bluuebunny/crossref_metadata_2025 huggingface dataset:
Expansion of human cytotoxic T lymphocytes for immunotherapy
Authors: Tan Rusung
Published: November 2023

The adoptive transfer of virus-specific, cytotoxic T-lymphocyte (CTL) lines or clones to humans has proved effective in the prevention and treatment of diseases caused by cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the first few months after bone-marrow transplantation (1-3). Apart from the benefit to patients, these studies have provided definitive evidence that CTLs are highly efficient at controlling some viral diseases in humans, and raise the possibility that similar therapy may be useful for other infections and tumours which elicit cellular immune responses. However, the generation of antigen specific CTLs in vitro does not necessarily imply anti-viral efficacy in vivo. Many viruses and some tumours have been shown to evade the cellular immune response by mechanisms as varied as the intricacies of the immune responses themselves. For instance, most members of the Herpesvirus family elaborate proteins that undermine the intracellular class I antigen-processing pathway (4), while other viruses manufacture molecular homologues that interfere with intra and intercellular signalling (5). In addition, some infected cells and tumours upregulate Fas-ligand thus arming themselves against Fas expressing lymphocytes (6-8). In patients with depressed CD4+ T-cell function due to therapeutic immunosuppression (for example after bone-marrow transplantation), the efficacy of the infused CTLs appears to correlate with the re-emergence of antigen-specific T-helper cells (2, 9). In diseases where there is no paradigm for protective host immunity, for example HIV infection, the use of CTL adoptive therapy has been less successful (10-13). One obstacle to their therapeutic effectiveness has been the short survival of infused HIV specific clones (13, 14): however, these studies have provided a clear demonstration that infused HIV-specific CTLs will home towards the sites of active HIV replication in lymphoid tissue (14).
Measurement of cells undergoing apoptosis
Authors: Furukawa Y , ham c. R M Bang
Published: November 2023

Apoptosis is a distinct mode of cell death that is responsible for the deletion of cells during development, and the deletion of superfluous cells from normal tissue; sometimes it also occurs in pathological situations. Apoptosis was originally detected because of the distinctive morphology of apoptotic cells, which allows them to be easily distinguished from healthy cells and from those dying by necrosis. Although different cell types do not always display all the hallmarks of apoptosis, cell death by apoptosis does have characteristic features such as shrinkage of the cell, membrane blebbing, chromatin condensation, and nuclear fragmentation (1).
Identification and genotypic characterization of filamentous fungi
Authors: Piercey-Normore Michele D , Egger Keith N
Published: November 2023

In the past decade a wide array of techniques, and an often bewildering number of acronyms, have been developed for detecting genetic variation in a variety of organisms, including fungi. It is not within the scope of this chapter to describe all of these techniques. Rather we will attempt to provide the reader with an understanding of the main classes of techniques, strategies for determining which are appropriate to answer the biological question being posed, and point out sources of information to assist in implementing the protocols.
Immunological methods for fungi
Authors: Thornton Christopher R
Published: November 2023

Immunological approaches to the study of fungi are well documented, beginning with the studies of Flor, DeVay, and others (1, 2) in the 1960s and earlier of the common antigenic relationships between fungal plant pathogens and their hosts using rabbit polyclonal antisera (pAbs). However, it was not until the advent of hybridoma technology and the production of monoclonal antibodies (mAbs) pioneered by Köhler and Milstein in the mid-1970s (3), that immunological methods began to provide the degree of specificity and reproducibility required by modern day fungal biologists. The complex structure of fungal cell walls and their extracellular glycoproteins, compared to organisms such as viruses, and the complexity of the soil and plant matrices in which they grow and reproduce, meant that traditional approaches employing pAbs found only limited applicability in studies of fungal biology. Hybridoma technology and the production of mAbs overcame many of these problems and revolutionized immunological studies of fungi, allowing detailed investigations of morphology, biochemistry, and physiology in pure culture through to the detection, quantification, and visualization of the components of fungal biomass in naturally infected plant and infested soil samples.
Cytogenetics in myeloid leukaemia
Authors: Potter A M , Watmore A
Published: November 2023

This chapter covers Three hematological disorders of myeloid cells: AML MDS and MPD. Both MOS and MPD have a propensity to evolve to acute leukemia. Indeed. the diagnosis of AML in these cases may be simply based on the blast count. The poorly defined boundaries between disorders is reflected in the commonality of the chromosome findings in the three conditions. The majority of chromosome changes in myeloid leukaemia, although characteristic of the disease, can also be observed elsewhere. This chapter attempts to identify those zibnormalitics considered exclusive to rnyc>loid kuk<1cmia (usually having a limited distribution within AML subtypes) and those strongly associated with myeloid disorders but occasionally appearing in other diseases. A third type of chromosome abnormality is also included. These are findings which are recur rent in myeloid disease. but frequently observed outside the myeloid lineage. These should not be considered as reliable lineage markers when set: alone. A, with all malignancies, a proportion of myeloid leukaemias show only random changes. These confirm the neoplastic nature of the disease but provide no further informalion.
Partial unfolding as a precursor to amyloidosis: a discussion of the occurrence, role, and implications
Authors: Kad Neil M , Radford Sheena E
Published: November 2023

