bluuebunny/crossref_metadata_2025 huggingface dataset:
The functioning of molecular switches in three dimensions
Authors: Wittinghofer Alfred
Published: November 2023

Two major groups of GTP-binding proteins have been identified. The first is rather small and includes FtsZ and tubulin, both of which polymerize to form fibre-like structures. The second is a major class and consists of many families or superfamilies sharing common sequence motifs and a common core structure. These are referred to as GTP-binding proteins or GTPases and they act as regulatory molecules in all eukaryotic cells (1). The common core structure is relatively well conserved within but not necessarily between families. The major families are described in the first eight chapters of this book and include the protein biosynthesis factors such as elongation factors Tu (EF-Tu) and G (EF-G) and their mammalian homologues EF-la and EF-2, the superfamily of Ras-related proteins, the a subunits of heterotrimeric G proteins, the signal recognition particle and its receptor together with the bacterial counterparts Ffh and FtsY, and the dynamin/Mx type of proteins (2, 3). In addition to these two groups there are a few GTP-specific metabolic enzymes, such as adenylosuccinate synthetase or PEP-carboxykinase, but these have no sequence conservation either between each other or to the proteins mentioned above, and will not be considered here any further. Although the protein biosynthesis factors were the first GTP-binding proteins to be discovered and many ground-breaking biochemical and structural studies have been carried out on these, this chapter will focus primarily on small GTP-binding proteins and G proteins since these are more closely related to each other and their biology in eukaryotic cells has been studied intensively in recent years. Structural aspects of GTP-binding proteins have been dealt with in earlier reviews (4, 5).
Toxins that affect neurotransmitter release
Authors: O’kane Cahir J , Schiavo Giampietro , Sweeney Sean T
Published: November 2023

As a perceptive observer once remarked, given enough genetic variation, evolution can select for machine-gun resistance in dogs. Less surreally, one outcome of evolutionary arms races between predators and prey has been the evolution of toxins that can immobilize their victims effectively and in small amounts, by interfering with synaptic transmission. A happier outcome is that some of these toxins have greatly aided our understanding of the roles of several key synaptic proteins that function in neurotransmitter release.
Dissecting the molecular mechanisms of neurotransmitter release in Drosophila
Authors: Pennetta Giuseppa , Wu mark N , Bellen Hugo J
Published: November 2023

Most intercellular communication in nervous systems relies on the release of neurotransmitters at chemical synapses. A detailed understanding of the presynaptic mechanisms underlying neurotransmitter release may not only provide basic insights into regulated secretion, but may also help us in the design of therapeutic agents to modulate this process. It has become apparent in the past five years that the vast majority of the proteins implicated in neurotransmitter release are extremely well conserved in the animal kingdom. Hence, model systems amenable to sophisticated genetic analyses such as C. elegans and Drosophila, are playing an important role in improving our understanding of the function of these proteins in vertebrates.
Representational difference analysis of cDNA
Authors: Hubank M , Schatz D G
Published: November 2023

Accurate analysis of gene expression has become achievable in recent years thanks to the development of a variety of sophisticated techniques (1). In this chapter we describe the polymerase chain reaction (PCR)-based subtractive hybridization technique of cDNA representational difference analysis (cDNA RDA). cDNA RDA can be used to identify genes whose expression differs between two or more populations, and unlike gene array approaches. requires only basic laboratory equipment. cDNA RDA is a flexible, relatively inexpensive, and highly effective technique in which target cDNA fragments are sequentially enriched by favourable hybridization kinetics and subsequently amplified by PCR. The positive selection of differences and removal of common genes targets identifi cation to only those genes which differ between populations, resulting in great sensitivity, and allowing application of the technique to very low amounts of starting material, including fluorescence-activated cell sorter (FACS) purified populations of cells.
Bacteriology of normally sterile body fluids
Authors: Murphy Olive , Freeman Roger
Published: November 2023

The detection of micro-organisms in a normally sterile body fluid has important diagnostic, therapeutic, and prognostic implications. Whilst culture of the infecting bacteria will allow identification and antibiotic sensitivity testing to be carried out, these infections are often serious and a rapid diagnosis is required to ensure correct chemotherapy. Various strategies have been adopted to accelerate the diagnosis with the development of rapid culture and non culture techniques. The recovery of a bacterium from these specimens should always be considered significant until proven othe1wise. Organisms should be identified to species level; not an arduous task as most infections are caused by a single species. This chapter describes current methods for the examination of the various categories of normally sterile body fluids and interpretation of these data.
Protein folding monitored by mass spectrometry
Authors: Robinson Carol V
Published: November 2023

