Effectiveness of pars plana Ahmed® valve implantation in patients with refractory glaucoma.

PURPOSE: To evaluate the success rate and complications of the Ahmed FP7 valve implanted via Pars Plana in a group of vitrectomized patients with refractory glaucoma and anterior segment abnormalities from January 2018 to June 2023. METHODS: Quasi-experimental, prospective study. Eleven eyes with refractory glaucoma were included. Participants underwent a comprehensive ophthalmic examination, including assessment of intraocular pressure (IOP) reduction, visual acuity, characterization of glaucoma type, and number of antiglaucoma medications. RESULTS: The mean baseline IOP was 37.3 ±â€¯11 mmHg, which decreased to 13.5 ±â€¯3.0 mmHg after one year. The qualified success rate was 63.7%, while the complete success rate was 36.3%. The most common diagnosis was neovascular glaucoma in 36.4% of cases. The most frequent postoperative complications were choroidal detachment and hypotony. CONCLUSIONS: Our data suggest that implantation of the Ahmed FP7 valve via pars plana is an effective and safe option for patients with refractory secondary glaucoma.

Healthcare Provider-Related Factors in the Diagnostic Delay of Cervical Cancer: A Cross-Sectional Study.

Background and objective Cervical cancer is the second most common malignancy among Indian women. In 2018, the World Health Organization (WHO) called for global action toward the elimination of cervical cancer through the triple-intervention strategy. One of its pillars is ensuring 70% screening coverage of eligible women with a high-performance test at least twice in their lifetime. Various factors contribute to the delayed diagnosis of cervical cancer, increasing the burden of the disease. In this study, we aimed to determine the healthcare provider (HCP)-related factors in the diagnostic delay of advanced cervical cancer. Methods This prospective cross-sectional study was conducted over two months in the cancer clinic of the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. We interviewed 384 women diagnosed with advanced cervical cancer [the International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IVB] by using a questionnaire to capture data inputs regarding the various healthcare services they had received in the past 10 years along with details of HCPs. The collected data were analyzed using the software STATA version 17.0. Results Among 384 participants, 185 (48.1%) had interacted with an HCP in the past 10 years; 157 (40.8%) of them had visited a healthcare facility. Among these 185 women, only 22.16% had been advised to undergo screening, and only 15.18% had been tested despite several having access to primary health centers within 10 km of their residence. The lack of screening guidance by HCPs accounted for 78% of delayed diagnoses of cervical cancer. Conclusions Based on our findings, a deficiency in screening guidance in the asymptomatic period by healthcare providers across various levels of our healthcare system contributed significantly to the delayed diagnosis of cervical cancer.

Machine learning models based on ultrasound and physical examination for airway assessment.

PURPOSE: To demonstrate the utility of machine learning models for predicting difficult airways using clinical and ultrasound parameters. METHODS: This is a prospective non-consecutive cohort of patients undergoing elective surgery. We collected as predictor variables age, sex, BMI, OSA, Mallampatti, thyromental distance, bite test, cervical circumference, cervical ultrasound measurements, and Cormack-Lehanne class after laryngoscopy. We univariate analyzed the relationship of the predictor variables with the Cormack-Lehanne class to design machine learning models by applying the random forest technique with each predictor variable separately and in combination. We found each design's AUC-ROC, sensitivity, specificity, and positive and negative predictive values. RESULTS: We recruited 400 patients. Cormack-Lehanne patients≥III had higher age, BMI, cervical circumference, Mallampati class membership≥III, and bite test≥II and their ultrasound measurements were significantly higher. Machine learning models based on physical examination obtained better AUC-ROC values than ultrasound measurements but without reaching statistical significance. The combination of physical variables that we call the "Classic Model" achieved the highest AUC-ROC value among all the models [0.75 (0.67-0.83)], this difference being statistically significant compared to the rest of the ultrasound models. CONCLUSIONS: The use of machine learning models for diagnosing VAD is a real possibility, although it is still in a very preliminary stage of development. CLINICAL REGISTRY: ClinicalTrials.gov: NCT04816435.

Evaluation of macular integrity, after retinal detachment surgery, using MAIA microperimetry.