An astounding feature of proteins is their ability to acquire a unique three-dimensional structure despite the vast sequence space accessible to the polypeptide chain. However, on rare occasions a polypeptide chain finds an energy minimum that is not the native state. These are often in the form of alternately folded structures, or insoluble aggregates. Usually regarded as an experimental nuisance, protein aggregation is now emerging as an exciting area of research with both biological and biotechnological importance. For example, heterogeneous recombinant proteins expressed in bacterial cells can be deposited as inclusion bodies, or the aggregation of proteins in vivo may cause deposition disorders such as Alzheimer’s or Creutzfeldt-Jacob disease. This chapter will not consider the intricacies and implications of the former (this is dealt with in (1)). Instead, the discussion here will focus on the significance of ordered aggregation of proteins into fibrous structures, which lead to a complaint known as amyloid disease. This ordered aggregation involves the association of the protein or peptide subunits into long fibrils with an overall cross-13 structure involving a long array of hydrogen-bonded 13-strands (2). Such fibrils are seen in a number of different human diseases e.g. Alzheimer’s disease, senile systemic amyloidosis, and dialysis related amyloidosis but it is not yet known whether the fibrils or their precursors are the pathogenic agents (see (3)). In this chapter we review the structure of amyloid fibres and describe current views on the possible mechanisms underlying the conversion of soluble protein into these insoluble aggregates.
Vertebrate Neurogenesis
Authors: Storey Kate G
Published: November 2023

The adult nervous system contains the greatest diversity of cell types of any tissue in the vertebrate body, and it is this variety which largely underlies the complexity of the thinking, behaving tissue that is the brain. Many of the molecular mechanisms underlying the critical steps leading to the formation of the vertebrate nervous system have now been identified. This process begins in the early embryo when cells become competent to respond to neural inducing signals, and extends on from the formation of neural precursors and the regulated production of neurons and glia within the patterned neural tube to axon outgrowth and guidance, target recognition, and synapse formation (see Chapter 7). These activities take place within a dynamic structure that begins as a flat neural plate, which undergoes a series of morphogenetic movements and defined patterns of cell proliferation that transform it into a neural tube with distinct regional characteristics.
Patterning of the Neural Crest
Authors: Erickson C A
Published: November 2023

Neural crest cells are mesenchymal cells that emigrate from the dorsal portion of the neural tube, and are remarkable both for their extensive migration and the multiple derivatives to which they give rise. For these reasons, the neural crest has been a popular model system with which to investigate problems of patterning. At the trunk level, neural crest cells take two major pathways of migration. The first is ventral between the neural tube and somites, and the cells that follow this path differentiate primarily into the neurons and glial cells of the peripheral nervous system, the secretory cells of the adrenal medulla, and the enteric nervous system of the gut. About a day later, neural crest cells migrate dorsolaterally between the ectoderm and the somites where they differentiate into the pigment cells of the skin. At the head level, the situation is even more complicated, because many more derivatives arise from the cranial neural folds and the patterns of migration are much more complex.
Rapid screening of phage displayed protein binding afinities by phage ELISA
Authors: DeLano Warren L , Cunningham Brian C
Published: November 2023

Monovalent phage display enables a single protein (or peptide) molecule to be presented on the surface of a phage particle. This protein is translated from a phagemid vector as a fusion linked to the natural pIII coat protein in an Escherichia coli cell coinfected with helper phage. The display achieves monova- lency since the fusion protein rarely substitutes for the native pIII protein from the helper phage genome. While display can be highly variable, typically just 0.05-5% of these phages actually display the protein of interest (1).
Substrate phage display
Authors: Matthews David J , Ballinger Marcus D
Published: November 2023

Substrate phage is a phage display technique that enables one to rapidly survey the substrate specificity of enzymes that recognize peptide substrates. The basic requirements of a substrate phage experiment are as follows:
In vivo and ex vivo selections using phage-displayed libraries
Authors: Hoffman Jason A , Laakkonen Pirjo , Porkka Kimmo , Bernasconi Michele , Ruoslahti Erkki
Published: November 2023

Phage display has emerged as a useful method to discover peptide ligands, and to minimize and optimize the structure and function of proteins (1-3). Phage dis- play screens have two basic components: the target macromolecule and the phage. The phage is used as a scaffold to display recombinant libraries of pep- tides, and provides the means to rescue and amplify peptides that bind a target macromolecule. Target macromolecules are commonly proteins but can be nucleic acids, carbohydrates, and phospholipids, and can be broadly classified as simple or complex depending on their purity (4-6). A pure protein, such as an antibody, immobilized on a solid support is a simple target, while a complex target would be the surface of a cell.
Screening phage libraries with sera
Authors: Monaci Paolo , Cortese Riccardo
Published: November 2023

