bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: Immunotherapeutic implications
Authors: El‐Awady Ahmed R. , Elashiry Mahmoud , Morandini Ana C. , Meghil Mohamed M. , Cutler Christopher W.
Published: March 2022

Extensive research in humans and animal models has begun to unravel the complex mechanisms that drive the immunopathogenesis of periodontitis. Neutrophils mount an early and rapid response to the subgingival oral microbiome, producing destructive enzymes to kill microbes. Chemokines and cytokines are released that attract macrophages, dendritic cells, and T cells to the site. Dendritic cells, the focus of this review, are professional antigen‐presenting cells on the front line of immune surveillance. Dendritic cells consist of multiple subsets that reside in the epithelium, connective tissues, and major organs. Our work in humans and mice established that myeloid dendritic cells are mobilized in periodontitis. This occurs in lymphoid and nonlymphoid oral tissues, in the bloodstream, and in response to Porphyromonas gingivalis. Moreover, the dendritic cells mature in situ in gingival lamina propria, forming immune conjugates with cluster of differentiation (CD) 4+ T cells, called oral lymphoid foci. At such foci, the decisions are made as to whether to promote bone destructive T helper 17 or bone‐sparing regulatory T cell responses. Interestingly, dendritic cells lack potent enzymes and reactive oxygen species needed to kill and degrade endocytosed microbes. The keystone pathogen P. gingivalis exploits this vulnerability by invading dendritic cells in the tissues and peripheral blood using its distinct fimbrial adhesins. This promotes pathogen dissemination and inflammatory disease at distant sites, such as atherosclerotic plaques. Interestingly, our recent studies indicate that such P. gingivalis–infected dendritic cells release nanosized extracellular vesicles called exosomes, in higher numbers than uninfected dendritic cells do. Secreted exosomes and inflammasome‐related cytokines are a key feature of the senescence‐associated secretory phenotype. Exosomes communicate in paracrine with neighboring stromal cells and immune cells to promote and amplify cellular senescence. We have shown that dendritic cell–derived exosomes can be custom tailored to target and reprogram specific immune cells responsible for inflammatory bone loss in mice. The long‐term goal of these immunotherapeutic approaches, ongoing in our laboratory and others, is to promote human health and longevity.
Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia
Authors: Pussinen Pirkko J. , Kopra Elisa , Pietiäinen Milla , Lehto Markku , Zaric Svetislav , Paju Susanna , Salminen Aino
Published: March 2022

Lipopolysaccharide is a virulence factor of gram‐negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe‐associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger‐associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation‐driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram‐negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.
Periodontitis and coronavirus disease 2019
Authors: Tamimi Faleh , Altigani Shiraz , Sanz Mariano
Published: March 2022

The coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 is usually a mild condition; however, in some cases it can result in severe sickness and even death. Thus, understanding the reasons behind these grave outcomes is of great importance. Coronavirus disease 2019 and periodontitis share some intriguing characteristics. They can both lead to systemic inflammation and alterations of coagulation pathways, and both share confounding factors, such as diabetes, hypertension, and obesity. Accordingly, a possible association between these conditions has been hypothesized in the literature. The objective of this review was to evaluate the scientific evidence linking these diseases and the possible underlying mechanisms. Evidence has shown that coronavirus disease 2019 presents oral manifestations and can even affect periodontal tissues. Moreover, some studies have shown a possible association between coronavirus disease 2019 severity and the presence of periodontitis. Current evidence suggests that this association could be explained through the direct role of periodontal bacteria in aggravating lung infections, as well as through the indirect effect of periodontitis in inducing systemic inflammation and priming of the immune system to an exacerbated reaction to severe acute respiratory syndrome coronavirus 2 infection. Future research is needed to confirm these observations and explore the possible role that periodontal care might play in the coronavirus disease 2019 pandemic.
Attachment voices promote safety learning in humans: A critical role for P2
Authors: Dou Haoran , Dai Yuqian , Qiu Yiwen , Lei Yi
Published: March 2022

Humans have evolved to seek the proximity of attachment figures during times of threat in order to obtain a sense of safety. In this context, we examined whether or not the voice of an intimate partner (termed “attachment voice”) could reduce fear‐learning of conditioned stimuli (CS+) and enhance learning of safety signals (CS−). Although the ability to learn safety signals is vital for human survival, few studies have explored how attachment voices affect safety learning. To test our hypothesis, we recruited thirty‐five young couples and performed a classic Pavlovian conditioning experiment, recording behavioral and electroencephalographic (EEG) data. The results showed that compared with a stranger’s voice, the voices of the partners reduced expectancy of the unconditioned stimulus (a shock) during fear‐conditioning, as well as the magnitude of P2 event‐related potentials within the EEG responses, provided the voices were safety signals. Additionally, behavioral and EEG responses to the CS+ and CS− differed more when the participants heard their partner’s voice than when they heard the stranger’s voice. Thus, attachment voices, even as pure vowel sounds without any semantic information, enhanced acquisition of conditioned safety (CS−). These findings may provide implications for investigating other new techniques to improve clinical treatments for fear‐ and anxiety‐related disorders and for psychological interventions against the mental health effects of the public health emergency.
Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID‐19 in chronic lymphocytic leukaemia?
Authors: Smith Carl Inge Edvard , Zain Rula , Österborg Anders , Palma Marzia , Buggert Marcus , Bergman Peter , Bryceson Yenan
Published: March 2022

