bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymptomatic subjects at high genetic risk of developing Alzheimer's disease: An OCT study
Authors: López‐Cuenca Inés 
Published: December 2022

AbstractOne of the major genetic risk factors for developing Alzheimer's disease (AD) is having a first‐degree family history of the disease. Approximately 40% of affected individuals have a family history of AD, and epidemiological studies indicate that the risk of AD in an individual with an affected first‐degree relative is four to ten times higher in cognitively healthy subjects. In addition, epidemiological studies have shown that transmission of the sporadic form of AD is both maternal and paternal, being the risk higher when it is the mother the affected patient, as it was associated with worse cognitive performance and a more predictable age of onset of the pathology. Among the possible explanatory genetic mechanisms, evidence of an inherited predisposition to cerebral metabolic reductions and atrophy in subjects with maternal family history suggests alterations in mitochondrial DNA (mtDNA), which is fully maternally inherited in humans.ApoE mediates another important genetic risk factor and this gene has been implicated in the modulation of Aβ metabolism and aggregation. The allele of APOE, ɛ4, increases the risk of AD threefold for each ɛ4 allele, and the risk is higher among people of European ancestry. Furthermore, ApoE ɛ4 has been reported to affect magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and cognitive biomarkers, and may have intrinsic effects on brain function. Likewise, ApoE ɛ4 + elevated levels of amyloid beta (Aβ) proteins are associated with episodic memory impairment and high risk for clinical AD, and ApoE ɛ4 carriers are also more vulnerable to environmental factors.There is a clear relationship between retinal and brain changes in AD. In preclinical stages, retinal changes have been reported on optical coherence tomography (OCT), as well as the existence of associations between quadrant‐specific retinal nerve fibre layer thickness and brain regions analysed by 3 T MRI. In addition, both family history of the disease (FH+) and ApoE ɛ4 genotype (ApoE ɛ4+) potentiate each other, contributing to the thinning of the cortex in the hippocampal region. Likewiss, a direct correlation has been observed between the volumes of brain areas measured by magnetic resonance imaging (MRI) and the thickness of specific retina regions using OCT in nondemented older adults.All of these observations support the value of the retina as a biomarker of AD. It is known that signs of dementia can appear decades before clinically detectable symptoms. For all these reasons, interest in finding new biomarkers of the disease has focused on the earliest stages of AD, seeking less invasive and less expensive diagnostic methods for early diagnosis of the disease. OCT, unlike other methods such as AB determination in CSF or PET, is a reliable and inexpensive non‐invasive diagnostic method that allows us to detect retinal changes in individuals at high risk for AD in preclinical stages of the disease, contributing to both early diagnosis and follow‐up of these individuals.
Neuroprotection in ophthalmology. Targets in the most frequent diseases. A clinician's point of view
Authors: Pastor Jose C. , Pastor‐Idoate Salvador , López‐Paniagua Marina , Para Marta , Blazquez Francisco , Murgui Esther , Coco‐Martín Rosa M. 
Published: December 2022

AbstractObjectives: To briefly review the most frequent ocular diseases in which a neuroprotective treatment would be needed and to present the results of a translational research based on the neuroprotective capacities of allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) in an ocular disease that currently lacks treatment, the non‐arteritic acute anterior ischemic optic neuropathy. (NA‐AION) considered as an infarct of the optic nerve head.Methods: After extensive preclinical evaluation of safety in rabbits, a prospective, non‐randomized, phase II clinical trial (Eudra CT number 2016–003029‐40 and ClinicalTrials.gov NCT03173638) was approved. Five patients with acute unilateral NA‐AION diagnosed within the first 2 weeks after symptom onset were included. After informed consent, patients received an intravitreal injection of 0.05 ml containing 150 μl of isotonic medium composed of Ringer's lactate, 0.5% human albumin, and 5 mM glucose, with a cell concentration of 1.5 × 106 cells/ml. The injection was administered using a 25‐gauge needle via the pars plana after topical anaesthesia. Patients were followed on days 1, 7, 30, 90, 180 and 1 year after injection. Safety was defined as the absence of an inflammatory reaction. The best‐corrected visual acuity, visual evoked potentials (VEP) and retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thicknesses were measured.Results: No patients had signs of intraocular inflammation at any time. An epiretinal membrane (ERM) developed in one patient. One phakic patient had a retrolental aggregate that did not progress to cataract. Four patients had visual improvement and three had increased amplitudes on the VEP recordings after treatment. The RNFL and GCL thicknesses decreased significantly in parallel with the visible papillary atrophy that developed during the follow‐up period.Conclusions: Despite development of an ERM in one patient and a possible cellular deposit in the retrolental space, the functional results are encouraging. A larger multicentre study of treated patients that includes a control group is currently running. The paracrine capacities of allergenic MSCs should be more extensively investigated in the clinic, taking advantage of their non‐immunogenicity, their ease of obtaining and their apparent safety.Financial support: Funded by Strategic Action in Health of the Institute of Health Carlos III (PIC18/00018), the Department of Regional Health of the Castilla y Léon Government (GRS 1928/A/19), and the Department of Education of the Castilla y León Regional Government (Grant VA077P17).
autophagy response in chronic neuronal oxidative stress
Authors: Behl Christian 
Published: December 2022