BACKGROUND AND OBJECTIVE: To describe visual function, macular integrity, and fixation stability using MAIA microperimetry (macular integrity assessment) after retinal detachment surgery. Evaluate if there are statistically significant differences between surgical approaches. MATERIALS AND METHODS: A prospective, comparative, interventional study was conducted, recruiting a total of 21 patients with rhegmatogenous retinal detachment and macula-off. Eleven patients underwent surgery using pars plana vitrectomy (PPV), and 10 patients underwent scleral buckle surgery. Clinical examinations and optical coherence tomography (OCT) were performed post-surgery. MAIA microperimetry was conducted at 6 months. RESULTS: Best-corrected visual acuity (BCVA) and the number of letters read improved over time in the operated eye but did not reach the level of the control eye (p = 0.001). No significant differences were found between the two surgical approaches in BCVA (p = 0.230) or the number of letters read (p = 0.608). Macular integrity in the operated eye did not match that of the control eye in both procedures (p = 0.05). No differences were detected between the two surgeries, either in macular integrity (p = 0.512) or fixation stability (p = 0.835). CONCLUSIONS: Following retinal detachment surgery, a decrease in BCVA and the number of letters read occurs, which does not reach the level of the control eye. No significant differences were observed between the two surgical approaches. Macular integrity in the operated eye does not match that of the control eye.

Thrombotic Event Prevention in Patients Undergoing Posterior Lumbar Arthrodesis: our experiencie. A retrospective case series study. / Prevención de eventos trombóticos en pacientes sometidos a cirugía de artrodesis lumbar por vía posterior: experiencia en nuestro centro. Estudio retrospectivo de casos.

INTRODUCTION: There is no generalized consensus regarding perioperative prophylaxis of venous thromboembolism (VTE), either on using or timing it in patients undergoing spine surgery. VTE is a current concern because, even though being an uncommon event, it can cause serious complications. The aim of the present study is to propose guidelines for the prevention of thrombotic events in posterior spinal surgery, either as deep vein thrombosis or pulmonary thromboembolism. If the number of patients getting prophylaxis drugs is reduced a subsequent reduction of the incidence of epidural hematoma can be expected. MATERIALS AND METHODS: A number of 235 patients who had undergone posterior spinal arthrodesis in the previous five years were studied. Mechanical thromboprophylaxis measures consisting of compression stockings were applied in all of them. Anticoagulant drugs were also applied whenever risk factors for thrombosis were observed. Early weight-bearing was resumed immediately after surgery. Demographic, clinical, and surgical variables were collected, as well as complications appearing during the follow-up period, that was scheduled at one, two, four, six and twelve months after the surgery. Thrombotic events, if present, were diagnosed by clinical and imaging tests such as ultrasound and CT angiography. RESULTS: From the total 235 patients of this series, one hundred and fifty-three cases met the study inclusion criteria. A total of four thrombotic events appeared, one in the form of deep vein thrombosis and other three in the form of pulmonary thromboembolism. These last patients suffering an embolism died because of it. None of the variables studied had statistical significance for the occurrence of a thrombotic event. All four patients who suffered thrombotic events were receiving anticoagulant drugs, in addition to mechanical compression stockings, because of the presence of risk factors for thrombosis. CONCLUSIONS: By applying the fore mentioned protocol, adequate prevention of thromboembolic events was achieved in this study population of patients undergoing posterior spinal surgery.

Prophylactic central lymph node dissection in cN0 papillary thyroid cancer: a comparative study of via breast and transoral approach versus via breast approach alone.

Background: Papillary thyroid cancer (PTC) progresses slowly and has a good prognosis, while the prognosis is worse if combined with central neck lymph node metastasis at an early stage. The different endoscope approaches may affect the thoroughness of lymph node dissection. This study aimed to compare the clinical efficacy and safety of prophylactic central lymph node dissection(CLND) for cN0 PTC performed via breast and transoral approach versus via breast approach alone. Materials and methods: A retrospective analysis of the surgical data of 136 patients with stage cN0 PTC was performed from August 2020 to December 2022. Among them, 64 underwent the breast and transoral approach (combined approach group), and 72 underwent the breast approach alone (breast approach group). The relevant indexes of surgery, the number of lymph nodes dissected, the occurrence of postoperative complications, and the cosmetic satisfaction of incision were statistically compared between the two groups. Results: The operation time of the combined approach group was 156.4 ± 29.8 min, significantly longer than that of the breast approach group, 119.6 ± 55.9 min, and the difference was statistically significant (P<0.05). The two groups of patients were compared in terms of intraoperative bleeding, postoperative drainage, hospitalization time, incision cosmetic satisfaction, and the occurrence of postoperative complications, and the differences were not statistically significant (P>0.05). The total number of lymph nodes retrieved in the central area (10.6 ± 7.1) and the number of positive lymph nodes (4.6 ± 4.9) in the combined approach group were significantly more than those in the breast approach group (7.4 ± 4.8, 1.6 ± 2.7), and the difference was statistically significant (P<0.05). The difference between the two groups in terms of the number of negative lymph nodes was not statistically significant (P>0.05). Conclusions: The study demonstrated that choosing the breast combined transoral approach for prophylactic CLND of cN0 PTC could more thoroughly clear the central area lymph nodes, especially the positive lymph nodes, which could help in the evaluation of the disease and the guidance of the treatment, while not increasing the postoperative complications. It provides a reference for clinicians to choose the appropriate surgical approach and also provides new ideas and methods for prophylactic CLND in patients with cN0 PTC.

Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Central Causation of Autism/ASDs via Excessive [Ca2+]i Impacting Six Mechanisms Controlling Synaptogenesis during the Perinatal Period: The Role of Electromagnetic Fields and Chemicals and the NO/ONOO(-) Cycle, as Well as Specific Mutations.

The roles of perinatal development, intracellular calcium [Ca2+]i, and synaptogenesis disruption are not novel in the autism/ASD literature. The focus on six mechanisms controlling synaptogenesis, each regulated by [Ca2+]i, and each aberrant in ASDs is novel. The model presented here predicts that autism epidemic causation involves central roles of both electromagnetic fields (EMFs) and chemicals. EMFs act via voltage-gated calcium channel (VGCC) activation and [Ca2+]i elevation. A total of 15 autism-implicated chemical classes each act to produce [Ca2+]i elevation, 12 acting via NMDA receptor activation, and three acting via other mechanisms. The chronic nature of ASDs is explained via NO/ONOO(-) vicious cycle elevation and MeCP2 epigenetic dysfunction. Genetic causation often also involves [Ca2+]i elevation or other impacts on synaptogenesis. The literature examining each of these steps is systematically examined and found to be consistent with predictions. Approaches that may be sed for ASD prevention or treatment are discussed in connection with this special issue: The current situation and prospects for children with ASDs. Such approaches include EMF, chemical avoidance, and using nutrients and other agents to raise the levels of Nrf2. An enriched environment, vitamin D, magnesium, and omega-3s in fish oil may also be helpful.

Executive Summary of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR) Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management.

The Airway section of the Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) present the Guidelines for the integral management of difficult airway in adult patients. This document provides recommendations based on current scientific evidence, theoretical-educational tools and implementation tools, mainly cognitive aids, applicable to the treatment of the airway in the field of anesthesiology, critical care, emergencies and prehospital medicine. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations and optimization in the progression of the application of strategies to preserve adequate alveolar oxygenation in order to improve safety and quality of care.

Prevalence of precancerous lesions and other cervical abnormalities among internally displaced women in Benue State Nigeria.

Introduction: visual inspection is a low-cost screening strategy that can be used to prevent cervical cancer in women. These techniques can improve screening health outcomes for internally displaced women (IDW) who have poor sexual and reproductive health and rights' behaviors and outcomes. This study aimed to determine the prevalence of precancerous lesions and other clinical features using a visual inspection with acetic acid (VIA) technique during a cervical cancer screening campaign in two internally displaced people (IDP) camps in Benue State, Nigeria. Methods: this was a cross-sectional study of 166 IDW who voluntarily participated in the study during a VIA cervical cancer screening campaign in two IDP camps in Benue State, Nigeria the screening was done by a group of qualified and trained healthcare workers and data was collected using a structured, pretested questionnaire. Results: a total of 99(60%) of the women had a first sexual experience at 16 years, while 78(47%) had more than 5 full-term pregnancies. Although only 72(43.4%) of the women acknowledged having more than one sexual partner, over 70% of the women stated that their sexual partner had another sexual partner. The prevalence of precancerous lesions among women was 10.8%. Smoking(p=0.003), age at menarche (p≤ 0.001) and sexual behaviors (p=0.009, p=0.004) were factors that had a statistically significant relationship with the presence of a precancerous lesion among the IDW. The study also highlights the high rate (95%) of cervicitis among the women and the relatively high rate (5.4%) of leukoplakia. Conclusion: the majority of IDW had sociodemographic and lifestyle characteristics that predisposed them to developing cervical cancer More targeted interventions aimed at improving the sociodemographic and lifestyle characteristics of IDW are recommended. In addition, there is a need to create awareness about cervical cancer among IDW and make screening available in camp facilities for early detection and management.