Infections with SARS‐CoV‐2 have been unduly severe in patients with haematological malignancies, in particular in those with chronic lymphocytic leukaemia (CLL). Based on a series of observations, we propose that an underlying mechanism for the aggressive clinical course of COVID‐19 in CLL is a paucity of plasmacytoid dendritic cells (pDCs) in these patients. Indeed, pDCs express Toll‐like receptor 7 (TLR7), which together with interferon‐regulatory factor 7 (IRF7), enables pDCs to produce large amounts of type I interferons, essential for combating COVID‐19. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors increased the number of pDCs, likely secondarily to the reduction in the tumour burden.
Assessing Variation and Change in Newspaper Portrayals of Muslims: The influence of the Trump Election and Differences across the United States in Local and National Papers*
Authors: Adamczyk Amy , Greene‐Colozzi Emily , Keles Senahan Kiyal , Murati Aida
Published: March 2022

Since Donald Trump’s political campaign, Americans have appeared increasingly divided over public opinion issues and U.S. policies with the media seemingly reflecting these divisions. One of Trump’s early initiatives was the “Muslim ban,” which restricted visitors from seven Muslim‐majority countries. Focusing on the portrayal of Muslims in over 900 hand‐coded articles, our study uses multilevel modeling techniques to examine how newspapers changed their frames and claimsmakers in discussions about Muslims before and after Trump was elected. After the election, newspapers were more likely to include government claimsmakers and an immigration frame and were less likely to mention a radical terrorist leader or portray Muslims as violent. Trump’s election and the ban may have ushered in a more sympathetic view of Muslims with more articles focused on them as victims of violence and negative expressions. Across counties, states, and newspapers and between the national versus local presses, we find almost no significant differences in how Muslims were portrayed.
A structuralist interpretation of the relational interpretation
Authors: Buonocore Giovanni
Published: March 2022

The present paper aims to provide an insight into the epistemological and metaphysical implications of a structuralist interpretation of Relational Quantum Mechanics (RQM). I will suggest that the ‘entity‐relation identity’ at the core of a particular formulation of Ontic Structural Realism represents the best framework against which to understand RQM, and, in turn, that this interpretation provides some support for the adoption of a structuralist viewpoint in Quantum Mechanics thus understood. The choice is motivated by the same revisionary metaphysics they both seem to offer, with respect to the notion of entity and of relation.
Hemodilution in high‐risk cardiac surgery: Laboratory values, physiological parameters, and outcomes
Authors: Mladinov Domagoj , Padilla Luz A. , Leahy Benjamin , Norman Joseph B. , Enslin Jacob , Camp Riley S. , Eudailey Kyle W. , Tanaka Kenichi , Davies James E.
Published: March 2022

Background

Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability, and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described.

Study design and methods

This observational cohort (2019–2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N = 66) and non‐ANH controls (N = 103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass.

Results

Intraoperatively, the ANH group received more albumin (p = .04) and vasopressor medications (p = .01), while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2) values were similar before and after hemodilution. During bypass, rSO2 were discretely lower in the ANH versus control group (right rSO2 p = .03, left rSO2 p = .05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, intensive care unit length of stay, kidney injury, stroke, or infection were demonstrated.

Discussion

This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high‐risk cardiac surgeries.
Calidad de vida relacionada con la salud en sujetos con VIH
Authors: Canova Barrios Carlos Jesús
Published: March 2022

