthostatic tachycardia syndrome between ages 12 and 18 years seen in the Emergency Department at a large tertiary care children’s hospital. These subjects were age- and sex-matched with controls, with volume of primary and total diagnoses assessed. Due to the relatively small number of subjects, a ± 3-year variance was used among control patients for age matching.

Results:

A total of 297 patients in each group were evaluated. The percentage of female patients was 80.5%. The median age of the subjects was 15.1 years (interquartile range 14.1–15.9), and the median age of controls was 16.1 years (interquartile range 14.4–17.4) (p < 0.00001). Patients with postural orthostatic tachycardia syndrome had greater gastroenterologic and headache diagnoses (p < 0.00001); controls had greater autonomic and psychiatric diagnoses.

Discussion:

Adolescent patients with postural orthostatic tachycardia syndrome who present to the Emergency Department have a preponderance of gastroenterologic and headache complaints versus controls.
Revealing the Statistics of Extreme Events Hidden in Short Weather Forecast Data
Authors: Finkel Justin , Gerber Edwin P. , Abbot Dorian S. , Weare Jonathan
Published: March 2023

Extreme weather events have significant consequences, dominating the impact of climate on society. While high‐resolution weather models can forecast many types of extreme events on synoptic timescales, long‐term climatological risk assessment is an altogether different problem. A once‐in‐a‐century event takes, on average, 100 years of simulation time to appear just once, far beyond the typical integration length of a weather forecast model. Therefore, this task is left to cheaper, but less accurate, low‐resolution or statistical models. But there is untapped potential in weather model output: despite being short in duration, weather forecast ensembles are produced multiple times a week. Integrations are launched with independent perturbations, causing them to spread apart over time and broadly sample phase space. Collectively, these integrations add up to thousands of years of data. We establish methods to extract climatological information from these short weather simulations. Using ensemble hindcasts by the European Center for Medium‐range Weather Forecasting archived in the subseasonal‐to‐seasonal (S2S) database, we characterize sudden stratospheric warming (SSW) events with multi‐centennial return times. Consistent results are found between alternative methods, including basic counting strategies and Markov state modeling. By carefully combining trajectories together, we obtain estimates of SSW frequencies and their seasonal distributions that are consistent with reanalysis‐derived estimates for moderately rare events, but with much tighter uncertainty bounds, and which can be extended to events of unprecedented severity that have not yet been observed historically. These methods hold potential for assessing extreme events throughout the climate system, beyond this example of stratospheric extremes.
Justification of the opportunities of obtaining silicate materials based on clay waste adsorbents
Authors: Anorov R. , Rakhmonov O. , Salikhanova D. , Khomidov F. , Abdurakhimov A.
Published: March 2023

The physicochemical composition of the used waste clay adsorbents was studied to justify the possibility of obtaining other silicate new products, and it was found that they did not differ from the original ones. It was determined that the chemical composition of all samples met the requirements for porous materials. It was determined that bentonites have the highest rate of increase.
Dialogue system for designing technological processes
Authors: Golovin Dmitry , Samotin Ivan , Pocebneva Irina , Vasilyeva Olga
Published: March 2023

The paper deals with the issues of automation of technological design, for which it is proposed to introduce the concept of a structured reference space of a technological process, which is understood as a special design created on a set of processes used in the manufacture of products, on which their ratio is set for individual subsets of the materialization processes of a product. To describe the reference space of the technological process, a method for solving methodological and mathematical problems is proposed - according to the information image of objects and processes; analysis and synthesis of processes; synthesis of equipment layout diagrams; machine methods of systematization. The latter made it possible to develop a qualitatively new approach to organizing data on technological processes, based on an object model for representing and processing information.
Numerical methods to calculate magnetic fields of magnetostriction level converter
Authors: Karpukhin E.V. , Bormotov A.N.
Published: March 2023

This article discusses the method for obtaining a system of finite- difference equations to calculate the magnetic fields of magnetostrictive level transducers (MLT) of the applied type. An optimal numerical method for their solution is presented. The formulated problem of finding the optimal width of the non-magnetic wall of the reservoir of the applied MLT is solved by using the finite-difference approximation of the Maxwell system. The article shows the method for obtaining such equations based on the method of grids and considers in detail the optimal method for their numerical solution. The results of mathematical modeling of the magnetic field of the applied MLT using the developed program make it possible to determine the optimal value of the non-magnetic wall width of the tank of the applied MLT, at which the strength of the longitudinal magnetic field of the permanent magnet will be sufficient to form an ultrasonic torsion wave in medium of magnetostrictive sound line.
Organization of major repairs of apartment buildings with energy-saving technologies
Authors: Zilberova Inna , Mailyan Vadim , Zilberov Roman
Published: March 2023