This chapter comprises a description of methods and procedures for screening phage-displayed peptide libraries using complex mixtures containing the target receptor. This is the case for many interesting biological systems such as serum, cerebrospinal and other biological fluids, cell or tissue surfaces, etc. In such cases the goal is to identify peptides that bind to a particular receptor molecule or to a set of receptors with specific properties.
Phage antibody libraries
Authors: Bradbury Andrew R M , Marks James D
Published: November 2023

The use of phage display to generate antibodies recognizing specific antigens is one of the more successful uses of the technology. This application requires a number of crucial steps common to all molecular diversity technologies: the creation of diversity, coupling of phenotype (antibody protein) to genotype (anti- body gene), selection, amplification, and analysis. Antibodies with affinities com- parable to those obtained using traditional hybridoma technology can be selected from either large na 1ve antibody libraries or from immune phage anti- body libraries. The affinity of initial isolates can be further increased, to levels unobtainable in the immune system, by using the selected antibodies as the basis for construction and selection of libraries where the antibody gene is diversified (see Chapter 14). In this chapter, we will discuss the issues in mating phagemid based single chain Fv (scFv) libraries on phage coat protein pIII and selecting and characterizing antigen specific antibodies. Many of the protocols, however, can be modified for alternative formats.
Interests and Principles in Political Life
Authors: Ginsberg Benjamin
Published: November 2023

For more than 200 years, the tale of George Washington and the cherry tree has symbolized the virtue of America’s first president and, by his example, the importance of integrity as an attribute of political leadership. Unfortunately, the cherry-tree story is a myth, concocted in 1806 by an enterprising preacher, Mason L. Weems, who hoped to bolster the flagging sales of his rather shallow biography of Washington.1
Elections and the Limits of Popular Government
Authors: Ginsberg Benjamin
Published: November 2023

Voting is the only form of political activity in which substantial percentages of Americans routinely engage. More than 60 percent of those eligible—over 122 million people—cast ballots in the 2004 presidential election. The percentage who report participating in other forms of political action, even other electorally related activities, is relatively small. In 2004, only 13 percent gave money to a campaign, 7 percent attended a meeting, and barely 3 percent actually worked to help elect a particular political candidate.1
Private Interests and Public Policies
Authors: Ginsberg Benjamin
Published: November 2023

Many policy analysts assert that government action is often required to correct what they call “market failure.” This concept refers to inequities, inefficiencies, or harmful externalities produced by the operations of private markets. The presumption underlying this idea is that government agencies and officials are motivated mainly by concern for the public’s welfare and will intervene in the private sector in ways that are likely to promote broad public interests.
Conclusion: Why Participate in Politics?
Authors: Ginsberg Benjamin
Published: November 2023

Americans are continually exhorted to participate; to make their views known; to vote for the best person; and, in a variety of other ways, to play an active role in political life. But for most people, most of the time, politics is not ennobling, particularly efficacious, or even interesting. Clausewitz was correct to equate politics with war. Each in its own way is an unrewarding, albeit sometimes necessary, activity for most participants. Common soldiers seldom find war an edifying experience, even when it can be said that the reasons to fight were valid and legitimate. In political combat, most participants are foot soldiers in battles fought for the benefit of others, for goals that are seldom fully revealed to the public at large.
Shoulders Of Giants
Authors: Hamilton W D
Published: November 2023

UP to 1963 my only ‘published’ writings were a story written when a child and filling a half page in Sevenoaks Preparatory School Magazine and a review of a popular book on dolphins for a New Zealand literary journal. The review was done when I was already a graduate student in London. The reasons why the editor of Landfall requested a review from a biology student so far away are, probably, first, chat he did not know other biologists, second, I was his godson, and, third, that he knew from my rare letters that I was working on something to do with social behaviour. Even then the lives of dolphins had a reputation for being unusual and complex. My ideas about them, as about the book, were very lightweight and my review does not merit inclusion in this book. However, the topic of dolphins and my godfather’s ‘nepotism’ in sending me the task are relevant in an odd way to the paper that follows.
Sorority Avenue
Authors: Hamilton W D
Published: November 2023

IN the late 1960s I was invited by Gerhard H. Schmidt of the University of Wiirzburg to write a chapter for a proposed multi-author volume on social insects to be published in German. He wanted me to explain my ideas about how relatedness affects the evolution of social insects. I was to write an English version that would be translated, The request was attractive because what I had written on social insects in 1964 (see Chapter 2) was overdue for revision and extension, besides which I was delighted at the idea of a translation specially reaching German readers.
Astringent Leaves
Authors: Hamilton W D
Published: November 2023

This paper was the first to be generated entirely from within my new job in America. Why had I moved? Partly it was the Brazilian experience of teaching attentive and interested graduate students that set me thinking that there might be better places to be a lecturer than at Imperial College. More, however, it was the return from the same Brazilian trip to find myself still in the same teaching rank that I had held 12 years before when I joined the college, and with various later comers promoted past me, which indeed had happened for some time.
Distal Clavicular Osteolysis Treated With Platelet-Rich Plasma: A Case Report
Authors: Kim Alexander R. , Covey Carlton J.
Published: November 2023