Genome wide association studies for carcass traits measured by video image analysis in crossbred lambs.

This is the first UK genome wide association study investigating potential links between Video Image Analysis (VIA) carcass traits and molecular polymorphisms in crossbred sheep. Phenotypic and genotypic data were collected from two crossbred lamb populations: Texel x Scotch Mule (TxSM, n = 2330) and Texel x Lleyn (TxL, n = 3816). Traits measured included live weights at birth, eight weeks and weaning (∼15 weeks). VIA-predicted traits included total weights and weights of fat, muscle and bone in the whole carcass and primal (hind leg, saddle, shoulder) regions. Within-breed heritabilities estimated for the VIA traits ranged from 0.01 to 0.70, indicating potential for inclusion of some traits in breeding programmes. The two crossbred populations differed in SNPs associated with different traits. Two SNPs on chromosomes two (s74618.1) and eight (s68536.1), respectively, reached genome-wise significance for TxSM, explaining <1% of trait variance, for whole carcass fat and muscle weights, hind leg and saddle fat weights and shoulder bone weights. For TxL, four SNPs reached genome-wise significance, on chromosome two for hind leg muscle weight (OAR2_117,959,202 and OAR2_11804335), on chromosome 10 for whole carcass bone weight (OAR19_8,995,957.1), and on chromosome 19 for weaning weight (s40847.1), each explaining <1% of trait genetic variation. Differences in apparent genetic control of carcass traits may be influenced by the lambs' cross-breed, but also by management decisions affecting environmental variance and trait definitions, which should be understood in order to define protocols for incorporation of carcass traits into (cross)breeding programmes. IMPLICATIONS: Combining VIA-measured carcass traits with conventional production traits in a breeding programme could potentially improve the production and product quality of meat sheep. Phenotypes for VIA traits could be collected relatively easily if VIA machines were present at all abattoir sites. The current study and future Genome Wide Association Studies may help to identify potentially informative molecular markers, that explain large proportions of the genetic variance observed in VIA-measured carcass traits. Including this information in the estimation of breeding values could increase the accuracy of prediction, increasing the potential rate of genetic improvement for product quality. This study confirms the polygenic architecture of the investigated carcass traits, with a small number of molecular markers that each explain a small amount of genetic variation. Further studies across breed types are recommended to further test and validate molecular markers for traits related to lamb carcass quality, as measured by video image analysis.

Mean airway pressure as a parameter of lung-protective and heart-protective ventilation.

Mean airway pressure (MAP) is the mean pressure generated in the airway during a single breath (inspiration + expiration), and is displayed on most anaesthesia and intensive care ventilators. This parameter, however, is not usually monitored during mechanical ventilation because it is poorly understood and usually only used in research. One of the main determinants of MAP is PEEP. This is because in respiratory cycles with an I:E ratio of 1:2, expiration is twice as long as inspiration. Although MAP can be used as a surrogate for mean alveolar pressure, these parameters differ considerably in some situations. Recently, MAP has been shown to be a useful prognostic factor for respiratory morbidity and mortality in mechanically ventilated patients of various ages. Low MAP has been associated with a lower incidence of 90-day mortality, shorter ICU stay, and shorter mechanical ventilation time. MAP also affects haemodynamics: there is evidence of a causal relationship between high MAP and low perfusion index, both of which are associated with poor prognosis in mechanically ventilated patients. Elevated MAP values have also been associated with high central venous pressure and lactate, which are indicative of ventilator-associated right ventricular failure and tissue hypoperfusion, respectively. MAP, therefore, is an important parameter to measure in clinical practice. The aim of this review has been to identify the determinants of MAP, the pros and cons of using MAP instead of traditional protective ventilation parameters, and the evidence that supports the use of MAP in clinical practice.

Endoscopic duodenal mucosa ablation techniques for diabetes and nonalcoholic fatty liver disease: A systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD). METHODS: We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively. FINDINGS: We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged. CONCLUSIONS: All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment. FUNDING: This study received no funding.