Introducción: Desde la identificación del VIH se ha avanzado en el desarrollo de tratamientos más seguros y eficaces que aseguren la sobrevida de los sujetos afectados, siendo el reto de los profesionales sanitarios el mejoramiento de la calidad de vida relacionada con la salud de estos. Objetivo: Analizar la calidad de vida relacionada con la salud de una muestra de pacientes con VIH de Buenos Aires, Argentina. Método: Estudio analítico, transversal y cuantitativo realizado durante los meses de enero a marzo de 2020. Participaron un total de 144 sujetos. Se administraron los cuestionarios SF-36 y Morisky-Green. Resultados: La muestra estuvo comprendida mayoritariamente por hombres, solteros, sin hijos y con estudios universitarios. El 49,30 % presentaba una buena adherencia al tratamiento. La Función física fue la dimensión mejor evaluada (92,19), mientras que la Vitalidad fue la peor percibida (61,42). El componente mental fue el más afectado. El sexo femenino, nivel de estudios primario, edad más alta, tenencia de hijos y la presencia de complicaciones se asociaron a una peor calidad de vida. Conclusiones: Se hace importante implementar acciones tendientes a mejorar la adherencia al tratamiento de los pacientes y promover estilos de vida favorecedores de la salud. Asimismo, el abordaje de los sujetos ha de ser integral, considerando las dimensiones psíquica, emocional, social y espiritual como parte de las áreas de atención. La calidad de vida debe ser un indicador de seguimiento para los profesionales sanitarios.
Perfil das mulheres com lesão de alto grau do colo do útero
Authors: Oliveira Iácara Santos Barbosa , Justino Araújo Cleidiane
Published: March 2022

Introdução: O Câncer do colo uterino é uma neoplasia maligna originada pelas alterações celulares no epitélio da cérvice uterina. Objetivo: Conhecer o perfil das mulheres diagnosticadas com lesão de alto grau do colo do útero em um município do interior de Minas Gerais. Métodos. Pesquisa de campo com levantamento de dados, descritiva e de abordagem quantitativa. Resultados: No período de 2016 a 2017 foram diagnosticados 202 casos novos de lesão de alto grau, sendo destes, 30,70% correspondem a mulheres que residem no município do estudo, em relação a faixa etária das mulheres,70% eram da faixa etária de 25 a 64 anos, ou seja, a mesma faixa etária recomendada pelo Ministério da Saúde para exames de rastreamento e detecção precoce do câncer de colo do útero, em relação a raça,70% das mulheres foram classificadas de cor branca. Já em relação a adesão ao tratamento proposto e preconizado, 30% das mulheres não aderiram. Conclusão: Concluímos com a realização deste estudo que o Câncer de Colo do Útero pode ser reduzido através de políticas públicas aplicadas a partir do conhecimento do perfil das mulheres diagnosticadas com lesão de alto grau.
Proyecto IniciaTIC 2020: aprender en casa a enseñar desde casa
Authors: Del Río-Fernández José Luis , Saldaña-Gómez Diana Priscila
Published: March 2022

Durante el confinamiento provocado por la pandemia del Covid-19, la implementación de docencia online mediante el uso de la tecnología educacional posibilita que las estudiantes de la carrera de Educación Inicial de la Universidad Nacional de Educación (UNAE) puedan realizar su correspondiente periodo de práctica pedagógica. Sobre esta realidad, se desarrolla un estudio de caso único de tipo indagatorio/exploratorio cuyo objetivo es identificar las fortalezas y debilidades encontradas a lo largo del proceso formativo. Los resultados demuestran que el análisis colectivo de las sesiones virtuales permite que las futuras docentes de preescolar vayan construyendo su propia identidad profesional en este singular contexto educativo.
Wall Energy Loss and Entropy Generation in Solar Ponds Using One-Dimensional and Two-Dimensional Transient Analyses
Authors: Verma Sunirmit , Das Ranjan
Published: March 2022

In this paper, wall thermal energy loss in a cylindrical solar pond is studied using one-dimensional (1D) and two-dimensional (2D) transient models. It is seen that for a given quantity of insulation applied around the pond wall, the negative effect of sidewall loss reduces as the pond size increases. Further, the optimal insulation thickness that eradicates all wall energy loss is larger when calculated from a spatially 1D model, as opposed to when radial temperature gradients are given consideration. The 2D model reveals a larger entropy generation than that calculated by a 1D model for an imperfectly insulated pond. So, for such ponds, the present model would calculate entropy generation in a more realistic manner. It is revealed that using simpler 1D in space models to estimate solar pond’s outer wall optimum insulation thickness will not lead to any problems as far as the thermal performance is the concern. But, since such models over predict the optimum value, they would invoke more cost. So, when financial and space constraints are present, then it is advisable to design the wall insulation in solar ponds using spatially multi-dimensional heat transfer models, for which the present work could prove to be useful.
Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia
Authors: Cramer Teresa , Gill Raminder , Thirouin Zahra S. , Vaas Markus , Sampath Suchita , Martineau Fanny , Noya Sara B. , Panzanelli Patrizia , Sudharshan Tania J. J. , Colameo David , Chang Philip K.-Y. , Wu Pei You , Shi Roy , Barker Philip A. , Brown Steven A. , Paolicelli Rosa C. , Klohs Jan , McKinney Rebecca Anne , Tyagarajan Shiva K.
Published: March 2022

Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75
NTR
) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the
Bdnf
gene in microglia or
Gphn
S268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO.
Perturbation of the deep-Earth carbon cycle in response to the Cambrian Explosion
Authors: Giuliani Andrea , Drysdale Russell N. , Woodhead Jon D. , Planavsky Noah J. , Phillips David , Hergt Janet , Griffin William L. , Oesch Senan , Dalton Hayden , Davies Gareth R.
Published: March 2022

Earth’s carbon cycle is strongly influenced by subduction of sedimentary material into the mantle. The composition of the sedimentary subduction flux has changed considerably over Earth’s history, but the impact of these changes on the mantle carbon cycle is unclear. Here, we show that the carbon isotopes of kimberlite magmas record a fundamental change in their deep-mantle source compositions during the Phanerozoic Eon. The
13
C/
12
C of kimberlites before ~250 Ma preserves typical mantle values, whereas younger kimberlites exhibit lower and more variable ratios—a switch coincident with a recognized surge in kimberlite magmatism. We attribute these changes to increased deep subduction of organic carbon with low
13
C/
12
C following the Cambrian Explosion when organic carbon deposition in marine sediments increased significantly. These observations demonstrate that biogeochemical processes at Earth’s surface have a profound influence on the deep mantle, revealing an integral link between the deep and shallow carbon cycles.
Novel optical photothermal infrared (O-PTIR) spectroscopy for the noninvasive characterization of heritage glass-metal objects
Authors: Marchetti Andrea , Beltran Victoria , Nuyts Gert , Borondics Ferenc , De Meyer Steven , Van Bos Marina , Jaroszewicz Jakub , Otten Elke , Debulpaep Marjolijn , De Wael Karolien
Published: March 2022

Optical photothermal infrared (O-PTIR) is a recently developed molecular spectroscopy technique that allows to noninvasively obtain chemical information on organic and inorganic samples at a submicrometric scale. The high spatial resolution (≈450 nm), lack of sample preparation, and comparability of the spectral results to traditional Fourier transform infrared spectroscopy make it a promising candidate for the analysis of cultural heritage. In this work, the potential of O-PTIR for the noninvasive characterization of small heritage objects (few cubic centimeters) is demonstrated on a series of degraded 16th century brass and glass decorative elements. These small and challenging samples, typically encountering limitations with existing noninvasive methods such as macroscopic x-ray powder diffraction and μRaman, were successfully characterized by O-PTIR, ultimately identifying the markers of glass-induced metal corrosion processes. The results clearly demonstrate how O-PTIR can be easily implemented in a noninvasive multianalytical strategy for the study of heritage materials, making it a fundamental tool for cultural heritage analyses.
Cell type–specific mechanism of Setd1a heterozygosity in schizophrenia pathogenesis
Authors: Chen Renchao , Liu Yiqiong , Djekidel Mohamed N. , Chen Wenqiang , Bhattacherjee Aritra , Chen Zhiyuan , Scolnick Ed , Zhang Yi
Published: March 2022

Schizophrenia (SCZ) is a chronic, serious mental disorder. Although more than 200 SCZ-associated genes have been identified, the underlying molecular and cellular mechanisms remain largely unknown. Here, we generated a Setd1a (SET domain containing 1A) haploinsufficiency mouse model to understand how this SCZ-associated epigenetic factor affects gene expression in brain regions highly relevant to SCZ. Single-cell RNA sequencing revealed that Setd1a heterozygosity causes highly variable transcriptional adaptations across different cell types in prefrontal cortex (PFC) and striatum. The
Foxp2
+
neurons exhibit the most prominent gene expression changes among the different neuron subtypes in PFC, which correlate with changes in histone H3 lysine 4 trimethylation. Many of the genes dysregulated in Setd1a
+/−
mice are involved in neuron morphogenesis and synaptic function. Consistently, Setd1a
+/−
mice exhibit certain behavioral features of patients with SCZ. Collectively, our study establishes Setd1a
+/−
mice as a model for understanding SCZ and uncovers a complex brain region– and cell type–specific dysregulation that potentially underlies SCZ pathogenesis.
A thrombin-triggered self-regulating anticoagulant strategy combined with anti-inflammatory capacity for blood-contacting implants
Authors: Wang Yanan , Wu Haoshuang , Zhou Zhongyi , Maitz Manfred F. , Liu Kunpeng , Zhang Bo , Yang Li , Luo Rifang , Wang Yunbing
Published: March 2022

Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the long-term function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.
Unraveling forced responses of extreme El Niño variability over the Holocene
Authors: Lawman Allison E. , Di Nezio Pedro N. , Partin Judson W. , Dee Sylvia G. , Thirumalai Kaustubh , Quinn Terrence M.
Published: March 2022