Atraumatic distal clavicular osteolysis (DCO) is a cause of shoulder pain in younger athletes, often resulting from weightlifting and activities with repetitive pressing and overhead lifting. Athletes will present with shoulder pain localized to the acromioclavicular (AC) joint, with tenderness to palpation over the joint exacerbated by provocative testing on examination. Conservative management often includes activity modification, oral analgesics, physical therapy, and corticosteroid injection. Distal clavicular osteolysis can be refractory to conservative management and these athletes are often referred for surgical consultation. Platelet-rich plasma (PRP) injections have been used to treat a wide variety of musculoskeletal injuries, but there have been no published studies assessing the efficacy of PRP injections specifically for distal clavicle osteolysis. We present a case of refractory DCO successfully treated with an ultrasound-guided PRP injection of the AC joint.
Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia
Authors: Swiecki-Sikora Allison L. , Lauder Abigail , Harris Adina , Tagai Erin K. , Deng Mengying , Jeronis Stacey L. , Houck Karen L. , Miller Suzanne M. , Hernandez Enrique
Published: November 2023

Objectives

The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children.

Materials and Methods

Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups.

Results

One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic (p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination.

Conclusions

In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.
Roflumilast 0.3% Cream: a Phosphodiesterase 4 Inhibitor for the Treatment of Chronic Plaque Psoriasis
Authors: Nicolas Samar E. , Bear Michael D. , Kanaan Abir O. , Coman Oana Andreia , Dima Lorena
Published: November 2023

Background:

Plaque psoriasis is a chronic dermatologic autoimmune disease that affects adults and children. Roflumilast 0.3% cream is currently the only topical phosphodiesterase 4 inhibitor indicated for the treatment of plaque psoriasis in patients 12 years or older.

Pharmacodynamics and Pharmacokinetics:

Roflumilast inhibits phosphodiesterase 4 inhibitor enzyme leading to the accumulation of cyclic adenosine monophosphate, which suppresses the inflammatory mediators interferon-γ and tumor necrosis factor-α. Roflumilast, applied once daily, reaches steady state by day 15 and has a half life of approximately 4 days in adults. Roflumilast undergoes extensive hepatic metabolism by cytochrome P450 enzymes and conjugation. Roflumilast is 99% bound to plasma proteins.

Clinical Trials:

Roflumilast efficacy and safety were evaluated in the DERMIS-1 and DERMIS-2 clinical trials. These identically designed, double-blind, vehicle-controlled phase 3 trials randomized 881 patients to roflumilast 0.3% cream or vehicle, applied once daily for 8 weeks. In DERMIS-1, the Investigator Global Assessment success rate was 42.4% with roflumilast 0.3% cream compared with 6.1% with the vehicle (32.3%–46.9%; P <0.001). Similarly, in DERMIS-2, the Investigator Global Assessment success rate was 37.5% with roflumilast 0.3% cream compared with 6.9% with the vehicle (20.8%–36.9%; P <0.001). Of 881 participants, 1% discontinued treatment with roflumilast cream due to adverse reactions compared with 1.3% treated with vehicle. Urticaria at the application site (0.3%) was the most common adverse reaction that led to discontinuation of roflumilast.

Therapeutic Advance:

To date, topical corticosteroids are the most commonly used agents to treat mild plaque psoriasis. Sensitive areas are often challenging to treat with existing topical therapy, including corticosteroids. Topical roflumilast has shown to be effective in treating sensitive areas, including skin folds, and may be an alternative to systemic therapy for some patients. The Food and Drug Administration approved topical roflumilast for the treatment of plaque psoriasis, including intertriginous areas, for patients 12 years or older.
Transfusion Practice
Authors: Kita Vanessa Yukie , Orsi Kelly Cristina Sbampato Calado , de Souza Adja Havreluk Paiva , Tsunemi Miriam Harumi , Avelar Ariane Ferreira Machado
Published: November 2023

The objective of this study was to compare hemolysis marker levels after in vitro infusion of red blood cells (RBCs) according to storage time, infusion rate, and peripheral intravenous catheter size. This is an experimental study with randomly administered RBCs in quintuplicate, according to storage time shorter than and longer than 14 days, as well as infusion rate (50 mL/h and 100 mL/h) using catheters with calibers of 14-, 18-, and 20-gauge. Aliquots were collected from RBCs (V1), after equipment and catheter (V2) free-flow filling and after controlled infusion through the catheter (V3). The hemolytic markers analyzed were degree of hemolysis (%), hematocrit (Ht) (%), total hemoglobin (THb) (g/dL), free hemoglobin (FHb) (g/dL), potassium (K) (mmol/L), and lactate dehydrogenase (LDH) (U/L), considering a probability of error ≤5%. Sixty experiments were performed with the analysis of 180 aliquots. When RBCs aged <14 days were used, all catheters tended to increase THb, FHb, and K; while >14 days, RBCs presented increased FHb and degree of hemolysis with catheters of 18-gauge and THb levels at 14-gauge. Among the conditions analyzed, only 20-gauge catheters (the smallest) did not influence changes in hemolysis markers, regardless of RBC storage time.
Elder Abuse
Authors: Hellwig Karen
Published: November 2023

