Summary
Background
Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and ...therefore it is important to identify new markers to better predict its clinical evolution.
Objectives
We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR‐203 and miR‐205 as biomarkers of prognosis in human tumours.
Methods
Seventy‐nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well‐established panel of murine skin cancer cell lines, and then selected miR‐205 and miR‐203 to evaluate their association with the clinical prognosis and evolution of human CSCC.
Results
miR‐205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR‐205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR‐205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR‐203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well‐differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR‐205 and miR‐203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR‐203 and miR‐205 expression, and pathological tumour features.
Conclusions
miR‐205 and miR‐203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR‐205 and miR‐203 as prognostic markers in CSCC.
What's already known about this topic?
Cutaneous squamous cell carcinoma (CSCC) is the second most common cancer in humans. Its incidence is increasing and it can evolve into a disease of poor prognosis.
MicroRNAs (miRNAs or miRs) have been implicated in the pathogenesis of several forms of cancer but its role in CSCC is not well understood.
What does this study add?
miR‐203 and miR‐205 display a mutually exclusive pattern of expression in CSCC.
miR‐203 is associated with features of favourable prognosis and miR‐205 is associated with poor outcome in CSCC.
What is the translational message?
miR‐203 and miR‐205 expression help to predict the prognosis of human CSCC.
miR‐203 and miR‐205 were associated with different CSCC traits in a mutually exclusive manner.
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Data analysis techniques such as machine learning have been used for assisting in triage and the diagnosis of health problems. Nevertheless, it has not been used yet to assist community pharmacists ...with services such as the Minor Ailment Services These services have been implemented to reduce the burden of primary care consultations in general medical practitioners (GPs) and to allow a better utilization of community pharmacists' skills. However, there is a need to refer high-risk patients to GPs.
To develop a predictive model for high-risk patients that need referral assisting community pharmacists' triage through a minor ailment service.
An ongoing pragmatic type 3 effectiveness-implementation hybrid study was undertaken at a national level in Spanish community pharmacies since October 2020. Pharmacists recruited patients presenting with minor ailments and followed them 10 days after the consultation. The main outcome measured was appropriate medical referral (in accordance with previously co-designed protocols). Nine machine learning models were tested (three statistical, three black box and three tree models) to assist pharmacists in the detection of high-risk individuals in need of referral.
Over 14'000 patients were included in the study. Most patients were female (68.1%). With no previous treatment for the specific minor ailment (68.0%) presented. A percentage of patients had referral criteria (13.8%) however, not all of these patients were referred by the pharmacist to the GP (8.5%). The pharmacists were using their clinical expertise not to refer these patients. The primary prediction model was the radial support vector machine (RSVM) with an accuracy of 0.934 (CI95 = 0.926,0.942), Cohen's kappa of 0.630, recall equal to 0.975 and an area under the curve of 0.897. Twenty variables (out of 61 evaluated) were included in the model. radial support vector machine could predict 95.2% of the true negatives and 74.8% of the true positives. When evaluating the performance for the 25 patient's profiles most frequent in the study, the model was considered appropriate for 56% of them.
A RSVM model was obtained to assist in the differentiation of patients that can be managed in community pharmacy from those who are at risk and should be evaluated by GPs. This tool potentially increases patients' safety by increasing pharmacists' ability to differentiate minor ailments from other medical conditions.
INTRODUCTIONThe global pandemic of COVID-19 has led to rapid implementation of telemedicine, but there is little information on patient satisfaction of this system as an alternative to face-to-face ...care. OBJECTIVETo evaluate urological patient satisfaction with teleconsultation during the COVID-19 pandemic. MATERIAL AND METHODSObservational, prospective, cross-sectional, non-interventional study carried out by telephone survey during the period considered as the peak of the pandemic (March-April 2020). A quality survey composed of 11 questions on urological care provided by physicians during the COVID-19 pandemic was conducted, selecting a representative sample of patients attended by teleconsultation. RESULTSTwo hundred patients were contacted by telephone to answer a survey on the quality of teleconsultation. The distribution of patients surveyed among the specialized consultations was homogeneous with the number of consultations cited in the period; 18% of them required assistance from family members. Sixty percent of patients avoided going to a medical center during the pandemic. Of the surveyed patients, 42% had cancelled diagnostic tests, 59% had cancelled medical consultations, 3.5% had cancelled treatments and 1% had cancelled interventions. Ten percent reported a worsening of urological symptoms during confinement. According to physicians, consultations were effectively delivered in 72% of cases, with teleconsultation being carried out by their usual urologist in 81%. Teleconsultation overall satisfaction level was 9 (IQI8-10), and 61.5% of respondents consider teleconsultation as a «health care option» after the healthcare crisis. CONCLUSIONTeleconsultation has been evaluated with a high level of satisfaction during the COVID-19 pandemic, offering continuous care to urological patients during the healthcare crisis. The perceived quality offers a field of optional telematic assistance in selected patients, which should be re-evaluated in a period without confinement measures.
Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as ...both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this knowledge, the synthesis, pharmacological evaluation and docking studies of a new class of indazoles has been performed. Pharmacological evaluation includes radioligand binding assays with 3H-CP55940 for CB1R and CB2R and functional activity for cannabinoid receptors on isolated tissue. Additionally, in vitro inhibitory assays of AChE/BuChE and the corresponding competition studies have been carried out. The results of pharmacological tests have revealed that three of these derivatives behave as CB2 cannabinoid agonists and simultaneously show BuChE inhibition. In particular, compounds 3 and 24 have emerged as promising candidates as novel cannabinoids that inhibit BuChE by a non-competitive or mixed mechanism, respectively. On the other hand, both molecules show antioxidant properties.