Uncertainty surrounding the future response of El Niño–Southern Oscillation (ENSO) variability to anthropogenic warming necessitates the study of past ENSO sensitivity to substantial climate forcings over geological history. Here, we focus on the Holocene epoch and show that ENSO amplitude and frequency intensified over this period, driven by an increase in extreme El Niño events. Our study combines new climate model simulations, advances in coral proxy system modeling, and coral proxy data from the central tropical Pacific. Although the model diverges from the observed coral data regarding the exact magnitude of change, both indicate that modern ENSO variance eclipsed paleo-estimates over the Holocene, albeit against the backdrop of wide-ranging natural variability. Toward further constraining paleo-ENSO, our work underscores the need for multimodel investigations of additional Holocene intervals alongside more coral data from periods with larger climate forcing. Our findings implicate extreme El Niño events as an important rectifier of mean ENSO intensity.
A unimorph nanocomposite dielectric elastomer for large out-of-plane actuation
Authors: Pu Junhong , Meng Yuan , Xie Zhixin , Peng Zihang , Wu Jianghan , Shi Ye , Plamthottam Roshan , Yang Wei , Pei Qibing
Published: March 2022

Dielectric elastomer actuators (DEAs) feature large, reversible in-plane deformation, and stacked DEA layers are used to produce large strokes in the thickness dimension. We introduce an electrophoretic process to concentrate boron nitride nanosheet dispersion in a dielectric elastomer precursor solution onto a designated electrode surface. The resulting unimorph nanocomposite dielectric elastomer (UNDE) has a seamless bilayer structure with 13 times of modulus difference. The UNDE can be actuated to large bending curvatures, with enhanced breakdown field strength and durability as compared to conventional nanocomposite dielectric elastomer. Multiple UNDE units can be formed in a simple electrophoretic concentration process using patterned electrode areas. A disc-shaped actuator comprising six UNDE units outputs large bidirectional stroke up to 10 Hz. This actuator is used to demonstrate a high-speed lens motor capable of varying the focal length of a two-lens system by 40 times.
Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters
Authors: Keshavarz Maryam , Faraj Tabrizi Schayan , Ruppert Anna-Lena , Pfeil Uwe , Schreiber Yannick , Klein Jochen , Brandenburger Isabell , Lochnit Günter , Bhushan Sudhanshu , Perniss Alexander , Deckmann Klaus , Hartmann Petra , Meiners Mirjam , Mermer Petra , Rafiq Amir , Winterberg Sarah , Papadakis Tamara , Thomas Dominique , Angioni Carlo , Oberwinkler Johannes , Chubanov Vladimir , Gudermann Thomas , Gärtner Ulrich , Offermanns Stefan , Schütz Burkhard , Kummer Wolfgang
Published: March 2022

The gallbladder stores bile between meals and empties into the duodenum upon demand and is thereby exposed to the intestinal microbiome. This exposure raises the need for antimicrobial factors, among them, mucins produced by cholangiocytes, the dominant epithelial cell type in the gallbladder. The role of the much less frequent biliary tuft cells is still unknown. We here show that propionate, a major metabolite of intestinal bacteria, activates tuft cells via the short-chain free fatty acid receptor 2 and downstream signaling involving the cation channel transient receptor potential cation channel subfamily M member 5. This results in corelease of acetylcholine and cysteinyl leukotrienes from tuft cells and evokes synergistic paracrine effects upon the epithelium and the gallbladder smooth muscle, respectively. Acetylcholine triggers mucin release from cholangiocytes, an epithelial defense mechanism, through the muscarinic acetylcholine receptor M3. Cysteinyl leukotrienes cause gallbladder contraction through their cognate receptor CysLTR1, prompting emptying and closing. Our results establish gallbladder tuft cells as sensors of the microbial metabolite propionate, initiating dichotomous innate defense mechanisms through simultaneous release of acetylcholine and cysteinyl leukotrienes.
Macrophage compartmentalization in the brain and cerebrospinal fluid system
Authors: Munro David A. D. , Movahedi Kiavash , Priller Josef
Published: March 2022

Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of niche signals and mechanical stimuli that instruct their tissue-specific identities. Whereas most CNS macrophages are tissue-embedded, the macrophages of the cerebrospinal fluid (CSF) system are bathed in an oscillating liquid. Studies using multiomics technologies have recently uncovered the transcriptomic and proteomic profiles of CSF macrophages, enhancing our understanding of their cellular characteristics in both rodents and humans. Here, we review the relationships between CNS macrophage populations, with a focus on the origins, phenotypes, and functions of CSF macrophages in health and disease.
Low back pain as an unusual presentation in a child with acute lymphoblastic leukaemia
Authors: Sanchez-Mostiero Daisy Olave , Boussati Jamela Merriam Aragon
Published: March 2022