In today’s Russia, development of new regulatory requirements related to major repairs of apartment buildings is much less needed than harmonization and enforcement of existing regulations. In order to meet the energy efficiency requirements for apartment buildings after major repairs, it is necessary to develop a set of energy-saving measures that will increase the energy efficiency of buildings and the comfort of living. The main particularities of the organization of repair and construction during major repairs include requirements for modeling the order of different types of work at each facility under financial and time constraints. This said, we can conclude that it is necessary to determine the optimal sequence of application of energy-saving technologies during repair and construction within the major repairs of apartment buildings and the effectiveness of the applied technology.
Representation of the interest identified with the help of it technologies
Authors: Shcherbakova Irina , Kovalchuk Nadezhda
Published: March 2023

In this paper we have examined the representation of the emotional state of “interest” identified with the help of it technologies. The purpose of our research was to reveal the main gender peculiarities of the representation of the emotional state “interest” identified with the help of it technologies. In the course of the research we have used the following methods: general scientific and partial scientific methods. During the methods of observation and the results obtained, it was concluded that the male character and the female character show interest through verbal and non-verbal means. Non-verbal means of representation are kinetic means, verbal - lexical means: nouns naming the emotion itself. It was concluded that the verbal means of representation of the emotional state “interest” act kinetic means, namely, eye movement (squinting, burning eyes, eyes wide open). Verbal means are lexical means: nouns naming the emotion itself. The peculiarities of gender manifestations of the emotional state of “interest” are different. Men are inclined to show non-verbal means of representation of the emotion of interest that is the pledge of further study of the kinesic means of representation of emotions. The female character represents preferably by verbal means, which is the basis for further study of the representation of the emotional states of the female character and the male character.
The method of multiple sampling by significance for the visualization of functionally defined scenes
Authors: Vyatkin Sergey , Dolgovesov Boris
Published: March 2023

In ray tracing methods, the key point is to choose the direction for the rays. If many rays are needed not everywhere, but only in some parts of the scene, it is reasonable to increase the selection in these places. As a result, computing resources are not wasted where there is no such need. That is, you need to make selections by significance. In this paper, the visualization of functionally defined scenes is considered. A method of multiple sampling by significance is proposed. The method uses weight functions for multiple sampling by significance. The weighting functions minimize the variance of the multiple sample estimation by significance. Weights can be negative, which reduces the variance. In addition, weights allow you to have additional flexibility when developing a sampling method that accelerates calculations. As a result, acceptable weights were obtained when modeling light transfer. The variance was reduced by using weights in the sample. The dependence of the mean square error on the number of samples is given. Highly realistic functionally defined scenes are visualized. The method is implemented using CPU and GPU. Diagrams of the method's performance are given.
Male crayfish (Faxonius obscurus, Decapoda: Cambaridae) claws are longer and stronger yet comparable in shape during the reproductive season
Authors: Graham Zackary A , Stubbs Megan B , Loughman Zachary J
Published: March 2023

Animal weapons are diverse and often exaggerated structures associated with sexual selection and male–male combat. Despite their diversity, our knowledge of these structures comes primarily from studies that focus on the size of the weapons and neglect other components, such as their shape or performance. Furthermore, weapons can exhibit species-level plasticity based on nutrition and other ecological variables, but few studies have documented seasonal variation in weapon plasticity. Here, we investigate how weapon size, shape and performance differ across adult male reproductive and non-reproductive Allegheny crayfish, Faxonius obscurus. Given that F. obscurus and other cambarid crayfishes exhibit cyclical moulting between reproductive and non-reproductive states, they provide an ideal system in which to investigate such questions. We found that claws of reproductive and non-reproductive male F. obscurus differ in all three weapon components we investigated; claws from reproductive males were longer, stronger and different in shape compared with claws from non-reproductive males. Wielding longer and stronger claws is likely to confer greater competitive success during the mating season, which demonstrates an unexplored pattern of seasonal weapon plasticity. We discuss these results considering our knowledge of the seasonality of weapon phenotypes and propose several avenues of future research using cambarid crayfish as a model system.
Knocking at the Door
Authors: Engel Kirsten G. , Derse Arthur
Published: March 2023