Mass spectrometry (1) is one of the more recent techniques to be applied to protein folding (2, 3). Much of the excitement surrounding its application derives from its ability to distinguish populations of folding intermediates. To obtain information that will distinguish protein molecules containing different amounts of secondary structure during a folding reaction, it is necessary to introduce a label. The pulse-labelling approach, developed for use in conjunction with NMR, described in Chapter 3, is ideally suited since the mass of protons and deuterons differ. Measuring the mass of the protein therefore reveals different amounts of protons and deuterons, on the basis of which partially folded states can readily be identified, since they contain numbers of deuterons intermediate between the numbers present in the unfolded and fully folded states. The challenge for mass spectrometry is to maintain the secondary struc ture during the ionization of the protein so that the label in solution is retained in the gas phase. Elcctrospray ionization (ESI-MS) is the method of choice since it produces multiply charged gas-phase ions by solvent evaporation from protein molecules in solution, with little perturbation of the secondary structure.
Assembly of multi-subunit structures
Authors: Seckler Robert
Published: November 2023

Many cellular proteins are oligomers of identical or different polypeptides, and in most cases, the biological activity of such proteins depends strictly on their quaternary structure. Modifying the assembly of such homo-oligomeric or hetero-oligomeric proteins could be a very specific and efficient way of drug targeting (1-3). This would be greatly facilitated by knowledge about the structural basis of subunit interface stability and of oligomer assembly mechanisms. The Protein Data Bank of three-dimensional structures now contains more than 2000 entries of oligomeric proteins and a number of very large multisubunit structures have been determined in recent years (Table 1). The folding and assembly pathways of many oligomeric proteins have been characterized over the past three decades (4-6) and equilibrium dissociation and unfolding transitions have been analysed for a number of dimeric and a very few higher-number oligomeric proteins (7, 8).
Cellular functions of molecular chaperones
Authors: Leroux Michel R , Hartl F Ulrich
Published: November 2023

Proteins are faced with the potential problems of aggregation and denaturation throughout their existence. First, they are synthesized on ribosomes as unfolded polypeptide chains that must reach their stably folded conformations, either as monomers or oligorneric species, or else be eliminated on the basis that they cannot serve useful purposes in the cell. This is no easy task, given that the aggregation-prone nascent polypeptide chain cannot fold to its native state until the complete protein (or individual protein domain) is freed from the ribosome. Secondly, the cellular environment is densely populated with macromolecules that increase the risk that the nascent polypeptide will become entangled with other cellular components and aggregate rather than fold. After their biogenesis, proteins must fulfil their cellular functions in limited time spans, within an environment that is highly regulated but may undergo fluctuations in temperature and chemical composition (due to exposure to external agents or to disease, for example). Such cellular insults can cause irreversible damage to proteins and consequently shorten their life span. Whether due to impaired function or to the time for natural turnover, the culminating point of a protein’s life is invariably to be unfolded and minced back to basic constituents by the cellular proteolytic degradation machinery.
Protein glycosylation
Authors: Ashford David A , Platt Fran
Published: November 2023

The most common co- and post-translational modification of eukaryotic proteins is the covalent attachment of oligosaccharides. The vast majority of cell surface and secreted proteins are glycosylated, as are the envelope proteins of many viruses. It is now clear that the presence of glycans on glycoproteins affects both the structural and functional properties of the protein, such as protein folding and conformation, stability to denaturation, solubility, and resistance to proteolysis as well as key biological properties such as receptor binding, modulation of enzyme activity, and cellular recognition events (1-5). This chapter is intended as a guide to the analysis of the glycosylation of proteins and to techniques for the manipulation of protein glycosylation. A previous title in the Practical Approach series (6) and other recent books and articles (7-10) have covered glycobiology, glycosylation, and carbohydrate analysis more extensively and they (and the references they contain) can provide more detail for readers who wish to know more.
Cell surface carbohydrates: cell type-specific expression
Authors: Fukuda Minoru
Published: November 2023

Cell surface carbohydrates are major components of the outer surface of mammalian cells and are very often characteristic of cell types. Carbohydrate structures change dramatically during mammalian development. Specific sets of carbohydrates are expressed at different stages of differentiation and in many instances these carbohydrates are recognized by specific antibodies, thus providing differentiation antigens (1-6). In mature organisms, expression of distinct carbohydrates is eventually restricted to specific cell types, providing cell type--specific carbohydrates. Aberrations in these cell surface carbohydrates are associated with various pathological conditions, including malignant transformation.
Diseases-with deficiencies in asparagine-linked glycosylation
Authors: Schachter Harry
Published: November 2023