Elder abuse is a major public health problem. Prior to the pandemic, approximately 1 in 10 older adults in the United States experienced elder mistreatment. In 2020, this number doubled to 1 in 5, a nearly 84% increase (Liu, 2022). More distressing is that in almost 60% of elder abuse and neglect cases, a family member is the offender and two-thirds of the perpetrators are adult children or spouses (Nursing Home Justice Team, 2021). Financial abuse is reportedly the fastest-growing form of elder abuse with theft scams at the forefront (Hillendahl, 2022). It is essential that healthcare providers, especially those who care for patients in their homes, understand what elder abuse is, how it can be identified, what conditions may lead to elder abuse, and what home care providers can do to properly intervene when it is suspected that older adults are being abused.
Impact of a Decision Support System on Fall-Prevention Nursing Practices
Authors: Jung Hyesil , Park Hyeoun-Ae , Lee Ho-Young
Published: November 2023

Objectives

The aim of this study was to develop a computerized decision support system (CDSS) that could automatically calculate the risk of falls using electronic medical record data and provide evidence-based fall-prevention recommendations based on risk factors. Furthermore, we analyzed the usability and effect of the system on fall-prevention nursing practices.

Methods

A computerized fall-prevention system was developed according to the system development life cycle, and implemented between March and August 2019 in a single medical unit with a high prevalence of falls. The usability was evaluated 1 month after CDSS implementation. In terms of time and frequency, changes in fall-prevention nursing practices were analyzed using survey data and nursing documentation, respectively. Finally, the incidence of falls before and after system implementation was compared to examine the clinical effectiveness of the CDSS.

Results

According to the usability test, the average ease of learning score (5.083 of 7) was the highest among 4 dimensions. The time spent engaged in fall-prevention nursing care per patient per shift increased, particularly for nursing diagnoses and planning. Moreover, the mean frequency of daily documented fall-prevention interventions per patient also increased. Particularly, nursing statements related to nonspecific interventions such as environmental modifications increased. However, the incidence of falls did not decrease after implementation of the CDSS.

Conclusions

Although adoption of the computerized system increased the time spent and number of records created in terms of fall-prevention practices in nurses, no improvement in clinical outcomes was observed, particularly in terms of fall rate reduction.
Interprofessional Learning in Multidisciplinary Healthcare Teams Is Associated With Reduced Patient Mortality: A Quantitative Systematic Review and Meta-analysis
Authors: Webster Craig S. , Coomber Ties , Liu Sue , Allen Kaitlin , Jowsey Tanisha
Published: November 2023

Objective

The aim of the study is to identify quantitative evidence for the efficacy of interprofessional learning (IPL) to improve patient outcomes.

Methods

We conducted a systematic review and meta-analysis of quantitative patient outcomes after IPL in multidisciplinary healthcare teams reported in the Medline, Scopus, PsycInfo, Embase, and CINAHL databases.

Results

In 2022, we screened 15,248 reports to include 20 and extracted rates of mortality and primary outcomes in conventional care groups and intervention groups (involving initiatives to promote IPL in multidisciplinary teams). The meta-analysis of the 13 studies reporting mortality outcomes demonstrated that the 7166 patients in the intervention group had a significant 28% (95% confidence interval [CI], 40%–14%; P < 0.0003) reduced risk of dying compared with the 6809 patients in the conventional care group. The meta-analysis of the 14 studies reporting other treatment-related adverse outcomes demonstrated that the 4789 patients in the intervention group had a significant 23% (95% CI, 33%–12%; P < 0.0001) reduced risk of experiencing an adverse outcome during care compared with the 4129 patients in the conventional care group. Sensitivity analysis, involving the exclusion of the 20% of individual studies with the widest 95% CIs, confirmed the precision and reliability of our findings.

Conclusions

We believe that our results are the first to demonstrate significant quantitative evidence for the efficacy of IPL to translate into changes in clinical practice and improved patient outcomes. Our results reinforce earlier qualitative work of the value of IPL, but further prospective quantitative and mixed-methods research is needed to better define such benefits.
Cost Savings Associated With Implementing 4 Total Joint Replacement Electronic Clinical Quality Measures Nationally: 2020–2040
Authors: Dykes Patricia C. , Curtin-Bowen Mica , Franz Calvin , Syrowatka Ania , Lipsitz Stuart , Sainlaire Michael , Businger Alexandra , Thai Tien , Chen Antonia F. , Schoenfeld Andrew J. , Lieberman Jay R. , Iorio Richard , O’Brien Todd , Blanchfield Bonnie , Katz Jeffrey N. , Jiranek William A. , Melnic Christopher , Bates David W.
Published: November 2023

Background

Digital transformation using widely available electronic data is a key component to improving health outcomes and customer choice and decreasing cost and measurement burden. Despite these benefits, existing information on the potential cost savings from electronic clinical quality measures (eCQMs) is limited.