In the emergency department (ED), many of our patients face critical illness or injury, with impact that extends far beyond themselves and profoundly affects their families and loved ones. While our primary obligation is to our patients, the engagement and support of families are important aspects of providing high-quality care in any setting. In the most acute and desperate moments, family presence during resuscitation, also known as family witnessed resuscitation (FWR), provides families with the opportunity to be present and connected with their loved one. Given the poor outcomes associated with cardiopulmonary resuscitation, FWR frequently results in families witnessing the final moments of the patient’s life. This experience is associated with many positive effects for survivors, including a more fluid transition to a healthy grief and bereavement process. Moreover, this intervention can have important benefits for patients and healthcare providers. Despite its recognized positive effects, FWR has evoked significant opposition and controversy because it represents a dramatic paradigm shift in our approach to care in the ED. This type of momentous change challenges the healthcare system and requires time, patience, and thoughtful consideration about how to overcome barriers and ensure best practice. For FWR, candid discussion among providers, with opportunities for education and training, is extremely important to facilitating change and improving the care of our patients and their families in the future.
Let’s Get It Right
Authors: Lamba Sangeeta , Goett Rebecca
Published: March 2023

Hospice care is a type of interdisciplinary healthcare for patients at the end of life that focuses on quality of life, comfort, and caring along the course of a patient’s terminal illness. In the United States, hospice care is defined by the Medicare Hospice Benefit and requires the patient to have a limited prognosis with a limited life expectancy as well as the goals of care that are aligned with comfort care. Most hospice care is provided at home with the family as the primary caregivers, although it may be provided in other settings, such as assisted living, long-term care facilities, and other community settings. Hospice providers manage the full spectrum of patient needs, including physical, spiritual, psychosocial, and emotional distress. Inpatient hospice units, where available, are utilized for patients when their care needs cannot be managed at home, such as those with significant and refractory symptoms. Referral to the hospice system of care, whether inpatient or outpatient, can be accomplished directly from the emergency department, provided that there are operational mechanisms in place to allow for transitions of care to hospice.
Global Aspect of Palliative Care
Authors: Flynn Emilee , Majzoub Imad El
Published: March 2023

Access to palliative care services remains extremely inadequate in resource-limited settings throughout the world. In nearly one-third of the world, there is no access to palliative care services. Yet low- and middle-income countries (LMICs) often have a much higher need for palliative care. Individuals in LMICs have limited access to regular surveillance and preventative care and therefore are diagnosed at more advanced stages of disease where options for curative therapy are sparse. Eighty-one percent of the individuals who experience significant suffering near the end of life died in LMICs. Access to opioid medications, which are essential analgesics, remains a challenge in LMICs. Over 5 billion people worldwide have extremely limited to no access to such medications. Opiophobia, lack of provider knowledge and comfort with opioid medications, restrictive national government policies and regulations, high medication cost, and cultural norms and values contribute to this disparity. While providers and policymakers should continue to advocate for improved access to opioids, the use of alternative symptom management strategies, including nonsteroidal anti-inflammatory drugs, antidepressants, anticonvulsants, antispasmodics, bisphosphonates, and corticosteroids, should be considered. In remote and rural areas, where access to palliative care would otherwise be nonexistent, trained community health workers (CHWs) can help provide support and guidance to patients and their families. The presence of CHWs has immensely contributed to reduced patient suffering at the end of life, even when opioids were unavailable or inaccessible.
Not One More Thing
Authors: Neugarten Carter , Wang David
Published: March 2023

Palliative care consultation in the emergency department (ED) can be helpful to ED teams, patients, and families alike. The emergency clinician may, through a more objective approach, be able to identify unmet palliative care needs, such as functional debility, symptom burden, and lack of prognostic awareness. Earlier palliative care involvement has been shown to significantly decrease hospital length of stay and cost, and it has demonstrated marked improvements in depression, anxiety, and well-being across multiple disease states. Subspecialty palliative care consultation in the ED can be helpful in several ways. First, it can assist with gaining a broader view of the clinical course and gather additional history and perspective that might not have been gained through coordination with other providers or additional historians. Consultants can help clarify a patient’s goals of care, assist with difficult symptom management, and help provide guidance on patients enrolled in hospice or with hospice enrollment from the ED. Palliative care consultants can also assist in disposition determination and help to create safe discharge and follow-up plans. There is a spectrum of models for how palliative care can support the ED, ranging from “as needed” palliative consultation by standard ED practice, to dedicating and embedding a multidisciplinary palliative care team into the ED.
Ibogaine: Ibogaine therapy as a method of care treatment for opioid dependence
Authors: Mash Deborah C.
Published: March 2023