The study of human disease, particularly of congenital disease, has traditionally provided a rich source of insight into biochemical pathways and their functions. The field of glycobiology has long been plagued by many unanswered questions concerning the biological functions of protein glycosylation. As described in other chapters of this book, a series of discoveries over the past 25-30 years has provided some answers. Human disease has contributed greatly to this enlightenment (1, 2). Table 1 lists six autosomal recessive diseases in which a defect in the synthesis of Asn-linked glycans (N-glycans) has been clearly demonstrated. Since at least 0.5-1% of the transcribed human genome is devoted to the production of proteins involved in the synthesis, degradation and function of glycoconjugates (3), many other such congenital diseases may exist. This chapter will focus on three of these diseases which have proved beyond any doubt that N-glycans are essential for normal human development, carbohydrate-deficient glycoprotein syndromes types I and II (or congenital disorders of glycosylation, CDG I and CDG II, as they are now called) in section A of the chapter and hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS, congenital dyserythropoietic anemia type II) in section B of the chapter.
DNA pooling methods for association mapping of complex disease loci
Authors: Barcellos Lisa F , Germer Soren , Klitz William
Published: November 2023

The rapid development and application of highly informative microsatellite markers throughout the human genome has greatly facilitated the identification of disease loci in hundreds of rare Mendelian disorders. Utilization of large multigenerational pedigrees with multiple affected individuals is a proven strategy for isolating chromosomal regions containing disease genes using microsatellite markers and traditional lod score linkage analysis. Linkage studies are often followed by association studies to further define the candidate region and to identify the putative disease gene. Linkage disequilibrium, the basis of marker associations, is typically found within a distance of 500 kb, about 0.5 (cM), although, in general, this distance may vary considerably according to population history, across different regions of the genome, and with marker type (1–4). Disease genes mapped to date, however, have shown linkage disequilibrium with markers sufficiently close to the disease gene to guide discovery of the disease locus. Examples of these successes include cystic fibrosis, Huntington disease, Wilson disease, Batten disease, Friedreich ataxia, myotonic dystrophy, torsion dystonia, hereditary haemochromatosis, diastrophic dysplasia, adult onset polycystic kidney disease, familial breast cancer, and many others.
Preparation of lymphocytes and identification of lymphocyte subpopulations
Authors: Plebanski Magdalena
Published: November 2023

This chapter provides the common methods used to isolate lymphocytes and accessory cells from humans and animals (see Section 2), handle them after recovery (see Sections 3 and 4) and, if necessary, sub fractionate them (see Sections 5 and 6). It provides general advice as to which methods may be best used for the particular objectives of your experiment, and cross-references to methods throughout the book. It is common when using a new method to follow it precisely. But what if your house is on fire while you are in the middle of purifying a lymphocyte subpopulation? Should you risk leaving your precious cells on the bench? To help avoid some dilemmas, in addition to standard methods, this chapter aims to provide a measure of the adaptability of different experimental procedures.
Immunohistochemistry of lymphoid organs
Authors: Biddolph Simon c. , Gatter kevin c.
Published: November 2023

Immunohistochemistry is a technique for localizing and identifying cellular or tissue components (antigens) by means of an antigen-antibody interaction, the site of the interaction being identified by the application of an appropriate labelling system. This technique plays an important part in diagnostic cellular pathology and biomedical research, and this chapter describes in detail the preparation of lymphoid cells and tissues for immunohistochemistry. It outlines the most frequently used labelling systems, and gives full details of the systems we find most useful in our laboratory. The distribution of different lymphocyte subpopulations in lymphoid tissue is also described.
Human CD4 culture
Authors: Gorak-stolinska P , Wallace d. , Kemeny a. Noble d. M
Published: November 2023

Advances in technologies to isolate, grow, and clone CD4 T cells of chosen specificities have facilitated our understanding of the generation of T-cell receptor diversity and the role of the MHC class I and class II gene products in antigen presentation (1-3). Antigen-specific T-cell lines have been used in the immunotherapy of cancer (4) and in the study of the immunopathology of chronic viral infections (5). Using T-cell clones, the rules governing the T-cell recognition of proteins and synthetic peptides are now being understood, thereby facilitating the production of synthetic vaccines that elicit either class Ior class II-restricted T-cell immunity (6).
Analysis of DNA-general methods
Authors: Ormerod M G
Published: November 2023

The measurement of DNA was one of the first and is still one of the most wide spread applications of flow cytometcy. Malignant cells are frequently aneuploid and there have been many studies of the possible prognostic significance of ploidy in human tumours. The content of DNA also gives information about the cell cycle, so that this measurement can be of value in cell biology. In particular, it can yield useful information about the action of cytotoxic drugs. The measurement of DNA may also be combined with estimation of an antigen, so that the expression of a particular protein through the cell cycle may be measured or, in a cell mixture, the ploidy or cell cycle of a particular class of cell estimated (see Chapter 5, Section 11, and Chapter 9).