AbstractAge‐associated neurodegenerative diseases like Alzheimer's and Parkinson's disease (PD) but also glaucoma is generally accompanied by intracellular stress, malignant accumulations of dysfunctional proteins and a disturbance of the proteostasis. Over time adaptation and increased resilience are measures to make neurons more stable against age‐ and disease‐related challenges. The hippocampal cell line HT22 has been used to illustrate the adaptive ability in response to oxidative stress by enhancing autophagic activity via especially the process of BAG3‐mediated selective macroautophagy.We extended the resistance protocol and generated a novel HT22 cell line that is resistant to thapsigargin, depleting intracellular Ca2+ stores and a potent inducer of ER stressor.We observed a significantly increased LC3B‐II and p62 flux in thapsigargin‐resistant (TgR) compared with HT22‐WT | ells at both, basal and starved conditions. Intriguingly, when looking at the process of ER‐phagy manifold changes are occurring in TgR cells.We suggest that the observed changes in autophagy‐related process, including ER‐phagy, may promote resistance against age‐related Ca2+ disturbance and Ca2+ stress in neuronal cells. Taken together, neuronal cell lines selected for a particular resistance allow molecular insights into neuronal adaptability.
Brain involvement in glaucoma: A new target in neuroprotection
Authors: Nucci Carlo 
Published: December 2022

AbstractGlaucoma is one of the leading causes of blindness worldwide. The mechanisms underlying glaucomatous involvement of the central nervous system are still not completely known. It has been hypothesized that glaucomatous degeneration may be the result of anterograde transsynaptic neurodegeneration triggered by ganglion cells' death. However, it has been also postulated that in some cases it may be the consequence of neurodegenerative diseases of the central nervous system such as Alzheimer's' Disease. Autophagy and perfusion deficits have been also implicated in the etiopathogenesis of glaucoma. The introduction of new neuroimaging techniques may help to extend the knowledge about this disease, consent early diagnosis and could be a valuable tool for assessing the therapeutic efficacy of novel neuroprotective strategies.
ROCK inhibitors in glaucoma medical treatment
Authors: Oddone Francesco 
Published: December 2022

AbstractRho kinase inhibitors are a novel advancement in glaucoma medical treatment and have been recently approved for instruction in the market in fixed combination with the prostaglandin analogue Latanoprost. They have a novel mechanism of action based on their ability to improve humour aqueous outflow through the conventional trabecular meshwork pathway.Rho family proteins are GTPases that localize in the intracellular side of plasma membrane and are activated by several plasma membrane signal receptors, including TGF‐β and hormones.Activated Rho then activates Rho‐associated protein kinases which further transmit the stimulus to downstream effectors. The whole pathway is involved in several cellular activities, including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, and remodelling of the ECM. ROCKs mediate pro‐fibrotic processes in many tissues and pathological conditions. In cultured human TM cells, exposure to a ROCK inhibitor caused retraction and rounding of cell bodies, as well as disruption of actin bundles and impaired focal adhesion formation. ROCKs have been associated when administered topically to a reduction in episcleral venous pressure that might contribute to their ocular hypotensive effects.MERCURY‐3, was a prospective, randomized, double‐masked, active‐controlled study to assess the efficacy, safety, and tolerability of the ROCK inhibitor netarsudil 0.02% in fixed combination with latanoprost 0.005% compared with the fixed combination of bimatoprost 0.03%/timolol 0.5%.The results of the study showed non inferiority of the netarsudil fixed combination despite a slightly worse local tolerability profile.Current management approaches aim to reduce IOP but do not tackle the principal site of increased outflow resistance that is the TM. ROCK inhibition shows for the first time the ability for directly modulating the TM permeability and represents a new clinical treatment for glaucoma.
Bilateral recurrent choroidal neovascularization in AZOOR
Authors: Follonosa Alejandro 
Published: December 2022