Ibogaine has been used as a botanical preparation from the root bark of Tabernanthe iboga for over one hundred years, both as a crude preparation and as semisynthetic ibogaine. Extracts derived from this plant have a long history of traditional medicinal and ceremonial use in Western Africa. Ibogaine is a polypharmacology drug that acts on several neurotransmitter systems, including biogenic amines (dopamine and serotonin [5-HT]), and peptidergic (opioid), cholinergic (neuronal nicotinic), and glutamatergic systems. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) recently granted approval to commence subject enrolment in a Phase 1/2a clinical trial of ibogaine. The Phase 1 part of the study will provide an assessment of safety at escalating doses of ibogaine, while the randomized, placebo-controlled Phase 2 part of the study is designed to provide proof of concept in patients who seek to detoxify from opioids. While there are no other ongoing GLP clinical trials in the United States or elsewhere, there is a large amount of information on the clinical use of ibogaine. These reports demonstrate that the drug not only helps manage the physical symptoms of opioid withdrawal, but also the behavioural aspects of addiction that drive relapse.
Other psychedelics
Authors: Linden James , Robin Daniel
Published: March 2023

This chapter will detail some of the lesser-known psychedelics. While lesser known, some of these are arguably the most potent molecules, and one could argue these hold the most potential for medicine. We will go on a small journey into a lesser-understood corner of plant medicine and psychedelics. Many of the psychedelics discussed so far in this publication have well-elucidated and reasonably well-developed psychopharmacology. The lesser knowns are similarly less understood and have novel effects, the causes of which are still essentially baffling. In the great pursuit of psychedelic science there has been an increased interest to understand the potential of these lesser knowns, which will be overviewed here. There are also significantly fewer clinical data available for these, in fact, none in some cases, at least not of huge or encouraging impact to humanity thus far. It gives great pleasure to present five lesser knowns.
Suicidal Narrative
Authors: Galynker Igor
Published: March 2023

This chapter introduces the concept of the suicidal narrative component of the narrative-crisis model of suicide, a coherent life story of progressive failure and alienation culminating in the perception of no future, which may trigger suicide crisis syndrome, thus increasing an imminent risk of suicidal behavior. Seven stages of the suicidal narrative, including entitlement to happiness, failure to redirect to more realistic goals, humiliating personal or social defeat, perceived burdensomeness, thwarted belongingness, and perception of no future, are described in great detail and illustrated with clinical case examples. The suicidal narrative interview algorithm outlined in this chapter can be used to assess suicide risk. The interview starts with a careful assessment of each of the suicidal narrative stages and concludes with the construction of the suicidal narrative, an outline of a life story that has gone awry. The proposed interview algorithm should be personalized to reflect the uniqueness of each clinical situation. Clinical cases provided in this chapter illustrate how the algorithm can be adjusted depending on the course of the interview.
The Narrative-Crisis Model of Suicide as a Framework for Suicide Prevention
Authors: Goncearenco Inna , Chennapragada Lakshmi , Rogers Megan L.
Published: March 2023

Chapter 10 provides an overview of applicable clinical interventions that have demonstrated promise in mitigating suicide risk at each stage of the suicidal process. The interventions are: lethal means counseling, safety planning, psychopharmacology, crisis management, psychotherapy, and skills coaching. Each treatment modality is placed in the framework of the narrative-crisis model of suicide (NCM) and addresses symptoms arising over the course of a suicidal episode and across all NCM stages: suicidal crisis syndrome, suicidal narrative, and trait vulnerabilities. The chapter also provides a brief overview of recent developments in digital interventions targeting suicidal thoughts and behaviors. Cultural considerations applicable to suicidality treatment are outlined, emphasizing the need for culturally competent approaches to suicide prevention and intervention. In conclusion, implications for future research and clinical practice are discussed.
Brain and Spinal Cord Function
Authors: Gluncic Vicko
Published: March 2023

The central nervous system (CNS) has two major subdivisions: the brain and the spinal cord. The brain controls the majority of body functions, including awareness, memory, thoughts, emotions, movements, speech, and sensations. In addition to being an “interface” between the brain and the spinal nerves, the spinal cord has some functional autonomy and participates in regulation of both ascending and descending signals. Both CNS components share embedded in cerebrospinal fluid, and their blood flow is tightly regulated. Moreover, their parenchyma is separated from the blood by the blood-brain barrier. As many anesthetic procedures interfere with CNS activities, either as the primary mode of action or as a side effect, sound knowledge of CNS anatomy and physiology is a basis for good anesthesia practice.
ASA Monitoring Standards
Authors: Eden Nikki , Rajan Shobana
Published: March 2023