All the established methods use dyes which bind specifically and stoichio metrically to nucleic acids and whose fluorescence is enhanced on binding. The properties of the more important of these compounds are described in Chapter.
Genome analysis in flamentous fungi
Authors: Farman Mark L
Published: November 2023

Fungal genome analysis is an extremely broad topic in the sense that the isolation of most fungal genes cloned to date was made possible by using techniques to analyse and manipulate the fungal genome. In this chapter I have focused on methods for genetic and physical mapping of chromosomes and large chromosomal fragments, as might be applied in the analysis of chromosome structure and for map-based cloning of genes. The first sections outline approaches and methods for mapping chromosomes and analysing intact chromosomal DNAs, while the later sections cover the construction and screening of bacterial artificial chromosome (BAC) libraries as a means of isolating and propagating large chromosome fragments for more detailed analyses. Many of the protocols provided are useful not only in chromosome walking studies but can also be applied or adapted for other uses, including isolation of genes from libraries.
Cell biology of the duplication cycle in fungi
Authors: Momany Michelle
Published: November 2023

Filamentous fungi undergo an ordered series of events during growth and division. These events include mitosis, periods of isotropic and polar growth, cytoskeletal rearrangements, and partitioning of cytoplasmic contents via septa (1). Because the cells within a hypha do not physically separate from one another these events are known as a ‘duplication cycle’ rather than a cell cycle.
Chromosome staining and banding techniques
Authors: Benn P A , Tantravahi U
Published: November 2023

Diagnostic cytogenetic laboratories routinely base their results on the analysis of banded chromosome preparations with band resolution levels of 400-650 bands per haploid chromosome set. Most laboratories use Giemsa banding as their primary technique and subsequently apply a variety of other staining methods or FISH to further characterize abnormal or unusual findings. In this chapter we review the chromosome staining methods available.

In many instances, FISH can complement or provide an efficient and appropriate alternative to the staining methods described. For example, the centromeric regions and telomeres can be readily distinguished by chromosome staining. However, FISH can also detect these regions and the use of a chromosome-specific centromere or subtelomere FISH probe is the preferred approach when there is a particular candidate chromosome under consideration as the source of an abnormality. The reader should refer to Chapter 6 for additional information on currently available FISH probes. Staining and banding is usually quicker and cheaper but lacks the specificity of Fish.
In situ hybridization
Authors: Leitch A R , Lim K Y
Published: November 2023

Gall and Pardue (1969) and John et al. (1969) were the first to localize nucleic acids directly to biological material (1, 2). They used radioactively labelled RNA to detect ribosomal DNA (rDNA) in cytological preparations. Since then, and particularly since the early 1990s, the uses of the method have exploded, so much so that it is now commonplace to find the method being used in both molecular and cell biology experiments. Indeed in situ hybridization, which can be used to localize DNA or RNA directly to biological material, should now be considered as routine as Southern or Northern hybridization. For further advice beyond this chapter and relating to the localization of DNA in situ, readers are welcome to contact either Dr Leitch or Dr Lim and for RNA in situ, either Dr Webb or Dr McFadden.
Introduction to phage biology and phage display
Authors: Russel Marjorie , Lowman Henry B , Clackson Tim
Published: November 2023

Display of peptides and proteins on filamentous phage-phage display-is an in vitro selection technique that enables polypeptides with desired properties to be extracted from a large collection of variants. A gene of interest is fused to that of a phage coat protein, resulting in phage particles that display the encoded protein and contain its gene, providing a direct link between phenotype and genotype. This allows phage libraries to be subjected to a selection step (e.g. affinity chromatography), and recovered clones to be identified by sequencing and re-grown for further rounds of selection. Since the initial description of the approach by Smith (1), it has become established as a powerful method for identifying polypeptides with novel properties, and altering the properties of existing ones (for reviews, see 2-5).
Identiication of novel ligands for receptors using recombinant peptide libraries
Authors: Cwirla Steven E , Dower William J , Gates Christian M , Wagstrom Christopher R , Schatz Peter J
Published: November 2023

Large libraries containing billions of random peptide sequences have proven to be a rich source of ligands for a wide variety of protein targets. Examples include cytokine and growth factor receptor antagonists and agonists (1-4), protease inhibitors (5, 6), and modulators of ligand gated ion channels (7). In most cases peptide ligands were isolated by screening phage display libraries against an immobilized purified protein. Recent reports indicate that even more com- plex targets such as whole cells and tissues can be used to identify peptides that bind specifically to cell surface antigens (8, 9). High affinity ligands 10-20 amino acids in length have been identified from both linear and cyclic peptide libraries. The majority of these sequences bear no resemblance to known ligands for that particular target protein. Indeed the strength of this technology and other combinatorial approaches is based on the notion that ligands to receptors can be identified without prior knowledge of the nature of the interaction.
Applications of RNA FISH for visualizing gene expression and nuclear architecture
Authors: Tam Rose , Shopland Lindsay S , Johnson Carol V , McNeil John A , Lawrence Jeanne B
Published: November 2023