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•A specific multitarget approach as potential therapeutic agents for Alzheimer's disease.•New indazole ethers designed from computational studies.•Novel family of CB2 receptor agonists and BuChE inhibitors.•Selected indazole derivatives show antioxidant properties.
We have tested the usefulness of several commercial anti-CD33 monoclonal antibodies (mAb) to determine the expression and localization of the two CD33 isoforms on several hematopoietic cell lines. ...The expression of the isoform CD33m, a CD33 transmembrane splice variant lacking the ligand-binding V immunoglobulin (Ig)-like domain, was detected by RT-polymerase chain reaction, western blot, confocal microscopy and flow cytometry on the membrane of several human cell types. CD33m was only detected by the anti-CD33 mAb HIM3-4 on the cell surface, whereas WM53, P67.6, 4D3, HIM3-4, WM54, D3HL60.251 or MY9 detected the CD33M isoform, indicating that HIM3-4 is the only mAb recognizing CD33 C(2) Ig domain. Accordingly, HIM3-4 binding to CD33 did not interfere with the binding of other antibodies against the CD33 V-domain. P67.6 mAb interfered with recognition by the rest of antibodies specific for the V domain. HIM3-4 staining could be increased after the sialidase treatment of all CD33(+) cells. However, this increase was stronger in activated T cells, suggesting a CD33 masking state in this cell population. Confocal microscopy analysis of CD33m HEK 293T-transfected cells revealed that this protein is expressed on the cell membrane and also detected in the Golgi compartment. CD33 is constitutively located outside the lipid raft domains, whereas cross-linked CD33 is highly recruited to this signaling platform. The unique ability of HIM3-4 mAb to detect the masking state of CD33 on different cell lineages makes it a good tool to improve the knowledge of the biological role of this sialic acid-binding Ig-like lectin.
The potential role of red deer (Cervus elaphus) as a reservoir of Mycobacterium avium subspecies paratuberculosis (MAP) infection is largely unknown. A total of 332 wild red deer were investigated ...using post-mortem examination, bacteriology and serology. Only three animals (1.12%) were found to have lesions on histopathological examination and no MAP bacteria were recovered on culture. The results suggest it is unlikely that wild red deer make a significant contribution to the maintenance of MAP infection in the region. The cross-reactivity of the ELISAs used indicates this diagnostic modality is ineffective in the detection of MAP infection in this species. The implications of these results for the control of this important pathogen in both livestock and wildlife are discussed.
Perifoveal exudative vascular anomalous complex (PEVAC) Sotomayor-Toribio, M.; López-Herrero, F.; Sánchez-Vicente, J.L. ...
Archivos de la Sociedad Española de Oftalmología (English ed.),
July 2023, 2023-Jul, 2023-07-00, Letnik:
98, Številka:
7
Journal Article
Recenzirano
We present three cases of patients aged 66, 80 and 23, who presented unilateral vision loss. Optical coherence tomography (OCT) in all of them showed macular oedema and a rounded lesion with ...hyperreflective wall, and fluorescein angiography (FAG) in two of them showed hyperfluorescent perifoveal aneurysmal dilations with exudation.
None of the cases showed response to treatment after one year of follow-up, finally being diagnosed with Perifoveal Exudative Vascular Anomalous Complex (PEVAC).
Se presentan 3 casos de pacientes, con 66, 80 y 23 años de edad, que presentaron una pérdida de visión unilateral. La tomografía de coherencia óptica (OCT) mostró edema macular junto con una lesión redondeada de pared hiperreflectiva y la angiografía con fluoresceína (AFG) de dos de ellos, dilataciones aneurismáticas perifoveales hiperfluorescentes con exudación.
Ninguno de los casos mostró respuesta al tratamiento tras un año de seguimiento, diagnosticándose finalmente de Complejo Anómalo Vascular Exudativo Perifoveal (PEVAC).
The major histocompatibility complex (MHC) contains the most variable functional genes described in vertebrates. Individuals from natural populations deal constantly with a diverse range of pathogens ...and the polymorphism at MHC loci is what determines the diversity of foreign antigens that the host immune system can recognize. Polymorphism at individual loci may result in variable MHC class II (MHC-II) haplotypes. We characterized for the first time, the allelic diversity at the second DRB locus of the MHC-II in the Iberian red deer Cervus elaphus hispanicus. The studied population was sampled from a fenced estate that has been managed for hunting purposes and may provide information of the effect of game management on the genetic diversity of this species. Deer presented high levels of variation at MHC-II DRB-2 with 18 different alleles detected in 94 individuals. However, a significant heterozygous deficiency was found for MHC-II DRB-2 locus (92.5% of individuals only amplified one allele), whereas genotype frequencies at three neutral microsatellite loci were according to Hardy-Weinberg equilibrium, with heterozygosity over 50%. The analysis of control Iberian red deer from different geographic locations identified two expressed DRB-2 loci with a high degree of heterozygosis. The annual diversity index of MHC-II DRB-2 alleles significantly decreased along the 16-year study period, which was confirmed with losses in microsatellite markers. Although we cannot exclude positive non-assortative mating and/or substructured breeding (Wahlund effect) within our reference population, such unexpected apparent homozygosity at MHC DRB-2 loci is suggestive of null alleles occurring at our population. The observed pattern could be the result of a founder effect in this recently established population. Nonetheless, the loss of MHC-II DRB-2 allele diversity could reflect the effects of inbreeding in this fenced population managed for hunting. These findings support the importance of immunogenetic studies to assess management decisions, especially in isolated ungulate populations.
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