AbstractWe present a case of acute zonal occult outer retinopathy (AZOOR) in a 61‐year‐old man who presented associated recurrent choroidal neovascularization as a complication in both eyes; he was managed with several intravitreal anti vascular endothelial growth factor (anti‐VEGF) injections in both eyes as well as with Prednisone and Methotrexate, which in improved the disease control.
brain mechanism of sight recovery
Authors: Röder Brigitte 
Published: December 2022

AbstractPatients who were born with total bilateral cataracts and who were treated late in life show permanent deficits in visual acuity and other basic visual functions. Some higher visual functions are more (face identity processing, coherent motion processing) and other higher order visual functions (biological motion processing, visual exploration) are less impaired than expected from the visual acuity loss. Moreover, the integration of the late available visual input with the intact sensory inputs (hearing, touch) seems to be partially altered. The present talk will focus on new behavioural, electrophysiological and both functional and structural brain imaging results aiming to uncover the neural mechanisms of sight recovery in patients who had suffered from an extended period of blindness before they underwent cataract removal surgery.
novel insights into neuronal and vascular damage glaucoma
Authors: Di Polo Adriana 
Published: December 2022

AbstractDespite decades of clinical and basic research, we still do not understand the factors that cause retinal ganglion cell death and loss of vision in glaucoma patients. This keynote lecture will provide insights into new mechanisms that lead to early neuronal and neurovascular dysregulation in glaucoma. Several pathological changes associated with retinal ganglion cell damage will be discussed including dendritic retraction and synapse loss, metabolic deficits, and loss of neurovascular coupling. The role of pericytes in retinal capillary function will be presented, including newly identified inter‐pericyte tunnelling nanotubes, and their impact on retinal ganglion cell viability. These new data will highlight therapeutic opportunities to alleviate key pathological processes and restore visual function in glaucoma and other optic neuropathies.
what can we learn from rare eye diseases
Authors: Bremond‐Gignac Dominique 
Published: December 2022

AbstractRare eye diseases are considered if the prevalence is lower than 1/2000 in the general population and are usually recognized in paediatric ophthalmologic practices. Even if not all ophthalmologists see these ocular diseases, the model mostly genetic, can be useful to treat other ocular anomalies in pathologies that are more common. We will expose new insights in congenital aniridia, a congenital panocular disorder characterized by complete or partial iris hypoplasia and foveal hypoplasia, resulting in nystagmus and reduced visual acuity. High‐resolution foveal imaging by spectral‐domain optical coherence tomography (SD‐OCT) may improve the diagnosis. Moreover, Leber congenital amaurosis is a new model for gene therapy and opens new therapeutic options. We will also provide update for congenital anterior segment malformations, vernal keratoconjunctivitis, albinism and OVCR in children.
How nurses use National Early Warning Score and Individual Early Warning Score to support their patient risk assessment practice: A fieldwork study
Authors: Langkjaer Caroline S. , Bundgaard Karin , Bunkenborg Gitte , Nielsen Pernille B. , Iversen Kasper K. , Bestle Morten H. , Bove Dorthe G. 
Published: December 2022

AbstractAimTo explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I‐EWS) are used and how they support nurses' patient risk assessment practice.DesignA qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019.MethodsData were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts.ResultsNEWS and I‐EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I‐EWS had the effect of enhancing nurse autonomy and responsibility for decision‐making in relation to patient care.ConclusionsEWS systems support nurses' patient risk assessment practice, providing useful information. I‐EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses.ImpactThe findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person‐centred nursing care.
Novel methodology for the evaluation of symptoms reported by patients with newly diagnosed atrial fibrillation: Application of natural language processing to electronic medical records data
Authors: Reynolds Matthew R. , Bunch Thomas Jared , Steinberg Benjamin A. , Ronk Christopher J. , Kim Hankyul , Wieloch Mattias , Lip Gregory Y. H. 
Published: December 2022