The American Society of Anesthesiologists sets a standard for monitoring during all anesthetic cases. Oxygenation, ventilation, circulation, and temperature are the four key components being measured. Included in these are pulse oximetry, capnography, end-tidal CO2, electrocardiography, arterial blood pressure, and temperature. With these, the anesthesiologist is able to obtain objective information that, when used with clinical acumen, will provide the highest level of patient care and safety. These standards must be met for every case, whether the anesthetic being delivered is general, regional, or monitored anesthesia care. However, these are only the minimum requirements, and further monitoring may be used at the discretion of the anesthesiologist.
Brain Volume
Authors: Shin John S. , Bui Timothy T.
Published: March 2023

Brain volume consists of cells, intracellular and extracellular fluid, and blood within cerebral vasculature. An increase in brain volume beyond the compliance of the system can lead to elevated intracranial pressure and irreversible ischemia. Brain fluid content can be rapidly reduced by an osmotic diuretic and/or a loop diuretic. Methods for decreasing cerebral blood flow include positioning to maximize venous drainage (head elevated, neck neutral); minimizing intrathoracic pressure; hyperventilating; inducing mild hypothermia; and administering intravenous anesthetics rather than inhaled agents. If not appropriately treated, increased brain volume can lead to compression of the vasculature, brain ischemia, and infarct, which can result in permanent neurologic deficits and death.
Truncal Nerve Blocks
Authors: Scholzen Elizabeth , Klesius Lisa
Published: March 2023

Truncal nerve blocks encompass a wide variety of nerve blocks. Intercostal, paravertebral somatic, ilioinguinal, and genitofemoral nerve blocks are described in this chapter. Intercostal and paravertebral blocks can be used as surgical or analgesic blocks for cases involving the chest wall, including thoracic and breast surgery, or for traumatic rib fractures. Ilioinguinal and genitofemoral nerve blocks come off the L1 and L2 nerve roots and can be used for inguinal hernia repair surgery as well as others. All of these nerve blocks can be performed with either a landmark-based or ultrasound-based approach. Complications of these nerve blocks vary depending on the block but share in common the complications of bleeding, infection, and potential nerve damage. Truncal nerve blocks are a broad category describing several nerve blocks. Intercostal, paravertebral somatic, ilioinguinal, and genitofemoral nerve blocks are described here.
Innervation of Pelvic Structures
Authors: Yi Peter , Vorenkamp Kevin E.
Published: March 2023

Structures of the pelvis are innervated by a complex array of nerves. The autonomic nervous system contributes the sympathetic and parasympathetic innervations of the pelvic organs, which have opposing actions. The sacral splanchnic nerves contribute sympathetic innervation to the pelvic organs, while the pelvic splanchnic nerves contribute parasympathetic innervation. Visceral nerve fibers converge with other types of nerves, forming a complicated network responsible for visceral innervation of the pelvic structures. Finally, somatic nerves from various plexuses send terminal nerves (sensory, motor, or a combination) to pelvic organs. Although the innervation of the pelvis may seem complicated, careful study of each component of the nervous system can be helpful for understanding the innervation of the organs in the pelvis.
Pharmacogenetics and Genetic Factors in Drug Dose-Response Relationships
Authors: Kapp Daniel Gonzalez
Published: March 2023

Pharmacogenetics and pharmacogenomics are related areas of research that aim to determine the relationship between genotypic variation, including changes in gene expression, and variations in drug response seen across patient groups. Understanding the genetic bases of variability in drug response due to altered pharmacokinetics (e.g., drug absorption, distribution, metabolism, excretion) or pharmacodynamics (e.g., drug receptor up- or downregulation) is essential for the practitioner to fully anticipate, recognize, and mitigate potential drug toxicity or ineffectiveness. The ultimate goal of pharmacogenetics and pharmacogenomics is to develop personalized medicine for individuals by leveraging knowledge of phenotypic variation in drug response due to genetic mutations, polymorphisms, or gene expression.
Malignant Hyperthermia
Authors: Papapetrou Peter , Ferguson Kris
Published: March 2023