Breaking Bad: Spontaneous Rupture of Incisional Hernia.

Spontaneous bowel evisceration from a ruptured, long-standing abdominal wall hernia is a very rare complication with significant morbidity and mortality, usually occurring in incisional or recurrent groin hernias. In this case report, we elucidate an unexpected scenario of spontaneous incisional hernia rupture leading to bowel evisceration, detailing the clinical presentation, diagnostic workup, and surgical management. By highlighting this rare complication, we emphasise the significance of vigilance in monitoring hernia patients and the necessity of expedited surgical intervention to prevent complications, optimise outcomes, and minimise morbidity.

Respiratory Viral Coinfections: Insights into Epidemiology, Immune Response, Pathology, and Clinical Outcomes.

Respiratory viral coinfections are a global public health threat that poses an economic burden on individuals, families, and healthcare infrastructure. Viruses may coinfect and interact synergistically or antagonistically, or their coinfection may not affect their replication rate. These interactions are specific to different virus combinations, which underlines the importance of understanding the mechanisms behind these differential viral interactions and the need for novel diagnostic methods to accurately identify multiple viruses causing a disease in a patient to avoid misdiagnosis. This review examines epidemiological patterns, pathology manifestations, and the immune response modulation of different respiratory viral combinations that occur during coinfections using different experimental models to better understand the dynamics respiratory viral coinfection takes in driving disease outcomes and severity, which is crucial to guide the development of prevention and treatment strategies.

Beyond the average effect of the innovation subsidies: Using case selection via matching to break impasse in delivering useful advice to policy makers.

Experts and stakeholders promote the combined use of counterfactual and theory-based approaches in program evaluation. We illustrated combined application of these two approaches in a single evaluation study of innovation subsidies, using "case selection via matching" and follow-up in-depth interviews. We conducted interviews in contrasting pairs of companies-one successful and one unsuccessful-which were otherwise similar on a defined set of covariates. Our procedure helped to reveal factors, which might be overlooked or simply not available in data at hand and hence not accounted for in analyses of the intervention effects. As such it extends beyond the average effect estimate to highlight causes of an intervention success or failure.

The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Heterogeneity and overlap in the continuum of linguistic profile of logopenic and semantic variants of primary progressive aphasia: a Profile Analysis based on Multidimensional Scaling study.

BACKGROUND: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce. METHODS: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [18F] FDG-PET. Correlations were performed between metabolic and behavioral data. RESULTS: Patients' profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space. DISCUSSION: Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups.

Experiences of women participating in a human papillomavirus-based screen-triage-and treat strategy for cervical cancer prevention in Malawi.

Objective: To explore the experiences of Malawian women who underwent a human papillomavirus (HPV)-based screen-triage-treat algorithm for cervical cancer (CxCa) prevention. This algorithm included GeneXpert® HPV testing of self-collected vaginal samples, visual inspection with acetic acid (VIA) and colposcopy for HPV-positive women, and thermal ablation of ablation-eligible women. Method: In-depth interviews were conducted with participants of a trial that evaluated the feasibility of a HPV-based screen-triage-treat algorithm among women living with HIV and HIV negative women in Lilongwe, Malawi. Participants were recruited from 3 groups: 1) HPV-negative; 2) HPV-positive/VIA-negative; 3) HPV-positive/VIA-positive and received thermal ablation. Interviews explored baseline knowledge of CxCa and screening, attitudes towards self-collection, and understanding of test results. Content analysis was conducted using NVIVO v12. Results: Thematic saturation was reached at 25 interviews. Advantages of HPV self-collection to participants were convenience of sampling, same-day HPV results and availability of same-day treatment. There was confusion surrounding HPV-positive/VIA-negative results, as some participants still felt treatment was needed. Counseling, and in particular anticipatory guidance, was key in helping participants understand complex screening procedures and results. Overall, participants expressed confidence in the HPV screen-triage-treat strategy. Discussion: HPV testing through self-collected samples is a promising tool to increase CxCa screening coverage. A multi-step screening algorithm utilizing HPV self-testing, VIA triage and thermal ablation treatment requires proper counseling and anticipatory guidance to improve patient understanding. Incorporating thorough counseling in CxCa screening programs can change women's perspectives about screening, build trust in healthcare systems, and influence healthcare seeking behavior towards routine screening and prevention.