Acute leukaemia is the most common childhood cancer. The clinical presentation of acute leukaemia includes fever, pallor, bleeding tendencies, hepatosplenomegaly, lymphadenopathy and bone pains. This case is about a 7-year-old boy who presented with 2 months of progressive low back pain after jumping into the sea. Radiologic workup showed compression fractures in the T6–L5 regions of the spine. Trauma and osteogenesis imperfecta were considered initially until the patient developed the classic features of leukaemia. Analysis of the bone marrow aspirate, 2 months after the sea incident, revealed B cell acute lymphoblastic leukaemia (ALL). The low back pain subsided after a week of chemotherapy. A symptom that involves bone pain in a child needs thorough evaluation because a delay in diagnosis affects the outcome of treatment. ALL has been lingering at the time of his accident and this has caused weakening of his spine that resulted in much more severe injury than would have occurred in the absence of the ALL.
Pretreatment with systemic corticosteroid can mask early symptoms of hypersensitivity reaction to hyaluronidase following peribulbar block
Authors: Gupta Ashok , Moharana Bruttendu , Saini Reeti , Gupta Arjun
Published: March 2022

Hyaluronidase is a hydrolytic enzyme that helps in breaking down hyaluronic acid, a component of the extracellular tissue matrix, thereby facilitating the dispersion of local anaesthetic drugs through tissue planes. It is a key component in peribulbar anaesthesia for ocular surgeries. Allergic response to hyaluronidase is relatively rare but a potentially vision-threatening complication. A preoperative intradermal hypersensitivity test is useful to detect such cases and avoid potential complications. Here we report a case of hypersensitivity reaction to hyaluronidase after peribulbar anaesthesia for cataract surgery where an intradermal hypersensitivity test was falsely negative, and presentation was delayed due to the use of preoperative systemic corticosteroids. However, correct, and timely diagnosis and treatment saved the eye from permanent vision loss.
Unusual Presentation of Pott’s puffy tumour in a child: our recent experience and review of the literature
Authors: McGee Alice Elizabeth , Cooper Fergus , Maini Sangeeta Kapur , Vallamkondu Vamsidhar
Published: March 2022

Pott’s puffy tumour (PPT) is a rarely seen, but highly important, complication of frontal sinusitis. Early recognition followed by prompt imaging and treatment of this condition are essential to improve patient outcomes and prevent complications. This case report describes an atypical presentation of radiologically confirmed PPT in a boy who presented with a 2.5-week history of progressive frontal headache and midline frontal swelling. Flexible nasendoscopy revealed no acute findings. Prompt CT imaging confirmed the diagnosis and early surgical intervention via endoscopic approach with aggressive antibiotic therapy led to good recovery. This case highlights the need to remember PPT in assessing any child or adolescent with a new forehead swelling, with or without sinusitis symptoms. If there is strong clinical suspicion, further imaging should not be delayed. Surgical intervention should be performed as early as possible to prevent intracranial complications; antibiotics alone are not sufficient.
Transoral robotic surgical excision of hypopharyngeal ectopic parathyroid adenoma causing primary hyperparathyroidism
Authors: James Tobias , Lester Shane
Published: March 2022

Ectopic parathyroid adenomas are a rare congenital anomaly despite the complex migration parathyroid glands undergo during development. Rarer still, these can be found in the hypopharynx, become adenomas and be the cause of primary hyperparathyroidism. We present a case of a woman in her 50s who underwent transoral robotic surgery (TORS) to remove her hypopharyngeal ectopic parathyroid adenoma and cure her primary hyperparathyroidism without complication. This is a radical change in practice compared with traditional open, transverse cervical approaches. We demonstrate the efficacy of using TORS for this unusual case, highlighting its versatility and the need to continue to search for opportunities to best use this advancing technology, especially when it can improve patient outcomes.
Changes to local area public sector spending and food purchasing in England: a longitudinal ecological study
Authors: Jenkins Rosemary H , Vamos Eszter P , Taylor-Robinson David , Mason Kate E , Laverty Anthony A
Published: March 2022

Objectives

Changes in public sector service spending may influence food consumption. We make use of changing local authority (LA) expenditure in England to assess impacts on food purchasing. We examine total LA service spending and explore two potential pathways: highways and transport spending which may affect access to food; and housing service expenditure which may affect household resources available to purchase foods.

Design

Longitudinal panel survey at the LA level (2008–2015) using fixed effects linear regression.

Setting

324 LAs in England.

Main exposure

Expenditure per capita on total LA services, highways and transport services, and housing services.

Main outcome measures

LA area estimates of purchasing of fresh fruits and vegetables, high in fat, sugar and salt (HFSS) foods, and takeaways at home, expressed as a percentage of total food and drink expenditure.