Fluorescence in situ hybridization is not a singular technique, but a versatile experimental approach that provides ever more precise molecular information directly in the context of cellular structure. This chapter will focus on one major aspect of the molecular cytological approach: the detection of nuclear RNAs, together with their genes or other biochemical components of the cell. Improvements in the development and application of FISH in recent years have demonstrated the value of this approach for studying gene expression as well as processing, transport, and function of various cellular and viral RNAs. Although the basic technique described here is also applicable to detection of cytoplasmic mRNA, our focus will be on methods optimized primarily for high resolution, high sensitivity detection of nuclear transcripts, in precise relation to other nuclear components.
Public Opinion: Myths and Realities
Authors: Ginsberg Benjamin
Published: November 2023

Many of the same Americans who believe in the Easter bunny think that public opinion is a significant force in political life. Perhaps not all would accept James Bryce’s famous assertion that popular support “has been the chief and ultimate power in nearly all nations at all times.”1 Most Americans, however, agree that citizens’ preferences have a good deal of influence over the government and its policies. Nearly 80 percent of those responding to a recent national survey said that the government listened to the people most or at least some of the time. More than 90 percent agreed that elections made the government pay attention to public opinion.2
Hamilton’S Rule
Authors: Hamilton W D
Published: November 2023

If Professor David Glass was cool towards my work at the London School of Economics, Professor Lionel S. Pemose, FRS, at University College was equally so. I believe he definitely saw in me the eugenical spectre I mentioned in the first introduction. Although supervised at the Gaitan Laboratory for 2 years I never had a desk there nor was ever invited to give any presentation to explain my work or my occasional presence to others. I think virtually no one I passed in the corridors or sat with in the library knew my name or what I was doing. Probably this was largely my own fault. I was a student who, if not offered or invited, wouldn’t request, and I think I didn’t ask for desk space either there or at LSE. In fact I had no idea at the time what was normal for graduate students and it is only after seeing arrangements made in other departments both in Britain and the US that my own situation as a graduate has come to seem odd. At the time I hardly knew what a PhD was. I just wanted access to libraries plus some pittance of support; these together would give me freedom to follow my puzzles. Apparently I needed affiliation to colleges to receive my grant and to be a part of London University; two colleges were kindly offering this and that was enough.
Elm And Australian
Authors: Hamilton W D
Published: November 2023

IT would be a gross understatement to say that sexuality was the only evolutionary problem worrying me in the mid-1970s. Generally at any one time I have a half dozen problems, some in the foreground of my mind, some like quiescent volcanoes at the back, some completely laid aside but not forgotten. But in those years one in particular besides sex had become major and was proving to be the special successor to one from the past. More than sex itself, it was proposing very clear-cut and even quantitative questions, similar to those I had had concerning optimal sex ratios under the various groupings and types of control that I had treated in the early 1960s. The new problem was that of dispersal.
In-Hospital Neurologic Complications, Neuromonitoring, and Long-Term Neurologic Outcomes in Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Fan Tracey H. , Premraj Lavienraj , Roberts Jacob , Lydston Melissa , Robba Chiara , Hager David , Suarez Jose I. , Battaglini Denise , Cho Sung-Min
Published: November 2023

OBJECTIVES:

Although delirium is well described in patients with sepsis, there are limited data on other neurologic complications. We aimed to systematically review the prevalence, neuromonitoring tools, and neurocognitive outcomes in sepsis patients with neurologic complications.

DATA SOURCES:

MEDLINE and six other databases (Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov) were searched through January 2023.

STUDY SELECTION:

Studies of adult patients with sepsis reported neurologic complications, use of neuromonitoring tools, neuropathology, and cognitive outcomes.

DATA EXTRACTION:

Two independent reviewers extracted the data. Random-effect meta-analyses were used to pool data.