Methods

We assessed the costs of implementing 4 eCQMs related to total hip and/or total knee arthroplasty into electronic health record systems across healthcare systems in the United States. We used published literature and technical expert panel consultation to calculate low-, mid-, and high-range hip and knee arthroplasty surgery projections, and used empirical testing, literature, and technical expert panel consultation to develop an economic model to assess projected cost savings of eCQMs when implemented nationally.

Results

Low-, mid-, and high-range projected cost savings for year’s 2020, 2030, and 2040 were calculated for 4 orthopedic eCQMs. Mid-range projected cost savings for 2020 ranged from $7.9 to $31.9 million per measure per year. A breakeven of between 0.5% and 5.1% of adverse events (measure dependent) must be averted for cost savings to outweigh implementation costs.

Conclusions

All measures demonstrated potential cost savings. These findings suggest that eCQMs have the potential to lower healthcare costs and improve patient outcomes without adding to physician documentation burden. The Centers for Medicare and Medicaid Services’ investment in eCQMs is an opportunity to reduce adverse outcomes and excess costs in orthopedics.
Experiences and Perceptions of Healthcare Stakeholders in Disclosing Errors and Adverse Events to Historically Marginalized Patients
Authors: Olazo Kristan , Gallagher Thomas H. , Sarkar Urmimala
Published: November 2023

Objectives

We sought to assess the experiences and perceptions of healthcare stakeholders involved in the response to historically marginalized patients who have been harmed in healthcare. We investigated the challenges in disclosing errors and adverse events and the types of tools and resources that would better address the needs of historically marginalized patient populations.

Methods

We conducted separate focus groups with two healthcare stakeholder groups: (1) frontline clinicians directly involved in the clinical care of historically marginalized patients and (2) risk and patient safety professionals involved in the hospital response to care breakdowns. We conducted an inductive analysis of the qualitative data to identify thematic clusters.

Results

We interviewed 7 clinicians and 5 risk safety professionals, with a total sample size of 12 participants. Participants shared multilevel challenges in responding to historically marginalized patients after harm (system-, organizational-, and patient-level), such as fragmentation of care, lack of standardized protocols, and patient mistrust. Participants also identified their desired tools and resources for disclosure to meet the needs of historically marginalized patients, which included culturally appropriate toolkits, disclosure training, and the inclusion of multidisciplinary healthcare team members in the disclosure process.

Conclusions

Our results suggest that multiple interventions will be needed to achieve the goal of prompt disclosure of errors and adverse events across all populations engaged in health care. Future studies should investigate the perspectives of historically marginalized patients and their family members on how error and adverse event disclosure conversations should unfold.
Evaluating the Effects of a General Anesthesia and Prone Position Nursing Checklist and Training Course on Posterior Lumbar Surgery: A Randomized Controlled Trial
Authors: Cai Jianshu , Jiang Miaomiao , Qi Haiou
Published: November 2023

Background

While general anesthesia in the prone position is one of the most utilized surgical positions, it predisposes to multiple types of complications. Existing studies on this topic are mostly literature reviews or focus on solving one complication, which limits their clinical use.

Objective

The aims of the study were to evaluate the effectiveness of a 22-item general anesthesia and prone position nursing checklist and specific training course at preventing complications related to general anesthesia in the prone position.

Design

The study used a randomized controlled trial.

Settings and Participants

Convenience sampling was used to recruit patients who underwent general anesthesia during posterior lumbar surgery from July 2021 to December 2021 at the Run Run Shaw Hospital, Zhejiang University School of Medicine Hospital.

Methods

Patients involved in the study were randomly assigned to the control (standard general anesthesia and prone position care) or experimental group (general anesthesia and prone position nursing checklist combined with specific training course in addition to standard general anesthesia and prone position care). Outcomes were pressure injuries, peripheral nerve injuries, ocular complications, and length of stay (LOS). Patient satisfaction, Numeric Pain Rating Scale (NRS) and the Oswestry Disability Scale were also measured.

Results

Compared with the control group, pressure injury, brachial plexus injury, and two ocular findings (foreign body sensation and blurry vision) were significantly less common in the intervention group (P ≤ 0.01). Participants who received standard general anesthesia and prone position care had lower self-reported satisfaction than those managed with the general anesthesia and prone position nursing checklist plus specific training course (P = 0.002). The checklist-based intervention also significantly reduced LOS (P = 0.000) and NRS (P = 0.000).

Conclusions

The intervention group had significant fewer general anesthesia in the prone position-related complications, improved satisfaction, reduced LOS, and lower NRS. These findings suggest that a general anesthesia and prone position nursing checklist in addition to a specific training course are beneficial to standardizing prone position nursing care during posterior lumbar surgery.
Adverse Events in Pediatric Inpatients: The Japan Adverse Event Study
Authors: Sakuma Mio , Ohta Yoshinori , Takeuchi Jiro , Yuza Yuki , Ida Hiroyuki , Bates David W. , Morimoto Takeshi
Published: November 2023

Objectives

Adverse events (AEs) represent an important cause of morbidity and mortality for pediatric inpatients; however, reports on their epidemiology in pediatrics, especially outside Western countries, are scarce. We investigated the incidence and nature of AEs in pediatric inpatients in Japan.