AbstractIntroductionUnderstanding symptom patterns in atrial fibrillation (AF) can help in disease management. We report on the application of natural language processing (NLP) to electronic medical records (EMRs) to capture symptom reports in patients with newly diagnosed (incident) AF.Methods and ResultsThis observational retrospective study included adult patients with an index diagnosis of incident AF during January 1, 2016 through June 30, 2018, in the Optum datasets. The baseline and follow‐up periods were 1 year before/after the index date, respectively. The primary objective was identification of the following predefined symptom reports: dyspnea or shortness of breath; syncope, presyncope, lightheadedness, or dizziness; chest pain; fatigue; and palpitations. In an exploratory analysis, the incidence rates of symptom reports and cardiovascular hospitalization were assessed in propensity‐matched patient cohorts with incident AF receiving first‐line dronedarone or sotalol. Among 30 447 patients with an index AF diagnosis, the NLP algorithm identified at least 1 predefined symptom in 9734 (31.9%) patients. The incidence rate of symptom reports was highest at 0–3 months post‐diagnosis and lower at >3–6 and >6–12 months (pre‐defined timepoints). Across all time periods, the most common symptoms were dyspnea or shortness of breath, followed by syncope, presyncope, lightheadedness, or dizziness. Similar temporal patterns of symptom reports were observed among patients with prescriptions for dronedarone or sotalol as first‐line treatment.ConclusionThis study illustrates that NLP can be applied to EMR data to characterize symptom reports in patients with incident AF, and the potential for these methods to inform comparative effectiveness.
Leadless cardiac ventricular pacing using helix fixation: Step‐by‐step guide to implantation
Authors: Laczay Balint , Aguilera Jose , Cantillon Daniel J. 
Published: December 2022

AbstractIntroductionLeadless cardiac pacemakers are an alternative modality to traditional transvenous pacemaker systems. Recently receiving Food and Drug Administration approval, the AVEIR VR leadless pacemaker system provides a helix based active fixation leadless pacemaker system. This step‐by‐step review will cover patient selection, preprocedural planning, device implantation technique, implant site evaluation, troubleshooting, short‐ and long‐term complications as well as future directions for leadless pacing.MethodsWe collected and reviewed cases from primary operators to provide a step‐by‐step review for implanters.ResultsOur paper provides a guide to patient selection, pre‐procedural planning, device im plantation technique, implant site evaluation, troubleshooting, short‐ and long‐term complications as well as future directions for leadless pacing.ConclusionThe helix based active fixation leadless pacemaker system is a safe and efficacious way to provide pacing support to patients and provides an alternative to transvenous pacing systems. Our review provides a step‐by‐step guide to implantation.
Socioeconomic and sex inequalities in parent‐reported adolescent mental ill‐health: time trends in four British birth cohorts
Authors: McElroy Eoin , Tibber Marc , Fearon Pasco , Patalay Praveetha , Ploubidis George B. 
Published: December 2022

BackgroundStudies using symptom‐based screeners have suggested that mental ill‐health has increased in adolescents in recent decades, however, few studies have tested the equivalence of their instruments, which is critical for inferring changes in prevalence. In addition, little research has explored whether socioeconomic position (SEP) and sex inequalities in adolescent mental health have changed over time.MethodsUsing structural equation modelling, we explored SEP and sex differences in harmonised parent reports of emotional and behavioural problems, using data from four UK birth cohorts: the 1958 National Child Development Study (NCDS'58; n = 10,868), the 1970 British Cohort Study (BCS'70; n = 8,242), the 1991–92 Avon Longitudinal Study of Parents and Children (ALSPAC'91; n = 5,389), and the 2000–01 Millennium Cohort Study (MCS'01; n = 9,338).ResultsCompared with the two earliest cohorts, members of MCS'01 had higher latent mean scores on emotional problems (both sexes), and lower scores on behavioural problems (females only). The associations between four indicators of SEP and emotional problems were strongest in MCS'01, with housing tenure having the strongest association. All four SEP indicators were associated with behavioural problems in each cohort, with housing tenure again more strongly associated with problems in the MCS'01. Mediation analyses suggested that the increase in emotional problems occurred despite broadly improving socioeconomic conditions.ConclusionsOur findings suggest that parent reports of adolescent emotional problems, but not behavioural problems, have risen in recent generations and this trend is not solely due to reporting styles. A failure to address widening social inequalities may result in further increases in mental ill‐health amongst disadvantaged young people.
A cross‐sectional study reveals a chronic low‐grade inflammation in achalasia
Authors: Ma Li‐Yun , Liu Zu‐Qiang , Chen Wei‐Feng , Yao Lu , Zhong Yun‐Shi , Zhang Yi‐Qun , Ma Li‐Li , Qin Wen‐Zhen , Hu Jian‐Wei , Cai Ming‐Yan , Zhang Zhen , Lin Sheng‐Li , Hu Hao , Zhou Ping‐Hong , Li Quan‐Lin 
Published: December 2022

AbstractBackground and AimImmune‐mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations.MethodsWe investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n = 341) and healthy controls (n = 80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis.ResultsNLR, MLR, CRP, globulin, IL‐6 and IL‐10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up‐regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases.ConclusionsPatients with achalasia suffered from chronic low‐grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.