DATA SYNTHESIS:

Seventy-four studies (n = 146,855) were included. Neurologic complications were reported in 38 studies (n = 142,193) including septic encephalopathy (36%, 95% CI, 27–46%; I2 = 99%), ischemic stroke (5%, 95% CI, 2.1–11.5; I2 = 99%), intracranial hemorrhage (2%, 95% CI, 1.0–4.4%; I2 = 96%), seizures (1%, 95% CI, 0.2–7%; I2 = 96%), posterior reversible encephalopathy syndrome (9%), and hypoxic-ischemic brain injury (7%). In the meta-regression analysis, pulmonary infection, sepsis induced by a gram-positive organism, higher sequential organ failure assessment score, acute physiology and chronic health evaluation II score at admission, and longer ICU length of stay were associated with higher risk of developing septic encephalopathy. Three studies (n = 159) reported postmortem neuropathological findings, acute brain injury was noted in 47% of patients. Twenty-six studies (n = 1,358) reported the use of neuromonitoring tools, electroencephalogram was the most used tool for seizure detection. Transcranial Doppler and near infrared spectroscopy were used for monitoring cerebral hemodynamic changes to detect early ischemia. Six studies reported cognitive outcomes (n = 415) up to 12 months postdischarge and cognitive impairment (≥ one domain) was reported in 30%.

CONCLUSIONS:

In-hospital neurologic complications are common in patients with sepsis. However, the mechanism and timing of those sepsis-associated complications are poorly understood and there are limited data on standardized neuromonitoring in this population.
Inframammary versus Periareolar Incision: A Comparison of Early Complications in Nipple-sparing Mastectomy
Authors: Cavalcante Francisco P. , Lima Ticiane O. , Alcantara Ryane , Cardoso Amanda , Ulisses Flora , Novita Guilherme , Zerwes Felipe , Millen Eduardo
Published: November 2023

Background:

Nipple-sparing mastectomy (NSM), either used therapeutically or prophylactically, may yield more complications than conventional mastectomy. The incision may affect aesthetic outcome and complication rates, with periareolar incisions being associated with nipple–areolar complex (NAC) necrosis.

Methods:

Early complications were compared between NSM performed in 2015–2022 using inframammary fold (IMF) or periareolar incisions.

Results:

Overall, 180 procedures in 152 patients (bilateral NSM = 28) were included (IMF = 104; periareolar = 76). Mean age (47 versus 43.9 years; P < 0.038), mastectomy weight (312.7 versus 246.8 grams; P < 0.001), implant volume (447.5 versus 409.0 mL; P = 0.002), and use of tissue expanders (68.4% versus 50.0%; P = 0.013) were all greater with periareolar incisions. Prepectoral reconstruction was more common with IMF (18.3% versus 3.9%; P = 0.004). Forty-three complications (23.9%) were recorded (periareolar n = 27, 35%; IMF n = 16, 15.3%; P = 0.0002). NAC necrosis accounted for 17 complications (22.4%) in the periareolar group versus nine (8.5%) in the IMF group (P = 0.002). Necrosis was predominantly moderate (n = 6, 8.3% versus n = 1, 1.0%, respectively) (P = 0.014). Unadjusted odds ratios (OR) for complications [3.05; 95% confidence interval (CI): 1.27–7.26] and necrosis (3.04; 95% CI: 1.27–7.27) were higher in the periareolar group. In the multivariate analysis, necrosis was associated with periareolar incisions [adjusted odds ratio (aOR): 2.92; 95% CI: 1.14–7.44]. Prepectoral reconstruction was associated with IMF incisions (aOR: 25.51; 95% CI: 3.53–184.23; P = 0.001) and with body mass index of more than 25–30 (aOR: 37.09; 95% CI: 5.95–231.10; P < 0.001). Therapeutic mastectomies (aOR: 68.56; 95% CI: 2.50–188.36; P = 0.012) and tissue expanders (aOR: 18.36; 95% CI: 1.89–178.44; P = 0.026) were associated with seromas.

Conclusions:

Both incisions are viable options; however, the risk of NAC necrosis increased with the periareolar approach. Further research is required.
The Implications of Virtual Learning on Plastic Surgery Education: A National Survey of Plastic Surgery Residents and Fellows
Authors: Arora Jagmeet S. , Pham Jason T. , Alaniz Leonardo , Khoshab Nima , Tang Cathy J.
Published: November 2023

Background:

Graduate medical education during the COVID-19 pandemic has seen the shift to a “virtual learning” format in many aspects of training. The purpose of this study was to describe the perceived strengths and weaknesses of virtual learning compared with a conventional, in-person format.

Methods:

A 45-question survey was sent to independent and integrated plastic surgery residents and postresidency fellows nationally. The survey collected basic demographic information and evaluated three general categories of virtual learning in comparison to an in-person format: (1) time, (2) learning proficiency, and (3) collaboration.