Methods

Trained pediatrician and pediatric nurses reviewed all medical documents of 1126 pediatric inpatients in 2 tertiary care teaching hospitals in Japan, and potential incidents were collected with patients’ characteristics. Age was categorized into 6 groups (neonates, infants, preschoolers, school-aged children, teenagers, and over-aged pediatric patients), and medical care when potential incidents occurred was classified into drug, operation, procedure/examinations, nursing, management, and judgment. Physician reviewers independently evaluated all collected incidents into AEs, potential AEs, medical errors, and exclusions and assessed their severity and preventability.

Results

A total of 1126 patients with 12,624 patient-days were enrolled, and 953 AEs, with an incidence of 76 (95% confidence interval, 71–80) per 1000 patient-days, were identified. Preventable AEs accounted for 23% (218/953) of AEs. The incidence of AEs tended to decrease with increasing age. The proportion of AEs that were preventable was highest in neonates (40%), and this proportion decreased as children aged. Both judgment and management-related AEs were considered preventable AEs, and judgment-related AEs were more severe AEs than no-judgment–related AEs; 43% were life-threatening.

Conclusions

Adverse events were common in Japanese pediatric inpatients, and their preventability and severity varied considerably by age category and medical care. Further investigation is needed to address which strategies might most improve pediatric patient safety.
Tepidibacter hydrothermalis sp. nov., a novel anaerobic bacterium isolated from a deep-sea hydrothermal vent
Authors: Dai Jie , Li Xue-Gong , Zhang Wei-Jia , Wu Long-Fei
Published: November 2023

A novel anaerobic heterotrophic bacterium, designated strain SWIR-1T, was isolated from a deep-sea hydrothermal vent field sample collected from the Southwest Indian Ridge at a depth of 2700 m. Phylogenetic analysis indicated that strain SWIR-1T belongs to the genus

Tepidibacter

, and the most closely related species are

Tepidibacter mesophilus

B1T (99.1 % 16S rRNA gene sequence similarity),

Tepidibacter formicigenes

DV1184T (94.6 %) and

Tepidibacter thalassicus

SC562T (93.9 %). Strain SWIR-1T shares 77.3–87.2 % average nucleotide identity and 21.5–35.7 % digital DNA–DNA hybridization values with the three type strains of

Tepidibacter

species. Cells of strain SWIR-1T were Gram-stain-positive, motile, short straight rods. Endospores were observed in stationary-phase cells when grown on

Thermococcales

rich medium. Strain SWIR-1T grew at 15–45 °C (optimum, 30°C), at pH 5.5–8.0 (optimum, pH 7.0) and with 1.0–6.0 % (w/v) NaCl (optimum, 2.0 %). Substrates utilized by strain SWIR-1T included complex proteinaceous, chitin, starch, lactose, maltose, fructose, galactose, glucose, rhamnose, arabinose, ribose, alanine, glycine and glycerol. The major fermentation products from glucose were acetate, lactate, H2 and CO2. Elemental sulphur, sulphate, thiosulphate, sulphite, fumarate, nitrate, nitrite and FeCl3 are not used as terminal electron acceptors. The main cellular fatty acids consisted of iso-C15 : 0 (28.4 %), C15 : 1 iso F (15.4 %) and C16 : 0 (9.8 %). The major polar lipids were phospholipids and glycolipids. No respiratory quinones were detected. Genomic comparison revealed a distinctive blended gene cluster comprising hyb-tat-hyp genes, which play a crucial role in the synthesis, maturation, activation and export of NiFe-hydrogenase. Based on the phylogenetic analysis, genomic, physiologic and chemotaxonomic characteristics, strain SWIR-1T is considered to represent a novel species within the genus

Tepidibacter

, for which the name Tepidibacter hydrothermalis sp. nov. is proposed. The type strain is strain SWIR-1T (=DSM 113848T=MCCC 1K07078T)
Alteriqipengyuania flavescens sp. nov., isolated from Pearl River Estuary sediment
Authors: Zhang Kun , Han Cheng Hui , Ling Juan , Yin Jianping
Published: November 2023

Two Gram-stain-negative, aerobic, rod-shaped, non-motile and golden yellow pigmented bacteria, designated as SCSIO 75105T and SCSIO 75732, were isolated from sediment in the Pearl River Estuary, Guangdong Province, PR China. Cells were positive for catalase and oxidase. Growth occurred at 10–37 °C (optimum, 28 °C), pH 6.0–10.0 (optimum, pH 7.0) and 0–5.0 % (w/v) NaCl (optimum, 2.0–3.0 %). The 16S rRNA gene analysis indicated that these two isolates shared a similarity of 100 % each other. The 16S rRNA gene sequence analysis indicated that these two isolates showed highest similarity to