Malignant hyperthermia (MH) is a rare genetic disorder than can be fatal in affected individuals that are exposed to potent volatile anesthetic agents and succinylcholine. Proper preoperative assessment and preparation can help avoid exposure of a patient to a triggering agent. In the event of exposure, prompt recognition of a suspected MH crisis is critical. Signs and symptoms of a hypermetabolic state could include hyperthermia, increased ETCO2, muscle rigidity, metabolic acidosis, and dysrhythmias. Treatment is made with dantrolene; treating manifestations of the hypermetabolic state such as cooling mechanisms, correcting acid-base imbalances and electrolyte abnormalities; as well as close monitoring for a recurrence of an MH crisis.
Rapid Metabolizers
Authors: Parker Nicholas M.
Published: March 2023

Enzymes in the family known as cytochrome P450 (CYP450) are involved in the metabolism of many drugs. A few key enzymes involved in drug metabolism (namely CYP2D6 and CYP2C19) may be overexpressed in some patients, known as ultrametabolizers. These patients are usually identified by genetic testing only after experiencing treatment failure or adverse reactions with certain drugs. Genetic variation in drug metabolism may exacerbate the effect of drug-drug interactions. Drugs that are metabolized by these two enzymes should be used cautiously in known or suspected ultrametabolizers. Anesthesiologists may have an important role in identifying ultrametabolizers given their ability to closely monitor their patients’ response to medications.
Addiction Versus Tolerance
Authors: Shah Anuj A. , Zaky Christine S.
Published: March 2023

Addiction involves a state of maladaptive behavior, such as the compulsion for taking a habit-forming substance, while tolerance is the decrease in the pharmacological effect of a drug. Addiction involves activation of the reward pathway that leads individuals to favor immediate reward over delayed but favorable responses. Tolerance to opioids, for example, according to two different theories, may involve desensitization and downregulation of opioid receptors. Management strategies of opioid tolerance include opioid-sparing therapies and opioid rotation. It is important for patients presenting for anesthesia and analgesia, from the active to the recovering addict, including those experiencing various effects of substance abuse, to work with an interdisciplinary healthcare team to manage their condition. This includes a comprehensive preanesthesia assessment and evaluation that provides insight for optimal care. Perioperative anesthetic management strategies may differ with the abused substance.
Acetaminophen
Authors: Uzodinma Ifomachukwu
Published: March 2023

Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic agents around the world. APAP works by central inhibition of cyclooxygenase (COX), thus limiting the adverse effects that are commonly seen with other nonsteroidal anti-inflammatory drugs (NSAIDs). APAP works synergistically with other analgesic agents and can specifically decrease opioid requirements. Acetaminophen is typically dosed at less than 4 g/d in healthy patients and greater than 2 g in individuals with any underlying liver pathology or alcoholism. If APAP is consumed at toxic levels, hepatocellular necrosis and progression to acute liver failure may result. Excess APAP creates reactive metabolites, specifically increased levels of NAPQI (N-acetyl-p-benzoquinone imine), which leads to glutathione depletion and eventual cytotoxicity. N-Acetylcysteine is treatment for APAP-induced liver toxicity as it helps replenish glutathione stores and reduces NAPQI to a nontoxic metabolite.
Coma
Authors: Robertson Hess , Boysen Philip G.
Published: March 2023

Coma is defined as a state of profound unconsciousness caused by disease, injury, or poison. A medical description would also include a patient that cannot be awakened, fails to respond to painful stimuli (or light and sound), and does not initiate voluntary actions. Coma is a medical emergency, unlike most diagnostic processes that follow an orderly progression. Two overriding principles apply to the comatose patient. The first is that coma is a true medical emergency. The second principle follows from the first principle. Managing the coma patient requires beginning diagnostic and therapeutic measures at the same time to improve patient outcome.
Paraplegia, Quadriplegia, Spinal Shock, Autonomic Hyperreflexia, Acute Spinal Cord Injury
Authors: Papapetrou Peter , Ferguson Kris
Published: March 2023

Spinal cord injury brings unique considerations and challenges to the anesthesiologist. These patients have altered physiologic changes to their cardiovascular and respiratory systems and necessitate meticulous airway management. For patients with lesions of T6 or higher, they can experience the unique though catastrophic consequences of autonomic hyperreflexia. Evaluation of the timing and location of the spinal cord lesion is important to anticipate the extent of these physiologic changes. Succinylcholine should be avoided in patients that sustained spinal cord injuries between 3 days and 6 months prior to surgery, as they may have a massive hyperkalemic response that can result in ventricular fibrillation and cardiac arrest.