Results:

In total, 108 surveys were submitted from 48 different training programs. Participants reported that virtual learning was more efficient (mean: 3.9), conducive to more free time (mean: 3.9), and a more comfortable medium for expressing opinions (mean: 3.5) and asking questions (mean: 3.6) compared with an in-person format. When stratified between training levels, the PGY 1–3 group reported more difficulties in exam preparedness (P = 0.05), motivation to study (P = 0.01) and less time-saving benefits (P = 0.05) with a virtual format than the PGY 4+ group. Lastly, respondents who had higher self-reported levels of multitasking were found to have lower mean Likert scale scores on all questions related to “time,” “learning proficiency,” and “collaboration” (P < 0.01).

Conclusions:

A virtual and in-person hybrid approach toward plastic surgery education may be beneficial for encouraging flexibility. Our results demonstrate impairment with collaboration and learning proficiency with a virtual format, especially with increased multitasking, but increased comfort with expressing opinions and asking questions.
Transmitted Drug Resistance and HIV Diversity Among Adolescents Newly Diagnosed With HIV in Spain
Authors: Epalza Cristina , Valadés-Alcaraz Ana , González-Alba José María , Beltrán-Pavez Carolina , Gutiérrez-López Miguel , Rubio-Garrido Marina , Fortuny Clàudia , Frick Marie Antoinette , Muñoz Medina Leopoldo , Moreno Santiago , Sanz José , Rojo Pablo , Navarro María Luisa , Holguín África ,   on behalf of the Cohort of the Spanish HIV/AIDS Pediatric (CoRISpe) and Adult (CoRIS) Networks
Published: November 2023

Background:

Virologic characterization of newly HIV-diagnosed adolescents could help to improve their specific needs. The objective was to describe the transmitted drug resistance mutations (TDR) and its transmission by clusters in this population in Spain.

Methods:

TDR to retrotranscriptase and protease inhibitors included in the WHO TDR list 2009 implemented in the Calibrated Population Resistance tool v8.0 (Stanford) were studied in HIV pol sequences from all HIV-diagnosed adolescents (12–19-year-old) enrolled during 2004–2019 period in the Spanish pediatric and adult (CoRISpe-CoRIS) cohorts. The found TDR were compared with the provided by the Stanford algorithm v9.0 2021. HIV-1 variants and transmission clusters were also studied.

Results:

Among 410 HIV-1 adolescents diagnosed, 141 (34.4%) had available ART-naive sequences. They were mostly male (81.6%), Spanish (55.3%) and with behavioral risk (92.2%), mainly male-to-male sexual contact (63.1%). TDR prevalence was significantly higher by Stanford versus WHO list (18.4% vs. 7.1%; P = 0.004). The most prevalent TDR by the WHO list was K103N (3.6%) and by Stanford E138A (6.6%), both at retrotranscriptase. E138A, related to rilpivirine/etravirine resistance, was absent in the WHO list. One in 4 adolescents carried HIV-1 non-B variants. We described 5 transmission clusters, and 2 carried TDR mutations.

Conclusions:

Our data suggest a high TDR prevalence in adolescents with a new HIV diagnosis in Spain, similar to adults, 2 active TDR transmission clusters, and the need for the WHO TDR list update. These findings could have implications for the options of the recently available rilpivirine-related long-acting treatment and in first-line regimen election.
Comparison of posterior capsule rupture rates during phacoemulsification using 3D heads-up visualization system and traditional microscopes
Authors: Jeon Hyun Sun , Kim Min Hwan , Joo Kwangsic , Park Sang Jun , Lee Eun Ji , Hyon Joon Young , Kim Tae-Woo , Park Kyu Hyung , Woo Se Joon
Published: November 2023

Purpose:

To compare the posterior capsule rupture (PCR) rates of cataract surgery using a traditional ophthalmic surgical microscope (OSM) and a 3D heads-up visualization system (HUVS).

Setting:

Single tertiary referral center.

Design:

Retrospective study.

Methods:

This study included 10 101 eyes that underwent phacoemulsification cataract surgery. Surgeries were performed using either 3D HUVS (1964 eyes, performed by 2 surgeons, HUVS group) or traditional OSM (8137 eyes, performed by 6 surgeons, OSM group) from February 2018 to June 2022. Data were collected based on the diagnosis-related group system, and the rate of PCR requiring vitrectomy and the surgical time were evaluated.

Results:

The PCR rates were not significantly different between the OSM (n = 63; 0.7%) and HUVS (n = 19; 0.9%, P = .392) groups. The mean surgical time was significantly longer in the HUVS group (14.7 ± 10.6 minutes) than in the OSM group (12.9 ± 9.9 minutes, P < .001). In the 3D HUVS group, there were no PCR cases among the initial 100 patients. In both groups, no significant difference was observed in the PCR rates over time. Although the difference was not statistically significant, the PCR rate decreased over time in the HUVS group.