Altererythrobacter ishigakiensis

CGMCC 1.14979T (97.3 %). However, a phylogenetic tree based on 288 orthologous clusters indicated that these two isolates were closely related to

Alteriqipengyuania halimionae

CPA5T. The average nucleotide identity, average amino acid identity, digital DNA–DNA hybridization and evolutionary distance values between the two isolates and

Alteriqipengyuania halimionae

CPA5T were 73.7–74.0 %, 65.2 %, 19.5 % and 0.24, respectively. The genomic DNA G+C content of both isolates was 65.2 mol%. The major cellular fatty acids were C18 : 1
 ω7c, C17 : 1
 ω6c and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), and Q-10 was the respiratory quinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid and one unidentified glycolipid. On the basis of the results of phenotypic, physiological, chemotaxonomic and genotypic characterization, strains SCSIO 75105T and SCSIO 75732 are considered to represent a novel species in the genus

Alteriqipengyuania

, for which the name Alteriqipengyuania flavescens sp. nov. is proposed. The type strain is SCSIO 75105T (=KCTC 92502T=MCCC 1K07993T).
N-acetylcysteine Microparticles Reduce Cisplatin-induced RSC96 Schwann Cell Toxicity
Authors: Kedeshian Katherine , Hong Michelle , Hoffman Larry , Kita Ashley
Published: November 2023

Objectives

Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin-induced demyelination of spiral or Scarpa’s ganglion neurons may play an additional role in drug-induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability. This work describes a cellular model of cisplatin-induced Schwann cell injury and investigates the ability of the antioxidant N-acetylcysteine to promote Schwann cell viability. A local delivery system of drug-eluting microparticles was then fabricated, characterized, and investigated for bioactivity.

Methods

RSC96 rat Schwann cells were dosed with varying concentrations of cisplatin to obtain a dose curve and identify the lethal concentration of 50% of the cells (LC50). In subsequent experiments, RSC96 cells were co-treated with cisplatin and both resuspended or eluted N-acetylcysteine. Cell viability was assessed with the CCK8 assay.

Results

The LC50dose of cisplatin was determined to be 3.76 μM (p=2.2 × 10−16). When co-dosed with cisplatin and therapeutic concentration of resuspended or eluted N-acetylcysteine, Schwann cells had an increased viability compared to cells dosed with cisplatin alone.

Conclusion

RSC96 Schwann cell injury following cisplatin insult is characterized in this in vitro model. Cisplatin caused injury at physiologic concentrations and N-acetylcysteine improved cell viability and mitigated this injury. N-acetylcysteine was packaged into microparticles and eluted N-acetylcysteine retained its ability to increase cell viability, thus demonstrating promise as a therapeutic to offset cisplatin-induced ototoxicity.

Lay Summary

Cisplatin is a chemotherapeutic agent known to cause balance and hearing problems through damage to the inner ear. This project explored cisplatin injury in a Schwann cell culture model and packaged an antioxidant into microparticles suitable for future drug delivery applications.
The sorting nexin requirement of the Vps68 recycling signal is context dependent
Authors: Kölling Ralf
Published: November 2023

Here we analyzed the recycling of the Vps55/Vps68 complex in the yeast endocytic pathway. Deletion ofVPS55andVPS68caused the same moderate stabilization of the endocytic cargo protein Ste6. No additive effect was observed by the double deletion, reinforcing the notion that both proteins form a functional unit. This is further underlined by the finding that the two proteins are dependent on each other for proper cellular localization. A tyrosine-based recycling signal was identified in the cytosolic tail of Vps68. Curiously, it turned out that the recycling signal was context dependent with respect to the usage of recycling factors. In its natural context, recycling was dependent on the sorting nexin Mvp1/SNX8 and independent of retromer. But, when the signal was inserted into a well-studied retromer substrate, the CPY receptor Vps10 devoid of its own signals, it became dependent on retromer and Snx3. This finding suggests that the availability of the recycling signal could be subjected to regulation. Previously, we obtained evidence that Vps68 cooperates with ESCRT-III in intraluminal vesicle (ILV) formation at late endosomes. It is thus conceivable that recycling of Vps55/Vps68 only occurs when its function in ILV formation is finished. Our data also suggest that recycling of Vps55/Vps68 could be regulated by phosphorylation. In addition, we identified Dcr2, the yeast orthologue of human sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), as a new factor involved in Mvp1 dependent recycling of Vps55/Vps68.

Article Summary

Some proteins in the endocytic pathway are recycled to the Golgi or to the plasma membrane and are thus spared from degradation in the lysosome or vacuole. Here a recycling signal was identified in the Vps55/Vps68 complex. The data suggest that the accessibility of the signal is regulated. Further, a new factor involved in the sorting nexin Mvp1/SNX8 dependent recycling of Vps55/Vps68 was identified. This factor is Dcr2, the yeast orthologue of human sphingo-myelin phosphodiesterase acid-like 3A (SMPDL3A).