Results

Total LA service spending decreased by 17% on average between 2008 and 2015. A 10% decrease in total LA spending was associated with a 0.071 percentage point decrease in HFSS (95% CI −0.093 to –0.050) and a 0.015 percentage point increase in takeaways (95% CI 0.006 to 0.024). A 10% decrease in highways and transport expenditure was associated with a 0.006 percentage point decrease in fruit and vegetable purchasing (95% CI −0.009 to –0.002) and a 0.006 percentage point increase in takeaway purchasing (95% CI 0.001 to 0.010). These associations were seen in urban areas only when analyses were stratified by rural/urban area status. A 0.006 percentage point decrease in HFSS purchasing was also seen with a 10% decrease in housing expenditure (95% CI −0.010 to –0.002).

Conclusion

Changes in LA spending may have impacts on food purchasing which are evident at the area level. This suggests that in addition to more prominent impacts such as foodbank use, austerity measures may have mixed impacts on food purchasing behaviours among the wider population. Individual-level research is needed to further elucidate these relationships.
Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK
Authors: Paisey Richard , Daniels Charles , Howitt Will , Greatorex Derek , Campbell Claire , Paisey Christopher , Paisey Rosamund , Frost Julie , Bromige Robert
Published: March 2022

Objective

To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity.

Design

General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases.

Results

325 subjects engaged in the programme and had sufficient data for analysis. Baseline characteristics were: age 47.8±12. 8 years; body mass index (BMI) 36.1±6.8 kg/m2; 79.1% female/20.9% male; 13.5% had type 2 diabetes. After 15±4 years weight had changed from 97.9±19 kg at baseline to 100±20.8 kg. 10 with diabetes at baseline were in remission at 3 months, but only two remained in remission at 5 years. 50 new cases of type 2 diabetes and 11 of impaired fasting glucose developed during follow-up. Only 5.9% who remained healthy at follow-up had maintained >10% body weight reduction. Neither diabetes incidence nor diabetes free survival were related to percentage body weight lost during VLCD. Only baseline BMI was related to development of new impaired fasting glucose or diabetes by 15 years (p=0.007). 37 subjects had a cardiovascular event. Age (p=0.000002) and degree of weight loss after VLCD (p=0.03) were significantly associated with subsequent vascular events.

Conclusion

Long-term maintenance of weight loss after VLCD was rare in this single centre retrospective study 15 years later. Glucose intolerance developed in 21.4%. Lasting remission of type 2 diabetes or prevention of later glucose intolerance were not achieved. Vascular events were more frequent in those who lost most weight. Risk management during weight regain should be studied in future to assess potential for reduction in adverse cardiovascular outcomes.
Patient journey during and after a pre-eclampsia-complicated pregnancy: a cross-sectional patient registry study
Authors: Bijl Rianne C , Bangert Sophie E , Shree Raj , Brewer Alina N , Abrenica-Keffer Norlisa , Tsigas Eleni Z , Koster Maria P H , Seely Ellen W
Published: March 2022

Objectives

To gain insight into the patient journey through a pre-eclampsia-complicated pregnancy.

Design

Cross-sectional patient registry study.

Setting

Online patient registry initiated by the Preeclampsia Foundation.

Participants

Women with a history of pre-eclampsia enrolled in The Preeclampsia Registry (TPR).

Primary and secondary outcome measures

Retrospective patient-reported experience measures concerning awareness of pre-eclampsia, timing and type of information on pre-eclampsia received, involvement in decision making regarding medical care, mental/emotional impact of the pre-eclampsia-complicated pregnancy and impact on future pregnancy planning.

Results

Of 3618 TPR-participants invited to complete the Patient Journey questionnaire, data from 833 (23%) responders were available for analysis. Most responders were white (n=795, 95.4%) and lived in the USA (n=728, 87.4%). Before their pre-eclampsia diagnosis, 599 (73.9%) responders were aware of the term ‘pre-eclampsia’, but only 348 (43.7%) were aware of its associated symptoms. Women with a lower level of education were less likely to have heard of pre-eclampsia (OR 0.36, 95% CI 0.21 to 0.62). Around the time of diagnosis, 29.2% of responders did not feel involved in the decision making, which was associated with reporting a serious mental/emotional impact of the pre-eclampsia experience (OR 2.46, 95% CI 1.58 to 3.84). Over time, there was an increase in the proportion of women who were aware of the symptoms of pre-eclampsia (32.2% before 2011 to 52.5% after 2016; p<0.001) and in the proportion of responders stating they received counselling about the later-life health risks associated with pre-eclampsia (14.2% before 2011 to 25.6% after 2016; p=0.005).

Conclusions

This study demonstrates that improved patient education regarding pre-eclampsia is needed, that shared decision making is of great importance to patients to enhance their healthcare experience, and that healthcare providers should make efforts to routinely incorporate counselling about the later-life health risks associated with pre-eclampsia.