Conclusions:

The results indicate that 3D HUVS-based cataract surgery performed by experienced cataract surgeons had a PCR rate similar to that of traditional OSM-based surgery during the 4-year study period. Although the surgical time was slightly longer with 3D HUVS, cataract surgery using 3D HUVS can be performed safely by experienced surgeons.
Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation
Authors: Zhang Mingru , Yan Weidong , Wang Tianlong , Pei Shengqiang , Wang Jing , Ji Bingyang , Wang Guyan
Published: November 2023

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1β (IL-1β) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.
Current approaches to overcome recurrent focal segmental glomerulosclerosis after kidney transplantation
Authors: Ahmad Syeda Behjat , Peleg Yonatan , Ahn Wooin
Published: November 2023

Purpose of review

Recurrent focal segmental glomerulosclerosis (FSGS) presents with nephrotic syndrome shortly after kidney transplantation. This review will overview the role of circulating permeability factors in disease pathogenesis and treatment options for recurrent FSGS.

Recent findings

Novel circulating permeability factors have been identified in serum samples. Current research is focused on detection of permeability factors as a marker of treatment response. Furthermore, novel monoclonal antibodies are being utilized to further induce remission.

Posttransplant recurrent FSGS can have a deleterious effect on allograft. Early detection of disease recurrence with prompt treatment is optimal for clinical remission. Plasmapheresis with anti-B cell therapy is considered the mainstay of treatment. Newer B cell therapies and detection of circulating factors in serum may help in providing targeted treatment in a subset of patients.
Factors that Motivate and Support Aging in Place
Authors: Kolotello Madison , Sithong Carolyn , Sinclair Wynnet
Published: November 2023

Previous research demonstrated a gap in research regarding low-income older adults who age at home. This research study focused on evaluating the motivation of low-income older adults who age in place and gaining an improved understanding of areas of motivation. The sample consisted of seven older adults in North Carolina who are affiliated with a non-profit. Data collection consisted of semi-structured interviews conducted in the participant's home. The research team conducted triangulation, theme development, and pattern development. The research revealed five themes: previous history, environmental factors, desire for safety, daily routines, and personal values. The themes are supported by the theoretical background of self-determination theory, Maslow's hierarchy of needs, and the Model of Human Occupation. It was concluded that previous history, external motivation, faith, and need for adequate housing are solid factors for older adults to age in place.
A Supportive Heart Failure Care Program to Reduce Hospital Readmissions
Authors: Hagan Claudine , Cygan Heide , Rockwell Laurie , Naccarato Karen , Bowers Tina , Katz Barbara
Published: November 2023

In the United States, heart failure (HF) is the leading reason for hospital readmissions, with 27% of Medicare recipients with HF being readmitted within 30 days The purpose of this quality improvement project was to decrease HF readmissions during their first 30 days of care with our home health agency. The Supportive Heart Failure Care education program was based on the results of a population assessment and included establishment of agency-wide best practices, nursing education sessions, and implementation of best practices focused on evidence-based self-management. After implementation of this project, the hospital readmission rate decreased from 32% to 21%. The nurses who completed the education sessions (N = 35) showed an increase in knowledge of 4.1% from pre-test scores. However, chart audits showed varying levels of documented practice in alignment with best practices. Although results of this project showed a small improvement in nurse knowledge and varied changes to documented practice, the overall project goal of decreasing hospital readmissions was achieved. Understanding individual and systems-level barriers to translating education to practice is needed to better meet the needs of home health nurses and the HF patients they serve.
Endometrioid Adenocarcinoma With “Burrowing” Invasion of the Cervix Represents a Separate Primary From the Concurrent Uterine Corpus Endometrial Endometrioid Adenocarcinoma: Histology, Immunohistochemistry, and Next-generation Sequencing Study of a Single Case
Authors: Li Yan , Chen Jackson , Niu Shuang
Published: November 2023

A small subset of endometrial endometrioid adenocarcinoma cases first reported in 2003, showed a distinct cervical component with a so-called “burrowing” invasion pattern. Initially, the cervical component was regarded as cervical involvement by the endometrial adenocarcinoma. However, a 2010 study argued that these cases actually might represent separate primary endometrial and cervical endometrioid adenocarcinomas. However, additional data on this topic are scarce. Here, we report a case of endometrioid adenocarcinoma with a “burrowing” cervical invasion that is morphologically distinct from the patient’s endometrial endometrioid adenocarcinoma. By comparing the morphology, immunophenotype, and genetic profile obtained by next-generation sequencing, we demonstrated that the cervical and endometrial tumors were of 2 separate primaries. Our report adds additional data to this unique phenomenon, and will hopefully help to reignite interest in investigating this controversial topic.
Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case
Authors: Zhao Zitong , Nadarajah Ravichandran , Busmanis Inny
Published: November 2023

Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.