Trial registration number

NCT02020174.
System analysis based on the cancer–immunity cycle identifies ZNF207 as a novel immunotherapy target for hepatocellular carcinoma
Authors: Wang Xu , Zhou Tao , Chen Xingyi , Wang Yu , Ding Yushi , Tu Haoyang , Gao Shengyang , Wang Haoyu , Tang Xinying , Yang Yong
Published: March 2022

Background

Immune checkpoint inhibitors as monotherapies for advanced hepatocellular carcinoma (HCC) fail to achieve satisfying results, while combination therapies show greater efficacy. Therefore, identifying new combined targets for immune checkpoint inhibitors could be promising.

Methods

We combined the cancer–immunity cycle score with weighted gene coexpression network and system analyses to screen immunosuppressive targets in HCC. In vitro and in vivo experiments were used to assess the effect of zinc finger protein 207 (ZNF207) on HCC immunity. RNA sequencing, metabolomic, cytokine array analysis, dual-luciferase reporter gene assay, and ChIP quantitative PCR assay were used to investigate the role of ZNF207 in tumor immunity regulation.

Results

The system analysis and experimental verification revealed ZNF207 as an immunosuppressive target in HCC. Hypoxia-induced upregulation of ZNF207 promoted HCC progression in immunocompetent mice while being associated with decreased CD8+T-cell infiltration and increased exhaustion. Mechanistically, the mitogen-activated protein kinase (MAPK)–chemokine C-X3-C-motif ligand axis was involved in ZNF207-mediated CD8+T-cell chemotaxis. Furthermore, ZNF207 transcriptionally regulated indoleamine 2,3-dioxygenase 1 and elevated kynurenine levels, leading to the exhaustion of CD8+T cells. Patients with lowerZNF207expression were more sensitive to antiprogrammed cell death protein 1 (PD1) therapy, and silencingZNF207could be beneficial to anti-PD1 combination therapy.

Conclusion

Our study implicates ZNF207 in suppressing the HCC microenvironment and showed the feasibility of targeting ZNF207 during anti-PD1 therapy in HCC.
Multimodal prognostic features of seizure freedom in epilepsy surgery
Authors: Alim-Marvasti Ali , Vakharia Vejay Niranjan , Duncan John Sidney
Published: March 2022

Objective

Accurate preoperative predictions of seizure freedom following surgery for focal drug resistant epilepsy remain elusive. Our objective was to systematically evaluate all meta-analyses of epilepsy surgery with seizure freedom as the primary outcome, to identify clinical features that are consistently prognostic and should be included in the future models.

Methods

We searched PubMed and Cochrane using free-text and Medical Subject Heading (MeSH) terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study was registered on PROSPERO. We classified features as prognostic, non-prognostic and uncertain and into seven subcategories: ‘clinical’, ‘imaging’, ‘neurophysiology’, ‘multimodal concordance’, ‘genetic’, ‘surgical technique’ and ‘pathology’. We propose a structural causal model based on these features.

Results

We found 46 features from 38 meta-analyses over 22 years. The following were consistently prognostic across meta-analyses: febrile convulsions, hippocampal sclerosis, focal abnormal MRI, Single-Photon Emission Computed Tomography (SPECT) coregistered to MRI, focal ictal/interictal EEG, EEG-MRI concordance, temporal lobe resections, complete excision, histopathological lesions, tumours and focal cortical dysplasia type IIb. Severe learning disability was predictive of poor prognosis. Others, including sex and side of resection, were non-prognostic. There were limited meta-analyses investigating genetic contributions, structural connectivity or multimodal concordance and few adjusted for known confounders or performed corrections for multiple comparisons.

Significance

Seizure-free outcomes have not improved over decades of epilepsy surgery and despite a multitude of models, none prognosticate accurately. Our list of multimodal population-invariant prognostic features and proposed structural causal model may serve as an objective foundation for statistical adjustments of plausible confounders for use in high-dimensional models.

PROSPERO registration number

CRD42021185232.
Do doctors have a responsibility to help patients import medicines from abroad?
Authors: Ghinea Narcyz
Published: March 2022

Almost any medicine can be purchased online from abroad. Many high-income countries permit individuals to import medicines for their personal use. However, those who import medicines face the risk of purchasing poor-quality products that may not work, or that may even harm them. Many people are willing to accept this risk for the opportunity to purchase more affordable medicines. This is especially true of individuals from low socioeconomic backgrounds who already struggle to afford the medicines they need if they are not subsidised by insurers or if copayments are high. As medicine prices and out-of-pocket healthcare spending continue to climb, the online marketplace provides an important alternative for individuals in high-income countries to source medicines. In this article, I argue that doctors have a responsibility to help patients access medicines online and I propose a framework that can be used to facilitate responsible personal importation.